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Write a title and summarize: Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario. We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years. Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants. Women with primary infection with T. gondii during pregnancy may exhibit no symptoms, but there is about a 50% risk of transmission to the fetus and the possibility of mild to profound injury to the unborn child in untreated women [1]. The risk of maternofetal transmission increases over the course of the pregnancy, from very low risk in the first trimester to nearly 100% in the final weeks of pregnancy. In the event of transmission, risk of injury to the fetus varies inversely with gestational age, with the risk of profound injury greatest in the first trimester and the possibility of mild disease or no recognized symptoms in later stages of gestation [1,6, 13,14]. Consequences of CT can include retinochoroiditis, hydrocephaly, cerebral calcifications, splenomegaly, hearing loss, blindness, and death [1,6, 15,16]. In countries with prenatal screening for primary infections and consequent pre- and postnatal treatment, rates of CT and severity of symptoms in infants are lower than in countries without screening programs or compared to historical data before screening was initiated [7,10,17,18]. In comparison, a recent study of children in the United States with CT who had no pre- or postnatal treatment found that 91% of the children referred had visual and/or mental impairment by age 12 [9]. The risk of CT is complicated, however, by the diversity of genotypes of T. gondii. Type II predominates in Europe and was thought to be the predominant genotype in North America [6,19–21]. Recent research has identified greater diversity in US wild and domestic animals than was previously thought [22–24]. Types I and III and atypical genotypes are more common in Central and South America [25–27]. These latter strains are more virulent and are associated with ocular disease even when acquired postnatally by immune-competent persons [28]. South American genotypes are also associated with more serious injuries in CT [19,20,28–30]. Prevalence of infection with T. gondii varies considerably in Europe, from 7% in Norway [31], 10% in the United Kingdom [32], 19% in Italy [33], 32% in Spain [34], 33% in Austria [31,35,36], and 34% in Slovenia [37], to 37 to 44% in France [7,38] (all reported since 2000). Over the past 20 years, prevalence has fallen rather dramatically in most of the high prevalence countries coincident with national education campaigns, which have perhaps led to changes in food preparation [7,31]. Systematic screening of pregnant women also plays an educational role in highlighting the importance of food safety and hygiene for the health of the unborn. Countries with high prevalence in the past similarly had high rates of primary infection in women during pregnancy. This may seem paradoxical since the higher the prevalence among women of child-bearing age, the higher will be the proportion of women entering pregnancy who are immune. Since prevalence, however, increases with age, the majority of young women are not immune and continue to be at risk, presumably with the same food preparation habits as before. The substantial drop in prevalence from the 1990s to the present was accompanied by a substantial drop in maternal incidence after an initial rise [7,17]. Austria in 1974, France in 1992, and Slovenia in 1995 initiated mandatory prenatal screening programs aimed at reducing maternofetal transmission as well as the severity of injury from CT. Numerous studies have reported that systematic prenatal screening and treatment were coincident with substantial reductions in maternofetal transmission and sequelae of CT [7,10,12,13,17,18,36,37,39–45]. No systematic economic evaluation of those programs, however, has been published. The countries with systematic prenatal screening and treatment programs face the paradox of successful prevention. Now there are so few children with serious, disabling symptoms of CT that it can appear that the risk of maternal infection does not warrant the expenditure for universal prenatal screening programs. Health budgets are under continual scrutiny. In some countries political currents have changed and the assumption of state responsibility for health is questioned. Moreover, there are diverse stakeholders in the decision to allocate funds to prenatal screening or to other national health needs: the Ministry of Health, insurance funds, the Ministry of Education, social security administrations, and families of affected children. The purpose of the current work is to compare the societal costs of CT under the Austrian national program of prenatal screening for primary toxoplasmosis with the societal costs that would have occurred in the absence of the screening program. In 1961, Thalhammer revealed a rate of CT of 78 per 10,000 live births for the Austrian population [46]. In response, mandatory prenatal screening for toxoplasma infection for all pregnant women was implemented in 1974 under the auspices of the national health care system [46,47]. This prenatal screening is part of a national prevention program called “Mother-Child-Booklet-Program” for all pregnant women and their infants through early childhood. The costs are covered by the government and the local health insurance funds; the program is free of charge for families. The Austrian national program is described in detail in previous works [12,31,48]. Serological prenatal screening is performed ideally on a bimonthly schedule, at 8,16,24, and 32 weeks of gestation as well as a maternal or neonatal test for women seronegative up to the time of birth and women who have not been tested during pregnancy. In women with proven seropositivity before the current pregnancy, no further toxoplasma testing is necessary. Women who are tested and found to have been seropositive before conception require only one test. Those with suspected primary infection during pregnancy are tested twice. In Austria during this screening program, the local laboratories used 9 different test methods for the detection of IgM Toxo antibodies, each performed according to manufacturer recommendations. In the case of primary infection in a pregnant woman or to clarify suspicious test results, blood samples were retested in the reference laboratory. The Toxoplasmosis Laboratory at the Medical University of Vienna routinely uses the in-house Sabin Feldman dye test, immunosorbent agglutination assay (ISAGA) -IgM (bioMérieux, France), VIDAS Toxo IgG Avidity (bioMérieux, Frankreich), and PCR diagnostics for the detection of toxoplasma infections in pregnant women and their children. In women with primary infection, amniocentesis and polymerase chain reaction of the amniotic fluid is recommended, but costs for those additional tests are not covered by the program. A positive result from amniocentesis identifies an affected fetus prenatally and influences the treatment during pregnancy. The routine PCR analysis used for the B1 gene after amniocentesis showed a sensitivity and specificity of 87. 2% and 99. 7%. Furthermore, the results revealed a positive predictive value and negative predictive value of 94. 4% and 99. 3% [48]. More recently, using the 529-bp PCR protocol improved sensitivity up to 100. 0% [49]. Pregnant women are treated after the diagnosis of primary infection until birth, and infants with proven or suspected congenital infection are treated during the first year of life. In cases of CT, additional investigation, including cranial ultrasound, funduscopy, and complete blood count, is part of the program. The screening program reached 93% of pregnant women over the period covered by this analysis, although the ideal schedule was not achieved for most women [31]. The Austrian Toxoplasmosis Register records the serology history and birth outcomes for 1,387,680 pregnant women from 1992 to 2008 [12]. All cases of CT are recorded in the Register and thus it provides the basis for evaluating the costs of the program and pediatric outcomes over the 17-year period. In 10% of women no toxoplasma testing was necessary due to proven seropositivity before pregnancy. Screening confirmed additional infected women, resulting in seroprevalence of 34. 4% used in the model [31]. The Register reported 70 women with primary infection of T. gondii and 8 cases of CT per year. The management of women and infants was stable, as was the rate of toxoplasma infection, during the observation period. Pediatric long-term follow-up revealed that 81% of infants with T. gondii infection did not show any clinical signs as of May 2013. All clinical variables for infection, transmission, and outcomes in infants are shown in Table 1. The maternal screening study was approved by the local ethics committee at the Medical University of Vienna, Vienna, Austria (824/2009). All adult subjects and parents of any child participants gave their informed consent orally in person or by telephone at the time of inclusion. The individuals were included in the nationwide toxoplasmosis register performed 1992‒2008 and their oral consent was documented in the register data file. Written consent could not be obtained, due to the fact that this was a nationwide study. The data were processed anonymously. The current economic study utilized anonymous data from the national screening program. The TreeAge program calculates all of the costs that occur in each scenario—the counterfactual (No screening) compared to all actual lifetime costs in Austria resulting under the screening scenario. Thus the TreeAge program attributes costs to the Screening scenario that result from treating infants who are infected despite the program, including those whose mothers were not screened or were screened inadequately, with the lifetime costs of follow-up, accommodation, and parental work time lost. In Austria, if there were no screening program, one must assume that the state would provide health care for a child born with, or who later develops, CT symptoms. So the costs of diagnosing and caring for a symptomatic infected child are not really costs of the screening program itself. They would occur (and in much larger numbers) without the national screening. The €8. 4 million a year under the Screening scenario represents the costs of the screening program plus the lifetime societal cost for the affected children born during the 17-year period. The screening program itself entails very little cost. It includes only testing all pregnant women (except those already known to be seropositive) and treating women with primary infection. It also would include the cost of treating the very few asymptomatic infected infants because without screening they would be missed, but with screening, they would be treated from birth. Under the screening program, there have been 70 incident infections in mothers per year. Without treatment, there would be a fetal infection rate of 0. 508 [12] and a probability of asymptomatic CT of 0. 06 [1]. Thus, there would be two asymptomatic infected newborns treated per year because of the screening program who would have been overlooked without screening (70 x 0. 508 x 0. 06 = 2. 10). Costs for each of those children would be: 5 infant IgG test, 5 infant IgM test, pediatric treatment, CBC, ECG, cranial ultrasound, and 17 funduscopies, which amount to €1,372. The costs of the screening program, shown in Table 4, total approximately €1. 9 million per year for all pregnancies, or €25 per pregnancy. A new diagnostic appears likely with a test cost of about €4. Recalculating with a test cost of €4 would reduce the total cost of prenatal screening and maternal treatment from about €1. 9 to about €1. 2 million (calculation not shown). The costs of the screening program can be compared to the cost of caring for a child whose mother is not treated. The costs for individual services and productivity losses are listed in Table 2, but each symptomatic child generates multiple kinds of costs. In the tree before rollback (calculation), Fig 1, all the costs for an individual child for each outcome are listed at the terminal node. For example, in the No-Screening scenario, a child with severe visual, cognitive, and hearing impairment (Terminal node #14 in Fig 1) will incur the following costs (assuming symptoms at birth that lead to testing, treatment, and follow-up care): 5 infant IgG tests, 5 infant IgM tests, pediatric treatment, CBC, ECG, cranial ultrasound, and 17 funduscopies, as well as the direct costs and productivity losses for child and parents associated with severe visual, cognitive, and hearing impairment, and special education costs. Fig 2 (Terminal node #14) shows the sum of those costs. The lifetime cost for one child with severe visual, cognitive, and hearing impairment is €1. 8 million (€1,778,210). Thus the costs of the entire screening program for one year are nearly the same as the potential costs for a single severely affected child whose mother was not treated. A child with only severe visual impairment generates costs of €482,811 (at terminal node #9). The costs for four such children exceed the annual cost of the screening program. Without prenatal treatment, more than 90% of infected children have been found to have some form of serious impairment [1,9, 52,53]. Prenatal screening with pre- and postnatal treatment as needed prevents or mitigates most injuries. Austria has 70 primary infections per year [12]. If we assume 50% maternofetal transmission without prenatal treatment, as seen in Austrian women who were not treated [12], that would be 35 cases of CT each year, rather than the 8 cases per year under the treatment program, with symptoms ranging from mild visual impairment to fetal death. Because the model calculates costs on a population basis, the cost of €426 in the tree is a cost per Austrian birth, which is multiplied by the number of births, resulting in potential costs of €35 million for the 35 children who would be infected under the No-Screening scenario. The screening program costs €1. 9 million per year while the societal costs of the No-Screening scenario are €35 million per year. It is useful to see these costs in relation to overall Austrian government spending and Gross Domestic Product (GDP). The annual cost of the screening and treatment program is 0. 007% of total Austrian public spending on health and 0. 003% of overall Austrian government spending. The annual cost of the program is 0. 0006% of Austrian GDP (Derived from data at www. focus-economics. com/country-indicator/austria/gdp-eur-bn; World Development Indicators, www. wdi. worldbank. org). Calculating just the impact on the Austrian public budget—that is, omitting the lifetime costs of lost earnings that fall on affected children, their families, and society, and VSL for fetal and infant deaths, we find that the maternal screening program is still cost-saving. As seen in Fig 3, and summarized in Table 3, expenditures by government and government-sponsored insurers, based on Austrian experience over the period 1992 to 2008, cost €33 per birth compared to an estimated €219 per birth if the prenatal screening program had not been implemented in Austria. (As explained above, this overstates the budgetary cost of the screening program itself because it includes diagnosis and care of children who would be cared for under the Austrian health care system even without a screening program.) Even from the extremely narrow budgetary perspective, the Austrian national program has more than paid for itself in reducing the costs to the state and state-sponsored institutions of treating and educating children injured by CT by €186 per birth for 1. 4 million births over the period. That amounts to a total budgetary saving of more than €258 million, or more than €15 million per year. Results of the sensitivity analysis show that the savings both to society and to the government budget are robust to variations in all costs. Varying costs by ±10% had a trivial effect on cost per birth in the No-Screening and Screening scenarios and consequently on the savings that result from screening, for both the full societal cost and for the public budget. Fig 4 shows an Incremental Tornado Analysis from the societal perspective. The x axis shows the difference in costs per birth between the No-Screening and Screening scenarios with an Expected Value (EV) of €323. The horizontal bars show the full variation in the Expected Value (savings per birth) resulting from the range of values for each cost parameter. Both Fig 4 and Table 5 demonstrate the trivial impact on the large savings that result from screening. The variation in VSL had the greatest effect on costs, but even then the difference between low and high values for savings was only €56 and the savings from screening never fell below €275 per birth. Fig 5 shows the one-way sensitivity analysis on VSL in the societal model, which again demonstrates that whether one includes only the loss of earnings (€800,000) or the upper bound of the OECD estimate for VSL (€6. 7 million), there is little impact on the savings derived from the screening program, showing the same minimum savings of €275 per birth seen in Fig 4 and Table 5. Fig 6 shows the Incremental Tornado Analysis for the Budget impact. The Expected Value, that is savings per birth, is €186. The variation in savings per birth never exceeds €17 and the minimum savings from the screening program for the budget is never less than €178 per birth, as seen also in Table 6. Successful screening and treatment programs, such as Austria’s, face two challenges, both of which derive from their success. As with other public health programs, the European prenatal screening programs and education campaigns confront the paradox of success. People do not see or hear about infants affected by CT as they did in the past when infant deaths or profound brain injuries and visual impairment of varying degrees were more common, due to high rates of CT. Prevention programs only seem expensive in the absence of disease. In the face of budget pressure, the absence of infants with injuries of CT can be misunderstood to mean there is no longer a risk. On the contrary, it has taken two decades of successful prenatal screening and treatment to make the risk invisible. Moreover, the success of education programs in reducing prevalence in the population, while it may protect women by making them more aware of the risk of eating undercooked meat and unwashed fruits and vegetables, actually creates a larger population of women still at risk of infection, and particularly so since even the water supply is a source of infection in some regions. The second challenge to the prenatal screening programs comes from the methodological debate over the validity of observational studies versus randomized controlled trials as the evidence base for interventions. Numerous authors have suggested that the question of efficacy of prenatal screening and treatment can only be adequately answered with randomized controlled trials (RCTs) [13,39,66,67]. RCTs, however, pose an insurmountable ethical problem in countries where prenatal screening has been associated with significant improvement in outcomes for infants whose mothers were treated prenatally. An RCT requires equipoise, which is lacking in countries with successful screening programs (Austria, France, and Slovenia, for example) and in countries with similar epidemiology and access to care. Without equipoise, it is doubtful that one could construct an ethical trial that would require random assignment of some pregnant women to denial of a treatment with demonstrated efficacy [6,7]. Blinding could be incompatible with informed consent. It is also unlikely that such trials would have sufficient power because, with informed consent, few parents would be likely to choose not to medicate. The resulting selection bias would also invalidate the results of the trial. This ethical question is not unique to prenatal screening programs for CT. Interventions to reduce smoking, for example, were implemented based on observational data. Any RCT assigning participants to smoking would not have passed ethical review. It has been impossible to construct valid RCTs for treating sexually transmitted diseases to reduce HIV incidence because observational studies and an earlier trial demonstrated that such treatment is beneficial [68]. Similarly, any other effective treatments for cofactor infections cannot ethically be withheld from controls [68,69]. Observational and historical data from Austria, France, and Slovenia, and perhaps even comparative data from the United States, have eliminated the equipoise necessary for an ethical RCT of prenatal screening and treatment for primary infection of T. gondii. The European screening programs for CT have had noteworthy success, reducing the number of deaths and profound injuries in affected infants. That success itself in reducing preventable suffering and death commends the programs for continuation. The cost savings for national health care systems and society at large reinforce the argument for continuation. CT is a health problem worldwide and it is not possible to eliminate all sources of infection for pregnant women, nor is a vaccine likely to be developed in the near future. There are, however, successful CT-prevention programs that are reducing clinical effects of CT and saving money for national health administrations and cost to society. Our results understate the benefits of following the Austrian national program because the costs associated with injuries to infants whose mothers were not tested in accordance with the protocol are attributed to the screening scenario [31]. If those mothers had been tested on schedule, the injuries in the infants would most likely have been fewer and less severe, as was the case for the infants tested on schedule. Another source of overstatement of costs of actual Austrian practice is that we show the direct costs of ideal compliance with the protocol in obstetric visits, including the cost for all susceptible women having five tests, whereas, in practice, 97% of women had fewer than three tests. With fewer tests, that also means shorter treatment and lower treatment costs than the ideal. The average time between tests was 14 weeks, rather than the prescribed eight weeks. For two women whose infants were profoundly affected, the time between tests was 19 weeks [31]. If Austrian practice were in full compliance with the protocol, actual direct costs of screening and prenatal treatment would have been slightly higher, but the costs of treatment and accommodation of infants injured by CT and the loss of their productivity and that of their parents would have been substantially lower because fewer infants would have slipped through the screening process. The costs of screening and preventive treatment are negligible compared to the costs of treatment and accommodation for infants whose injuries are not prevented. Net benefits strongly favor screening. As demonstrated by the Austrian national program, prenatal screening and treatment result in substantial cost saving, both from the conventional societal perspective and even from the narrow perspective of budgetary impact. Results in both cases are robust to wide variations in parameter values. Our data show the positive economic value of such a prevention measure. In summary, our findings of this economic analytic-decision model represent an important base for the discussion regarding implementation or continuation of prenatal screening for toxoplasma infection.

Title: Congenital toxoplasmosis in Austria: Prenatal screening for prevention is cost-saving Summary: Toxoplasma gondii is a widespread parasitic disease. In the event of primary infection during pregnancy, this parasite can be transmitted from mother to unborn child. Clinical presentation of congenital toxoplasmosis varies from asymptomatic to life-threatening risk for the fetus and infant and in later life. Prevention programs and screening strategies of health care providers vary in different countries. Austria has implemented mandatory prenatal screening for toxoplasmosis for four decades. The screening is free of charge for families and costs are covered by national health care providers. Compliance with the national program is good and outcomes for infected pregnant women and their infants since 1992 are well documented. We compared lifetime costs of screening, treatment, and follow-up with costs in a No-Screening scenario in an economic decision-analytic model. Prenatal screening resulted in substantial cost savings due to reduction in congenital toxoplasmosis and consequent injuries in affected children.

lay_plos

en

Summarize: BACKGROUND OF THE INVENTION The invention relates to stick-deodorant or the like containers wherein the deodorant substance is loaded against a piston within the bore of an elongate housing, and wherein a base-operating member is exposed for rotation at the lower end of the housing and drives the piston via an upstanding threaded stem which is part of the base-operating member. The deodorant or the like substance which must be loaded into such a container is melted by heat and poured as a liquid into the open upper end of the housing, being thereafter allowed to solidify into a stick, upon cooling to ambient temperature. The melted substance is of low viscosity and therefore has a tendency to leak through the region of stem-thread engagement to the piston, so that various measures have been adopted to minimize the involved loss of dispensable substance and the unsightliness of substance that may have exuded via clearance needed for rotary actuation of the base-operating member. Among the techniques adopted to reduce such leakage is to design the thread engagement to be full at and near the down-position limit of the piston, and to provide for ratcheting engagement of the piston to the lead screw or stem when in the down-position limit, the ratchet engagement being desired to assure against inadvertent piston displacement due to vibration in the course of handling and transportation, from the container manufacturer to the filling house. Typically, the ratchet formations may have an angular distribution of six teeth poised for axially confronting engagement at the down position of the piston, and the thread engagement may be characterized by a triple lead of 0.0625-inch pitch threads, meaning a piston advance of 0.1875-inch, for each full rotation of the base-actuating member. However, even with the indicated measures, and even with special provision for chilling the poured substance, there are such adverse combinations of departure from exact fit of the parts that leakages continue to plague the filling house. BRIEF STATEMENT OF THE INVENTION It is an object to provide improved mechanism in a container of the character indicated, for eliminating leakage problems of the character indicated. A specific object is to provide seal action in such a mechanism, the seal being effective regardless of adverse combinations of tolerance variation in threadedly engaged parts. Another specific object is to provide improved ratchet action to retain the down-limiting position of the piston, with full circumferentially continuous loading of the sealed relation. A further specific object is to achieve the above objects with minimum modification of existing container dies and with no loss of volumetric capacity of a given container size. The invention achieves the above objects by providing circumferentially continuous axially confronting seal formations on the underside of the piston and at the base end of the threaded stem of a container of the character indicated. The seal formations take various forms but in every case provide a downward projection from the underside of the piston, axially engageable with a smooth annular surface of the stem at the down position. Ratchet action is such as to retain any one of a large plurality of angular positions of the piston with respect to the stem, the plurality being in such subdivision of a single turn of thread action as to provide plural ratchet escapements in the course of compressionally loading the seal, thus assuring retention of axially compressionally loaded seal action. The seal is so effective as to prevent leakage and to avoid the need for special chilling of filled containers, so that cooling to ambient temperature may occur in inventory or in transport, as long as filled containers are kept upright. DETAILED DESCRIPTION The invention will be illustratively described in detail in conjunction with the accompanying drawings, in which: FIG. 1 is a longitudinal sectional view of a container of the invention, the piston portion being shown as separate half sections, and at different elevations, to better show its construction; FIG. 2 is an enlarged fragmentary longitudinal sectional view of coacting seal and ratchet-engageable components of FIG. 1; FIG. 3 is a further enlarged fragmentary sectional view of the seal of FIGS. 1 and 2; FIG. 4 is a view similar to FIG. 3, to show another seal embodiment; FIG. 5 is a view similar to FIG. 3, to show a further seal embodiment; FIG. 6 is a view similar to FIG. 3, for a still further embodiment. The container of FIG. 1 comprises three parts having propulsion coaction, namely, an elongate tubular housing 10 having a cylindrical bore 11, a base-operating member 12 supported for rotation at the closed lower end of housing 10 and having an upstanding threaded stem 13 extending within housing 10, and a piston member 14 with a hub 15 in threaded engagement to stem 13. A closure cap 16 is removably threaded to the open upper end of housing 10. Each part is of injection-molded plastic, the material of piston 14 being suitably polyethylene, and more compliant than the material (suitably ABS, or polypropylene) of the other parts. The lower end of housing 10 includes a bottom wall 17 slightly recessed from a rim 18 which derives thrust-bearing support from a radial shoulder 19 of base member 12. The central region of wall 17 has plural axially compliant radially inward fingers 20 having snap-locking engagement beneath a cylindrical flange 21 at the lower end of the threads of stem 13 and at offset D from the web 22 of base member 12; snap-locking will be understood to occur as housing 10 is first assembled to base member 12, via stem 13, whereby these parts are self-retaining. Piston member 14 is characterized by a web 23 and upper skirt 24 to define an upwardly open cup for reception of deodorant or the like filling substance (not shown). A circumferentially continuous lip 25 and plural angularly spaced ribs 26 engage the bore 11 for peripherally sealed and axially stabilized piloted support of the piston member 14 throughout its range of threaded advance on stem 13. Dependent from web 23 is an outer skirt 27 which abuts housing web 17 to determine the lowermost position of piston member 14. Finally, an inner and shorter skirt 28 depends from the hub region of piston 14, being sized for telescoping reception of the stem flange 21 when in the lowermost position. In accordance with the invention, and with additional reference to FIG. 2, flange 21 is formed with a circumferentially continuous annular surface 30 having compressionally loaded sealing coaction with an axially confronting formation of the wall of hub 15, within skirt 28; and the telescopically lapped adjacent surfaces of skirt 28 and flange 21 are configurated for fine-tooth ratchet or detent action. Suitably, the ratchet action derives from engagement between a continuous succession of axially extensive radially inward rib formations 28' in the bore of skirt 28, and a plurality of spaced axially extensive radially outward rib formations 29--29' on the periphery of the hub or flange 21. As shown, plural ribs 29 occur at angularly spaced groupings, with single ribs 29' in spaced interlace between groupings 29. The space between rib formations 29--29' will be understood to permit a degree of circumferential and radial accommodation in the course of ratcheting engagement with the inner ribs 28' of skirt 28, skirt 28 being thin enough to exhibit compliant transient deformation as necessary to adopt successive ratcheting engagements in the course of approach to the lowermost position of piston member 14. FIGS. 2 and 3 are on a sufficiently enlarged scale to reveal the seal formation of piston hub 15 to be a single annular rib 31 of uniform section, depending from the inner radial wall of hub 15 and poised for circumferentially continuous axially compressed sealing engagement with surface 30, upon achieving the lowermost position of piston member 14. This seal action is effective due to the several ratchet-position escapements which occur in the course of compressionally loading the engagement, coupled with the annulus of contact attributable to compliant local flattening of rib 31 by reason of the axially loaded engagement. In the arrangement of FIG. 4, the rib 31 is one of two concentric ribs 31-32 integrally formed with hub 15 for concurrent coaction with the confronting stem surface 30, thus establishing a double-seal engagement. In the arrangement of FIG. 5, a frusto-conical lip 33 is an integral formation of piston hub 15, and a ring 34 depends integrally from hub 15 to provide extended length of the internal threads of hub 15. In the course of establishing seal closure, lip 33 is radially inwardly deflected via its abutment with surface 30. In the arrangement of FIG. 6, both a frusto-conical lip 35 and a thread-extending ring 36 are axially more extensive than in FIG. 5, the lip being contoured on its convex surface for broader-area seal contact. In the sealed position the seal lip 35 is inwardly deflected and compliantly stressed into axially loaded sealing contact with surface 30. The described structures will be seen to meet all stated objects. Sealing effectiveness is in each case circumferentially continuous and axially preloaded, as well as being located so close to the threaded-engagement region as to effectively contain any hot filling liquid which may seep through the threads of the engagement. Strong axial preloading of the seal action is available by reason of the many ratchet positions per 360° of possible hub (15) to flange (21) angular relationships, there being several such engagements between the angular relation in which initial seal contact is made, and the final such engagement at which point the seal is axially preloaded and necessarily circumferentially continuous. Later on, long after a hardened stick has formed, a customer using the container will encounter only slight initial torsional resistance as the substance is propelled from the fully retracted position, the resistance being attributable to releasing escapement of the ratcheted engagement. Typically, in a so-called two-ounce stick-deodorant container, the bore 11 of the housing is of 1.45-inch diameter, and the bore of skirt 28 is of 0.38-inch diameter. The plurality of radially inward ribs 28' in the bore of skirt 28 is 40, to a radial depth of 0.010-inch, and the unstressed radial interference with radially outward ribs 29--29' of similar radial depth is in the order of 0.004 to 0.005-inch; two rib groups 29 are diametrically opposed, in a plurality of nine ribs for each group, with diametrically opposed single ribs 29' in interlaced symmetry between groups 29, so that for each ratchet engagement twenty ribs of hub 21 engage in twenty of the forty spaces between adjacent ribs 28' in the bore of the skirt 28 of piston hub 15. Also, typically, there is at least one escaping ratchet engagement in the course of axially compressing the circumferentially sealed engagement, thus assuring that axial compression of the seal will hold, from the time of container manufacture, throughout the liquid-filling and solidifying process, and until the time of the customer' s use of the loaded container. While the invention has been described in detail for preferred embodiments, it will be understood that modifications may be made within the scope of the invention.

Summary: The invention contemplates sealed lead-screw propulsion mechanism for the piston of a container for stick deodorant or the like substance, wherein the container must be filled by hot melted substance which becomes the stick after it has been allowed to cool. The seal is operative when the piston is in its lower-most position within the container, so that liquid (melted) substance cannot seep through the region of lead-screw engagement to the piston. Once the substance has solidified, there is no further need for the seal, beyond retention of aromatic ingredients, i.e., until the product has reached the ultimate consumer; and the seal is operable only upon first dispensing use of the container.

big_patent

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Summarize: People are placing fewer orders for french fries and sugary drinks at restaurants, giving a boost to establishments that sell more low-calorie items, according to a study scheduled for release Thursday. An analysis of 21 fast-food and sit-down restaurant chains between 2006 and 2011 found that lower-calorie food and beverages fueled the chains' growth. The study was funded by the Robert Wood Johnson Foundation and conducted by the Hudson Institute, a policy-research organization. Enlarge Image Close Christian Science Monitor/Associated Press Panera posts calorie information on menus nationwide and says a fifth of its customers order lower-calorie items. Above, a New York Panera. The study found that restaurants that increased lower-calorie servings experienced an average 5.5% increase in same-store sales. That compared with a 5.5% decrease among chains selling fewer lower-calorie servings. "The bottom line is, if restaurants don't get more aggressive behind these low-calorie products, they're leaving sales on the table," said Henry Cardello, director of the Hudson Institute's Obesity Solutions Initiative and lead author of the report. "It's a business imperative." The findings might make restaurant chains feel better about efforts around the U.S. to get them to post calorie information. The Hudson study found that the number of lower-calorie food and beverage servings sold increased 2.5% to 18.7 billion, while the number of higher-calorie servings sold fell 4.2% to 31.2 billion. The analysis examined restaurant servings and traffic from market-research firm NPD Group Inc. and publicly available sales data from the restaurant chains. Lower-calorie servings were defined as sandwiches and entrees containing 500 or fewer calories, beverages with 50 or fewer calories per eight ounces and side dishes, appetizers and desserts with 150 or fewer calories. Related Video Diners have been part of the American way of life for more than a century. But these restaurants are losing their popularity. MarketWatch's Christopher Noble discusses five things that your diner probably isn't telling you. (Photo: AP) Federal regulations requiring operators of restaurants with 20 or more outlets to post calorie counts are expected to take effect early next year. Some chains, including McDonald's Corp. and Panera Bread Co., already post calorie information on menu boards nationwide. Several chains have created sections on their menus featuring smaller portions and low-calorie offerings, such as Fit Fare at Denny's Corp. restaurants and Au Bon Portions at ABP Corp.'s Au Bon Pain chain. Early studies on how posting calorie information affects consumer behavior have proved mixed. Some have found that providing calorie information has steered consumers toward healthier options, while others have found no noticeable shift. After Panera posted calorie counts on its menu boards in 2010, the company noticed that 20% of customers began ordering lower-calorie items. Chili's Grill & Bar, a unit of Brinker International Inc., said sales of items containing less than 675 calories increased after it featured two new items on that Lighter Choices lineup on menu inserts in December. McDonald's declined to comment on the Hudson study, but when the company in September said it would begin posting calorie information nationwide, Jan Fields, then-president of McDonald's USA, said the company hadn't noticed a change in behavior in the cities that already required posted calorie counts. Mr. Cardello, a former food-and-beverage industry executive, said he was surprised to find that fast-food chains sold a slightly higher percentage of lower-calorie food servings than sit-down restaurants did. Margo Wootan, the director of nutrition policy at the Center for Science in the Public Interest, said the report was consistent with what she has seen in restaurants. "Americans are more interested than ever in healthy eating," she said. But she warned that consumers still aren't as good about watching their calories when they dine out as when they eat at home, in part because large serving sizes at restaurants lead to overconsumption. Her nonprofit advocacy group wasn't involved in the Hudson study. Ms. Wootan said several studies have linked frequent restaurant visits with higher obesity rates. One showed that women who eat out more than five times a week consume about 290 more calories on average each day than women who eat out less often. "My biggest concern is that oftentimes, there are only a few healthy options at restaurants amid a much larger array of unhealthy choices," she said. Driven by pressures like consumer demand and looming federal regulations that will require them to post calorie counts on menus, restaurant chains around the country are adding more nutritious choices and shrinking portion sizes. The smaller portions, which are not necessarily cheaper, are the first step toward reversing the practice of piling more food on a plate than anyone needs in a single meal, a trend that began nearly three decades ago. Besides making a contribution to customers’ health, restaurant owners are finding that the move is paying off financially. Sbarro for example, is offering a “skinny slice,” with a different mix of cheese and more vegetables at 270 calories. Longhorn Steakhouse has smaller portions of beef that qualify for its lower calorie Flavorful Under 500 menu. “Menu labeling is part of it, but there’s also been a lot of finger-pointing at the industry by the media and others, including customers, that is spurring the movement,” said Anita Jones-Mueller, a registered dietitian who is president and founder of Healthy Dining Finder, a Web site that helps users find restaurants with healthy options using ZIP codes. One gauge — the number of restaurants with vetted healthy options listed on the site — has increased more than 2,000 percent, and many have been added just in the last couple of years, Ms. Jones-Mueller said. “Customers really want these items, so restaurants are working to make them more appealing,” she said. Hank Cardello, director of the obesity solutions initiative at the Hudson Institute, a public policy research organization, has been studying the impact that lower-calorie menu options have on restaurants’ business. “Lower-calorie menu items were driving restaurant growth over the last several years, no doubt about it,” Mr. Cardello said. The results of his research were published Thursday in a report financed in part by the Robert Wood Johnson Foundation. The Obama administration’s health care act, which was passed in 2010, included a provision requiring restaurants and food establishments with 20 or more locations to post the calorie counts of standard items on their menus. The final regulations are expected soon, with compliance likely to be required by 2014. Some restaurant chains have already begun posting calorie counts. After perusing Longhorn Steakhouse’s lower-calorie menu, Denise Garbinski, a registered dietitian in San Francisco, said the portion sizes were bigger than the four ounces she typically recommended, but that it was “a step in the right direction.” “What they’re trying to do here is cut back on portion size, which is brilliant,” Ms. Garbinski said. “I always tell people to ask for a to-go container when they first order and then put half of the meal in it before they eat, but this takes that step out of the process.” While the move by restaurants to more nutritional menu offerings is driven by external factors, many operators are finding that cutting calories, sodium, sugar and fat pays off. “It’s doing great,” Brian Bailey, co-founder and chief executive of the Ichor Restaurant Group, said of the company’s new restaurant concept, Baja Pizzafish. “To serve fish tacos in Ohio is testament not only that the food tastes good, but that people really want it.” The chain, which opened in July, offers the option of brown rice in its rice bowls, and three ounces of grilled salmon, steak or shrimp can be added. Mr. Bailey describes the dishes as, “smaller amounts of protein and more fresh vegetables.” Other menu items include thin-crust pizzas with potatoes and other lean toppings, salads and tortilla wraps. The company also operates the Old Carolina Barbecue Company, a chain of six restaurants. It has added a new menu for its catering operation, the Lighter Side of Old Carolina, that features grilled chicken wraps, carved turkey sandwiches and chicken salad made with light mayonnaise. “I don’t want to describe this as the anti-barbecue,” he said. “It’s more like I’m hedging my bets on comfort food.” Matt Friedman, founder and chief executive of Wing Zone, said the company’s decision to add Skinny Dippers, fried chicken breast nuggets with no breading, to its menu in January was as much about business as about offering customers a healthier choice.

Summary: Turns out that offering patrons lower-calorie options isn't just a good move for waistlines, it's a "business imperative" for restaurants, says the lead author of a new study. The report from the Hudson Institute finds that sales were up 5.5% between 2006 and 2011 at restaurants that increased their healthy menu choices and down by 5.5% at those that didn't, reports the Wall Street Journal. It holds true for both fast-food and sit-down restaurants. "The bottom line is, if restaurants don't get more aggressive behind these low-calorie products, they're leaving sales on the table," says the study's author. The results dovetail with new federal rules that will soon require chains with more than 20 stories to post calorie counts. McDonald's and others already have begun doing so. The healthier alternatives include smaller portions slices, like the "skinny slice" at Sbarro, notes the New York Times.

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Summarize: Lola Ogunyemi is on Facebook. To connect with Lola, sign up for Facebook today. From a very young age, I’ve been told, “You’re so pretty … for a dark-skinned girl.” I am a Nigerian woman, born in London and raised in Atlanta. I’ve grown up very aware of society’s opinion that dark-skinned people, especially women, would look better if our skin were lighter. I know that the beauty industry has fueled this opinion with its long history of presenting lighter, mixed-race or white models as the beauty standard. Historically, and in many countries still today, darker models are even used to demonstrate a product’s skin-lightening qualities to help women reach this standard. This repressive narrative is one I have seen affect women from many different communities I’ve been a part of. And this is why, when Dove offered me the chance to be the face of a new body wash campaign, I jumped. Dark is beautiful: the battle to end the world's obsession with lighter skin Read more Having the opportunity to represent my dark-skinned sisters in a global beauty brand felt like the perfect way for me to remind the world that we are here, we are beautiful, and more importantly, we are valued. Then one morning, I woke up to a message from a friend asking if the woman in a post he’d seen was really me. I went online and discovered I had become the unwitting poster child for racist advertising. No lie. If you Google “racist ad” right now, a picture of my face is the first result. I had been excited to be a part of the commercial and promote the strength and beauty of my race, so for it to be met with widespread outrage was upsetting. Calls were being made to boycott Dove products, and friends from all over the world were checking on me to see if I was OK. I was overwhelmed by just how controversial the ad had become. If I had even the slightest inclination that I would be portrayed as inferior, or as the “before” in a before and after shot, I would have been the first to say an emphatic “no”. I would have (un)happily walked right off set and out of the door. That is something that goes against everything I stand for. However, the experience I had with the Dove team was positive. I had an amazing time on set. All of the women in the shoot understood the concept and overarching objective – to use our differences to highlight the fact that all skin deserves gentleness. I remember all of us being excited at the idea of wearing nude T-shirts and turning into one another. We weren’t sure how the final edit was going to look, nor which of us would actually be featured in it, but everyone seemed to be in great spirits during filming, including me. Then the first Facebook ad was released: a 13-second video clip featuring me, a white woman, and an Asian woman removing our nude tops and changing into each other. I loved it. My friends and family loved it. People congratulated me for being the first to appear, for looking fabulous, and for representing Black Girl Magic. I was proud. Then, the full, 30-second TV commercial was released in the US, and I was over the moon again. There were seven of us in the full version, different races and ages, each of us answering the same question: “If your skin were a wash label, what would it say?” Again, I was the first model to appear in the ad, describing my skin as “20% dry, 80% glowing”, and appearing again at the end. I loved it, and everyone around me seemed to as well. I think the full TV edit does a much better job of making the campaign’s message loud and clear. There is definitely something to be said here about how advertisers need to look beyond the surface and consider the impact their images may have, specifically when it comes to marginalized groups of women. It is important to examine whether your content shows that your consumer’s voice is not only heard, but also valued. I can see how the snapshots that are circulating the web have been misinterpreted, considering the fact that Dove has faced a backlash in the past for the exact same issue. There is a lack of trust here, and I feel the public was justified in their initial outrage. Having said that, I can also see that a lot has been left out. The narrative has been written without giving consumers context on which to base an informed opinion. While I agree with Dove’s response to unequivocally apologise for any offense caused, they could have also defended their creative vision, and their choice to include me, an unequivocally dark-skinned black woman, as a face of their campaign. I am not just some silent victim of a mistaken beauty campaign. I am strong, I am beautiful, and I will not be erased.

Summary: Lola Ogunyemi grew up being told she was pretty... "for a dark-skinned girl." So when Dove offered her the chance to model in one of its body wash campaigns, she jumped at it. "Having the opportunity to represent my dark-skinned sisters in a global beauty brand felt like the perfect way for me to remind the world that we are here, we are beautiful, and more importantly, we are valued," she writes in the Guardian. Unfortunately, soon after the ad debuted, Ogunyemi discovered she "had become the unwitting poster child for racist advertising." In the ad, which Dove pulled after it was posted online to massive backlash, Ogunyemi is shown removing a brown shirt... to reveal another model in the next clip, this one white and wearing a lighter shirt. "If I had even the slightest inclination that I would be portrayed as inferior, or as the 'before' in a before and after shot, I would have been the first to say an emphatic 'no,'" she writes. But her time at the shoot was positive, with the Dove team portraying the ad's objective as using "our differences to highlight the fact that all skin deserves gentleness." The Facebook ad that ended up sparking so much backlash, "a 13-second video clip featuring me, a white woman, and an Asian woman removing our nude tops and changing into each other," was something Ogunyemi was proud of and that her friends and family loved. But she acknowledges the full ad, a 30-second TV commercial, "does a much better job of making the campaign's message loud and clear." She says she understands the outrage, but she thinks "the snapshots that are circulating the web" are missing a lot of context. Dove would have been within its rights to defend "their creative vision, and their choice to include me, an unequivocally dark-skinned black woman, as a face of their campaign," she writes, emphasizing that she is not a victim. Click for her full column.

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Summarize: BACKGROUND OF THE INVENTION The field of the invention generally pertains to toilet seat covers. The invention relates more particularly to a toilet seat cover assembly for use as a combination toilet seat cover and auxiliary bathroom seat with self-positioning, retractable backrest. Bathrooms have traditionally been the smallest room in virtually all institutions and homes. Much of the bathroom space is typically reserved for such traditional bathroom fixtures as a bathtub or shower, a wash basin, and a toilet. Unfortunately, this leaves very little free space available for even small furniture items, such as a chair, for momentarily sitting and resting. A place to sit in the bathroom is often needed, however, for handicapped persons, convalescents, senior citizens, or anyone who fatigues easily. In many cases, the availability of a place to sit in the bathroom can significantly reduce the risk of falling and injuring oneself. Due to the inadequate space, conventional toilet seat covers have often been used as provisional, impromptu bathroom chairs when necessary. However, because toilet seat covers are not particularly designed for use as a seat, they are unable to comfortably support a seated person as would a typical chair. For example, unlike a chair, neither the toilet seat cover or the toilet itself provides any back support when a person sitting on the toilet seat attempts to lean back. While some toilets incorporate the use of water tanks, they are not designed or suited to support a lateral force applied by a person leaning against it. Additionally, with the exception of some toilets especially made for use by handicapped persons, the height of the toilet seat and toilet seat cover when lowered is typically lower than an average-sized chair, which can make sitting and standing up much more difficult. In light of these and other limitations of the conventional toilet seat cover, various toilet seat covers and accessories have been developed to improve the utility, comfort, and/or aesthetic appearance of the conventional toilet seat cover, as well as the toilet seat and toilet in many cases. In most cases, however, the need to provide a comfortable, chair-like seating area in the bathroom while conserving space has been ill-addressed, if at all. For example, in U.S. Pat. No. 2,434,889, a toilet seat accessory is shown for use as a combination toilet seat cover and auxiliary juvenile toilet seat. The auxiliary juvenile toilet seat is hinged to a conventional toilet seat, and a backrest separately hinged to the auxiliary juvenile toilet seat. Use of the backrest, however, is limited only for children and not adults. Additionally the backrest can only be used in conjunction with the auxiliary juvenile toilet seat, which may often be unnecessary. Further, because the hinging action of the backrest is independent of the hinging action of the auxiliary juvenile seat, this requires multiple independent actions by the user to correctly set up and use the backrest instead of one. And finally, the backrest disclosed in the '889 patent is not designed or suited to rest or lean against at all. As shown in FIG. 6 of the '889 patent, although the stop member 28 and resilient spring member 27 function to prevent the support member 24 from moving up in the slot 26, there is nothing to prevent the support member 24 from moving down and exiting the slot 26. This is particularly true when a lateral force is applied, such as that exerted by a person leaning against the backrest. Additionally, U.S. Pat. No. 4,368,551 discloses a commode enclosure with a bottom closure cabinet and a top closure cabinet, for completely enclosing a toilet and water tank. The bottom closure cabinet has a hinged seating portion capable of swinging open to allow access to a toilet seat and the toilet. While the commode enclosure may be used as a seating area, it is essentially designed to enhance the aesthetic appearance of the conventional toilet. The all-enclosing features of the bottom and top closure cabinets are intended to cover up the drab and ordinary appearance of the conventional toilet bowl. It does so, however, by conspicuously taking up an extensive amount of bathroom space. Moreover, its demanding space requirement is compounded by its inability to completely retract or store away when accessing the toilet, which may cause discomfort or otherwise interfere with the conventional manner in which the toilet and toilet seat are used. BRIEF SUMMARY OF THE INVENTION It is an object of the present invention to provide a simple and compact toilet seat cover assembly which economizes bathroom space by functioning as a combination toilet seat cover and an auxiliary bathroom seat. It is a further object of the present invention to provide a comfortable toilet seat cover assembly which provides a comfortable, chair-like bathroom seat having a backrest and an easily manageable seat elevation for sitting down and standing up. It is a still further object of the present invention to provide a simple, easy-to-operate toilet seat cover assembly with a retractable backrest capable of self-positioning itself during operation of the toilet seat cover assembly. It is a still further object of the present invention to provide a non-obtrusive toilet seat cover assembly which installs and operates without interfering with the underlying movement and operation of the conventional toilet seat (and conventional toilet seat cover if attached). The present invention is for a toilet seat cover assembly for use with a toilet having a hinged toilet seat and functioning as a combination toilet seat cover and auxiliary bathroom seat with self-positioning, retractable backrest. The toilet seat cover assembly includes a cover having a platform portion with a top surface and a bottom surface, and a perimeter sidewall portion below the bottom surface of the platform portion with a pair of ends and a top edge joined to the platform portion. In a first preferred embodiment, the toilet seat cover assembly includes a housing structure having a pair of vertical sidewalls positioned on opposite sides of the toilet and rigidly joined together by a connector wall. In the first preferred embodiment, the perimeter sidewall portion is hingedly secured to the pair of vertical sidewalls by means for hingedly securing the cover to the pair of vertical sidewalls. In a second preferred embodiment, the perimeter sidewall portion is hingedly secured to the toilet by means for hingedly securing the cover to the toilet. In both the first and the second preferred embodiments, the means for hingedly securing the cover has a pivot axis extending through the pair of ends of the perimeter sidewall portion and parallel to a pivot axis of the hinged toilet seat. Additionally, the means for hingedly securing the cover functions to pivot the cover between a closed position over the hinged toilet seat and an open position remotely pivoted away from the hinged toilet seat. The toilet seat cover assembly also includes a backrest having a base portion with an upper surface and a lower surface, and an upright portion with a front surface, a rear surface, an upper end, and a lower end joined to the upper surface of the base portion. The base portion is hingedly secured to the cover by backrest hinging means, and contacts the cover along the lower surface when in the closed position. The toilet seat cover assembly also has means for actuating the backrest hinging means when the cover is moved between the open and closed positions. Preferably, the means for actuating the backrest hinging means is a stopper positioned behind the upright portion of the backrest facing the rear surface, and is affixed between the pair of vertical sidewalls of the housing structure in the first preferred embodiment. In both the first and second preferred embodiments, the rear surface comes into sliding contact with the stopper, which then operates to position the upright portion generally parallel to the cover when in the open position and generally perpendicular to the cover when in the closed position. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of the first preferred embodiment of the toilet seat cover assembly as generally seen from the left side and in the closed position. FIG. 2 is a perspective view of the first preferred embodiment of the toilet seat cover assembly as generally seen from the right side and in the closed position. FIG. 3 is a perspective view of the first preferred embodiment of the toilet seat cover assembly in the open position. FIG. 4 is a cross-sectional view of the first preferred embodiment of the toilet seat cover assembly taken along the line of 4--4 of FIG. 1. FIG. 5 is a perspective exploded view of the first preferred embodiment of the toilet seat cover assembly as generally seen from the rear underside. FIG. 6A is a side view of the first preferred embodiment of the toilet seat cover assembly in the closed position. FIG. 6B is a side view of the first preferred embodiment of the toilet seat cover assembly in a partially open position with the backrest just contacting the stopper. FIG. 6C is a side view of the first preferred embodiment of the toilet seat cover assembly in a further partially open position from FIG. 6B with the stopper pivoting the backrest. FIG. 6D is a side view of the first preferred embodiment of the toilet seat cover assembly in the fully open position. FIG. 7 is a perspective view of the second preferred embodiment of the toilet seat cover assembly in the open position. FIG. 8 is a perspective exploded view of the second preferred embodiment of the toilet seat cover assembly as generally seen from the rear underside. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring now to the drawings, FIGS. 1-4, 6A-D, and 7 show the toilet seat cover assembly, generally indicated by reference character 10, as it is used in conjunction with a toilet, generally indicated by reference character 11. FIGS. 1, 2, 4, and 6A show the toilet seat cover assembly 10 in a closed position, and FIGS. 3, 6D, and 7 show the toilet seat cover assembly 10 in a fully open position. As can be best seen in FIGS. 3 and 7, the toilet 11 includes a toilet bowl 12, a toilet bowl rim 13, and a toilet seat 14 hingedly secured to a rearward portion 15 of the toilet 11 by hinges 16. The toilet seat cover assembly 10 has a cover, generally indicated by reference character 17 (FIGS. 1-8), having a platform portion 18 with a top surface 19 and a bottom surface 20. Preferably, the platform portion 18 has an outer rim 21 (FIGS. 1, 2, 4, and 7) which follows the contour of the toilet seat 14 and toilet bowl rim 13, and a linear rear rim 22 (FIGS. 3-4, 7, and 8) near the rearward portion 15 of the toilet 11. The cover 17 also includes a perimeter sidewall portion 23 having a pair of ends 25 and a top edge 24 joined to the platform portion 18. Preferably the top edge 24 is joined to the platform portion 18 at the outer rim 21 (FIGS. 1, 2, 4, and 7), with the perimeter sidewall portion 23 and the platform portion 18 integrally formed together as a single unit. Preferably still, the cover 17 also includes at least two cover support members 50 (FIGS. 3 and 7) affixed to the bottom surface 20 of the platform portion 18 which contacts the toilet seat 14 when in the closed position. Together with the means for hingedly securing the cover 27 (see FIGS. 5 and 8), the cover support members 50 function to support the weight of a person sitting on the toilet seat cover assembly 10. The cover support members are composed of a suitably rigid material capable of supporting the weight of a person, such as molded plastic, or dense elastomeric material. In a first preferred embodiment (FIGS. 1-6D) the toilet seat cover assembly 10 also includes a housing structure, generally indicated by reference character 33, to which the cover 17 is hingedly secured. The housing structure 33 has a pair of vertical sidewalls 34 positioned on opposite sides of the toilet 11 near the rearward portion 15 and rigidly joined together by a connector wall 35. In this first embodiment, as shown in FIGS. 1-4, and 6A-D, the cover 17 is hingedly secured to the pair of vertical sidewalls 34 by means for hingedly securing the cover 27 to the pair of vertical sidewalls 34. As can be best seen in FIG. 5, the means for hingedly securing the cover 27 to the pair of vertical sidewalls 34 has a pivot axis 28 extending through the pair of ends 25 of the perimeter sidewall portion 23, and preferably through downward extensions 25' of the pair of ends 25. The pivot axis 28 is also parallel to a pivot axis (not illustrated) of the hinged toilet seat 14 (FIG. 3). Preferably, the means for hingedly securing the cover 27 to the pair of vertical sidewalls 34 comprises a pair of pivot pins 29 secured to the pair of ends 25 via a plurality of fasteners 30. As shown in FIG. 5, the pair of pivot pins 29 extend outward in opposite directions through the pair of ends 25 and pivotally mount on a pair of support enclosures 31 (FIGS. 1-3) fixedly secured on the pair of vertical sidewalls 34. Preferably the pair of pivot pins 29 pivotally mount on the pair of support enclosures 31 by bearing means 32 to ensure smooth and durable hinging movement. As can be seen in FIGS. 1-3, the housing structure 33 of the first preferred embodiment can be a modular component of a larger structure, such as a universal fixture unit. In this manner, the toilet seat cover assembly 10 can be specifically integrated into the design of a bathroom to serve an important ergonomic and/or space-conserving purpose and decor. As can be seen in FIG. 7 a second preferred embodiment of the toilet seat cover assembly 10 is shown hingedly securing the cover 17 to the toilet 11 by means for hingedly securing the cover 27 to the toilet 11. As can be best seen in FIG. 8, and similar to the first preferred embodiment shown in FIG. 5, the means for hingedly securing the cover 27 to the toilet 11 has a pivot axis 28 preferably extending through the downward extensions 25' of the pair of ends 25 of the perimeter sidewall portion 23. And the pivot axis 28 is also parallel to a pivot axis (not illustrated) of the hinged toilet seat 14 (FIG. 7). Preferably, and similar to the first preferred embodiment, the means for hingedly securing the cover 27 to the toilet 11 also comprises a pair of pivot pins 29 secured to the pair of ends 25 via a plurality of fasteners 30. However, unlike the first preferred embodiment (FIG. 5), the pair of pivot pins 29 (FIG. 8) extend inward through the pair of ends 25 toward the toilet 11 and each other to pivotally secure to the toilet 11. In one embodiment the means for hingedly securing the cover 27 to the toilet 11 includes a C-shaped bracket 36 (FIG. 7) having an aperture at each end and mounted on the rearward portion 15 of the toilet 11. The pivot pins 29 can thus extend through the apertures of the C-shaped bracket 36 to pivotally secure the cover 17 to the toilet 11. The toilet seat cover assembly 10 also includes a backrest, generally indicated by reference character 37, having a base portion 38 with an upper surface 39 and a lower surface 40, and an upright portion 41 with a front surface 42, a rear surface 43, an upper end 44, and a lower end 45 joined to the upper surface 39 of the base portion 38. Preferably the upright portion 41 forms a generally L-shaped cross-section with the base portion 38. However, the upright portion 41 can be joined anywhere on the upper surface 39 of the base portion 38. As can be best seen in FIGS. 5 and 8, the base portion 38 is hingedly secured to the cover 18 by backrest hinging means 46, and contacts the cover 18 along the lower surface 40 when in the closed position. The backrest hinging means 46 can be any suitable hinging means, such as a conventional piano hinge 46, secured with a plurality of fasteners 47. Preferably the backrest hinging means 46 functions to hingedly secure the base portion 38 to the linear rear rim 22 of the platform portion 18. And in one embodiment of the cover 17 (FIGS. 5 and 8), the pair of ends 25 of the perimeter sidewall portion 23 coextensively protrude beyond the linear rear rim 22 of the platform portion 18 to expose the top edge 24 of the perimeter sidewall portion 23 near the pair of ends 25. This enables the lower surface 40 of the base portion 38 to rest on top of the exposed top edge 24 near the pair of ends 25 when the cover 17 is in the closed position. And in the closed position, the forward position of the backrest hinging means 46 relative to the backrest 37 enables the backrest 37 to support a lateral force typically exerted by a person leaning back against the upright portion 41. Lastly, the toilet seat cover assembly 10 also includes a means for actuating the backrest hinging means 51 when the cover is moved between the open and closed positions. Preferably, as shown in FIGS. 6A-D, and 7, the means for actuating the backrest hinging means 51 is a stopper 51 positioned near the rearward portion 15 of the toilet 11 behind the upright portion 41 and facing the rear surface 43. In the first preferred embodiment (FIGS. 6A-D), the stopper 51 is affixed between the pair of vertical sidewalls 34 of the housing structure 33. As can be seen in FIGS. 6A-D, operation of the toilet seat cover assembly 10 involves a double-hinging movement of the cover 17 and backrest 37 when the cover 17 is handled and moved between the open and closed positions. The double-hinging movement operates in two stages: movement prior to sliding-contact with the stopper 51 (FIGS. 6A-B), and movement during sliding-contact with the stopper 51 (FIGS. 6C-D). In the first stage (FIGS. 6A-B), as the cover is initially raised from the closed position, the backrest 37 pivots together with the cover 17 about the pivot axis 28. During the first stage the lower surface 40 of the base portion 38 continues to remain in contact with the cover 17 up until the rear surface 43 comes into contact with the stopper 51 (FIG. 6B). The second stage begins when the upper end 44 of the rear surface 43 comes into contact with the stopper (FIG. 6B) and the stopper prevents the upper end 44 of the backrest 37 from retracting further. During the second stage the stopper 51 functions to actuate the backrest hinging means 46 by effectively keeping the upper end 44 of the backrest 37 stationary while the top surface 19 of the cover 17 is raised to approach the backrest 37 (FIG. 6C). The point of contact between the rear surface 43 of the upright portion 41 and the stopper 51 is characteristically a roll-slide contact point having two degrees of freedom. The roll-slide character of the contact enables the backrest 37 to slide against the stopper 51, as well as pivot or "roll" relative to it. The cover 17 is continually raised until the base portion 38 fully contacts and rests on the rearward portion 15 of the toilet 11 along its lower surface 40. In both the first and second preferred embodiments, the stopper 51 functions to position the upright portion 41 generally parallel to the cover 17 when in the fully open position and generally perpendicular to the cover 17 when in the closed position. Additionally, the downward extensions 25' of the pair of ends serve to retract the cover 17 further back towards the rearward portion 15 of the toilet 11 when pivoted to the open position. In this manner, the toilet seat cover assembly 10 can be used as an auxiliary bathroom chair while it functions to cover the toilet bowl 12 and toilet seat 14 as would a conventional toilet seat cover. And the toilet seat cover assembly 10 does not interfere with the conventional operation and use of the toilet seat 14 when moved to the open position. In particular, the toilet seat cover assembly 10 will not interfere with the underlying hinging movement of the toilet seat 14, and the toilet seat 14 can still be raised and propped up in an upright position. The toilet seat cover assembly 10 is preferably constructed from durable plastic or similarly rigid material. Additionally, as shown in FIGS. 1 and 2, padding 48 and 49 can be affixed to the top surface 19 of the platform portion 18 and the front surface 41 of the upright portion 40, respectively, to improve the comfort level of the toilet seat cover assembly 10 even further. The terms "generally parallel orientation" and "generally perpendicular orientation" of the upright portion 41, as used herein, are understood to define approximations of the angular relationship between the upright portion 41 of the backrest 37 and the platform portion 18 of the cover 17 at the fully open and closed positions, respectively. The actual angle measure between the upright portion 41 and the platform portion 18 in the open and closed positions can fall within an acceptable range of ±20 degrees from true parallel or true perpendicular, respectively. The present embodiments of this invention are thus to be considered in all respects as illustrative and not restrictive; the scope of the invention being indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Summary: A toilet seat cover assembly for use as a combination toilet seat cover and auxiliary bathroom seat with self-positioning, retractable backrest. The assembly includes a cover which is hinged to either the toilet or a housing structure positioned on either side of the toilet. A backrest having a base portion and an adjoining upright portion is hinged to the cover at the base portion such that when the cover is raised from a closed position to an open position, the backrest pivots with the cover until it contacts a stopper. At such point, and as the cover is continuously raised, the stopper urges the backrest to hinge separately from the cover and to retract in a compact manner.

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Summarize: Image copyright Getty Images Doug Engelbart, who has died aged 88, never really made any money from inventing the mouse. Here are 10 others who didn't get to be billionaires. 1. LEDs When Nick Holonyak Jr invented the first practically useful LED in 1962 he predicted it would one day replace Edison's lightbulb. Holonyak's colleagues have said he should be given the Nobel Prize but he humbly says: "It's ridiculous to think that somebody owes you something. We're lucky to be alive, when it comes down to it." 2. Post-It Notes 3M sell billions of Post-It Notes each year but its inventors describe themselves as "comfortably off" not wealthy. They were the co-creation of Dr Spencer Silver, who in 1968 developed an adhesive that had a "removability characteristic", and his colleague Art Fry hit on the idea of a bookmark that would stay in place in his hymnbook. 3. AK-47 The Kalashnikov rifle, or AK-47, was invented by Soviet Army soldier Mikhail Kalashnikov while recovering in hospital from injuries sustained in World War II. Kalashnikov claimed his creation was for the benefit of his country. Image copyright Getty Images 4. Sapphire stylus Marie Killick invented a sapphire stylus for a record player but could not license it and despite years of litigation never made any money. In 1958 she won a lawsuit against Pye but went bankrupt the following year. 5. Hovercraft Sir Christopher Cockerell used a vacuum cleaner and tin cans to test his theories as he developed the hovercraft, which first crossed between Calais and Dover in 1959. Cockerell was knighted but fought for years to get a lump sum from the National Research Development Corporation. Image copyright PA 6. Tetris Russian computer programmer Alexey Pajitnov's game Tetris was developed alongside colleagues at a Russian government-funded research centre in 1985. He only started getting royalties 10 years later when he formed The Tetris Company. 7. The Wind-Up Radio Inventor Trevor Baylis recently said he can no longer afford to live in his home in Twickenham, London, because despite millions of sales around the globe, the company he went into business with were able to tweak his design and he lost control over the product and profits. "Most of us don't do it for the money but for the buzz," says Baylis. "I know that at least I've left my mark with the radio, the wind-up torch and other things I've invented." Image copyright Getty Images 8. Karaoke machines Japanese businessman Daisuke Inoue made money from playing drums in a backing band which let bar goers take the mic and have a go at singing. One time when he couldn't make a gig he put the backing music on tape instead and later made 11 Karaoke (empty orchestra) machines which he leased out. He didn't patent his invention and barely made a yen. 9. MP3 The MP3 quickly became the standard for transferring music over the internet. German PhD student Karlheinz Brandenburg started work on the project in the 1980s but because there was no money to distribute the software it was marketed as shareware. Image copyright Getty Images Image caption Sir Tim Berners-Lee earned billions, but only in kudos 10. World Wide Web And finally, no-one would have stumbled across this list save for Sir Tim Berners-Lee, who created the web to help scientists working at the European research lab at Cern. He says the secret of the rapid success of his invention was the fact he made it freely available. Not all inventors are driven to make money but some want to make a contribution to the "common good", says Dr Tilly Blyth, Keeper of Engineering and Technology at the Science Museum. "We tend to focus on the commercial development but in fact its often public and government research that has got it to that stage," Dr Blyth says. "If you look at the iPhone you think it's a great invention from Steve Jobs and Apple but look at the vital components like the screen, the chip and the processor and their origins were all in government-funded research." "A lot of the real cutting-edge research comes from the pure and blue sky thinking done in public research facilities for the good of humanity rather than to make money." THE story most often told about Christopher Cockerell is that he invented the hovercraft by experimenting with a device made from two empty cans and a vacuum cleaner. Some accounts say one of the cans had contained cat food and the other coffee. Some maintain that both were coffee cans. In other versions a pair of kitchen scales is mentioned. Sir Christopher (as he later became) seems not to have clarified these technical points. He was content for this homely story to become part of inventors' folklore, unencumbered by too much detail. Everything was stacked against becoming an inventor, he once said. People did not really want new ideas, even when they offered a better way of doing something. He had first learnt this as a child, when his mother declined to have her sewing machine powered by Christopher's steam engine. But “some silly chaps seem to be driven” to inventing. Britain, he believed, needed more silly chaps like George Stephenson, James Watt and Richard Arkwright, who had given the world its first industrial revolution. What could be more encouraging to their successors than the knowledge that a great invention could be given birth with a couple of cans salvaged from the dustbin? This was an antidote to the gloomy notion that would-be inventors these days needed to work in the sort of scientific palaces where Nobel prize-winners seek drugs that will enable people to live for ever. Simple-tech was still with us. As a piece of engineering, the Cockerell hovercraft, travelling on a cushion of air and released from the friction of water, was in the elegant tradition of Stephenson's steam locomotive. There would always be a market, too, for what might be called primitive-tech. In someone's mind there was surely an idea waiting to be born as brilliant as the paper clip and the safety pin. Sir Christopher never found that golden fleece, but he never gave up the search and in the course of a long life patented more than 70 inventions. The rewards With all these inventions to his credit, Sir Christopher felt that he should have been rich. The hovercraft, versatile, fast, able to operate independently of harbours, was in demand throughout the world after the prototype first crossed the English Channel successfully in 1959. This conveyance, described in its patent as “neither an aeroplane, nor a boat, nor a wheeled land-vehicle”, was, it was claimed, the all-purpose craft of the future. To a large extent this claim has been realised. It is reckoned that in the past 40 years some 600m people have travelled by hovercraft. But not all of them have travelled in a hovercraft more than once. The vehicle's movement, especially over choppy seas, can encourage nausea. Hovercraft still ply the English Channel, where the craft first flew, but many people prefer the steamers or the tunnel. Its future may be more as a transport for uncomplaining soldiers. American marines are enthusiastic about the hovercraft and it is widely used in the Russian army. In Finland coastguards have found that it goes well over ice. Car-size hovercrafts have become a toy for the rich. In America there are hovercraft races. One way or another the hovercraft has been quite a success. The name has gone into the language. “Hovercraft will always be around,” Sir Christopher predicted. Had he been an entrepreneur as well as an inventor he might indeed have made a fortune. But creativity and salesmanship do not always go together. In 1955 he had shown an early model of the craft, about two feet long, to the British government. A bad move to involve the bureaucrats, perhaps, but he was a patriot and thought the hovercraft might have a military use. The government agreed, and classified it as a state secret. Later the government took the hovercraft off the secret list and put up some money to develop it commercially; and later still helped to set up a corporation to market the vehicle. Sir Christopher surrendered his patents to the corporation. In 1969 he received £150,000 ($1.6m in today's money) in settlement of his claims, a knighthood from a grateful government and the admiration of his colleagues. “Numerous medals”, he notes in a biographical entry in a reference book. “I've enjoyed life,” Sir Christopher remarked, “but it would have been nice to treat my wife to dinner once in a while.” He may have felt bitter, but he was never poor. He had a comfortable childhood in Cambridge, where his father was director of the Fitzwilliam Museum. He gained an engineering degree and worked for Marconi. During the second world war at Marconi he was part of the team that invented a radio direction-finder which was fitted to British bombers. He liked messing around in boats, and after the war bought a boatyard in Norfolk. As a business it was a failure, but it was here that he first experimented with his tins; and mulled over the possibilities of generating electricity from the movement of sea waves, an idea that once seemed silly but now seems less so. But for the silly chaps, said Christopher Cockerell, we would still be living in the stone age. Suzanne Vega: “The Mother of the MP3”? Suzanne has been referred to as the “Mother of the MP3” as it was her voice that was used as the model for Karlheinz Brandenburg’s [pictured at right] compression algorithm. From Business 2.0 Magazine: “To create MP3, Brandenburg had to appreciate how the human ear perceives sound. A key assist in this effort came from folk singer Suzanne Vega. I was ready to fine-tune my compression algorithm, Brandenburg recalls. Somewhere down the corridor a radio was playing [Vega s song] Tom s Diner. I was electrified. I knew it would be nearly impossible to compress this warm a capella voice. Because the song depends on very subtle nuances of Vega s inflection, the algorithm would have to be very, very good to select the most important parts of the sound file and discard the rest. So Brandenburg tested each refinement of his system with Tom s Diner. He wound up listening to the song thousands of times, and the result was a code that was heard around the world. When an MP3 player compresses music by anyone from Courtney Love to Kenny G, it is replicating the way that Brandenburg heard Suzanne Vega.” Pat DiNizio: “You’re Fired!” Suzanne hired Pat DiNizio, the frontman from The Smithereens, as an assistant when they both worked in an office, before both their careers took off. Dennis Diken’s liner notes from the CD version of “Especially for You”: ” Suzanne Vega had been Pat’s boss at an office job in NYC and once had the honor of *firing* his butt.” No hard feelings, as Suzanne appeared on Pat’s song “In A Lonely Place” on The Smithereen’s 1986 record “Especially For You.” Hanging with Ani When Suzanne was in her early twenties before she had a record deal, she used to go to Buffalo and play at a bar called Nietzches. She didn’t have enough money for a hotel so the promoter arranged for her to stay with a family whenever she played there, which was quite a bit between 1982 and 1984, or thereabouts. This family included a young girl of about 12 or 13 who was studying dance at that time. Her name? Ani DiFranco. Plumb Names Herself After Suzanne’s “My Favorite Plum” Singer songwriter Plumb, whose first two albums each sold over 100,000 copies, took her name from Suzanne’s song, “My Favorite Plum” Plumb writes, “It’s an honor to have named myself artistically Plumb after one of Suzanne Vega’s greatest works, “My Favorite Plum” off of her 1996 Nine Objects of Desire album. Suzanne has been and continues to be highly influential to my songwriting. She possesses the ability to be vulnerable, honest and poetic while still being metaphorical enough so that her songs can take on their own meaning to the listener. That’s the kind of songwriter I aspire to be, and Suzanne Vega has paved that path for me to follow.” Sounds like Tom’s Diner? There have been quite a few recordings which have interpolated “Tom’s Diner.” From Will Smith to REM to Easy-E, Tupac, Jars of Clay and Destiny’s Child: Eazy-E – “Switchez” 3/26/02 3/26/02 Ludacris – “Playpen To the State Pen” 8/2/02 8/2/02 J Davis Trio – “Squinted-Eyed Justice” 8/2/02 8/2/02 Jene – “If He Knew” 5/30/02 5/30/02 Sarah Connor – “French Kissing” 11/5/01 11/5/01 Sev7en – “Friday NIght” 7/13/00 7/13/00 Lil’ Kim – “Brreak for Love” 5/22/00 5/22/00 T. One – “Tom’s Diner (Rap Verstion)” 2/11/00 2/11/00 Terror Squad – “Droaq” 6/3/99 6/3/99 Disco Elements – “Disco Lessons Part 1” 6/1/98 6/1/98 Destiny’s Child – “Know That” 1/26/98 1/26/98 Dave Hollister – “Come In The Door Pimpin” 8/21/98 8/21/98 Jars of Clay – “Good Coffee, Strong Coffee” 7/28/97 7/28/97 Chazz – “If You” 9/22/97 9/22/97 D-Devils – “Paranoid In Hell” 1/12/01 1/12/01 Will Smith – “Lean” 10/1/97 10/1/97 2Pac – “Dopefiend’s Diner” 10/13/97 10/13/97 Bingo Hand Job (REM) – “Tom’s?” 1991 1991 After One – “Tom’s Diner Rap” 1991 1991 Marilyn Whitelaw & Mark Davies – “Jeannie’s Diner” 1991 1991 n.d.a. Project – “Tom’s Diner” 1991 1991 MIchigan & Smiley – “Tom’s Diner” 1991 1991 Beth Watson – “Waiting At The Border” 1991 1991 Nikki D. – “Daddy’s Little Girl” 1991 1991 Peter Behrens – “Dep De Do Dep” 1991 More Music-related Fun Facts: Suzanne was the first artist on stage at the very first Lilith Fair Suzanne’s first gig was at Carnegie Hall with Pete Seeger at age 12 Performed with Grateful Dead in ’88 Christine Lavin’s song, “Mysterious Woman” was written as a tribute and a good-natured parody of Suzanne. Performed at Glastonbury in 1989 in a bulletproof vest. The band “Bingo Hand Job” which recorded a track on “Toms Album” is actually REM. The second woman to win the MTV prize for “Best Female” for”Luka” beating Cher. Soul Coughing’s record, “Ruby Vroom” named after Suzanne’s daughter, Ruby. Amy Ray of the Indigo Girls was quoted in a July 2000 AP interview as saying that the group’s initial goal was “to get big enough to open for Suzanne Vega.” Share on Facebook

Summary: Despite what you may think, a smash-hit of an invention doesn't necessarily set an inventor up for life. (Witness Doug Englebart, who invented the computer mouse but didn't see a dime from it.) As the BBC points out, there are plenty of others who failed to make billions (or even thousands) from their famous creations. On the list: Post-It Notes: Spencer Silver (who came up with the unique adhesive) and Art Fry (who had the "bookmark" idea) say they aren't rich, just "comfortably off." Karaoke machine: Daisuke Inoue failed to patent his creation, which spun out of a gig he had playing backing drums at a bar whose patrons provided the vocals; one day he couldn't make it, and put his music on a tape. MP3: Karlheinz Brandenburg started working on the MP3 in the 1980s, using the song "Tom's Diner" by Suzanne Vega. As the BBC explains, "because there was no money to distribute the software it was marketed as shareware." Hovercraft: Sir Christopher Cockerell made the mistake of getting the British government involved with his invention, which he thought would have a military function; he surrendered his patents to the corporation the government set up around the vehicle. He was eventually awarded a lump sum worth $1.6 million in today's money, a fraction of what he likely would have made in the private market. Click to see the complete list.

multi_news

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Summarize: By. Jonathan O'Callaghan. Hundreds of thousands of video gamers are right now plugged into one computer game. But it’s not the latest Call of Duty or Fifa – it’s a science based game called EyeWire in which users map the neurons of a brain. And information collected from the gamers using the crowdsourcing programme has been used to map neurons in an eye’s retina for the first time. An online video game known as EyeWire has been used to help map the neurons in the retina of a mouse, which can in turn be applied to that of a human. Outlined in the journal Nature, the study relied on information crowdsourced by thousands of gamers. The popular game has been running since late 2012 and shows how games can be used to help research in various branches of science. In this image, different cells in the retina have been traced in various colours by gamers. The findings were announced in the journal nature by a team including Professor Sebastian Seung of the Massachusetts Institute of Technology (MIT). Light from an object passes through your pupil into your eye. Depending on how bright the light is, your iris changes size. The lens then focuses this light onto the your retina at the back of your eye. The retina is composed of light-sensitive neurons known as photoreceptors that change light signals into electrical signals. These are then transmitted to the brain where an image is formed. Professor Seung’s lab at MIT has been running the hugely popular EyeWire game since late 2012, which contributed to the study. The latest discovery is a huge boon for the game and shows how useful crowdsourcing can be in various branches of science. In the game, players are given layers of a a retina - in this case one of a mouse - which is similar to a human’s in many ways. By making a plastic print of a retina, a 3D replication is made on a computer screen. Gamers are then tasked with individually mapping out the neurons by scrolling up and through the various layers. In EyeWire, users are given blocks of cells within a retina of a mouse that has been moulded in plastic and scanned into the system. Gamers then intricately study the layers of cells and trace out the paths of neurons. Together, with multiple gamers tackling the same section, an accurate map of the neuron is made and a 3D representation, as seen in this image, can be made. Here in yellow-green is a starburst amacrine cell, while in blue is a single bipolar. Multiple users tackle different parts of the membrane and, to eliminate errors, some map the same cells as others. As neurons are mapped, gamers gain points, with expert users going keeping an eye on things in case mistakes are made. The game doesn’t require users to have any background in biology though, allowing anyone to pick up and get involved with the project. ‘You no longer have to have a PhD in neuroscience,’ said Amy Robinson, creative director of EyeWire, told NBC News. ‘You could be a high-school student, or a sculptor, a dental assistant or retiree. All you have to have is now an Internet connection and an interest in gaming.’ Over 120,000 gamers have signed up from 100 countries to play EyeWire. But to solve this particular retina challenge, a selection of just over 2,000 of the best ‘EyeWirers’ mapped the so-called starburst amacrine cells, which are found in the retina, and they are all listed as co-authors on the paper. The EyeWire team are now looking at new challenges for their gamers to overcome. These include taking a look at the connections between smells and emotional responses. Here another starburst amacrine cell is shown in red, along with three bipolar cells. Starburst cells are used by retinas for selecting a direction to look, and they also help retinas develop over time. Bipolar cells, meanwhile, act as signal couriers between photoreceptors (which gather light) and ganglion cells that take the signals into the cortex of the brain. Aside from retinas, it is hoped that future EyeWire projects will map other functions of the brain as well

Summary: Thousands of video gamers have used an online programme to help scientists map neurons in retinas. The game they are playing is EyeWire, which launched in 2012 and has over 120,000 gamers across 100 countries. While playing users work together to 'trace' the paths of neurons throughout 3D representations of cells. In this instance the information was used to see how information is transmitted from the eye to the brain. But in future the game could be used to map other brain functions such as how smells are linked to emotions.

cnn_dailymail

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Write a title and summarize: When the primary visual cortex (V1) is damaged, the principal visual pathway is lost, causing a loss of vision in the opposite visual field. While conscious vision is impaired, patients can still respond to certain images; this is known as ‘blindsight’. Recently, a direct anatomical connection between the lateral geniculate nucleus (LGN) and human motion area hMT+ has been implicated in blindsight. However, a functional connection between these structures has not been demonstrated. We quantified functional MRI responses to motion in 14 patients with unilateral V1 damage (with and without blindsight). Patients with blindsight showed significant activity and a preserved sensitivity to speed in motion area hMT+, which was absent in patients without blindsight. We then compared functional connectivity between motion area hMT+ and a number of structures implicated in blindsight, including the ventral pulvinar. Only patients with blindsight showed an intact functional connection with the LGN but not the other structures, supporting a specific functional role for the LGN in blindsight. Damage to the primary visual cortex (V1) that may occur following a stroke causes visual loss in the corresponding part of the visual field (homonymous hemianopia, [1]). However, extensive research has shown that some patients retain an ability to respond to images inside their scotoma, even though they may not consciously see them [2]. This phenomenon is called blindsight, and recent work applied diffusion MRI and tractography in patients with V1 damage to try to uncover which pathways may underlie this residual visual function [3]. A connection between the lateral geniculate nucleus (LGN) and human motion area, hMT+, was found to be intact in patients with blindsight but was absent or impaired in patients without blindsight. The other pathways tested, which included a connection between hMT+ and the superior colliculus (SC), and with hMT+ in the opposite hemisphere, did not show this pattern. Unfortunately, a limitation of diffusion MRI is that it investigates purely structural connections, which may not relate directly to the function under investigation [4]. Furthermore, seed-based tractography is restricted to pathways chosen by investigators (see also [5–7]), which in this case did not include a connection with the thalamic pulvinar nucleus. Neither a specific role for the LGN nor a functional connection to hMT+ has been shown in human blindsight and would significantly advance our understanding of how patients respond to visual images in the absence of V1. The current study investigated behavioural and functional MRI responses to speed of motion in a group of patients with V1 damage in adulthood (n = 14), and healthy age-matched controls (n = 8). Patients were categorised as blindsight positive or negative according to their ability to detect the visual stimulus within their blind visual field. We then compared measures of activity and functional connectivity between the two patient groups and healthy controls. Patients with blindsight demonstrated significant fMRI activity in hMT+ in the damaged hemisphere, with a relatively preserved hMT+ response to speed in the blind hemifield. Critically, patients with blindsight also showed intact functional connectivity between hMT+ and LGN in the damaged hemisphere, which was absent in patients without blindsight. This was specific to the LGN, as both patient groups demonstrated preserved functional connectivity between hMT+ and (i) ventral pulvinar, (ii) SC, and (iii) contralateral hMT+, which was no different than in healthy controls. The pulvinar, in particular, is implicated in human and nonhuman primate studies in which V1 is damaged early in life [8,9]; however, this region is yet to be evaluated in adult-onset blindsight. Our findings support a critical functional role for the LGN and its specific connection with hMT+ in adult human blindsight, reinforced by recent evidence for an intact anatomical connection between these structures [3]. Blindsight-positive patients demonstrated significant fMRI activity in contralateral hMT+ for moving versus static dots in the blind hemifield (Fig 1Ai and 1Aii). Overall hMT+ blood oxygen level–dependent (BOLD) signal change for all 5 speeds was significantly greater than baseline (Fig 1Aiii, t = 3. 0, p = 0. 02, df = 7). Activity was somewhat lower in intensity and spatial extent than the sighted field or healthy controls (Fig 1C), but there was no significant difference between blind and sighted responses in blindsight-positive patients (Fig 1Aiii t = 1. 3, p = 0. 2, df = 39). Whilst the absence of a significant difference may result from a lack of power (n = 8), blindsight-negative patients with a lower ‘n’ (Fig 1B) showed a marked effect of hemifield (paired t = 2. 9, p = 0. 007, df = 29) and no demonstrable hMT+ activity for moving versus static dots in the blind hemifield (Fig 1Bi and 1Bii) nor averaged across all conditions (Fig 1Biii, t = 0. 6, p = 0. 6, df = 5). In addition to hMT+ activity, blindsight-positive patients with right V1 damage (Fig 1Aii, n = 2) showed activity in Jülich-defined right V2 and left V4, although there was no such activity in patients with left V1 damage (n = 6). In blindsight-negative patients, visual-evoked responses also appeared within small regions of ipsilesional V4 and V2, as well as the occipital pole and inferior parietal lobule, implying that activity in these regions was insufficient for motion perception. It was noteworthy that overall hMT+ signal change in the undamaged hemisphere was also slightly reduced in both patient groups compared to age-matched controls. A possible explanation is that unilateral V1 damage can negatively impact sighted processing in the opposite hemisphere, perhaps via a disturbance of interhemispheric interactions [10,11]. Speed of motion (0°–32°/s) had a significant impact on hMT+ activity in the sighted hemifield of patients and equivalent left hemifield of controls (2-way ANOVA: F (4,14) = 5. 1, p < 0. 001), with no effect of participant group (Fig 1iv, F (2,14) = 2. 2, p = 0. 12). In the blind hemifield of patients (right hemifield of controls) there was a similar effect of speed (F (4,14) = 3. 5, p = 0. 01) but also group (F (2,14) = 7. 4, p = 0. 001). The pattern of responses in blindsight-positive and -negative patients differed markedly. Blindsight-positive patients showed a positive relationship between hMT+ signal change and speed (r = 0. 8,5 speeds), whilst the correlation coefficient was negative in blindsight-negative patients (r = −0. 6). This difference was not simply driven by a difference between motion and static responses, as excluding the static conditions increased the significance even further (r = 0. 67 versus r = −0. 99, z = −2. 44, p = 0. 01). Specifically, blindsight-positive patients showed a relatively ‘normal’ hMT+ relationship with speed in the blind hemifield that was similar to the pattern in healthy controls (Pearson r = 0. 89, p = 0. 04,5 speeds) and patients’ own sighted hemifield (r = 0. 98, p < 0. 01). This was not the case for blindsight-negative patients, either when compared to controls (r = 0. 21, p = 0. 7) or to their own sighted hemifield (r = 0. 29, p = 0. 6). To determine how activity in hMT+ correlated with subcortical activity, we examined the fMRI time series after stimulus-evoked responses had been regressed out. Specifically, we compared the residual pattern of activity in hMT+ with (i) LGN, (ii) ventral pulvinar, (iii) SC, and (iv) hMT+ in the opposite (undamaged) hemisphere, using subject-specific regions of interest (ROIs) (S3 Fig). We also performed whole-brain analyses to measure the voxels where neural activity most closely matched the time series of hMT+ and these subcortical structures. LGN–V1 correlation in the nondamaged hemisphere (Fig 2A) was similar across all participant groups (F = 1. 0, p = 0. 4, df = 2). Bilateral hMT+ correlation was also very similar across all groups, indicative of preserved functional connection between hMT+ in patients irrespective of blindsight status (Fig 2B, F = 1. 9, p = 0. 2, df = 2). There was a significant effect of participant group on LGN–hMT+ correlation (Fig 3A, F = 10. 1, p = 0. 001, df = 2). Pairwise analysis for the damaged hemisphere showed that blindsight-negative patients had a significantly lower mean correlation coefficient compared to blindsight-positive patients (−0. 03 ± 0. 08 SE versus 0. 25 ±0. 03 SE, t = 3. 6, p = 0. 003, df = 12) and remained at zero. In contrast, functional connectivity between hMT+ and ventral pulvinar (Fig 3B) or hMT+ and SC (Fig 3C) showed no effect of group (F = 0. 5, p = 0. 6, df = 2, for both ROIs) and no difference between blindsight-positive and -negative patients in the damaged hemisphere (pulvinar: t = 0. 9, p = 0. 4, SC: t = 0. 5, p = 0. 6, df = 12). Blindsight-negative patients also showed a hemispheric difference for LGN (t = 3. 0, p = 0. 01, df = 10) but not ventral pulvinar connectivity (t = 2. 1, p = 0. 06, df = 10). This suggests that the key difference in functional connectivity between blindsight-positive and -negative patients was the presence of a functional connection between hMT+ and LGN in the damaged hemisphere. We performed an additional analysis without regressing out stimulus-evoked responses and found the same results (one-way ANOVA F = 4. 3, p = 0. 02, df = 2; paired t = 3. 4, p = 0. 005, df = 12), implying that in patients with blindsight this functional connection was also present during visual function. These analyses, however, have not evaluated whether differences in connectivity were specific to our predefined regions of interest or if they reflect a global process independent of the ROIs and our hypothesis. To address this, we performed an additional whole-brain mixed effects analysis measuring the voxels where neural activity most closely matched the time series of LGN, ventral pulvinar, and hMT+. This technique was used to generate seed region correlation maps, in which the ‘seed’ ROI should necessarily demonstrate a high correlation coefficient represented by a beta of 1 [12]. Co-active regions would similarly possess a high beta, with maps retaining a high spatial resolution since every voxel is tested [13]. As expected, group correlation maps showed a high beta in the ‘seed’ regions, reflecting consistency between subject-specific ROIs and their precise transformation to standard space (Fig 4). When LGN was the ‘seed’ region, control participants also demonstrated a relatively high beta in a small region of the calcarine cortex corresponding to retinotopically active V1 (Fig 4Aiv and 4Civ), reflecting the functional geniculostriate pathway. A similar region of calcarine cortex was co-activated in the undamaged hemisphere of patients when the seed was LGN in the same hemisphere (Fig 4Cv and 4Cvi). For LGN in the damaged hemisphere of both patient groups, there was no demonstrable V1 co-activation (Fig 4Av and 4Avi), likely reflecting the damage to that region (and/or its input). In contrast, blindsight-positive patients showed a relatively high beta in hMT+ of the damaged hemisphere compared to other participant groups and a small region of calcarine cortex in the undamaged side (Fig 4Aii). In contrast to the LGN, when ventral pulvinar was used as the ‘seed’, all groups showed robust co-activity in the SC, an area known to share an important connection with the pulvinar [14,15]. There was also notable connectivity with V1 in the undamaged hemisphere (Fig 4D, [16]) but no major connectivity with hMT+ (Fig 4B). When hMT+ was used as the ‘seed region’ (Fig 5), controls demonstrated marked functional connectivity throughout the visual cortex, including hMT+ in the opposite hemisphere and V1 in both hemispheres, consistent with previous reports [17]. In subcortical regions, connectivity was also demonstrable in the LGN bilaterally, albeit to a lesser extent (Fig 5A and 5B, left column). No equivalent connectivity was seen in the ventral pulvinar or SC, although these regions were co-activated in both hemispheres of all three participant groups if a slightly lower beta threshold of 0. 32 was used (rather than 0. 35). This pattern of connectivity was likely to reflect the major visual pathway and its rich network of intra- and interhemispheric connections. A very similar pattern was demonstrated in blindsight-positive patients, except for a relatively low beta in calcarine cortex of the affected hemisphere, reflecting the region of tissue damage. This was less apparent in blindsight-negative patients. Blindsight-negative patients also showed relatively poor connectivity with LGN, particularly in the damaged hemisphere, where ipsilateral geniculate co-activity was not demonstrable even when a low threshold was applied (beta > 0. 2). Of the eight blindsight-positive patients, only half could discriminate direction of motion above chance. We were interested in whether this subgroup showed greater BOLD activity and/or connectivity compared to blindsight-positive patients who were unable to discriminate motion direction. Indeed, these four patients did show slightly stronger motion responses in hMT+ (0. 3 ± SE 0. 13 versus 0. 1 ± 0. 07, t = 1. 6, p = 0. 2, df = 6), as well as slightly greater LGN/hMT+ functional connectivity (0. 27 ± 0. 05 versus 0. 22 ± SE 0. 06, t = 0. 6, p = 0. 5, df = 6), although the differences were relatively small and nonsignificant. To investigate the behavioural–neuroimaging association further, we performed a correlation analysis between mean behavioural performance in both experiments and fMRI activity and connectivity across all patients (n = 14). hMT+ motion responses showed a weak but positive correlation with behavioural performance (r = 0. 38, p = 0. 18), as did LGN–hMT+ connectivity (r = 0. 38, p = 0. 18). There was also a positive but weaker correlation between behavioural performance and pulvinar–hMT+ (r = 0. 29, p = 0. 31) or SC–hMT+ connectivity (r = 0. 21, p = 0. 47). More notable was a significant correlation between behavioural performance and the ratio of blind to sighted fMRI responses in hMT+ (r = 0. 62, p = 0. 018). In other words, patients with the strongest hMT+ activity for motion in the blind field relative to their sighted field performed best at behavioural assessments of blindsight using the same visual stimuli. In order to determine the extent to which blindsight performance and the underlying neural mechanisms relate to the size of the lesions, we quantified the damage in each patient. Lesion size did not differ significantly between blindsight-positive and -negative groups (t = 1. 5; df = 12; p = 0. 16), although blindsight patients on average had smaller lesions (13,693 mm3 ± 1,825 mm3 SEM) than those without blindsight (21,212 mm3 ± 5355 mm3 SEM). This is illustrated by the summed lesion masks for each patient group on a standard space template (S2D and S2E Fig) and the individual lesion maps in structural space (S4 Fig). Reflecting the small difference in lesion size between the two patient groups, there was a moderate inverse relationship between lesion size and behavioural performance across both tasks (r = −0. 48; p = 0. 08). However, there was no relationship between lesion size and functional LGN–hMT+ connectivity (r = 0. 21, p = 0. 5), or hMT+ signal change (r = −0. 24, p = 0. 4). Thus, lesion size did not appear to be a critical factor in determining neural response. Aside from lesion size, the degree to which lesions involve hMT+ and its innervating connections would also be critically important. Lesion maps (S4 Fig) suggest that the lesion of one blindsight-negative patient (P12) did encroach upon hMT+, while it appeared intact in the other five blindsight-negative patients, including its afferent white matter. P1 also had a large lesion extending to the posteromedial border of hMT+; however, this should not have impacted upon the subcortical or interhemispheric white matter connections (see S4 Fig for map). Accordingly, we quantified lesion involvement of hMT+ and its surrounding white matter in each patient (S5 Fig). We found no difference when comparing blindsight-positive and -negative patients (t = 1. 7, p = 0. 11, df = 12), and hMT+ lesion size showed no association with LGN–hMT+ functional connectivity (t = 1. 6, p = 0. 13, df = 13), hMT+ activity (t = 1. 4, p = 0. 19, df = 13), or behavioural performance (t = 1. 6, p = 0. 13, df = 13) in paired t tests using lesion size as the dependent variable. When recruiting a relatively large group of patients, it is challenging to ensure a completely homogenous lesion pattern. However, any specific differences in lesion size or extent can be informative. P12, whose lesion may have encroached on hMT+, demonstrated weak functional connectivity (outside one SD of the mean) in all three subcortical pathways (pulvinar–hMT+: r = 0. 004, SC–hMT+: r = −0. 13) and between hMT+ bilaterally (r = 0. 33), and this contributed to slightly lower averages for pulvinar, collicular, and interhemispheric (but not LGN) connectivity in blindsight-negative patients (see Fig 2B and Fig 3B and 3C). The variability amongst naturally occurring human V1 lesions has been highlighted as a limitation of human research compared to nonhuman primates [18]. It certainly emphasizes the limitations in carrying out individual case studies, which have predominated in the blindsight literature over the last several decades. However, the heterogeneity in the precise location of structural damage can also be extremely useful and has permitted patients to be classified according to their distinct residual visual performance. By determining which connections and characteristic fMRI responses are consistent amongst blindsight-positive and -negative patients, it may be possible to identify which underlying structures and pathways are involved. To summarise our results, blindsight-positive patients showed (i) significant neural activity in hMT+ to motion stimuli in the ‘blind’ visual field, (ii) a relatively preserved response to speed in hMT+, and (iii) a correlation between resting BOLD signal in LGN and hMT+ in the damaged hemisphere. None of these findings were demonstrable in patients without blindsight. However, blindsight-negative patients did show functional connectivity between hMT+ and (i) SC and (ii) ventral pulvinar that was no different to healthy controls or patients with blindsight, suggesting that the LGN has a specific functional role in blindsight. In summary, we identified a functional connection between LGN and hMT+ in patients with blindsight that was absent in patients without blindsight, despite a retained functional connection with ventral pulvinar and SC. This supports a critical functional role for the LGN in human blindsight, and in particular its connection with hMT+, reinforced by recent evidence for an intact anatomical connection between these structures [3]. Our results also revealed that hMT+ does not require intact V1 for a normal speed response, although it does require a functional connection with the LGN. This suggests that the LGN may support motion-selective input to hMT+ in the absence of V1. These results focus on behavioural and neural responses to visual motion, which is a critical component of blindsight (see [66] for recent review). In future work, it will be necessary to explore how such pathways interact with other aspects of blindsight function and whether distinct tasks or stimuli might engage separate mechanisms in the absence of V1. Fourteen patients with adult-onset unilateral V1 damage took part in this study (see S1 Table for details). The location of any additional non-V1 damage is shown in S2D and S2E Fig, and S4 Fig. No patients sustained damage to subcortical structures, including the LGN and pulvinar. Average age at the time of participation was 55. 6 years ± 15. 2 SD; average time after pathology onset was 49 months (6–252 months). Eight age-matched, healthy participants (50. 1 ± 14. 6 SD years) served as controls. Written informed consent was obtained from all participants, and ethical approval was provided by the Oxford Research Ethics Committee (Ref B08/H0605/156). All experiments adhered to the Declaration of Helsinki. Visual stimuli were generated using MATLAB (Mathworks) and the Psychophysics Toolbox [67,68]. Each dot was 0. 075° in diameter and had an infinite lifetime, with an average dot density of 8 dots/°2. Visual stimuli consisted of an aperture of 5° or 8° diameter containing static or coherently moving black dots (luminance 0. 5 cd/m-2) at 4,8, 20, or 32°/s on a uniform grey background of luminance 50 cd/m-2. Stimuli were positioned inside a region of dense visual field loss in patients a minimum of 2. 5° from fixation (S6 Fig). The extent to which stimuli covered the scotoma (as a percentage) was estimated for each patient from the Perimetry Visual Field Index (VFI), provided in S6 Fig. Stimulus size and position was matched as closely as possible in eight age-matched controls (S2A Fig), with no significant difference in distance between fixation and stimulus edge (x or y coordinates) when comparing patients to controls (mean x = 3. 6 ± 0. 30 SE patients versus 3. 8 ± 0. 4 SE controls, t = 0. 4, p = 0. 7, df = 20; mean y = 0. 65 ± 0. 66 SE patients versus 0. 49 ± 0. 68 SE controls, t = 0. 2, p = 0. 9, df = 20). Stimuli in blindsight-negative patients were also no deeper into the visual field than blindsight-positive patients (stimulus edge 4. 0° ± SD 0. 9 in blindsight-positive versus 3. 5° ± SD 1. 2 in blindsight-negative patients, t = 0. 9, p = 0. 4, df = 12). To select the stimulus location in patients, we required a perimetry threshold p < 0. 005 or < −20dB (which ever was more stringent) for pattern deviation compared to age-matched controls at the stimulus location. This meant that the patients in our study were unable to see even the brightest unattenuated stimuli at that location in the visual field. To verify that we had not inadvertently chosen locations in blindsight-positive patients that were more sensitive than those in blindsight-negative patients, we calculated the average pattern deviation by taking the value closest to the stimulated location using Humphrey Perimetry. The residual visual sensitivity was no different in the two groups (−32. 8dB ± SE 0. 8 blindsight positive versus −33. 2dB ± SE 0. 9 blindsight negative, t = 0. 3, p = 0. 8, df = 12). Outside the scanner, two behavioural experiments were performed: (1) 2AFC temporal detection and (2) 2AFC direction discrimination (S1 Fig). The experiments were conducted on the same day as scanning, using a 60-Hz CRT monitor at a viewing distance of 68 cm. Throughout behavioural experiments, participants were asked to maintain fixation, with the investigator observing this in real time using an Eyelink 1000 Eye Tracker (SR Research Limited, Ontario, Canada). Anyone making even a small eye movement into their damaged hemifield was given specific instruction not to do so, and it was explained that these data would have to be discarded. At the start of the experiment, an identical, static test stimulus was used to confirm that patients were unable to see the stimulus at its selected size and location in the visual field. This was done using a predicted aperture size and locus based upon prior perimetry results. Stimulus location had to be restricted to the boundary of the fMRI display, which subtended 23° horizontally and 13° vertically. This influenced whether a 5° or 8° diameter stimulus was chosen, as the stimulus had to stay inside the ‘blind’ field while remaining on screen. The stimulus of choice was an 8° diameter aperture, but if this was not possible, the stimulus was reduced to 5° diameter. If the criteria were unachievable using either stimulus size, the patient was excluded from the study. If the patient was able to see any part of the test stimulus whilst fixating on the central cross, the aperture was repositioned 0. 5° deeper into the scotoma (according to the Perimetry report) until the patient could no longer see any part of the stimulus at all. Any trials with eye position more than 1° from fixation were excluded from analysis. The presence or absence of residual visual function (blindsight) was determined according to patients’ ability to detect stimuli above chance, i. e., Experiment 1. Specifically, this was defined as achieving either an average score or a score for individual conditions that was significantly above chance, using a statistical threshold of p < 0. 05 and a cumulative binomial distribution. This was an identical method to our previous work, except that the stimulus was moving dots rather than a drifting Gabor [33]. We selected stimulus location based upon perimetry results, as detailed above. Necessarily, this meant that all patients showed the same abnormal visual performance for their test locations. Aside from demonstrating the same visual sensitivity on perimetry, stimuli in blindsight-negative patients were no deeper into the visual field than they were for blindsight-positive patients, suggesting this was not a critical factor for the difference in behavioural performance. Previous blindsight studies have employed a variety of visual stimuli (moving dots, gratings, moving bars, high luminance targets [31,37,63,69]) and a number of different techniques for assessment, including 2AFC, indirect behavioural performance, saccadic eye movements, and navigational performance (e. g., [5,70–72]). It is also common to target only one retinal location in blindsight testing [31,37,63,69,70]. The critical point for the definition of blindsight is that patients show significant performance despite absent visual capacity in the targeted region of the visual field. We ensured that a conservative threshold was used to target truly ‘blind’ regions of scotoma, which we demonstrated to be no different in patients with or without blindsight. Since we were particularly interested in the role of hMT+, we assessed whether a moving stimulus could be detected without awareness for our definition of blindsight. Using these criteria, eight patients were categorized as ‘blindsight positive’, as they could detect the stimulus inside their blind hemifield significantly above chance (P2, P3, P5, P8, P10, P11, P13, P14). Of these individuals, four could also discriminate motion direction above chance (Experiment 2; P5, P8, P10, P14). With regard to subjective awareness, only two patients reported any awareness of the stimuli during the experiment (P3 and P10). Both had been completely unaware of static dots in the pre-experiment assessment, in which static dots were positioned at the same coordinates, without fast onset/offset. For moving stimuli, P10 reported knowing that something was there, but was unable to distinguish what it was. P3 also could not describe what she saw, suggesting she had been looking at ‘streaks or shadows’. Both patients were at ceiling on the detection task, but P3 remained at chance on the direction discrimination task. Of note, five of the patients (P3, P8, P10, P11, P13) took part in a previous fMRI study [33], in which they also demonstrated significant blindsight performance for detection of a drifting Gabor. Eye movements were defined as a change in fixation towards the scotoma of 1 degree or more. This would capture all eye movements irrespective of their type, i. e., saccadic, slow drift, nystagmus. The threshold of 1 degree ensured that stimuli could never be directly fixated but would always remain inside the scotoma. Although microsaccades were possible, these would not bring the visual stimulus into the seeing portion of the visual field. This methodology was the same as previous work (Fig 2B in [33]), in which we also provided examples of successfully identified saccades. Seven trials were removed from analysis in Experiment 1 and 2 trials from Experiment 2 due to eye movements of more than 1 degree towards the stimulus calculated from retrospective eye tracker data analysis. At the time of the experiment, a further 6 trials were flagged for exclusion in Experiment 1 and 4 in Experiment 2 due to real-time observation of the experimenter or feedback from the patient. In total, this accounted for 0. 93% of trials in Experiment 1 and 0. 54% of trials in Experiment 2 that were excluded from analysis due to inappropriate eye position. The same stimuli were viewed during fMRI, presented separately to each hemifield. Stimuli during scanning were presented on a 1,280 × 1,040 resolution monitor at the back of the MRI scanner bore. Participants viewed stimuli via a double mirror mounted on the head coil. When in position, the screen subtended a visual angle of 23° × 13°. The same 5 speed levels were presented separately to each hemifield, representing a 10-condition block design (S2B Fig). For each block, the aperture of moving or stationary black dots appeared for 16 s. Direction coherence was 100%, and dots moved at a constant speed. Angle of drift changed at random every two seconds from a choice of 8 directions. A 10-s rest period followed each block. Throughout all experiments, participants performed a task to maintain fixation by pressing a button every time a central fixation cross changed colour from black to red (S2B Fig). Colour changes occurred at random, lasting 300 ms in duration, and participants were instructed at the start to try not to miss any red crosses. It was emphasised that they must try to maintain fixation throughout and avoid moving their eyes around the screen. An EyeLink 1000 eye tracker (SR Research Limited, Ontario, Canada) was again used to confirm central fixation by recording eye position (see section fMRI eye tracking). Scanning took place using a 3T Siemens Verio MRI scanner at the Functional Magnetic Resonance Imaging Centre of the Brain (FMRIB, University of Oxford). At the start of each sequence, magnetisation was allowed to reach a steady state by discarding the first five volumes, an automated feature of the scanner. T2*-weighted EPI volumes covered 34 sequential 3-mm slices (repetition time, TR 2000 ms; echo time, TE 30 ms) with three runs, each lasting 260 s. In a single session lasting 13. 2 min, 396 functional volumes were acquired. For one participant (P4) we collected one additional session of fMRI data. For three patients, we collected four runs of data (i. e., 526 volumes, P1, P2, P3). For one patient (P7) and one control, we only collected two runs of data, i. e., 266 volumes (8. 9 min). We also acquired a high-resolution (1 mm3) whole-head T1-weighted MPRAGE anatomical image (TE 4. 68 ms; TR 2040 ms; flip angle, 8°) and a field map (TE1,5. 19 ms; TE2,7. 65 ms; 2 mm3) for each participant. fMRI preprocessing and statistical analyses were carried out using tools from FMRIB' s Software Library (FSL, www. fmrib. ox. ac. uk/fsl). Non-brain tissue was excluded from analysis using the Brain Extraction Tool (BET) [73], motion correction was carried out using MCFLIRT [74], and images were corrected for distortion using field maps. For cortical ROIs and group contrast maps, spatial smoothing used a Gaussian kernel of FWHM 5 mm, and high-pass temporal filtering (Gaussian-weighted least-squares straight line fitting, with sigma = 13. 0 s) was applied. For all subcortical ROI analyses, no spatial smoothing was applied to ensure that signals were not contaminated with adjacent structures. Functional images were registered to high-resolution structural scans using FLIRT [75] and to a standard Montreal Neurological Institute (MNI) brain template using FLIRT and FNIRT [76]. This enabled us to transform anatomical and probabilistic regions of interest into functional space for analysis (see S3 Fig for an illustration of subcortical ROIs in functional, structural, and standard space for each participant). Eye movements during fMRI can be a legitimate concern when considering results for visual stimulation inside a scotoma. In this study, three main lines of evidence suggest that this was not a problem and could not have accounted for the results. First, concurrent eye movement data was collected on most patients using an eye tracker positioned at the base of the MRI bore (n = 10). All of these patients underwent successful eye-tracker calibration, with accurate data throughout fMRI runs. For this group of patients, the mean number of eye movements was 5. 8 ± 3. 5 SEM, defined as a movement of 1. 5 degrees or more towards the scotoma. This accounted for <0. 3% of the scan duration, suggesting that any effects on the results are likely to be negligible. To confirm this, when scanner volumes corresponding to eye movements were regressed out of analyses, the results remained unchanged (r > 0. 99). For the patients without eye movement data, there had been difficulty either with calibration due to their dense field loss or with visualisation due to the presence of corrective acuity lenses. In those situations, direct visualisation was used via video recording of the pupil to observe any overt eye movements during the experiment. Second, participants performed over 90% on a concurrent behavioural task that required fixation throughout the experiment (S2C Fig). Brief colour changes of the fixation cross (300-ms duration) occurred at frequent and random intervals, and participants were given a window of 1 s to press a button connected to the stimulus computer via a parallel port, being specifically instructed not to miss any red crosses or move their eyes around the screen. In addition, before the fMRI scan, all participants took part in behavioural testing lasting at least 60 min, focussed on their damaged region of vision. Participants became very experienced at maintaining fixation during this assessment. hMT+ masks were derived from probabilistic maps (Jülich atlas implemented in FSL) [77,78]. These were transformed into functional space for patients and controls to ensure consistency between participant groups. V1 masks in controls and in the undamaged hemisphere of patients were functionally defined so that they corresponded to stimulated regions of calcarine cortex. In native space, average hMT+ ROI volume was 94. 8 ± 35. 2 SD voxels in patients and 100. 9 ± 42. 0 SD voxels in controls (t = 0. 5, p = 0. 6, df = 42). Average V1 ROI volume was 16. 2 ± 7. 5 SD voxels in patients (undamaged hemisphere) and 24. 4 ± 7. 1 SD voxels in controls (averaged across hemispheres), the small volume reflective of the small 5°- or 8°-diameter stimulus used. For the LGN and SC, binary masks were created by manual inspection and drawing over the anatomical T1-weighted images [79], using a radiological brain atlas to aid identification of landmarks (See S3 Fig for masks in all patients). The average LGN volume in patients measured 248 mm3 in the right and 246 mm3 in the left. In controls, average LGN volume was 240 mm3 in the right and 239 mm3 in the left. The average SC volume in patients was 195mm3 in the left and 177 mm3 in the right. For the ventral pulvinar, binary masks were created in MNI152 standard space according to the description of Arcaro and colleagues [50]. It was possible to visualise the nucleus as a region of low T1 intensity relative to surrounding tissue in the posterior most part of the thalamus. Masks were transformed to anatomical and functional space for each participant and were manually inspected to ensure accuracy (S3 Fig). Average ventral pulvinar volume was 385 mm3 in the left and 365 mm3 in the right. There were no significant differences in ROI volume between blindsight-positive and -negative patients. Lesion masks were drawn manually in structural space (S4 Fig). For S2D and S2E Fig, these were nonlinearly transformed to standard space and binarised before being summed. To assess whether lesions encroached upon hMT+ and/or its surrounding white matter, we created subject-specific cuboidal ROIs that were centred on the ‘centre of gravity’ of the ipsilesional hMT+ ROI in structural space. The isotropic cubes measured 40 × 40 × 40 mm3, thus containing 64,000 1-mm3 voxels (see S5A and S5B Fig for examples in P6 and P12). We superimposed the binarized lesion mask over the cuboidal mask and counted the number of voxels that overlapped (red voxels in S5B Fig). The voxel counts are shown in the table in S5 Fig. All graphs, signal change calculations, and correlation statistics were calculated using data from participants’ native space. For region of interest analysis, each experimental condition (e. g., left hemifield, 8°/s speed) was entered into the general linear model as a separate explanatory variable and was contrasted against the baseline fixation task to generate contrast of parameter estimates (COPEs) for each condition in every voxel. Signal change was then extracted from regions of interest within functional-space for each individual. The percentage of signal change was calculated by scaling the COPE by the peak-peak height of the regressor and dividing by the mean over time. These measures were averaged across participants to generate group plots for signal change as a function of the condition under investigation and were used in all correlation and regression analyses. For whole-brain group analyses (Figs 4 and 5), it was necessary to align patient brains to a uniform pathological template with lesions located in the same ‘left’ hemisphere corresponding to a ‘right-sided’ visual field deficit. This required that the structural and functional images of three patients (P3, P5, P12) be flipped in the horizontal plane. All activation coordinates and images were in MNI space, with beta values displayed on mean structural images for the group transformed to standard space. For the whole time series analyses, a value for residual BOLD signal in the ROI was obtained for each volume, and this was plotted against time. This was done separately for each participant and performed in functional space. As control participants demonstrated slightly different hMT+ localization in left and right hemispheres, we decided to show hMT+ group maps for left and right V1 lesions separately. This generated a group size of n = 6 for blindsight-positive patients with left V1 lesions (Fig 1Ai), n = 5 for blindsight-negative patients with left V1 lesions (Fig 1Bi), n = 2 for blindsight positive-patients with right V1 lesions (Fig 1Aii), and n = 1 for blindsight-negative patients with a right V1 lesion (Fig 1Bii). Mixed effects analyses were used for all group analyses where n > 3. A statistical threshold of p < 0. 001 uncorrected was used to test for significance within V1 and extrastriate cortex, for which there were a priori hypotheses. Elsewhere, correction for multiple comparisons was made using a cluster threshold of p < 0. 05 unless otherwise stated. Statistical tests to quantify differences in functional activity and co-activation between ROIs or participant groups were implemented in Excel or MATLAB. For overall hMT+ percent BOLD responses (Fig 1, bar charts), activity was averaged across all five motion speeds (0–32°/s). Two statistical analyses were then performed: (i) mean activity comparing sighted and blind hemifield (and hemisphere) used a paired t test and (ii) mean activity compared to baseline using a one-sample t test versus zero. A two-way ANOVA was also used to assess the effect of participant group and speed on blind hemifield responses (right hemifield in controls) and separately on sighted hemifield responses (left hemifield in controls). In fMRI time series correlations, it is known that task conditions can influence intrinsic temporal correlations (e. g., see [12,17]). To ensure that correlations only reflected resting block activity, we used the residuals timeseries for ROIs once stimulus responses had been regressed out. This allowed us to determine resting ROI1 versus ROI2 correlation analyses for each participant. For correlation analyses, two main statistical methods were used. For correlations between participant groups, a Pearson correlation coefficient was derived from mean activity in ROI1 versus ROI2 at each level of speed, i. e., n = 5. For correlations between ROIs within participant groups, a Pearson correlation coefficient was determined separately for each participant (activity in ROI1 versus ROI2, at each level of speed). We then calculated weighted averages of r coefficients for the group, using a Fischer transformation to approximate correlations to a normally distributed measure (Figs 2 and 3). A significant effect of group was determined by performing a one-way ANOVA. Pairwise comparisons between participant groups or ROIs were then calculated using post-hoc t tests. One-sample t tests were used to compare r coefficients to zero. Whenever activity was compared in the same participant, a paired correlation analysis was performed. For each participant, the raw signal time series for the seed ROI was entered into the model as an explanatory variable. This was applied to the filtered and motion corrected whole brain timecourse. Stimulus conditions were also entered as regressors so that the model would better describe the data. Since the model was identical to the ROI time series, the parameter estimate was always 1 in the seed region. Any participant with voxels outside the seed region with a parameter estimate >1. 5 were excluded from analysis, as these results were likely to be driven by noise. This was only a problem when using subcortical structures as seeds, as these are small regions with relatively weak signal that are more susceptible to artefact. This led to the exclusion of three participants from subcortical seed analyses (both hemispheres); two were blindsight positive (P5, P10), and one was blindsight negative (P7). Corroborating this, the raw LGN signal range in those three participants was significantly greater than the other 11 patients (66. 6 ± SD 10. 5 versus 39. 6 ± SD 6. 07, t = 2. 2, p = 0. 04) and controls (30. 6 ± 1. 9, t = 5. 2, p < 0. 001, df = 12). To generate seed region correlation maps (Figs 4 and 5), the COPEs for each included participant were entered into a higher-level mixed effects analysis, and output parameter estimate (beta) maps were used to represent seed region correlation maps. This was performed separately for each participant group and for each seed region. The resulting maps were not intended to determine statistical significance but to allow visual inspection of the results from the separate groups. Visualisation thresholds were based upon control participants, and an optimal cutoff was used to display correlations in either V1, visual subcortex, and/or hMT+ without excess background noise. The same thresholds were applied to all participant groups. For LGN-oriented maps (Fig 5Aiv–5Avi and 5Biv–5Bvi), although not shown, no other subcortical regions showed equivalent beta levels, although ventral pulvinar was co-activated in both hemispheres of all participant groups when using a reduced threshold of 0. 32.

Title: Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar Summary: When the primary visual cortex (V1) is damaged in one hemisphere, we lose the ability to see one half of the world around us. Clinical tests show that in this blind region of vision, we cannot see even the brightest flashes of light. However, many years of research have shown that individuals who are blind in this way may still respond to certain images in the 'blind' area of vision, even though they are often unable to describe what they'see' and may be unaware of seeing anything at all. This is called blindsight, and researchers are trying to understand the pathways underlying this phenomenon. A recent study mapped a physical pathway of connections in the brain that could account for blindsight in humans. However, the functional nature of this pathway has never been shown. In this study, we assess a group of patients with damage to V1, some of whom demonstrate blindsight and some of whom do not. We compare neural responses and functional connectivity and show that a functional connection in this pathway is critical for blindsight. We also reveal new insights into how speed and motion are likely to be processed in the healthy brain.

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Summarize: Actress Jane Seymour Claims Arnold Schwarzenegger Has Two Other Love Children Email This Actress Jane Seymour said she was not at all surprised when news of Arnold Schwarzenegger's Seymour told The former 'Bond' girl also went on say, "From what I gather, I think there will be lots of information coming people's way." And then Seymour dropped the bombshell. "I heard about two more [out of wedlock kids] somebody else knows about. I even met someone who knows him well." Actress Jane Seymour said she was not at all surprised when news of Arnold Schwarzenegger's love child became public and went on to say that she was aware of more children that the former California governor had outside of his 25 year marriage.Seymour told CNN that she wasn't even surprised when she heard the news of Schwarzenegger and Maria Shriver's separation. "I was not even remotely surprised. The moment I heard it, that there was an announcement of their separation -- he was obviously jumping the gun before everyone else told the world of the news."The former 'Bond' girl also went on say, "From what I gather, I think there will be lots of information coming people's way."And then Seymour dropped the bombshell. "I heard about two more [out of wedlock kids] somebody else knows about. I even met someone who knows him well." http://xml.channel.aol.com/xmlpublisher/fetch.v2.xml?option=expand_relative_urls&dataUrlNodes=uiConfig,feedConfig,entry&id=691977&pid=691976&uts=1273167996 http://www.popeater.com/mm_track/popeater/music/?s_channel=us.musicpop&s_account=aolpopeater,aolsvc&omni=1&ke=1 http://cdn.channel.aol.com/cs_feed_v1_6/csfeedwrapper.swf PopScene: Week's Hottest Pics Gabourey Sidibe attends The American Cancer Society's Choose You luncheon on May 5th in New York City. Amy Sussman, Getty Images Amy Sussman, Getty Images PopScene: Weeks Hottest Pics The 'Dr Quinn, Medicine Woman' actress does reveal who she feels for the most during this time of crisis for the Schwarzenegger and Shriver. "I feel sorry for the kids."Seymour is not the only one who has an opinion of Schwarzenegger's affair and love child; former governor of Alaska Sarah Palin also spoke on the affair "I feel so bad for his children," she said. "It must be quite embarrassing for them....You know, it's an irresponsible and, really, a pretty disgusting thing that he did, pretty much denying that he had a child for ten years."She added, "That's how I look at it. It speaks to his character. It's sad." No one in'sfamily was surprised when they found out she was the mother of's love child... because, well, she liked the fellas.Sources very close to Baena tell TMZ... she was extremely aggressive when it came to chasing men -- like a heat-seeking missile. They say her flirting was often "inappropriate," but her tactics frequently worked -- at least short-term.Our sources says Baena almost always made the first move -- going after whomever she wanted -- and Arnold was no different.We're told when news of Arnold's affair with a household staff member broke, but before the baby mama was named, Baena's friends and family knew it was her.

Summary: Arnold Schwarzenneger could find himself facing one of the costliest divorces in Hollywood history, if he and Maria Shriver do decide to "terminate" their marriage. The New York Post reports that the couple's worth is somewhere between $200 million and $400 million, which means Shriver could stand to walk away with more than $100 million. Though they likely have a prenup, it could easily be tossed due to Schwarzenegger's cheating, meaning Shriver and Schwarzenegger would split their assets evenly. Meanwhile, TMZ digs up more dirt on Mildred Patricia Baena, the former household staffer who bore Arnie's love child. The gossip site calls her a "maneater" who liked to chase the fellas, as well as a "self-hating woman" who "trash-talked Hispanics" and would often tell her fellow staff members that, as a source recalls, "white people were better."

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Summarize: BACKGROUND OF THE INVENTION The present invention relates to devices for providing an electrical interface between a patient and an electrical physiological monitoring, sensing or measuring equipment. More particularly, the present invention relates to apparatus capable of effecting a temporary electrical interconnection between the skin surface of a patient and the input connection for electrical medical data acquisition equipment and is particularly useful in establishing a secure but adaptably flexible electrical interface between a selected area of the skin and the input for electrical physiological measuring, sensing or detecting systems such as electrocardiograms and other electrical monitoring systems of the type which require a low, constant resistance interconnection with a patient. A variety of devices have been developed in the past for acquiring medical data on a patient from electrical parameters associated with the patient. Some devices sense the electrical conductivity within the patient while others measure various other parameters including internal resistance and the like. Such medical electrical measurement or testing systems are necessarily sensitive because of the low levels of electrical activity involved and require relatively constant and low resistance interfacing with the skin of the patient. It was early recognized that merely strapping an electrical connector to the skin of a patient would produce an unpredictable interface resistance thus discounting the measurement acquired. An early practice has been to specially treat the skin area of the patient so as to reduce the electrical resistance at the surface and to include a conductive gel between the electrode and the skin of the patient to further reduce the interface resistance. Thus a variety of devices have been developed for the purpose of combining the adhering functions and the conductive gel retaining functions in a common housing. For instance, Phipps et al No. 3,170,459 shows an electrode combination formed of a plurality of bonded insulator layers with an electrode connector button exposed to a cavity in which gel can be inserted. Similar unitary electrode connector assemblies have been shown in Mason U.S. Pat. No. 3,518,984, Yuan U.S. Pat. No. 3,572,323 and Weyer U.S. Pat. No. 3,845,757. An electrode with a snap-on connector and an oversized conductive gel retaining disc for filling the cavity under the connector in response to attachment compression is shown in U.S. Pat. No. 3,882,853 by Gofman et al. However, the aforementioned prior art connectors are difficult to recharge or clean and sterilize for reuse particularly where an internal cavity is incorporated. Ultrasonic cleaning of the gel cavity type electrode is reasonably satisfactory but necessarily delays availability of the electrodes for further use. One approach that has been suggested for avoiding delays in electrode availability is to use disposable electrodes such as in Sessions U.S. Pat. No. 3,805,769 wherein a bonded disc arrangement with a snap-type of connector is formed as a unit and thrown away after utilization. However, it is important that the connector button for the electrode exhibit high quality electrical interfacing characteristics, silver and silver chloride combinations being particularly attractive in this regard. Thus the use of such materials for the electrode is prohibitively expensive for inclusion in a disposable application. Furthermore, although many of the prior art interfacing electrode assemblies are reasonably satisfactory for static measurement, it is frequently important that the electrical measurements be continuously maintained even during relatively violent physical activity in order to acquire meaningful data on the patient. Security of the interface connection under such conditions is vital since a loose connection will result in noisy readings and useless data. Beyond this, there is a need for an electrical interfacing apparatus which can remain attached to a bed-ridden patient for continuous monitoring of vital functions and the like. Therefore, there has been a continuing need for an electrical interfacing arrangement between a patient and medical sensing or monitoring apparatus which establishes a reliably secure attachment while accommodating movement of the patient without detracting from the constant, minimal resistance at the interface. Furthermore, there is a continuous need for an interfacing arrangement which permits retention of the more expensive electrode so that it can be quickly and effectively prepared for further use while allowing disposal of the less expensive conductive gel. Summary of the Invention The present invention resides in an electrode and interfacing pad arrangement which defines an electrical interconnection between a patient and electrical medical measurement or sensing equipment so as to accommodate flexing movement of the patient and minimizes potential loose connections or unintended removal. The electrode assembly in accordance with the present invention is formed of a flexible housing of insulating material which has a flat surface removably securing to the patient. An electrical conductor, pellet or button is embedded within the insulator housing so that a surface thereof is externally exposed through the housing as part of the interior portion of the housing flat surface that is attached to the patient. A suitable conductive lead is then arranged to provide electrical communication between the conductor button and the other electrical medical equipment by extension through yet another surface of the housing. The electrical interfacing in accordance with this invention is completed by a disposable pad assembly which has a base frame of a flexible, closed cell material with this base frame being formed of relatively thin configuration with opposite flat surfaces. A bore extends through the pad assembly, and an adhesive on one side surrounds the bore and is arranged in conformity with the configuration of the electrode flat surface for retaining it in proximity to the base frame so that the electrical conductor overlays the pad bore. A second adhesive surface substantially covers all of the opposite base frame surface around the bore so as to retain the base frame to the patient. The base frame bore is filled with an electrically conductive gelatin so as to complete a relatively constant, low resistance electrical circuit between the area of the patient beneath the bore and the electrical conductor surface. By this configuration, the electrode can be easily cleaned such as by wiping with alcohol, since all of the surfaces thereof are substantially flat and the pads thrown away and replaced after use. The disposable interfacing pad can be formed in a triangular configuration to optimize the number of electrodes which can be placed on a given skin surface area of the patient. Further, the electrode can be configured of a relatively low, rounded edge profile with a smaller outer perimeter than the outer perimeter of the pad, thus further reducing the prospect of accidental removal or loosening of the electrode such as by movement of an active patient or a bed-ridden patient. The gel can be retained within the pad by means of an open-celled carrier or retained between thin gel permeable discs such as of felt or the like. Still further, the triangular configuration of the pad permits optimization of packaging in protective cartridges for storage and transportation prior to use. An object of the present invention is to provide a novel and improved electrical interface between a patient and electrical medical equipment. Another object of the present invention is to provide a novel and improved reliably secure electrical interface between a patient and medical equipment with relatively constant, low electrical resistance. Yet another object of this invention is to provide a highly flexible electrical interface between a patient and electrical medical equipment which can accommodate movement of the patient without significant variations in the interface resistance or prospects of unintended loosening or detachment of the electrode. A further object of the present invention is to provide an electrical interface between the patient and electrical medical equipment which permits disposal of the low cost conductive gel retaining portion and retention of the more expensive electrode in a manner which permits rapid sterilization of the electrode for reuse. The foregoing and other objects, features and advantages of the present invention will be more apparent in view of the following detailed description of exemplary preferred embodiments. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of an electrode and an interfacing pad assembly in accordance with the present invention. FIG. 2 is a bottom plan view of the electrode assembly of FIG. 1. FIG. 3 is a section view of the interfacing pad of FIG. 1. FIG. 4 is a top plan view of the interfacing pad of FIGS. 1 and 3. FIG. 5 is a side partially sectioned view of an attached electrode and interfacing pad arrangement. FIG. 6 is a side section view of an alternate arrangement of the interfacing pad structure. FIG. 7 is a top view of a storage tray adapted for retention of a plurality of the interfacing pads; and FIG. 8 is a section view taken along lines 8--8 of FIG. 7. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 shows a perspective view of a relatively permanent electrode assembly 10 and disposable interfacing pad 11 as it would be positioned immediately prior to attachment to a patient. Essentially, electrode housing 10 is a relatively permanent structure which is reusable whereas interfacing pad 11 is typically discarded after use. A sectioned view of the complete attachment of both assemblies to a patient is shown in FIG. 5. Electrode assembly 10 includes a circular disc-like main frame or housing 15 which is formed in a thin, flexible configuration but which has embedded therein a button-like electrical conductor or pellet 16 which forms the interior portion of the lower flat surface of housing 15. That is, housing 15 is typically formed of a rubber or rubber-like material, a flexible plastic such as a urethane polymer, or the like. The conductor 16 is formed of materials which (1) have good electrical conductivity characteristics, (2) have relatively low constant electrical resistance at the interfacing surface, and (3) are relatively inert chemically to the interface environment. In this regard, satisfactory results are obtained by fabricating conductor 16 as a silver/silver chloride composition pellet, such as, sintered silver/silver chloride or a silver central portion plated with a foil of silver chloride or the like. A conductor wire 18 is bonded as by welding, soldering, metalized epoxy bonding or the like to the interior surface of pellet 16 and passes through an external lead 19 to a conventional probe 20 for attachment to electrical medical measuring or sensing equipment [not shown]. Note that wire 18 can be compressively bonded into pellet 16 when it is formed if separate bonding is not desired. A stress relief coil 22 can be included at the leading edge of conductor wire 19 and partially embedded in housing 15. FIG. 2 shows a bottom plan view of the electrode assembly 10. In FIG. 2, it can be seen that the lower surface 17 of pellet 16 forms the interior portion of the bottom flat surface of housing 15 and is flush mounted with that surface. Accordingly, the entire electrode assembly 10 can be quickly cleaned and sterilized immediately subsequent to use, such as, by an alcohol cleaning process and is therefore almost immediately available for repeated usage. The disposable interfacing pad assembly 11 of the FIG. 1 embodiment is illustrated in the section view of FIG. 3 taken along lines 3--3 of FIG. 1. This pad includes a triangularly shaped base frame 24 which is preferably of a closed cell, highly flexible foam material. Typically, base frame 24 will be between 1/16 and 1/8 inches thick. One material found to be particularly suitable for base frame 24 is Volara polyethylene available from the Voltek Corporation rated at 4 pounds per cubic foot, 60 pores per inch which molds into a skinned (i.e. high density, glossy surface) closed cell, moisture resistant form in use. However, polyurethane has also been found to be generally acceptable as would be any material which results in a thin, flexible, chemically inert and closed cell structure. Preferably, the outer triangular perimeter of base frame 24 is formed in an equilateral triangle of about 1.5 to 2.5 inches on each side with rounded corners as shown. This configuration permits maximum placement of electrodes within a minimal area on a patient while still retaining the security of attachment. The base frame 24 has a central bore 25 therethrough which is typically on the order of 0.50 to 0.75 inches in diameter and has an adhesive disc 26 which has double adhesive surfaces thereon attached to the upper side of base frame 24. The outer perimeter of disc 26 conforms with the outer perimeter of electrode housing 15 so as to provide a substantial adhering surface therebetween. Still further, the interior of double adhesive disc 26 has a hole 28 therethrough which is smaller than the bore 25 and slightly smaller than the gel carrier 30. Gel carrier 30 is preferably formed of an open cell plastic foam and typically saturated with conventional conductive gel such as a sodium chloride based electrolyte, commercially available such gels being the pastes or creams offered under tradenames of &#34;EKG-Sol,&#34; &#34;Redux,&#34; &#34;GE Jel,&#34; and the like. However, carrier 30 is thicker than base frame 24 (up to twice the thickness of frame 24 having been found to be satisfactory) but of slightly narrower width than bore 25 as illustrated in FIG. 3. This is particularly evident in the top view of assembly 11 as presented in FIG. 4. Accordingly, double adhesive sided disc 26 provides the concurrent functions of retaining conductive gel carrier 30 in place relative to base frame 24 while further permitting passage of carrier 30 through opening 28 thereof to surface 17 of conductor pellet 16. Further, the entire lower surface 31 of base frame 24 has an adhesive coating thereon for attachment to the patient. The various adhesive surfaces mentioned are composed of suitable conventional materials, examples being non-toxic pressure sensitive coatings of a resin solution of a low molecular weight acrylic polymer, hypoallergenic acrylate based adhesives, etc. The complete attachment of electrode assembly 10 and interfacing pad assembly 11 to the surface area 32 of a patient is shown in the partially sectioned view of FIG. 5. By dimensioning the gel carrier 30 so that it is thicker than base frame 24 but of a smaller diameter than bore 25 through base frame 24, the attachment of both assemblies to the patient and each other via the adhesive interfaces of disc 26 and surface 31 compresses pad 30 so as to fill the cavity of bore 25 shown in FIG. 5 and further force the upper surface of carrier 30 against the lower surface 17 of pellet 16 so as to insure a constant, low resistance interface between skin surface 32 and electrical conductor pellet 16. This arrangement further minimizes any deterioration of the adhesive security between the elements since any gel oozing is substantially prevented. Still further, by dimensioning double adhesive disc 26 and housing 15 to be in the range of 1.0 to 1.25 inches in diameter, the outer edges of housing 15 will be inwardly displaced from the outer perimeter edges of triangular base frame 24 thus forming an overall concave configuration which will minimize the prospect of unintended removal or loosening of the completed assembly from the patient. By maintaining base frame 24 and housing 15 with minimal thicknesses wherever possible, the entire assembly is sufficiently flexible to conform to movement of the skin surface area 32 without loss of adhesion or any substantial variation in the resistance at this interface. The triangular pad 24 is preferably of a closed cell urethane plastic or foam whereas the gel carrier 30 is an open cell urethane foam. The electrode 16 is preferably sintered or compressed silver/silver chloride or a silver chloride coated or thin plated silver conductor of about 0.050 inch thickness. A prospective alternate arrangement for the disposable interfacing pad is shown in FIG. 6. As with FIGS. 3 and 4, the base frame 34 is preferably triangular shaped and has an adhesive coating 35 on the lower side thereof and a disc 36 on the upper surface which is adhesively coated on both sides. However, the conductive gelatin 38 is retained between two separate gel saturable pads 40 and 42 so that the central bore through disc 36 is greater than the central bore through base frame 34. For instance, if bore or cavity 38 has a 0.5 inch diameter, pads 40 and 42 are typically of 9/16 inch diameter. The inner area or chamber 38 can be completely gelatin filled or can be filled with an open celled carrier similar to that mentioned previously except closely conforming to or slightly greater than the dimensions of the central bore through base frame 34. Pads 40 and 42 are of felt, loosely woven material or the like. FIGS. 7 and 8 illustrate a storage and shipment tray 45 which has a substantially flat plate 46 from which depends a plurality of triangularly shaped depressions or cells 47-49. These cells each contain one triangular interfacing pad such as 51-53. The section view of FIG. 8 which is taken along lines 8--8 of FIG. 7 illustrates a typical cross-section of a retaining cell such as cell 48. A thin protective foil 54 is placed over the entire tray. Each cell includes a lower depression or well area 55 to accommodate the central gel carrier 58 so that it is clear of the sidewalls of tray 45 and also clear of the protective foil 54. The disposable pad 52 can be adhered to the walls of cell 48 via adhesive layer 56 which can be the same as the lower adhesive layers 31 described previously for FIGS. 1-5. Thus by fabricating tray 45 from molded, low cost plastics, the disposable pads can be retained in place by their own adhesive surfaces and yet stored so that the gel carriers 58 are not in contact with any surface other than the retaining disc. The protective foil 54 further prevents drying of the gelatin in carrier 58. In fabricating the pad, its triangular shape is preferably an equilateral triangle developed on the perimeter of a 1.5 to 3.0 inch diameter. The gel is conventional and preferably has good hygroscopic characteristics. That is, it typically includes hygroscopic agents for preventing or reducing dry-out. The dry-out of the conductive gel is further reduced by constructing base frame 24 of closed cell materials as mentioned thereby preventing moisture migration from the gel in carrier 30 into the base frame 24. The gel, paste or cream used can also include fungicides and bacteriacides as is known in the art. Typically, skin preparation techniques may be applied prior to attachment of the electrodes as is also known in the art. Note that peelback-type protective strips can be included on one or both of the external adhesive sufaces of the disposable pad if this should be desirable for individual pad storage or storage within a tray as shown in FIGS. 7 and 8. Disc 26 can be fabricated from commercially available double adhesive surfaced strips of about writing paper thickness (about 0.005 inches), one example being the product produced by Remco Tape Products Company of Los Angeles, California which has silicon coated protective paper foils over the adhesive surfaces. Thus disc 26 can be cut from such materials and one protective covering removed for attaching disc 26 to base frame 24 leaving the other protective covering in place for removal immediately prior to use with electrode assembly 10. The lower surface of base frame 24 has adhesive layer 31 applied thereto from any material which is FDA approved for non-toxic, medical applications. These adhesives are typically available from transfer tapes such as part number 1552 produced by the Medical Products Division of Minnesota Mining and Manufacturing Company of St. Paul, Minnesota. A particularly attractive example of materials for carrier 30 is the Scott Industrial Foam rated at 40 pores per inch from the Foam Division of the Scott Paper Company of Chester, Pennsylvania. This is a reticulated polyurethane foam which provides a highly flexible structure with continuous open passageways therethrough as a result of well controlled reticulation and bubble size. The carrier thereby exhibits excellent gel penetration characteristics. In constructing electrode assembly 10, it has been found that treatment of the surface of pellet 16 with a primer and molding of housing 15 of a solid polyurethane results in a rugged, highly flexible structure with excellent adherence between housing 15 and electrical connector pellet 16 despite stretching and flexing of housing 15. This bonding is particularly advantageous in assuring the integrity of assembly 10 for quick cleaning and re-use purposes. It has also been found that forming housing 15 so that it is about 1/16 inch thick at the beginning of the curved edges and tapered upward to about one-eighth inch at the center or around the raised area for accommodating lead 19 and stress relief coil 22, housing 15 will follow the flexing movements of pad assembly 11 without loss of the security of attachment and without resistance modulation at the interface. Although the present invention has been described with particularity relative to the foregoing detailed description of exemplary preferred embodiments, various modifications, additions, changes and applications other than those specifically mentioned herein will be readily apparent to those having normal skill in the art without departing from the spirit of this invention.

Summary: An electrical interconnection is provided between a patient and physiological sensing or monitoring equipment. A permanent electrode is formed with a thin flexible housing which encases an electrical connector such as a pellet or nodule so that a portion of that connector is externally exposed on one surface. A disposable pad formed of a thin flexible base frame has a central bore and a double-faced adhesive disc on one side for attachment of the electrode surface containing the connector and concurrently retaining a conductive gel within the disposable pad for electrical communication with the electrode conductor. The adhesive on the opposite surface of the disposable pad is adapted to secure the pad to a selected area of the skin of the patient.

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Summarize: CLOSE Skip in Skip x Embed x Share Lt. Matt Harris of the Columbus Police Department provided new information about the death of Jackie Watts to reporters Monday afternoon. Justin Mack/IndyStar Animal-lover was found dead amid Flat Rock River. Body of lost dog was found on bank. Buy Photo Lt. Matt Harris of the Columbus Police Department discusses the investigation into the death of Jackie Watts (Photo: Justin L. Mack/IndyStar)Buy Photo COLUMBUS, Ind. — The last time Jackie Watts was seen alive, she had just finished saving some animals and was likely giving her all in an attempt to save one more. Witnesses say that Watts' final moments were spent along the Flatrock River in pursuit of Ringo, a 10-year-old poodle suffering from cataracts who was separated from his family just days earlier, according to police. They say Watts was seen Friday afternoon chasing the small white dog one moment and that she was gone the next. The next time anyone saw Watts or Ringo was when their bodies were discovered over the weekend by investigators from the Columbus Police Department. Watts' autopsy, completed Monday, revealed she accidentally drowned, according to the Bartholomew County Coroner's Office. Watts, a 33-year-old Indianapolis woman known for her selfless nature and love of animals, dedicated her life to helping creatures that could not help themselves. "At a young age, Jackie developed a love for animals. To say that this was Jackie’s passion would be an understatement," John Quick, a Watts family friend, said in a statement on their behalf. "Jackie volunteered with the Kentuckiana Boxer Rescue and Indy Claw Animal Rescue, where she was a member of the board of directors. She also fostered multiple dogs and rabbits. She cared deeply about the well-being of animals. If she believed she could help an animal in need, she was going to do so without hesitation. We know that Jackie gave her life for what she believed in. "As her family, we are eternally gratefully for the time that we had with Jackie. During this difficult time, we find solace in the stories of Jackie’s impact on those that knew her, especially the memories that we have of Jackie as a wife, daughter and sister." The words from Watts' family kicked off a Monday afternoon news conference that also saw Columbus Police Lt. Matt Harris provide a more detailed timeline of events leading up to Watts' death. "She was the kind of person that when there was an animal sick and dying, she would take these animals in... and provide them hospice care," Harris said. "So to hear someone making the statement that she was trying to help a lost dog and, sadly, it appears that she lost her life doing so... it's a big loss." According to Harris, the timeline began around 1:30 p.m. Friday when Watts dropped of a rabbit and two dogs at a home in Columbus. Shortly before 2 p.m., she was seen on a security camera leaving the home and heading toward Washington Street. Around 2 p.m. Friday a witness saw a woman matching Watts' description chasing a small white dog in the area of 23rd and Washington streets, but that tip didn't come in until hours later, police said. Another witness told police that a woman who looked like Watts was seen chasing after a dog in a sweater near Flatrock River. Between 2:15 p.m. and 3 p.m. Friday, an abandoned vehicle was reported on Riverside Drive. Police received another call about a suspicious white sedan around 4:51 p.m. Friday. Friday's timeline ends with a report of a missing person shortly before 5 p.m. Watts' family grew concerned when she didn't make it back from dropping off the animals and contacted the authorities. Officials searched the area around the abandoned car until dark and resumed the search Saturday morning. The ground search continued around 7:45 a.m. Saturday, Harris said. Roughly 15 minutes later, Watts was found on a sandbar in Flatrock River. There were no signs of a struggle and no indication that any foul play was involved in Watts' death. Less than 10 minutes later, police received a tip about the missing dog. On Sunday afternoon, after the waters of Flatrock Rock receded, police returned to the area to continue their investigation. They found Ringo's body shortly after 2 p.m. south of Noblitt Park on the river's east bank. A follow-up conversation with the witness who saw a woman chasing a dog near the river affirmed the earlier report, police said. The witness said the woman was last seen running south toward the low-head dam. Watts' family expressed gratitude in their statement read by Quick, stating that they continue to be overwhelmed by love and support from family, friends and the entire community. "We are deeply moved that so many of you shared in the effort to help our Jackie. We would like to take this opportunity to tell you about the wonderful woman she was," said the family's statement. "In the days following Jacquelyn’s passing, we have learned of many kind acts honoring her memory. It has lifted up our hearts to see that Jackie has touched so many lives." In addition to volunteering at a number of organizations dedicated to the well-being of animals, Watts also served as a teaching assistant at Indianapolis Public Schools and as an events coordinator for Big Brothers Big Sisters of Indianapolis. "And through her vocation as a Esthetician, Jackie saw beauty and value in everyone," said the statement. "She was an inspiration to those that knew her. Always placing others before herself, she lived and loved with great humility." Lt. Harris - "Bottom line, we lost a wonderful person." pic.twitter.com/TBZxCpvAym — Justin L. Mack (@justinlmack) March 6, 2017 Statement from the family of Jackie Watts read by Dr. John Quick pic.twitter.com/8Bdq1qDQCR — Justin L. Mack (@justinlmack) March 6, 2017 The rest of the statement from Watts' family pic.twitter.com/SpSgOUz0MW — Justin L. Mack (@justinlmack) March 6, 2017 Call IndyStar reporter Justin L. Mack at (317) 444-6138. Follow him on Twitter: @justinlmack. Read or Share this story: http://indy.st/2n6fT7U Please enable Javascript to watch this video COLUMBUS, Ind. – Columbus police said during a news conference on Monday they believe Jacquelyn Watts died while trying to help a lost dog near the river. An autopsy of Watts’ body was performed on Monday, and her cause of death was ruled to be an accidental drowning. Police reiterated that no foul play was involved. According to police, Watts went to Columbus to drop off her dogs and a bunny with family on Friday afternoon. Witnesses told police they saw a person matching Watts’ description chasing after a small white dog wearing a sweater near the Flatrock River a short time later. Watts was planning to go out of town on a trip with her husband that evening, and when she didn’t return home, her family reported her missing. Her vehicle was found in the 2300 block of Riverside Drive Friday around 5 p.m. The car was running, the flashers were on, her purse was still inside, and the passenger door was slightly open. Police say there was no sign of a struggle. Investigators searched the area for Watts, but the river was moving at a very swift pace and it made the search difficult. They found Watts’ body on a sandbar in the river on 8:30 a.m. Saturday morning. Also on Saturday, a picture of a missing white dog named Ringo began circulating on social media. Officers say witnesses confirmed it was the same dog Watts was seen chasing near the river. Police think Jackie Watts died while chasing a missing dog "Ringo" near the Flatrock river. pic.twitter.com/duz3Kfd3Oy — Jesse Wells (@JesseWellsNews) March 6, 2017 Ringo's body was later found on a bank on the east side of the river. “The bottom line is we lost a very special person,” Columbus Lt. Matt Harris said. “It’s my understanding that Jackie was the type of person that when there was an animal that was sick, she would take that animal in and provide hospice care. So to hear someone making the statement that she was trying to help a lost dog and sadly appears she lost her life doing so, that doesn’t seem out of character for her.” The Watts family sent this letter to authorities: We would first like to express our deepest gratitude to the public safety agencies that worked tirelessly to find Jackie. Your professionalism and sincere regard for our family will never be forgotten. We continue to be overwhelmed with the outpouring of love and support from family, friends, and members of the community. We are deeply moved that so many of you shared in the effort to help our Jackie. We would like to take this opportunity to tell you about the wonderful woman she was. In the days following Jacquelyn’s passing we have learned of many kind acts honoring her memory. It has lifted up our hearts to see that Jackie has touched so many lives. Jackie’s compassion for others was evident throughout her life. From her work as a teaching assistant in the Indianapolis Public Schools, as Events Coordinator for Big Brothers Big Sisters of Indianapolis, and through her vocation as a Esthetician, Jackie saw beauty and value in everyone. She was an inspiration to those that knew her. Always placing others before herself, she lived and loved with great humility. At a young age, Jackie developed a love for animals. To say that this was Jackie’s passion would be an understatement. Jackie volunteered with the Kentuckiana Boxer Rescue and Indy Claw Animal Rescue where she was a member of the board of directors. She also fostered multiple dogs and rabbits. She cared deeply about the wellbeing of animals. If she believed she could help an animal in need, she was going to do so without hesitation. We know that Jackie gave her life for what she believed in. As her family, we are eternally gratefully for the time that we had with Jackie. During this difficult time, we find solace in the stories of Jackie’s impact on those that knew her, especially the memories that we have of Jackie as a wife, daughter and sister. We will continue to celebrate her life through the memories that she has left in our lives. “Oh that we would all be filled with enough passion to give our lives for what we believe in.” IndyClaw Rescue, where Watts worked for five years, posted this touching message on Facebook:

Summary: Jackie Watts loved animals-and that love may have led to the 33-year-old Indiana woman's death over the weekend. Watts was last seen Friday afternoon near Flat Rock River in Columbus, chasing a small white dog wearing a sweater-Ringo, a 10-year-old poodle with cataracts, who had gotten separated from his owners days prior. Watts' family reported her missing that night after she failed to return home from an errand, and police started searching around her car, which was found apparently abandoned near the river, its flashers on, CBS4 reports. On Saturday morning, Watts' body was found on a sandbar in the river. On Sunday afternoon, Ringo's body was also found on a riverbank, the Indianapolis Star reports. An autopsy revealed Watts' cause of death was accidental drowning, and police found no signs of a struggle or foul play. "At a young age, Jackie developed a love for animals. To say that this was Jackie's passion would be an understatement," says her family in a statement through a family friend, which notes that she volunteered with multiple animal organizations and fostered animals. "She cared deeply about the well-being of animals. If she believed she could help an animal in need, she was going to do so without hesitation. We know that Jackie gave her life for what she believed in." In a moving Facebook tribute to Watts, one of the rescues with which she volunteered said that a sick dog Watts loved had to be put down Saturday: "Jackie will be waiting for Laverne to hug and kiss on her like she did all the bunnies and dogs."

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Write a title and summarize: Here, the IPCC is setting the scene: Mitigation must happen and happen fast against a background of fast-rising CO2 emissions. Greenhouse gas releases were higher between 2000 and 2010 than they have ever been in human history, and the global economic crisis produced only a temporary lull in emissions. In addition, about half of all the carbon that humans have pumped into the atmosphere since 1750 has been emitted in the past 40 years. Second, CO2 emissions from fossil fuel combustion and industrial processes contributed about 78% of total greenhouse gas emissions from 1979 to 2010. This brings us to another take-home message of this report - that experts believe there needs to be a huge shift towards clean energy and away from carbon-intensive energy sources if we are to head off the worst effects of global warming. The panel says that, driven by a global increase in population and economic activity, global surface temperature increases will be between 3.7C and 4.8C in 2100 if no new action is taken. Scenarios reaching atmospheric concentration levels of about 450ppm CO2 equivalent by 2100... include substantial cuts in anthropogenic GHG emissions by mid-century through large-scale changes in energy systems and potentially land use The figure of 450 parts per million (ppm) concentration of CO2 in the atmosphere is about the limit we must not exceed in order to keep temperature change under 2C (3.6F) by the end of this century. The 2C target was agreed by the UN as a way of avoiding dangerous changes in the climate. But keeping greenhouse emissions under 450ppm by 2100 will be an uphill struggle. It will involve major changes to the way the world gets its energy - requiring a tripling or quadrupling of the share of low-carbon energy from renewables such as solar and wind, nuclear energy or other less polluting options. It will also necessitate changes in the way we use land, including reforestation - trees absorb CO2 and are therefore a natural "sink" for this greenhouse gas. The message from the IPCC is that despite the scale of the challenge, the changes required are within our grasp and even offer opportunities (renewables could offer energy security, preventing access to fossil fuel supplies being used as a political weapon). If the world does overshoot the 450ppm limit, technologies such as Bio-Energy Carbon Capture and Storage (Beccs) might have to be deployed widely. But the panel indicates which scenario would be preferable, pointing out: "The availability and scale of these and other carbon dioxide removal (CDR) technologies and methods are uncertain," and, it adds "associated with challenges and risks". Since AR4 [the IPCC's previous assessment report in 2007], many RE technologies have demonstrated substantial performance improvements and cost reductions, and a growing number of RE (renewable energy) technologies have achieved a level of maturity to enable deployment at significant scale Some supporters think that perceptions of renewable energy sources are lagging behind the reality, and this report says that while the sector is growing, renewable technologies still need the support of policy makers if their market shares are to increase. There will be a price tag: The economic costs of mitigation vary widely depending on the assumptions used in simulations and the technologies deployed. Scenarios that keep atmospheric concentrations of CO2 under 450ppm by 2100 are associated with losses in global consumption (economic activity) of 1% to 4% in 2030, for example. However, the report warns that if mitigation steps are delayed, or if access to technologies such as Bio-Energy with Carbon Capture and Storage (Beccs) is limited for any reason, the costs of mitigation will increase still further in the medium to long term. And there are likely to be many other benefits from steps to reduce greenhouse gas emissions, in addition to those related to curbing global warming. The benefits include a reduction in air pollution, which causes millions of premature deaths worldwide each year. Another is energy security - clean energy sources can help reduce our dependence on other countries for supplies of gas, for example. The report actually backs the use of gas in the switch to a low-carbon economy. It says that efficient natural gas power generation could act as a "bridge technology", if its use is phased out in the second half of this century. Follow Paul on Twitter.

Title: Climate mitigation report: Key findings Summary: A UN panel has released its much-anticipated report into strategies for curbing global warming. In their "summary for policymakers" members of the Intergovernmental Panel on Climate Change (IPCC) say the world must rapidly move away from carbon-intensive fuels. The BBC News website's science editor Paul Rincon breaks down the key findings. Total anthropogenic GHG (greenhouse gas) emissions have continued to increase over 1970 to 2010 with larger decadal increases toward the end of this period.

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Write a title and summarize: Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains. S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901. Further chromosomal deletions in fliD (CVD 1901D) or flgK (CVD 1901K) were then engineered, resulting in the export of unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined using a novel mouse LD50 model to accommodate the human-host restricted S. Paratyphi A. The immunogenicity of the attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype ATCC 9150. Mucosal (intranasal) immunization of mice with strain CVD 1901 expressing cell-associated flagella conferred superior protection (vaccine efficacy [VE], 90%) against a lethal intraperitoneal challenge, compared with the flagellin monomer-exporting mutants CVD 1901K (30% VE) or CVD 1901D (47% VE). The superior protection induced by CVD 1901 with its cell-attached flagella was associated with an increased IgG2a∶IgG1 ratio of FliC-specific antibodies with enhanced opsonophagocytic capacity. Our results clearly suggest that enhanced anti-FliC antibody-mediated clearance of S. Paratyphi A by phagocytic cells, induced by vaccines expressing cell-associated rather than exported FliC, might be contributing to the vaccine-induced protection from S. Paratyphi A challenge in vivo. We speculate that an excess of IgG1 anti-FliC antibodies induced by the exported FliC may compete with the IgG2a subtype and block binding to specific phagocyte Fc receptors that are critical for clearing an S. Paratyphi A infection. Four human host-restricted Salmonella enterica serovars cause clinically indistinguishable typhoid (Salmonella Typhi) and paratyphoid (S. Paratyphi A, B and [uncommonly] C) fever [1]. Multiply antibiotic resistant S. Paratyphi A have emerged in Asia, accompanied by increased incidences of paratyphoid fever in endemic populations [2], [3] and in travelers [4]. Whereas vaccines exist to prevent typhoid fever, there is no licensed vaccine to prevent S. Paratyphi A disease. Vaccines for preventing typhoid fever include the purified Vi capsular polysaccharide administered parenterally and attenuated Vi-negative strain Ty21a given orally as a live vaccine [5]. Vi conjugated to recombinant exotoxin A of Pseudomonas aeruginosa conferred on Vietnamese children a high level of efficacy in a field trial [6], [7]. Vi-based vaccines cannot protect against paratyphoid disease as S. Paratyphi A does not express Vi. Oral Ty21a confers moderate cross protection against S. Paratyphi B [8] but not S. Paratyphi A [9]. Despite the public health need [4], there have been few reports on modern S. Paratyphi A vaccine development [10], [11]. Attenuated Salmonella strains can be employed as mucosally-delivered vaccines or as “reagent strains” to achieve safe, high-yield production of purified antigens for manufacture of parenteral (conjugate) vaccines. A Salmonella surface antigen that has generated renewed interest in the role that it may play in protection is the flagellum. Flagella mediate intestinal epithelial and macrophage inflammation following infection and contribute to early host innate immune responses against Salmonella [12]. Flagellin (FliC), the monomer of flagellar filaments that induces these effects, is being incorporated into fusion proteins linked to otherwise poorly immunogenic antigens and haptens, providing adjuvant activity to enhance immune responses to those moieties [13]–[15]. The flagellum is a complex motility organelle composed of >20 different proteins that form a basal body, hook, filament and an export system. The major extracellular part of the flagellum comprises ∼20,000 FliC monomers that are exported and assembled at the terminus of a growing filament. Between the hook and filament is a short junction formed by two hook-associated proteins, FlgK and FlgL [16], [17]. S. Typhimurium mutants defective in FlgK or FlgL synthesize FliC monomers that do not polymerize and are released into the culture medium [17]. A capping structure of five FliD molecules at the end of the filament also promotes FliC polymerization [16], [18], [19]. Deletion of fliD in S. Typhimurium incapacitates the ability of transported FliC to polymerize [20], [21]. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains. Mutants were constructed with deletions in fliD or flgK, resulting in export of unpolymerized FliC, without impairing its overall expression. These strains allowed us to investigate whether expression of FliC as cell-attached flagellin filaments versus exported monomers, would influence the immune response or protection elicited by these live vaccines. All animal experiments carried out in this work were approved by the University of Maryland Baltimore Office of Animal Welfare Assurance (OAWA), under approved Animal Use Protocol 0409006. S. Paratyphi A wild-type and mutant strains (Table 1) were propagated on animal product-free LB Lennox medium (Athena ES, Baltimore, MD). Lennox agar plates were prepared by addition of 1. 5% agar (Difco, BD, Franklin Lakes, NJ). Guanine (0. 001% v/v) was added for ΔguaBA mutant strains. Liquid cultures were incubated at 37°C, 250 rpm, at a ratio of 1∶10–1∶20 vol∶vol medium∶flask (high-aeration conditions). For low-aeration growth conditions, the flasks were filled to 75% of their volume with the medium, and shaken at 80 rpm. Time course experiments in liquid culture were seeded with an overnight culture, inoculated to 0. 01 OD600; samples were removed at regular intervals for determining culture turbidity at OD600 or plating. For each growth experiment, two flasks were cultured per strain, and each experiment was performed twice. Swimming and swarming assays were carried out on fresh Lennox plates containing 0. 3% and 0. 5–0. 7% agar, respectively. Glucose was added to a final concentration of 0. 5% for swarm plates. The swim plates were inoculated by stabbing the center with bacteria harvested from 1. 5% Lennox plates. The swarm plates were inoculated by pipetting a 10-µl fresh culture, grown in liquid Lennox media to 0. 5–0. 6 OD600, onto the surface of the center of the agar plate. All motility experiments were performed in triplicates and repeated at least twice. Swim and swarm ability are expressed as the radius of the mobility zone; for no swim, the radius of growth was >1 mm and for no swam, 10 mm. Deletion of fliD and flgK genes was performed by λ Red-mediated mutagenesis [22] essentially as described [23]. Primers (listed in Table 2) were designed to replace most of the gene of interest with a kanamycin resistance cassette flanked by the Flippase Recombination Targets, FRTs. The kanamycin cassette was later deleted via λ Red recombinase, leaving an FRT scar sequence. Bacterial protein samples were normalized as follows. Cell pellets were washed in 0. 125 M Tris-HCl, pH 6. 8, brought to 10 OD600 in the same buffer and diluted 1∶3 with Laemmli sample buffer (Bio-Rad Laboratories, Hercules, CA). Supernatants were brought to the equivalent lowest OD600 culture per experiment, by addition of 0. 125 M Tris-HCl, pH 6. 8, and diluted 1∶1 with Laemmli buffer. The protein samples were boiled for 10 min, and 10-µl aliquots were loaded onto 10% SDS-PAGE gels. For anti-FliC blots, monoclonal antibodies (BioVeris, Gaithersburg, MD) diluted 1∶1000 were used for 1 h incubation. Detection was performed with secondary peroxidase-labeled goat anti-mouse IgG (KPL, Gaithersburg, MD), followed by application of the ECL PLUS Western blotting detection system (GE Healthcare, Buckinghamshire, UK). Coomassie blue-stained gels and developed blots were scanned with a V700 Photo EPSON Scan (digital ICE technologies) using SilverFast SE imaging software (LaserSoft Imaging, Sarasota, FL), and quantitated with QuantityOne software (Bio-Rad). S. Paratyphi A FliC was prepared from strain CVD 1902 using the shearing. CVD 1902 was chosen for purification of flagella for two reasons. First, it was genetically engineered from the attenuated strain CVD 1901 to hyper-express flagellin by deletion of the clpX gene (Table 1), which together with clpP encodes the ClpXP ATP-dependent protease that degrades the master flagella positive regulator complex FlhD/FlhC, resulting in large amounts of flagella being over-produced [24]. Second, it is an attenuated strain and as such does not pose an occupational risk when cultured in large volumes for antigen purification. Bacterial cultures were grown overnight under low aeration conditions in 2-liter flasks containing Lennox broth supplemented with guanine. Cell pellets were washed and resuspended in PBS, and sheared for 3 min at high speed in a Waring laboratory blender. The sheared suspension was centrifuged twice at 7,000×g for 10 min, and the supernatant was collected and centrifuged at 100,000×g for 3 h to pellet the filaments. The pellet was suspended in saline at 4°C overnight, centrifuged at 7,000×g, and the clear supernatant containing flagellar filaments was transferred to a new tube. Protein concentration was determined with the BCA assay (Pierce, Rockford, IL). Purity was assessed by SDS-PAGE and Coomassie blue staining. The amount of contaminating LPS was quantified using the resorcinol sulfuric acid assay [25] using a standard curve generated with purified S. Paratyphi A LPS. This FliC preparation was determined to be 98. 3% pure. UF membranes with different Mr cut-offs were used for gradient separation of flagellin monomers from purified filaments. Supernatants collected from bacterial cultures grown under high-aeration conditions and containing flagellin monomers and/or sheared flagella, were first normalized to equal concentrations of FliC by passing supernatants through a 30-kDa cut-off Amicon membrane (Millipore, Billerica, MA). The concentrated retentants were then passed through a 100-kDa cut-off Amicon membrane. The resulting filtrates were further passed through an additional 30-kDa membrane. Bacteria collected from swarm colonies were suspended in PBS to an OD600 of 1. 0 and were incubated with 300 mesh Formvar coated copper grids (Electron Microscopy Services, Hatfield, PA) for 20 min. Grids were gently blotted and placed on 50 µl drops of 2% ammonium molybdate (Sigma Aldrich, St. Louis, MO) for 2 min. After air-drying, grids were observed with a JEOL electron microscope JEM-1200EX (JEOL, Toyko, Japan). For all experiments, 6 week-old female BALB/c mice were purchased from Charles River Breeding Laboratory Inc. (Wilmington, MA) and maintained in a biohazard animal facility. Anesthesia (isofluorane dispensed through a precision vaporizer) was used for blood collection from the retro-orbital plexus. All studies were approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Maryland Baltimore School of Medicine, and conducted in accordance with NIH guidelines [23]. For assessment of virulence, the hog gastric mucin assay was used [26]. Mice were injected by the intraperitoneal route (i. p.) with increasing 10-fold dilutions of bacteria; bacteria were harvested from overnight Lennox plates and suspended in PBS mixed with 10% (wt/v) Difco hog gastric mucin (Becton-Dickinson, Sparks, MD) to a final volume of 0. 5 ml per mouse. Groups of six mice per dose per strain were tested. Mice were observed twice daily for 3 days for mortality or any signs of significant morbidity (ruffled fur, weight loss of 20% or more, collapse, difficulty breathing or severe dehydration), and those showing the above signs were euthanized according to IACUC directives. 72 h post-challenge, surviving mice were euthanized using CO2 asphyxiation followed by cervical dislocation. LD50 values were calculated by logistic regression analysis. Fresh vegetative cultures of CVD 1901, CVD 1901D or CVD 1901K were pelleted, washed with PBS, and brought to a final concentration of ∼1011 cfu/ml. 10-µl aliquots were applied intranasally on day 0,14, and 28 to mice (5 µl/nostril, ∼109 cfu per mouse; 10–15 mice per group). A group immunized with PBS served as a negative control. Blood samples were collected prior to and after immunization and sera were stored at −70°C. Mice were challenged on day 56 with 3. 3×105 cfu per mouse of wild-type ATCC 9150 S. Paratyphi A, freshly prepared as described above for the LD50 studies. Iron (8 µl of 5% ammonium iron (III) citrate to 1 ml of mucin) was added to the bacterial suspension to increase virulence [27]. Following the challenge, mice were monitored every 6 h for 72 h for mortality or any signs of significant morbidity. Total IgG antibodies and IgG subclasses against S. Paratyphi A flagella were determined by ELISA as previously described [28]. Briefly, 96-well plates were coated with S. Paratyphi A flagella (5 µg/well) or LPS (10 µg/ml). Samples were diluted in 10% dried milk in PBS containing 0. 05% Tween 20 (PBSTM) and tested in duplicates. Specific antibodies were detected using HRP-labeled goat anti-mouse IgG, IgG1 and IgG2 (KPL Inc. Gaithersburg, MD) diluted in PBSTM followed by TMB Microwell Peroxidase Substrate solution (KPL). Titers were calculated by interpolation in a standard curve as the inverse of the dilution that produces an OD value of 0. 2 above the blank (ELISA units/ml). Bactericidal activity was assessed by a complement-mediated lysis of S. Paratyphi A using sera from immunized mice. Fresh vegetative wild-type ATCC 9150 (flagellated) or 9150K (non-flagellated) bacterial suspensions (106 cfu/ml) were mixed with 30% guinea pig complement (Sigma-Aldrich, St. Louis, MO), added (1∶1) to heat-inactivated (56°C, 20 min) serially-diluted mouse sera, and incubated for 1 h at 37°C. Following incubation, bacteria were counted by plating. End point titers were defined as the last dilution that induced a ≥50% reduction in the number of bacteria incubated with complement alone without addition of serum. Antibody-mediated bacterial uptake by macrophages was measured by seeding J774A. 1 cells into 24-well microdilution plates and growing in DMEM supplemented with 5% FCS at 37°C with 5% CO2 to a confluent layer (2×105 cells/well). Fresh vegetative wild-type ATCC 9150 bacteria were incubated with heat inactivated mouse serum (10% in PBS) for 30 min on ice, then added to the cell monolayer at a ratio of 1∶1. Following centrifugation (100×g, 10 min), the microdilution plate containing the monolayer and opsonized bacteria was incubated at 37°C with 5% CO2 for 30–45 min. External bacteria were removed by replacing the media with fresh media containing 100 µg/ml gentamicin, incubating for 30–45 min, followed by three PBS washes. The cells were lysed with 0. 5% Triton x-100 and internalized bacteria were counted by plating. LD50 was estimated by logistic regression analysis. Continuous variables were compared among the groups using Kruskal-Wallis analysis of variance. Proportions in two groups were compared using the Fisher' s exact test. Two-sided p-values<0. 05 and one-sided p-values<0. 025 were considered statistically significant. Four S. Paratyphi A wild-type strains were compared for growth rate, bacterial cell yield and ability to express FliC, including American Type Culture Collection strain ATCC 9150 and three clinical isolates Q82b (Mali), EAR6473 (Chile) and 15. 067 (Chile). No significant differences in growth rate (Fig. 1A) or overall protein electrophoretic profiles (Fig. 1C) were observed among the strains, but ATCC 9150 consistently reached the highest cell yield when grown in rich liquid medium (Fig. 1B). FliC was a major component of the secretomes of all four strains (Fig. 1C, middle panel). The high amounts of flagellar protein found in the supernatants are a consequence of shear forces acting upon the cells during growth in shake flasks, causing filament shearing from the cell surface. Among the four strains, the Chilean isolate 15. 067 expressed lower levels of FliC (Fig. 1C, lower panel). To compare flagellar protein expression further, “swim” and “swarm” motilities were tested, each providing evidence of flagella functionality [29]. Swimming is assayed by growing the bacteria on semisolid medium (0. 2–0. 4% agar) where bacterial cells swim through water-filled channels in the agar, whereas swarming is observed following inoculation on the surface of solid medium (0. 5–0. 8% agar). Notably, swarming is associated with greater flagella expression than swimming [29]. In accordance with FliC expression (Fig. 1C), strain 15. 067 had reduced motility (Fig. 1D). We next tested whether variations of flagellar expression affect virulence in mice. Since S. Paratyphi A is avirulent in mice when administered orally or intranasally (i. n.), we adopted a mouse model used for S. Typhi (another human host-restricted pathogen) to determine LD50, in which bacteria are suspended in hog gastric mucin prior to intraperitoneal (i. p.) injection of BALB/c mice. This model has been used to assess the attenuation of candidate oral S. Typhi vaccines pre-clinically [26], [30] and reasonably predicted responses of humans given those strains in Phase 1 trials [31], [32]. Accordingly, young mice were injected i. p. with 10-fold dilutions of bacteria in 10% (w∶v) hog gastric mucin. ATCC 9150 was the most virulent, with an LD50 value of 52 cfu/mouse, while strains Q82b, EAR6473 and 15. 067 exhibited LD50 values of 846,199 and 692 cfu/mouse, respectively (Fig. 1E). ATCC 9150, with its excellent growth characteristics, copious flagella production and high virulence in mice, was therefore selected as the wild-type parent for construction of our vaccine candidates; the available genomic sequence of ATCC 9150 provided another rationale for using this strain [33]. To export flagellin as monomers, we targeted two chromosomal loci, FliD (flagellar cap protein) and FlgK (a hook-filament junction protein), shown in S. Typhimurium to encode hook-associated proteins [17], [20], [34]. To assure the safety of our candidate strains, we first introduced a deletion in the chromosomal guaBA operon of ATCC 9150, which encodes two essential enzymes, inosine monophosphate dehydrogenase (GuaB) and guanine monphosphate synthetase (GuaA), involved in the de novo guanine nucleotide biosynthesis pathway. Resulting strain CVD 1901 was then further deleted for fliD (yielding CVD 1901D) or flgK (CVD 1901K). The fliD or flgK deletions were also introduced into ATCC 9150, leading to 9150D and 9150K. ATCC 9150 and the resulting five isogenic strains possessed indistinguishable growth rates when cultured under high aeration in appropriately supplemented rich liquid medium (data not shown). Thus, neither the guaBA, fliD or flgK mutations impaired growth, although bacterial cell yields were somewhat lower compared to ATCC 9150 (Fig. 2A top panel). As expected, analysis of secreted protein confirmed that higher FliC levels were found in supernatants of the ΔfliD and ΔflgK mutants compared to supernatants from their parental strains (Fig. 2A lower panel). Differences in FliC expression between the fliD and flgK mutants and their parents were pronounced when bacteria were propagated as stationary broth cultures (low-aeration) where shear forces acting upon the cells are much lower. Under these conditions, no free FliC was observed in supernatants of either parental strain, yet FliC levels in supernatants of the fliD and flgK mutant cultures were as high as when grown under aerated conditions (shown for CVD 1901 and derived mutants, Fig. 2B). Immunoblotting with anti-FliC under low-aeration growth showed that the parental strain retained most flagella on the bacterial cells. In contrast, the mutants exhibited almost undetectable levels of FliC on the cell surface; CVD 1901D showed some residual FliC, while none was detected on the surface of CVD 1901K (Fig. 2C). Export of FliC from the mutants was elucidated by a three-step characterization (Fig. 3A schema), using serial ultrafiltration (UF) membranes. First, conditioned media of CVD 1901, CVD 1901D and CVD 1901K cultures were adjusted to equivalent FliC concentrations using 30-kDa cutoff UF (Fig. 3A upper gel). Then, 100-kDa (Fig. 3A middle gel) followed by 30-kDa cutoff membranes allowed separation of monomeric from polymeric flagellin. Following the final 30-kDa passage, CVD 1901K supernatant contained the highest amount of flagellin, with less in the CVD 1901D supernatant and almost none in concentrate of the parental CVD 1901 strain (Fig. 3A lower). Thus, flagellin molecules in supernatants from cultures of the fliD and flgK mutants are in the unassembled form. However, in accordance with the results shown in Fig. 2C, some flagellin expressed by the CVD 1901D mutant is cell-associated, sheared off the cell surface during growth, and retained within the 100-kDa filter. As a control, all culture supernatants were heat-treated to dissociate the polymeric flagella and indeed some FliC was observed in the filtrate of the parental CVD 1901 strain following the 100-kDa UF (Fig. 3A middle and lower). Second, comparing flagella functionality revealed identical swim and swarm diameters (% of plate) for ATCC 9150 versus CVD 1901; 39% versus 43% for swim and 45% versus 69% for swarm, respectively (Fig. 3B). Strains 9150D and CVD 1901D showed only swimming motility with a diameter of 11% and no swarming, while 9150K and CVD 1901K showed neither swim nor swarm motility. Decreasing the agar concentration in the swarming plates allowed swarming of the ΔfliD mutants, while the ΔflgK mutants remained non-motile (Fig. 3B). Finally, bacterial samples from the 0. 7% swarm plates were examined by electron microscopy (EM). The negative stained bacterial cell images establish that the ΔflgK mutant is completely devoid of surface flagella, while the ΔfliD mutant carries one or two filaments (Fig. 3C). Virulence of the mutants was compared to wild-type ATCC 9150 by inoculating 6 week-old mice i. p. with bacteria suspended in hog gastric mucin. An LD50 value of 8. 8 bacteria per mouse was calculated for the wild-type (Fig. 4). In contrast, CVD 1901 showed an LD50 of 3. 0×107 cfu/mouse. The LD50s for 9150D, 9150K, CVD 1901D and CVD 1901K were 17,49,3. 4×106 and 2. 0×107 cfu/mouse, respectively (Fig. 4). These results show clear attenuation only for strains harboring the guaBA deletion. Deletion of either fliD or flgK from ATCC 9150 attenuated the resulting strain by only half a log and did not work synergistically with the guaBA deletion. Whereas deletion of flgK or fliD in S. Paratyphi A did not alter bacterial virulence in this model, these mutations may nevertheless influence the protection conferred by vaccine strains also deleted in guaBA. Accordingly, we examined the ability of these mutants to protect against a S. Paratyphi A lethal challenge. Mice were immunized i. n. with ∼1×109 cfu of CVD 1901, CVD 1901D or CVD 1901K on days 0,14 and 28. Control mice received PBS. The i. n. route was chosen based on the robust immunity [35], [36] and protection [37] induced by attenuated S. Typhi administered by this route. Three weeks after the last immunization, mice were challenged with a lethal dose of wild-type ATCC 9150 (3. 3×105 cfu/mouse plus iron, see Materials and Methods). All control mice succumbed within 24 hours post-challenge (Table 3). The vaccine strains differed in their protective capacity, with CVD 1901 conferring significantly superior protection compared to CVD 1901D or 1901K. Serum IgG antibodies against FliC and LPS rose progressively after each immunization (Fig. 5A), reaching similar levels for all strains. Unlike CVD 1901 (which expresses many) and CVD 1901D (expresses a few) surface-associated flagella, CVD 1901K is devoid of flagella at the time of administration. Hence, FliC antibodies induced by CVD 1901K represent responses to de novo FliC synthesized in vivo, rather than antigen present at the time of immunization. The slightly higher titers detected in the mice immunized with CVD 1901D may reflect the combined effect of surface-associated and secreted FliC. Overall, there was no significant correlation between anti-FliC or anti-LPS antibody titers and survival (Fig. 5B), nor a correlation of survival with antibodies to S. Paratyphi A outer membrane protein fractions (data not shown). Thus, no serum IgG responses against major Salmonella surface antigens correlated with protection in this model. Since the overall level of anti-FliC IgG among the immunized groups did not correlate with efficacy, we examined IgG antibody subtypes. While all three vaccine strains induced similar levels of anti-FliC IgG2a antibody, CVD 1901D and CVD 1901K induced strikingly high levels of anti-FliC IgG1, which were 50- and 10-fold higher than those induced by CVD 1901, respectively (Fig. 6A, p = 0. 012). The IgG2a∶IgG1 geometric mean ratios were 1. 2,0. 036, and 0. 051 for CVD 1901, CVD 1901D, and CVD 1901K respectively, implying that a functional IgG2a-biased response, rather than elevated (and likely competing) IgG1 antibodies, might correlate with enhanced protection (Fig. 6B; p = 0. 042). Noting the differences in anti-FliC IgG subtype antibody responses induced by the different live vaccines, we next studied functional activity of the antibodies. Antibody switching to different IgG subclasses requires T-cell help (TH) during antigen priming; the presence of IgG1 reflects TH2 subset activity, whereas IgG2a indicates a TH1-type response. Since live vaccine carrying cell-associated FliC exhibited higher potency compared with flagellin-secreting strains, we further examined the potential contribution of the TH1-associated antibody response induced by these strains in protection against S. Paratyphi A challenge. The TH1 subset is responsible for many cell-mediated functions and favors the production of IgG2a antibodies with opsonophagocytic capacity that bind to high-affinity Fc receptors on macrophages [38]. These antibodies activate the complement system more readily than IgG1 antibodies [39] and efficiently mediate antibody-dependent cell-mediated cytotoxicity [40]. Complement-mediated antibody killing (bactericidal) of wild-type ATCC 9150 was assessed by incubating bacteria with serial dilutions of heat-inactivated sera from immunized mice to which guinea pig complement was added. Sera from naïve mice established the background activity. For the three sera sets, analogous bactericidal titers against ATCC 9150 were detected with no significant differences between the groups (Fig. 7A, p = 0. 28). Similar results were obtained when the assay was repeated with the non-flagellated 9150K strain (Fig. 7A, p = 0. 22), indicating that anti-FliC antibodies do not play a major role of S. Paratyphi A complement-mediated killing in this mouse model. We next examined opsonophagocytic activity using a macrophage culture assay that probes the ability of the sera to facilitate uptake of ATCC 9150. Average numbers of intracellular bacteria of 3862,2383 and 2131 per 5×106 bacteria per well were recovered for sera from mice immunized with CVD 1901, CVD 1901D, and CVD 1901K, respectively (Fig. 7B), indicating a clear increased uptake for CVD 1901 sera (p = 0. 0002). These data suggest enhanced anti-FliC antibody-mediated clearance of the organism by phagocytic cells induced by vaccines expressing cell-associated rather than exported FliC, which might be contributing to the vaccine-induced survival from S. Paratyphi A challenge in vivo. Flagellar protein is highly immunogenic and immunomodulatory via stimulation of TLR5, yet questions remain over its role in mediating protection against Salmonella [41]–[45]. Whereas purified Phase 1 flagella filaments or FliC subunits from S. Typhimurium [46] or S. Paratyphi A [10] inoculated parenterally protect mice against parenteral challenge with wild-type Salmonella of the homologous serovar, equipoise exists over whether flagellar protein contributes to protection when presented by live mucosal or parenteral inactivated whole cell vaccines. Flagellin expression is not needed for live oral S. Typhimurium vaccines to protect against wild-type challenge [47], while human studies indicate an important role for cell-associated flagella in the protection conferred by parenteral inactivated whole cell typhoid vaccines. Inactivated whole cell vaccines (most derived from wild-type strain Ty2) that provided superior protection also elicited higher anti-flagellar antibodies [48], [49]. Importantly, no efficacy was observed in a large-scale controlled field trial when the inactivated vaccine was based on non-flagellated S. Typhi mutant TNM1, derived from strain Ty2 [50], suggesting that inactivated whole cell vaccines must express flagella in order to protect humans [50]. We employed attenuated S. Paratyphi A to investigate the protective capacity of the flagellar subunit protein FliC expressed by live mucosal vaccines. Since mucosally-administered live vaccines assure in vivo expression and presentation of flagellar antigens in a native form, we engineered S. Paratyphi A ATCC 9150 with specific deletions affecting flagella filament biosynthesis. SDS-PAGE and western blotting (Fig. 2A–C), UF fractionation (Fig. 3A), motility assays (Fig. 3B) and EM (Fig. 3C) established the phenotypes of these FliC-exporting mutants. While ATCC 9150 and CVD 1901 almost exclusively produce flagellar protein as polymer filaments, 9150D and CVD 1901D (lacking flagellum cap protein) express only one or two filaments. In contrast, 9150K and CVD 1901K (lacking a flagellar hook-associated protein) are completely devoid of flagella. Studies with S. Typhimurium explain why fliD mutants carry a few intact flagellum polymers. In ΔfliD S. Typhimurium mutants [17], the tips of the hooks are intact and serve as effective heteronuclei for soluble FliC units to re-associate and form a functional flagellum. A filament already initiated has higher affinity for the newly added monomers, which elongate the single filament rather than form more short filaments. Our engineered strains mutated in fliD or flgK but unaltered in growth characteristics or virulence (Fig. 4) provided a uniform background to explore the contribution of flagellar protein to immunity and protection. Mucosal immunization of mice with the live vaccines followed by subsequent i. p. challenge with virulent S. Paratyphi A showed prominent differences in the level of protection conferred in the face of a potent challenge that killed 100% of control mice (Table 3). CVD 1901 carrying many intact cell-attached flagella conferred 90% vaccine efficacy (p = 0. 0002), while CVD 1901D with just a few cell-attached flagella provided 47% efficacy (p = 0. 026); CVD 1901K with no attached flagella elicited only 30% efficacy (p = 0. 15). Mortality was significantly lower in CVD 1901 recipients (1/10 mice) than in mice immunized with CVD 1901K (7/10 mice, p = 0. 01) or CVD 1901D (8/15 mice, p = 0. 04). These data indicate an advantage for live mucosal Salmonella vaccines having cell-attached FliC filaments. The serum anti-FliC IgG titer did not correlate with protection. In fact, the less protective live vaccines that export flagellin subunits actually stimulated slightly higher anti-FliC IgG antibody titers (Fig. 5A–B). However, when we dissected the anti-FliC response we found that while all three vaccine strains induced IgG2a anti-FliC, the flagellin-secreting strains (CVD 1901D and 1901K) induced significantly higher IgG1 anti-FliC titers (Fig. 6, p = 0. 012). IgG1 or IgG2a serum antibody responses in mice imply induction of TH2- or TH1-type subsets, respectively. Thus, both soluble and cell-attached polymeric FliC evoke TH1-directed switching to IgG2a but the IgG1 response is related to context. Whereas strong serum IgG1 anti-FliC responses were elicited by soluble exported FliC, this protein did not induce a strong IgG1-dependent TH2 response when presented as a bacterial cell-attached polymer, as observed for CVD 1901. Others have reported that mucosal administration of purified S. Typhimurium flagellin elicits a strong TH2-type response [51]–[53], while attached flagella on S. Typhimurium induce predominantly a TH1-dependent response [53]. Thus, the type of response against S. Typhimurium FliC did not seem to be determined by any intrinsic properties of FliC but rather appeared to be influenced by the form in which FliC was encountered, either as a soluble or cell-associated antigen [53]. Both monomeric and polymeric FliC induced TH2 responses provided these proteins were intact and not attached to cells, and only FliC on cells induced mainly a TH1 response [53]. Similar observations have been shown for Lactobacillus-associated and soluble FliC [54], indicating a general mechanism for anti-FliC antibody switching. We document the identical behavior for S. Paratyphi A FliC protein. However, our study advances the field since, in contrast to earlier reports, we presented FliC in vivo as attached whole flagella or as FliC monomers exported by live bacteria; previously, flagellin monomers or polymers were administered as purified protein. Although many studies have described the immune responses to FliC, we report an association between a specific IgG subtype and protection. Vaccination with monomeric flagellin-exporting live vaccines induced stronger IgG1 anti-FliC responses but less protection against challenge with virulent S. Paratyphi A, suggesting that a pronounced TH2 response does not predict functional immunity. One must ponder why certain specific antibodies elicited following vaccination with whole organisms fail to protect. One possibility is that some antibodies in excess may compete or block specific phagocyte Fc receptors that endocytose or phagocytose antibody-coated microorganisms [55]. Overwhelming Fc receptors may interfere with clearance of the pathogen. An excess of IgG1 anti-FliC antibodies induced by the exported FliC may prevent binding of the IgG2a subtype anti-FliC that is critical for clearing S. Paratyphi A infection. Alternatively, certain antibodies that lack relevant biological activity may actually enhance rather than control infection; thus, the high IgG1 anti-FliC may enhance the uptake of bacteria into cells without triggering killing. Antibodies that engage Fc receptors and enhance infection have long been known for Chlamydia trachomatis [56]. The TH1 subset is responsible for cell-mediated functions such as activation of cytotoxic T cells and production of opsonization-promoting IgG antibodies that bind to high-affinity Fc receptors and interact with the complement system. TH1 cells produce IL-2 and IFN-γ that promote the differentiation of fully cytotoxic TC cells, which are suited to respond to intracellular pathogens. IFN-γ is a defining cytokine of the TH1 subset and activates macrophages to increase microbicidal activity [57]. IFN-γ secretion by TH1 cells also induces antibody class switching to IgG classes (IgG2a in the mouse) that support phagocytosis and complement fixation. Finally, in immunized mice most Salmonella-specific cells secreting IFN-γ are also FliC-specific [46]. Complement-dependent serum bactericidal antibodies [SBA] are one functional serological response in humans exposed to Salmonella pathogens or vaccines [58]. Our results show that SBA did not correlate with protection (Fig. 7A). Replacing the flagellated WT S. Paratyphi A ATCC 9150 utilized in the SBA assay with non-flagellated strain 9150K, did not alter SBA titers, indicating that anti-FliC antibodies did not function in this assay or contributed only inconsequentially. SBA must bind antigenic determinants on or very near the bacterial surface so that complement may interact with lipid membrane components. Thus, antibodies directed against flagella may be ineffective as SBA. By contrast, we found antibodies mediating opsonophagocytic activity to be a useful functional correlate of protection against S. Paratyphi A (Fig. 7B), as has also been proposed for invasive non-typhoidal Salmonella infections [59]. A difference was observed in the opsonophagocytic activity of sera collected from mice immunized with CVD 1901 versus sera from mice immunized with CVD 1901D or 1901K. Sera from CVD 1901 mice readily mediated uptake of virulent S. Paratyphi A by phagocytes. For every human vaccine for which a correlate of immunity exists [60], the correlate is a serum antibody. Live Salmonella vaccines elicit both cell-mediated and antibody responses and our studies shed light on the role of immune responses to flagellar protein elicited by a rationally-attenuated S. Paratyphi A live vaccine. In addition, the unpolymerized FliC monomers produced by our engineered strains could be exploited as subunit vaccines or as a platform for engineered FliC-heterologous antigen fusions that might not otherwise be supported within the confines of a polymerized flagellum. An additional byproduct of our research is the demonstration of a small animal model that allows, following mucosal immunization, the efficacy of live S. Paratyphi A vaccines to be assessed, including discernment among various candidates.

Title: Cell-Associated Flagella Enhance the Protection Conferred by Mucosally-Administered Attenuated Salmonella Paratyphi A Vaccines Summary: Salmonella enterica serovar Paratyphi A is a pathogen that causes a systemic disease that is marked by serious complications and, if untreated, high mortality. The study of S. Paratyphi A pathogenesis and vaccine development has been extremely challenging since S. Paratyphi A is human host-restricted and no appropriate animal model exists. Since there is currently no licensed vaccine to prevent paratyphoid fever caused by this organism, our study represents a pioneering attempt to develop and refine a vaccine against S. Paratyphi A. We employed live attenuated strains which allow in vivo presentation of bacterial antigens via the natural route of infection, without the complications associated with antigen production and purification for subunit vaccines. For determining protective immunity against infection, we developed a mouse model that allowed evaluation of vaccine efficacy. We used our system to examine the protective capacity of a major Salmonella antigen, the flagellum. Due to its unique immunogenic properties, the flagellum is considered a major immune mediator, but its role in protection is controversial. We clearly show that cell-associated flagellar protein, presented by mucosally administered attenuated bacterial live vaccines, provides superior protection when compared to strains exporting FliC monomers, and we discuss possible mechanisms of immunity.

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Summarize: Gingrich's support on the rise this month PRINCETON, NJ -- Republicans are most likely to name Mitt Romney and Newt Gingrich as their first choice for their party's 2012 presidential nomination, with Herman Cain close behind. Among all Republicans nationwide, Romney is the choice of 20% and Gingrich 19%. Among Republican registered voters, Gingrich is at 22% and Romney at 21%. These results are based on a USA Today/Gallup poll of 1,062 Republicans and Republican-leaning independents conducted Nov. 13-17. Compared with the prior poll, conducted Nov. 3-6, Gingrich's support has increased from 12% to 19% among all Republicans. His support has gone up in each of the last three polls after bottoming out at 4% in August, and is now at his highest for the campaign to date. Meanwhile, Cain, who has been dogged by allegations of sexual harassment, has seen his support dip slightly, from 21% to 16%. However, it remains well above the levels from earlier this year, which were generally in the single digits. Rick Perry's support also slipped, to 8% in the latest poll, conducted after the two most recent candidate debates, including the Nov. 9 debate in which Perry failed to remember the names of all three cabinet departments he vowed to shut down if elected. Perry's support has declined in each of the last three updates after peaking at 29% in mid-August, shortly after he entered the race. Romney, meanwhile, has been the leader or tied for the lead in nearly every poll conducted since May, when the Republican field largely came into shape. Romney Appeals Equally to Conservatives, Moderates Most of the candidates, including Romney, receive roughly equal support from conservative and moderate or liberal Republicans. Cain and, in particular, Gingrich, have greater appeal to conservative Republicans. Overall, Gingrich has a slight edge over Romney and Cain among conservatives, while Romney has a wider margin over the others among moderates and liberals. Conservatives outnumber moderates and liberals by better than 2-to-1 in the Republican rank-and-file. Gingrich and Cain appear to have benefited most from the decline in Perry's support. In Gallup's August update, when Perry was the overall leader, 33% of conservative Republicans favored him, making him the clear leader in that subgroup. At that time, 16% of conservative Republicans supported Romney, 5% Cain, and 4% Gingrich. Older Republicans Lean Heavily to Gingrich, Romney Republican presidential nominee preferences vary significantly by age. If the nomination were contested solely among senior citizens, it would be a two-man race between Gingrich (34%) and Romney (28%), with 6 in 10 Republicans aged 65 or older supporting one of those two candidates, and no other candidate above 8% in that age group. In fact, Gingrich's support is heavily concentrated among Republicans who are at least 50, while his support is 4% among Republicans younger than 30. This pattern may reflect the fact that he has been out of public office for more than a decade, and thus a less familiar figure to younger Republicans. Cain and Ron Paul do much better among younger than among older Republicans, a consistent finding for Paul throughout the campaign. And while Romney is competitive with the leaders in every age group, his support tends to be greater among older Republicans. Older Americans in general are more likely to vote in elections than younger Americans, suggesting that Gingrich's and Romney's greater support among older Republicans may translate better to actual voting than Cain's and Paul's among younger Republicans. Implications With the first official nominating contest, the Iowa caucuses, now just six weeks away, there is no clear national front-runner for the Republican nomination. Romney remains at the top of the list, along with Gingrich, whose campaign has mounted a comeback in recent weeks, and Cain. Gingrich's rise coincides with the recent declines of Perry and, to a lesser extent, Cain, Typically, well before the Iowa caucuses, Republicans have anointed a dominant front-runner who wound up being the nominee. The major exception was in the last campaign, when Rudy Giuliani led national polls by a healthy margin for much of 2007 but was largely uncompetitive in the 2008 primaries and caucuses. Thus, the current contest stands to be the most competitive and perhaps most unpredictable for the Republican nomination since 1972, when the parties shifted the power to choose their presidential nominees away from party leaders at the national convention to the rank-and-file voters in state primaries and caucuses. Track every angle of the presidential race on Gallup.com's Election 2012 page. Sign up to get Election 2012 news stories from Gallup as soon as they are published. Who's on first? Now it's former House speaker Newt Gingrich, who leads the Republican presidential field among registered voters in a new USA TODAY/Gallup Poll. Gingrich is the sixth candidate or potential candidate to top the survey this year – following in the footsteps of former Arkansas governor Mike Huckabee, real-estate tycoon Donald Trump, former Massachusetts governor Mitt Romney, Texas Gov. Rick Perry and former Godfather's Pizza CEO Herman Cain. STORY: Gingrich's rise INTERACTIVE: Poll tracker Gingrich has the support of 22% of Republicans and Republican-leaning independents. That's a single, statistically insignificant percentage point ahead of Romney. Cain, who was tied with Romney at the top less than two weeks ago, has dropped to third in the wake of allegations of sexual harassment and questions about his command of policy. Cain's loss has been Gingrich's gain. Gingrich's support shot up among those 50 and older, to 31% from 18% in the Gallup Poll earlier this month. Most of that came at the expense of Cain, whose support among this age group dropped from 22% to 11%. Rick Perry also lost ground in the 50-and-older crowd, from 12% to 6%. Overall, Perry is now fifth in the field, at 8%, unchanged from last time. Texas Rep. Ron Paul ranks fourth at 9%. The other big gain for Gingrich was among those with postgraduate degrees. His support among the most highly educated Americans rose to 28% from 10%. They had been the education group that gave him his lowest support; now, they give him the highest. Cain's support among postgrads dropped to 10% from 23%.

Summary: Newt Gingrich is getting his turn on the merry-go-round that has been the top spot in Republican primary polling. A new USA Today/Gallup poll has Gingrich on top among registered Republican voters with 22%, though that's just a hair ahead of Mitt Romney's 21% and within the poll's margin of error. Herman Cain has fallen back into the pack with 16%, while Rick Perry is languishing in fifth with 8%-behind Ron Paul's 9%. Gingrich's biggest base of supporters: the elderly. Only 4% of people under age 30 support Gingrich, but 27% of those between 50 and 64 do, and among the 65+ crowd that figure jumps to 34%. Romney, too, enjoys strong support among the Social Security crowd, with 28% of the 65+ vote, while Herman Cain's support is concentrated among younger voters. Overall, "there is no clear national frontrunner," Gallup concludes, calling the race the most competitive GOP contest since 1972.

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Summarize: By MICHAEL RUSSO mrusso@startribune.com Paul Deutsch played hooky from beer-league game at Bloomington Ice Gardens on Wednesday night. The 51-year-old, who began tending goal at the tender age of 37, instead wore a Wild jersey during warmups Wednesday night prior to the Wild’s game against the Nashville Predators. After the Wild got word that Niklas Backstrom, slated to be the starter, would have to miss the game for a non-serious personal matter, it recalled third goalie Matt Hackett from the Houston Aeros. But Hackett’s plane didn’t arrive until just prior to gametime, so the Wild signed Deutsch, who owns a screen printing and embroidery story in Richfield, to an amateur contract Wednesday afternoon to fill in during warmups and potentially back up Josh Harding if Hackett’s plane was late. It wasn’t. Backstrom should be back with the team in a few days, Hackett back in Houston. But Deutsch still got to wear No. 33 during warmups with his daughter’s Eastview Under-14 youth team cheering on from a suite. “I actually was shaking while I was signing [the contract],” said Deutsch, who filled in “Minnesota Roosevelt Junior Varsity defenseman -- 1978,” as his previous team on the contract. Deutsch, a former Roosevelt High School teammate of former Wild assistant Mike Ramsey, used to fill in for injured Wild goalies during practices on an emergency basis. “Every 10 minutes, we used to watch the shade of his face change,” former Wild center Wes Walz said. “It would go from white to pink to bright red. When it got dark red, you knew you were close to the end of practice. “The forwards that hadn’t scored in quite some time, they all had to go down to Paul’s end to get their confidence up.” Goalie coach Bob Mason called Deutsch at work at 3 p.m. The contract needed to be into the NHL offices by 4 p.m. He faxed it over, rushed to the arena and signed three more hard copies. He took over Backstrom’s locker-room stall and got to sit through coach Mike Yeo’s pregame meetings. “It’s pretty intense,” he said. Deutsch didn’t take a physical and jokingly hoped that a poppy seed muffin he ate would pass the league’s drug tests. He said the size of his pads were legal because they previously belonged for former Wild goalie Manny Fernandez. His agent? Tom Westcott, a salesman at Maplewood Toyota, Deutsch joked. His style? Joked friend and former Roosevelt teammate Mark Hultgren: “Three options – the puck misses the net, it hits him or it goes in.” All jokes aside, a nervous Deutsch said a half-hour before warmups, “Practice is one thing. I have to tell ya, the game faces are on, and I don’t see those very often. Usually it’s a practice, and we’re calm and we’re laughing and we’re ha-ha-ha. “But gameday is a lot different, so I’m trying to stay out of the way and not get in any trouble.” He fared well in warmups, “let the guys fire away” on him and hoped Harding would come out of it healthy. If not, he’d “say a quick prayer that he’ll be OK.” Deutsch said he began goaltending at age 37. “When you play senior men’s hockey and you show up to the rink and there is no goalie, there is no game,” Deutsch said. “So that’s how I started playing. I was tired of coming, walking into the room and, ‘Oh rats.’” Wild players got a kick out of it. Two hours before the game, Dany Heatley was asked if he met the Wild’s new goalie. “Haven’t met him yet. I heard he’s old, man -- like 60,” Heatley said. Thank you for visiting TwinCities.com-Pioneer Press. We are sorry the article that you requested is no longer available.

Summary: The NHL's Minnesota Wild signed an emergency goalie today, which is news only because the guy is 51 years old and owns an embroidery store. As it turns out, Jim Deutsch won't have to suit up for an NHL game, but he came thisclose, reports the Minneapolis Star Tribune. The team got in a pickle when it found out usual starter Nik Backstrom couldn't play in tonight's game. Backup Josh Harding got the nod, and the team called up a minor league goalie to back up Harding. Problem: It wasn't a sure thing that the minor league goalie's plane would arrive in time. The team turned to Deutsch, who plays beer-league hockey and is a buddy of former Wild assistant coach Mike Ramsey, notes the Pioneer Press. (He had occasionally filled in for injured goalies during team practices.) He signed a nonpaying contract to be an amateur tryout- "I actually was shaking while I was signing it, and it was pretty cool," he says-and soon after took the ice for pregame warmups. His daughter's youth team cheered him on as Minnesota players fired away on him. After warmups, the minor league goalie's plane arrived, and Deutsch's NHL career ended.

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Summarize: This is a continuation, division, of application Ser. No. 08/277,940, filed Jul. 20, 1994 U.S. Pat. No. 5,769,960, which is in turn a continuation of application Ser. No. 08/039,024, filed Mar. 25, 1993, now abandoned, which is in turn the U.S. national phase of PCT/GB91/01635, filed Sep. 24, 1991. FIELD OF THE INVENTION The present invention relates to a golf bag for carrying golf clubs. BACKGROUND OF THE INVENTION Conventional golf bags are usually tubular in shape and are generally Constructed to carry up to 14 clubs. The clubs are turned upside down and inserted into the bag handle downwards so that the head of the club (which strikes the ball) is uppermost. The heads of the clubs are usually numbered to assist selection of the correct club. Conventionally, the inside of the bag is sub-divided into compartments by parallel webs, such that the clubs are aligned in rows. However, it is found that the club heads do not all fall naturally into a parallel alignment, which makes reading the numbers on the club heads somewhat difficult. Moreover, the clubs are not usually held in individual specific locations so that it is not easy to arrange the clubs in a numbered sequence and to keep the clubs in that sequence as the bag is carried around. It is known to provide internal plastic tubes to define individual club locations, but nevertheless the clubs are still usually arranged in rows. Golf bags are also known in which the clubs are arranged in a single line around the periphery of the bag. This facilitates location of a desired club from within the sequence, but such bags make poor use of available space and tend to be wider than normal. British patent specification GB2178966 discloses a golf bag having a series of tubes intended to carry clubs having telescopic shafts, which zips up the rear from the base to allow access to the clubs. British patent specification GB291934 describes a golf bag which is also split up the rear to allow contraction and expansion of the mouth of the bag. A V-shaped piece is fitted into the split, and may accommodate some of the smaller clubs. U.S. Pat. Nos. 4,227,559 and 4,334,564 show golf bags composed of a single line of tubes for receiving the clubs. For storage the bags may be opened out into a flat configuration. It is an object of the present invention to mitigate these problems and to provide a golf bag in which the selection of golf clubs is facilitated. SUMMARY OF THE INVENTION The present invention provides a golf bag for carrying golf clubs which comprises a generally tubular bag member having a base and a side wall depending therefrom, the side wall being divided longitudinally along a front thereof, so as to provide a pair of opposed sidewall edges, edge members being provided along each sidewall edge, each edge member being pivotally mounted at its lower end, opening means operatively connected to the sidewall edge members for enabling movement apart of the edge members, such that the bag member is opened out at its upper end in a fan-like manner, and a series of golf club retaining locations arranged around the inner circumference of the sidewall, such that opening of the sidewall by operation of the opening means presents the clubs in a fan-like serial manner. In the present specification, the front of the bag will be understood to be that part of the bag normally provided with a strap or handle for carrying. As in conventional bags, two pockets are normally provided, a smaller pocket at the lower end of the front of the bag for holding golf balls and other small items, and a larger pocket extending about two thirds of the way up the rear of the bag for holding larger items such as articles of clothing. The fan-like opening of the bag presents the clubs in an easy-to-see organised serial arrangement and helps the desired club to be located with the minimum of searching. The club heads tend to fall into a generally parallel arrangement, each head approximately radically of the sidewall circumference. The longitudinal division of the bag generally extends to substantially the base thereof, so as to maximise the degree of opening. In fact, it is preferred that the sides of the longitudinal division converge so as to come closer together at the top than at the base when the bag is closed. Usually, the lower part of the longitudinal division will be partially covered by the front pocket and possibly a web of loose material extending over the bottom third or half of the longitudinal division. Whilst a sidewall is referred to, it should be understood that this can be replaced by equivalent frame structure. The bag will however generally include a suitable weatherproof outer covering to protect the clubs. The golf club retaining locations arranged around the inner circumference of the bag member are preferably a series of lightweight tubes, or hook-section flaps; or a series of pockets sewn into the bag member. In order to provide structural integrity, it is preferred that the central golf club retaining locations be rigidly held in a generally semi-circular arrangement by suitable frame members, whilst the retaining location on either side thereof are free to fan out when the bag is opened. Means are preferably provided for holding the bag member in its opened configuration. This may be in the form of an elbow joint having either a free end attached to a respective side of the longitudinal division and which is straightened in order to open the bag. The elbow joint may form part of an over-centre mechanism. The elbow joint may be moved downwardly in order to straighten it and open the bag, its downward travel being limited by a longitudinal pillar forming part of the frame of the bag and disposed at the front thereof. In this way, one end of the carrying strap for the golf bag may be attached (directly or indirectly) to the elbow joint such that when the bag is carried, the weight of the bag causes the joint to close, thereby closing the bag member. Alternatively, the bag may be provided with means which bias it into the open configuration, such as a strip of spring material (e.g. metal or plastics) secured around the upper end. Means are then provided to draw together the sidewalls in the closed configuration, for example draw strings, against the biasing. Preferably looking means are provided for locking the bag in the closed position, and possibly also the open position. In a particularly preferred embodiment of the invention, a pair of legs are provided at the rear of the bag for supporting the bag in a generally upright position when the bag is set down on the ground. It is particularly convenient if the mechanism for opening the bag member is connected to means for throwing out the legs from a retracted position alongside the bag member. Typically, the legs are thrown out at 30°-35° to the line of the tubular bag member. Preferably, the legs are thrown out in a generally radial direction so as to form a tripod-like configuration. If desired, closure means, such as a clip or strap may be provided at an upper end of the longitudinal division for securing the bag in its closed position when the bag is not being used. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the present invention will now be described by way of example only in conjunction with the attached drawings wherein; FIG. 1 is a perspective sketch of a golf bag according to a first embodiment of the invention in its open state; FIG. 2 is a front elevation thereof showing the bag in the state; FIG. 3 is a sectional elevation along 3--3 of FIG. 5; FIG. 4 is a plan view of the golf bag in its closed state; FIG. 5 is a plan view of the bag in its open state. FIG. 6 is a part-cutaway front elevation. (from below) of a second embodiment of the golf bag; FIG. 7 is a side elevation with the sidewall material removed to show the closure mechanism (bag closed); FIG. 8 is a side elevation (sidewall removed) showing the bag in its open position resting on its extended legs; FIG. 9 is a side view of the bag; FIG. 10 is a plan view of the bag in its closed position; and FIG. 11 is a plan view of the bag in its open position with legs extended. FIG. 12 is a partial front elevational view thereof showing the bag in the closed state. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS As shown in FIG. 1 and 2, the golf bag comprises a generally tubular bag member 2 having a base 4. A plurality (usually 14) of plastic tubes 6 are arranged around the periphery of the bag member and secured in place by means of a strap 8 stitched between each tube to the bag member 2. In use, golf clubs (not shown) are inserted handle-first into the respective tubes. The golf bag is strengthened by means of a frame of lightweight construction such as aluminium alloy, and comprises a pillar 10 at a front thereof and depending rearwardly therefrom are an upper ring member 12 and a lower ring member 14. The lower ring member 14 has a generally semi-circular rear portion which passes behind the centremost six plastic tubes in order to provide support therefor. The upper ring member 12 also has a semi-circular rear portion which lies in front of the centremost six plastic tubes. The upper and lower ring members 12, 14 are interconnected at the rear of the bag by an upright frame member 16. The front of the bag member 2 is divided longitudinally and the edges of the longitudinal division are strengthened by means of edge members 18,20 formed of angle metal. The bottom of each member 18,20 is hingedly attached to the base of the bag member. In the closed state of the bag, the members 18,20 are closer together at the top than at the bottom i.e. they diverge downwardly. This limits the angle at which the clubs are inclined when the golf bag is opened and makes for a stabler structure both in the open and closed state. For clarity, the front pocket is omitted from FIGS. 1 and 2. The bag may be opened by means of an elbow mechanism comprising a pair of links 22,24 pivotally attached at their outer ends to respective edge members 18,20 and pivotally attached in the centre to a lever 26, which is in turn pivotted at its rear end to the upright frame member 16. When lever 26 is raised, the elbow joint collapses and the bag closes Until the upper ends of edge members 18,20 abut one another. A ring 28 is provided at the front of the lever 26, and an eye 30 is attached to the pillar 10, to allow a shoulder strap to be fitted between them. The arrangement is shown in more detail in FIG. 3, which also shows the front pocket 32 and rear pocket 34. A bowl-shaped base member 36 is provided in the base of the bag to hold in place the lower ends of the tubes 6. The golf bag also includes a pair of legs 40,42 which in the normal closed position of the bag lie to either side of the rear pocket 34 (see FIG. 4), but which are thrown outwardly to the position shown in FIGS. 3 and 5 by the action of moving the lever 26 downwardly to open the bag. This allows the bag to rest on its chamfered base portion 44 in its open position at an angle which is both stable and suitable for presenting the clubs in an orderly manner to the player. Thus, the upper d of each leg 40,42 includes a cranked portion 46. Each leg is pivotted at the bend of the crank 48 to the rear of the lower frame ring 14. The upper end of each leg is pivotted at 50 to a linkage 52 which is in turn pivotally connected at 54 to the lever 26. In this way, downward movement of the lever 26 causes pivotal movement of the cranked leg about pivot 48 to throw the legs outwardly to an angle of about 30-35 relative to the line of the bag. The golf bag may be used in the following manner. When the golf bag is in the open position as shown in FIGS. 1 to 3 and 5, the front of the bag is held open by links 22,24, and lever 26 resting on the top of pillar 10. In this configuration, the six central plastic tubes are rigidly retained in place by rings 12,14, whilst the outer tubes at either side thereof are fanned outwardly so that the golf clubs contained in the tubes are presented in an orderly serial manner to the player. Usually, the woods are placed on the lefthand side (looking at FIG. 1) whilst the irons number from the highest number in the central area to the lowest number at the righthand end. The bag is tilted backwardly and rests on legs 40,42. At this angle, the club heads are conveniently viewed and tend to adopt positions roughly parallel to each other in a generally radial direction. This greatly facilitates reading the numbers on the bottom of the club heads, so assisting location and selection of the chosen club. When the shot has been played, the club is replaced in the bag and the bag is closed by lifting lever 26 or by using a strap fixed between ring 28 and eye 30. Either way, the effect of the weight of clubs in the bag is to raise lever 26. Raising lever 26 has two effects. Firstly, the elbow joint comprised of links 22,24 is bent, thereby bringing together the upper ends of edge members 18,20 and closing the front of the bag to a configuration suitable for carrying. Secondly, raising the lever 26 pulls linkage 52, thereby operating crank 46 and drawing legs 40,42 inwardly to lie against the side of the bag member on either side of the rear pocket 34. Thus, in a single movement of raising lever 26 by picking up the bag, the bag is both closed and the legs retracted. The bag can then be conveniently carried to a new location where can be set down by a reverse of the above procedure for playing a new shot. The bag is set down on the ground in an upright position. Lever 26 is pushed downwardly, thereby opening the bag and throwing out the legs. Finally, the bag is tilted backwards so as to rest on the legs, when a new club may be selected. A second embodiment is shown in FIGS. 6-11 which is generally similar to the first embodiment, except that the mechanism for opening and closing the bag (and extending the legs) is different. Generally similar items use same reference numbers. In the second embodiment, the plastic tubes 76 for holding the golf clubs are hook-shaped in cross-section, each comprising a flange portion 77 sewn or adhered to the sidewall (or integrally moulded therewith) and a free generally semi-circular portion 78. This arrangement minimises weight and makes good use of available space, allows the clubs to dry, and also facilitates relative movement of the tubes when the sidewall is opened out. If necessary a loose strap 8 (not shown) may also be provided to support the tubes 76. As particularly shown in FIG. 6, the base 4 is injection moulded or vacuum-formed to include a peripheral U-shaped ridge 80 which adds strength and also serves to locate the ends of the golf club handles. A bar 82 is also provided in the base, which assists pivotting of the base to the inclined position (FIG. 8) where it forms a tripod with extended legs 40, 42. As shown in FIG. 7, the bag includes an interior frame formed of front pillar 85 and rear pillar 86 which are and ached to base 4 at their lower end, interconnected part-way up by cross-member 87, and interconnected at the top by top member 88 and brace 89. In order to bias the bag into the open configuration, a strip of spring steel 90 is attached to the top of the sidewall and secured to the upper end of rear pillar 86. A curved rigid plate 92 is also attached of the rear pend of the rear pillar so as to hold rigidly the central clubs and also to mount the legs 40, 42. Each leg is removably received in a socket 93 on a hinge body 94 mounted on plate 92, which allows the legs to be clipped in or out for storage. A carrying handle 96 is attached to front pillar 85., The bag may be closed against the bias of the spring steel by operating a lever 100 which is pivotally mounted at 102 to top member 88 and comprises a handle portion 104 and a crank portion 106. The free end of the crank portion is pivotted at 108 to S-shaped spring linkages 110, 111 each of which is in turn pivotally connected at its other end to a point 112 on the hinge socket 93 spaced away from the hinge itself. Thus downward movement of lever 100 acts to extend the legs 40, 42. The S-spring linkage acts to resiliently bias the legs into the extended position, and also allows for the non-alignment of the movement of the lever 100 and the hinges. The lever 100 may be locked in the raised position (with the bag in the closed state) by means of arm 114 and catch 124. Arm 114 is pivotted at 118 to rear pillar 86, and at its free end has a tongue 120 which engages a notch 122 in the lever 100, thereby preventing movement of the lever. The catch 124 is pivotted at 126 to the lever and has a free end (not shown) which underlies the tongue 120 in its engaged position. Pushing down on the other end 128 of the catch disengages the arm when the bag is to be opened. The free end of arm 114 is attached at 134, 136 to each edge member 18, 20 by a respective cord 130, 132. The cords also pass through respective eyes 138, 142 on either side of top member 88. Thus, on raising lever 100 to close the bag, arm 114 is thereby moved upwards drawing the cords with it, and so pulling together edge members 18, 20 to close the bag. As shown in FIGS. 6 and 7, a carrying strap 150 is attached to the free end of lever 100. Thus, picking up the bag by the carrying strap automatically raises the lever, closes the bag and retracts the legs.

Summary: A golf bag for golf clubs is divided longitudinally up its front and the edge is stiffened by edge members (18, 20). Golf club retaining tubes (6) or flaps (76) are arranged serially around the periphery of the sidewall of the bag. A lever (26, 100) operates to open the front of the bag and to present the club heads in an organized serial manner, which assists finding the selected club. The handle also extends a pair of legs (40, 42), which form a stand for the bag.

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Summarize: La cannabis è una pianta erbacea che presenta 3 sotto specie, sativa, indica e ruderalis. A ciclo annuale, può diventare alta quasi 3 metri e presenta le caratteristiche foglie a margine dentellato che possono possedere da 5 a 13 punte. Pianta dalla storia antichissima, ha accompagnato la civiltà umana con diversi usi, anche a seconda della specie. I più rinomati sono sicuramente quello tessile, sopratutto nel nostro paese, farmacologico, grazie alle numerosi metaboliti che contiene e psicotropo, partendo da riti religiosi di antiche civiltà, passando dai poeti francesi del 880 e arrivando fino alla progressiva legalizzazione dei giorni nostri. La resina, prodotta dalla cannabis, contiene fino a 60 cannabinoidi, 100 terpenoidi, 20 flavonoidi. Nell'ultimo periodo numerosi studi si stanno concentrando sugli effetti soprattutto del primo gruppo, ma il forte dibattito culturale ed etico, attorno all'uso di questa pianta, influisce, a modalità alterne, sulla ricerca farmacologica. Noi ci soffermeremo solo sulle ricerche terminate e riconosciute. Il THC è uno dei maggiori principi attivi della cannabis con proprietà psicotrope. Si lega ai recettori Cb1 e Cb2 rilasciando glutammato e dopamina. Alcune ricerche sembrano provare che un uso prolungato di THC può provocare danni, ma la bassa tossicità di questo elemento e le alte dosi usate per la ricerca scoraggiano questa tesi. Per subire un'overdose di questa sostanza o dei danni, si dovrebbero assumere quantità poco realistiche di principio attivo. Il CBD è un metabolita presente nella marijuana legale, che attualmente è acquistabile nei negozi italiani. Può modulare l'attività del recettore della serotonina 5-HT ottenendo effetti: Alcune ricerche proverebbero la sua capacità di fermare la diffusione delle metastasi al seno e di altri tumori.

Summary: È la pianta più discussa, chiacchierata, ma anche amata dell'intero regno vegetale. Portatrice di una millenaria cultura, più volte nella storia, ci siamo soffermati eticamente e praticamente sulle sue molteplici funzioni. A causa di un dibattito, spesso furente, si tende ad assorbire molti preconcetti da entrambe le fazioni, che non aiutano a fare chiarezza. Qui presentiamo un piccolo focus sulla cannabis, i derivati e gli svariati suoi usi, compresi quelli non strettamente inerenti alle sue capacità psicotrope.

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Summarize: "Puntiamo ad arrivare a un accordo tra le due famiglie per placare tutte le ostilità". Così spiega a Fanpage.it Paolo Sevesi, uno degli avvocati incaricati dalla famiglia materna a seguire il caso sull'affidamento di Eitan, il bimbo di 6 anni unico sopravvissuto alla strage del Mottarone e portato sabato pomeriggio in Israele all'insaputa della zia paterna, riconosciuta dalla Procura di Pavia come l'unico tutore legale. Come conferma anche l'avvocato Sevesi, "il bambino ora si trova in un ospedale di Tel Aviv e non è stato privato della libertà personale". Ora il nonno materno, il 58enne Shmuel Peleg, che due giorni fa ha messo su un aereo privato Eitan e lo ha portato in Israele, è indagato per sequestro di persona con l'aggravante della giovane età del piccolo. "Dal momento che però Eitan è in libertà non è corretto parlare di sequestro ma piuttosto di sottrazione di minori", aggiunge l'avvocato. "L'obiettivo ora è mettersi d'accordo". Resta adesso da chiarire anche la posizione della nonna materna di Eitan: secondo alcune informazioni la donna si trovava in Italia ed è stata coinvolta nel rapimento di Eitan. La nonna però sostiene di essere rientrata il giorno prima e di non essere coinvolta nel reato tanto non è iscritta nel registro degli indagati.

Summary: Il legale della famiglia in Israele di Eitan, il bimbo di 6 anni unico sopravvissuto alla strage del Mottarone e portato sabato pomeriggio in Israele dal nonno materno all'insaputa della zia affidataria di Pavia, fa sapere a Fanpage.it che si sta lavorando per trovare un accordo tra le famiglia in vista anche dell'udienza del 22 settembre. Poi l'avvocato Paolo Sevesi conferma che Eitan ora si trova in ospedale a Tel Aviv e che il bambino non è stato privato della sua libertà personale.

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Write a title and summarize: The progenitor cells of the developing liver can differentiate toward both hepatocyte and biliary cell fates. In addition to the established roles of TGFβ and Notch signaling in this fate specification process, there is increasing evidence that liver progenitors are sensitive to mechanical cues. Here, we utilized microarrayed patterns to provide a controlled biochemical and biomechanical microenvironment for mouse liver progenitor cell differentiation. In these defined circular geometries, we observed biliary differentiation at the periphery and hepatocytic differentiation in the center. Parallel measurements obtained by traction force microscopy showed substantial stresses at the periphery, coincident with maximal biliary differentiation. We investigated the impact of downstream signaling, showing that peripheral biliary differentiation is dependent not only on Notch and TGFβ but also E-cadherin, myosin-mediated cell contractility, and ERK. We have therefore identified distinct combinations of microenvironmental cues which guide fate specification of mouse liver progenitors toward both hepatocyte and biliary fates. The cells which populate the hepatic diverticulum during development and later serve as the source of liver parenchyma are termed bipotential progenitor cells, or hepatoblasts, as they are capable of differentiating toward both hepatocytic and biliary epithelial cell fates. While differentiation of liver progenitors toward a hepatocytic fate is guided chiefly by signaling through Wnt, HGF, and FGF (Micsenyi et al., 2004; Berg et al., 2007; Schmidt et al., 1995), biliary fate is regulated by Notch and TGFβ signaling (Kodama et al., 2004; Clotman et al., 2005; Zong et al., 2009). Specifically, a gradient of TGFβ activity caused in part by expression of TGFβR2 and TGFβR3 in the periportal region leads to differentiation of progenitors toward a biliary epithelial fate (Clotman et al., 2005). In patients with Alagille syndrome, mutations in the ligand JAG1 or receptor NOTCH2 are associated with bile duct paucity and cholestasis (Li et al., 1997; Oda et al., 1997; McDaniell et al., 2006). Zong et al. further underlined the importance of Notch in particular for both biliary cell fate and morphogenesis by showing that deletion of the Notch effector Rbpj results in reduction of both biliary fate and abnormal tubulogenesis (Zong et al., 2009). Thus, the progenitor cells of the developing liver integrate a diverse set of biochemical cues during fate specification. Several recent lines of evidence suggest, however, that liver progenitor cells are influenced not only by biochemical cues but also biophysical parameters in their microenvironment. Using combinatorial extracellular matrix (ECM) protein arrays, we showed that TGFβ-induced biliary differentiation of liver progenitor cells is coordinated by both substrate stiffness and matrix context and is further correlated with cell contractility (Kourouklis et al., 2016). Several groups have established mechanosensing via the transcriptional co-activator YAP and further elaborated a novel role for this protein in the developing cells of the liver (Camargo et al., 2007; Dupont et al., 2011; Yimlamai et al., 2014; Lee et al., 2016). This is particularly interesting in the context of liver progenitor fate specification because YAP has been shown to regulate both Notch signaling and TGFβ in liver cells (Yimlamai et al., 2014; Lee et al., 2016). However, the potential link between mechanical sensing and the fate specification of liver progenitor cells has yet to be fully defined. Here, we utilize microarrayed patterns of ECM co-printed with Notch ligands to provide a controlled biochemical and biomechanical environment for liver progenitor cell differentiation. We characterize spatially-localized, segregated differentiation of these progenitor cells toward biliary fates at the periphery of patterns and hepatocytic fates near the center of patterns. We employ traction force microscopy (TFM) to measure cell-generated forces, observing high stresses coincident with peripheral biliary differentiation. Further, we explore the dependence of peripheral biliary differentiation of progenitors on mechanotransduction pathway activity and expression of the Notch ligands Jag1 and Dll1. Collectively, our findings provide support for a model of liver progenitor differentiation which includes mechanical signaling as a key regulator of spatially-segregated progenitor differentiation and downstream biliary morphogenesis. We have previously observed peripheral expression of the biliary marker osteopontin (OPN) in liver progenitors on arrayed patterns containing both ECM proteins and Notch ligands (Kaylan et al., 2016). In order to better characterize the expression profile of cells in the periphery vs. center, we fabricated arrays of circular patterns (∼600 μm diameter) containing the ECM protein collagen I paired with either control IgG or Fc-recombinant Notch ligands (DLL1, DLL4, and JAG1). These ligands were pre-conjugated to Protein A/G so as to increase ligand functionality by clustering and orientation. Bipotential mouse embryonic liver (BMEL) progenitor cells, which are capable of assuming a hepatocytic or biliary fate (Strick-Marchand and Weiss, 2002), were seeded on these Notch ligand arrays and cultured under differentiation conditions for t=72h, at which point we immunolabeled for OPN and the hepatocytic marker albumin (ALB). Within these defined multicellular geometries, we observed OPN+ cells at the periphery of patterns while ALB+ cells were located centrally (Figure 1A). Counts of cells that were OPN+ peaked at the periphery and increased with the presentation of Notch ligands, particularly DLL4 (Figure 1B). However, counts of cells that were ALB+ cells indicated central localization and only moderate induction by ligand in the center of patterns (Figure 1C). Multiple regression analysis of these data generated coefficient estimates (β) for each presented ligand, corresponding to the mean change in cell counts from control IgG (Figure 1E and Figure 1F). These coefficient estimates confirmed increases in both peripheral OPN+ (β=37. 5, P<0. 001) and central ALB+ (β=5. 64, P<0. 001) cell counts upon presentation with DLL4. Evaluation of the expression of the biliary transcription factor SOX9 and hepatocytic transcription factor HNF4A revealed segregation similar to that of OPN and ALB (Figure 1D). Specifically, SOX9-expressing cells were at the periphery while HNF4A-expressing cells were central. We also evaluated expression of the biliary marker cytokeratin 19 (CK19) (Figure 1—figure supplement 1) and observed 1. 6 times greater intensity in cells at the periphery compared to those in the center (P<0. 001) (Figure 1—figure supplement 1). We observed peripheral expression of both OPN and CK19 at t=24h, suggesting that segregation starts earlier than t=72h and is less likely to be dependent on cell motility mechanisms (Figure 1—figure supplement 2A). Measurements of cell density across the island at t=72h indicated uniform density with radius, ruling out cell condensation as a mechanism of differentiation (Figure 1—figure supplement 2B). In preliminary experiments, we determined that patterns of approximately 600 µm diameter would lead to consistent patterned differentiation. Accordingly, for most our studies here, 600 µm diameter patterns were utilized. However, to examine potential effects of pattern diameter, we generated complementary array sets that resulted in cellular island diameters of 300 µm and 1000 µm, in addition to 600 µm (Figure 1—figure supplement 3A). Quantification of peak OPN+ cell counts on these pattern sizes indicated that biliary differentiation remained confined to the periphery independent of pattern size (Figure 1—figure supplement 3B). Together, these data establish spatially-segregated liver progenitor fates in arrayed patterns with central hepatocytic differentiation and peripheral biliary differentiation. We next asked if Notch signaling is necessary for peripheral biliary differentiation in arrayed patterns. We treated cultures with an inhibitor of Notch signaling (γ-secretase inhibitor X, GSI) and observed reduction in OPN+ cell counts at the periphery (Figure 2A and B). Prompted by previous experiments which showed that liver progenitor differentiation is sensitive to substrate stiffness (Kourouklis et al., 2016), we also evaluated progenitor differentiation on soft (4 kPa) rather than stiff (30 kPa) substrates, observing decreased counts of peripheral OPN+ cells and similar responsiveness to GSI (Figure 2A and B, Figure 2—figure supplement 1). Multiple regression analysis of these data confirmed reduction in peripheral OPN+ with both GSI treatment (β=-9. 99, P<0. 001) and culture on 4 kPA substrates (β=-3. 10, P=0. 00292) (Figure 2—figure supplement 2). ALB+ cell counts increased with GSI treatment (β=5. 41, P<0. 001), suggesting that hepatocytic differentiation is inhibited by active Notch signaling (Figure 2—figure supplement 3 and Figure 2—figure supplement 2). We also evaluated expression of SOX9 and HNF4A, observing reduction in peripheral SOX9 expression and an increase in central HNF4A expression on soft substrates compared to stiff (Figure 2C). Quantification of immunolabel intensity for SOX9 and HNF4A on both soft and stiff substrates confirmed our qualitative observations (Figure 2D), indicating a 74. 7% increase in overall SOX9 intensity on 30 kPa substrates (relative to 4 kPa substrates, P<0. 001) and 40. 6% increase in overall HNF4A intensity on 4 kPa substrates (relative to 30 kPa substrates, P<0. 001). Using in situ hybridization of mRNA, we characterized the expression of Notch family members in arrayed patterns of liver progenitors. To do so, we validated several probes against Jag1, Dll1, and Notch2 (data not shown). When used to detect mRNA in arrayed patterns fabricated on stiff (30 kPa) substrates, we observed peripheral localization of Jag1, Dll1, and Notch2 (Figure 2E). Presentation of the ligand DLL4 induced rearrangement of this expression pattern, specifically causing an increase in centrally-located cells expressing mRNA for each gene. On soft (4 kPa) substrates, we observed similar mRNA expression for cells presented with IgG but no longer observed ligand-induced central expression for Jag1 and Notch2. This loss of ligand-induced central expression on soft substrates suggests that the responsiveness of liver progenitors to Notch ligand is enhanced by stiffer substrates. Collectively, these data show that segregation of liver progenitor fates is dependent on both Notch signaling and substrate stiffness. Previous studies have delineated a role for TGFβ in liver progenitor differentiation (Clotman et al., 2005), and we have described interactions between TGFβ and Notch signaling in this context (Kaylan et al., 2016). To determine if TGFβ is involved in the generation of biliary cells at the periphery of the arrayed patterns, we treated cells with an inhibitor of TGFβ type I receptor kinase signaling (SB-431542) or stimulated with exogenous TGFβ1 (Figure 3A). Treatment with SB-431542 reduced the peripheral count of OPN+ cells while increasing central expression of HNF4A (Figure 3A, Figure 3—figure supplement 1). In contrast, treatment with TGFβ1 increased counts of OPN+ cells uniformly across the patterns irrespective of ligand presented (Figure 3A and B), in agreement with previous efforts showing uniform induction of OPN on patterns of smaller diameter (150 µm) (Kourouklis et al., 2016). Similarly, in situ hybridization for Jag1, Dll1, and Notch2 mRNA showed uniform induction across the patterns with TGFβ1 treatment (Figure 3—figure supplement 2). Interestingly, we observed loss of cell–cell junctional interactions in cells treated with TGFβ1, which is thought to be a consequence of inhibition of E-cadherin expression by the Snail family of transcription factors (Cano et al., 2000; Vincent et al., 2009). To ascertain the impact of E-cadherin function without activation of the other regulatory programs of TGFβ, we treated cells with a functional antibody against E-cadherin (DECMA) (Figure 3A). In contrast with our observations following treatment with TGFβ1, we observed differential responsiveness to control IgG and DLL4 presentation (Figure 3B). Specifically, presentation of DLL4 to cells treated with DECMA resulted in uniform induction of OPN+ cells across the patterns. We confirmed this observation using the Kolmogorov–Smirnov test, which showed that the difference between the IgG and DLL4 probability density distributions (measured by D, the supremum distance) was greater for DECMA (D=0. 437, P<0. 001) compared to both DMSO (D=0. 0655, P<0. 001) and TGFβ1 (D=0. 0848, P=0. 0350). Last, although inhibition of TGFβ by treatment with SB-431542 reduced OPN+ cell counts, mRNA in situ hybridization of cultures treated with SB-431542 indicated that both Jag1 and Notch2 remain expressed at the periphery (Figure 3C). However, SB-4315412 treatment reduced expression of both Jag1 and Notch2 in centrally-located cells presented with DLL4 (Figure 3C), which we had previously observed in untreated cultures (Figure 2E). These data therefore demonstrate that TGFβ only partially regulates fate segregation and that these effects are additionally mediated by cell–cell junctional interactions through E-cadherin. Others have established a role for mechanical stresses in multicellular pattern formation and stem cell differentiation, specifically observing collection of mechanical stresses at the corners and edges of geometric shapes (Nelson et al., 2005; Ruiz and Chen, 2008; Kilian et al., 2010; Ma et al., 2015). Having previously demonstrated a combinatorial role for biochemical and biomechanical stimuli in liver progenitor cell fate (Kourouklis et al., 2016), we hypothesized that mechanical stress gradients are involved in the segregation of liver progenitor fates arrayed patterns. To obtain theoretical predictions of mechanical stress, we used finite element modeling (FEM) of an active layer (i. e., the cell monolayer) of 600 µm diameter bound to a passive substrate with fixed lower boundary (Figure 4A). We observed peak stresses of 150 Pa at the periphery of the active layer (Figure 4B), in agreement with previous simulations (Nelson et al., 2005). Next, we used TFM to obtain experimental measurements in liver progenitor cells, observing that traction stresses are collected at the periphery of patterns on both 30 kPa and 4 kPa substrates (Figure 4C). The peak magnitude and distribution of stresses across the patterns did not vary with ligand presentation (Figure 4D). However, we did observe that central cells (R<0. 75) on 30 kPa substrates exerted stresses averaging to 32. 9 Pa, which was statistically greater than the 16. 2 Pa of stress exerted by cells on 4 kPa substrates (P<0. 001). TFM measurements of cells treated with GSI showed that Notch signaling was not upstream of traction stress generation at the periphery (Figure 4—figure supplement 1). In contrast, inhibition of TGFβ by treatment with SB-431542 resulted in more uniform traction stress distributions in cells presented with both IgG and DLL4 (Figure 4—figure supplement 2). Intriguingly, treatment with functional antibody against E-cadherin (DECMA) resulted in more uniform traction stress distribution in cells presented with IgG but not DLL4, indicating that ligand presentation in the context of reduced cell–cell interactions induces cell-generated traction stresses. In sum, these data show that mechanical stresses are collected at the periphery, coincident with peripheral biliary fate, and are further dependent on TGFβ signaling and E-cadherin interactions between cells. Having established the presence of gradients of mechanical stress in patterns, we next hypothesized that these gradients are involved in the segregated differentiation of liver progenitors. In order to first determine whether regulation by this gradient of mechanical stress is consistent with known modes of Notch signaling, we used a lattice-based computational model described by the groups of Elowitz and Sprinzak (Sprinzak et al., 2010; Formosa-Jordan and Sprinzak, 2014). We adapted their computational model to include: (1) fixed boundary conditions to better represent the physical boundary of our arrayed patterns; and (2) an additional term representing the effect of the stress gradient on expression of both Notch receptor and ligand, as observed in our mRNA in situ hybridization experiments. A model of trans-activation (Kt=10 and Kc=0) with increasing stress gradient strength (b=0,0. 5,5) produced segregation of fates qualitatively similar to our experimental results (Figure 5A). Concentration profiles of Notch receptor and repressor, a measure of Notch signaling activity, in models including trans-activation and steeper stress gradients were also qualitatively consistent with our experimental data (Figure 5B). Notably, simulations without stress suggested a biphasic distribution of receptor, which we did not observe experimentally. As experimental validation, we treated cells with blebbistatin (Figure 5C), an inhibitor of myosin II ATPases, and observed reduced peripheral OPN+ cell percentages (Figure 5D). These observations are in agreement with our previous experiments (Kourouklis et al., 2016), indicating that myosin-mediated contractility is necessary for peripheral biliary differentiation. TFM measurements obtained in parallel indicated loss of peripheral traction stresses in cells treated with blebbistatin (Figure 5D), in agreement with the known action of this inhibitor. These simulations demonstrate that a simple model of Notch trans-activation coupled with an external stress gradient is consistent with our experimental findings. In order to ascertain which specific mechanotransduction pathways are involved in this process, we treated cells with inhibitors for ERK (FR180204) and ROCK (Y-27632) (Figure 6A). We observed that FR180204 reduced OPN+ cell percentages at the outer edge of the patterned domains (Figure 6B), which is in accordance with our previous studies suggesting involvement of ERK in biliary differentiation (Kourouklis et al., 2016). In contrast, inhibition of ROCK resulted in increased peripheral OPN+ cell percentages extending centrally (Figure 6A and B). Consistent with the respective functions of the proteins targeted by these inhibitors, TFM measurements indicated loss of peripheral traction stresses in cells treated with Y-27632 but not FR180204 (Figure 6C). Analysis of Jag1 and Notch2 mRNA expression in cells treated with FR180204 indicated that inhibition of ERK signaling results in direct reduction in expression of both ligand and receptor (Figure 6D). Furthermore, we observed that the Hippo pathway effector YAP exhibited increased expression at the periphery of arrayed patterns on both 30 kPa and 4 kPa substrates (Figure 6E), though the expression of YAP was not altered by the presence of Notch ligands in the arrayed domains (data not shown). This observation of peripheral YAP expression is especially interesting in light of recent findings regarding the demonstrated role of YAP in biliary fate (Yimlamai et al., 2014) and suggests a potential role for the Hippo pathway in progenitor fate segregation. Collectively, these data show that peripheral biliary differentiation is dependent on myosin-mediated cell contractility and ERK signaling and is decoupled from mechanical stress when ROCK is inhibited. Studies of Alagille syndrome, a genetic disorder which results in bile duct paucity, have shown that the Notch ligand JAG1 is necessary for bile duct formation (Li et al., 1997; Oda et al., 1997). Our previous work has also shown that the Notch ligand Dll1 can modulate differentiation toward both biliary and hepatocytic fates (Kaylan et al., 2016). We therefore hypothesized that the Notch ligands Jag1 and Dll1 are involved in the segregation of liver progenitor fates in arrayed patterns. Using lentiviral shRNA vectors, we knocked down Jag1 (shJag1) and Dll1 (shDll1) in liver progenitors and cultured them on arrayed patterns (Figure 7A and B). We observed that shJag1 cells exhibited reduced OPN+ cell counts at the periphery (β=-16. 3, P<0. 001) while, in contrast, counts of peripheral shDll1 cells that were OPN+ increased (β=20. 1, P<0. 001), observations confirmed by quantification (Figure 7C) and regression analysis (Figure 7—figure supplement 1). In agreement with the data for OPN, only shJag1 cells exhibited loss of peripheral SOX9 expression (Figure 7D). Interestingly, knockdown of both Jag1 and Dll1 resulted in decreased central HNF4A expression (Figure 7B and D). TFM of shJag1 and shDll1 cells showed no reduction in cell-generated traction stresses by ligand knockdown compared to control cells (data not shown). These data establish contrasting roles for Jag1 and Dll1 in biliary differentiation in which Dll1 has the unanticipated function of antagonizing biliary fate and, further, suggest that the ligands are involved in hepatocytic differentiation of progenitor cells. Here, we utilized microarrayed patterns of ECM co-presented with Notch ligands to provide a biochemically- and biophysically-defined microenvironment for liver progenitor differentiation. In these patterns, we observed spatially-localized, segregated differentiation of progenitors toward biliary fates peripherally and hepatocytic fates centrally. Other groups have made similar observations using both 2D and 3D engineered systems as part of studies investigating the differentiation of mesenchymal and induced pluripotent stem cells (Ruiz and Chen, 2008; Kilian et al., 2010; Ma et al., 2015; Lee et al., 2015). In these other cell types, pathways related to cell contractility (e. g., RhoA, ROCK, RAC1) and cell–cell adaptor proteins (e. g., E-cadherin) were both implicated. We show in this work that cell contractility is a key inducer of biliary fate in liver progenitors and elaborate roles for cell–cell interactions and mechanotransduction pathway activity in addition to established regulation by Notch and TGFβ signaling. We have previously examined the role of substrate stiffness in the context of TGFβ-induced biliary differentiation, finding that progenitor cells cultured on fibronectin are sensitive to stiffness whereas cells cultured on collagen IV differentiated independent of stiffness (Kourouklis et al., 2016). On collagen I patterns, we observed that high substrate stiffness (E∼30kPa) increases peripheral biliary differentiation, Notch family member expression, and responsiveness to cell-extrinsic ligand presentation (Figure 2). In contrast, low substrate stiffness (E∼4kPa) was more supportive of hepatocytic fate, particularly in the pattern center (Figure 1 and Figure 2). These findings are consistent with other recent efforts toward delineating the impact of substrate stiffness on hepatocyte function, which have identified potential mechanisms of transcriptional and epigenetic repression of HNF4A in hepatocytes experiencing increased cytoskeletal tension (Desai et al., 2016; Cozzolino et al., 2016). By integrating TFM with the array platform, we were able to localize traction stresses and associated cell contractility to the pattern periphery, coincident with biliary differentiation (Figure 4). Paradoxically, treatment with inhibitors of actomyosin contractility (blebbistatin and Y-27632) resulted in divergent fate trajectories. Blebbistatin, a direct inhibitor of myosin ATPase, reduced both peripheral traction stress and downstream biliary differentiation as expected, whereas Y-27632, an inhibitor of myosin light chain phosphorylation by ROCK, increased peripheral differentiation and extension of differentiation centrally (Figure 5 and Figure 6). It is possible this divergence is due to the antagonism of ROCK against RAC1-induced adherens-junction formation (Wildenberg et al., 2006), suggesting that increased cell–cell interactions in the context of reduced cytoskeletal tension is supportive of biliary fate. Further evidence for this hypothesis is our observation of uniform induction of biliary fate by DLL4 presentation in cells with adherens junctions inhibited by DECMA (Figure 3), results which raise the additional possibility that Notch ligand–receptor binding is dependent on adherens junction formation. Lowell et al. provide evidence of such a mechanism in human keratinocytes, observing mutual exclusion of E-cadherin and Delta ligand and further noting that ligand expression promotes cell–cell interactions independent of adherens junction formation (Lowell et al., 2000). Interestingly, treatment with an inhibitor of TGFβ (SB-431542) reduced biliary differentiation and increased hepatocytic differentiation but failed to abolish peripheral expression of Jag1 and Notch2 (Figure 3). It is therefore not likely that TGFβ signaling is the single factor responsible for peripheral biliary fate and associated gradient formation, though it may act through autocrine or paracrine regulation to enable differentiation by other mechanisms. For instance, Zavadil et al. showed that TGFβ serves as a leading signal in the biphasic activation of HEY1 via interactions with SMAD3 and SMAD4 transcriptional regulators, whereas the lagging signal consisted of sustained HEY1-mediated activation of JAG1 signaling dependent on ERK (Zavadil et al., 2004). In the context of liver progenitor fate, this model would require only moderate amounts of autocrine TGFβ to activate the Notch transcriptional machinery leading to ligand expression and associated biliary differentiation. In support of this model, inhibition of ERK signaling with FR180204 reduced both biliary differentiation and peripheral expression of Jag1 and Notch2 (Figure 6). Last, our observation of peripherally-expressed cytoplasmic YAP (Figure 6) is intriguing in light of recent literature regarding the role of YAP as a mechanosensor (Dupont et al., 2011) and regulator of liver cell fate (Yimlamai et al., 2014; Lee et al., 2016) and might serve as a mechanistic effector downstream of peripherally-induced cytoskeletal tension in progenitor cells. Our observations of peripherally-expressed Jag1, Dll1, and Notch2 (Figure 2) are especially striking in light of the TFM data showing colocalization with peak traction stresses. Although we have demonstrated dependence of peripheral expression of ligand and receptor on substrate stiffness and ERK signaling, the exact mechanism linking traction stress to Notch ligand and receptor expression remains unidentified. Answering this question is crucial in order to define the role of cytoskeletal stress relative to Notch and TGFβ in biliary differentiation of liver progenitors. TFM of progenitor cells treated with GSI places generation of traction stresses prior to Notch-mediated biliary differentiation (Figure 4—figure supplement 1). In contrast, TFM of cells treated with SB-431542 provides evidence that TGFβ is upstream of traction stress (Figure 4—figure supplement 2), in accordance with the biphasic model described above in which TGFβ serves as an initial stimulus to Notch activity as well as potential feed-forward induction of cell contractility by TGFβ under conditions of mechanical stress (Tomasek et al., 2002). Recent descriptions of new modes of non-canonical Notch signaling provide other potential mechanisms linking cytoskeletal stress and Notch through ligand–intermediate filament interactions (Antfolk et al., 2017) or Notch transmembrane domain-mediated activation of RAC1 signaling (Polacheck et al., 2017). To gain insight into how cell mechanical stress may influence the Notch pathway, we explored the utility of incorporating mechanical stress into a multicellular model of Notch pathway dynamics (Figure 5). The results of this integrated model demonstrate that the introduction of mechanical stress as a positive regulator of Notch receptor and Notch ligand expression is sufficient to generate a patterning response with enhanced peripheral Notch activation. Notably from the in situ hybridization experiments, the presence of the Notch ligand DLL4 in the arrayed domains appeared to enhance central expression of Jag1 and Notch2 mRNA on 30 kPa but not 4 kPa substrates (Figure 2). This observation would suggest that DLL4 is acting to enhance Notch signaling centrally on 30 kPa. However, cells presented with DLL4 on 30 kPa substrates exhibited preferential biliary differentiation at the periphery with minimal biliary differentiation centrally, indicating that central expression of Notch pathway components may not be sufficient for biliary differentiation. Taken together, these findings suggest that the spatial distribution of mechanical stress signals may impact cell differentiation not only by influencing the expression of Notch pathway members but also through interactions with downstream Notch-mediated transcription or through cooperation with TGFβ and ERK, which is required for differentiation. Furthermore, future experiments incorporating additional quantitative measurements of spatial mRNA expression will be useful in identifying subtler patterns of Notch ligand and receptor expression. Knockdown of cell-intrinsic Jag1 and Dll1 further revealed distinct roles in both biliary and hepatocytic differentiation of progenitor cells (Figure 7). The reduction of central HNF4A with knockdown of either ligand is particularly interesting and suggests a role for cell–cell interactions with ligand-presenting cells in hepatocytic differentiation. The loss of biliary differentiation with Jag1 knockdown is consistent with the known role of Jag1 expressed in the mesenchyme of the portal vein (Hofmann et al., 2010). The unanticipated increase in OPN+ cells as a consequence of Dll1 knockdown, however, has fewer precedents and suggests an cell-intrinsic inhibitory role in contrast with that of Jag1. Although we used multiple Notch ligands (DLL1, DLL4, JAG1) in arrays, we have largely focused on presentation of DLL4 to progenitor cells due to its consistent activation of progenitor cells. The differential cell-extrinsic activity of the ligands might be explained in part by the known preferential affinity of ligands for specific receptors (Yamamoto et al., 2012; Andrawes et al., 2013) as well as recent evidence showing that DLL4 binds Notch receptors with greater affinity and requires less mechanical tension to activate signaling (Luca et al., 2017). It may also be a consequence of ligand presentation in the array format, which is known to be a function of molecular weight and charge (Flaim et al., 2005; Reticker-Flynn et al., 2012). Despite the previously established role of substrate stiffness in hepatocellular differentiation, one of the unexpected observations of these studies was the significant cooperative effect that substrate stiffness exhibited with multicellular geometry. Although substrate stiffness did not substantially influence mechanical stress profiles as measured by TFM (Figure 4), substrate stiffness altered the baseline levels of hepatocyte and biliary markers, with stiffer substrates promoting biliary differentiation and reducing hepatocyte differentiation (Figure 2). Overall, this observation highlights the importance of considering tissue stiffness as a potential variable within current and future studies examining other regulatory signals, such as Notch. In addition, future studies could examine a broader range of geometries, including non-circular. Our analysis of different pattern sizes suggested that peripheral differentiation was independent of diameter (Figure 1—figure supplement 3). As a result, with decreasing diameter, a greater fraction of the cells are at the periphery and exhibit biliary differentiation. Subsequent studies could be aimed at further reducing pattern size or even patterning single cells to determine if there is a size that balances mechanical stress and other intercellular signals for achieving optimal biliary differentiation. Although the array patterns we used represent a relatively simple 2D geometry, we anticipate that the mechanisms regulating progenitor differentiation investigated here will serve as a foundation for future efforts employing 3D culture models while also helping to identify candidates for future manipulation in vivo. Interestingly, during liver development, biliary differentiation is initiated as a ductal plate consisting of a layer of differentiating progenitor cells that encircle the portal vein (Ober and Lemaigre, 2018). Based on our findings related to the spatial patterning of progenitor differentiation, it is reasonable to hypothesize that the structure of the portal vein may play a role in defining the geometric and mechanical cues presented to the nascent biliary cells. In these studies, we utilized BMEL cells, which are untransformed and have been demonstrated to exhibit bipotential differentiation both in vitro and in vivo (Strick-Marchand and Weiss, 2002; Strick-Marchand et al., 2004). Accordingly, they represent a robust model cell type for controlled in vitro studies investigating microenvironmental regulation of progenitor fate specification. Building on our findings presented here, the cellular microarray approach could be adapted for investigating the differentiation of immortalized human bipotential cell lines and, ultimately, primary or stem cell-derived human liver progenitors. Finally, the mechanoresponsiveness of liver progenitors has crucial implications not only for development but also disease. Cholangiocytic cells derived from transitional progenitors have been implicated in the pathogenesis of cholangiopathies, cholangiocarcinomas, and related disorders through compensatory ductular reactions (Gouw et al., 2011) and are further thought to play a role in regenerating the liver by transdifferentiation (Boulter et al., 2012; He et al., 2014; Raven et al., 2017). The mechanisms we describe here may contribute to early sensing of and differentiation responses to the stiff, fibrotic microenvironments in both ductular reactions and regeneration, contributing to the biliary fates observed in these contexts. We utilized BMEL 9A1 cells between passages 30 and 36. These cells were cultured as previously described (Strick-Marchand and Weiss, 2002). Briefly, cells were seeded on tissue culture plastic coated with collagen I (0. 5 mg/ml) and subsequently cultured under controlled environmental conditions (37°C and 5% CO2). Treatment with trypsin-EDTA (0. 25% v/v) for ≤10 min was used to detach cells for subculturing. Basal media for expansion consisted of RPMI 1640 with fetal bovine serum (10% v/v, FBS), penicillin/streptomycin (1% v/v, P/S), L-glutamine (1% v/v), human recombinant insulin (10 µg/ml, Life Technologies, 12585–014), IGF-2 (30 ng/ml, PeproTech, 100–12), and EGF (50 ng/ml, PeproTech, AF-100–15). Differentiation media consisted of Advanced RPMI 1640 (Life Technologies, 12633–012) with FBS (2% v/v), P/S (0. 5% v/v), L-glutamine (1% v/v), and minimum non-essential amino acids (1% v/v, Life Technologies, 11140–050). BMEL cells tested negative for Mycoplasma spp. using the MycoProbe Mycoplasma Detection Kit (R&D Systems, #CUL001B). We confirmed expression of liver-specific genes and proteins in bulk cultures using PCR, immunocytochemistry, and western blot as previously described (Strick-Marchand and Weiss, 2002; Kaylan et al., 2016; Kourouklis et al., 2016). Additionally, bipotential differentiation capacity of BMEL cells was confirmed using bulk cultures within standard tissue culture plates with or without treatment with TGFβ1 (Kaylan et al., 2016; Kourouklis et al., 2016). During microarray-based differentiation experiments, cells were seeded on arrays at 1E6 cells/slide (immunocytochemistry) and 500E3 cells/dish (TFM). Cells were allowed to adhere to arrays for 2 hr before addition before 2× washes with differentiation media and subsequent addition of experiment-specific treatments. All growth factors and drugs used in these experiments were prepared and reconstituted according to the instructions of the manufacturers; see Table 1. The control, shJag1, and shDll1 cells were generated by lentiviral transduction with shRNA constructs targeting a non-mammalian sequence, Jag1, and Dll1, respectively, the details and validation of which we have described elsewhere (Kaylan et al., 2016). Polyacrylamide (PA) hydrogels were prepared following previous protocols (Aratyn-Schaus et al., 2010; Tse and Engler, 2010; Wen et al., 2014). Briefly, 25×75 mm glass microscope slides were washed with 0. 25% v/v Triton X-100 in dH2O and placed on an orbital shaker for 30 min. After rinsing with dH2O, slides were immersed in acetone and placed on the shaker for 30 min. The acetone wash was followed by immersion in methanol and another 30 min on the shaker. The slides were then washed with 0. 2 N NaOH for 1 hr, rinsed with dH2O, air-dried, and placed on a hot plate at 110°C until dry. For silanization, the cleaned slides were immersed in 2% v/v 3- (trimethoxysilyl) propyl methacrylate in ethanol and placed on the shaker for 30 min. The silanized slides were washed with ethanol on the shaker for 5 min, air-dried, and again placed on the hot plate at 110°C until dry. For fabrication of hydrogels with specific elastic moduli, two prepolymer solutions with different acrylamide/bis-acrylamide percentage (w/v) ratios were prepared to achieve elastic moduli of 4 kPa (4% acrylamide, 0. 4% bis-acrylamide) and 30 kPa (8% acrylamide, 0. 55% bis-acrylamide) with similar porosity (Wen et al., 2014). Each of these prepolymer solutions were mixed with Irgacure 2959 (BASF, Corp.) solution (20% w/v in methanol) at a final volumetric ratio of 9: 1 (prepolymer: Irgacure). This working solution was then deposited onto slides (100 µl/slide) and covered with 22×60 mm cover glasses. The sandwiched working solution was transferred to a UV oven and exposed to 365 nm UV A for 10 min (240E3 µJ). After removing the cover glasses, the slides were immersed in dH2O at room temperature for 3 d in order to remove excess reagents from the hydrogel substrates. Before microarray fabrication, hydrogel substrates were thoroughly dehydrated on a hot plate for ≥15 min at 50°C. Microarrays were fabricated as described previously (Flaim et al., 2005; Brafman et al., 2012; Kaylan et al., 2016). Biomolecules for arraying were diluted in 2× growth factor buffer (38% v/v glycerol in 1× phosphate-buffered saline [PBS], 10. 55 mg/ml sodium acetate, 3. 72 mg/ml EDTA, 10 mg/ml CHAPS) and loaded in a 384-well V-bottom microplate. Collagen I (rat tail, EMD Millipore, 08–115) was prepared at a final concent µg/ml. Fc-recombinant Notch ligand solutions were prepared at a final concentration of 104 µg/ml and included: Fc-JAG1 (R&D Systems, 599-JG-100), Fc-DLL1 (R&D Systems, 5026-DL-050), and Fc-DLL4 (Adipogen, AG-40A-0145-C050). All Notch ligand conditions were pre-conjugated with Protein A/G (Life Technologies, 21186) at a minimum 1: 6 molar ratio (A/G: ligand) before arraying. Human IgG (104 µg/ml final, R&D Systems, 1–001-A) was arrayed as a control in experiments involving Notch ligands. A robotic benchtop microarrayer (OmniGrid Micro, Digilab) loaded with SMPC Stealth microarray pins (ArrayIt) was used to transfer biomolecules from source plate to polyacrylamide hydrogel substrate, producing ∼600 µm diameter arrayed domains. For other pattern sizes, we used Xtend pins (LabNEXT) at 200 µm and 700 µm diameter. Fabricated arrays were stored at room temperature and 65% RH overnight and left to dry under ambient conditions in the dark. Prior to cell culture, the arrays were sterilized with 30 min UVC while immersed in 1× PBS supplemented with 1% (v/v) P/S, after which cells were seeded on arrays as described above. Images of entire arrays were converted to individual 8-bit TIFF files per channel (i. e., red, green, blue, and gray) by Fiji (ImageJ version 1. 51n) (Schneider et al., 2012; Schindelin et al., 2012). Image size was reduced to ∼50 megapixels/channel by binning to reduce memory requirements during computational analysis. The IdentifyPrimaryObjects and IdentifySecondaryObjects modules of CellProfiler (version 2. 2. 0) (Kamentsky et al., 2011) were used to identify nuclei for cell counts and regions marked by fluorescence. The MeasureObjectIntensity module was used to quantify single-cell intensity. The location of arrayed conditions within each image was automatically determined relative to manually-located dextran-rhodamine markers. The centroid of each island was calculated and used to assign a radial distance to each cell for analyses of spatial localization within arrayed patterns. Samples were fixed in paraformaldehyde (4% w/v in 1× PBS) for 15 min. Samples intended for labeling of secreted proteins (namely ALB and OPN) were treated with brefeldin A (10 µg/ml, R&D Systems, 1231/5) for 2 hr prior to fixation. Fixed samples were permeabilized with Triton X-100 (0. 25% v/v in 1× PBS) for 10 min and incubated in blocking buffer (5% v/v donkey serum and 0. 1% v/v Triton X-100 in 1× PBS) for 1 hr at room temperature. We incubated samples for 1 hr at room temperature or overnight at 4°C with one or two of the primary antibodies listed in Table 2 diluted in blocking buffer. The next day, we incubated samples for 1 hr at room temperature with one or two of the following secondary antibodies diluted in blocking buffer: DyLight 488-conjugated donkey anti-rabbit IgG (1/50 from stock, Abcam, ab96919), DyLight 550-conjugated donkey anti-mouse IgG (1/50 from stock, Abcam, ab98767), and DyLight 488-conjugated donkey anti-goat IgG (1/50 from stock, Abcam, ab96935). Samples were mounted in Fluoromount G with DAPI (Southern Biotech, 0100–20) and imaged no earlier than the day after mounting using an Axiovert 200M microscope (Carl Zeiss, Inc.) and associated Zen Pro software. In order to capture entire arrays as one image for later analyses, we utilized the tiling feature of Zen Pro. We performed in situ hybridization as previously-described (Biehl and Raetzman, 2015; Aujla et al., 2015). Samples were fixed in paraformaldehyde (4% w/v in 1× PBS) for 10 min, permeabilized with 0. 3% Triton X-100 in 1× PBS for 15 min, and digested with Proteinase K (0. 1 µg/ml) for 15 min at 37°C. Afterwards, samples were acetylated, pre-hybridized, and incubated in hybridization solution with linearized, digoxigenin-labeled probes for Jag1, Dll1, or Notch2 at 55°C. Prior to initiation of hybridization, probes were denatured for 3 min at 95°C. After overnight incubation, samples were washed in 50% 0. 5× formamide solution and 0. 5× sodium citrate and subsequently blocked (10% heat-inactivated sheep serum, 2% bovine serum albumin and 0. 1% Triton X-100 in tris-buffered saline). Following blocking, slides were incubated with anti-digoxigenin antibody (see Table 2) diluted in blocking buffer for 1 hr. Next, samples were washed with tris-buffered saline of increasing alkalinity (pH = 7. 5,9. 5) and incubated overnight in NBT/BCIP developing solution (Roche, 11 681 451 001). Samples were subsequently fixed with paraformaldehyde (4% w/v in 1× PBS for 10 min), mounted in Fluoromount G with DAPI (Southern Biotech, 0100–20), and imaged similarly to the immunofluorescently-labeled samples described above. For TFM experiments, we adjusted our protocol in order to fabricate the PA hydrogels in glass-bottom 35 mm Petri dishes (Cell E&G, GBD00002-200) rather than on 25×75 mm microscope slides. This enabled us to perform TFM on live cells at 37°C and 5% CO2. To measure the cell-generated forces, we added 1 µm far-red fluorescent beads (0. 2% v/v, Life Technologies, F-8816) to the working solution (Wang and Lin, 2007; Wang et al., 2002) and fabricated hydrogels with embedded beads by exposure to 365 nm UV A for 10 min. We subsequently completed the hydrogel and array fabrication protocols as described above and seeded cells on the arrays. After completion of experiment-specific treatments, the arrays were transferred to an incubated (37°C and 5% CO2) Axiovert 200M microscope (Carl Zeiss, Inc.). The microscope was used to capture phase contrast and far-red fluorescent micrographs to record cellular position and morphology along with bead displacement before and after cell dissociation with sodium dodecyl sulfate (1% v/v in 1× PBS). For analysis, we calculated the traction fields from the displacements using standard methods (Butler et al., 2002; Wang et al., 2002) which we have adapted for analysis of cell microarrays elsewhere (Kaylan et al., 2017). We next analyzed the captured images in MATLAB software (MathWorks, Inc) using Bio-Formats (Linkert et al., 2010) in conjunction with a set of custom scripts (see Source code 1–7). Specifically, the border of each island was identified, allowing calculation of a best fit ellipse and centroid. A previously-described digital image correlation program was used to calculate the displacement field between the contracted and relaxed state (Bar-Kochba et al., 2015). Cell island contraction was simulated using COMSOL Multiphysics software (COMSOL Inc., Burlington, MA) as already described (Nelson et al., 2005) using previously-determined parameter values (Sato et al., 1990; Folkman and Moscona, 1978). Briefly, the model was comprised of an active layer bound to a passive substrate with fixed lower boundary. The cell island (20 µm height, 600 µm diameter) was modeled as an isotropic linearly-elastic material with Young’s modulus of 1. 5 kPa, Poisson’s ratio of 0. 48, thermal conductivity of 10 Wm-1K-1, and coefficient of expansion of 0. 05 K-1. The substrate was modeled as an isotropic linearly-elastic material with Young’s modulus of 30 kPa and Poisson’s ratio of 0. 48. Contraction was induced in the model by reducing the temperature by 5 K (see Source code 8). Our computational model for Notch signaling is based on that of the groups of Elowitz and Sprinzak (Sprinzak et al., 2010; Formosa-Jordan and Sprinzak, 2014), extending their approach to include the effect of an external gradient of a morphogen which regulates expression of Notch ligand and receptor. The model outputs a hexagonal lattice with fixed (rather than periodic) boundaries containing individual cells with their respective Notch, Delta, and repressor concentrations as determined by the following equations: (1) dNidτ=αn−KtNi⟨Di⟩−KcNiDi−γnNi+σ (b) (2) d⁢Did⁢τ=αd1+ (Riθr) h-Kt⁢Di⁢⟨Ni⟩-Kc⁢Ni⁢Di-γd⁢Di+σ⁢ (b) (3) d⁢Rid⁢τ=αr⁢ (Kt⁢Ni⁢⟨Di⟩γ𝑛𝑑) mθ𝑛𝑑m+ (Kt⁢Ni⁢⟨Di⟩γ𝑛𝑑) m-γR⁢Ri Where N is Notch receptor concentration, D is Delta ligand concentration, R is repressor concentration, σ is the stress gradient function, Kc is the constant representing strength of cis-interactions, Kt is the constant representing strength of trans-interactions, b is the base constant for steepness of the stress gradient, α is the maximal production rate, γ is the maximal degradation rate, h is the cooperativity of Delta inhibition, m is the cooperativity of repressor activation, and θ is the Hill coefficient. Subscript i indicates index within the hexagonal lattice while angle brackets denote ensemble value of neighbers of cell i. These equations were evaluated with and without the stress function (σ) under various strengths of cis- and trans-interactions. The model defines σ to be a linear function of the radius of the island, thereby increasing expression of Notch ligand and receptor with radius in accordance with our mRNA in situ hybridization data (see Source code 9–11). Array experiments consisted of at least three biological replicates with 18 total islands per combination of arrayed condition, treatment, cell type, and readout. Counts of cells positive for immunolabels are plotted as mean values representative of an individual island. Line plots of both percentages of positive cells and mechanical stress were calculated using local polynomial regression fitting and are shown with 95% CI ribbons in gray to allow for direct statistical comparisons, that is P<0. 05 if the 95% CI ribbons for two conditions do not overlap. The percentage of cells positive for an immunolabel (namely ALB and OPN) was calculated relative to cell counts in each of 30 radial bins across every island. Multiple regression analyses were performed in R using the base lm () function (R Core Team, 2017, R Foundation for Statistical Computing) and are presented as coefficient estimates (β) and associated 95% CI. All β coefficients in regressions represent mean changes in cell counts, for which positive β represents increased cell counts and negative β represents decreased cell counts. For each regression model, we confirmed homoscedasticity, normal distribution of residuals, and the absence of leveraged outliers using residual-fit, Q-Q, and scale-location plots. For select comparisons in the text, Welch’s two-sample t-test was performed in R using the base t. test function. For all hypothesis testing, P<0. 05 was considered significant and P-values below P=0. 001 are denotated as P<0. 001.

Title: Spatial patterning of liver progenitor cell differentiation mediated by cellular contractility and Notch signaling Summary: Children are said to be a product of both nature and nurture - of their genes and the environment in which they are raised. The cells of the growing liver are not so different in this sense. As the liver of a fetus develops, immature cells called liver progenitors mature to become one of two types of adult cells: the hepatocytes that form the bulk of the liver, or the biliary cells that make up the bile duct. The traditional view is that genetic factors mainly control which cell type the progenitor cells become. However, recent research suggests that the environment around the cells matters more in this process than once thought. Cells can respond to the physical properties of their environment, such as the structure and stiffness of the surrounding tissue. These properties change as the liver develops, and can also be altered by disease. For example, damaged liver cells can spit out proteins that harden and form stiff scars. This raises a question: do changes in stiffness affect how progenitor cells behave? To answer this question, Kaylan et al. printed collagen in circular patterns and grew liver progenitor cells on them. The cells at the edges of the circular patterns matured into bile duct cells, while those in the center became hepatocytes. The stiffness felt by the cells was then determined by measuring the level of mechanical stress that they experienced. This revealed that the cells at the edge of the collagen pattern - the cells that became bile duct cells - were under most stress. In addition, more bile duct cells formed when progenitor cells were grown on a stiffer collagen pattern. Overall, the results reported by Kaylan et al. suggest that the stiffness of the environment, and the resulting stresses on a progenitor cell, can influence how it matures. As well as helping us to understand how the liver develops, this knowledge could also help us to treat a group of diseases called cholangiopathies, in which the bile ducts become inflamed. These diseases are thought to be caused by certain cells (which are similar to liver progenitor cells) maturing to become incorrect cell types. Future studies could determine if preventing changes in stiffness in the environment of these cells, or slowing their response to such changes, would help patients.

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Summarize: Tower Hamlets's Muslim mayor Lutfur Rahman sparked a storm of protest tonight after raising the Palestinian flag over the town hall ‘in solidarity with Gaza’. Barely 24 hours after it emerged Mr Rahman is to face trial over claims he committed widespread voting fraud, he ordered the flag to fly ‘in support of a ceasefire and peace’. Jewish leaders condemned the move as 'destructive' for community relations as local residents said the council should concentrate on 'potholes and bins' and not international conflicts. Scroll down for video. Tower Hamlets Mayor Lutfur Rahman tweeted this photo of the Palestinian flag flying outside the town hall. Mr Lutfur said he had taken the decision to fly the flag ‘in solidarity with Gaza’ but Tory party chairman Grant Shapps condemned the 'empty, flag-waving gesture politics' Mr Rahman was a member of the Tower Hamlets Labour Party and was its candidate to be the first directly elected mayor of the borough in 2010. But he was expelled from the Labour party after allegations surfaced about his close links with an Islamic extremist group called the Islamic Forum of Europe. He is accused of using illegal tactics to win the mayoral election in Tower Hamlets, East London, in May. Just yesterday it emerged four voters had won their big to have a damaging dossier of evidence heard at a full trial. Mr Rahman has strenuously denied allegations of electoral fraud. Today Mr Rahman risked provoking fresh controversy with his decision to fly the flag of Palestine over the town hall in Mulberry Place, off Clove Crescent. He tweeted a photograph of the flag, with the message: ‘Palestinian flag flying at Town Hall in solidarity with #Gaza and in support of a ceasefire & peace.’ The move risks angering the Jewish community in the east London borough and fuelling divisions in a borough increasingly used to making headlines for the wrong reasons. A recent review found the council's handling of the local and European election count was 'inadequate'. Tonight Tory party chairman Grant Shapps told MailOnline: 'This is an administration that cannot even organise their own election count, let alone intervene on foreign affairs in the Middle East. 'What we need is an immediate ceasefire and continued humanitarian aid, rather than empty, flag-waving gesture politics.' Mayor Rahman should remember that he is flying a flag from a British town hall in support of an organisation that is regarded across Europe and the world as terrorist. It is totally inappropriate. It is also destructive of relations between the communities that make up our capital city. It is not thought that there are any rules stopping the flying of the flag over a public building. Jonathan Arkush, vice president of the Board of Deputies of British Jews, said: 'Mayor Rahman should remember that he is flying a flag from a British town hall in support of an organisation that is regarded across Europe and the world as terrorist. 'It is totally inappropriate. It is also destructive of relations between the communities that make up our capital city.' The decision to fly the flag from the town hall Mulberry Place, off Clove Crescent in the East London borough risks causing community divisions. There was immediate condemnation of the decision on Twitter, with some arguing the council should concentrate on 'potholes and bins' In a statement Mr Rahman said: 'We are flying the Palestinian flag over the town hall as a humanitarian gesture of our solidarity with the people of Gaza. 'In addition to the current military onslaught, the blockade of Gaza is causing a humanitarian catastrophe. Over 1,000 people have been killed, most of them women and children. An urgent aid corridor needs to be opened to allow those injured to receive treatment and medical care. 'We mourn the loss of life in this tragic conflict. We call on our Prime Minister to help create a lasting peace that breaks the cycle of violence between Israelis and Palestinians and prevents any further loss of innocent lives.' An estimated 1,200 Palestinians and 55 Israelis have been killed in the conflict. Israel launched its offensive in Gaza after a surge in rocket fire from the territory. Hamas, which controls Gaza, has said it will not stop fighting until a blockade on the area, maintained by both Israel and Egypt, is lifted. Already this month there have been angry rows about Preston Town Council and Bradford Council flying the Palestinian flag. David Israel of the Leeds Jewish community said the Preston council was wrong to take sides in the conflict. innocent Israeli civilians have suffered through war and conflict,' he told the BBC. 'If you're going to put up one flag you need to put up the other flag to show support for innocent civilians on both sides on the conflict.' Others backed the move, saying they were 'proud' of Mr Lutfur for taking the controversial decision. Earlier Mr Cameron announced an extra £3 million aid for Gaza as he repeated his call for an unconditional ceasefire to stop the conflict. Britain has already given £7 million in aid. Speaking during a Q&A session with workers in Warrington, Mr Cameron said the £3 million would ‘help make sure the people in Gaza have the basic necessities of life, the food, the shelter and the assistance that they need’. Prime Minister David Cameron today announced an extra £3million for the humanitarian crisis in Gaza. He went on: ‘We should be very clear that we want an unconditional, immediate, humanitarian ceasefire that applies to everybody. 'What we are seeing happening in Gaza is completely tragic and ghastly, the loss of life is appalling, it is heart-rending watching these scenes on our television. 'But while calling for an unconditional, immediate ceasefire, we do have to be clear about a couple of points.' Mr Cameron added: 'Yes, it is awful what is happening in Gaza and the loss of life, but we do have to remember, whenever we have had a ceasefire in the last few days, it has been a ceasefire that has been obeyed and observed by the Israelis but it has not been observed by Hamas. 'Hamas continue the rocket attacks that are not aimed at military targets or political targets. They are aimed, indiscriminately, into Israel in order to do the maximum damage they possibly can. 'And so we do have to understand that that has to stop in order for there to be a lasting ceasefire.'

Summary: Lutfur Rahman ordered move 'in support of a ceasefire and peace' Move risks angering Jewish community in the east London borough. Critics say the council should concentrate on 'bins and potholes' Tory chairman Grant Shapps condemns 'empty, flag-waving gesture politics' Follows rows about Palestinian flags at town halls in Bradford and Preston. David Cameron announces an extra £3million in humanitarian aid for Gaza. Prime Minister blames Hamas for repeatedly breaking ceasefires with Israel.

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Summarize: For five years, Miami-Dade County’s sex offender law has sparked national headlines, as homeless parolees have been forced to move from street corners to parking lots because of a law that prohibits them from squatting near public spaces where children gather. Now, the dozens of homeless sex offenders — shuffled from under the Julia Tuttle Causeway to a Shorecrest street corner and finally to a parking lot near train tracks and warehouses just outside Hialeah — have a voice arguing on their behalf. On Thursday, the national chapter of the American Civil Liberties Union filed a lawsuit in federal court reasoning that Miami-Dade County and the state Department of Corrections have violated the offenders’ basic rights to personal safety, and to maintain a home. The suit doesn’t name the ACLU’s clients, referring to them as John Doe 1, 2 and 3. Never miss a local story. Sign up today for a free 30 day free trial of unlimited digital access. SUBSCRIBE NOW “It undermines public safety. It’s harder to find a job and maintain treatment. Housing stability is just as critical to these folks as to anyone else,” said Brandon Buskey, staff attorney for the Criminal Law Reform Project at the ACLU in New York City. But the man behind the controversial county ordinance said no one has the right to demand where they live. Ron Book, the powerhouse state lobbyist and chair of the Miami-Dade Homeless Trust, said the courts have upheld the residency restrictions, and the ACLU is simply regurgitating an issue that’s been dealt with. “The U.S. Supreme Court has said they’re entitled to live places that don’t endanger the health, safety and welfare of law-abiding citizens of the U.S. But they’re entitled to take their $350 to the courthouse,” Book said of the ACLU. “I don’t support those with sexual deviant behavior living in close proximity to where kids are.” The 22-page lawsuit, filed in the U.S. Court’s Southern District, calls the county ordinance vague, says it doesn’t allow sex offenders their due process, and adds that it leaves them in a vulnerable position and unsafe. “These individuals, who frequently subsist on meager incomes after being released from prison, are unable to locate stable, affordable housing in Miami-Dade County. This transience is primarily because the ordinance arbitrarily renders off-limits broad swaths of housing,” according to the complaint. Assistant County Attorney Gerald Sanchez said the county won't comment on pending litigation. At the center of the battle between the ACLU and Miami-Dade is a law approved in 2010 called the Lauren Book Safety Ordinance. Lauren Book, Ron Book’s daughter, was sexually molested by a trusted nanny for six years, starting when she was 11. Lauren Book-Lim, now married and 29, is an advocate for the sexually abused. The 2010 ordinance was created after nearly 100 offenders were sent scrambling from squalid living conditions under the Julia Tuttle Causeway. The new law doesn’t allow offenders on parole within 2,500 feet of schools, parks, bus stops, or any other place children might congregate. Before the law, Miami-Dade followed a less restrictive state-created 1,000-foot law. But the county ordinance had unintended consequences: It left sex offenders with few living options and almost immediately became a hot-button issue around the nation, even the world. There’s even a Wikipedia page about it. Miami-Dade’s sexual offender homelessness issue first came to light in late 2009, when images of 92 homeless sex offenders living in plywood and cardboard sleeping quarters tucked under the Julia Tuttle Causeway at the height of the recession were splashed across TV. At the time, the county was still following the 1,000-foot state law. Though the homeless offenders had been living there for about three years, embarrassed officials put up “No Trespassing” signs under one of the main causeways linking Miami and Miami Beach, and tore down the rickety structures. A promise to spend $1 million to find housing for the offenders didn’t solve the problem. The new, tougher, 2,500-foot ordinance was created mainly because of the Julia Tuttle fiasco. By 2012, another group of a few dozen showed up at a street corner in Shorecrest, a tiny residential and commercial neighborhood in Miami’s northeast corner. They slept on sidewalks and a median just off busy 79th Street. That was until Miami Commissioner Marc Sarnoff opened Little River Pocket Park a couple months later, on a piece of barren city-owned land between some homes that at the time was filled with rusted toys and a metal carport frame. The park was only a few hundred feet from where the offenders called home. They had to leave again. Then in the summer of 2013, 54 offenders were ushered out of a trailer park on the outskirts of Allapattah. This time they were living too close to a school for troubled kids called The Miami Bridge Youth and Family Services. State correction officials said they were unaware the facility was even considered a school when they first ushered the offenders to the trailer park. So off the offenders went again, this time to a Hialeah-area parking lot at Northwest 71st Street and 36th Court, surrounded by warehouses and train tracks. There are no bathrooms and there is no electricity. Many sleep without a roof over their heads. Others sleep in cars or in makeshift tents, defecating in a field nearby. Howard Simon, executive director of the Florida chapter of the ACLU said no entity should be allowed to strip anyone of their basic rights and force them into “dangerous and squalid conditions.” “This is the second chapter of the same sad story,” he said. “The county provoked international outrage when it forced people to live under the Julia Tuttle bridge. Now it’s forcing people to live alongside railroad tracks.” A civil rights group has filed a lawsuit seeking to overturn an “inhuman” ordinance that it says forces registered sex offenders in Miami to live in a squalid and rodent infested open-air camp without toilets or running water. According to the American Civil Liberties Union, dozens of released inmates have no choice other than to sleep nightly on the exposed area of land next to railway tracks because of the county ordinance that prohibits them residing within 2,500 feet of any school. The lawsuit, filed Thursday at the US district court in Miami, comes four years after a public outcry led to the dismantling of a notorious similar shantytown of more than a hundred sex offenders under the Julia Tuttle causeway in the city. It claims the ordinance denies the plaintiffs their constitutional right to personal safety and accuses Miami-Dade County officials of reclassifying a youth centre as a school last year so it could evict offenders from a nearby mobile home park, forcing them to sleep rough. “The conditions are horrid,” ACLU attorney Brandon Buskey said of the makeshift camp that springs up every night in a bleak warehouse district of the city close to the border with neighbouring Hialeah. “It’s a scramble to find food and water. There are no toilets, no sanitation, and many sleep on mats or in chairs. Disease, exposure to the elements, no drinkable water, these conditions make it extremely difficult to find and maintain stable employment and psychological treatment, which are the only two factors proven to reduce the likelihood of reoffending. “Housing restrictions like Miami-Dade’s have no impact on reoffending and, are more likely to increase it.” The ACLU says the problem was created by the adoption of the county ordinance in January 2010, which removed all previous municipal restrictions on offenders’ residence and led to the disbandment of the five-year-old causeway encampment. Many of the offenders who lived there moved into the River Park mobile home park, one of the few locations in Miami thought to be eligible under the ordinance with affordable housing. But in 2013 the Miami-Dade police department, which is responsible for enforcing the ordinance, received a complaint that the park was too close to the Miami Bridge family centre, which acts as an emergency shelter for youths. Even though the ordinance refers specifically only to “public or private kindergarten elementary, middle or secondary schools”, the county decided to designate Miami Bridge as a school because it offered educational programmes, the ACLU said. As a result, almost a hundred registered offenders living at River Park were ordered to move out, and most have ended up spending their nights at the railway encampment instead. Jeff Hearne, legal panel chairman of the ACLU’s Miami chapter, told the Guardian that on an average night 70 or more men arrive at the site from about 8pm onwards, setting up their mats, lawn chairs or tents, and stay until dawn the following morning. The men have to use nearby bushes as a toilet, he said, looking out for snakes and rodents in the dark before they go. “It’s pretty bleak,” he said. “You’ve got people in their 70s to men in their 20s. The shocking thing is many of them are not actually homeless. They have places they can stay, and they do during the day, it’s just that the ordinance forces them here at night. It makes no sense.” Three camp residents feature in the lawsuit as plaintiffs, all named John Doe to protect their identities. The first, a man now in his 50s, was convicted in 1992 of lewd and lascivious conduct with a 14-year-old. He has a mental disability and has fallen ill several times while sleeping at the tracks, the lawsuit claims. Plaintiff number two, in his late 40s, was convicted in 2006 of molesting a 14-year-old. He says the Florida department of corrections, which is also named in the complaint as a defendant, approved the camp as his official residence. The third complainant, a man in his 50s, has a 1999 conviction involving two teenagers. He says he was evicted from his apartment in March because of the ordinance and has been sleeping in a vehicle at the camp every night since. “Sending someone just out of jail into homelessness makes no sense, not for the person and not for the public,” said Nancy Abudu, legal director of the ACLU of Florida. “The Miami-Dade ordinance is not just unworkable, it’s unconstitutional.” The group, through the lawsuit, argues that the ordinance violates the US constitution and Florida statues and is therefore invalid. It is seeking a judge’s order permanently barring the county from enforcing it. A spokeswoman for Miami-Dade mayor Carlos Gimenez said he won’t comment on pending litigation

Summary: Following their release from prison, registered sex offenders are experiencing "horrid" conditions in Miami: Living outdoors near train tracks, they have no running water or toilets, and they share their camp with rats, the American Civil Liberties Union says in a suit. Their living area is a result of Miami-Dade County rules, which ban them from living within 2,500 feet of a school, the Guardian reports. "Housing restrictions like Miami-Dade's have no impact on reoffending and are more likely to increase it," says an ACLU lawyer. "It's a scramble to find food and water," and "many sleep on mats or in chairs." The suit says those living at the site are being denied a constitutional right to safety. It also holds that county officials decided to count a youth center as a school last year in order to drive the group out of a trailer park in the area, thus prompting the move to the camp. The leading figure supporting the 2,500-foot ordinance is a powerful lobbyist named Ron Book, the Miami Herald reports. His daughter suffered molestation by her nanny, and the law is named after her. Book says courts have already backed the law, and he doesn't "support those with sexual deviant behavior living in close proximity to where kids are."

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Summarize: A Darwin woman has been receiving death threats after starting a crocodile conservation group. The woman, who wants to be known only by her nickname of 'Broady', started the NT Crocodile Conservation & Protection Society last week after reports the Northern Territory government is considering a crocodile cull in response to a fatal crocodile attack earlier this month. Within 24 hours of starting the group, the mother-of-one, who works in the crocodile industry, had received five death threats via Facebook. Scroll down for video. A Darwin mother started a crocodile conservation group after part-albino crocodile, Michael Jackson, was killed for fatally attacking a fisherman earlier this month. 'Three were insinuations that I should go for a swim with the crocodiles, that sort of thing. Another guy told me if he saw me on the river he'd capsize my boat,' she told Daily Mail Australia. Broady believes the threats came from 'fishermen with bees in their bonnets' and said while they were unpleasant, she is unfazed by their comments. 'It didn't scare me, it didn't deter me, all it did was p*** me off and make me want to fight harder.' Bob Irwin, the father of Crocodile Hunter Steve Irwin, who gave his support to the newly-founded society, said he had received threats over the forty years he has been working in environmental conservation, but added that 'death threats or any threats of physical violence are totally out of order'. 'The problem here in Australia is, we’ve got very very few predatory animals and we don’t seem to give them the just recognition they deserve, they are really important to the health of our environment. We have to look after our predatory animals the same as we do any fluffy furry koala,' he told Daily Mail Australia. 'I’m just really pleased we have a group of young Australians in the Northern Territory who are prepared to get out there,' he said. Mr Irwin added that the group was'very brave' and would 'cop a bit of flak' because 'when it comes to crocodiles you do get people with very strong views indeed.' Bob Irwin, pictured with his son Steve Irwin, has come out in support of the conservation group saying they were 'brave' for standing up to 'cowboys' Broady started the conservation group after a famous crocodile 'Michael Jackson' was shot and killed for fatally attacking a fisherman on the Adelaide River. Michael Jackson was a 4.5-metre pied leucistic crocodile, which meant he had a distinctive white head but a pigmented body. Broady was motivated to start the conservation group after a popular Northern Territory crocodile, Michael Jackson, was shot and killed for attacking a local fisherman. Tran Van Lanh, 57, was killed by the crocodile in front of his wife while fishing in the Adelaide River on August 18. After the death, the 4.5 metre crocodile, who had a distinctive white head, was killed by authorities so Mr Lanh's remains could be recovered. Broady describes Michael Jackson, who was pied leucistic, meaning he had pigmentation on his body but an albino head, as'very dear to my heart'. 'I lived on the Adelaide River and he used to sit outside my house. I used to watch him while I did the dishes,' she said. 'He was so genetically rare, he was one in a million, he was so amazing… Generally [leucistic crocodiles] are attacked quite aggressively by other crocodiles and birds, so to get him out in the wild to the size he was, was a miracle.' Broady started a petition for Michael Jackson to be captured and have his stomach pumped, rather than be killed, and had even lined up a buyer in the U.S. willing to pay several hundred thousand dollars for the crocodile, but her campaign was unsuccessful. The society started by Broady aims to give a voice to those who are concerned about crocodile culls and trophy-hunting and she is hoping they will be able to achieve non-profit status. 'We're not out there to say all the fishermen are bad. It's about finding common ground and finding a solution that works for everyone.' 'Croc selfies', featuring people posing in front of or on top of crocodile traps in the Northern Territory have drawn strong criticism. A man fishes from on top of a crocodile trap. Chief Minister Adam Giles said the death of Mr Lanh two weeks ago was 'a sign that the density and population of crocs in the NT is becoming somewhat of an issue' and that the cabinet would consider culling as a long-term policy as well as safari hunting. 'It's not about going out and randomly killing crocs, it's about having a well-developed plan that protects the interests of the animal but also the interests of the general public,' Mr Giles said. Adam Britton, Senior Research Associate at Charles Darwin University, says that while there are significantly more crocodiles in the Northern Territory waters than there used to be, the crocodile population is merely returning to its natural levels. Saltwater crocodiles were almost driven to extinction by hunting in the 1960s and it is estimated their population dropped to about 3,000. Now, there are approximately 100,000 saltwater crocodiles in the Northern Territory, the result of a management program that was put in place in 1971. Mr Britton says the management program has been doing 'an excellent job' of restoring the ecological balance that was threatened by the low numbers of crocodiles and said that since they have increased in number, crocodiles have become a significant economic asset for the Northern Territory as well. Brutus, a six-metre crocodile who is missing its front foreleg, is another famous crocodile in the Adelaide River near Darwin. Brutus the crocodile pictured last month eating a shark. In the 1970s, the saltwater crocodile population dropped to 3,000 due to excessive hunting. A management program was implemented to restore their numbers, which involved protecting the species. Now there are an estimated 100,000 saltwater crocodiles in the Northern Territory. On average crocodiles kill one person every two years in Australia. This year, four people have died in crocodile attacks in the Northern Territory. Tran Van Lanh, 57, was killed by the crocodile in front of his wife while fishing in the Adelaide River on August 18. The remains of 22-year-old Travis Costa were found inside a saltwater crocodile in Tiwi Islands north of Darwin earlier this month. In June a 62-year-old man was snatched by a large crocodile from a boat moored in Kakadu National Park. In January a 12-year-old Aboriginal boy was killed by a crocodile while swimming with friends at a billabong in Kakadu. 'Some vocal people believe they should be curbed and the question has to be looked at very carefully... I don’t think it’s going to achieve anything close to what people are hoping it will achieve, it will reverse the progress we’ve seen with crocodiles over the last few decades. 'It will affect a significant number of people without necessarily saving any lives,' he told Daily Mail Australia. Mr Britton added that having a large cull of crocodiles in the state would be 'folly'. 'If the NT government said: "It's open season on crocodiles and we're going to remove 50,000 crocs from the wild", there would be some fairly serious repercussions of the way people see Australia.' Mr Britton said that according to statistics one person is killed by crocodiles in the country every two years, but there has been a 'cluster' of deaths in recent months. As well as the crocodile attack that claimed Mr Lanh, there have been three other deaths in the Northern Territory from crocodile attacks so far this year. Earlier in August the remains of 22-year-old Travis Costa were found inside a saltwater crocodile in Tiwi Islands north of Darwin; a 62-year-old man was snatched by a large crocodile from a boat moored in Kakadu National Park in June and in January a 12-year-old Aboriginal boy was killed by a crocodile while swimming with friends, also at Kakadu. Mr Britton said it was too early to tell if the deaths were a trend or a statistical 'blip' and said it was more helpful to compare the number of crocodile fatalities in Australia with those in surrounding countries, where fatalities from crocodile attacks were much more common, despite smaller populations of the animals. Mr Britton added that while he is not in favour of a large-scale cull of the animals, he does think it is necessary to kills crocodiles who attack humans. 'I think it's an unfortunate necessity in most situations if a crocodile has killed someone, that crocodile has learned that it can successfully attack and kill someone at that location, that makes it incredibly dangerous. I would rather see that crocodile killed and removed from the system,' he said. He added that in the case of Michael Jackson it was 'unfortunate' because he was a very popular animal, but that considering he lived right next to a busy boat ramp 'it would have been madness' to let him live after he had successfully killed a human

Summary: Darwin woman, known as 'Broady', started a crocodile conservation group. Within 24 hours she had received five death threats from local fishermen. Steve Irwin's father Bob has expressed his support for the group. Conservation group started as NT government considers crocodile cull. Fisherman, 57, was killed by a crocodile earlier this month, the fourth crocodile-related death in the NT this year.

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Summarize: Background CPSC was created in 1972 under the Consumer Product Safety Act to regulate certain consumer products and address those that pose an unreasonable risk of injury; assist consumers in evaluating the comparative safety of consumer products; and promote research and investigation into the causes and prevention of product-related deaths, injuries, and illnesses. CPSC’s jurisdiction is broad, covering thousands of types of manufacturers and consumer products used in and around the home and in sports, recreation, and schools. CPSC does not have jurisdiction over some categories of products, including automobiles and other on-road vehicles, tires, boats, alcohol, tobacco, firearms, food, drugs, cosmetics, medical devices, and pesticides. Other federal agencies—including the National Highway Traffic Safety Administration; Coast Guard; Bureau of Alcohol, Firearms, Tobacco, and Explosives; Department of Agriculture; Food and Drug Administration; and Environmental Protection Agency—have jurisdiction over these products. Consumers and others previously were able to report safety problems or concerns about consumer products through CPSC’s toll-free hotline; the U.S. mail, or a form on CPSC’s website submitted through e-mail and they can continue to use these methods in lieu of submitting reports through SaferProducts.gov. CPSIA and CPSC define “harm” as injury, illness, or death or risk of injury, illness or death. 15 U.S.C. § 2055a(g); 16 C.F.R. § 1102.6(b)(4). be published. As required by statute, CPSC disclaims any responsibility to guarantee the accuracy of a report. The submitter of an incident report on SaferProducts.gov must fit into one of five categories: (1) consumers; (2) local, state, and federal government agencies; (3) health care professionals; (4) child service providers; and (5) public safety entities. CPSC regulations specify that “consumers” include, but not be limited to, users of consumer products, family members, relatives, parents, guardians, friends, attorneys, investigators, professional engineers, agents of a user of a consumer product, and observers of the consumer products being used. CPSIA requires the following information when submitting a report of harm: (1) description of the consumer product sufficient to distinguish the product as a product or component part regulated by CPSC; (2) identity of the manufacturer or private labeler by name; (3) description of the harm related to use of the consumer product; (4) approximate or actual date of the incident; (5) category of submitter; (6) submitter’s contact information; (7) submitter’s verification that the information contained therein is true and accurate; and (8) consent to publication of the report of harm. 15 U.S.C. § 2055a(b)(2)(B); C.F.R. § 1102.10(d). Subject to §§ 1102.24 and 1102.26, CPSC will publish reports of harm containing all the required information. required to contact the submitters for further information.transmits a copy to manufacturers, importers, and private labelers identified in the reports, to provide them with the opportunity to comment. Qualifying reports and manufacturer comments submitted for publication are then available on SaferProducts.gov (see fig. 1). CPSC Has Used Various Approaches to Inform the Public about SaferProducts.gov, but Has Not Established Metrics to Assess Its Efforts CPSC’s efforts to promote SaferProducts.gov formed part of a larger effort to increase the public’s awareness of the agency. CPSC has taken a variety of approaches to inform the public about SaferProducts.gov, many of which are consistent with key practices for consumer education planning. However, CPSC has not established metrics for its efforts. As a result, the agency does not know which of its efforts have had the most impact on increasing awareness and use of SaferProducts.gov. Outreach about SaferProducts.gov Has Been Part of an Effort to Increase Awareness of CPSC CPSC’s efforts to inform the public about SaferProducts.gov have been part of a larger effort to increase the public’s awareness of the agency. According to CPSC officials, certain segments of the public may not be aware of the agency or its mission in product safety, much less be aware of SaferProducts.gov. Likewise, roughly one-third of the 37 consumers who participated in our website usability tests were aware of CPSC or its mission. To promote awareness of CPSC, officials have conducted public information campaigns related to various product safety hazards such as fire hazards and those involving children’s products, issued press releases about product recalls, and used social media. Officials said that media stories promoting the use of SaferProducts.gov have had the benefit of promoting CPSC as a resource not only for information about product recalls (for which the agency is most commonly known), but also as a place where consumers can raise concerns about the safety of consumer products. In addition to the outreach efforts noted above, CPSC has planned initiatives to assess the public’s awareness of the agency as a whole. In fiscal year 2011, CPSC’s Office of Communications received funds to award a contract to plan and conduct field surveys to assess consumer awareness of the agency. CPSC and a contractor are developing the survey tool. These surveys are to cover such areas as the public’s knowledge and awareness of the safety issues for which CPSC is responsible, how the agency’s work affects consumers, and how the public responds to product recalls and other safety hazards that CPSC communicates. CPSC officials told us that they plan to administer the survey in 2013, but have been awaiting approval of the survey from the Office of Management and Budget. CPSC also recently redesigned its main website, CPSC.gov, based on feedback from the public. According to CPSC officials, this redesign allowed the agency to provide a more visible link to SaferProducts.gov. CPSC Has Used a Variety of Approaches to Inform the Public about SaferProducts.gov As it has for publicizing the agency, CPSC has used a variety of approaches to inform the public about SaferProducts.gov, including the use of social and other media. Before launching SaferProducts.gov, CPSC hosted a web conference on January 11, 2011, to inform interested stakeholders such as consumer groups and the public about the site’s search function and the information required to submit an incident report.2011, CPSC promoted the new website through print and other media. According to CPSC officials, the agency’s promotional strategy emphasized both the public’s ability to search SaferProducts.gov for reports and submit such reports. In addition, near the 1-year anniversary of SaferProducts.gov, CPSC launched three public service Around the time it launched SaferProducts.gov in March announcements (PSAs) about SaferProducts.gov, sending these PSAs to local and national media and making them available on online media channels, such as YouTube (http://www.youtube.com). According to CPSC officials, the agency has a contract with a video production company to produce and distribute the videos. CPSC officials said that the PSAs have been among the 10 most-viewed videos on CPSC’s YouTube channel. They added that it was difficult to attract extensive television coverage or the best airtime slots given CPSC’s PSA budget of about $50,000 for fiscal year 2012. Further, the officials said that PSAs can cost from $700,000 to $1 million to produce, distribute, and air during prime viewing or listening times. The agency also has distributed informational materials to target audiences at conferences and community events; referenced the site in speeches and presentations by the Chairman, Commissioners, and staff; and held press interviews to promote the site, according to CPSC officials. For example, CPSC developed a series of brochures, including some tailored to specific professional sectors, such as health care, child care, public safety, and government. CPSC officials noted that they have mentioned the site at conferences, particularly those aimed at minority populations and professional groups. The agency also has made a data feed of the incident reports available to third-party software developers to create mobile applications and provided information for developers in a frequently asked questions page on SaferProducts.gov. In conducting its public information efforts, CPSC has employed a number of strategies consistent with key practices for consumer education planning that we identified in a prior report. For example, CPSC has worked with stakeholders such as consumer groups (a key practice) to promote SaferProducts.gov, and used a variety of media (another key practice) to promote the site. CPSC also has identified “messengers” such as consumer groups and state attorneys general to assist with publicity, and identified the resources needed for publicity (other key practices). Most of the consumer product safety experts we interviewed from nine groups representing consumers, researchers, and various industries stated that CPSC has been taking appropriate measures to promote the site. However, some also suggested that CPSC could conduct more targeted outreach to other professional groups, such as those in health care, and other populations, such as parents. CPSC Has Not Established Metrics to Evaluate Its Outreach on SaferProducts.gov While CPSC has employed many of the key practices for consumer education planning as described previously, it has not employed one of the key practices that could further improve the efficacy of its outreach for SaferProducts.gov. Specifically, CPSC has not established metrics, such as process and outcome metrics, to measure the success of its outreach In its 2013 performance budget request, as part of an effort to efforts.increase awareness of the agency, CPSC has a goal for the number of visits to CPSC.gov. However, CPSC does not have a similar goal for the number of visits to SaferProducts.gov, although it collects such data (as discussed in the next section of this report). Similarly, CPSC has not determined whether its efforts to publicize SaferProducts.gov at conferences or through PSAs have led to increased use of SaferProducts.gov after the events. CPSC also has not incorporated tools or features on the site (such as a drop-down menu on the homepage that would ask users to select an option such as “conferences,” “PSAs,” “printed materials,” or “media”) to identify how the user learned about and arrived at the site. The information generated by such tools also may provide CPSC with ideas for additional metrics to measure awareness and use of the site. CPSC has not established metrics to evaluate its outreach efforts for SaferProducts.gov because the agency has been focused on increasing awareness of CPSC and improving the functionality of CPSC.gov. CPSC officials said that in comparison with SaferProducts.gov, CPSC.gov received almost 10 times as many visits each month. Officials have said they may focus on evaluating outreach efforts for SaferProducts.gov in the future. However, without current metrics to assess the efficacy of its outreach for SaferProducts.gov, CPSC will not know which of its efforts— for instance, promoting the site at conferences and using PSAs—have had the most impact on increasing awareness and use of SaferProducts.gov, or be able to best target its limited resources to increase use of the site. CPSC Collects Limited Data about the Use of SaferProducts.gov CPSC collects limited data about the use of SaferProducts.gov. To track use, CPSC collects data on the number of visitors, most frequently visited pages, and number of reports received, among other metrics. CPSC also collects some data about the category of person who is submitting a report. However, CPSC does not collect any data about who is using the site to search for information. In particular, CPSC has not sought to collect demographic data, such as age, gender, or income. In mandating this report, Congress required us to assess whether a broad range of the public uses the site. However, CPSC’s limited data collection related to use of the site made it difficult to conduct such an assessment. Website Use Remained Relatively Constant, with Searches and Submission of Reports Constituting Frequent Uses According to CPSC officials, the agency’s primary measure of the extent of use of SaferProducts.gov is the number of visitors each month. CPSC collects these data through web analytics software. According to CPSC’s data, visits to SaferProducts.gov exceeded 100,000 each month since June 2011, a few months after the launch of the site (see fig. 2), peaking at about 238,000 in November 2012. CPSC officials have not been able to identify the reasons for the increase in visits. CPSC also collects data on the most frequently visited pages each month (see fig. 3). These data show that users frequently used the site to search for information—for example, to search for recalled products or incident reports submitted by other users of the site. CPSC also collects data on the number of reports received each month through SaferProducts.gov, as well as by phone, e-mail, postal mail, and fax. These data show that users submitted more than 1,000 reports from all sources each month from March 2011 through December 2012 (see fig. 4). CPSC collects some data about the categories of persons using SaferProducts.gov to submit incident reports but does not collect additional data such as age, gender, or income level of the submitters or others who use the site to search for information. When completing a report, CPSC requires submitters to state whether they are consumers, represent a government agency, or are health care or other professionals, among other categories of user. As shown in table 1, our analysis of more than 12,000 reports posted on SaferProducts.gov as of January 2013 found that most report submitters—about 97 percent—identified themselves as consumers, results consistent with our prior reporting. As stated previously, “consumers” include, but are not limited to, users of consumer products, family members, relatives, friends, attorneys, investigators, and others. Representatives of government agencies and public safety entities, as well as health care professionals, child service providers, and medical examiners and coroners also submitted reports. CPSC also asks report submitters to state their relationship to the victim of the incident (such as self, parent, or spouse). As shown in table 2, of those who identified themselves as consumers, most identified themselves as the victims of an incident. However, many submitters did not specify a relationship. Of those who did specify a relationship to the victim, 4,463, or 60 percent, reported that they were the victims, and 1,867, or 25 percent, reported that their child was the victim (see table 3). CPSC asks that submitters specify the location of the reported incident, including the country and state. Most submitters providing this information—about 90 percent—reported that the incident took place in the United States (see table 4). Submitters also reported that incidents took place in other countries or did not specify where the incident took place. In addition, states with the highest population—such as California, Texas, New York, Florida, and Illinois—had the most reported incidents (see fig. 5). Beyond these data, CPSC does not request or obtain additional details about the users of SaferProducts.gov. According to CPSC officials, the agency also cannot distinguish new users from returning users because CPSC’s web analytics software has not been configured with “cookies” to capture these data. Officials have cited resource and privacy concerns as reasons for not collecting these data, although they said they have been considering using cookies in the future. In addition, CPSC does not collect more specific demographic information such as age, gender, or income level from the submitters of reports or other site users, citing an interest in minimizing the reporting burden on users. As an example, CPSC has not requested that site users voluntarily provide this information during the report submission process or after submitting a report. Congress required us to assess whether a broad range of the public uses SaferProducts.gov, but CPSC’s limited data collection made it difficult to conduct such an assessment. In addition, standards for internal control in the federal government state that agencies should have timely, relevant information for management decision-making purposes.result of its limited data collection about users of the site, CPSC has been limited in its ability to target its marketing and outreach efforts on specific groups, populations, or areas to achieve the goal of increasing use of the site. Consumer Testing Showed SaferProducts.gov to Be Generally Useful, but Identified Areas for Improvement As discussed earlier in this report, our website usability tests focused on asking consumers in our testing sessions to judge if SaferProducts.gov was easy to use. We had the consumers perform various tasks (such as searching for recalled products and submitting mock incident reports) and asked for opinions about the site’s usefulness. A moderator facilitated the sessions and we elicited feedback from participants. In addition, a GSA official with expertise in website usability assessed SaferProducts.gov, and another GSA official reviewed the site for website accessibility. Consumers Said the Site Was Easy to Use, but Noted a Few Search Functions and a Registration Page as Problematic Many consumers in our testing sessions generally found SaferProducts.gov easy to use, but they encountered difficulties with certain aspects of the two main functions: searching for information and Of the 37 consumers who participated in our submitting incident reports.testing sessions, 20 found SaferProducts.gov easy to use as indicated by their responses to a questionnaire we administered following each test session. For example, almost all the consumers were easily able to determine what initial steps to take to search for or report a product that may be unsafe. In addition, the expert evaluator reviewing the site at our request described the site as clean and easy to navigate. In conducting the search tasks, consumers generally were able to find recalled products using basic key word searches. But some search functions, including those that required more complicated searches such as use of an advanced search function to narrow results, posed challenges. For example, in one testing session, no consumers were able to complete a task that required them to narrow their search by injury, time period, and location. In another session, the calendar function, which filters the results by time period, posed particular challenges. Five of the eight consumers in that session experienced difficulties in having to enter and, when seeking to make one change, re-enter all the dates to focus their search on products recalled within a particular time period. The expert evaluator from GSA experienced similar challenges in using the calendar function. In addition, when asked to search for and compare safety information for two products—one for which there were search results and one for which there were none—almost all the testers had difficulty interpreting the lack of search results for the latter product. For example, while some testers assumed that a search for a product that produced no results indicated that the product was safe, others did not make this presumption. In our testing sessions, most consumers were not sure which product to purchase based on their searches and roughly a quarter indicated that they would leave SaferProducts.gov to search other websites if they found no results on SaferProducts.gov. In contrast to SaferProducts.gov, other websites inform users of a possibly incorrect search term, such as a typographical error, which helps users interpret the results of their searches and identify potential errors. During the usability tests, consumers experienced fewer challenges using the reporting function than the search function. To submit an incident report, consumers must enter information on a series of pages that include a combination of required and optional fields. During our testing, consumers found the instructions for submitting a report to be generally clear. For example, almost all the testers thought the instructions for submitting information about the incident, product, and victims were clear. However, 15 of the 37 consumers in our test sessions expressed concern about apparently needing to register before submitting a report and generally did not notice that they could continue without registering (see fig. 6). By registering on SaferProducts.gov, site users can save their reports to complete at a later time and receive updates on the status of reports. When reaching the registration page, over a third of the consumers in our focus group sessions said that they would not be inclined to register. In one session, seven of nine consumers said they would not be inclined to register and thought that having to register was a deterrent to completing a report. In another session, none of the participants noticed the option to skip registration. Some of those who noticed that they could skip registration emphasized that the option should be more prominent—for example, placed alongside the registration box rather than below it where it might not be immediately visible. Likewise, as an issue of website usability, the expert evaluator from GSA reviewing the site on our behalf noted that the “continue without registering” option was not prominent enough and stated that registration may deter users from continuing the report submission process. In addition, some consumers in our testing sessions said that the reporting pages contained too many questions and described the submission process as cumbersome, particularly for busy individuals such as parents. To address this, one consumer suggested grouping all of the required fields on one page. The expert evaluator from GSA also suggested that all the questions in the reporting process should be reviewed to determine if each was necessary. When CPSC first developed SaferProducts.gov, the agency conducted three focus groups—one with consumers and one with professionals—to test the site and assess users’ experience with it.testing only addressed the incident reporting function, not the search function, and focused on (1) awareness of how and where to submit a safety complaint and (2) general reactions to the site. CPSC has not conducted additional usability testing since launching SaferProducts.gov in March 2011. As mentioned previously, CPSC officials have said that issues such as assessing the level of awareness of CPSC and redesigning CPSC.gov were higher priorities than assessing and improving SaferProducts.gov. CPSC’s focus group A number of resources across the federal government are available to help agencies in making their websites more usable. For example, as cited previously, GSA’s First Fridays Usability Testing Program is designed to teach agency officials how to find and fix usability problems at no cost to the agency. The program’s services are (1) formal tests, (2) quick tests, (3) mobile tests, (4) observation, and (5) expert evaluation.GSA also offers DigitalGov University, which includes courses in web design and usability best practices. In addition, the Department of Health and Human Services (HHS) operates two usability labs, both of which are free of charge to other federal agencies, to evaluate websites to ensure that they are easy-to-use and useful. Furthermore, GSA and HHS maintain HowTo.gov and Usability.gov, respectively, to provide guidance and resources to help agencies create websites that are usable, useful, and accessible. Because of the usability issues in the areas we identified, consumers may not take advantage of all the features of SaferProducts.gov, and consumers may be dissuaded from completing and submitting incident reports. As a result, CPSC may not be obtaining all possible information from consumers that can help inform its safety assessments and other regulatory efforts. Consumers Initially Were Not Aware of SaferProducts.gov and Thought the Site’s Purpose Was Unclear, but Found the Site Generally Useful after Using It None of the consumers in our test sessions previously had heard of SaferProducts.gov, although a few were familiar with CPSC as an agency involved in recalling certain products. In addition, 5 of the 37 consumers who participated in our tests said that the purpose of SaferProducts.gov was not clear based on its name and the initial information on the home page. In our testing sessions, roughly a third of the consumers commented that the name of the website—SaferProducts.gov—and the home page did not accurately convey what consumers could and could not do on the site. For example, when asked about their impressions of SaferProducts.gov, over a quarter of the testers thought that they would find information about safe products, such as a list of products that meet certain standards or a rating of products. These consumers did not appear to notice information on the home page indicating that they would only find information on unsafe products (see fig. 7). In our testing sessions, several consumers commented that the website would be more aptly named UnsafeProducts.gov. In addition, during our one-on-one testing sessions in Washington, D.C., two of the testers had difficulty distinguishing between recall notices and incident reports, which serve Likewise, although the expert evaluator from GSA different purposes.was able to obtain a general sense of the purpose of the site, he noted that a tagline (brief text that gives users an immediate idea of what the site does) would help reinforce the site’s purpose. In one testing session, a few consumers also said that it was not apparent from looking at the home page that CPSC did not regulate certain categories of products, such as automobiles and medications, although more than half of the consumers in our testing sessions said at the outset that they routinely searched online for safety information on particular products. Similarly, none of the consumers in our testing sessions noticed that they could be directed to the agency’s main site, CPSC.gov, by clicking on certain links in SaferProducts.gov. Only the expert evaluator noticed that by opening a recall notice, the website user would leave SaferProducts.gov and go to CPSC.gov. However, as consumers completed the various tasks in the testing sessions, they better understood the website’s features and functions. In responding to our closing questions about their overall experiences in using the site, most said that they would use SaferProducts.gov again now that they were aware of it. For example, some consumers found information about product recalls the most useful component of the site and said they would give more weight to this information. In our testing sessions, about one-quarter of the consumers also found value in the incident reports, noting that they helped website users understand whether products that had not yet been recalled had safety issues. Two of the consumers commented that they found the content of the reports to be more credible than other websites that provide a forum for consumer complaints. In addition, a few consumers pointed to the amount of detail in the reports, such as the incident description, location, and date as particularly helpful. Nevertheless, because of the usability issues in the areas we identified (for example, not having a clear and “up-front” statement of what the site contains and how it can be used), consumers may not use all of the site’s available features and be dissuaded from completing and submitting reports. CPSC officials also acknowledged that awareness of the agency could be heightened if consumers were informed about CPSC while using or searching SaferProducts.gov. Conclusions CPSC has used many approaches to inform the public about SaferProducts.gov, employing many key practices of consumer education planning in the process. Incorporating the promotion of SaferProducts.gov into its broader effort to increase awareness of the agency has represented a logical approach that has prevented duplication. However, our work confirms CPSC’s perception that public awareness of SaferProducts.gov is likely low. For example, none of the participants in our usability tests had heard of SaferProducts.gov prior to the testing. Although CPSC has employed many of the key practices for consumer education planning, it has not established metrics to measure the success of its efforts. By establishing such metrics, the agency would be better able to determine which of its outreach efforts had the most impact on increasing awareness and use of the site and thus could more effectively target its limited resources to increase use of the site. In addition to establishing and using metrics, more data about the use of SaferProducts.gov could help CPSC target its marketing and outreach. Currently, CPSC collects limited data about the use of SaferProducts.gov. For example, it collects data on the number of visitors, but not whether they are using the site to search for information—one of the main functions of the site. It also does not collect demographic data about the users’ age, gender, or income. These types of data could help CPSC identify groups, populations, or areas on which to focus to further increase use of the site. Our usability testing with consumers identified other ways in which CPSC may increase the use of SaferProducts.gov. Although our testing revealed that many consumers found the site generally easy to use, it also revealed that certain search functions, site registration, and lack of a clear statement of purpose posed challenges for some users. By improving the site in these areas, CPSC could help ensure that consumers take advantage of all the features of the site and are able to search for and report information in an easy and convenient manner. Making these improvements also may provide CPSC with additional reports from consumers to inform its safety assessments and other regulatory efforts. Recommendations for Executive Action To improve the awareness, use, and usefulness of SaferProducts.gov, CPSC should take the following three actions: establish and incorporate metrics to assess efforts to increase awareness and use of SaferProducts.gov, look for cost-effective ways of gathering additional data about the users and their use of SaferProducts.gov, and implement cost-effective usability improvements to SaferProducts.gov, taking into account the results of any existing usability testing or any new testing CPSC may choose to conduct. Agency Comments and Our Evaluation We provided a draft of this report to CPSC for review and comment. In commenting on the draft report, the Chairman and Commissioners stated that they support the report’s recommendations. Specifically, they stated that CPSC staff will look for cost-effective ways to improve awareness of SaferProducts.gov, improve the usability of the site based on research on best practices in web design, and gather additional metrics about users. The Chairman and Commissioners’ comments are reprinted in appendix III. CPSC also provided technical comments that we incorporated in the report as appropriate. We are sending copies of this report to interested congressional committees and to the Chairman and Commissioners of CPSC. In addition, the report will be available at no charge on GAO’s website at http://www.gao.gov. If you or your staff members have any questions about this report, please contact me at (202) 512-8678 or cackleya@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found on the last page of this report. GAO staff who made major contributions to this report are listed in appendix IV. Appendix I: Objectives, Scope, and Methodology The objectives of our report were to examine (1) the Consumer Product Safety Commission’s (CPSC) efforts to inform the public about SaferProducts.gov, (2) who has been using the website and to what extent, and (3) the extent to which consumers have found the website to be useful. For the first objective, we reviewed CPSC marketing, budget, evaluation, and planning documents to determine the status of the agency’s public information efforts related to SaferProducts.gov. We sought to determine whom CPSC had been targeting; how, if at all, the agency was evaluating the outcomes of its efforts; and any future plans to promote awareness and use of the site. We compared CPSC’s efforts with criteria on key practices for consumer education planning. We interviewed consumer product safety experts from nine groups representing consumers, researchers, and various industries to determine what additional steps, if any, CPSC could take to better inform the public about SaferProducts.gov. We identified these experts through our prior work or based on recommendations from those we interviewed. For context, we interviewed an official in CPSC’s Office of Communications and reviewed CPSC’s strategies to increase awareness of the agency as a whole. See GAO-12-30. reliability and determined that, for the purposes of this report, the data were sufficiently reliable. We did not review specific incident descriptions that individuals filed and do not attest to the reliability of that information. For the third objective, we conducted website usability tests with 37 consumers—who represented a mix of demographic characteristics in terms of age, gender, and educational level—to obtain their views on how easy it was to use SaferProducts.gov and how useful they found the website. We conducted the tests in Washington, D.C., Dallas, Texas, and San Francisco, California. We chose these locations for geographic dispersion and ease of testing. We followed the protocols and used the Washington, D.C. facilities of the General Services Administration (GSA) for our testing conducted through the First Fridays Usability Testing Program. At this location, GSA recruited three volunteer testers on our behalf. Consistent with the GSA program protocols, a moderator facilitated the testers’ execution of various website tasks, such as searching for recalled products and submitting mock incident reports. We followed similar protocols in San Francisco and Dallas. To identify the participants in San Francisco and Dallas, we worked with a contractor to recruit prospective testers who had a mix of demographic characteristics. We held two focus groups in each location, for a total of four groups. Two groups had eight participants per group and the other two groups had nine participants per group. In all four groups, a moderator facilitated the testers’ execution of various tasks, as was done in Washington, D.C. Although the results of our usability tests are not generalizable to all U.S. consumers, they provided us with in-depth, interactive feedback and detailed perspectives from a range of website users about the usability challenges associated with SaferProducts.gov. To supplement our approach, we requested and reviewed an expert evaluation conducted by the First Fridays program manager. The GSA official evaluated SaferProducts.gov based on the following criteria: (1) accessibility—the ability of people with physical or mental disabilities to use the site; (2) identity and purpose—whether the site clearly presents its purpose, including what the site offers and what a user can do on it; (3) clarity—the ability to read and digest content; (4) navigation—how easily users can find information; and (5) design and content—focusing on the layout, headers, and design. Another GSA official provided a more in- depth accessibility review of SaferProducts.gov to identify issues that users with disabilities might encounter when navigating the site. According to GSA, although an expert evaluation can be a useful starting point for determining a website’s usability strengths and weaknesses, the expert evaluation emphasizes the importance of the user experience. In addition, we reviewed various other website usability resources and criteria, including Usability.gov, to understand the key practices for making websites easy to use and helpful. We conducted this performance audit from July 2012 to March 2013 in accordance with generally accepted government auditing standards. Those standards require that we plan and perform the audit to obtain sufficient, appropriate evidence to provide a reasonable basis for our findings and conclusions based on our audit objectives. We believe that the evidence obtained provides a reasonable basis for our findings and conclusions based on our audit objectives. Appendix II: GAO Script, Including Questions and Tasks, for Usability Testing with Consumers Appendix III: Comments from the U.S. Consumer Product Safety Commission Appendix IV: GAO Contact and Staff Acknowledgments GAO Contact Staff Acknowledgments In addition to the individual named above, Debra Johnson, Assistant Director; Meghana Acharya; Mark Bird; William Carrigg; Jeremy Cluchey; Meredith Graves; Ronald Ito; Sarah Kaczmarek; May Lee; Marc Molino; Patricia Moye; Barbara Roesmann; Andrew Stavisky; and Julie Trinder made key contributions to this report.

Summary: In the wake of increased product recalls in 2007-2008, Congress passed the Consumer Product Safety Improvement Act of 2008 (CPSIA). Among other things, CPSIA required CPSC to establish a database on the safety of consumer products that is publicly available, searchable, and accessible through the CPSC website. In response, CPSC launched SaferProducts.gov (http:// www.saferproducts.gov ) in March 2011, which has two main functions--to provide (1) a mechanism for online reporting of product safety issues and (2) the ability to search for these issues or others, such as recalls. CPSIA also required GAO to study the general utility of the website. This report examines (1) CPSC's efforts to inform the public about SaferProducts.gov, (2) who is using the website and to what extent, and (3) the extent to which consumers have found the website to be useful. To do this, GAO analyzed agency documents and data from 2011 to 2012; interviewed CPSC officials, researchers, and consumer and industry groups; reviewed federal standards, guidance, and best practices for website usability; and conducted website usability tests with 37 consumers in three locations. The Consumer Product Safety Commission (CPSC) has used various approaches to inform the public about SaferProducts.gov, including using social media, public service announcements, and printed materials, and promoting the site during speeches and events. CPSC's efforts to inform the public about SaferProducts.gov have been part of a larger effort to raise awareness about the agency as a whole. While CPSC has employed many key practices for consumer education planning, it has not established metrics for measuring the success of its efforts. Without such metrics, the agency cannot determine which efforts have had the most impact on increasing awareness and use of the site. While CPSC collects some data on the category of persons, such as consumers or health care professionals, who submit reports (one of the main functions of the site), it does not collect data about who is using the site to search for information (the other main function). In addition, to minimize the reporting burden on users, CPSC has not asked for demographic data about the users (such as their age, gender, or income level). Therefore, it was difficult for GAO to assess, as mandated by Congress, whether a broad range of the public has used the site. Moreover, without such data, CPSC has been limited in its ability to target its marketing and outreach efforts to increase use of the site. Many consumers in GAO's usability tests thought the site generally was easy to use and had helpful information, but identified areas for improvement. The consumers generally could perform basic searches and follow instructions to report an unsafe product, and although none were aware of the site before the tests, most said they would use the site again. However, some of the search functions posed challenges. In addition, some consumers expressed concern about registering with the site and said this might prevent them from completing a report. Other consumers were not clear about the site's purpose, thinking it would focus on safe rather than unsafe products. By addressing the usability challenges GAO identified, CPSC could help users take full advantage of all the available features of SaferProducts.gov. Furthermore, cost-effective federal resources exist across the government to help agencies improve the usefulness of their sites.

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Summarize: Johnny Kock, 68, tried to import £1b of cocaine hidden in boxes of washing powder. A drugs kingpin who tried to import an estimated£1billion of cocaine hidden in boxes of washing powder has been jailed for 25 years. Johnny Kock, 68, posed as a respectable businessman in his huge European operation to 'flood the streets' with cocaine. Kock, from Wavertree, Merseyside, used a pond liner company as cover to ship in vast amounts of cocaine in boxes of washing powder. Millions of pounds of drugs were found in a single consignment but a further 57 shippings had already taken place, leading experts to believe he was responsible for £1bn worth of drugs being brought into Britain. Sentencing him to 25 years behind bars at Liverpool Crown Court yesterday, Judge Mark Brown said: 'In terms of the amounts of cocaine, this must be one of the biggest ever offences considered by the courts.' Grey-haired Kock was arrested last October when police discovered cocaine worth £26m and 110,000 Euros in two separate seizures in the German city of Bremen and the Channel Tunnel town of Coquelles, in northern France. At the time of the bust, 125kg of cocaine was said to be destined for a warehouse within the Knowsley Industrial Park complex, in Kirkby, Liverpool. Police also found £4,570 in his van and £7,170 at the home he shared with partner Deborah Fagan in Wavertree – said to be money obtained through his drug importing business. The court was told that the seized shipments were just two out of 57 shipments known to have been delivered to Kock's business Aquaries Pondliner Ltd, based in the Old Swan area of Liverpool. Judge Brown said the amount of cocaine brought in by Koch was between one and six tonnes. The National Crime Agency said that if 6,000 kilos of cocaine was imported, it would be potentially worth £960m on the streets. Kock used a pond liner company as cover to ship in vast amounts of cocaine in boxes of washing powder. Kock pleaded guilty to conspiracy to evade the prohibition on the importation of class A drugs, concealing criminal property and two counts of possession of criminal property. He later tried to change his plea on the drug case to not guilty, claiming he thought he was moving cannabis and never opened the packages. That bid failed following a two-day court hearing this week. Kock was arrested last October when police discovered cocaine worth £20m and 110,000 Euros in two separate seizures in the German city of Bremen and the Channel Tunnel town of Coquelles, in northern France. Alex Leach, prosecuting, said the value of the recovered drugs alone was an estimated £26m, never mind the other shipments that got through. He told the court: 'The prosecution case is that each of the 57 loads contained somewhere between 23 and 107 kilos of cocaine. 'It's at the very highest level of drug importation into this country. The scope of this conspiracy stretches far beyond the two loads that were recovered.' Judge Brown went further, saying: 'This really is the top end of the scale is it not? When you are in the order of six tonnes, and high purity at that? 'It was in my opinion a relatively simple but audacious way of getting class A drugs into the UK. 'Whilst it isn't possible for the prosecution to determine precisely the weight of cocaine you imported it was obviously a vast amount, at least between 1,300kg and 6,000kg, worth many, many millions of pounds. 'Also this was high purity cocaine that no doubt would have been cut up for street dealing. 'This case highlights the ease with which vast amounts of cocaine can be imported into this country. 'You must have known you were playing for high stakes both in financial reward and the consequences if discovered. 'I'm satisfied that was a risk you were willing to take therefore it follows there must be a very substantial term of imprisonment.' Judge Brown also congratulated the officers who brought Kock to justice, saying they had closed down a significant avenue to drugs, which he called a 'cancer on society', to enter the UK. Kock's partner Fagan, was jailed for 12 months in April after admitting charges related to the drugs money

Summary: Johnny Kock, 68, tried to import £1bn of cocaine in washing powder boxes. Was arrested last October when police discovered £26m of cocaine. Police found the drugs in two separate seizures in Germany and France. The court was told the seizures were just two out of 57 shipments delivered to his business in Kirkby, Liverpool. He was sentenced to 25 years in prison at Liverpool Crown Court yesterday. Judge Mark Brown said: 'In terms of the amounts of cocaine, this must be one of the biggest ever offences considered by the courts'

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Summarize: When he applied for a job on Mr. de Blasio’s City Council staff, Alex Navarro-McKay recalled an unconventional stage of the process — an interview with Ms. McCray. She greeted him at the door of the couple’s Park Slope home, sat him down on the living room couch, then asked him about his experiences and goals. The close working relationship “definitely struck me as new and unusual,” said another Council staff member, Abeni Crooms. Aides stressed that Ms. McCray’s power was wielded informally and quietly. She is not known to issue assignments to staff, or to formally dictate policy to her husband, they said. Still, Mr. de Blasio conceded that he relied so frequently on his wife that he was wary of missing the kind of outside perspectives “that make sure the two of us don’t sometimes see the world too narrowly.” Friends and aides sense that behind the couple’s mutual reliance is an abiding desire to upend what they see as the tired assumptions about political marriages. Mr. de Blasio has no patience for even the language surrounding such a union, telling a church congregation not long ago that his family had banished the old cliché about the great woman behind every great man. “We don’t accept that phrase anymore — it went out with the stagecoach,” he said. “In our house,” he added, the woman stands “beside.” He takes pains to put that philosophy into practice, offering lavish introductions of his wife at almost every event (“a great activist,” “a great writer”), pushing her to speak up in meetings and ensuring, in ways big and small, that she shares the spotlight. During a visit to a food pantry a few days ago, Mr. de Blasio switched places with her to avoid blocking her in front of the cameras. The couple is highly attuned to the political benefits of their biracial union. During Mr. de Blasio’s run for public advocate four years ago, Ms. McCray sat in on focus groups in which minority voters talked about the strong appeal of the family’s racial diversity — images of which Mr. de Blasio featured prominently in campaign brochures and mailers. In an email to his staff back then, Mr. de Blasio said his wife believed that the campaign literature was “striking a nerve, maybe a post-Obama one” and that she wished to further promote it. Mr. de Blasio’s office declined to comment on the previously undisclosed emails that were provided to The New York Times, but did not dispute any of the quotes from them. Ms. McCray and Mr. de Blasio seem unbothered by inevitable comparisons to first couples, like the Clintons, whose reputation as a package deal bred scrutiny and resentment. Instead, they revel in introducing a similar model to City Hall. “We are obviously not like any couple that has been there before,” Mr. de Blasio said. Ms. McCray, who currently holds no job outside of advising her husband, has no official role in the transition process. But that was also the case during Mr. de Blasio’s mayoral campaign, when she nevertheless had an outsize influence. It was Ms. McCray, after all, who selected the symbolically rich location for Mr. de Blasio’s speech announcing his candidacy: the yard in front of the family’s humble rowhouse in Park Slope. It was Ms. McCray who assiduously courted the endorsement of Una Clarke, a beloved former councilwoman in central Brooklyn who, like her, is Caribbean-American. “I don’t think we had a meeting at which she was not present,” Ms. Clarke said. And it was Ms. McCray who prompted the campaign to contemplate the repercussions of a high-risk strategy: participating in an act of civil disobedience. Earlier this year, Ms. McCray proposed being arrested during a protest to support women’s rights. Her idea laid the groundwork for Mr. de Blasio’s own headline-grabbing arrest a few weeks later over the planned closure of a hospital in Brooklyn. It fell to Mr. de Blasio’s campaign manager, Bill Hyers, to brief the candidate. “I think I am going to get your wife arrested,” he told Mr. de Blasio. “What?” a startled Mr. de Blasio replied. “No, no,” Mr. Hyers explained. “She wants to.” Bill de Blasio’s wife, Chirlane McCray, was fed up. An ad for her husband’s political opponent was running on her favorite radio station, and she wanted the de Blasio campaign to respond. “How much money do I have to raise this week to deal with this affront?” she wrote in a blunt email to her husband’s top aides in 2009, mischievously warning that if the ad interrupted a cherished R & B show, “I might get road rage.” Such interventions from Ms. McCray were not unusual: Mr. de Blasio urged his political team to heed her words. In an email of his own, he shared his wife’s suggestions for how best to disseminate a campaign brochure in the race for public advocate that featured the diverse de Blasio family. (One idea: “Give it out at beauty salons.”) The email’s subject line was telling: “This is the word of Chirlane.” Publicly, Mr. de Blasio remains vague about the kind of role Ms. McCray, a 59-year-old poet and writer, will occupy in his administration. But dozens of conversations with aides, a review of previously undisclosed emails and an interview with the couple suggest there is little precedent in New York for the intense day-to-day political partnership that the mayor-elect and his wife intend to bring to City Hall on Jan. 1.

Summary: When it came to tough campaign questions, Bill de Blasio relied on wife Chirlane McCray's counsel-and that relationship is poised to continue while he's mayor of New York City. "We are obviously not like any couple that has been there before," de Blasio tells the New York Times, which cites "little precedent" in Gracie Mansion for the pair's political alliance. The pair, however, do draw comparisons to the Clintons. "She is the most important adviser I have," says de Blasio, adding that McCray's contributions to his administration will fit a "partnership model" reminiscent of the work of "well-known senior advisers down through history." McCray plays a key role in policy and strategy decisions, choosing staff, and writing speeches. When a radio ad for de Blasio's opponent angered her, she wrote to aides to address it; an email from de Blasio to staffers, labeled "This is the word of Chirlane," pushed her ideas on brochure distribution. Her exact duties aren't specified or formal, but she's "most often the person who is right," de Blasio tells the Times. One concern, however, is the risk of insularity. The incoming mayor wants to "make sure the two of us don't sometimes see the world too narrowly." Click for the full profile.

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Summarize: After giving a speech that emphasized the Islamization of Libya, the head of the transitional government on Monday tried to reassure the Western powers who helped topple Moammar Gadhafi that the country's new leaders are moderate Muslims. Libyan Transitional National Council chairman Mustafa Abdul-Jalil, right, and Ali Tarhouni, Libyan National Transitional Council's minister for Oil and Finance, second left, greet Libyan veterans during... (Associated Press) Libyan Transitional National Council chairman Mustafa Abdul-Jalil, left, looks on, as Ali Tarhouni, Libyan National Transitional Council's minister for Oil and Finance, right, delivers a press conference... (Associated Press) Just as in neighboring Tunisia and Egypt, Islamists have emerged from yet another Arab Spring uprising as the most powerful group in the country. How far they will go will be decided at the ballot box _ in Tunisia this week, in Egypt in November and in Libya within eight months. National Transitional Council leader Mustafa Abdul-Jalil said Sunday that Islamic Sharia law would be the main source of legislation, that laws contradicting its tenets would be nullified, and that polygamy would be legalized. "I would like to assure the international community that we as Libyans are moderate Muslims," said Abdul-Jalil, who added that he was dismayed by the focus abroad on his comments Sunday on polygamy. A State Department spokeswoman said the U.S. was encouraged that he had clarified his earlier statement. The stir created by Abdul-Jalil's address in Benghazi, the eastern Libyan city where the anti-Gadhafi uprising was born in mid-February, came as international pressure mounted on him to investigate the circumstances of Gadhafi's death. Abdul-Jalil ordered an inquiry to establish whether the deposed Libyan leader was killed in an execution-style slaying after being captured alive Thursday by fighters in his hometown of Sirte or whether he died in the crossfire as government officials have suggested. State Department spokeswoman Victoria Nuland reiterated U.S. support for a full investigation but said "it's now time for Libya to move on." She endorsed the NTC's proposed timeline for next steps in the democratic transition, and said Libyans "with no blood on their hands" must be ensured "a place in the new Libya, and that they are safe and they are included." She also called a Human Rights Watch report that dozens of Gadhafi supporters were found dead with bullet wounds in the back of the head and their hands tied, "extremely disturbing." She said U.S. Ambassador to Libya Gene Cretz raised Washington's concerns with the council and asked them to conduct another investigation. Gadhafi's body went on public display since Friday in a commercial refrigerator in the port city of Misrata, where residents lined up to see it. Late Monday, an APTN crew saw vehicles driving away from the refrigerator, and Associated Press reporters saw that it was empty. A military commander said the bodies were handed over to authorities for burial. Ibrahim Beit al-Mal, a spokesman for the fighters, said he expected that the bodies of Gadhafi, his slain son Muatassim and former Defense Minister Abu Bakr Younis would be buried Tuesday in an unmarked grave in a secret location. Abdul-Jalil said earlier that the transitional government has established a committee to determine what to do with Gadhafi's body, adding that the decision will be governed by a religious edict by the head of the Islamic Fatwa society. Several videos have emerged showing Gadhafi was alive when he was captured and taunted and beaten by revolutionary fighters in Sirte. The Boston-based international news site GlobalPost posted a video showing Gadhafi's captors ramming a stick into his buttocks through his pants. Guma al-Gamaty, a London-based spokesman for the National Transitional Council, said Abdul-Jalil had an obligation at the dawn of a new era to assure Libyans that Islam will be respected. "This doesn't mean that Libya will become a theocracy. There is no chance of that whatsoever. Libya will be a civic state, a democratic state and, in principle, its laws will not contradict democracy," he said. It is the kind of assurance Western powers that supported the anti-Gadhafi fighters with airstrikes and diplomatic backing may have been looking for. In Washington, Nuland stressed the importance of creating "a democracy that meets international human rights standards, that provides a place for all Libyans and that serves to unify the country." She said the U.S. was encouraged that Abdul-Jalil clarified his earlier statements on the topic, but hedged on an overall U.S. assessment of systems based on Sharia. "We've seen various Islamic- based democracies wrestle with the issue of establishing rule of law within an appropriate cultural context," Nuland said. "But the No. 1 thing is that universal human rights, rights for women, rights for minorities, right to due process, right to transparency be fully respected." French Foreign Ministry spokesman Bernard Valero played down the comments. "We have confidence that the Libyan people, who have courageously freed themselves from 42 years of dictatorship, will build a lawful state, in conformity with the principles and universal values shared by the international community," Valero said in an online briefing Monday. Many Libyans welcomed Abdul-Jalil's comments as a chance to overturn Gadhafi's rulings as he cracked down on Islamists in his later years. Others were critical, saying it was the wrong time to raise the issue. Hana el-Gallal, a human rights activist, said she was not against the implementation of Sharia law but only if done correctly. "For me, the speech was not up to the historical moment we are going through. We know the Quran and we know the basics of our religion. We are not against polygamy but it is better to regulate it," she said. "Maybe he is trying to make sure that we are not going to be a Westernized country. I don't know what kind of threat he faces," she added. Libya is a deeply conservative Muslim nation, with most women wearing headscarves or the all-encompassing niqab. Islamists were heavily repressed under Gadhafi and are eager to have their say, raising the prospect of a battle for influence between hard-line and moderate Muslims. Already several attacks have occurred on shrines in and around Tripoli belonging to Muslim sects whose practices are seen as sacrilegious. Abdul-Jalil singled out banks charging interest as something that will be abolished to conform with Sharia laws that equate bank interest with usury. He also said that a Gadhafi-era law that sets conditions on Libyan men wishing to take a second wife, including the written approval of the first wife, will have to be nullified since the Quran allows men to take up to four wives. "If we follow Islamic principles, then Islam does ban interest. This is an Islamic rule that can't be negotiated. Some banks are following the Islamic way, which is sharing losses or profits.... Quran is the higher constitution for all Muslims," Abdul-Jalil said on Monday. Implementing Sharia in Libya may not necessarily mean the North African nation will turn into regimes like clergy-ruled Iran or Afghanistan under the Taliban. The extent of how far Sharia law can be applied depends in large part on the interpretation of a large body of Quranic verses and sayings and deeds of Muhammad, Islam's seventh century prophet. Sharia law is enshrined the constitution of a number of Middle Eastern countries with Muslim majorities, but the role it plays in society varies according to interpretations. Some nations, such as Iran and Saudi Arabia, follow a stricter interpretation that mandates cutting off the hands of thieves, the heads of murderers and stoning adulterers to death. Those who drink alcohol are publicly flogged. Others, such as Egypt, state that Sharia is a main source of legislation but have largely secular laws. "It may not be quite be the country that NATO thought it was fighting for (when Sharia is implemented in Libya)," said David Hartwell, a British-based Libya expert. "But the huge amounts of oil and gas in Libya will make everyone learn how to reconcile themselves with the new Libya." Gadhafi's approach to Islam has changed through his nearly 42 years as leader. On coming to power in 1969, he pushed for an interpretation of Islam that encouraged the fight against European colonial powers in Libya and across the globe. He banned alcohol in line with the faith's teachings and turned against liberals and leftists during his early years in power. In later years, however, Gadhafi saw militants as a threat to his authoritarian rule. He jailed and put to death many of them while sending agents of his powerful security organs to monitor and, in some cases, arrest Libyans showing signs of piety, such as frequenting mosques to offer dawn prayers. Islamists are a small minority among Libya's population of 6 million, but they were by far the largest and most powerful faction among the fighters who battled pro-Gadhafi forces in eight months of civil war. Abdul-Jalil, analysts said, was likely to have given his address an Islamic slant as a nod to those fighters who were united with other factions by the common goal of ousting Gadhafi but now are jockeying to fill the political vacuum left by his ouster. "Abdul-Jalil's religious rhetoric reflects moderate Islam," said Ali Ahmida, a Libyan who chairs the Department of Political Science at the University of New England at Biddeford, Maine. "His address was an attempt to appease the Islamic groups that fought Gadhafi, but should have come as no surprise in Libya, where Islam plays a much bigger role than it does in neighboring countries." The emergence of Libya's Islamists as the strongest faction in the wake of Gadhafi's removal repeats a pattern seen in Tunisia and Egypt. Early signs from Tunisia's parliamentary election Sunday show that a once-banned Islamist party, Ennahda, has a commanding lead in the first vote since a popular uprising forced President Zine El-Abidine Ben Ali to flee the country on Jan. 14. In Egypt, Islamists also are poised to emerge as the largest bloc when a parliamentary election is held next month. It will be the first nationwide election since Hosni Mubarak, Egypt's ruler of 29 years, was ousted in February. ___ Hendawi reported from Cairo. Associated Press writers Karin Laub in Misrata and Maggie Michael in Cairo contributed to this report. WARNING: IMAGES BELOW ARE PARTICULARLY GRAPHIC AND UPSETTING. SIRTE, Libya — An analysis of video obtained by GlobalPost from a rebel fighter who recorded the moment when Col. Muammar Gaddafi was first captured confirms that another rebel fighter, whose identity is unknown, sodomized the former leader as he was being dragged from the drainpipe where he had taken cover. A frame by frame analysis of this exclusive GlobalPost video clearly shows the rebel trying to insert some kind of stick or knife into Gaddafi's rear end. Full coverage: Death of Muammar Gaddafi GlobalPost correspondent Tracey Shelton said there is some question as to whether the instrument was a knife from the end of a machine gun, which Libyans call a Bicketti, or some kind of stick. This latest video discovery comes as international and human rights groups call for a formal investigation into how the former Libyan leader was killed. In video clips that have emerged of his capture, Gaddafi can be seen injured but alive. Later he is seen with what appears to be gunshot wounds to his head and chest. According to the Geneva Conventions, however, abuse of prisoners under any circumstance is not permissable. Related: Gaddafi to be buried in "secret desert location" Here is a frame by frame look at the attack. Below the frames is video decoding the cell phone footage of the capture. And, finally, at the bottom is the full video. You can see the attempt to sodomize Gaddafi at the 16 second mark. WARNING: Extremely graphic DECODING MUAMMAR GADDAFI'S CAPTURE: FULL VIDEO OF MUAMMAR GADDAFI'S CAPTURE:

Summary: While Libyan rebels say Gadhafi will be buried tomorrow, it appears one freedom-fighter sodomized the former leader during his capture and murder last week. A closer look at video of the scene shows a rebel inserting a stick or knife into Gadhafi's rear end as he is dragged from a drainpipe, GlobalPost reports. It was likely a knife from the end of a gun, called a Bicketti, or a Becker Knife known popularly as a BKT. International and human rights groups were already calling for an inquiry into Gadhafi's death; any abuse of prisoners is not permitted by the Geneva Convention. The video and stills are here, but be warned-the content is gruesome. As for his funeral, a rebel spokesman says Gadhafi, his son Muatassim, and the former defense minister will be buried tomorrow at a hidden location in an unmarked grave, the AP reports.

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Summarize: "Look at those spangles, Miss Bart--every one of 'em sewed on crooked." The tall forewoman, a pinched perpendicular figure, dropped the condemned structure of wire and net on the table at Lily's side, and passed on to the next figure in the line. There were twenty of them in the work-room, their fagged profiles, under exaggerated hair, bowed in the harsh north light above the utensils of their art; for it was something more than an industry, surely, this creation of ever-varied settings for the face of fortunate womanhood. Their own faces were sallow with the unwholesomeness of hot air and sedentary toil, rather than with any actual signs of want: they were employed in a fashionable millinery establishment, and were fairly well clothed and well paid; but the youngest among them was as dull and colourless as the middle-aged. In the whole work-room there was only one skin beneath which the blood still visibly played; and that now burned with vexation as Miss Bart, under the lash of the forewoman's comment, began to strip the hat-frame of its over-lapping spangles. To Gerty Farish's hopeful spirit a solution appeared to have been reached when she remembered how beautifully Lily could trim hats. Instances of young lady-milliners establishing themselves under fashionable patronage, and imparting to their "creations" that indefinable touch which the professional hand can never give, had flattered Gerty's visions of the future, and convinced even Lily that her separation from Mrs. Norma Hatch need not reduce her to dependence on her friends. The parting had occurred a few weeks after Selden's visit, and would have taken place sooner had it not been for the resistance set up in Lily by his ill-starred offer of advice. The sense of being involved in a transaction she would not have cared to examine too closely had soon afterward defined itself in the light of a hint from Mr. Stancy that, if she "saw them through," she would have no reason to be sorry. The implication that such loyalty would meet with a direct reward had hastened her flight, and flung her back, ashamed and penitent, on the broad bosom of Gerty's sympathy. She did not, however, propose to lie there prone, and Gerty's inspiration about the hats at once revived her hopes of profitable activity. Here was, after all, something that her charming listless hands could really do; she had no doubt of their capacity for knotting a ribbon or placing a flower to advantage. And of course only these finishing touches would be expected of her: subordinate fingers, blunt, grey, needle-pricked fingers, would prepare the shapes and stitch the linings, while she presided over the charming little front shop--a shop all white panels, mirrors, and moss-green hangings--where her finished creations, hats, wreaths, aigrettes and the rest, perched on their stands like birds just poising for flight. But at the very outset of Gerty's campaign this vision of the green-and-white shop had been dispelled. Other young ladies of fashion had been thus "set-up," selling their hats by the mere attraction of a name and the reputed knack of tying a bow; but these privileged beings could command a faith in their powers materially expressed by the readiness to pay their shop-rent and advance a handsome sum for current expenses. Where was Lily to find such support? And even could it have been found, how were the ladies on whose approval she depended to be induced to give her their patronage? Gerty learned that whatever sympathy her friend's case might have excited a few months since had been imperilled, if not lost, by her association with Mrs. Hatch. Once again, Lily had withdrawn from an ambiguous situation in time to save her self-respect, but too late for public vindication. Freddy Van Osburgh was not to marry Mrs. Hatch; he had been rescued at the eleventh hour--some said by the efforts of Gus Trenor and Rosedale--and despatched to Europe with old Ned Van Alstyne; but the risk he had run would always be ascribed to Miss Bart's connivance, and would somehow serve as a summing-up and corroboration of the vague general distrust of her. It was a relief to those who had hung back from her to find themselves thus justified, and they were inclined to insist a little on her connection with the Hatch case in order to show that they had been right. Gerty's quest, at any rate, brought up against a solid wall of resistance; and even when Carry Fisher, momentarily penitent for her share in the Hatch affair, joined her efforts to Miss Farish's, they met with no better success. Gerty had tried to veil her failure in tender ambiguities; but Carry, always the soul of candour, put the case squarely to her friend. "I went straight to Judy Trenor; she has fewer prejudices than the others, and besides she's always hated Bertha Dorset. But what HAVE you done to her, Lily? At the very first word about giving you a start she flamed out about some money you'd got from Gus; I never knew her so hot before. You know she'll let him do anything but spend money on his friends: the only reason she's decent to me now is that she knows I'm not hard up.--He speculated for you, you say? Well, what's the harm? He had no business to lose. He DIDN'T lose? Then what on earth--but I never COULD understand you, Lily!" The end of it was that, after anxious enquiry and much deliberation, Mrs. Fisher and Gerty, for once oddly united in their effort to help their friend, decided on placing her in the work-room of Mme. Regina's renowned millinery establishment. Even this arrangement was not effected without considerable negotiation, for Mme. Regina had a strong prejudice against untrained assistance, and was induced to yield only by the fact that she owed the patronage of Mrs. Bry and Mrs. Gormer to Carry Fisher's influence. She had been willing from the first to employ Lily in the show-room: as a displayer of hats, a fashionable beauty might be a valuable asset. But to this suggestion Miss Bart opposed a negative which Gerty emphatically supported, while Mrs. Fisher, inwardly unconvinced, but resigned to this latest proof of Lily's unreason, agreed that perhaps in the end it would be more useful that she should learn the trade. To Regina's work-room Lily was therefore committed by her friends, and there Mrs. Fisher left her with a sigh of relief, while Gerty's watchfulness continued to hover over her at a distance. Lily had taken up her work early in January: it was now two months later, and she was still being rebuked for her inability to sew spangles on a hat-frame. As she returned to her work she heard a titter pass down the tables. She knew she was an object of criticism and amusement to the other work-women. They were, of course, aware of her history--the exact situation of every girl in the room was known and freely discussed by all the others--but the knowledge did not produce in them any awkward sense of class distinction: it merely explained why her untutored fingers were still blundering over the rudiments of the trade. Lily had no desire that they should recognize any social difference in her; but she had hoped to be received as their equal, and perhaps before long to show herself their superior by a special deftness of touch, and it was humiliating to find that, after two months of drudgery, she still betrayed her lack of early training. Remote was the day when she might aspire to exercise the talents she felt confident of possessing; only experienced workers were entrusted with the delicate art of shaping and trimming the hat, and the forewoman still held her inexorably to the routine of preparatory work. She began to rip the spangles from the frame, listening absently to the buzz of talk which rose and fell with the coming and going of Miss Haines's active figure. The air was closer than usual, because Miss Haines, who had a cold, had not allowed a window to be opened even during the noon recess; and Lily's head was so heavy with the weight of a sleepless night that the chatter of her companions had the incoherence of a dream. "I TOLD her he'd never look at her again; and he didn't. I wouldn't have, either--I think she acted real mean to him. He took her to the Arion Ball, and had a hack for her both ways.... She's taken ten bottles, and her headaches don't seem no better--but she's written a testimonial to say the first bottle cured her, and she got five dollars and her picture in the paper.... Mrs. Trenor's hat? The one with the green Paradise? Here, Miss Haines--it'll be ready right off.... That was one of the Trenor girls here yesterday with Mrs. George Dorset. How'd I know? Why, Madam sent for me to alter the flower in that Virot hat--the blue tulle: she's tall and slight, with her hair fuzzed out--a good deal like Mamie Leach, on'y thinner...." On and on it flowed, a current of meaningless sound, on which, startlingly enough, a familiar name now and then floated to the surface. It was the strangest part of Lily's strange experience, the hearing of these names, the seeing the fragmentary and distorted image of the world she had lived in reflected in the mirror of the working-girls' minds. She had never before suspected the mixture of insatiable curiosity and contemptuous freedom with which she and her kind were discussed in this underworld of toilers who lived on their vanity and self-indulgence. Every girl in Mme. Regina's work-room knew to whom the headgear in her hands was destined, and had her opinion of its future wearer, and a definite knowledge of the latter's place in the social system. That Lily was a star fallen from that sky did not, after the first stir of curiosity had subsided, materially add to their interest in her. She had fallen, she had "gone under," and true to the ideal of their race, they were awed only by success--by the gross tangible image of material achievement. The consciousness of her different point of view merely kept them at a little distance from her, as though she were a foreigner with whom it was an effort to talk. "Miss Bart, if you can't sew those spangles on more regular I guess you'd better give the hat to Miss Kilroy." Lily looked down ruefully at her handiwork. The forewoman was right: the sewing on of the spangles was inexcusably bad. What made her so much more clumsy than usual? Was it a growing distaste for her task, or actual physical disability? She felt tired and confused: it was an effort to put her thoughts together. She rose and handed the hat to Miss Kilroy, who took it with a suppressed smile. "I'm sorry; I'm afraid I am not well," she said to the forewoman. Miss Haines offered no comment. From the first she had augured ill of Mme. Regina's consenting to include a fashionable apprentice among her workers. In that temple of art no raw beginners were wanted, and Miss Haines would have been more than human had she not taken a certain pleasure in seeing her forebodings confirmed. "You'd better go back to binding edges," she said drily. Lily slipped out last among the band of liberated work-women. She did not care to be mingled in their noisy dispersal: once in the street, she always felt an irresistible return to her old standpoint, an instinctive shrinking from all that was unpolished and promiscuous. In the days--how distant they now seemed!--when she had visited the Girls' Club with Gerty Farish, she had felt an enlightened interest in the working-classes; but that was because she looked down on them from above, from the happy altitude of her grace and her beneficence. Now that she was on a level with them, the point of view was less interesting. She felt a touch on her arm, and met the penitent eye of Miss Kilroy. "Miss Bart, I guess you can sew those spangles on as well as I can when you're feeling right. Miss Haines didn't act fair to you." Lily's colour rose at the unexpected advance: it was a long time since real kindness had looked at her from any eyes but Gerty's. "Oh, thank you: I'm not particularly well, but Miss Haines was right. I AM clumsy." "Well, it's mean work for anybody with a headache." Miss Kilroy paused irresolutely. "You ought to go right home and lay down. Ever try orangeine?" "Thank you." Lily held out her hand. "It's very kind of you--I mean to go home." She looked gratefully at Miss Kilroy, but neither knew what more to say. Lily was aware that the other was on the point of offering to go home with her, but she wanted to be alone and silent--even kindness, the sort of kindness that Miss Kilroy could give, would have jarred on her just then. "Thank you," she repeated as she turned away. She struck westward through the dreary March twilight, toward the street where her boarding-house stood. She had resolutely refused Gerty's offer of hospitality. Something of her mother's fierce shrinking from observation and sympathy was beginning to develop in her, and the promiscuity of small quarters and close intimacy seemed, on the whole, less endurable than the solitude of a hall bedroom in a house where she could come and go unremarked among other workers. For a while she had been sustained by this desire for privacy and independence; but now, perhaps from increasing physical weariness, the lassitude brought about by hours of unwonted confinement, she was beginning to feel acutely the ugliness and discomfort of her surroundings. The day's task done, she dreaded to return to her narrow room, with its blotched wallpaper and shabby paint; and she hated every step of the walk thither, through the degradation of a New York street in the last stages of decline from fashion to commerce. But what she dreaded most of all was having to pass the chemist's at the corner of Sixth Avenue. She had meant to take another street: she had usually done so of late. But today her steps were irresistibly drawn toward the flaring plate-glass corner; she tried to take the lower crossing, but a laden dray crowded her back, and she struck across the street obliquely, reaching the sidewalk just opposite the chemist's door. Over the counter she caught the eye of the clerk who had waited on her before, and slipped the prescription into his hand. There could be no question about the prescription: it was a copy of one of Mrs. Hatch's, obligingly furnished by that lady's chemist. Lily was confident that the clerk would fill it without hesitation; yet the nervous dread of a refusal, or even of an expression of doubt, communicated itself to her restless hands as she affected to examine the bottles of perfume stacked on the glass case before her. The clerk had read the prescription without comment; but in the act of handing out the bottle he paused. "You don't want to increase the dose, you know," he remarked. Lily's heart contracted. What did he mean by looking at her in that way? "Of course not," she murmured, holding out her hand. "That's all right: it's a queer-acting drug. A drop or two more, and off you go--the doctors don't know why." The dread lest he should question her, or keep the bottle back, choked the murmur of acquiescence in her throat; and when at length she emerged safely from the shop she was almost dizzy with the intensity of her relief. The mere touch of the packet thrilled her tired nerves with the delicious promise of a night of sleep, and in the reaction from her momentary fear she felt as if the first fumes of drowsiness were already stealing over her. In her confusion she stumbled against a man who was hurrying down the last steps of the elevated station. He drew back, and she heard her name uttered with surprise. It was Rosedale, fur-coated, glossy and prosperous--but why did she seem to see him so far off, and as if through a mist of splintered crystals? Before she could account for the phenomenon she found herself shaking hands with him. They had parted with scorn on her side and anger upon his; but all trace of these emotions seemed to vanish as their hands met, and she was only aware of a confused wish that she might continue to hold fast to him. "Why, what's the matter, Miss Lily? You're not well!" he exclaimed; and she forced her lips into a pallid smile of reassurance. "I'm a little tired--it's nothing. Stay with me a moment, please," she faltered. That she should be asking this service of Rosedale! He glanced at the dirty and unpropitious corner on which they stood, with the shriek of the "elevated" and the tumult of trams and waggons contending hideously in their ears. "We can't stay here; but let me take you somewhere for a cup of tea. The LONGWORTH is only a few yards off, and there'll be no one there at this hour." A cup of tea in quiet, somewhere out of the noise and ugliness, seemed for the moment the one solace she could bear. A few steps brought them to the ladies' door of the hotel he had named, and a moment later he was seated opposite to her, and the waiter had placed the tea-tray between them. "Not a drop of brandy or whiskey first? You look regularly done up, Miss Lily. Well, take your tea strong, then; and, waiter, get a cushion for the lady's back." Lily smiled faintly at the injunction to take her tea strong. It was the temptation she was always struggling to resist. Her craving for the keen stimulant was forever conflicting with that other craving for sleep--the midnight craving which only the little phial in her hand could still. But today, at any rate, the tea could hardly be too strong: she counted on it to pour warmth and resolution into her empty veins. As she leaned back before him, her lids drooping in utter lassitude, though the first warm draught already tinged her face with returning life, Rosedale was seized afresh by the poignant surprise of her beauty. The dark pencilling of fatigue under her eyes, the morbid blue-veined pallour of the temples, brought out the brightness of her hair and lips, as though all her ebbing vitality were centred there. Against the dull chocolate-coloured background of the restaurant, the purity of her head stood out as it had never done in the most brightly-lit ball-room. He looked at her with a startled uncomfortable feeling, as though her beauty were a forgotten enemy that had lain in ambush and now sprang out on him unawares. To clear the air he tried to take an easy tone with her. "Why, Miss Lily, I haven't seen you for an age. I didn't know what had become of you." As he spoke, he was checked by an embarrassing sense of the complications to which this might lead. Though he had not seen her he had heard of her; he knew of her connection with Mrs. Hatch, and of the talk resulting from it. Mrs. Hatch's MILIEU was one which he had once assiduously frequented, and now as devoutly shunned. Lily, to whom the tea had restored her usual clearness of mind, saw what was in his thoughts and said with a slight smile: "You would not be likely to know about me. I have joined the working classes." He stared in genuine wonder. "You don't mean--? Why, what on earth are you doing?" "Learning to be a milliner--at least TRYING to learn," she hastily qualified the statement. Rosedale suppressed a low whistle of surprise. "Come off--you ain't serious, are you?" "Perfectly serious. I'm obliged to work for my living." "But I understood--I thought you were with Norma Hatch." "You heard I had gone to her as her secretary?" "Something of the kind, I believe." He leaned forward to refill her cup. Lily guessed the possibilities of embarrassment which the topic held for him, and raising her eyes to his, she said suddenly: "I left her two months ago." Rosedale continued to fumble awkwardly with the tea-pot, and she felt sure that he had heard what had been said of her. But what was there that Rosedale did not hear? "Wasn't it a soft berth?" he enquired, with an attempt at lightness. "Too soft--one might have sunk in too deep." Lily rested one arm on the edge of the table, and sat looking at him more intently than she had ever looked before. An uncontrollable impulse was urging her to put her case to this man, from whose curiosity she had always so fiercely defended herself. "You know Mrs. Hatch, I think? Well, perhaps you can understand that she might make things too easy for one." Rosedale looked faintly puzzled, and she remembered that allusiveness was lost on him. "It was no place for you, anyhow," he agreed, so suffused and immersed in the light of her full gaze that he found himself being drawn into strange depths of intimacy. He who had had to subsist on mere fugitive glances, looks winged in flight and swiftly lost under covert, now found her eyes settling on him with a brooding intensity that fairly dazzled him. "I left," Lily continued, "lest people should say I was helping Mrs. Hatch to marry Freddy Van Osburgh--who is not in the least too good for her--and as they still continue to say it, I see that I might as well have stayed where I was." "Oh, Freddy----" Rosedale brushed aside the topic with an air of its unimportance which gave a sense of the immense perspective he had acquired. "Freddy don't count--but I knew YOU weren't mixed up in that. It ain't your style." Lily coloured slightly: she could not conceal from herself that the words gave her pleasure. She would have liked to sit there, drinking more tea, and continuing to talk of herself to Rosedale. But the old habit of observing the conventions reminded her that it was time to bring their colloquy to an end, and she made a faint motion to push back her chair. Rosedale stopped her with a protesting gesture. "Wait a minute--don't go yet; sit quiet and rest a little longer. You look thoroughly played out. And you haven't told me----" He broke off, conscious of going farther than he had meant. She saw the struggle and understood it; understood also the nature of the spell to which he yielded as, with his eyes on her face, he began again abruptly: "What on earth did you mean by saying just now that you were learning to be a milliner?" "Just what I said. I am an apprentice at Regina's." "Good Lord--YOU? But what for? I knew your aunt had turned you down: Mrs. Fisher told me about it. But I understood you got a legacy from her----" "I got ten thousand dollars; but the legacy is not to be paid till next summer." "Well, but--look here: you could BORROW on it any time you wanted." She shook her head gravely. "No; for I owe it already." "Owe it? The whole ten thousand?" "Every penny." She paused, and then continued abruptly, with her eyes on his face: "I think Gus Trenor spoke to you once about having made some money for me in stocks." She waited, and Rosedale, congested with embarrassment, muttered that he remembered something of the kind. "He made about nine thousand dollars," Lily pursued, in the same tone of eager communicativeness. "At the time, I understood that he was speculating with my own money: it was incredibly stupid of me, but I knew nothing of business. Afterward I found out that he had NOT used my money--that what he said he had made for me he had really given me. It was meant in kindness, of course; but it was not the sort of obligation one could remain under. Unfortunately I had spent the money before I discovered my mistake; and so my legacy will have to go to pay it back. That is the reason why I am trying to learn a trade." She made the statement clearly, deliberately, with pauses between the sentences, so that each should have time to sink deeply into her hearer's mind. She had a passionate desire that some one should know the truth about this transaction, and also that the rumour of her intention to repay the money should reach Judy Trenor's ears. And it had suddenly occurred to her that Rosedale, who had surprised Trenor's confidence, was the fitting person to receive and transmit her version of the facts. She had even felt a momentary exhilaration at the thought of thus relieving herself of her detested secret; but the sensation gradually faded in the telling, and as she ended her pallour was suffused with a deep blush of misery. Rosedale continued to stare at her in wonder; but the wonder took the turn she had least expected. "But see here--if that's the case, it cleans you out altogether?" He put it to her as if she had not grasped the consequences of her act; as if her incorrigible ignorance of business were about to precipitate her into a fresh act of folly. "Altogether--yes," she calmly agreed. He sat silent, his thick hands clasped on the table, his little puzzled eyes exploring the recesses of the deserted restaurant. "See here--that's fine," he exclaimed abruptly. Lily rose from her seat with a deprecating laugh. "Oh, no--it's merely a bore," she asserted, gathering together the ends of her feather scarf. Rosedale remained seated, too intent on his thoughts to notice her movement. "Miss Lily, if you want any backing--I like pluck----" broke from him disconnectedly. "Thank you." She held out her hand. "Your tea has given me a tremendous backing. I feel equal to anything now." Her gesture seemed to show a definite intention of dismissal, but her companion had tossed a bill to the waiter, and was slipping his short arms into his expensive overcoat. "Wait a minute--you've got to let me walk home with you," he said. Lily uttered no protest, and when he had paused to make sure of his change they emerged from the hotel and crossed Sixth Avenue again. As she led the way westward past a long line of areas which, through the distortion of their paintless rails, revealed with increasing candour the DISJECTA MEMBRA of bygone dinners, Lily felt that Rosedale was taking contemptuous note of the neighbourhood; and before the doorstep at which she finally paused he looked up with an air of incredulous disgust. "This isn't the place? Some one told me you were living with Miss Farish." "No: I am boarding here. I have lived too long on my friends." He continued to scan the blistered brown stone front, the windows draped with discoloured lace, and the Pompeian decoration of the muddy vestibule; then he looked back at her face and said with a visible effort: "You'll let me come and see you some day?" She smiled, recognizing the heroism of the offer to the point of being frankly touched by it. "Thank you--I shall be very glad," she made answer, in the first sincere words she had ever spoken to him. That evening in her own room Miss Bart--who had fled early from the heavy fumes of the basement dinner-table--sat musing upon the impulse which had led her to unbosom herself to Rosedale. Beneath it she discovered an increasing sense of loneliness--a dread of returning to the solitude of her room, while she could be anywhere else, or in any company but her own. Circumstances, of late, had combined to cut her off more and more from her few remaining friends. On Carry Fisher's part the withdrawal was perhaps not quite involuntary. Having made her final effort on Lily's behalf, and landed her safely in Mme. Regina's work-room, Mrs. Fisher seemed disposed to rest from her labours; and Lily, understanding the reason, could not condemn her. Carry had in fact come dangerously near to being involved in the episode of Mrs. Norma Hatch, and it had taken some verbal ingenuity to extricate herself. She frankly owned to having brought Lily and Mrs. Hatch together, but then she did not know Mrs. Hatch--she had expressly warned Lily that she did not know Mrs. Hatch--and besides, she was not Lily's keeper, and really the girl was old enough to take care of herself. Carry did not put her own case so brutally, but she allowed it to be thus put for her by her latest bosom friend, Mrs. Jack Stepney: Mrs. Stepney, trembling over the narrowness of her only brother's escape, but eager to vindicate Mrs. Fisher, at whose house she could count on the "jolly parties" which had become a necessity to her since marriage had emancipated her from the Van Osburgh point of view. Lily understood the situation and could make allowances for it. Carry had been a good friend to her in difficult days, and perhaps only a friendship like Gerty's could be proof against such an increasing strain. Gerty's friendship did indeed hold fast; yet Lily was beginning to avoid her also. For she could not go to Gerty's without risk of meeting Selden; and to meet him now would be pure pain. It was pain enough even to think of him, whether she considered him in the distinctness of her waking thoughts, or felt the obsession of his presence through the blur of her tormented nights. That was one of the reasons why she had turned again to Mrs. Hatch's prescription. In the uneasy snatches of her natural dreams he came to her sometimes in the old guise of fellowship and tenderness; and she would rise from the sweet delusion mocked and emptied of her courage. But in the sleep which the phial procured she sank far below such half-waking visitations, sank into depths of dreamless annihilation from which she woke each morning with an obliterated past. Gradually, to be sure, the stress of the old thoughts would return; but at least they did not importune her waking hour. The drug gave her a momentary illusion of complete renewal, from which she drew strength to take up her daily work. The strength was more and more needed as the perplexities of her future increased. She knew that to Gerty and Mrs. Fisher she was only passing through a temporary period of probation, since they believed that the apprenticeship she was serving at Mme. Regina's would enable her, when Mrs. Peniston's legacy was paid, to realize the vision of the green-and-white shop with the fuller competence acquired by her preliminary training. But to Lily herself, aware that the legacy could not be put to such a use, the preliminary training seemed a wasted effort. She understood clearly enough that, even if she could ever learn to compete with hands formed from childhood for their special work, the small pay she received would not be a sufficient addition to her income to compensate her for such drudgery. And the realization of this fact brought her recurringly face to face with the temptation to use the legacy in establishing her business. Once installed, and in command of her own work-women, she believed she had sufficient tact and ability to attract a fashionable CLIENTELE; and if the business succeeded she could gradually lay aside money enough to discharge her debt to Trenor. But the task might take years to accomplish, even if she continued to stint herself to the utmost; and meanwhile her pride would be crushed under the weight of an intolerable obligation. These were her superficial considerations; but under them lurked the secret dread that the obligation might not always remain intolerable. She knew she could not count on her continuity of purpose, and what really frightened her was the thought that she might gradually accommodate herself to remaining indefinitely in Trenor's debt, as she had accommodated herself to the part allotted her on the Sabrina, and as she had so nearly drifted into acquiescing with Stancy's scheme for the advancement of Mrs. Hatch. Her danger lay, as she knew, in her old incurable dread of discomfort and poverty; in the fear of that mounting tide of dinginess against which her mother had so passionately warned her. And now a new vista of peril opened before her. She understood that Rosedale was ready to lend her money; and the longing to take advantage of his offer began to haunt her insidiously. It was of course impossible to accept a loan from Rosedale; but proximate possibilities hovered temptingly before her. She was quite sure that he would come and see her again, and almost sure that, if he did, she could bring him to the point of offering to marry her on the terms she had previously rejected. Would she still reject them if they were offered? More and more, with every fresh mischance befalling her, did the pursuing furies seem to take the shape of Bertha Dorset; and close at hand, safely locked among her papers, lay the means of ending their pursuit. The temptation, which her scorn of Rosedale had once enabled her to reject, now insistently returned upon her; and how much strength was left her to oppose it? What little there was must at any rate be husbanded to the utmost; she could not trust herself again to the perils of a sleepless night. Through the long hours of silence the dark spirit of fatigue and loneliness crouched upon her breast, leaving her so drained of bodily strength that her morning thoughts swam in a haze of weakness. The only hope of renewal lay in the little bottle at her bed-side; and how much longer that hope would last she dared not conjecture.

Summary: Lily is working as a milliner and getting reprimanded by the forewoman for sewing the spangles onto a hat crookedly. She's in a small room with about twenty other working women. It seems that Lily separated from Mrs. Hatch a few weeks after Selden visited. She went back to Gerty, who convinced her that she could use her artistic abilities to make and sell hats. Of course, she wouldn't have to do the grunt-work of sewing - she could just be in charge of the final touches, like ribbons or feathers. Er, not so much. Lily is basically at the bottom of the totem pole since she can barely get her stitches straight. Meanwhile, Gus Trenor and Simon Rosedale "rescued" Bertie Van Osburgh from Mrs. Hatch, and now they all blame Lily for trying to trap him in a marriage beneath his dignity. Mrs. Fisher felt guilty at setting Lily up with Mrs. Hatch in the first place, so she goes to Judy Trenor and tries to get her to take Lily back as a friend. But Judy is having none of it. Mrs. Fisher reprimands Lily, who should have known better than to take money from Mr. Trenor. So Mrs. Fisher and Gerty placed Lily as a milliner in Madam Regina's hat shop. Lily began her work in January, and has been a milliner for about two months now. All the other women laugh at her because she used to be a member of the social elite, but now she's just a terrible hat maker. Awkwardly enough, the other women talk about the ladies who will receive these hats - like Mrs. Dorset and Mrs. Trenor. Miss Haines, the forewoman, tells Lily that her spangles are so awkward that she had better just give the hat to another woman to finish and "go back to binding edges." After leaving work, Lily remembers that, when she was rich, she used to think that the working classes were an interesting group of people. Now, she just finds them to be boring. She returns to her ugly, ill-furnished apartment. On the way, she stops at a chemist's to fill one of Mrs. Hatch's old prescriptions which she pretends is her own. It's for a drug to help her sleep at night. The pharmacist remarks that it's strong and she should be careful not to take too much. Uh-oh. Lily hurries back to her apartment but, on the way, bumps into Rosedale. Lily is so out of it that she can barely carry a conversation, but he offers to get some tea with her and she complies. Rosedale is enthused to have bumped into Lily, and wants to hear all about her life. Lily doesn't hold back; she tells him everything about her current situation. He is shocked that a beautiful woman like Lily has to work for a living. When he asks about the inheritance from her aunt, Mrs. Peniston, Lily explains the whole situation with Gus Trenor and why she owes the money. It's the first time she's really comes clean about everything. She wants someone to hear her story, and she hopes that the news will reach Judy Trenor, who will finally understand that Lily didn't mean to take money from Gus and that she's trying to pay it back. Rosedale offers to help her, but Lily says walking her home is help enough. Later, alone in her rooms, Lily wonders why she revealed everything to Rosedale like that. She determines that she's very lonely, cut off most of her friends - even Mrs. Fisher. Lily's avoiding Gerty, too, because she's afraid of accidentally bumping into Selden while she's over there. Lately she's been turning more and more to the sleeping medication, which at least allows her to wake every morning with a feeling of "obliteration." Meanwhile, she's tempted to use the ten grand inheritance to start her own hat shop, but she worries that, if she does, it might take years to make enough to pay Trenor back, and she doesn't want to remain under his obligation in the meantime. Lily is also concerned that she isn't strong enough to avoid temptation until she gets her inheritance. She also knows that, as another temptation, Rosedale would be more than happy to lend her the money she needs to pay back Trenor.

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Write a title and summarize: SECTION 1. SHORT TITLE. This Act may be cited as the ``Reduce and Cap the Federal Workforce Act of 2010''. SEC. 2. REDUCTION AND LIMITATION ON THE TOTAL NUMBER OF FEDERAL EMPLOYEES. (a) Definition.--In this Act-- (1) the term ``agency''-- (A) means an executive agency as defined under section 105 of title 5, United States Code; and (B) shall not include-- (i) the Executive Office of the President; (ii) the Central Intelligence Agency; (iii) the Federal Bureau of Investigation; or (iv) the Secret Service; and (2) the term ``employee''-- (A) means an employee of any agency; and (B) shall not include any employee-- (i) employed by a Federal entity described under paragraph (1)(B); or (ii) designated by the Director of National Intelligence for exclusion for purposes of national security. (b) Agencies Other Than the Department of Defense and the Department of Homeland Security.-- (1) Determination of number of employees.--Not later than 90 days after the date of enactment of this Act, the head of each agency (other than the Department of Defense and the Department of Homeland Security) shall collaborate with the Director of the Office of Management and Budget and determine-- (A) the number of full-time employees employed in that agency on February 16, 2009; and (B) the number of full-time employees employed in that agency at the end of that 90-day period. (2) Reductions by attrition.--If the number of full-time employees employed in an agency determined under paragraph (1)(A) is less than the number of full-time employees employed in that agency on the date occurring 90 days after the date of enactment of this Act, the head of that agency shall ensure that no individual is appointed as a full-time employee in that agency until the number of full-time employees employed in that agency is reduced by attrition to that number determined under paragraph (1)(A). (3) Offset in number of employees.-- (A) In general.--After an agency has reached the number of full-time employees to be in compliance with paragraph (2), the head of that agency shall ensure that the number of full-time employees in that agency is offset by a reduction of 1 full-time employee at that agency for each individual who is appointed as a full-time employee in any agency. (B) Offset if reductions unnecessary.--If the number of full-time employees employed in an agency determined under paragraph (1)(A) is more than the number of full-time employees employed in that agency on the date occurring 90 days after the date of enactment of this Act, the head of that agency shall ensure that the number of full-time employees in that agency is offset by a reduction of 1 full-time employee at that agency for each individual who is appointed as a full-time employee in any agency. (c) Department of Defense and the Department of Homeland Security.-- (1) Determination of number of employees.--Not later than 90 days after the date of enactment of this Act, the Secretary of Defense and the Secretary of Homeland Security shall collaborate with the Director of the Office of Management and Budget and determine the number of full-time employees employed in the Department of Defense and the Department of Homeland Security at the end of that 90-day period. (2) Offset in number of employees.--After the 90-day period described under paragraph (1), the Secretary of Defense and the Secretary of Homeland Security shall ensure that the number of full-time employees in the Department of Defense and the Department of Homeland Security determined under paragraph (1) is offset by a reduction of 1 full-time employee at the applicable department for each individual who is appointed as a full-time employee in that department. (d) Information on Total Employees.-- (1) In general.--Except as provided under paragraph (2), the Director of the Office of Management and Budget shall-- (A) publicly disclose-- (i) the total number of Federal employees; (ii) the number of Federal employees in each agency; and (iii) the annual rate of pay by title of each Federal employee at each agency; and (B) update the information described under subparagraph (A) not less than once a year. (2) National security exception.--The Director of National Intelligence may exclude any employee from information to be disclosed under paragraph (1) for purposes of national security.

Title: A bill to provide for a reduction and limitation on the total number of Federal employees, and for other purposes Summary: Reduce and Cap the Federal Workforce Act of 2010 - Requires the head of each executive agency: (1) to determine the number of full-time agency employees on February 16, 2009 (2009 number) and the number of full-time agency employees on the date occurring 90 days after enactment of this Act (current number); (2) if the 2009 number is lower, to ensure that no new employee is appointed until the 2009 number is attained through attrition; and (3) if the current number is lower or once the 2009 number is attained, to maintain that number by offsetting each new appointment by a reduction. Excludes the Department of Defense (DOD), the Department of Homeland Security (DHS), the Executive Office of the President, the Central Intelligence Agency (CIA), the Federal Bureau of Investigation (FBI), and the Secret Service. Requires the Secretary of Defense and the Secretary of Homeland Security to: (1) determine the current number of full-time employees of DOD and DHS; and (2) maintain that number by offsetting each new appointment by a reduction. Requires the Director of the Office of Management and Budget (OMB) to: (1) publicly disclose the total number of federal employees, the number of federal employees in each agency, and the annual rate of pay by title of each federal employee at each agency; and (2) update such information at least once a year. Authorizes the Director of National Intelligence to exclude any employee from such information for purposes of national security.

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Write a title and summarize: Although it has been known for nearly a century that strains of Trypanosoma cruzi, the etiological agent for Chagas' disease, are enzootic in the southern U. S., much remains unknown about the dynamics of its transmission in the sylvatic cycles that maintain it, including the relative importance of different transmission routes. Mathematical models can fill in gaps where field and lab data are difficult to collect, but they need as inputs the values of certain key demographic and epidemiological quantities which parametrize the models. In particular, they determine whether saturation occurs in the contact processes that communicate the infection between the two populations. Concentrating on raccoons, opossums, and woodrats as hosts in Texas and the southeastern U. S., and the vectors Triatoma sanguisuga and Triatoma gerstaeckeri, we use an exhaustive literature review to derive estimates for fundamental parameters, and use simple mathematical models to illustrate a method for estimating infection rates indirectly based on prevalence data. Results are used to draw conclusions about saturation and which population density drives each of the two contact-based infection processes (stercorarian/bloodborne and oral). Analysis suggests that the vector feeding process associated with stercorarian transmission to hosts and bloodborne transmission to vectors is limited by the population density of vectors when dealing with woodrats, but by that of hosts when dealing with raccoons and opossums, while the predation of hosts on vectors which drives oral transmission to hosts is limited by the population density of hosts. Confidence in these conclusions is limited by a severe paucity of data underlying associated parameter estimates, but the approaches developed here can also be applied to the study of other vector-borne infections. Since the Brazilian physician Carlos Chagas discovered the parasite Trypanosoma cruzi in 1909, much research has been devoted throughout the Americas to the study of its transmission and control, primarily in the domestic and peridomestic settings in which it is passed to humans, via triatomine insect vectors of the subfamily Triatominae (Hemiptera: Reduviidae). Although control measures have succeeded in preventing new infections among humans in some areas of Brazil, Uruguay, Chile, and Argentina, the parasite, which is native to the Americas, remains endemic in sylvatic settings as far north as the United States, being limited only by the habitats of the several vector species. In each region, the epidemiology of sylvatic T. cruzi transmission differs in important particulars, as each host and vector species has certain peculiarities—behaviors or immunities—which have led to adaptations in the ways by which the infection is maintained. In the United States, sylvatic hosts (which rapid urbanization often brings into peridomestic settings) include primarily raccoons (Procyon lotor) and opossums (Didelphis virginiana) in the southeast and woodrats (Neotoma micropus) in Texas, although dogs and armadillos have also been cited as significant, and the parasite is also found in skunks, foxes, squirrels, mice, and other Neotoma spp. (Vectors do feed upon birds, reptiles and amphibians as well, but these are refractory to T. cruzi infection [1], and hence incompetent hosts.) There are over 130 species of triatomine vectors, of which 11 are known to inhabit the southern United States, 8 of them in Texas [2]. Two of the most important in the southeastern U. S. [2], [3] are Triatoma sanguisuga, found from central Texas all the way east to islands off the Atlantic coast, and Triatoma gerstaeckeri, associated primarily with woodrat nests and domestic settings from central Texas south into Mexico as far as the state of Queretaro [4]. In addition, there are different strains of T. cruzi circulating in these populations. Strains are classified within six major groups known as Type I and Type IIa through IIe. Of these, only Types I and IIa are known to circulate in the United States [5], and it is widely believed (primarily from experiments in mice, e. g., [6]–[8]) that the strains circulating in the U. S. are less virulent than those in Latin America, where the incidence of Chagas' disease in humans is much higher: an estimated 16–18 million people (only a handful of autochthonous cases have been diagnosed in the United States [9], though it has also been estimated that as many as half a million people in the U. S. may harbor the parasite, due to migration from Latin America). Among sylvatic hosts in the United States, raccoons and other placental mammals are associated with Type IIa infections, while opossums are associated with Type I infections [5]. T. cruzi may be transmitted in a number of ways. Historically, the primary infection route, especially in South America, has involved the vector' s feeding process, in which a bloodmeal from an infected host can transmit the parasite to the vector, where it lives in the insect' s gut, and defecation by an infected vector on the host following the bloodmeal can result in stercorarian transmission to the host. In sylvatic hosts this may occur when the animal scratches the bite and inadvertently rubs the parasite-contaminated matter into the lesion. However, among humans there have recently been other transmission avenues of greater concern: the parasite can be passed from one human to another through blood transfusion and organ transplants, congenitally from mother to child through the placenta, and oral transmission by consumption of food contaminated by vectors has been blamed for outbreaks in South America. In fact, these avenues of transmission may also be important for sylvatic hosts as well: vertical (congenital) transmission has been verified experimentally among rats [10] and supported by circumstantial evidence among lemurs [11] and other animals, and oral transmission to hosts through their predation upon vectors (raccoons, opossums, and even woodrats are opportunistic feeders that commonly include insects in their diets) has even been suggested by some [12], [13] to be the primary means of T. cruzi transmission to hosts in some cycles in the U. S. Indeed, T. sanguisuga and T. gerstaeckeri are known to be so cautious in their feeding behavior as to avoid climbing up entirely onto hosts during feeding [3], and often defecate 30 minutes or more after feeding ends, making them likely to be rather inefficient at stercorarian transmission to hosts. Both oral and stercorarian transmission to hosts, however, as well as bloodborne transmission to vectors, may be amplified by changes in vector behavior caused by infection with T. cruzi. Many disease vectors are known to increase their feeding rate when infected, due to parasites building up inside their digestive tracts and impeding feeding. This behavior has been verified for one species of triatomine vector and trypanosome [14], but not documented for Chagas vectors and T. cruzi. Many of the still-unanswered questions regarding sylvatic T. cruzi transmission cycles may be exceptionally difficult to address through direct observation in the laboratory and field: for instance, which of the several transmission pathways is really dominant in each cycle? (We may think of a cycle as a specified host, vector, parasite strain, and geographic region, although in practice such cycles communicate with each other, primarily via vector dispersal.) Mathematical models have proven a useful tool in many fields, including ecology and epidemiology, as they can describe, predict, and provide evaluation measures for phenomena which may be difficult to observe directly. Population biology models consisting of dynamical systems (usually systems of differential equations, see, e. g., [15]), which describe the spread and growth of populations over time, have made notable contributions to disease control beginning notably with Ronald Ross' s study of malaria transmission in the early 1900s [16], for which he later won the Nobel Prize. Such mathematical modeling of T. cruzi transmission has to date involved primarily household-based modeling of vector infestations and human infection (but see below for a notable exception), although in the past decade geospatial models have been developed to describe vector distribution, disease risk, and relevant ecological niches [2], [17]. The ability of mathematical models to explain and predict depends not only on the underlying assumptions about the biological processes (demographic, infection-related and other) used to construct them, but also on knowing the values of certain fundamental parameters, most of which can be observed directly: information such as average lifespan, population density, or the probability of a host becoming infected from consuming an infected vector. For instance, the ability of a given population to invade or persist in a habitat often depends on threshold quantities such as a reproductive number (which can be calculated in terms of these fundamental parameters) being above or below a critical value. The best-known of these is the basic reproduction number for an infection or population [18], [19], denoted, which typically signals persistence of the population precisely when. In practice, however, the parameters' values for a given transmission cycle change seasonally, from one region to another, and even from study to study (especially if sample sizes are small). As a result, the critical link between theoretical models and empirical data provided by parameter estimation requires a broad perspective and familiarity with a range of empirical literature. As noted above, numerous mathematical modeling studies have been published of T. cruzi transmission to humans (e. g., [20]–[22]), but almost none have been published on the sylvatic transmission cycles that maintain the parasite. Decades of studies have established details of the life cycles of T. cruzi hosts and vectors in the United States, but studies focused on measuring infection parameters are only just beginning to appear (e. g., [13]). Mathematical models can bridge this gap by facilitating calculation of these parameters using enzootic prevalence observations together with known information on the life histories of host and vector species. The aims of the present study are to estimate values for those measures of host and vector life histories and T. cruzi infection which have been observed directly in the literature via an extensive review, and then to illustrate a method by which other key infection-related parameters can be calculated using mathematical models. One of the important aspects of the sylvatic T. cruzi transmission cycle which models can help investigate is density dependence in the infection rates. (In this paper the term “rate” refers to a frequency per unit of time at which an event occurs. The term “proportion” will be used to refer to ratios which do not involve time, such as disease prevalence.) Infectious disease transmission is driven by contact processes between susceptible and infective individuals, and sylvatic transmission of T. cruzi in particular depends on both the vector-initiated process of taking bloodmeals and the host-initiated process of predation on vectors. The rates at which these two contacts occur depend in part on the host and vector population densities, and in part on the ratio of those densities, due to the saturation that occurs when this ratio is too high or too low. That is, the per capita contact rate is a function of the vector-host density ratio, so that the total contact rate is the product of this function and the respective (host or vector) density. Ratio-dependent contact rates, which were used in epidemiological models as early as Ross' s classic malaria model [16], are also a well-established notion in the study of predator-prey systems [23], [24], and the present study will illustrate how these correspond to the density-dependent effects observed in the transmission of T. cruzi (e. g., [25]). Saturation in contact processes—the notion that given rates can increase only up to a certain point—has also been studied extensively in the contexts of both predator-prey systems (e. g., [26]) and mathematical epidemiology (leading to the distinction between mass-action incidence for low densities and standard incidence for high densities). Predation and infection are superimposed in the transmission of vector-borne infections, and empirical studies [25], [27] have observed a corresponding density dependence in which per-vector biting rates decrease at high vector-host ratios. Per capita contact rates thus increase with the density ratio only up to a certain limit, so that the total contact rates (per capita rates multiplied by host or vector density) then become functions of one density or the other alone. When the ratio of vectors to hosts is low, hosts are plentiful relative to vectors, so on the one hand each vector can feed as often as it wants (that is, at its preferred feeding frequency), but on the other hand an average host has a hard time finding vectors to consume, making both contact processes limited by the number of vectors. When the ratio of vectors to hosts is high, however, there are not enough hosts upon which for the vectors to feed at their desired frequency (requiring them to find other blood sources), but the hosts are able to eat until reaching satiation, so that both contact processes are limited by hosts. One recent theoretical study [28] developed a mathematical model for sylvatic transmission of T. cruzi and determined that the way in which the two contact processes saturate can affect not only vector population densities but also whether the infection cycle persists. Another study [29] found that such a model coupled to one involving human infection explained observed domestic prevalence data better than a model of exclusively domestic transmission. In order for a mathematical model to predict the rate at which new infections occur, it is necessary to derive quantities such as threshold density ratios from empirical data, so as to understand in what phase of saturation the causative contact processes are operating. This paper presents a way to do so. This paper derives estimates for the key biological parameters needed to model sylvatic Trypanosoma cruzi transmission cycles in Texas and the southeastern United States involving raccoons, Virginia opossums, woodrats, and the two vector species Triatoma sanguisuga and Triatoma gerstaeckeri. Many of these parameters can be estimated directly via an extensive literature review, but infection and contact rates will be estimated indirectly using estimated prevalence levels and a few properties of some relatively simple dynamical population models. The results will also be used to address the issue of saturation in the two infectious contact processes. The intention is to provide well-informed direct estimates of as many quantities as possible and a method for computing other estimates which can be applied to models designed to address a broad spectrum of questions. An exhaustive literature review was used to derive estimates for basic demographic information on host and vector species, as well as those epidemiological parameters for which direct estimation is possible. The review initiated with a Medline search on “Triatoma sanguisuga”, “Triatoma gerstaeckeri”, or “Trypanosoma cruzi”, together with “United States”—or, for general demographic information on hosts, keywords used were “raccoon”, “opossum” and “woodrat”. From the over 1000 resulting articles, only those (approximately 80) which reported data on one of the quantities estimated in the Results section of this paper were kept. The vast majority of the papers discarded focused exclusively on genetics or microbiology, rather than population biology, and were discarded from the title and abstract; the full text of all other articles was examined for relevant data. Results were found (and kept) in English, Spanish, and Portuguese. References in the sources were then checked manually as well. Gray literature was not specifically sought except for non-Chagas-related demographic information on host species not identified in scientific literature, but was checked when it appeared as a reference in another source. Additional references were added at reviewers' suggestions. Well-established properties of nonlinear dynamical systems models were then used to estimate infection rates based on prevalence and known parameters, and to frame the estimation of the threshold population-density ratios that determine whether host or vector population densities drive each type of infectious contact. (Specific simple models are used as illustrations in the Results section, but the approach outlined can be applied to a wide variety of dynamical systems, and results are not meant to be limited to the models given.) Models were used (and will be discussed) only where necessary to help estimate relevant quantities. In every case, epidemiological quantities were estimated as time-averaged values over an entire year, in order not to allow seasonal fluctuations (which impact both host and vector populations significantly) to prevent study of endemic steady states and prevalence. Basic demographic information on host and vector species is necessary for all modeling of T. cruzi transmission cycles. Numerous studies have published data supporting the estimation of average lifespans for raccoons [30]–[34], opossums [12], [34], [35], and woodrats [36, and references therein]; reproductive rates for raccoons [30]–[32], opossums [34], [37], and woodrats [37]; population densities for raccoons [32], [38]–[47], opossums [40], [41], [48], and woodrats [36], [49], [50]; average lifespans for T. sanguisuga [3], [51] and T. gerstaeckeri [3], [52], [53]; reproductive rates for T. sanguisuga [3], [12], [51] and T. gerstaeckeri [3], [53]; and, in a single case, vector population density [54]. Discussion and development of estimates for these quantities are provided in Text S1. Table 1 summarizes these estimates (including SI equivalents) for the demographic parameters of each species. Vertical transmission of T. cruzi has been widely documented in humans, and estimated to occur with frequency between 1 and 10 percent in Latin America [55]–[58]. Because the parasite is transmitted through the placenta and blood supply to the fetus, vertical transmission is possible among placental mammals, but it is generally not believed to occur among marsupials. A study in Venezuela found a vertical transmission rate among Wistar rats (Rattus norvegicus) of 9. 1% for a strain of T. cruzi isolated from dogs, but none at all for a strain isolated from humans [10]. Another study in Georgia (USA) found that a Type IIa strain of T. cruzi isolate from Georgia was twice as likely to be vertically transferred in mice as a Type I isolate from South America [11]. In the absence of any data on vertical transmission among raccoons, we might reasonably estimate that Type IIa strains are transmitted congenitally roughly 10% of the time (as a proportion,), with Type I strains transmitted as much as an order of magnitude less frequently (say). There is almost no published data on rates of oral infection with T. cruzi (which could be estimated directly by multiplying the predation rate of hosts upon vectors by the probability of infection following consumption of an infected vector), although the possibility of oral transmission has long been documented. Olsen et al., writing in the early 1960s, referenced a “postulate” that oral transmission was the primary route of infections for opossums in Alabama, with insects consisting of 43% of opossums' diet by mass, and 60% by volume [12]; Roellig et al. recently extended this notion to include raccoons as well [13]. One recent source wrote, “Animals can easily become infected with T. cruzi when an infected triatomine bug is ingested. ” [59] However, despite a significant body of research on what raccoons, opossums and woodrats eat, a literature review revealed no data on how much (or how often) they eat (in order to estimate predation frequency). Rabinovich et al. [60] observed 33 instances of predation when each of 13 female white-eared opossums (Didelphis albiventris) was placed with 10 infected Triatoma infestans for a day, but the rather high predation rate estimate that would result from this data is skewed by the experimental conditions, e. g., the fact that both opossums and bugs were starved for a period of time prior to the experiment, and the opossums had no other available food. Since predation is opportunistic and there are other insects available to the hosts as well, we will therefore estimate predation to occur for all hosts no more often than one triatomine every 3 or 4 days, which equates to an upper bound of about vectors/yr/host. However, it may also be orders of magnitude lower. (Woodrats are of course much smaller than raccoons and opossums, and hence eat less, but vectors are found much more easily in woodrat nests, at least by humans, so we will assume opportunity balances out total volume.) The probability (or proportion) of infection of a host following consumption of an infected vector can be estimated from three experiments in which uninfected hosts were fed vectors infected with T. cruzi. Yaeger conducted 11 trials of an experiment in which an uninfected Virginia opossum (D. virginiana) was fed two Rhodnius prolixus vectors [61] infected with a Type IIe strain; 3 of these trials resulted in infection, yielding an estimate for of. Roellig et al. [13] conducted 2 trials of an experiment in which an uninfected raccoon was fed 3 R. prolixus vectors infected with strain IIa; both trials resulted in infection (yielding an estimate for of 1). Finally, the aforementioned study by Rabinovich et al. [60] produced its own estimate of 0. 075 for the infection probability of white-eared opossums by eating T. infestans infected with an unspecified strain of T. cruzi (presumably not IIa); since their experiment combined oral and stercorarian transmission (all 6 of the 13 opossums who ate a bug were also verified to have been bitten by at least one other bug, except for the opossum who ate all 10 of the bugs placed with her), it is impossible to disentangle the raw oral transmission data in a way that can be pooled with the other two experiments. Yaeger' s estimate for opossums is precisely twice that of Rabinovich et al., although the difference is not inordinate. Roellig et al.' s data is based on so few trials that no great significance can be ascribed to the resulting high estimate for raccoons, but it is nevertheless suggestive that the probability of oral transmission may vary significantly by host species and by parasite strain (opossums appear not to become infected when exposed to Type IIa T. cruzi [62], and hence may be more difficult to infect with any Type II strain) —not to mention vector species—which is entirely consistent with the speculation of some biologists that North American strains may have adapted in response to local conditions. Obtaining a single estimate for opossums requires an assumption that differences due to species (D. virginiana vs. D. albiventris), vector species, and possibly parasite strain are negligible, in which case we can take a weighted average of. To estimate oral infection probability for raccoons we are left with either the above 100% estimate or else an average across all host species (including opossums) of. There is likewise no published research on the extent to which infection with T. cruzi increases vector behaviors in T. sanguisuga or T. gerstaeckeri that promote infection. Añez and East [14] found that triatomine bugs of the genus Rhodnius, a common T. cruzi vector in South America, probed or bit an average of 6. 5 times as often when infected with the parasite Trypanosoma rangeli as when uninfected, prior to engorging. This differential behavior may amplify by a factor (say) not only the biting rate of infected vectors but also their availability for predation due to increased mobility driven by hunger, so that the effective vector density for infection behaviors is rather than. However, D' Alessandro and Mandel [63] found no difference in the feeding behaviors of R. prolixus infected by T. cruzi. Although such frequencies can be expected to vary widely by species (of parasite as well as vector), it would be consistent with research on South American species to expect no differential behavior in infected T. sanguisuga or T. gerstaeckeri. In the case where we wish to investigate the possible effects of such an amplification factor, however, it is worth noting Añez and East' s value. Research suggests that in general sylvatic hosts do not suffer mortality from T. cruzi infections, even though high mortality rates have been reported for dogs, and the long-term risks have been verified for humans. Also, the mice which die from T. cruzi infections in laboratory experiments are often injected with considerably higher concentrations than a single horizontal transmission is likely to produce initially. We may therefore assume (following, e. g., [64]) that in general the sylvatic hosts under study have no significant additional mortality caused by infection with T. cruzi. Table 2 summarizes these parameter estimates. (Table 3 defines additional variables and parameters used in later sections.) Estimation of the per capita infection rates for vector transmission must be made indirectly, as at present there are few published data on both the vector biting rate and the proportion of feedings which result in an infection in each direction (host to vector and vice versa). (Two notable exceptions are [65], which estimated the probability of vector infection per feeding for a specific South American cycle, and [60], which estimated the probability of stercorarian infection of opossums D. albiventris at 0. 06 [95% CI: 0. 023,0. 162] per infected T. infestans bite). Instead, given the long history of established T. cruzi infections in the regions of interest, we shall assume that the parasite has reached endemic equilibrium in the host and vector populations, and use published data to estimate [endemic] prevalence in both host and vector. This will allow us to use the formulas derived from our population dynamics model which express endemic equilibrium prevalence as a function of model parameters, to calculate the infection rates necessary to produce those endemic levels. With prevalence levels and all other parameter values known, it will be possible to solve for the infection rates. But first we must estimate prevalence. Reported prevalences are given in Tables 4–8 for raccoons, opossums, woodrats, T. sanguisuga and T. gerstaeckeri in the southeastern United States and northern Mexico. Asterisks (*) denote studies which published paired estimates of host and vector prevalence. For host prevalence, the method of diagnosis is given as [hemo]culture, serology (IFAT = Indirect Fluorescent Antibody Test, IHA = indirect hemagglutination assay), either (both culture and serological tests were performed, and a single positive is reported as positive), blood smear (BS), or xeno [diagnosis]. The dagger after the citations to Lathrop and Ominsky [66] marks joint prevalence reported for a mixed population of 6 T. sanguisuga and 9 T. gerstaeckeri. As evidenced by Table 4, dozens of studies have reported prevalence figures for the infection of raccoons with T. cruzi in the past fifty years, in states throughout the southeastern quarter of the United States. As observed by several researchers, notably Yabsley et al. [67], the method used to determine infection can have a significant effect on the results: in particular, the parasite is often only found in the blood (by hemoculture or blood smears) during the initial (acute) period of infection, while the immune system takes some time to develop antibodies to T. cruzi, so that serological tests like IFAT and ELISA are more likely to detect chronic infections. It is therefore best to use both methods in order to capture both acute and chronic infections. Most studies reported prevalence based only on blood cultures until about ten years ago, and as can be seen in Table 4 there is a marked difference in the prevalences reported based on hemoculture studies as compared to serological or both. Ten of the sixteen blood-based studies reported prevalences of 15% or less (seven of these reported prevalences of 1. 5% or less, and the mean of all 16 values is under 20%), whereas apart from a single, small-sample (n = 12) zero value, the studies which included serological results reported a mean of over 50% prevalence. There is also some notable geographic variation. Infection rates near the central part of the country appear to be relatively high, with studies from Kentucky, Missouri, Oklahoma and central Tennessee all reporting prevalences of well over 50%, with a total prevalence of 106/163 or 65%. On the other hand, the region directly east of that, from the mountains to the Atlantic, has little or no infection: studies from Maryland, Virginia, West Virginia and even eastern Tennessee adjacent to Virginia all report effectively zero prevalence, the exception being a study of raccoons in the suburban area of Fairfax County, Virginia, near Washington, D. C., where increased opportunity for foraging results in a higher raccoon population density. Prevalence among raccoons in Georgia and neighboring South Carolina ranges from 33% to 60% except for one hemoculture-based study which reported 22%. Pooling these 7 studies yields an overall prevalence of 351/908 or 38. 7%, heavily weighted by the large study of Brown et al. [68]. Moving west along the Gulf Coast, there is no data apart from Olsen et al.' s study from eastern-central Alabama in the early 1960s until we reach Texas, where there are only two small studies from 1977–1978. We shall take the figure of 24% from central Texas, rather than that of 0% from south Texas, as being representative of prevalence among raccoons in the central and eastern part of the state. Examining the reported prevalences for opossums, there is a clear tendency for the studies which used both blood culture and serology to report higher prevalences (see Table 5), with the exception of the early datum from Texas, which was of such a small sample size (n = 8) that it cannot be claimed to be representative. There is nearly an order of magnitude difference in sample size between the three largest studies [68]–[70] and the next largest, and these three show, on the one hand, nearly identical hemoculture-based prevalences between Texas (16%) and Florida and Georgia (17%, consistent with the more recent Georgia figure of 15. 4% [71]), and, on the other hand, a prevalence that nearly doubles when both hemoculture and serology are taken into account (28% in Georgia [68]). Although some of the smaller studies suggest that in places the prevalence of T. cruzi in opossums may be much higher than this, we shall use Brown et al.' s 28% figure as representative of prevalence in both the southeast and Texas. The four earliest reported prevalences of T. cruzi infection in Texas woodrats are relatively close to each other (ranging from 21. 4% to 34. 9%, see Table 6) but used hemocultures or blood smears rather than serology, which may imply an underestimate; the two reports from west Texas, both serological, are higher but come from much smaller samples. We shall nevertheless pool the data to obtain an overall prevalence of 225/678 or 33. 2%. Very few studies have reported infection prevalence for the vector T. sanguisuga east of Texas (see Table 7). The studies published by Hays, Olsen and their collaborators in the 1960s give prevalences of around 6% in eastern central Alabama, but the two more recent studies in Georgia and Louisiana agree on values an order of magnitude higher. It is likely that infection prevalence does vary by location, but for an overall average we shall pool the two more recent reports, for a total prevalence of 56. 5% in the southeast. In Texas, reported prevalences appear to fluctuate within a range of 17% to 44%. Pooling all but the first two studies (since the second gave no absolute numbers) yields an overall prevalence of 135/543 or 24. 9%. Early studies had T. cruzi prevalence in the vector T. gerstaeckeri varying widely from 5% to 92% (see Table 8), and despite some slight convergence, results continue to fluctuate from 26. 5% to 77. 4%, even among relatively large () samples (we exclude from further discussion the small sample from Queretaro in central Mexico). Since these studies typically collected vectors from woodrat nests, it is likely that there may be considerable variation in infection proportions from one nest to another. The three reports from the state of Nuevo León, Mexico, just south of Texas, also fit within this range. We will therefore pool all studies for which raw data is given (noting that the rate given in Galavíz et al. is close to that in the study by Martínez-Ibarra et al., on which Galavíz was second author, and that the data in deShazo is likely incorporated into the study by Sullivan et al. given the dates, and the fact that deShazo and Sullivan were the same person), to derive an overall prevalence of 572/1259 or 45. 4%. Note that all collections of vectors in Texas were made from either woodrat nests or peridomestic environments, while collections in the southeast mention association with both raccoons and opossums. This complicates the matter of disentangling the various transmission cycles (for instance, are vectors in raccoon dens in Texas infected at the same level as vectors in nearby woodrat nests?), which may be especially important where different strains of T. cruzi are involved, as with opossums (typically infected with type I) and raccoons (typically infected with Type IIa) in the southeast. In the absence of more complete data, however, we can do no better at present than use these figures as applying across hosts in a given habitat. As a brief aside, we also note reports of prevalence in Texas among the vector Triatoma neotomae, uniquely identified with woodrat nests, of 87. 5% by deShazo [72], 11/17 (64. 7%) by Sullivan et al. [73], 27/31 (87%) by Eads et al. [74], and 2/3 (66. 7%) by Burkholder et al. [54], the latter three of which combine to give an overall prevalence of 40/51 or 78. 4%, significantly higher than that of most other vector species. As the vector' s habitat is confined to one or two regions of Texas, however, we will not consider it further. Table 9 summarizes these prevalence estimates for Texas and the southeast. Most quantities dealing with the T. cruzi infection process itself must be estimated indirectly by inference, since (as illustrated in the previous subsection) little or no published data exists on quantities such as probabilities of infection and even species-specific contact rates. Instead, one can use population models of transmission dynamics to back-calculate the effective infection rates given observed endemic prevalences and the known demographic parameter estimates. The specific calculations and expressions involved are model-dependent—for example, one model may distinguish between oral and stercorarian infection rates for hosts, while another uses a single term with a net host infection rate—but the general idea remains the same: to use equations for the observed endemic equilibrium to solve for the desired parameters. (Note this method assumes that observed infection prevalence represents a steady endemic state.) Table 3 summarizes all model variables and parameters used in modeling discussions in this and the following sections, except for those already defined in Table 2. To illustrate this technique with a minimum of model parameters, we here consider a scenario with a single host and single vector species, each at a constant population density, and only a single (net) route to infection. The simplest vector infection model has the formHere and are the densities of infected hosts and vectors, respectively, as functions of time, and are the host and vector densities as before (here assumed constant over time), and are the respective infection rates, and and are the mortality rates. In each differential equation the first term describes the rate of new infections, and the second describes removal by natural mortality (we assume no recovery from infection). Here for simplicity we use so-called standard incidence to describe the total infection rates, and defer discussion of saturation in the relevant contact processes until the next section. This model is mathematically equivalent to the classical Ross model for malaria transmission [16], although removal of infected hosts here is due to natural death (not recovery as in Ross' s model) and for simplicity the [here constant] vector-host ratio that is explicit in Ross' s model has been absorbed into (the following subsection on saturation in contact processes will address how the infection rates depend on this ratio). If we define proportional infection levels,, then the equilibrium conditions for this model (setting the time derivatives and to zero for the steady state) can be written asWe can solve these equations for the infection rates and, so that in case we know the prevalence levels, (assumed positive) and also the mortality rates,, we can calculate the corresponding infection rates: We can apply this result to the transmission cycle between raccoons and T. sanguisuga in the southeastern U. S. using the prevalence estimates, derived in the previous section and the mortality rates /yr, /yr from Table 1 (assuming opportunistic host predation on vectors does not significantly impact vector mortality), to obtainIf we instead consider opossums (, /yr) and T. sanguisuga in the southeastern U. S., we get insteadThe fact that in both cases reflects the higher prevalence found in vectors compared to hosts,, consistent with the observation (e. g., [3]) that T. sanguisuga and T. gerstaeckeri are so cautious as to rarely walk entirely onto a host, therefore making (stercorarian) transmission to hosts much less likely than transmission to vectors through bloodmeals. Note that this model assumes no vertical transmission, and treats all transmission routes (here, stercorarian and oral for the host) as one to produce an estimated overall infection rate. Any such distinctions must be made in the model used to derive the infection rates. For instance, if we wish to take into account vertical transmission of T. cruzi among placental hosts such as raccoons, then we add a corresponding term to the equation for (if hosts are assumed to reproduce according to a logistic law, at a total rate): If we assume the host population to have reached its equilibrium value, then the new term simplifies to, and the differential equation simplifies to its previous form, with replaced by: This means that the only change made in the two expressions for infection rates is to multiply (and hence) by: The vector infection rate is unaffected, but in the case of raccoons infected with Type IIa T. cruzi in the southeastern U. S., the vertical transmission estimate of for Type IIa yields an estimated horizontal transmission rate of. Similar adaptations can be made for models which distinguish between stercorarian and oral transmission to hosts, or address differential behavior of infected vectors, etc., although sufficiently complicated models may require solving equilibrium conditions numerically once other parameter values are substituted, if closed-form expressions for endemic equilibria are not available. Finally, in order to complete a model description of T. cruzi transmission dynamics, it is necessary to address the specific forms of the host-vector contact processes that drive infection: host predation upon vectors, which can produce oral transmission, and vector feeding upon hosts, which can produce bloodborne and stercorarian transmission. Here, too, mathematical models can help identify and articulate the key parameters that determine those forms. Since both types of contact processes are predation-driven, we begin with a brief review of considerations from the well-developed area of predator-prey modeling. Mathematical models have enormous predictive and explicative power in the study of biological systems, especially those where the feasibility of large-scale field studies is limited. Dynamical systems have managed to capture the nonlinear contact processes at the heart of many population biology questions in ecology and epidemiology, but their descriptive ability as models hinges on having accurate estimates for the biological parameters that measure key rates and quantities. Any study of the dynamics of sylvatic Trypanosoma cruzi infection must include both demographic and epidemiological information on the hosts and vectors involved. As seen in the preceding sections and Text S1, a thorough literature review is sufficient to determine many of the most basic demographic parameters for the host and vector species that drive T. cruzi transmission in the southeastern quarter of the U. S., but many aspects of the contact processes which actually cause infection remain poorly understood. Simple dynamical systems models can be used to back-calculate infection rates from data on zoonotic prevalence, as well as to pinpoint what specific biological data needs to be gathered to complete parametrization of the models. In the present study, these data include: vector population densities, the probability of vertical transmission in raccoons and other hosts, the probability of oral infection per host type (and per vector consumed), the (maximum) rate at which hosts consume vectors, the extent to which T. cruzi infection changes the relevant behaviors of the vectors T. sanguisuga and T. gerstaeckeri, infection prevalence among Texas vectors outside woodrat nests and peridomestic sites, and the threshold vector-host density ratios which determine saturation for both contact processes. The rough estimates derived in this paper regarding the latter ratios and suggest that host predation on vectors is saturated in vectors (largely because this predation is opportunistic), and therefore dependent on host density for each host, whereas the vector feeding process is saturated in vectors only for the larger hosts (raccoons and opossums), which have a relatively low population density, and saturated in hosts for the woodrats that are the predominant host from central Texas south to Mexico, since woodrats occur at a higher density and return to the same nests on a long-term basis, making these nests efficient feeding sites for the vectors. Since T. sanguisuga and T. gerstaeckeri are widely believed to be inefficient vectors, the vector feeding process is primarily responsible for prevalence in vectors, and it is therefore interesting to note that T. sanguisuga appears to have a higher prevalence in many parts of the southeast (especially those closest to the center of the U. S.) than T. gerstaeckeri does in Texas, where it has ready access to abundant hosts. It is important to keep in mind, however, that the uncertainty in several parameter estimates (notably the effective vector population density) limits the confidence one can place in the conclusions regarding contact process saturation. Of course, all models, however complex, remain caricatures or sketches of reality, and have their limitations. Dynamical systems models are limited in their predictive power not only by the accuracy of the estimates used for the biological rates that parametrize them, but also by the correctness and completeness of the assumptions that underlie every term in each equation. This paper is meant to connect these theoretical models to the many empirical studies that add detail to our understanding of the T. cruzi infection process in the U. S. Further studies are already in progress developing models that begin to incorporate the multiple infection mechanisms described in this work and the literature reviewed within, as well as the effects of dispersal and migration connecting the various evolving habitats (such as central Texas and the southeastern U. S.) where T. cruzi is in zoonosis. Readers interested in the question of vector feeding preferences for different types of host are referred to the studies [25] and [27].

Title: Estimating Contact Process Saturation in Sylvatic Transmission of Trypanosoma cruzi in the United States Summary: The parasite Trypanosoma cruzi, transmitted by insect vectors, causes Chagas' disease, which affects millions of people throughout the Americas and over 100 other mammalian species. In the United States, infection in humans is believed rare, but prevalence is high in hosts like raccoons and opossums in the southeast and woodrats in Texas and northern Mexico. The principal U. S. vector species appear inefficient, however, so hosts may be primarily infected by congenital transmission and oral transmission caused by eating infected vectors. Mathematical models can evaluate the importance of each transmission route but require as inputs estimates for basic contact rates and demographic information. We estimate basic quantities via an exhaustive review of T. cruzi transmission in the southern and southeastern U. S., and use properties of mathematical models to estimate infection rates and the threshold (saturation) population-density ratios that govern whether each infection process depends on host or vector density. Results (based on extremely limited data) suggest that oral transmission is always driven by host density, while transmission to vectors depends upon host density in cycles involving raccoons and opossums, but upon vector density in cycles involving woodrats, which live in higher concentrations.

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Write a title and summarize: During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells. CD8 TFR modestly limit HIV replication in follicular helper T cells (TFH), impair TFH IL-21 production via Tim-3, and inhibit IgG production by B cells during ex vivo HIV infection. CD8 TFR induce TFH apoptosis through HLA-E, but induce less apoptosis than conventional CD8 T cells. These data demonstrate that a unique regulatory CD8 population exists in follicles that impairs GC function in HIV infection. In chronic HIV and SIV infection, viral replication is concentrated in B cell follicles in secondary lymphoid tissues [1–5], although factors that promote this are not fully understood. Follicular helper T cells (TFH), which reside in the secondary lymphoid follicles, are highly permissive to HIV [6] and exhibit anti-apoptotic properties [7,8] which likely contributes to viral persistence. We have previously shown that virus-specific CD8 T cells are present at lower frequencies inside the follicle compared to outside the follicle in HIV and SIV infection [2,9], which may contribute to impaired viral clearance in the follicle. While CD8 T cells are present in the follicle, little is known about the function of these cells. We have previously reported that CD4 follicular regulatory T cells (TFR) are increased in number, exhibit heighted regulatory capabilities, and impair TFH proliferation and function in ex vivo HIV and in vivo SIV infection [7]. We hypothesized that follicular CD8 T cells may also have regulatory functions that further contribute to immune dysregulation in chronic HIV infection. Regulatory CD4 T cell populations can be readily identified based on expression of CD25 [10,11], and Foxp3 [12], their canonical transcription factor. Nevertheless, a consensus phenotype for CD8 Tregs has yet to be described. CD8 Tregs in the thymus and periphery of mice do not constitutively express Foxp3 [12], and Foxp3-expressing CD8 T cells do not encompass CD8 Treg populations [13]. CD8 Tregs have been described in humans, but have limited defining characteristics, and most lack Foxp3 [14]. Thus, it is essential to demonstrate regulatory function with any CD8 Treg phenotype [15,16]. In mice, CD8 Treg function is dependent on B and T lymphocyte expression of Qa-1, the murine equivalent of HLA-E, which binds to the TCR of CD8 T cells [17–19]; CD8 Treg function correlates with the affinity and duration of this interaction [18,20]. A specific subset of CXCR5hiCD44hi CD8 Tregs (henceforth defined as CD8 TFR in this work) was found to limit germinal center (GC) size and prevent autoimmune disease in mice [19]. The main targets of CD8 TFR are CD4 T cells [17], specifically TFH [19]. In autoimmune-prone mice, CD8 TFR limit TFH expansion and autoantibody production [21]. CD8 TFR expressing CD122 (IL-2Rβ) in mice were also shown to inhibit CD8 T cell function through a mechanism involving IL-10 production, but not requiring TGFβ [22]. CD8 TFR differ from conventional CD8 T cells in their potent suppressive mechanisms and their dependence on IL-15 for function [19]. Importantly, cells with the CD8 TFR phenotype (CXCR5hiCD44hi CD8+) have recently been identified in humans [23]. In the context of HIV infection there is limited evidence of CD8 Tregs. Stimulation of CD8 T cells isolated from HIV-infected patients with HIV peptides was shown to drive regulatory CD8 T cell function [24]. Suppressive function of HIV-specific CD8 T cells was further shown to be dependent on IL-10 production [25,26]. These HIV-specific CD8 T cells that produced IL-10 lacked both CD25 and Foxp3, but were able to prevent HIV-specific cytolytic function [26]. Tim-3 has been previously shown to mediate CD4 Treg suppression [27] and impair virus-specific CD8 T cell responses [28]. CD8 T cells co-expressing PD-1 and Tim-3 have both exhausted effector function and produce high levels of IL-10 during chronic viral infection [29]. Upregulation of Tim-3 on CTL is strongly correlated with reduced cytotoxicity [30] and viral persistence [31]. Additionally, Tim-3+ CD8 T cells were increased in frequency and positively correlated with plasma viral load in progressive HIV infection [32]. Increased frequencies of CD8 T cells are also found in follicles of HIV-infected individuals compared to seronegative individuals [1], but little is known about their functional properties. No studies to date have evaluated CD8 TFR in HIV or SIV infection and their potential role in HIV replication and persistence. In this study, we describe CD8 TFR phenotype and function in secondary lymphoid tissues during ex vivo HIV infection of human tonsils and in vivo SIV infection. We define CD8 TFR as CD3+CD8+CXCR5hiCD44hi cells and find that most follicular CD8 T cells in human and rhesus macaque secondary lymphoid tissues are CD8 TFR. CD8 TFR exhibit an enhanced regulatory phenotype in the context of ex vivo HIV infection and chronic SIV infection and are expanded in chronic SIV infection. In contrast to conventional CD8 T cells, CD8 TFR are able to impair TFH effector function via Tim-3 and inhibit GC B cell IgG production. Further, CD8 TFR modestly reduce HIV replication in TFH and induce less TFH apoptosis than conventional CD8 T cells in HIV infection ex vivo. Induction of TFH apoptosis by CD8 TFR is dependent on HLA-E. This work provides the first functional analysis of follicular CD8 T cell populations in the context of lentiviral infections and suggests that CD8 TFR contribute to impaired TFH function and GC dysfunction during HIV infection. First, we determined the fraction of follicular CD8 T cells within human tonsils that exhibit a CD8 TFR phenotype two days following spinoculation with X4- or R5-tropic GFP reporter virus or mock spinoculation. CD8 TFR are defined as viable CD3+CD8+CXCR5hiCD44hi cells and conventional CD8 T cells (CD8 conv) defined as all other CD3+CD8+ cells as shown in representative flow cytometry plots in Fig 1A. The percentages of CD8 TFR are not significantly altered 2 days after HIV spinoculation compared to mock-spinoculated cells (Fig 1B). Using flow cytometry counting beads to show the average of 3 experiments, we confirmed that CD8 TFR did not increase numerically in the context of ex vivo HIV infection (S1 Fig). Additionally, we confirmed that percentages of CD8 T cells that are CD8 TFR do not differ between day 0, prior to any spinoculation or cell culture, and day 2 following mock spinoculation and 2 days in culture media (S2 Fig). Next, we analyzed CD8 regulatory and exhaustion molecules (Tim-3, CD122, IL-15R, and IL-10), the CD4 Treg mediator GITR [33], and perforin expression on CD8 TFR and CD8 conv in the of context HIV infection ex vivo. First, there are no significant differences in CD122, IL-10 or perforin expression in CD8 TFR between day 0 and day 2 in mock-spinoculated cultures (S2 Fig). Tim-3 is expressed on a significantly greater percentage of CD8 TFR compared to CD8 conv in all culture conditions (i. e., mock-, X4-, and R5-spinoculated cultures) and there are no differences related to HIV infection (Fig 1C). Perforin expression is lower in CD8 TFR compared to CD8 conv in all culture conditions, and is not altered by spinoculation (Fig 1D). The percentage of IL-10+ CD8 TFR is significantly higher following both X4- and R5-spinoculation compared to mock-spinoculated cultures, and is significantly higher than the percentage of IL-10+ CD8 conv in each condition (Fig 1E). X4- and R5-spinoculation leads to significantly higher percentages of IL-15R+ CD8 TFR compared to mock spinoculation, and there are greater percentages of IL-15R+ CD8 TFR compared to IL-15R+ CD8 conv after HIV spinoculation (Fig 1F). The percentage of GITR+ CD8 TFR does not increase after HIV spinoculation, but the frequency of GITR+ CD8 TFR is greater than the frequency of GITR+ CD8 conv in all conditions (Fig 1G). CD122 is expressed on a greater percentage of CD8 TFR after X4-spinoculation compared to mock-spinoculation, and is expressed on a greater percentage of CD8 TFR compared to CD8 conv in all conditions (Fig 1H). There are not high levels of or significant differences in expression of the exhaustion molecule PD-1 or the inhibitory CD4 Treg receptor CTLA-4 between CD8 TFR and conventional CD8 T cells (S3A Fig). Further, a majority of CD8 TFR have an effector memory as opposed to central memory profile, and express more IL-10, CD122, and GITR and less perforin than conventional CD8 T cells regardless of effector or central memory cell designation (S3B Fig). Downregulation of CCR7, the extrafollicular retention molecule, combined with upregulation of CXCR5, the follicular homing molecule, is crucial for migration of CD4 T cells into follicles [34]. It has previously been shown in human tonsils that CXCR5+CD8+ T cells were located in the follicles of human tonsils by immunofluorescent tissue staining [35]. We determined the phenotype of CD8 T cells expressing the follicular homing phenotype CXCR5+CCR7- after mock-, X4-, and R5-spinoculation of human tonsil cells. A median of more than 90% of CXCR5+CCR7- cells are CD8 TFR in all conditions whereas only a minority of CD8 conv exhibit a follicular homing phenotype (Fig 2A). We further analyzed CCR7 expression on both CD8 TFR and CD8 conv. The percent of CCR7 positive cells is significantly higher in CD8 conv than CD8 TFR (Fig 2B). We next investigated whether CD8 TFR are able to suppress the GC reaction by inhibiting TFH proliferation and cytokine production, B cell function, or both. T cell proliferation is dependent on IL-2, and IL-21 production by TFH is critical for B cell affinity maturation in the GC [36]. We therefore determined whether CD8 TFR inhibit IL-2 and IL-21 production by TFH. As whole tonsil cells were spinoculated for the data generated in Figs 1 and 2, all sorted populations were spinoculated to mirror previous conditions and allow exposure to HIV. We find that CD8 TFR inhibit both IL-2 (S4A Fig) and IL-21 (Fig 3A) production by TFH in sorted X4- and R5-spinoculated cultures. This inhibition is dose-dependent on the ratio of CD8 TFR to TFH and does not occur when TFH are cultured with CD8 conv (S4B Fig). To investigate potential mechanisms regulating IL-21 production in TFH, we blocked Tim-3 in 1: 1 CD8 TFR: TFH co-cultures. Blockade of Tim-3 abrogates the effect of CD8 TFR and preserves the percent of IL-21+ TFH at levels similar to TFH cultured alone (representative examples: Fig 3B, all data and 3C), but this is not observed in TFH and CD8 TFR co-culture with isotype control antibodies (Fig 3B and 3C) or TFH and CD8 conv co-cultures (S4C Fig). There is not a consistent trend in alteration of TFH proliferation rates, as determined by proliferation dye dilution, in the presence of CD8 TFR when cultured at a 1: 1 ratio (S5 Fig). Next, we determined if CD8 TFR influence total IgG production in tonsil cultures. We cultured isolated GC B cells (CD19+CD38+) with CD8 conv, CD8 TFR, and/or TFH at equal ratios, mock- or X4-spinoculated the cells, and stimulated them with CpG-B for 6 days. There is not increased IgG production in TFH and B cell co-cultures compared to B cells alone, likely due to the use of CpG-B that activates B cells directly through TLR9. In X4-spinoculated experiments, adding CD8 TFR to B cells alone or to B cells and TFH leads to decreased IgG production, however, adding CD8 conv to B cells has no effect on IgG production (Fig 3D). As HIV replication is highly concentrated within TFH ex vivo [6] and in vivo [1,4, 5], we next investigated the effect of CD8 TFR on HIV replication in ex vivo infected tonsillar TFH using GFP-reporter viruses. Both the percentage of GFP+ TFH and the MFI of GFP is modestly reduced when sorted TFH are co-cultured 1: 1 with CD8 TFR (Fig 4A) following either X4- or R5-spinoculation. Co-culture with CD8 conv, on the other hand, does not alter HIV replication in TFH (S6 Fig). We next investigated potential mechanisms by which CD8 TFR reduce HIV replication in TFH. In mice, CD8 TFR inhibit TFH responses via Qa-1 [19], the mouse equivalent of the HLA-E molecule. To determine whether this mechanism restricts viral replication in TFH, we added HLA-E blocking antibodies to co-cultures. Blocking HLA-E interactions in 1: 1 CD8 TFR and TFH co-cultures has no effect on viral replication (Fig 4B). HIV replication has also been shown to be inhibited by IL-10 in PHA-blasted PBMCs and cell lines [37]. Nevertheless, we do not observe differences in viral replication in co-cultures of CD8 TFR and TFH with addition of IL-10 neutralizing antibodies (Fig 4C). However, inhibition of HIV replication in TFH by CD8 TFR is contact-dependent, as inhibition is not observed when cells are separated by transwell membranes in 4 separate experiments (Fig 4D). As CD8 TFR are located within the follicle, their ability (or lack thereof) to kill TFH is important for understanding their role in the follicular concentration of HIV replication. In mice, CD8 TFR are able to recognize and kill autoreactive TFH via Qa-1 interaction [19]. Therefore, we wanted to determine if HLA-E, the human equivalent of Qa-1, similarly allowed CD8 TFR to kill TFH in tonsil cultures. As tonsil cells are from HIV-uninfected subjects, we did not expect to see virus-specific killing and looked broadly at TFH apoptosis rates using Annexin-V. We investigated the rate of apoptosis in mock-, X4-, and R5-spinoculated TFH alone or in co-culture with CD8 TFR or CD8 conv. After cell populations were sorted, all cells were spinoculated, cultured together at 1: 1 ratios for 2 days, and stained for Annexin-V to determine apoptosis rates of TFH. When cultured at a ratio of 1: 1 with TFH, CD8 TFR induce less apoptosis in TFH than CD8 conv (representative examples: Fig 5A, cumulative data and 5B). We find that the rate of apoptosis in TFH is reduced further by blocking HLA-E in 1: 1 CD8 TFR and TFH co-cultures (Fig 5A and 5B). Blocking HLA-E in CD8 conv/TFH co-cultures has no effect (Fig 5A and 5B). The use of count beads during co-culture analyses shows that conventional CD8 T cells reduce the number of TFH in both X4- and R5-spinoculation, while co-culturing TFH with CD8 TFR reduces TFH numbers to a lesser extent (Fig 5C). Next, we investigated the effects of SIV infection on the frequency of CD8 TFR in secondary lymphoid tissues in vivo. Using the same phenotype as in 1A for human tonsils, we define CD8 TFR as viable CD3+CD8+CXCR5hiCD44hi cells (Fig 6A). We compared the percentage of CD8 TFR in disaggregated spleen and lymph nodes from chronically SIV-infected rhesus macaques to those from SIV-uninfected controls and find that percentages of CD8 TFR are increased a median of 4-fold during SIV infection compared to uninfected controls (Fig 6B). Additionally, we determined whether the proportion of SIV-specific cells differed among CD8 conv and CD8 TFR. We find that the frequency of SIV-Gag specific CD8 TFR is similar to that of CD8 conv (Fig 6C). There were positive, but statistically insignificant correlations between the percent CD8 TFR or percent tetramer+ CD8 TFR and viral loads (S7 Fig). We determined the expression of key CD8 regulatory molecules on CD8 TFR in rhesus macaques as done with human tonsils in Fig 2. In chronically SIV-infected animals, there is a significantly greater frequency of Tim-3+ CD8 TFR compared to CD8 conv (Fig 6D). Perforin expression on CD8 conv is significantly greater in SIV-infected compared to SIV-uninfected animals, while CD8 TFR do not display this trend and have significantly less perforin than CD8 T conv in SIV-infected animals (Fig 6E). The percentage of CD8 TFR that produce IL-10 is higher than CD8 conv in both SIV-uninfected and chronically SIV-infected macaques. Furthermore, the percentage of CD8 TFR that produce IL-10 is higher in SIV-infected compared to uninfected animals (Fig 6F). The percentage of IL-10 producing CD8 conv is similar in uninfected and SIV-infected macaques (Fig 6F). The percentage of Galectin-9 (Gal-9) + CD8 TFR tends to be higher than the percentage of Gal-9+ CD8 T conv in SIV-infected animals, but differences were not statistically significant (S8 Fig), while GITR is significantly increased on CD8 TFR in both SIV-uninfected and SIV-infected animals (Fig 6G). As shown previously for human tonsils in Fig 2, we determined the phenotype of CD8 T cells expressing the follicular homing profile CXCR5+CCR7- in lymph node and spleen of uninfected or chronically SIV-infected rhesus macaques. The vast majority of CXCR5+CCR7- cells are CD8 TFR (median 89% of uninfected, 93% of SIV-infected) whereas only a minority of CD8 conv exhibit a follicular homing phenotype (Fig 7A). We further analyzed CCR7 expression on both CD8 TFR and CD8 conv. The percent of CCR7 positive cells is significantly higher in CD8 conv than CD8 TFR in both SIV-infected and uninfected rhesus macaques (Fig 7B). Further, we performed immunofluorescent staining of lymph node and spleen tissue sections to determine the precise location of CXCR5+ CD8 T cells. As shown in representative images (Fig 7C), the follicle was defined as CD20+ (white) and the number of CD8 T cells (green) expressing CXCR5 (red) were counted as either inside the follicle or in the extrafollicular zone. Most CXCR5+ CD8 T cells, a median of 91% in chronically infected rhesus macaques and a median of 93% in uninfected rhesus macaques, were found inside of the follicle (Fig 7D). In light of findings above indicating that the vast majority of CXCR5+CD8+ T cells exhibit a CD8 TFR phenotype, it is reasonable to conclude that most cells with that phenotype reside in the follicle. Utilizing isolated CD8 TFR and TFH from chronically SIV-infected rhesus macaques, we determined if CD8 TFR regulated TFH function or apoptosis rates. Using disaggregated lymph node cells from 2 SIV-infected animals, we find that IL-21 production by TFH is inhibited when cultured with equal numbers of CD8 TFR (Fig 8A) but not CD8 conv (S9A Fig). IL-21 production by TFH is not reduced in co-cultures treated with Tim-3 neutralizing antibodies in culture (Fig 8A). The percentage of apoptotic TFH, determined by Annexin-V staining, is increased when TFH are cultured with equal numbers of CD8 TFR (Fig 8B). When HLA-E interactions are blocked with neutralizing antibodies in TFH: CD8 TFR co-cultures, the percentage of Annexin-V+ TFH decreases (Fig 8B) but not when cultured with CD8 conv (S9B Fig). This is the first study to examine the role of CD8 TFR in the context of HIV and SIV infection. We determined that the majority of follicular CD8 T cells in human tonsils, as well as in secondary lymphoid tissues from rhesus macaques, exhibit a CD8 TFR phenotype. Of all the CD8 T cells expressing the follicular homing profile CXCR5+CCR7-, 90% or more of these cells are CD8 TFR in both human tonsils and rhesus macaque lymphoid tissues. Furthermore, their percentage is higher in lymph nodes and spleens of chronically SIV-infected rhesus macaques compared to uninfected macaques. A greater percentage of CD8 TFR express IL-10 and CD8 TFR express relatively lower levels of perforin compared to CD8 conv. In ex vivo HIV spinoculation and chronic SIV infection, CD8 TFR inhibit IL-21 production by TFH and IL-21 production is rescued by Tim-3 blockade. Further, CD8 TFR inhibit IgG production by B cells in ex vivo HIV infection. Additionally, CD8 TFR significantly, albeit modestly, reduce TFH permissivity to HIV ex vivo through contact-dependent mechanisms. Compared to CD8 conv, CD8 TFR induce a low level of TFH apoptosis. Blocking HLA-E interaction in CD8 TFR and TFH co-cultures further reduces TFH apoptosis rates. Collectively, these studies demonstrate that CD8 TFR constitute the majority of CD8 cells in B cell follicles and contribute to impaired GC function in lentiviral infections. Multiple factors may account for the inability of CD8 T cells to control HIV and SIV replication in the follicles. Heightened permissivity of TFH [6] combined with a paucity of virus-specific CTL in B cell follicles may foster virus replication at those sites [2,9, 38]. Previous work in rhesus macaques has shown that CD8 is downregulated on SIV-specific cells entering the follicle [39] and CD8 downregulation leads to impairments of CTL cytokine production and proliferation [40]. It has been proposed that virus-specific CD8 T cells are exhausted in chronic infection [41,42] or that virus escape mutations prevent virus-specific CD8 T cells from recognizing infected cells [43,44], but these hypotheses do not fully account for the follicular concentration of HIV replication. Here, we show that most of the follicular CD8 T cells in humans and rhesus macaques are CD8 TFR, CD8 TFR induce TFH apoptosis at lower rates than CD8 conv, and blocking HLA-E recognition further reduces CD8 TFR–mediated apoptosis in TFH. We also demonstrate that CD8 TFR produce a modest, but statistically significant reduction in HIV replication in human tonsil cells infected ex vivo. In the LCMV-infected mouse model, Leong et. al. [45] recently found that mice reconstituted with CXCR5+CD8 LCMV-specific T cells had 50% fewer LCMV-producing TFH compared to mice reconstituted with CXCR5-CD8 T cells. Additionally, this study showed that CXCR5+CD8 LCMV-specific T cells express less perforin and are less efficient killers of LCMV-infected cells than their CXCR5- counterparts ex vivo [45]. These findings are consistent with our findings in the ex vivo HIV infection model and in chronic SIV infection that CD8 TFR express less perforin than conventional CD8 T cells in both human tonsils and rhesus macaque lymphoid tissues, and that they induce modest reductions in HIV replication and TFH apoptosis ex vivo. In marked contrast, He et. al. [46], reported profound reductions between 100- and 1,000-fold in splenic viral loads in the presence of CXCR5+CD44hiCD8 T cells compared to CXCR5-CD44hiCD8 T cells using the LCMV-infected mouse model. Reasons for the discrepancy between this study and that of Leong et. al. are not clear, as similar markers were used to define follicular populations of CD8 T cells in their studies, and these were the same markers that we used to define TFR CD8 populations in our study. An important area of future investigation will be to determine if CD8 TFR killing capacity can be boosted numerically and functionally to reduce follicular HIV replication in vivo. Mechanisms that underlie the modest reduction in HIV replication induced by CD8 TFR in our studies are not clear. This could be due to general immune suppressive mechanisms, such as lowering TFH activation levels, or alternatively through cell killing. Previous work has shown that CD4 Treg suppressed HIV replication in other CD4 T cell populations through contact-dependent inhibitory mechanisms rather than inducing cytotoxicity [47]. CD4 and CD8 regulatory cell subsets likely have complex roles in HIV infection, as evidenced by their ability to inhibit effector functions, and also reduce HIV replication. Further, CD8 TFR may promote the follicular HIV reservoir by inhibiting TFH IL-21 production, as it has been shown that ART combined with IL-21 therapy results in lower viral loads and lower intestinal cell-associated SIV DNA in rhesus macaques when compared to ART alone [48]. Determining at which point in the virus life cycle immune regulatory mechanisms inhibit viral replication could provide useful information to promote a balance of effector cell function and inhibition of HIV replication. As CD8 TFR display an ability to interfere with HIV replication ex vivo, future studies will be needed to determine if CD8 TFR inhibit viral replication or eliminate virus producing cells, as these both have distinct implications for HIV cure strategies. In this study, we show that CD8 TFR expand in chronic SIV infection. However, we do not see this expansion in our ex vivo tonsil model after 2 days of infection. A likely explanation for this discrepancy is that the expansion of CD8 TFR is a result of antigen-specific expansion in chronic HIV or SIV infection, and therefore not recapitulated in an acute infection model. This is supported by our data that show CD8 TFR are SIV-specific at a similar frequency as CD8 conv. We have previously reported that total levels of CD8 expression in lymph node follicles increase in chronically HIV-infected subjects compared to seronegative individuals [1]. The present study demonstrates that the increase of follicular CD8 T cells in chronic HIV infection is likely due to an expansion of CD8 TFR. Therapies aimed at generating protective virus-specific CTL in patients will need to verify that cytotoxic responses, as opposed to regulatory responses, are being produced in the follicle. An interesting question remaining is how CD8 TFR are generated during HIV and SIV infection. It has been suggested that persistence of antigen is the cause of functional impairment of HIV-specific effector responses [49]. TFH are expanded in HIV [4,50] and SIV [3] infection, upregulate HLA-E upon HIV infection [51], and constant antigenic stimulation occurs in the follicle and GC [52,53]. It is possible that CD8 TFR are generated through contact with HLA-E on TFH as they enter follicular and GC regions. These interactions could convert effective CTL into CD8 TFR and allow for HIV persistence in the follicle. Further investigation as to whether CD8 TFR migrate into the follicle or are converted from precursors after migrating into the follicle will be an important aspect of potentially manipulating or preventing this response to promote cytotoxicity. It was shown that CD8 T cells from IL-15 knock-out mice lose suppressive capabilities [19]. Importantly, CD8 Treg from these mice were unable to suppress TFH number, GC expansion, and IgG production. Interestingly, expansion and cytotoxicity of CD8 T cells is impaired in IL-21 knockout mice, but the combination of IL-21 and IL-15 synergistically improves CD8 effector function [54]. Additionally, IL-15 has been shown to have therapeutic potential as an adjuvant in HIV vaccines [55,56] and in restoring CTL function [57,58]. Here, we find that CD8 TFR have elevated IL-15R expression and suppress TFH IL-21 production in HIV infection ex vivo. As CD8 TFR have access to HIV-infected TFH in the GC, it will be interesting to determine if the use of IL-15 and IL-21 in HIV therapy increases CD8 TFR cytotoxic function and promotes the elimination of HIV-infected TFH. In chronic HIV infection expression of exhaustion markers such as PD-1 [42] and Tim-3 [29] correlate with diminished cytotoxic capacity. The inhibitory cytokine IL-10 was specifically produced by Tim-3+PD-1+ CD8 T cells after stimulation with LCMV peptides, suggesting Tim-3 is a potential target to limit regulatory cytokine production and promote CTL function. We find that inhibition of Tim-3 prevents impairment of TFH function by CD8 TFR. Thus, Tim-3 blockade could provide a new mechanism to reverse CD8 regulatory functions and perhaps boost TFH function. Further studies addressing the inhibitory mechanisms of CD8 TFR and their role in TFH impairment would be useful to determine how to boost the high quality response of TFH to HIV vaccines. Previous work in mice showed that CD8 TFR do not directly suppress antigen-specific antibody production [19], however CD8 T cells have been shown to directly suppress non-specific antibody responses in other models [59]. A previous study found that both CXCR5-CD8+ and CXCR5+CD8+ human tonsil cells supported IgG production by CD19+ B cells in uninfected, unstimulated conditions [35]. Here we find that CD8 TFR are able to directly suppress total IgG production by B cells in a stimulated, HIV-spinoculated culture. This is not observed when B cells are cultured with CD8 conv, indicating a unique effect of CD8 TFR on GC B cells. A previous study using human tonsil cells showed that CD4 Treg were also able to suppress IgG production by B cells [60]. Thus, the mechanism for direct suppression of B cells could be a general feature of all regulatory T cell subsets, through common expression of Tim-3 or GITR, or a mechanism unique to CD8 TFR such as sequestration of IL-15 since IL-15 knock-out mice have been shown to produce less IgG [61]. Further, it is unknown at this time if CD8 TFR can suppress antibody production elicited by TFH, but it is likely as CD8 TFR strongly inhibited IL-21 production by TFH. Future studies to determine whether CD8 TFR suppress HIV-specific antibody responses are warranted. CD8 TFR suppression of B cell function could potentially account for why HIV-infected individuals have poor responses to T cell-independent vaccines, such as the polysaccharide vaccines against pneumococcus [62] and S. typhi [63]. A better understanding of the role of CD8 TFR in generation of antigen-specific antibody responses could lead to innovative strategies to improve vaccine responses in HIV-infected individuals. Reduction of pro-inflammatory responses prior to high-dose SIV challenge prevented mucosal transmission [64], suggesting regulatory immune cell function could be an important aspect of reducing HIV infection and replication. Interestingly, the induction of immune tolerance via CD8 Tregs was shown to have a protective role in rhesus macaques prior to SIV challenge [65]. Specifically, non-classical MHC-Ib/E restricted CD8 T cells from SIV-immunized animals inhibited CD4 T cell activation and SIV replication within autologous CD4 T cells infected ex vivo, but only if the CD8 T cells were added within 48 hours [65]. We similarly observe that CD8 TFR reduce HIV replication in TFH ex vivo after 2 days. Taken together with our results that CD8 TFR induce less apoptosis in TFH than conventional CD8 T cells, we hypothesize that CD8 TFR would limit cellular activation and HIV replication within TFH on a per cell basis whereas CTL would reduce the number of HIV-infected TFH. However, these data were obtained in an ex vivo infection model and lack HIV-specific responses, so further studies in vivo would be necessary to determine if CD8 TFR and CTL differentially affect the follicular HIV reservoir. Although we observe only modest reductions in HIV replication in tonsil cells infected ex vivo, our data supports the notion that inflammation and cellular activation promote HIV infection and replication. However, regulation of infected cells may have drawbacks, as opposed to benefits prior to infection. An in-depth analysis is necessary to determine if immune regulatory activity on infected cells is inhibiting replication pre- or post-integration and if this promotes formation of the latent HIV reservoir. In this study, we find that most follicular CD8 T cells are CD8 TFR and they potently impair TFH and GC B cell responses. The heightened regulatory function and relative lack of cytolytic potential of CD8 TFR could contribute to viral persistence in the follicle and impairments of humoral immunity that are characteristic of HIV and SIV infection. This is a novel mechanism of regulation of humoral immunity and remains to be explored in the context of other human diseases. Development of therapies that block CD8 TFR interaction with TFH and GC B cells could lead to novel approaches to improve the quality of antibody responses in HIV infection. Human tonsils were obtained from the Colorado Children’s Hospital (Aurora, Colorado, USA) following routine tonsillectomy from individuals at low risk for HIV infection. Use of tonsil specimens for these studies was reviewed by the Colorado Multiple Institutional Review Board and determined to not constitute human subjects research (COMIRB approval no. APP001-1), in accordance with guidelines issued by the Office of Human Research Protections (http: //www. hhs. gov/ohrp/policy/checklists/decisioncharts. html), and consequently, informed consent was not required. All research involving human subjects conformed to the principles set forth in the Declaration of Helsinki and was approved by the Colorado Multiple Institutional Review Board. Rhesus macaques were cared for according to the guidelines of the Animal Welfare Act and the NIH for housing and care of laboratory animals. Animal experiments were approved by the Institutional Animal Care and Use Committee of the University of Wisconsin (IACUC; protocol G00632). Procedures were performed to ensure that discomfort was limited to that unavoidable in the conduct of the research plan. Animals were housed at the Wisconsin National Primate Research Center (WNPRC), which is accredited by American Association of Accreditation of Laboratory Animal Care (Animal Welfare Assurance No. A3368-01). Sedatives were applied as necessary for blood and tissue collections and analgesics were used when determined appropriate by veterinary medical staff. Animals were fed standard monkey chow twice daily. Pain, distress, animal behavior, food and drink consumption was monitored and adjustments were made as necessary. SIV-infected rhesus macaques were singly housed, but had visual and auditory contact with at least one social partner, permitting the expression of non-contact social behavior. Animals had access to more than one category of enrichment at WNPRC. The IACUC proposal included a written scientific justification for any exclusion from some parts of the enrichment plan. Research-related exemptions are reviewed at least annually. Lymph nodes and spleen were obtained from 6 SIVmac239-infected and 6 uninfected Indian rhesus macaques (Macaca mulatta). Animals were infected either intravenously or intrarectally with SIVmac239, and had been infected from 12 to 241 weeks (median, 19. 5 weeks) at the time that specimens were obtained. Plasma SIV RNA concentrations ranged from 3. 78 to 6. 45 log10 copies/ml (median, 5. 45 log10 copies/ml), and CD4+ T cell counts ranged from 291 to 422 cells/mm3 (median, 362 cells/mm3). Of SIV-infected animals, 2 were female and ranged in age from 7 to 8 years old. Of SIV uninfected animals, 2 were female and ranged in age from 10 to 23 years old. Tissues were either shipped overnight on ice in cold RPMI 1640 and disaggregated, or disaggregated and cryopreserved at the Wisconsin National Primate Research Center and later shipped on liquid nitrogen to the University of Colorado. The HIV-1 NL4-3-based CXCR4 (X4) -tropic green fluorescent protein (GFP) reporter virus NLENG1-IRES [66] and the CCR5 (R5) -tropic GFP reporter virus NLYUV3-GFP [67] were used for tonsil cell infections. Virus stocks were prepared by transfecting 293T cells (ATCC) with either X4 or R5 plasmid constructs (Effectene, Qiagen 301425) in complete DMEM (DMEM + 10% FBS, pen/strep, and non-essential amino acids), collecting supernatants, and spinning at 800 x g to remove debris. Viral stocks were stored at -80°C prior to use. After disaggregation, 5 x 106 tonsil cells were spinoculated with either GFP reporter virus or a mock spinoculation with an equal volume of complete DMEM for 2 hours at 1200 x g at room temperature. Cells were washed to remove unbound virus and media, and cultured for 2 days at 37°C with 5% CO2 in RPMI with 10% FBS, L-glutamine, and pen/strep (R10) at a density of 1. 5 x 106 cells/mL. Cells were collected and immediately processed for analysis by flow cytometry. Cells were blocked for 20 minutes with 2% BSA in PBS at 4°C and then stained for 30 minutes at 4°C in the dark. The following anti-human conjugated antibodies were used: CD3-APCCy7-UCHT1 (Tonbo 25–0038), CD8-eVolve605-RPA-T8 (eBioscience 83–0088), CD19-FITC-SJ25C1 (Tonbo 35–0198), CD38-violetFluor450-HIT2 (Tonbo 75–0389), CXCR5-PE-MU5UBEE (eBioscience 18–9185), PD-1-APC EH12. 2H7 (BioLegend 329908), GITR-PECy7-eBioAITR (eBioscience 12–5875), CD44-APC-IM7 (Tonbo 20–0441), Tim3-APC-344823 (R&D FAB2365A), IL-15R-FITC-eBioJM7A4 (eBioscience 11–7159), CD122-V421-Mikβ3 (BD 562887), PD-1-APC-EH12. 2H7 (BioLegend 329908), CTLA-4-PECy5-BNI3 (BD 561717), CD62L-PE-SK11 (BD 341012), and CCR7-PECy7-3D12 (BD 557648). The same antibody panel was used for rhesus macaque cell staining with the exception of CD3 SP34-2 (BD 557757). All analyses were performed on Ghost Dye 510 (Tonbo 13–0870) negative cells. Cells were fixed with 2% paraformaldehyde. Fresh human tonsil cells were typically 70–90% viable after culture and cryopreserved rhesus macaque cells ranged from 40–80% viability after freeze/thaw. All antibodies were used at one test per 106 cells. Data were acquired on a custom LSR II flow cytometer (Serial # H47100196, BD Immunocytometry System, San Jose, CA) with BDFACS Diva (v6. 1) and with a configuration of 6 filters (755LP, 685LP, 670LP, 635LP, 600LP, 550LP, and 505LP) on a blue laser (488 nm), 6 filters (750LP, 690LP, 635LP, 595LP, 505LP, and 450/50) on a violet laser (405 nm), and 3 filters (755LP, 685LP, and 670/30) on a red laser (633 nm). FCS files were analyzed using FlowJo (v10. 7, Tree Star, Ashland, OR). Briefly, biotinylated MHC class I monomers were loaded with peptides (NIH Tetramer Core Facility) and converted to MHC tetramers with APC streptavidin (Prozyme PJ27S). The MHC class I monomer Mamu-A*001: 01 molecule loaded with SIV Gag CM9 (CTPYDINQM) peptides was used. Cryopreserved disaggregated lymphoid tissue cells were thawed, and 1–2 x 106 disaggregated cells were resuspended in 100 μL of tetramer staining buffer (5% fetal bovine serum in PBS with 0. 06% sodium azide) and incubated with APC-labelled Gag CM9 tetramer concurrently with CXCR5-PE-MU5UBEE, CD8-eFlour605-RPA-T8, CD44-eFluor450-IM7, CD3-APC Cy7-SP34-2 and Ghost Violet 450 viability in the dark for 40 minutes at room temperature. SIV-uninfected (R05021 mesenteric lymph node, RhA578 inguinal lymph node, R05018 axial lymph node, and R05091 spleen) and chronically SIV-infected (R03111 spleen, Rh2123 spleen, R02017 inguinal lymph node, Rh2284 spleen, Rhax18 spleen, R02116 inguinal lymph node, and Ro1038 inguinal lymph node) rhesus macaque lymphoid tissues were analyzed as follows. Four micron frozen tissue samples were fixed in 1% paraformaldehyde and stained with Rabbit anti CD20 (Abcam, Cambridge, MA), Rat anti CD8 (Bio Rad, Hercules, CA) and mouse anti CXCR5 (NIH NHP Reagent Resource) followed by detection with AF647 Donkey anti rabbit, AF594 Goat anti Mouse (highly cross absorbed) and AF488 Goat anti rat (highly cross absorbed) (Thermo Fisher Scientific, Waltham, MA). Sections were counterstained with DAPI and imaged on a Leica IMI6000 inverted fluorescent microscope. Ten 40X images were analyzed using Qwin (Leica Microsystems) by first defining the follicular region and counting CD8+CXCR5+ cells within each region and calculating the frequency of cells both in and out of the follicle. An adjacent section was stained for CD20 only and visualized using Vector HP Immpress and Vector Red (Vector Laboratories, Burlingame, CA) and the total follicular and extrafollicular area determined using Qwin. The percentage of CD8+CXCR5+ cells in the follicle was determined based on the frequency of cells within the follicular and extrafollicular regions and the total areas of each region. Human tonsil and rhesus macaque lymph node cells were sorted using a MoFlo Astrios EQ. Cells were sorted into TFH (CD3+CD8-CXCR5+), conventional CD8 (CD3+CD8+CXCR5-), CD8 TFR (CD3+CD8+CXCR5hiCD44hi), and GC B cell (CD19+CD38+) populations. After sorting, all tonsil cell subsets were spinoculated with X4- or R5-HIV GFP reporter viruses and cultured in R10. All cell populations were spinoculated to mirror whole tonsil cell cultures and allow for all cell populations to be exposed to virus. For measurements of TFH cytokine production, TFH were seeded at 1 x 105 cells in a 24 well plate and CD8 TFR were added at ratios of 1: 1,1: 10, and 1: 50. After 2 days, TFH were stimulated to measure IL-2 and IL-21 by ICS. For blocking experiments, TFH and CD8 TFR or conventional CD8 were cultured at a 1: 1 ratio in the presence of 500 ng/μL anti-Tim-3 (Biolegend 345003) antibodies or 500 ng/μL anti-HLA-E (Biolegend 342602) antibodies for 2 days. In transwell assays, 4 x 104 TFH were cultured in the bottom compartment and 4 x 104 CD8 TFR or conventional CD8 T cells were added to the upper compartment of 96-well permeable support plates (Corning CLS3386) and cultured for 2 days. After 2 days of culture, tonsil cells were stimulated with 50 ng/mL of phorbol 12-myristate 13-acetate (PMA, Sigma P8139) and 1 μg/mL of ionomycin (Sigma I3909) in the presence of protein transport inhibitor containing monensin (BD GolgiStop) for 5 hours. Cells were then harvested, blocked and stained for surface markers as above, and then fixed and permeabilized using BD CytoFix/Cytoperm kit (554714) according to manufacturers’ instructions. Cells were then stained at 4°C for 30 minutes and analyzed for IL-2-PE-MQ1-17H12 (BD 559334), IL-10-eFluor450-JES3-9D7 (eBioscience), IL-21-AF647-3A3-N2. 1 (BD 560493), and perforin-FITC-Pf344 (Mabtech 3465–7). All cytokine analyses were normalized to a mock-spinoculated control that received monensin but was not stimulated. After sorting, 5 x 104 GC B cells and CD8 TFR TFH were cultured in the presence or absence of TFH at ratios of 1: 1: 1. Cells were co-cultured in R10 for 6 days in 96 well plates and treated with either 2. 5 μg/mL of CpG-B or were unstimulated. Media was collected and spun at 5,000 x g to remove cellular debris and stored at -80°C. ELISAs were performed using the total IgG kit (Ready set go, eBioscience 88–50550) according to manufacturer’s instructions. Briefly, 96 well plates were coated overnight with anti-human IgG and culture supernatants were diluted at a 1: 10 ratio for detection. Supernatants were incubated on pre-coated plates for 2 hours, washed, and incubated with HRP anti-IgG for 1 hour. After addition of HRP substrate, plates were analyzed on a plate reader at 450 nm and IgG calculated based on standards. TFH (CD3+CD8-CXCR5+CD25-) were sorted and stained with proliferation dye (Cell Proliferation Dye eFluor670, eBioscience 65–0840) at a concentration of 0. 5 μM. In a 96-well plate, pre-coated with 5 μg/mL anti-CD3 (Tonbo 40–0037) in PBS at 37°C for 2 hours, 104 TFH per well were cultured for 4 days in 200 μL R10 containing 2 μg/mL anti-CD28 (Tonbo 40–0289) and 10 U/mL IL-2 with an equal number of sorted CD8 TFR (CD3+CD8+CXCR5hiCD44hi) or alone. At day 4, cells were stained with viability dye (Ghost Violet 450, Tonbo 13–0863) and analyzed by flow cytometry. Comparisons of uninfected and SIV-infected rhesus macaque spleen or lymph nodes were performed using non-parametric Mann Whitney tests. Comparisons of tonsil cultures were performed using unpaired Mann Whitney or Friedman non-parametric tests. In direct comparisons of paired data, a paired Wilcoxon ranked sums test was performed to compare the two group medians of interest. Significance is denoted in each figure by asterisks, as * = p < 0. 05, ** = p< 0. 01, and *** = p < 0. 001. All statistical tests were performed with GraphPad Prism 6.

Title: Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection Summary: HIV is a chronic infection and is never completely cleared from the body, despite successful antiretroviral therapy that reduces plasma viral loads to undetectable levels and restores CD4 T cell counts. While undetectable in plasma, HIV is able to hide in various niches throughout the body. One such niche are CD4 T cells residing in the follicles and germinal centers of secondary lymphoid tissues. The dynamics of these regions that lead to persistence of HIV-infected cells remain unclear. However, recent evidence strongly suggests that CD8 cytotoxic T lymphocytes, which are able to kill HIV-infected cells outside of these regions, are present at low numbers in follicles and germinal centers. Here, we further advance these recent findings by showing that the few CD8 T cells within the follicle have potent regulatory functions rather than conventional cytotoxic functions. Thus, the CD8 T cells entering these regions of HIV persistence not only fail to kill HIV-infected cells, but promote impairments in humoral immunity. These findings identify a new obstacle that must be taken into account to improve immune responses and clearance of HIV.

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Write a title and summarize: Gabun (französisch Gabon) ist ein Staat in Zentralafrika. Im Norden grenzt er an Kamerun und Äquatorialguinea sowie im Osten an die Republik Kongo. Seine Westküste liegt am Golf von Guinea. Durch das Land verläuft der Äquator. In dem zu großen Teilen von Regenwald bedeckten Land herrscht ein tropisches Klima. Die Hauptstadt des rund zwei Millionen Einwohner zählenden Landes ist Libreville. Neben verschiedenen Bantu-Sprachen sprechen die meisten Einwohner der ehemaligen französischen Kolonie Französisch. Die Öleinnahmen des Landes finanzieren einen großen Teil des Staatsbudgets. Seit 1967 wird das Land von der Familie Bongo regiert und gilt vielen internationalen Beobachtern als Diktatur. Nach 42 Jahren übernahm der heutige Präsident Ali-Ben Bongo Ondimba 2009 nach einer umstrittenen Wahl die Herrschaft von seinem Vater Omar Bongo. == Geographie Gabun liegt an der westlichen Atlantikküste Zentralafrikas, von wo aus es sich in östliche Richtung bis kurz vor das Kongobecken erstreckt. Die Küstenlänge beträgt 885 km. Das westliche Küstentiefland steigt nach etwa 200 Kilometern stufenförmig bis zur Niederguineaschwelle im Osten an. Der höchste Berg Gabuns ist bisher nicht festgelegt. Es existieren verschiedene (fehlerhafte) Angaben, die bis zu 500 Höhenmeter voneinander abweichen. Die höchsten Erhebungen im Nordosten und Süden reichen bis knapp über 1000 m ü. d. M. Mehr als 70 Prozent der Landfläche sind von tropischem Regenwald bedeckt. In einigen Regionen Gabuns findet sich sehr altes Gestein, das bis auf das Proterozoikum (rund 2 Milliarden Jahre vor heute) datiert werden kann. In den entsprechenden Formationen wurden unter anderem Gabonionta, mögliche frühe Formen mehrzelligen Lebens, und insgesamt 17 natürliche Kernreaktoren gefunden, deren bekanntester der Naturreaktor Oklo ist. === Hydrologie Größter Fluss des Landes ist der Ogooue (ca. 1200 km), der sich mit seinen zahlreichen Nebenflüssen tief in das Gelände des Hochlands eingeschnitten hat. Etwa des Landes werden durch sein Einzugsgebiet entwässert. Darüber hinaus gibt es noch den Nyanga und mehrere Küstenflüsse. === Flora und Fauna In der Region Gabuns ist eine hohe biologische Vielfalt zu finden. Nach Schätzungen leben 64.000 Elefanten, 25.000 Gorillas und 35.000 Schimpansen in Gabun. 680 Vogelarten wurden nachgewiesen, sowie 320 Arten von Orchideen. Seltene und teilweise endemische Arten sind Flachlandgorillas, Mandrills, Waldelefanten, Bongo-Antilopen und Buntkopf-Felshüpfer. Die Landschaften Gabuns reichen von Savanne und Küste bis zu dichtem tropischem Regenwald. 2002 wies die Regierung rund 10 % der Landfläche als Nationalparks aus, was weltweit zu den höchsten Flächenanteilen gehört. Die 13 Nationalparks werden von der National Agency for National Parks verwaltet und betreut. Touristisch am bekanntesten sind das Reserve de la Lope, aber auch der Ivindo Nationalpark oder der Loango-Nationalpark. == Bevölkerung Gabun gehört zu den am dünnsten besiedelten Ländern Afrikas. Es hat etwa drei Viertel der Fläche Deutschlands, aber nur knapp doppelt so viele Einwohner wie Köln. 90 % der Bevölkerung lebt in und um die drei größten Städte: Libreville mit ca. 700.000, Port-Gentil mit ca. 140.000 und Franceville mit ca. 110.000 Einwohnern. Die Landesmitte und der Norden sind weitgehend menschenleer. Der jährliche Bevölkerungszuwachs betrug 2019 2,5 Prozent. Die zusammengefasste Fruchtbarkeitsziffer lag 2019 bei 3,9 Kindern pro Frau und somit unter dem afrikanischen Durchschnitt. Seit dem Höchststand von 5,7 im Jahr 1983 ist der Wert kontinuierlich gesunken. Frauen haben eine Lebenserwartung von 68,7 und Männer von 64,4 Jahren (Stand 2019). 37,2 Prozent der Bevölkerung sind unter 15 und 3,5 Prozent über 65 Jahre alt. === Volksgruppen Auf dem Staatsgebiet Gabuns leben etwa 40 verschiedene Völker bzw. ethnische Gruppen; die Mehrheit der Bevölkerung sind Angehörige von Bantu-Völkern. Davon sind die mit Abstand größte und politisch einflussreichste Volksgruppe die Mpongwe-Fang, die etwa ein Drittel der Gabuner stellen (Mpongwe 31 %, Fang 7 %). Kleinere Gruppen sind die Mbete (15,5 %), die Bapunu (15 %, mit der Sprache Punu), die Tsabatis (14 %), die Batazis (9,5 %) und die Bateke (4 %). Außerdem gibt es 1,5 % Pygmäen - die im Nordosten und Süden lebenden Ureinwohner - sowie ungefähr 60.000 Franzosen (meist in den Städten). Ausländer - viele davon Angestellte eines multinationalen Erdölkonzerns - spielen eine große Rolle im Bildungswesen und in der Wirtschaft. Im Jahre 2017 waren 13,8 % der Bevölkerung im Ausland geboren. === Sprachen Die Amtssprache Französisch wird von rund 80 Prozent der Gesamtbevölkerung beherrscht, wobei es ein Drittel der Einwohner der Hauptstadt Libreville als Muttersprache spricht. Im Alltag werden überwiegend Bantusprachen gesprochen. Die wichtigste Bantusprache ist das Fang, daneben haben auch das Mbere, das Punu, das Teke und das Njebi Bedeutung. Insgesamt werden 42 Sprachen und Idiome gesprochen. === Religionen Etwa 65 Prozent der Einwohner bezeichnen sich als Christen (rund 60 % als Katholiken und ca. 5 % als Anhänger verschiedener protestantischer Kirchen). Viele von ihnen pflegen weiterhin bestimmte Formen afrikanischer Religiosität. Ein großer Teil der übrigen Bevölkerung hängt zumeist den traditionellen Volksreligionen, vor allem dem Bwiti, an. Eine Minderheit von rund 12 % bekennt sich zum Islam, darunter Präsident Bongo und zahlreiche Ausländer. === Bildungswesen Es besteht offiziell eine zehnjährige allgemeine Schulpflicht. Etwa die Hälfte der Schulen des Landes Gabun sind in konfessioneller oder privater Trägerschaft. Die Analphabetenquote beträgt allerdings weiterhin etwa 29 %. === Gesundheitswesen Die Kindersterblichkeit lag 2019 bei 34 pro 1000 Geburten und die Müttersterblichkeit bei 291 pro 100.000 Geburten (Stand 2017). 86 % der Geburten können medizinisch betreut werden (Stand 2008). Die AIDS-Rate wird je nach Quelle auf zwischen 8,0 % und 5,9 % geschätzt (siehe auch: HIV/AIDS in Afrika). Die medizinische Versorgung ist oft unzureichend. 2015 waren 7 % der Bevölkerung unterernährt, was eine der niedrigsten Raten in Afrika ist. Lambarene in Gabun beherbergt das von Albert Schweitzer begründete und bis zu seinem Tod 1965 von ihm geleitete Urwaldkrankenhaus. == Geschichte === Europäischer Einfluss Der Name Gabun leitet sich aus dem portugiesischen Wort "Gabao" ab und bedeutet "Umhang". Als im 15. Jahrhundert portugiesische Seefahrer die Küste des Landes erreichten, gaben sie der Mündung des Flusses Komo wegen dessen eigentümlicher Form den Namen Gabao. Nach der Besiedlung des Gebietes erlangten die französischen Siedler 1839 eine erste Hoheit über das Gebiet. 1854 wurde Gabun mit Goree und anderen französischen Siedlungen vereinigt, Goree 1858 in den Senegal wiedereingegliedert. 1888 wurde Gabun Teil von Französisch-Kongo und 1910 als selbständiger Teil von Französisch-Äquatorialafrika wieder ausgegliedert. Am 8. bis 12. November 1940, als campagne du Gabon bzw.bataille de Libreville bezeichnet, erfolgte die Einnahme von Gabuns Hafen durch Forces francaises libres (FFL) unter De Gaulle und britischen Verbänden. Der bis dahin von Vichy-treuen Truppen gehaltene und nun strategisch bedeutsame Hafen fiel damit an die Alliierten. Die loi-cadre Defferre wurde 1956 unter französischer Verwaltung eingeführt und damit das allgemeine aktive und passive Frauenwahlrecht. Als Französisch-Äquatorialafrika 1958 aufgelöst wurde, erlangte Gabun als Gabunische Republik die Autonomie. === Unabhängigkeit und Diktatur Omar Bongos Am 17. August 1960 erlangte Gabun die Unabhängigkeit von Frankreich unter Präsident Leon M'ba, dem 1967 nach dessen Tod Omar Bongo nachfolgte. Das Frauenwahlrecht wurde bei der Unabhängigkeit bestätigt. Die Gründung der Parti Democratique Gabonais (PDG) erfolgte am 12. März 1968. Mit dieser Einheitspartei regierte er das Land lange Zeit mit harter Hand. Gabun führte in den 1990er Jahren ein Mehrparteiensystem ein und verabschiedete eine neue Verfassung, die eine Reform der Regierungsorganisationen und transparentere Wahlen ermöglichte. Die relativ geringzahlige Bevölkerung, die enormen Rohstoffvorkommen und Hilfe von außen ermöglichten Gabun sich im Laufe der Zeit zu einem florierenden Staat in Afrika zu entwickeln. Staatspräsident Omar Bongo war der am längsten herrschende Staatschef in Afrika; er starb am 8. Juni 2009 in Barcelona an Herzstillstand. === Seit dem Machtwechsel 2009 Die Senatspräsidentin Rose Francine Rogombe wurde zur Übergangspräsidentin gewählt mit dem Auftrag, innerhalb von 45 Tagen Neuwahlen zu organisieren. Am 30. August 2009 gewann der Verteidigungsminister Ali Bongo die Wahlen und wurde damit Nachfolger seines Vaters als Staatspräsident. Er erreichte mit 140.000 Stimmen 41,73 % der abgegebenen Stimmen bei 800.000 Wahlberechtigten. Auf den früheren Innenminister Andre Mba Obame und auf einen weiteren Oppositionskandidaten entfielen je etwa 87.000 Stimmen. Am Wahltag kam es in der Hafenstadt Port-Gentil, einer Hochburg der Opposition, lokal zu Krawallen durch Anhänger des unterlegenen Kandidaten, in die etwa 600 Personen, vorwiegend männliche Jugendliche, verwickelt waren. Es wurden ein Polizeiposten und ein Gefängnis gestürmt und 300 Gefangene befreit. Die Gelegenheit wurde genutzt, um zahlreiche Geschäfte, vorwiegend die von libanesischen Immigranten, zu plündern. Die von den unterlegenen Kandidaten verlangte Neuauszählung der Stimmen ergab keine Veränderung des Wahlergebnisses. Daher wird das Ergebnis von diesen noch immer nicht anerkannt. Da aber sowohl europäische als auch Wahlbeobachter der Afrikanischen Union die Rechtmäßigkeit und Richtigkeit dieser Wahlen bestätigt haben, kam es am 17. Oktober 2009 zur Amtseinführung Ali Bongos. Bei der Präsidentschaftswahl 2016 wurde Bongo knapp mit 49,8 Prozent gegenüber 48,23 Prozent für Jean Ping im Amt bestätigt. Von Oktober 2018 bis Februar 2019 hielt sich Bongo wegen einer Krankheit im Ausland auf. Nach einem Putschversuch "zur Wiederherstellung der Demokratie" durch Offiziere der Streitkräfte Gabuns am 7. Januar 2019 kehrte Bongo zurück und ernannte ein neues Kabinett. == Politik === Politisches System Nach der Verfassung vom 28. März 1991 ist Gabun eine präsidiale Republik mit einem Mehrparteiensystem. Der Präsident ist Staatsoberhaupt und Oberbefehlshaber der Streitkräfte und wird für 7 Jahre vom Volk direkt gewählt und kann nach einer Verfassungsänderung von 2003 unbegrenzt wiedergewählt werden. Vollziehendes Organ ist die Regierung unter Vorsitz des Premierministers (wird vom Präsidenten ernannt). Der Präsident übt gemeinsam mit ihm und dem Regierungskabinett, das dem Präsidenten verantwortlich ist, die Exekutivgewalt aus. Die Legislative hingegen liegt beim Zweikammerparlament, das aus dem Senat (mit 91 Mitgliedern, die von den Regional- und Gemeinderäten auf 6 Jahre gewählt werden) und der Nationalversammlung besteht. Die Nationalversammlung hat 120 Abgeordnete, die für 5 Jahre gewählt werden. Das aktuelle Rechtssystem umfasst rechtsgeschichtliche Elemente mit Ursprüngen in der französischen Kolonialzeit sowie im traditionellen Stammesrecht. Einflussreichste Parteien: === Menschenrechte In Gabun arbeiten viele Kinder, die von Menschenhändlern aus ihrer Heimat verschleppt wurden, vor allem Mädchen von 8 bis 15 Jahren aus Togo, Benin und Nigeria. Die Gefängnisse sind überfüllt und die Haftbedingungen sehr hart. Lebensmittel, hygienische Bedingungen und Belüftung sind mangelhaft. Medizinische Versorgung ist so gut wie nicht vorhanden. Selbstzensur werde in der Presse häufig unternommen, da es nach den Angaben der international tätigen Nichtregierungsorganisation Reporter ohne Grenzen im Land sehr häufig zu Polizeigewalt gegen Journalisten kommt. In Gabun entwickelt sich zunehmend eine Zivilgesellschaft. Federführend war unter anderem das Engagement des Aktivisten Marc Ona, welcher 2009 den Goldman Environmental Prize erhielt. Homosexualität ist in Gabun seit 2020 legal. Vorher warnte jedoch noch das Auswärtige Amt der Bundesrepublik: "Offen vorgetragene Bekenntnisse zur Homosexualität" werden von größeren Bevölkerungsteilen als "Verstoß gegen die guten Sitten" betrachtet und würden nicht verstanden. === Außenpolitik 2010/11 war das Land über einen nicht-ständigen Sitz im Sicherheitsrat der Vereinten Nationen in New York und Genf und bei der UNESCO in Paris vertreten. Weiterhin wurden in der nichtafrikanischen Welt Botschaften in Frankreich, Großbritannien, Italien, USA, Russland, Belgien (Brüssel), Brasilien, Kanada, Saudi-Arabien, China, Libanon, Südkorea und Japan eingerichtet. Gabun ist bei der Bundesrepublik Deutschland in Berlin durch die außerordentliche und bevollmächtigte Botschafterin, Marianne Odette Bibalou Bounda, akkreditiert. Deutschland wiederum hat in der Hauptstadt Libreville eine Botschaft eingerichtet, die zugleich für Sao Tome und Principe zuständig ist, jedoch nicht für Rechts- und Konsularaufgaben. Außerordentlicher und bevollmächtigter Botschafter ist Pascal Richter. Gabun ist Mitglied der International Cocoa Organization. === Militär Die Streitkräfte Gabuns gliedern sich in Armee, Luftwaffe und Marine und verfügen über 5000 Mann. Gabun gab 2017 knapp 2,1 Prozent seiner Wirtschaftsleistung oder 299 Millionen US-Dollar für seine Streitkräfte aus. === Verwaltung Der Staat gliedert sich in neun Provinzen, diese wiederum in 37 Departements. Daten 1993, 2003, und 2013 basierend auf Zensus, 2020 auf Projektion. == Wirtschaft und Verkehr Reiche Naturschätze sowie eine liberale Wirtschaftspolitik begünstigten die wirtschaftliche Entwicklung Gabuns. Das Bruttoinlandsprodukt betrug 2016 19.056 Dollar (KKP) je Einwohner, was vergleichbar mit dem Einkommensniveau von Argentinien war. Gabun ist somit eines der reichsten Länder Subsahara-Afrikas. Dennoch leben etwa 80 Prozent der Bevölkerung unterhalb der Armutsgrenze. Auch wenn Gabun gemäß Human Development Index im letzten Jahrzehnt im Bereich mittlerer bis hoher menschlicher Entwicklung lag, lebt etwa ein Drittel der Bevölkerung in extremer Armut. Über 90 % des Bruttoinlandsprodukts wird von nur 10 % der Bevölkerung verbraucht. Die Arbeitslosenrate wird 2015 mit 28 % angegeben und liegt damit sehr hoch. Die meisten Beschäftigungsverhältnisse sind informeller Natur und Unterbeschäftigung ist weit verbreitet. Die wichtigsten Handelspartner sind die Vereinigten Staaten, China und Frankreich. Es sind nach Angaben des Präsidenten Ali Bongo konkrete Projekte zum Ausbau des öffentlichen Verkehrswesens, des überregionalen Straßennetzes und zur nachhaltigen Landwirtschaft vorhanden und teilweise bereits in Ausführung. Gabun ist in die regional-staatliche Wirtschafts- und Währungsorganisation CEMAC eingebunden, zu der neben Gabun auch Kamerun, Äquatorialguinea, die Republik Kongo, der Tschad und die Zentralafrikanische Republik zählen. Die CEMAC ist damit ein rund 55 Millionen Menschen umfassender Wirtschaftsraum. Gabun ist über den CFA-Franc BEAC mit einem festen Wechselkurs an den Euro gebunden. Im Global Competitiveness Index, der die Wettbewerbsfähigkeit eines Landes misst, belegte Gabun Platz 108 von 138 Ländern (Stand 2016-17). Im Index für wirtschaftliche Freiheit belegte Gabun 2017 Platz 103 von 180 Ländern. === Kennzahlen Alle BIP-Werte sind in US-Dollar (Kaufkraftparität) angeben. === Bodenschätze Gabun ist einer der rohstoffreichsten Staaten Afrikas, mit erheblichen Erdölreserven vor der Küste. Dementsprechend zählen zu seinen Hauptexportgütern Rohöl und Erdölprodukte, auf die zirka 82 Prozent seiner Exporteinnahmen entfallen. Im Landesinneren werden Mangan, Uran, Eisenerze und Gold gefördert. Mangan ist nach Erdöl und Holz das drittwichtigste Exportgut. Die ehemals großen Uranvorräte bei Franceville (u. a. Lagerstätte um Oklo) sind weitestgehend erschöpft. Es ist das erklärte Ziel des neuen Präsidenten, die vorhandenen Einnahmen aus Rohstoffverkäufen verstärkt für die Verbesserung der nationalen Infrastruktur zu verwenden. === Landwirtschaft Weiterhin gehört Gabun zu den größten Tropenholz-Exportländern Afrikas - der ausgedehnte Waldbestand ermöglicht die extensive Nutzung zahlreicher Hölzer. Etwa zwei Drittel der Landesfläche sind noch von tropischem Regenwald bedeckt; für das Edelholz Okoume hat Gabun das Weltmonopol. Die nationale Gesetzgebung verlangt allerdings eine nachhaltige Bewirtschaftung des Waldes und der Export unbehandelter Hölzer unterliegt Restriktionen. Elf Prozent des Staatsgebietes sind bereits als Reservate ausgewiesen und werden mit Unterstützung Frankreichs, der EU und neuerdings auch der USA betreut. Exportiert werden außerdem Kaffee, Kakao, Kautschuk (zur Gummiherstellung), Palmöl, Zucker und Erdnüsse. Es werden etwa 25.000 Tonnen Zucker produziert, von denen der größte Teil im Land selbst verbleibt. Der Anbau von Grundnahrungsmitteln dient vor allem dem Eigenbedarf im Land, kann diesen jedoch nicht vollständig decken. === Industrie, Energie Gabuns Industrie besteht zum größten Teil aus Holz- und Papierindustrie sowie Textil- und Nahrungsmittelindustrie. Drei agrarindustrielle Betriebe wurden bereits privatisiert. Einen Teil der Energie bezieht das Land durch die Wasserkraft, hauptsächlich im Süden des Landes. 1997 wurde der gabunische Wasser- und Stromversorger SEEG in private Hand übergeben. === Staatshaushalt Der Staatshaushalt umfasste 2016 Ausgaben von umgerechnet 3,464 Mrd. US-Dollar, dem standen Einnahmen von umgerechnet 2,917 Mrd. US-Dollar gegenüber. Daraus ergibt sich ein Haushaltsdefizit in Höhe von 3,8 % des BIP. Die nationale Staatsverschuldung betrug 2016 62,0 % des BIP. 2006 betrug der Anteil der Staatsausgaben (in % des BIP) folgender Bereiche: === Münzen Seit 2012 gibt Gabun jährlich die Sammler- und Anlagemünze Silberunze Afrikanischer Springbock zum Nennwert von 1000 Francs CFA heraus. === Verkehr Die einzige Eisenbahnstrecke des Landes verbindet die Hauptstadt Libreville mit der Stadt Franceville im Landesinneren. Das gesamte Straßennetz umfasste 2007 etwa 9170 km, wovon 1097 km asphaltiert sind. Daneben ist das Land von einem Fernstraßennetz durchzogen, dessen Straßen drei Kategorien zugeordnet werden, nämlich den Nationalstraßen, den Regionalstraßen und den Lokalstraßen. == Kultur === Medien Bei der Rangliste der Pressefreiheit 2017, welche von Reporter ohne Grenzen herausgegeben wird, belegte Gabun Platz 108 von 180 Ländern. Bei der Situation der Pressefreiheit im Land gibt es laut der Nichtregierungsorganisation "erkennbare Probleme". In Gabun befindet sich der Standort des ältesten panafrikanischen Rundfunksenders - Radio Africa No. 1. Der Sender ist auch für die Infrastruktur des Landes von großer Bedeutung, er ermöglicht den Schulbetrieb, unterstützt die Verwaltung der durch Regenwälder und schlechte Straßenverbindungen oft über Monate unzugänglichen Gebiete. Das Internet wurde 2016 von 10,3 % der Bevölkerung genutzt. === Sport Die beliebtesten Sportarten in Gabun sind Basketball und Fußball. Gabun trug 2012 (gemeinsam mit Äquatorialguinea) und 2017 die Fußball-Afrikameisterschaft aus. Eine der bekanntesten Personen Gabuns ist der Fußballspieler Pierre-Emerick Aubameyang, der zurzeit beim FC Arsenal unter Vertrag steht. Gabun nimmt seit 1972 an den Olympischen Spielen teil. Der einzige olympische Medaillenträger aus Gabun ist Anthony Obame, der bei den Olympischen Sommerspielen 2012 in London Silber im Taekwondo gewann. === Schnitzkunst Einige Kulturen Gabuns sind bekannt für ihre Schnitzkunst, besonders die Fang, die Kota, die Punu und die Tsogo. Aus dem Gebiet der Kota im Osten des Landes stammt ein spezieller Typ von Reliquiarfiguren, die den Urahn des jeweiligen Klans versinnbildlichen; sie bestehen zumeist aus einem Holzkern, aus dem ein ovales Gesicht, teilweise ohne Mund, skulptiert und dann mit Folie und Lamellen aus Edelmetallen (meist Kupferfolie) beschlagen wird. Über dem Kopf befindet sich oft ein mondsichelförmiger Aufsatz, der Hals ruht auf einem hochkant gestellten Rechteck. Diese Reliquiarfiguren waren Vorbilder für den Maler Pablo Picasso. Er bediente sich des Öfteren dieser Figuren für seine Werke. So malte er 1907 eine Reihe von Variationen dieses Motivs. == Einzelnachweise -0.6833333333333311.5Koordinaten: 1° S, 12° O

Title: Gabun Summary: Gabun ist ein Staat an der Westküste von Afrika. Es liegt am Golf von Guinea, welcher zum Atlantischen Ozean gehört. Das Land liegt auf dem Äquator. Deshalb ist es dort tropisch heiss. Der wichtigste Fluss des Landes ist der Ogooue, der in den Golf von Guinea fliesst. Das Land ist etwa sechsmal so gross wie die Schweiz. Die Schweiz hat aber viermal so viele Einwohner. Die knapp zwei Millionen Einwohner verteilen sich über vierzig verschiedene Völker. Jeder Dritte Gabunese gehört zum Volk der Fang. Die meisten Einwohner leben in den grossen Städten wie der Hauptstadt Libreville. Etwa zwei Drittel der Einwohner bezeichnen sich als Christen. Die übrigen verteilen sich auf traditionelle Stammesreligionen und Muslime. Im Vergleich zu den meisten Ländern Afrikas geht es Gabun gut. Allerdings gibt es nur wenige reiche Menschen. Ein Drittel der Bevölkerung ist sogar sehr arm. Das Land hat viele Bodenschätze wie Erdöl, Gold und Eisen. Das Land verkauft auch viel wertvolles Holz, dazu Kaffee, Kakao, Zucker, Palmöl und Kautschuk zur Herstellung von Gummi. Die Industrie verarbeitet vor allem Holz und stellt Papier her. Seit dem Ende des Mittelalters sind europäische Schiffe an der Küste Gabuns gelandet. Schliesslich hat Frankreich eine Kolonie daraus gemacht. Im Jahr 1960, dem Afrikanischen Jahr, wurde die Republik Gabun unabhängig. Zwar hatte das Land einen Präsidenten, der vierzig Jahre lang regiert hat. Allerdings gab es keine Kriege und Bürgerkriege, unter denen viele andere Länder gelitten haben.

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Summarize: By Cox Media Group National Content Desk A Bristol, Tenn., couple wants to tie the knot again. On Aug. 20, 2014, just 19 days after their first wedding, Justice Stamper was in a car accident that caused amnesia and other serious injures. Her memory loss went as far back as five weeks before the wedding, which she confessed she didn't remember happening. FREE APPS NOW FACEBOOK TWITTER Stories of the day... "I was heartbroken and instantly said I would do it all again for her," her husband, Jeremy Michael Clayton Stamper wrote on the GoFundMe page. He is trying to raise $5,000 by Aug. 1 so the couple can have their second wedding on the anniversary of their first. So far he has raised $2,620 for what he is calling the Stamper Wedding Round 2. Husband Plans Second Wedding for Wife Who Lost Memory in Car Crash: 'She Deserves Everything and More' A Beautiful Day She Can't Remember Justice Stamper Their Second Wedding Kayla Williams Justice Stamper can't remember the most special milestone in her life – her wedding day, Aug. 1, 2014.The 20-year-old had been planning her wedding since she was a little girl, and as she got older, the details became more clear. Justice envisioned an intimate, country-themed wedding, complete with sunflowers and splashes of the colors blue and yellow.The lucky guy? Jeremy Stamper, now 21, whom she met at Sunday school when she was just 10 years old."I had the biggest crush on her," Jeremy, who lives with Justice in Bristol, Tennessee, tells PEOPLE. "But we didn't start dating until high school."It didn't take long for the high school sweethearts to talk about marriage."We kind of just knew we were meant to be together," Justice tells PEOPLE. "It was pretty instant."On Sept. 30, 2012, Jeremy went in front of the entire congregation at their church in their hometown of Marion, Virginia, and proposed to Justice."He taped the ring underneath a bottle cap to hide it, and he was so nervous that he just gave me the entire bottle," she says, laughing. "It was so cute and so special."But when Justice tries to think back on the days following that sweet proposal, she can't remember a single thing – she can't even remember the day they said "I do."On Aug. 20, 2014, just weeks after their Aug. 1 wedding at Hungry Mother State Park in Virginia, Justice was in a car accident and was injured so badly that she barely survived."I was at work and I got a call from Justice. She was just bawling and couldn't stop," Jeremy says. "I got in my car and drove to her as fast as I possibly could."While on her way to her aunt's house, Justice was making a left turn when a car rear-ended her at 50 m.p.h, pushing her and her car about 50 feet to the right side of the road.As she began the slow process of her recovery, it took her about a month and a half to admit to Jeremy that she couldn't remember their wedding day or the months leading up to it."She said to me, 'I don't want you to be mad, but I do not remember the wedding,' " Jeremy says. "I, of course, was very upset, but I told her right then and there, 'We will do it again.' "Justice looked at their wedding photos and watched their video over and over, but "nothing came back to me," she says. "It's like going to a foreign country and not understanding what anyone is saying. It's very confusing."Jeremy has kept his word – on Aug. 1, the couple will have another wedding, so that they can both look back and remember the moment together.Jeremy is currently in school and working, but Justice can't do either because she is still struggling from the accident. That's why this time around, they're not planning the wedding alone.Without telling Justice, Jeremy created a GoFundMe page, asking people to help donate whatever they could to help make their wedding a reality. Their goal is $5,000."Our first wedding was beautiful and perfect," he says, "but this time, I want Justice to truly be blown away. She really deserves it."While they plan their nuptials, Justice is dealing with PTSD from the trauma and struggling every day with her speech and short-term memory."I'm lucky to be alive," Justice says. "And I'm so lucky to have Jeremy. Without him, I wouldn't have made it."And unlike their first wedding, which was attended by 75 people, this ceremony will have a much longer guest list."We are inviting everyone who helps us make this wedding happen," she says. "We want everyone to celebrate with us if they can." Jeremy Stamper Hello,Yes, you read it correctly, the Stamper Wedding Round 2. Are you confused a little bit? Well, let me tell you what this is all about. August 1st 2014 myself and my beautiful wife got married out at Hungry Mother State Park and it was perfect. We had our wedding, reception, and even honeymooned in the Smokey Mountains. We were at the top of the world, newlyweds and our whole lives head of us. We had big plans until August 20th 2014 just 19 days after the wedding. While I was working, my wife was traveling just down the road to her aunt's house and to meet me when I got off work when it happened. She was yielding to oncoming traffic to turn left on a side road when she was rearended at a dead stop at about 50 MPH plus. The exact speed is not known. She was nearly killed in the impact but by the grace of God she survived. The injuries were endless and she has now finially to maximum medical improvement and was released from her physical treatments.About a month after the accident she finially told me. She said "I don't want you to be mad...." I was heart broken and instantly said I would do it all again for her. She has memory loss from about 5 weeks before the wedding, which is when we actually started to plan and put the wedding ideal into motion, and up to the accident. She didn't even know we were married. She couldn't believe it. I promised her I would take care of her and now here we are, The Stamper Wedding Round 2.We have truly been through some rough times and we really could use any help anyone can offer. We are doing this fund raiser to take the load off of us and to help us do it again on our one year anniversery so we can have a memory that we both can talk about and reminisce without someone getting upset.Please, I ask for whatever you can give to help me give my wife, Justice Stamper. the perfect wedding (again), that she will remember and we can move on in our lives. I have set the goal to $5,000 to allow us to comfortably afford this with what I am making working which means anything over that will make it easier on us to make it happen and give her the wedding she can't forget no matter what. Anything is greatly appreciated. Share this and spread the word as much as possible! Please and if anyone wishes to donate and doesn't see this as a safe website or a scam PLEASE contact me through my email or instant message on facebook and we can find an alternative way for someone to donate to The Stamper Wedding Round 2!Thank youGod Bless

Summary: Justice Stamper won't soon forget the day her high school sweetheart got down on one knee in front of the entire congregation at their church in their hometown of Marion, Va., where they first met at age 10. "He taped the ring underneath a bottle cap to hide it, and he was so nervous that he just gave me the entire bottle," she tells People. "It was so cute and so special." What Justice doesn't remember is her actual wedding day, Aug. 1, 2014. Though the ceremony went off without a hitch, she was in a car accident less than three weeks later that almost killed her and left her with no memory from about five weeks before the day, reports WPXI. "She said to me, 'I don't want you to be mad, but I do not remember the wedding,'" husband Jeremy Stamper says. "I told her right then and there, 'We will do it again.'" The Tennessee couple is now planning a second wedding on their first anniversary, with the help of strangers. Jeremy-who's working and going to school while Justice struggles with PTSD and difficulties with speech and short-term memory-set up a GoFundMe page, hoping to raise $5,000 for the event, dubbed the Stamper Wedding Round 2. More than $4,300 has been raised as of this writing. "Our first wedding was beautiful and perfect," he says, "but this time, I want Justice to truly be blown away. She really deserves it." And you could be among the guests: "We are inviting everyone who helps us make this wedding happen," says Justice, whose first wedding was attended by just 75 people. "We want everyone to celebrate with us if they can."

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Summarize: Islamic State militants have'massacred' at least 80 Yazidis after they refused to convert to Islam, it has been claimed. The insurgents allegedly stormed into the small village of Kojo in northern Iraq, where they spent five days trying to persuade villagers to take up their religion. When they refused, the male members of the ancient sect were reportedly rounded up and shot dead, while more than 100 women and girls were kidnapped. Scroll down for video. Terrified: Islamic State militants have'massacred' at least 80 Yazidis after they refused to convert to Islam, it has been claimed. Above, displaced Yazidis shelter are seen at a park near the Turkey-Iraq border yesterday. 'They arrived in vehicles and they. started their killing this afternoon,' senior Kurdish official Hoshiyar. Zebari told Reuters yesterday. 'We believe it's because of their creed: convert or. be killed.' The women and girls abducted from the village, situated around 12 miles south of Sinjar, were being taken to the ISIS-controlled cities of Mosul and Tal Afar, the official said. It comes as the Islamic State's continued push to the border with the Kurdish region has sparked a series of U.S. airstrikes and sent tens of thousands of Yazidis and Christians fleeing for their lives. Yesterday, Yazidi parliamentarian Mahama Khalil said the alleged massacre had taken place during a one-hour period. Waiting: Members of Yazidi community rest as they try to cross to Turkey, in Zakho, 300 miles north of Baghdad. Injured: The insurgents allegedly stormed into the small village of Kojo in northern Iraq yesterday, before spending five days trying to persuade villagers to take up their religion. Above, an injured Yazidi boy. Meanwhile, the resident of a nearby village claimed to have been told details of the bloodshed by an Islamic State fighter. 'He told me that the Islamic State. had spent five days trying to persuade villagers to convert to Islam and. that a long lecture was delivered about the subject today,' said the. villager. 'He then said the men were gathered. and shot dead. The women and girls were probably taken to Tal Afar. because that is where the foreign fighters are.' However, the account could not be independently confirmed. Islamic State militants have killed at least 500 members of Iraq's Yazidi ethnic minority during their offensive in the north, according to Iraq's human rights minister. Panic: It comes as the Islamic State's continued push to the border with the Kurdish region has sparked a series of U.S. airstrikes and sent tens of thousands of Yazidis and Christians fleeing for their lives. Hidden away: Yazidis who fled the violence from ISIS forces in Sinjar shelter on Mount Sinjar earlier this week. Mohammed Shia al-Sudani said the Sunni militants had also buried some of their victims alive, including women and children. Some 300 women were kidnapped as slaves, he added. Meanwhile, American military officials last night claimed airstrikes from drones destroyed two. armed vehicles south of the Iraqi town of Sinjar. In a statement, U.S. Central Command said Kurdish forces had. reported that Islamic State militants were attacking civilians in the. village of Kawju. Officials said remotely piloted aircraft identified and then followed an. armed vehicle to a roadside area near Sanjar, before striking and destroying two vehicles in the area. Sick: British jihadist Nasser Muthana posted this claim on his Twitter account saying that he and other Islamic State fighters had captured hundreds of Yazidi and were holding them hostage in Syria. Jihadist: Nasser Muthana is a 20-year-old former Cardiff schoolboy who featured prominently in the Islamic State's first professionally produced English language propaganda video. It comes just days after a British jihadist made sick claims on Twitter that Islamic State militants are holding hundreds of Iraqi women as slaves in Syria. Former Cardiff schoolboy Nasser Muthana appeared to refer to reports that 300 women were snatched from the Yazidi community near Mount Sinjar, where ISIS cornered thousands of refugees in a ten-day siege. The tweet also alluded to claims that the women were intended to be given to young jihadists as wives. It read: 'I can confirm that we have hundreds of yazidi slave women now in Syria, how about that for news!' Before: Former Cardiff schoolboy Nasser Muthana uploaded images with the stark warning: 'Army base buildings before and after, I'm getting good with these bombs' When his claims were questioned by a known sympathiser, he sounded more sincere. Da Masked Avenger asked him: 'In all seriousness. What's the truth of this matter?' Muthana replied: 'I'm not lying.' The message was posted on Wednesday, but has since been deleted and his claims cannot be independently verified. Fears are now growing for the captured women amid claims they could be used to bear children to break up the Kurdish-speaking group's bloodline. After: The young jihadist, who describes himself on Twitter as a'soldier of the Islamic State', said last month the UK government should be 'afraid' of his bomb-making skills. The minority group is originally Aryan. and has retained a fairer complexion, blonde hair and blue eyes by only. marrying within the community. But in a furious bid to convert all non-Muslims, ISIS jihadists have vowed to impregnate the hostages. Addressing. the kidnapping, Adnan Kochar, chairman of the Kurdish Cultural Centre. in London, told MailOnline: 'The Kurds and Yazidis are originally. Aryans. 'But because. the Yazidis are such a closed community they have retained a fairer. complexion, blonder hair and bluer eyes. They don't marry non-Yazidis. 'ISIS. have taken around 300 women from Sinjar to give to jihadists to marry. and make pregnant to have a Muslim child. If they can't kill all. Yazidis, they will try to smash the blond bloodline.' Threat: Nasser Muthana posted a message on Twitter last month warning that the UK government should be afraid of him returning to the country with his new bomb making skills. Find: Muthana claims to have found this prayer mat inside the army base. He says it offers devotion to the Prophet Mohammed's daughter and is therefore in breach of Islamic law as evidence of practicing idolatry. Muthana. - who featured in a chilling ISIS recruitment video - has been a. prolific user of social media in recent months, posting horrific. pictures of mutilated Iraqi soldiers and other taunting claims about the. Islamic State's uprising in Iraq. He has previously warned that ISIS fighters would slaughter any Yazidi men they captured in northern Iraq and would enslave their women and children. 'Kuffar [non-believers] are afraid we. will slaughter Yazidis, our deen [religious path] is clear we will kill. their men, take their women and children as slaves insha Allah,' he posted on Twitter. He also posted a message on Twitter warning that. the UK government should be afraid of him returning to the country with. his new bomb making skills. Friends: Reyaad Khan (left), who is also from Cardiff, appeared alongside Muthana (right) in the ISIS propaganda video, urging other young Muslims in the West to join them in jihad. The 20-year-old's boast about the Yazidi. women came just days after he uploaded before and after images of a. military building being destroyed by one of homemade bombs. They appeared on his new Twitter page under the username Abul Muthanna@abulmuthanna313 after deleting his previous profile last month. He. was reportedly unhappy with the high levels of attention it received. following his appearance in the Islamic State's recruitment video. Formerly. a prospective medical student, Muthana was joined in Syria by his. younger brother Aseel, 17, who has now spoken of his willingness to die. fighting for ISIS. The. Muthana brothers, who grew up in Cardiff after their father moved there. from Yemen as a teenager, are among hundreds of young men from Britain. who have flown to Syria to join the rebels. Their friend Reyaad Khan, 20, also from Cardiff, said he had 'fireworks' for the U.S. if they returned to fight in Iraq. Reyaad Khan and Nasser Muthana are among the British jihadists fighting with ISIS in Iraq that are using social networking sites to lure young Muslim teenagers from the UK into joining the Islamic State fanatics. The extremists, who boast of ‘slaughtering’ innocent Yazidis and ‘taking their women as slaves’, are advising 15-year-olds that they are ‘not too young’ to die fighting for Allah. Asked by a British 18-year-old girl if she is too young to join, one of them replied: ‘I know sisters younger than you. I heard of maybe 16-year-olds being here from UK. You aren’t too young.’ Before they fled: Jihadists Reyaad Khan and Nasser Muthana (circled) hand out food to the needy in Cardiff last year. Both have been tweeting about their involvement with IS while on the front line. They are informing their British ‘brothers and sisters’ every day how to make their way to Iraq, claiming they are ‘ordered’ to defy their parents and fight jihad. The British IS fighters, who refer to themselves as the ‘Baadiya Boys’ after their original base in Syria, include Khan and Muthana. The former Catholic college students have been joined on the frontline by young Muslim men and women from across the UK, including a group of five friends from Portsmouth, two of whom have already been killed

Summary: Militants allegedly stormed into the small village of Kojo in northern Iraq. They'spent five days trying to persuade villages to take up their religion' When they refused, male members of the sect were reportedly shot dead. Women and girls were allegedly kidnapped during the one-hour'massacre' Comes as U.S. airstrikes have have destroyed two armed vehicles in Iraq. ISIS's push to border has sent tens of thousands of Yazidis fleeing for lives. On Wednesday, British jihadist claimed women being held as slaves in Syria. Nasser Muthana, 20, previously featured in chilling ISIS recruitment video. Appeared with friend Reyaad Khan attempting to recruit Western Muslims.

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Summarize: Background To carry out its responsibilities under the nation’s environmental laws, EPA conducts an array of activities, such as promulgating regulations; issuing and denying permits; approving state programs; and issuing enforcement orders, plans, and other documents. Many of these activities may be subject to legal challenge. Environmental Statutes and Lawsuits against the Federal Government Generally, the federal government has immunity from lawsuits, but federal laws authorize three types of suits related to EPA’s implementation of environmental laws. First, most of the major environmental statutes include “citizen suit” provisions authorizing citizens—including individuals, associations, businesses, and state and local governments—to sue EPA when the agency fails to perform an action mandated by law. These suits are often referred to as “agency-forcing” or “deadline” suits. Second, the major environmental statutes typically include judicial review provisions authorizing citizens to challenge certain EPA actions, such as promulgating regulations or issuing permits. Third, the Administrative Procedure Act authorizes challenges to certain agency actions that are considered final actions, such as rulemakings and decisions on permit applications. As a result, even if a particular environmental statute does not authorize a challenge against EPA for a final decision or regulation, the Administrative Procedure Act may do so. Table 1 lists key environmental laws under which EPA takes actions—or that govern EPA actions—that may be subject to challenge in court. Supporters of provisions allowing legal challenges to actions of the federal government assert that they provide a check on the authority of federal agencies as they carry out—or fail to carry out—their duties. For example, in passing the 1977 Clean Air Act amendments, a key sponsor indicated that authorizing citizens to sue agencies to compel them to carry out their duties is integral to a democratic society. According to others, citizen suits against government agencies have achieved benefits, such as ensuring the implementation of congressional directives or accelerating regulatory programs. Similarly, the Administrative Procedure Act arose out of the expansion of the federal government in the New Deal, with concerns about agencies’ adjudicative powers, their exercise of delegated legislative power by rulemakings, and the scope of review of agency administrative action by courts. A lawsuit challenging EPA’s failure to act may begin when the aggrieved party sends EPA a notice of intent to sue, if required, while a lawsuit challenging a final EPA action begins when a complaint is filed in court. Before EPA takes final action, the public or affected parties generally have opportunities to provide comments and information to the agency. In addition, administrative appeals procedures are available—and in many cases required—to challenge EPA’s final action without filing a lawsuit in a court. For example, citizens can appeal an EPA air emission permit to the agency’s Environmental Appeals Board. These administrative processes provide aggrieved parties with a forum that may be faster and less costly than a court. If a party decides to pursue a case, the litigation process generally involves filing of a complaint, formal initiation of the litigation; motions to the court before trial, such as asking for dismissal of the case; and hearings and court decisions. Throughout this process, the parties to the litigation can decide to reach a settlement. Negotiations between the aggrieved party and EPA may occur anytime after the agency action, at any point during active litigation, and even after judgment. A common remedy sought in litigation against EPA under the statutes listed in table 1 is for the court to set aside an EPA regulation or permit decision and to require EPA to reconsider that regulation or permit decision. The Equal Access to Justice Act In the United States, parties involved in litigation generally pay their own attorney fees and costs, except in instances in which Congress has provided exceptions for policy reasons, such as to encourage citizens to bring suits to enforce the law. In these instances, as well as some common-law exceptions, a prevailing plaintiff may seek award of its attorney fees and court costs from the losing party. Many of the environmental statutes in table 1 contain such exceptions authorizing courts to award fees, which, according to Justice, include awards against the federal government. In 1980, Congress enacted the Equal Access to Justice Act (EAJA) authorizing the award of attorney fees and costs to parties that prevail in certain lawsuits against the federal government; the payments are made from Treasury’s Judgment Fund and agency appropriations. While the federal government was already subject to some of these exceptions in environmental statutes, before EAJA was enacted, the federal government in many other cases was not subject to these exceptions and therefore was not authorized to make payments to prevailing parties. As the 1980 conference committee report for EAJA explains, the act’s premise is that individuals, corporations, partnerships, and labor and other organizations do not seek review of or defend against unreasonable government actions because of the expense involved, as well as a disparity in expertise and resources between the government and the individual or organization involved. For those cases brought under statutes that do not make the federal government subject to pay fees and costs, EAJA thus allows payment of the attorney fees and other costs if the organizations sought review of a government action and prevailed. (See app. II for a detailed description of the act.) Except as otherwise specifically provided by law, EAJA authorizes the award of the following costs to be paid from Treasury’s Judgment Fund or an agency’s appropriations, as indicated:  Court costs of prevailing parties against the United States in any civil action. These costs may include fees for the clerk and marshal, reporter, printing, witnesses, copies, docket fees, and interpreters and court-appointed experts and may include an amount equal to the filing fees. Payment of costs made under this section generally are paid by Treasury’s Judgment Fund.  Reasonable attorney fees and expenses of a prevailing party to the same extent as any other party where a statutory or common-law exception provides for award of fees to a prevailing party. Regarding the environmental statutes in table 1, according to Justice, many of the relevant provisions under which EPA may be sued provide for award of such fees against EPA, independent of EAJA. Nevertheless, EAJA makes EPA subject to fee awards under all the environmental statutes’ provisions authorizing courts to award attorney fees and expenses. Therefore, in many—but not all—of the environmental lawsuits against EPA, a court may award attorney fees and expenses of a prevailing party against the agency, independently or as a result of EAJA section 2412(b). Payment of awards made under this section generally are paid by Treasury’s Judgment Fund.  Attorney fees and expenses of a prevailing party in most other cases—that is, when the relevant statute does not authorize courts to award attorney fees and expenses, and no common-law exception applies—unless the court finds that the position of the United States was substantially justified or that special circumstances make an award unjust. Two laws listed in table 1—the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act—as well as some individual provisions of other statutes, do not authorize payment of fees to prevailing parties. As a result, in cases brought against EPA under these statutes and provisions, courts award payment of fees under EAJA section 2412(d). Payment of awards made under this section is generally made from agency appropriations. In addition, to settle a case, the government may agree to pay a plaintiff court costs and attorney fees and expenses. Payments made in connection with settlements are paid in the same manner as a court award for the case. Some in Congress have expressed concerns that the use of taxpayer funds to make EAJA payments depletes limited funding; these individuals have called for transparency of these expenditures. Originally, EAJA provided for governmentwide reporting on its use and cost. For judicial proceedings, EAJA required the Director of the Administrative Office of the U. S. Courts to report annually to Congress on EAJA court activity, including the number, nature, and amounts of awards; claims involved; and any other relevant information deemed necessary to aid Congress in evaluating the scope and effect of awards under the act. The responsibility for this reporting was transferred to the Attorney General in 1992. In addition, EAJA required the Chairman of the Administrative Conference of the United States to submit an EAJA report annually to Congress on administratively awarded fees and expenses. Then, in December 1995, the Federal Reports Elimination and Sunset Act of 1995 repealed the Attorney General’s reporting requirement for fees and expenses awarded under EAJA and also discontinued reporting of governmentwide administrative awards of fees and costs under EAJA after fiscal year 1994. We have previously reported certain governmentwide EAJA data, as well as data focused on selected agencies. In 1995, we reported data on the number of cases and amounts of awarded plaintiff attorney fees exceeding $10,000 against nine federal agencies for cases closed during fiscal years 1993 and 1994. In 1998, we provided information on the history of EAJA, the extent to which one provision of the act was used governmentwide from 1982 to 1994, and the provision’s use by the Department of Labor and other agencies. The governmentwide data for fiscal year 1994 showed, among other things, that the Departments of Health and Human Services and of Veterans Affairs accounted for most EAJA payments in court proceedings, under the provision that applies when the substantive law does not authorize award of attorney fees and costs. The Number of Environmental Litigation Cases against EPA Showed No Discernible Trend over 16 Years, and Stakeholders Stated That Various Factors Affected Yearly Numbers The number of environmental litigation cases brought against EPA each year from fiscal year 1995 through fiscal year 2010 varied but showed no discernible trend. According to the stakeholders we interviewed, a number of factors—particularly presidential administration, the passage of new regulations or amendments to laws, or EPA’s failure to meet statutory deadlines—affect the number of environmental litigation cases each year and the type of plaintiffs who bring them. No Trend Was Discernible in the Number of Cases Brought against EPA from Fiscal Year 1995 through Fiscal Year 2010 The number of environmental litigation cases brought against EPA each year from fiscal year 1995 through fiscal year 2010 varied but did not change systematically over time. The average number of new cases filed each year was 155, ranging from a low of 102 new cases filed in fiscal year 2008 to a high of 216 cases filed in fiscal year 1997 (see fig. 1). From fiscal year 1995 through fiscal year 2001, the average number of new cases was 170; from fiscal year 2002 through fiscal year 2010, the average number of new cases was 144, a difference of 26 fewer new cases on average. The average number of new cases in these periods varied from the long-term average of 155 cases by less than 10 percent. In all, Justice defended EPA in nearly 2,500 cases from fiscal year 1995 through fiscal year 2010. The greatest number of cases was filed in fiscal year 1997, which, according to a Justice official, may be explained by the fact that EPA revised its national ambient air quality standards for ozone and particulate matter in 1997, which may have caused some groups to sue. In addition, according to the same official, in 1997 EPA implemented a “credible evidence” rule, which also was the subject of additional lawsuits. The fewest cases against EPA (102) were filed in fiscal year 2008, and Justice officials were unable to pinpoint any specific reasons for the decline. In fiscal years 2009 and 2010, the caseload increased. A Justice official said that it is difficult to know why the number of cases might increase because litigants sue for different reasons, and some time might elapse between an EPA action and a group’s decision to sue. As shown in figure 2, most cases against EPA were brought under the Clean Air Act, which represented about 59 percent of the approximately 2,500 cases that were filed during the 16-year period of our review. Cases filed under the Clean Water Act represented the next largest group of cases (20 percent), and the Resource Conservation and Recovery Act represented the third largest group of cases (6 percent). The lead plaintiffs filing cases against EPA during the 16-year period fit into several categories. The largest category comprised trade associations (25 percent), followed by private companies (23 percent), local environmental groups and citizens’ groups (16 percent), and national environmental groups (14 percent). Individuals, states and territories, municipal and regional government entities, unions and workers’ groups, tribes, universities, and a small number of others we could not identify made up the remaining plaintiffs (see table 2). Appendix I gives more information about our method of developing these categories and classifying cases. According to the stakeholders we interviewed, a number of factors— particularly a change in presidential administration, the passage of regulations or amendments to laws, and EPA’s failure to meet statutory deadlines—affect plaintiffs’ decisions to bring litigation against EPA. Stakeholders did not identify any single factor driving litigation, but instead, attributed litigation to a combination of different factors. According to most of the stakeholders we spoke with, a presidential administration is an important factor in groups’ decisions to bring suits against EPA. Some stakeholders suggested that a new administration viewed as favoring less enforcement could spur lawsuits from environmental groups in response, or industry groups could sue to delay or prevent the administration’s actions. For example, a presidential administration that seems to favor less enforcement of requirements under environmental statutes could motivate increased litigation. Other stakeholders suggested that if an administration is viewed as favoring greater enforcement of rules, industry may respond to increased activity by bringing suit against EPA to delay or prevent the administration’s actions, while certain environmental groups may bring suit with the aim of ensuring that required agency actions are completed during an administration they perceive as having views similar to the groups’ own. Most of the stakeholders also suggested that the development of new EPA regulations or the passage of amendments to environmental statutes may lead parties to file suit against the new regulations or against EPA’s implementation of the amendments. When EPA issues new or amended regulations, parties may take issue with the specific new provisions. One stakeholder noted that an industry interested in a particular issue may become involved in litigation related to the development of regulations because it wishes to be part of the regulatory process and negotiations that result in a mutually acceptable rule. In addition, several of the stakeholders noted that if EPA does not meet its statutory deadlines, organizations or individuals might sue to enforce the deadline. In such suits, interested parties seek a court order or a settlement requiring EPA to implement its statutory responsibilities. In addition, some stakeholders said that some statutes are broadly written or contain vague language or definitions; such statutes are more likely to be litigated because different parties want to define the terms and set precedent for future cases. For example, a stakeholder representing states’ perspectives said that under the Clean Water Act, an area of frequent litigation is the definition of “navigable waters.” Through lawsuits, litigants have argued about whether a certain body of water comes within the definition and can therefore be regulated under the act. A few stakeholders identified two other factors that may affect litigation: (1) the maturity of the statute in question and (2) the use of existing laws to address new problems. The stakeholders said that the focus of litigation over a particular statute changes with time, as early cases may set precedents that will affect how the statute is implemented later. Also, a representative of an environmental organization said that because no major rewriting of any environmental statutes has occurred in 20 years, plaintiffs are increasingly bringing suits, and judges are making decisions, about how to interpret statutes in situations for which rules were not explicitly written. For example, parties disagree over whether the Clean Air Act should be used to regulate greenhouse gases, such as carbon dioxide, methane, and nitrous oxide—substances that some stakeholders say the act was not originally designed to regulate. Available Data Indicate That Costs Associated with Environmental Litigation against EPA, including Payments to Plaintiffs, Have Varied over the Past 10 Years with No Discernible Trend Data available from Justice, Treasury, and EPA show that the costs associated with environmental litigation cases against EPA have varied from year to year with no discernible trend. Justice’s Environment and Natural Resources Division spent a total of about $43 million to defend EPA in these cases from fiscal year 1998 to fiscal year 2010, averaging $3.3 million per year. Some cost data from the Department of Justice are not available, however, in part because Justice’s Environment and Natural Resources Division and the U.S. Attorneys’ Offices do not have a standard approach for maintaining key data for environmental litigation cases. For example, while the Environment and Natural Resources Division tracks attorney hours by case, the U.S. Attorneys’ Offices do not. Treasury paid a total of about $14.2 million to prevailing plaintiffs for attorney fees and costs related to these cases from fiscal years 2003 through 2010, averaging about $1.8 million per year. EPA paid a total of $1.4 million from fiscal year 2006 through fiscal year 2010 in attorney fees and costs, averaging about $280,000 per year. On Average, Justice Spent at Least $3.3 Million a Year Defending EPA against Environmental Litigation in Fiscal Year 1998 through Fiscal Year 2010 Our analysis of data from Justice’s Environment and Natural Resources Division found that from fiscal year 1998 through fiscal year 2010, Justice spent at least $3.3 million on average annually to defend EPA against environmental litigation, for a total of $43 million. (The Environment and Natural Resources Division fiscal year 2010 budget was $110 million.) The U.S. Attorneys’ Offices’ database, however, does not contain information on attorney hours worked by case, which meant that we could not include the time these attorneys spent on each case in our estimate. According to Justice officials, however, the $3.3 million average per year represents the majority of Justice’s time spent defending EPA each year, given that the U.S. Attorneys’ Offices handle a small number of environment-related cases each year. Overall, as shown in figure 3, annual costs increased by an average of about 3 percent each year from fiscal year 1998 through 2010, ranging from a low of $2.7 million in fiscal year 1998 to a high of $3.9 million in fiscal year 2007. Justice maintains separate, decentralized databases containing environmental case information and does not have a standard approach for collecting and entering data on these cases. Without a standard approach, it is it difficult to identify and summarize the full set of environmental litigation cases and costs managed by the department agencywide. Specifically, the department’s Environment and Natural Resources Division and the U.S. Attorneys’ Offices maintain different case management systems, and these systems do not use the same unique number to identify cases, making it possible to track cases within each component but not to align and merge cases from the two components. Because the U.S. Attorneys’ Offices may assist the Environment and Natural Resources Division in certain case activities, a single case may appear in both systems, each with a different unique identifier. The only piece of data in both databases that can in practice be used to identify cases managed by both components is the court number, yet neither system has adopted the standard court number format used in the federal judiciary’s Public Access to Court Electronic Records system, an electronic service that allows public access to case and docket information from federal appellate, district, and bankruptcy courts. According to an official of the Executive Office for U.S. Attorneys, the individual U.S. Attorneys’ Offices may enter the court numbers in the specific formats used by the courts in their individual jurisdictions, although the official also said that there is no formal or written guidance for proper format of court numbers. Without such standard identifying numbers, it is difficult to identify a full and unduplicated list of environmental litigation cases and to derive descriptive statistics on costs, statute, or opposing parties. Because the department’s data on environmental litigation cannot be reliably merged or aggregated to provide summary information on environmental cases, we had to use an iterative electronic and manual process to compile data from the two systems to conduct our review and identify the full set of environmental litigation cases and associated costs. Moreover, not only are the two Justice databases separate, but the two agency components do not collect the same types of data on environmental cases. Specifically, the U.S. Attorneys’ database does not collect data on the number of hours attorneys spend on an individual case or information on the statute under which a case is filed. As a result, it is impossible to gather complete data on all environmental litigation cases and costs from these databases. For example, we were unable to calculate the total number of hours that Justice attorneys worked on environmental cases—and hence, total costs of attorney time—because the U.S. Attorneys’ time is not tracked by case. By employing an iterative electronic and manual process to standardize the court numbers associated with all cases and matching cases from the two systems by these numbers, we were ultimately able to merge the two sets of data on environmental litigation cases managed by Justice’s Environment and Natural Resources Division and the U.S. Attorneys’ Offices for purposes of this report. Justice officials said, however, that they do not plan to change their approach to managing the data because they use the data in each system to manage individual cases, not to identify and summarize agencywide data on cases or trends. Officials said that their systems were designed for internal management purposes and not agencywide statistical tracking. Furthermore, while funds are spent to maintain the systems, officials indicated that the systems are old, and adding data fields or otherwise making changes to the systems may be technically infeasible or too costly. Justice officials said that the department previously sought to develop and implement a single case management system to gather common data agencywide, but the project was terminated in 2010 after a 2009 Office of the Inspector General report found that the project was more than 2 years behind the initial estimated completion date and that the project’s total cost would be more than $18 million over budget. Because the two Justice components are not regularly required to merge and report their data in a systematic way, we are not making a recommendation regarding these data or systems. On Average, Treasury Paid Successful Plaintiffs $1.8 Million Annually from the Judgment Fund over the Last 8 Years, and EPA Paid about $280,000 a Year over the Last 5 Years In addition to Justice’s costs of defending EPA, costs of litigation include payment of attorney fees and court costs to plaintiffs who prevail in lawsuits against EPA. As part of the payment process, Justice negotiated payment amounts with prevailing parties before finalizing the amount to be paid. For most of the claims under the 10 environmental statutes in this report, payments to successful plaintiffs were made from Treasury’s Judgment Fund. Justice defended approximately 2,500 EPA-related cases filed from fiscal year 1995 through fiscal year 2010, but the number of environmental litigation cases from which plaintiffs received payments was small, representing about 8 percent of all cases. In addition, EPA made a small number of payments for attorney fees and costs under the appropriate provision of EAJA. From fiscal year 2003—the first year for which Treasury’s Judgment Fund data are available—through fiscal year 2010, Treasury made, on average, 26 payments totaling $1.8 million per year for EPA-related environmental cases. The average Judgment Fund payment was $68,600 per payment. Treasury paid a total of about $14.2 million out of its Judgment Fund to prevailing plaintiffs for attorney fees and costs related to these cases (see fig. 4). The largest share of monies (46 percent) were made in cases filed by national environmental groups, followed by monies paid for cases filed by local environmental and citizens’ groups (29 percent). The payments ranged from as little as $145, to the administrator of a law school clinic for a Clean Air Act suit, to as much as $720,000, to a private law firm for a Clean Water Act suit. According to Justice officials, payments are made either to the plaintiff or to the plaintiff’s attorneys. Appendix III lists payments from Treasury’s Judgment Fund for the environmental statutes in our review. Fluctuations in annual payments may occur, according to Justice officials, because payments to plaintiffs can be made several years after a case is completed, in part because Justice attempts to negotiate settlements of attorney fee claims before seeking a determination by the courts regarding claims that cannot be settled. Officials said that through this process of negotiation, the department pays plaintiffs, in the majority of cases, an amount that is much lower than requested. To determine attorney fees for each case, Justice considers, among other things, documentation by the plaintiff, including such factors as (1) the number of hours the plaintiff’s attorneys spent on the case, which must be documented by the plaintiff; (2) the job description of the person spending time on the case (e.g., the costs for a paralegal and a lead counsel would be very different); (3) the specific tasks performed; and (4) applicable law in the jurisdiction, such as limits on hourly attorney fees or total amounts that courts have approved in the past. Although Justice may conclude that the hours are justified, fees may still be denied because of court precedent. Each time fees are negotiated, depending on the amount, Justice’s Assistant Attorney General or the relevant Environment and Natural Resources Division Section Chief must approve the result, pursuant to applicable regulations and delegations. From fiscal year 2006—the first year for which EPA specifically tracked the payments by type of claim—through fiscal year 2010, EPA made 14 payments, totaling $1.4 million, for attorney fees and other costs under EAJA. EPA made an average of 2.8 payments per fiscal year, with an average payment of about $100,000. On average, EPA paid about $280,000 per year. The largest share of the monies (61 percent) went to payments for claims filed by local environmental groups, followed by monies (23 percent) for claims filed by national environmental groups. Although workers’ groups filed comparatively few lawsuits, one such group did receive a single payment of $230,000 in fiscal year 2010 (see fig. 5). The EPA payments ranged from $1,179, which was paid to an individual for a Clean Water Act suit in 2010, to $472,967, which was paid to an environmental group for two Clean Water Act suits, including one appeal. Appendix III contains a list of payments by payee. Agency Comments and Our Evaluation We provided a draft of this report to EPA, Justice, and Treasury for their review and comment. EPA did not provide comments, and Justice and Treasury had technical comments, which we incorporated as appropriate. As agreed with your offices, unless you publicly announce the contents of this report earlier, we plan no further distribution until 30 days from the report date. At that time, we will send copies to the appropriate congressional committees, the Attorney General of the United States, the Secretary of the Treasury, the Administrator of EPA, and other interested parties. In addition, the report will be available at no charge on the GAO Web site at http://www.gao.gov. If you or your staff members have any questions about this report, please contact me at (202) 512-3841 or trimbled@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found on the last page of this report. GAO staff who made major contributions to this report are listed in appendix IV. Appendix I: Objectives, Scope, and Methodology This report describes (1) trends, if any, in environmental lawsuits against the Environmental Protection Agency (EPA) from fiscal year 1995 through fiscal year 2010, as well as stakeholders’ views of factors affecting any trends, and (2) Justice’s recent costs for representing EPA in defensive environmental lawsuits and the federal government’s recent payments to plaintiffs. To examine the changes over time to EPA’s environmental litigation caseload, we obtained and analyzed data on lawsuits filed against the agency from databases maintained by two components within the Department of Justice—the Case Management System database maintained by Justice’s Environment and Natural Resources Division and the Legal Information Office Network System database maintained by Justice’s U.S. Attorneys’ Offices. We obtained and analyzed data from these databases for lawsuits: filed in federal court from fiscal year 1995 through fiscal year 2010 (Oct. 1, 1994, through Sept. 30, 2010); in which EPA was the lead defendant, excluding cases in which EPA was a defendant but the lead defendant identified by Justice was another agency, such as the U.S. Army Corps of Engineers;  brought under 10 major environmental statutes implemented by or applying to EPA, including the Clean Air Act; Clean Water Act; Safe Drinking Water Act; Resource Conservation and Recovery Act; Comprehensive Environmental Response, Compensation, and Liability Act (Superfund); Emergency Planning and Community Right- to-Know Act; Federal Insecticide, Fungicide, and Rodenticide Act; Federal Food, Drug, and Cosmetic Act; Toxic Substances Control Act; and the Endangered Species Act as it applies to EPA. We excluded cases filed under the National Environmental Policy Act (NEPA) because these cases are managed by a number of sections within the Environment and Natural Resources Division, and because, according to Justice officials, few cases are filed under NEPA with EPA as the lead defendant. We also excluded the Freedom of Information Act, Discrimination in Federal Employment Act, Fair Labor Standards Act, and other generally applicable laws because the intent was to focus on challenges to EPA’s core work in implementing environmental laws. Likewise, we excluded bankruptcy cases and cases heard in state court unless they were moved to federal court. To determine if the data were reliable for our purposes, we checked them for completeness and legitimate values. When we were uncertain of the data’s accuracy, we requested clarification from the source of the data. Within each database, we checked for duplicate records and either combined data across records into one record or removed unnecessary records. To compile a list of all cases of EPA lawsuits, we needed to identify duplicate cases across the two databases. Because the common field in the two systems—court number—is not kept in the same format, it was necessary for us to standardize court numbers into one format. To do so, we used the standard court number format used in the federal judiciary’s Public Access to Court Electronic Records (PACER) system, an electronic public-access service that allows users to obtain case and docket information from federal appellate, district, and bankruptcy courts. After electronically processing reports of matched and unmatched cases, we conducted extensive manual review of the data to (1) confirm that matched cases from the two databases were in fact the same and (2) identify cases that were the same but were still not found with the electronic process. Manual checks of selected individual court cases were performed using the PACER system to correct information, such as EPA’s role in the case, the names of plaintiffs, and court numbers. We analyzed selected data elements—such as plaintiffs’ names, filing and disposition dates, and relevant statute—over time to identify any trends in litigation. We also used the data on plaintiffs to identify categories of plaintiffs that have filed suit against EPA. To do this analysis, we used a process known as content analysis, searching national databases for information on each plaintiff and then using this information to code the plaintiffs according to rules developed by our internal team of analysts and specialists in program evaluation methods. Our team created 13 categories into which plaintiffs were coded (see table 3). We evaluated the reliability of our plaintiff categories using two pretests on simple random samples of 40 and 41 plaintiffs, respectively. A minimum of five analysts independently coded the samples to ensure they had a common understanding of the categories and made the same coding decisions. For each pretest, we estimated the analysts’ agreement rates adjusted for the possibility of agreement by chance. These “kappa” statistics estimate the reliability of each category. In the first pretest, the analysts agreed 74 percent of the time across all categories and 71 to 91 percent of the time for the individual categories other than “unknown,” using the combined category of “local environmental and citizens’ groups.” On the basis of the results of the first pretest, we refined the definitions of the categories and conducted the second pretest. In the subsequent pretest, the analysts agreed 87 percent of the time across all categories and 84 to 95 percent of the time for the individual categories other than “unknown” and “other.” These agreement rates suggested that the analysts could reliably classify the plaintiffs according to common standards in academic literature on intercoder agreement. Classifying the plaintiffs helped us quantify the number of cases brought each year against EPA by different types of groups. After validating the categories, we searched in public databases of organizations for information that would allow us to classify each plaintiff. We used the Nexis Encyclopedia of Associations and the Nexis Company Profile data systems, both of which identify organizations by North American Industry Classification System and Standard Industrial Classification. To the extent possible, we used these codes to classify plaintiffs. If these sources were not sufficient, we searched the Web pages of each organization for self-reported information. For the “individual” category of plaintiff, we confirmed through court records that those people were in fact suing as private individuals and not, for example, as mayors or attorneys general of a state. In some cases, insufficient information was available in Justice’s databases to determine a given plaintiff’s identity. In such cases, we looked up the case in the PACER system. Six analysts conducted the content analysis of plaintiffs in the Case Management System and the Legal Information Office Network System. Discrepancies in coding were discussed, and agreement was reached among the analysts or resolved through a group analyst review. To obtain stakeholder perspectives on environmental litigation trends and the factors that underlie them, we interviewed officials from EPA and Justice; representatives from the offices of five state attorneys general and one state environment department; representatives from six environmental groups; and six industry trade associations. We also spoke with a representative of the National Association of Attorneys General. Additionally, we interviewed one academic expert who has published extensively on environmental litigation in legal journals (see table 4). We selected these representatives on the basis of input from government officials and other interviewees. We asked the interviewees for their perspectives about factors that can affect trends in the types of lawsuits against EPA. We then performed a content analysis to group and summarize their responses. Not all stakeholders provided views on all issues, and statements from our sample of stakeholders cannot be generalized to all groups. To determine Justice’s costs for representing EPA in defensive environmental lawsuits and the government’s payments to plaintiffs, we obtained data on three components of costs: (1) Justice’s costs for its attorneys’ time defending EPA, (2) payments for attorney and other costs from the Department of the Treasury’s Judgment Fund for some cases that the government lost, and (3) payments for attorney and other costs by EPA for some cases that the government lost. For the first component, we obtained data from Justice on the number of cases per year that involved any of the 10 statutes in our scope, as well as the number of hours Justice attorneys spent working on these cases. To calculate costs, we multiplied the total hours worked in a given year by that year’s average hourly pay rate—ranging from $41 to $66 per attorney for fiscal years 1998 through 2010—which we received from Justice. To adjust for uncompensated overtime, we reduced the reported annual hours the attorneys worked by 15 percent, an amount that Justice estimated represents overtime worked by its attorneys. To adjust the attorneys’ salaries to include benefits and related agency overhead, we increased the attorneys’ salaries by 84.3 percent, a factor that was provided to us by Justice on the basis of its actual 2009 costs. To ensure that attorney costs are comparable across years, we adjusted annual pay rates by applying the consumer price index for all urban consumers from the Department of Labor, Bureau of Labor Statistics, and inflated all pay rates to constant 2010 dollars. When we reported single payments, however, we did not adjust these figures to constant dollar figures. To determine the second and third components of litigation costs— Treasury’s Judgment Fund and EPA’s payments to plaintiffs—we obtained and analyzed data from Treasury and EPA. First, we obtained and analyzed data from the Department of the Treasury’s Judgment Fund Internet Claims System, which tracks the progress of plaintiffs’ claims for Judgment Fund payments from the time they are sent to Treasury until the time they are paid. To identify data on payments related to the environmental statutes in our scope, we matched Treasury’s data with data from Justice’s two databases and eliminated payments that did not correspond with cases in our scope. When information was determined to be missing, we asked Treasury to provide us with additional information. In particular, we learned that Treasury’s data included payments that were issued but were not cashed or were returned; we worked with Treasury to remove these payments to avoid counting these as actual payments and overrepresenting the amount paid from the Judgment Fund. We deleted Superfund cases because we were unable to discern from available information whether the Superfund-related payments were for attorney fees and court costs or for reimbursements of site cleanups, which is a different category of payment than what is within our scope. Similarly, to identify EPA payments to plaintiffs within our scope under the Equal Access to Justice Act, we obtained EPA data on payments made to plaintiffs and manually matched these cases with the cases in Justice’s two databases. When certain case information was determined to be missing, we did additional research on these cases using PACER and corrected the data. Inconsistent formatting of key data elements produced significant problems for completing our analysis and required significant manual review by us and Justice. If we did not find the necessary information from available sources, we asked EPA to send us relevant portions of the internal voucher packages used to request payment. We conducted this performance audit from June 2010 through July 2011, in accordance with generally accepted government auditing standards. Those standards require that we plan and perform the audit to obtain sufficient, appropriate evidence to provide a reasonable basis for our findings and conclusions based on our audit objectives. We believe that the evidence obtained provides a reasonable basis for our findings and conclusions based on our audit objectives. Appendix II: Key Provisions and Historical Reporting under the Equal Access to Justice Act In the United States, parties involved in litigation generally bear their own attorney fees and costs. For policy reasons, including encouraging citizens to bring suits to enforce the law, Congress has provided exceptions to this rule for cases brought under several statutes, such as the Civil Rights Act. In these instances, as well as some common-law exceptions, a prevailing plaintiff may seek awards of its attorney fees and court costs from the losing party. Historically, the federal government had sovereign immunity from some of these exceptions, but in some instances, the statutes also waived sovereign immunity so that a court could award fees and costs against the federal government, as well as a private party. According to Justice, many of the key environmental statutes’ provisions authorizing award of attorney fees and costs apply to the federal government. For example, EPA pays attorney fees under several provisions of the Clean Air Act and the Clean Water Act. Furthermore, in 1980, the Equal Access to Justice Act (EAJA) was enacted to waive sovereign immunity for the remaining statutes authorizing award of fees and costs, as well as to authorize the awarding of fees and costs in other cases. As the 1980 conference committee report for EAJA explains, the act’s premise is that individuals, corporations, partnerships, and labor and other organizations did not seek review of or defend against unreasonable government actions because of the expense involved, which was compounded by the disparity in expertise and resources between the government and the individual or organization involved. EAJA was intended to help certain individuals, partnerships, corporations, and labor and other organizations by paying the attorney fees and other costs if the federal government brought an administrative or judicial action and lost because the action was not substantially justified. EAJA seeks to (1) encourage parties that are the subject of unreasonable federal government action to seek reimbursement for attorney fees and other costs, (2) restrain overzealous regulators, and (3) ensure that the government pays for the cost of refining and formulating public policy. EAJA authorizes the award of the following:  Court costs of prevailing parties against the United States in any civil action. These costs may include fees for the clerk and marshal, reporter, printing, witnesses, copies, docket fees, and interpreters and court-appointed experts and may include an amount equal to the filing fees.  Attorney fees and expenses against the United States of a prevailing party to the same extent as any other party, codified at 28 U.S.C. § 2412(b) and hereinafter referred to as “subsection b.” That is, where there is a statutory or common-law exception that provides for award of fees to a prevailing party, such exceptions also apply to the federal government. Regarding the 10 environmental statutes covered in this report, many of the relevant provisions under which EPA may be sued provide for award of such fees. However, EAJA makes EPA subject to fee awards under all the environmental statutes’ provisions authorizing courts to award attorney fees and expenses. According to Justice, many of the environmental suits against EPA involve provisions that authorize fee awards independent of EAJA, but a small number may fall into EAJA subsection b. A feature of this subsection is that it does not itself limit the eligibility of prevailing plaintiffs, nor expressly limit the hourly rate of attorney fees; however, the statute requires that the fees be “reasonable.” Additionally, any award of fees made under this section is subject to any limitations that would apply to analogous awards against private parties, as may be provided by the underlying statute.  Attorney fees and expenses of a prevailing party in cases even when no statutory or common-law exception exists to make a private defendant liable for such fees, unless the court finds that the position of the United States was substantially justified or that special circumstances make an award unjust. This subsection of EAJA, codified at 28 U.S.C. § 2412(d) and hereinafter referred to as “subsection d,” authorized the award of these fees against the federal government in civil court actions, while another subsection authorized the award of these fees in certain agency adjudications such as when a party files an appeal of an agency decision to the EPA Environmental Appeals Board. Two of the 10 laws covered in this report—the Federal Insecticide, Fungicide, and Rodenticide Act and the Federal Food, Drug, and Cosmetic Act—as well as some individual provisions of other statutes, do not authorize payment of fees to prevailing parties. Cases brought against EPA under these statutes and provisions, then, fall into EAJA subsection d. This subsection limits the prevailing plaintiff’s eligibility to receive payment by defining an eligible party as, at the time the lawsuit is filed, either an individual with a net worth below $2 million or a business owner or any partnership, corporation, association, local government, or organization with a net worth below $7 million and fewer than 500 employees. Tax-exempt nonprofit organizations and certain agricultural marketing cooperatives are considered parties regardless of net worth. Payment of attorney fees by federal agencies under statutes independently authorizing awards against federal agencies and under subsection b are made from the Judgment Fund, which is a permanent, indefinite appropriation available to pay many money judgments against the United States. Payment of attorney fees by federal agencies under subsection d is generally made from agency appropriations. Table 5 summarizes key attributes of the three authorizing situations under which EPA may pay fees and costs. Originally, EAJA provided for governmentwide reporting on its use and cost. For judicial proceedings, EAJA required the Director of the Administrative Office of the U.S. Courts to report annually to Congress on EAJA court activity, including the number, nature, and amounts of awards; claims involved; and any other relevant information deemed necessary to aid Congress in evaluating the scope and effect of awards under the act. The responsibility for this reporting was transferred to the Attorney General in 1992. In addition, EAJA required the Chairman of the Administrative Conference of the United States to submit an EAJA report annually to Congress on administratively awarded fees and expenses. Then, in December 1995, the Federal Reports Elimination and Sunset Act of 1995 repealed the Attorney General’s reporting requirement for fees and expenses awarded under EAJA and also discontinued reporting of governmentwide administrative awards of fees and costs under EAJA after fiscal year 1994. Currently, there are no statutory requirements in effect for agency or governmentwide reporting of payments made under EAJA for either administrative or judicial proceedings. According to officials from the Administrative Conference of the United States, the conference has begun to obtain and compile such information for fiscal year 2010, noting that there has been continued interest in Congress (including pending legislation) regarding data about payments under EAJA. Officials told us the conference has requested EAJA data from 50 government agency conference members, as well as a few additional agencies that had previously reported EAJA activity to the conference. The chairman plans to publish a report for fiscal year 2010 later in 2011. We have previously reported certain governmentwide EAJA data, as well as data focused on selected agencies. In 1996, we reported data on the number of cases and amounts of awarded plaintiff attorneys’ fees exceeding $10,000 against nine federal agencies for cases closed during fiscal years 1993 and 1994. In 1998, we provided information on the history of EAJA, the extent to which one provision of the act was used governmentwide from 1982 to1994, and the provision’s use by the Department of Labor and associated agencies. The governmentwide data showed, among other things, that the Departments of Health and Human Services and of Veterans Affairs accounted for most EAJA payments in court proceedings, under the provision that applies when the substantive law does not authorize award of attorney fees and costs. Appendix III: Department of the Treasury and Environmental Protection Agency Payments This appendix provides data on payments for attorney fees and court costs made by the Department of the Treasury for fiscal year 2003 through fiscal year 2010 and by the Environmental Protection Agency (EPA) for fiscal year 2006 through fiscal year 2010. Payments for attorney fees and expenses and court costs may be made to a plaintiff or directly to a plaintiff’s attorney. In cases involving multiple plaintiffs, one or more plaintiffs or their attorneys may receive payment. The first plaintiff named in the case title does not necessarily receive the payment. Table 6 shows payments from the Judgment Fund. In addition to payments from the Judgment Fund, EPA made payments under EAJA to successful plaintiffs. Table 7 shows payments made by EPA for fiscal year 2006 through fiscal year 2010. Appendix IV: GAO Contact and Staff Acknowledgments GAO Contact Staff Acknowledgments In addition to the individual contact named above, Susan Iott (Assistant Director), Jacques Arsenault, Elizabeth Beardsley, Jennifer Beveridge, Colleen Candrl, Ellen W. Chu, Bernice Dawson, Cindy Gilbert, Cynthia Grant, Anne K. Johnson, Rebecca Makar, Mehrzad Nadji, and Jeff Tessin made key contributions to this report.

Summary: The Environmental Protection Agency (EPA) faces numerous legal challenges as it implements the nation's environmental laws. Several statutes, such as the Clean Air and Clean Water Acts, allow citizens to file suit against EPA to challenge certain agency actions. Where EPA is named as a defendant, the Department of Justice provides EPA's legal defense. If successful, plaintiffs may be paid for certain attorney fees and costs. Payments are made from the Department of the Treasury's Judgment Fund--a permanent fund available to pay judgments against the government, as well as settlements resulting from lawsuits--or EPA's appropriations. For this review, GAO was asked to examine (1) the trends in and factors affecting environmental litigation for fiscal years 1995 through 2010 and (2) Justice's recent costs and recent plaintiff payments from the Judgment Fund and EPA. To conduct this review, GAO obtained and analyzed data from two Justice databases on cases filed under 10 key environmental statutes. To gain stakeholder views on any trends and factors that might affect them, GAO interviewed representatives of environmental and industry groups, state attorneys general, and other experts. GAO estimated the costs of litigation handled by Justice attorneys and payments made for attorney fees and court costs from the Judgment Fund and EPA funds. No trend was discernible in the number of environmental cases brought against EPA from fiscal year 1995 through fiscal year 2010, as the number of cases filed in federal court varied over time. Justice staff defended EPA on an average of about 155 such cases each year, or a total of about 2,500 cases between fiscal years 1995 and 2010. Most cases were filed under the Clean Air Act (59 percent of cases) and the Clean Water Act (20 percent of cases). According to stakeholders GAO interviewed, a number of factors--particularly a change in presidential administration, new regulations or amendments to laws, or EPA's not meeting statutorily required deadlines--affect environmental litigation. The costs borne by Justice, EPA, and Treasury also varied without a discernible trend from fiscal year 1998 through fiscal year 2010. Justice spent at least $43 million, or $3.3 million annually, to defend EPA in court during this time. In addition, owing to statutory requirements to pay certain successful plaintiffs for attorney fees and costs, Treasury paid about $14.2 million from fiscal year 2003 through fiscal year 2010--about $1.8 million per fiscal year--to plaintiffs in environmental cases. EPA paid approximately $1.4 million from fiscal year 2006 through fiscal year 2010--about $280,000 per fiscal year--to plaintiffs for environmental litigation claims under relevant statutes. (All amounts are given in constant 2010 dollars.) Justice officials said that they negotiate payments with the successful plaintiffs, who generally receive less than originally requested. Complicating efforts to analyze trends in cases and costs is that Justice maintains data on environmental cases in two separate data systems and does not have a standard approach for maintaining the data. As a result, it is difficult to identify and summarize the full set of cases and costs managed by Justice. Nonetheless, using an iterative electronic and manual process, GAO was able to merge the two sets of data for its purposes. Justice officials said that they do not need to change their approach to managing the data, however, because they do not use it to summarize case data agencywide. Moreover, the officials said they lack resources to adapt their aging systems to accept additional data.

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Summarize: Background SSA administers two programs under the Social Security Act that provide benefits to people with disabilities who are unable to work: Disability Insurance (DI) and Supplemental Security Income (SSI). According to SSA policy, to be eligible for either DI or SSI, an adult must be unable to engage in “substantial gainful activity”—typically work that results in earnings above a monthly threshold established each year by SSA—because of a medically determinable physical or mental impairment that is expected to last at least 12 months or result in death. Established in 1954, the DI program provides monthly benefits to workers (and their spouses and dependents) whose work history qualifies them for disability benefits and whose impairment is disabling. In 2007, SSA paid about $99 billion in DI benefits to about 8.1 million workers, spouses, and dependents. The average monthly benefit was $1,004 for disabled workers. SSI is a means- tested income assistance program created in 1972 that provides a financial safety net for people who are aged, blind, or disabled, and have low incomes and limited assets. Unlike the DI program, SSI has no prior work requirements. In 2007, SSA paid about $37 billion in SSI benefits. As of December 2007 about 7.4 million recipients received an average monthly benefit of $468. Some individuals with disabilities receive both DI and SSI benefits if they meet both DI’s work history requirements and SSI’s income and asset limits. Disability Determination Process The process to determine a claimant’s eligibility for SSA disability benefits is complex, involving several state and federal offices. The disability determination process, which is the same for DI and SSI claimants, involves an initial determination of disability and provides up to two levels of administrative review within SSA. A claimant first completes an application, or claim, for DI or SSI benefits, which includes information regarding illnesses, injuries, or conditions and a signature giving SSA permission to request medical records from medical care providers. Once the SSA field office staff verify that nonmedical eligibility requirements are met, the claim is sent to the state’s DDS office for determination of medical disability. If the claim is approved, a claimant will be notified and will receive benefits, including limited retroactive benefits for some DI claimants. Additionally, if the claim is approved, a claimant may become eligible for Medicaid or Medicare health coverage. If the claim is rejected, a claimant has 60 days to request that the DDS reconsider its decision. If the DDS reconsideration determination concurs with the initial denial of benefits, the claimant has 60 days to appeal and request a hearing before an SSA administrative law judge (ALJ). A claimant may appeal an unfavorable administrative law judge decision to SSA’s appeals council, which includes administrative appeals judges and appeals officers and, finally, to federal court. SSA and DDS officials (examiners and ALJs) determine disability using a five-step sequential process based on evidence such as medical findings and statements of functional capacity obtained during the initial determination process and updated as necessary at each appeal level. (See fig. 1.) Development of Medical Evidence for Initial Determinations Generally, SSA requires DDSs to develop a complete medical history for each claimant for at least a 12-month period prior to the application. SSA guidance directs DDSs to request records from all providers who have treated or evaluated the claimant during this time period, except those who treated only ailments clearly unrelated to the claimed impairment. DDSs generally pay providers for records and SSA pays the DDSs to cover these expenses. Each DDS determines its payment rates for medical and other services necessary to make determinations, subject to certain limits. DDSs request laboratory reports, X-rays, doctors’ notes, and other information used in assessing the claimant’s health and functional capability from many types of providers including: physicians or psychologists; hospitals; community health centers; schools (for child claimants); and Department of Veterans Affairs (VA), military, or prison health care facilities. In addition to medical evidence, DDSs review statements from the claimant or others about the claimant’s impairment and ability to perform daily activities. SSA directs DDSs to make “every reasonable effort” to help the claimant obtain medical reports, which SSA defines as one initial medical records request and, if needed, one follow-up request within 10 to 20 days, when providers have not responded, unless experience with a particular provider warrants more time. DDSs allow a minimum of 10 days after the follow-up request for the provider to reply. When records indicate the claimant has been to other medical providers, DDSs also contact those providers for records. Generally records are placed in the claimant’s case record. SSA regulations require that disability determinations place more, and in some cases controlling, weight on the opinions of a claimant’s treating providers. For example, a treating provider’s opinion about the nature and severity of the claimant’s impairment should generally be given controlling weight where their opinion is well supported by other substantial evidence in a claimant’s case record. In claims where the gathered medical and nonmedical evidence is insufficient to support a disability determination, DDSs may order consultative exams or tests. DDSs pay providers to perform these examinations and SSA pays them to cover these costs. SSA regulations require that payments to providers for consultative exams not exceed the highest rate paid by federal or other state agencies for the same or similar services. The regulation allows states to determine the rates of payment and, as a result, DDS rates of payment for consultative exams vary nationwide. SSA regulations specify the types of providers who may perform these exams or tests, and require DDSs to recruit, train, and oversee them. SSA regulations also state that the claimant’s own provider is generally the preferred source for consultative exams if qualified, equipped, and willing to perform the exams. (See fig. 2.) Claimant To support DDSs’ efforts to process claims quickly, SSA has established an expedited process for claims in which a determination of disability is likely. In September 2007, SSA implemented its Quick Disability Determination process nationwide after testing it in the Boston region. This process uses a computer model using certain key terms in the claim file to identify claims for which a decision of disability is likely and medical evidence establishing disability can be easily obtained. DDSs can use expedited processes for these claims; for example, DDS staff in a couple of states we visited explained how they request and receive medical records for Quick Disability Determination cases by fax. SSA reported, for fiscal year 2007, that the national average processing time for all initial claims was 83 days. By comparison, during the pilot, the Boston region decided Quick Disability Determination claims in an average of 11 days. SSA also has policies to expedite claims involving diseases such as certain types of cancer that are terminal or otherwise so severe that they clearly meet SSA’s definition of disability. SSA performs a quality assurance review of a sample of more than 30,000 DDS decisions each year. SSA assesses the accuracy of the DDSs’ determination and the sufficiency of the documentation for the DDSs’ compliance with requirements for medical records collection and consultative exams process. Decisional deficiencies occur when a different determination should have been made, and documentation deficiencies occur when additional documentation is necessary in order to make the correct determination. SSA also collects extensive data on spending for consultative exams and requires DDSs to routinely report substantial budget, program operations, and management data to SSA. Electronic Medical Record Collection In 2004, President Bush called for widespread adoption of interoperable electronic health records within 10 years and issued an executive order assigning the coordination of the effort to the Department of Health and Human Services. Under the department’s leadership, volunteer organizations designated to develop standards for the health care industry have prepared initial certification criteria for health information technology such as electronic patient records and records management systems. As businesses, providers decide when and whether to invest in these certified systems. Another executive order in 2006 directs certain federal agencies to “utilize, where available, health information technology systems and products that meet recognized interoperability standards.” HHS also has awarded several contracts related to health information technology to address issues such as standardization, networking, and privacy and security. SSA collection of medical evidence is affected by the Health Insurance Portability and Accountability Act of 1996 (HIPAA) which defines the circumstances in which an individual’s health information may be used or disclosed. In addition, HIPAA’s security provisions require entities that hold or transmit health information to maintain reasonable safeguards to protect the information against unauthorized use or disclosure and ensure its integrity and confidentiality. DDSs Face Challenges Obtaining Medical Records from Claimants’ Providers Determining eligibility for disability benefits is a complex, challenging task. DDS officials identified obtaining records from claimants’ medical providers as a major challenge to DDS examiners’ ability to quickly compile the necessary evidence for disability determinations. DDSs cited problems with the consistency of provider response to record requests, both in timeliness and completeness of records submitted. DDSs have responded to these challenges by conducting additional follow-up contacts with medical providers and claimants, and more than half of the 51 DDSs we surveyed reported adjusting their payment methods. Although SSA routinely reviews DDSs’ compliance with medical records collection requirements, SSA does not systematically identify and review the effectiveness of promising DDS medical evidence collection practices. Medical Providers Do Not Respond Consistently to DDS Requests for Records DDS officials identified provider response to medical records requests as a challenge in our survey of 51 DDSs. One DDS director reported in our survey that more than 300 providers in the state were considered “nonproductive” so that the DDS must send claimants who are patients of those providers to consultative exams when evidence from other sources is insufficient. One DDS director noted that public health clinics and hospitals are overburdened providing patient care and that medical records programs get short shrift. According to both DDS officials and providers we interviewed, generating records for disability claims takes lower priority than patient care and costs money for medical records staff time and contracted copy services, for example. One DDS official told us that some providers do not bill the DDS for records because the state’s centralized payment system is slow and generates payments that are hard to reconcile with invoices. Examiners in another state told us that some providers refuse to submit requested records for claimants with unpaid bills, or charge the claimants instead of the DDS. DDSs also can have difficulty obtaining medical records when medical records are purged or moved to another location, or when facilities close or are destroyed. DDSs request records from all providers who have treated the claimant for at least the 12 months preceding the application for benefits, except those who treated only minor ailments clearly unrelated to the claimed impairment or when the claimed disability began more recently. As a result, the volume of records requested is high: 13 DDSs reported sending over 200,000 requests in fiscal year 2007. Provider response to these requests for medical records is inconsistent; some submit records to the DDSs within 10 days, others never respond at all. Timeliness of medical record receipt is a central concern because SSA tracks how long it takes to process initial claims, and measures DDSs against regulatory performance standards. SSA reported that the national average processing time for initial claims was 83 days in fiscal year 2007. Although not all DDSs were able to complete our survey question on the volume of medical record requests and timeliness of provider responses, 32 of the 37 DDSs who did provide numbers reported receiving responses for up to 40 percent of their requests for medical records within 10 days. However, a substantial number of requests for medical records go unfulfilled. As shown in figure 3, 14 DDSs received less than 80 percent of requested records. Another 14 DDSs did not provide sufficient data in response to our survey to calculate the percentage of requests for which they received medical records. DDS examiners request records from various types of providers including physicians or psychologists in individual or group practices; hospitals; community health centers; schools (for child claimants); and VA, military, or prison health care facilities. As shown in table 1, DDS directors we surveyed reported that some types of providers are more responsive to medical records requests than others. The task of obtaining a complete medical history is further complicated when claimants do not identify all their medical providers when applying for benefits. Almost all of the 51 DDS directors (48) we surveyed reported that examiners at least sometimes identify providers who had not been listed on the claimant’s application. Examiners may find out about additional medical providers as they review the records in the file, for example, and must generally request records from those providers. In our review of 100 initial claim files, we identified 19 in which DDS examiners requested records from providers who had treated the claimant but had not been identified on the application. In addition to contacting multiple providers, DDS examiners must develop evidence for all of the claimed impairments, which can be numerous and include both mental and physical conditions. During our site visits, DDS claims examiners told us that claims involving mental impairments posed particular documentation challenges, noting that some claimants with mental impairments may have difficulty obtaining treatment or accurately describing their medical histories. Furthermore, SSA regulations include some specific requirements for collecting evidence of mental impairments. For example, generally where there is indication of a possible mental impairment, SSA regulations establish a special technique to be used when evaluating the severity of mental impairments, which includes rating the claimant’s degree of functional limitation in four broad functional areas and recording the results of this evaluation on a standard document. The opinions of providers with an ongoing treatment relationship with the claimant are a particularly important source of evidence for disability determinations. Treating providers’ opinions about the nature and severity of the claimant’s impairment often are given great deference in SSA regulations. Examiners must give controlling weight to treating providers’ opinions if they are not inconsistent with the other substantial evidence in the case record and are well supported by medically acceptable clinical and laboratory diagnostic techniques. Yet, of the 51 DDSs we surveyed, none reported that half or more were willing to provide such opinion statements, and 15 indicated that none or almost none were willing to provide the statements. Almost all DDSs (48 of 51) reported asking for treating sources’ opinion statements in their initial medical records requests, but as table 2 shows, DDSs are not always successful at obtaining those statements, even after multiple requests, and the statements they receive are not always helpful in making their determinations. A good and useful MSS both states a quantification of the effects of the condition on the claimant’s ability to function and an explanation as to how the assessment is supported by the evidence. These are rare. More often we receive “less useful” MSS’s that only do the first part. Treating sources are generally OK with just sending records or including a statement such as “the patient has severe rheumatoid arthritis, remains under my care, and can’t return to work for the foreseeable future.” When we get such an MSS, we either are left to refute it or return it to the TS for a better underlying analysis. This annoys them and usually does not come to a beneficial or happy result. DDS officials and providers described various reasons why treating providers may be reluctant to submit medical source statements. Treating providers may be concerned that submitting their medical opinion to the DDS might interfere with the doctor-patient relationship, and they also typically focus on diagnosis and treatment rather than evaluation of functional ability. Providers also may have limited knowledge of SSA standards or the physical or mental requirements for different types of work. Almost All DDSs Engage in Additional Follow-up Contacts to Encourage Provider Response; about Half Have Modified Their Payments SSA regulations and guidance specify the timing of DDS requests for medical records but leave the methods of contact up to each DDS. If it does not receive records after one request, the DDS must make one follow-up request within 10 to 20 days unless the provider is known to take longer to respond. After that, the DDS must generally give the provider an additional 10 days and then may send the claimant for a consultative exam if needed. Requests by mail remain the most prevalent method for requesting medical records, used at least very often by 42 of the 51 DDSs surveyed. All use fax to some extent, with slightly more (27) reporting they use fax at least often and 24 reporting using fax sometimes. During our site visits, 6 of the 28 DDS examiners we interviewed told us that some providers raise concerns about privacy or compliance with HIPAA, for example, by insisting on a hard copy of the claimant’s signed authorization to release medical records. According to SSA, hard-copy, fax, or electronically transmitted versions of its official authorization form, signed and dated by the claimant, all comply with relevant state and federal laws and regulations, including HIPAA. Once records are received, the DDS may need further contact with providers to clarify ambiguities or request additional information. SSA guidance require examiners to recontact a provider whose medical report contains ambiguities, conflicts either internally or with other evidence, is incomplete, or is not based on medically acceptable clinical and laboratory diagnostic techniques. In addition, SSA guidance directs the DDS’s examiners to recontact a treating provider if the report contains an opinion on an issue reserved for SSA, such as whether the claimant is disabled or has a condition that meets one of the medical listings, without identifying the basis for that opinion. If the initial recontact SSA requires is not successful, DDSs report pursuing additional approaches to encourage providers to submit or clarify records. These include making additional follow-up calls to providers, their assistants, or medical records staff and asking claimants to get in touch with their providers about sending in the records. In addition, DDSs conduct outreach to emphasize the importance of submitting medical records and contact providers to resolve questions about privacy. Privacy of medical records came up frequently in our discussions of the medical evidence collection process: DDS officials in each of the five states we visited indicated that some providers relay concerns about patient privacy and compliance with applicable protections. DDS professional relations officers also supplement the examiners’ contacts via provider education and outreach to medical societies. If information in the medical records requires clarification, DDS medical consultants, such as physicians or psychologists, also may contact providers directly. SSA guidance permits DDSs to obtain verbal statements from treating providers, then send summaries of those statements to the providers for their signatures to expedite the DDS determination process. In addition to following up with providers and claimants, more than half of the 51 DDSs we surveyed reported modifying their payment methods for medical records. To encourage provider response, 34 of the 51 DDS directors surveyed reported taking steps to improve the timeliness of their payments and 6 reported increasing their payment amounts. While only 30 DDS directors reported in our survey that their payment rates were high enough to ensure adequate medical records collection, some DDS directors commented that they had heard from some types of providers that their rates were not adequate; psychologists or other specialty providers, for example, reported that payments were adequate for some types of providers but not others. Asked in the survey how their payment rates compare with prevailing rates for medical records in their states, 3 of the 51 DDSs reported that their payment rates were above prevailing rates in their states, 19 reported that the rates were about the same, and 20 reported that their payment rates were below prevailing rates. Vermont’s DDS instituted an incentive payment for prompt response because that state prohibits providers from charging for providing copies of health care records requested to support a claim or appeal under any provision of the Social Security Act or any other federal or state needs-based program. SSA Conducts Quality Assurance Reviews, but Does Not Gather Some Key Data on Varied DDS Approaches to Collecting Medical Records While SSA conducts quality assurance reviews and collects data on program operations from DDSs, it has not systematically evaluated the effectiveness of the DDSs’ varied approaches to collecting medical records. SSA regularly reviews DDSs’ compliance with requirements for medical records collection as part of its quality assurance review of a sample of more than 30,000 DDS decisions each year. These reviews take place before the DDS determination is communicated to the claimant, and SSA returns the claim to the DDS for additional work if SSA reviewers find that additional medical evidence or analysis is needed. These reviews assess both the accuracy of the DDSs’ determinations and the sufficiency of the documentation the DDSs obtained. Decisional deficiencies occur when the DDS should have made a different determination, and documentation deficiencies occur when additional documentation is necessary in order to make the correct determination. Errors related to the collection of medical evidence include cases in which insufficient medical evidence was obtained to support the DDS determination, for example, to establish that the claimant’s impairment is severe or expected to last at least 12 months or result in death. SSA also requires DDSs to routinely report substantial budget, program operations, and management data to SSA. While these data help SSA oversee the DDSs, they may lack some key measures that SSA could use to evaluate the effectiveness of different DDSs’ medical records collection practices. For example, not all DDSs’ computer systems routinely track the total number of requests they send and the timeliness of provider responses. Of the 51 DDS directors we surveyed, 14 did not provide complete responses on the number of medical record requests they sent and received responses to, and others were able to provide only estimates. The lack of consistent data on receipts of medical records from providers limits SSA’s ability to evaluate the effectiveness of different DDSs’ medical records collection activities—evaluations which could lead to wider adoption of practices that are found to be successful and cost effective. Nationally consistent data could help SSA assess whether some DDSs’ approaches are more effective than others or whether adoption of new approaches, such as incentive payments for prompt provider response, yields faster submission of records. DDSs Face Challenges Recruiting and Retaining Qualified Consultative Exam Providers Recruiting and retaining enough medical providers to conduct consultative exams was frequently cited by DDS representatives as one of the main challenges to medical evidence collection, in part because of provider concerns about missed appointments or DDS payment rates for consultative exams. Responses to these challenges include scheduling consultative exams with medical providers whose practices focus primarily on performing disability evaluations and adjusting payments, for example, by paying providers for the time they spend preparing for a consultative exam that a claimant fails to attend. Recruitment and Retention of Consultative Exam Providers Is Difficult We frequently heard from DDS directors, both during our site visits and in response to our survey, about their difficulty finding medical providers to conduct consultative exams. It is even difficult for DDSs to obtain consultative exams from claimants’ treating physicians—the preferred source for consultative exams according to SSA guidance and regulations. For example, 41 of the 51 DDS directors we surveyed reported that their offices routinely ask claimants’ treating providers if they are willing to perform a consultative exam if needed, but 34 of these directors reported that claimants’ treating providers are never or almost never willing to perform these exams. According to DDS officials and providers, reasons for this reluctance may include concern about disrupting the doctor-patient relationship through involvement in the disability claim and dissatisfaction with DDS payment rates. These inquiries often are included in the requests for medical records sent by the DDSs to claimants’ treating providers. For example, in our review of 100 claim files for initial disability determinations, 45 files contained one or more requests for medical records that included an inquiry about the providers’ willingness to perform a consultative exam. However, only 2 claimants’ files had records of consultative exams conducted by the treating provider. In many cases, DDSs make this request in the form of a yes or no question that accompanies their requests for medical records or by asking providers to contact them if they would be interested in performing a consultative exam. Often providers either indicate they are not willing to perform a consultative exam or leave the question blank. In some cases, the requests for records indicate that the absence of a response will be interpreted as an indication that they are not interested. One reason why the DDSs may face difficulty recruiting and retaining consultative exam providers is the frequency with which disability claimants miss their consultative exam appointments. DDS directors reported in our survey that claimants fail to attend approximately 16 percent of consultative exam appointments on average, with 40 of the 51 directors providing this information. When asked the reason why claimants fail to attend these appointments, DDS directors reported that claimants sometimes miss appointments for reasons including transportation challenges, unmet needs for someone to accompany the claimant to the appointment, reluctance to take part in the exam, or inability to attend due to a mental or physical health condition. Regardless of the reason for claimants’ failure to attend scheduled exams, several DDS examiners we spoke with identified missed consultative exams as a major problem which may affect providers’ willingness to participate. If a claimant misses an appointment, providers lose revenue if they are unable to substitute another patient and cannot bill the DDSs for the missed exam. When asked to what extent provider concerns about missed consultative exam appointments posed challenges, almost half of DDS directors (24 of 51) reported that such concerns posed challenges to a great or very great extent, although some DDSs (20) reimburse providers for time spent preparing for missed consultative exams. Current payment rates also may contribute to the DDSs’ challenges recruiting and retaining consultative exam providers who submit high- quality reports. Almost all DDS directors (50 of 51) reported that DDS fee schedules posed a challenge, at least to some extent, to recruiting and retaining a panel of highly qualified consultative exam providers. Several DDS officials told us current consultative exam payment rates affect their ability to recruit and retain consultative exam providers in their states. For example, California DDS officials commented that current consultative exam payment rates are below prevailing payment rates in the state. Wyoming DDS officials also told us that payment rates pose challenges to the recruitment of providers for Wyoming’s consultative exam provider pool. Consultative exam payment varies among DDSs nationwide. SSA regulations require that payments to providers for consultative exams not exceed the highest rate paid by federal or other agencies in the state for the same or similar services. Within those parameters, DDSs vary in the type of payment rates they use as benchmarks for consultative exams. (See fig. 4.) Many DDS directors (17 of 51) also indicated that in their opinion current payment amounts in their states are not high enough to ensure that the DDS receives timely, high-quality consultative exam reports. For those DDSs, seven also reported that consultative exam reports only sometimes demonstrated sufficient familiarity with the claimants’ medical records and history to support the assessment. Some DDSs Rely on High- Volume Consultative Exam Providers or Pay Providers for Preparing for Missed Appointments Some DDSs have adopted responses to the challenge of recruiting and retaining consultative exam providers by (1) relying on high-volume providers whose practices focus primarily on performing disability evaluations and (2) adjusting consultative exam payments. As shown in figure 5, most DDSs (32 of 51) report they often use high-volume providers to conduct consultative exams for claimants in their state. Twenty-nine indicated that using these providers has a moderately positive or very positive effect on the quality of the consultative exam reports they receive. At least one DDS has taken the concept of high-volume consultative exam providers one step further. The New York DDS expanded its use of high- volume consultative exam providers by hiring contractors to recruit consultative exam providers and manage claimants’ appointments. New York DDS officials reported that the majority of consultative examinations now are conducted through these contractors in areas of the state covered by contracts. As described to us by New York DDS officials, these contracts provide for extensive training of new consultative exam providers that can last several months, content and timeliness requirements for exam reports, and quality assurance including surveys of claimants and inspection of providers’ facilities. Some DDSs have adjusted their payments for consultative exams to address recruitment challenges in their states. For example, Wyoming currently pays usual and customary rates that providers receive for similar exams throughout the state. Wyoming DDS officials reported that they make use of such a structure due to the sparse population and small number of medical providers that service their state, approximately 1,000. According to Wyoming DDS officials, a relatively small portion of these providers are willing to perform consultative exams for the DDS and they believe that without usual and customary payment, even fewer providers would be willing to conduct them. In addition, many DDSs (20 of 51) pay consultative exam providers for the time they spend preparing for exams that claimants fail to attend, which may help DDSs retain their consultative exam provider pool. Among those 20 DDSs reporting that they offer such payments, the average payment provided was about $44. Finally, DDSs engage in various activities to facilitate claimant attendance at consultative exams. The most common activities reported are reminder letters and telephone calls and reimbursement for travel costs (see table 3). Examiners at two of the DDSs we visited described arranging for consultative exam providers to perform in-home evaluations for claimants whose impairments kept them confined to their homes. Examiners noted that “third parties”—family members or social workers listed as contacts on the application for benefits—may help facilitate consultative exam appointments, especially for claimants who are homeless or who have mental or developmental impairments. SSA Reviews Consultative Exams and DDS Decisions, but Does Not Evaluate DDS Practices to Address Recruitment and Retention Challenges While SSA evaluates consultative exams as part of its quality assurance review process and collects data on spending for consultative exams, it has not evaluated the effectiveness of varied DDS responses to challenges related to recruiting and retaining consultative exam providers. SSA reviews consultative exams as part of its ongoing quality assurance reviews of more than 30,000 randomly sampled initial disability determinations. SSA reviewers assess the claim file for errors including unnecessary consultative exams; consultative exam from an improper source (such as failure to use a psychiatrist or psychologist to evaluate a mental disorder); or incomplete, inadequate, or unsigned consultative exam reports. Despite these overall quality reviews, SSA officials indicated they were unable to locate any studies SSA has conducted to evaluate the effectiveness of varied DDS collection practices. By undertaking such studies, SSA program managers could identify promising DDS practices to recruit and retain consultative exam providers or evaluate their effectiveness and potential for wider adoption and thereby improve accountability by facilitating wider adoption of DDS practices with the potential to help the agency achieve its service delivery goals, such as making the correct decision early in the process. SSA currently does not collect some information, such as nationally comparable data on missed consultative exams, that could help SSA evaluate DDS practices that may hold promise for improved recruitment and retention of consultative exam providers in other states. SSA Has Made Progress in Moving to Electronic Collection of Medical Records, but Faces Challenges Shifting to the Use of Electronic Medical Records SSA’s transition from paper medical records to the use of electronic images of medical records has increased opportunities for program efficiencies and agency collaboration. SSA prefers and encourages providers to submit medical records online, but it continues to receive a little more than half of these records in paper form. SSA has only conducted limited studies of the problems related to electronic submission of medical records and has not taken additional steps necessary to facilitate greater use of online submission options. In anticipation of the medical community’s replacement of paper with uniform electronic medical records, SSA is developing procedures to electronically request and receive electronic medical records and analyze them in ways that are expected to make the medical evidence collection process and disability decision making more efficient. Use of Electronic Images Enables SSA and DDSs to Collaborate More Efficiently As a step toward automating its disability process, SSA has successfully adopted the use of electronic images of medical records instead of paper copies for new claimants. Electronic images of medical records—records scanned, faxed, or uploaded into SSA’s computer database—are an important step in SSA’s transition to an automated process, as these images can be submitted, stored, and accessed electronically by authorized staff from distant locations. Electronic medical evidence—even in the form of electronic images—facilitates collaboration between SSA and DDSs. For example, electronic files have enabled SSA to implement a new process for resolving disagreements concerning DDS disability decisions reviewed by SSA before initial decisions are finalized. Rather than having SSA reviewers in each regional office review DDS decisions only in that region, electronic access to records enables staff in other regions and policy staff in SSA headquarters to review cases remotely. SSA introduced this process to promote more nationally consistent interpretations of SSA policy. Additionally, SSA and DDSs are able to shift workloads from office to office without mailing records, which takes time and increases the risk that records will be lost. However, SSA officials and DDS directors told us electronic image records have limitations in that they cannot be electronically analyzed and searched. Almost all surveyed DDS directors (50 of 51) reported that having medical records in electronic folders has increased productivity, but some indicated that frustrations exist, such as some computer system usage problems. For example, several DDS examiners told us they were frustrated by occasional data system interruptions, due in part to performance problems with SSA’s computer system. The SSA system manages large amounts of data across multiple SSA and DDS computer systems. Over half of DDS directors (27 of 51) reported that one of the challenges to medical evidence collection was performance problems with SSA’s integrated computer system, and most (38 of 51) reported that improvement in the stability or responsiveness of the system would add a great or moderate value to the DDSs’ medical evidence collection efforts. SSA Has Made Progress in Developing Options for Submitting Records Electronically, but More than Half Are Still Submitted on Paper One of SSA’s goals is to receive all medical records electronically. SSA maintains several avenues for providers to submit medical evidence online, and nearly all DDS directors (48 of 51) reported that DDS outreach to providers very often addressed options for electronic submission. Some providers, however, have told DDS officials they find SSA’s online submission options inconvenient, difficult to use, or beyond their technical expertise. For example, many providers do not use SSA’s Electronic Record Express Web site to submit records, although it was designed to provide an efficient option for submitting medical records. This Web site limits the number of files that can be sent at one time, which is problematic for large providers such as big hospitals or medical centers. Additionally, infrequent users must call a designated DDS official to reset expired passwords if too much time has passed between submissions. SSA officials told us some providers opt to pay a commercial service to submit medical records, because the service provides for the submission of many files at once, which can be a more efficient option for providers of large volumes of medical records. SSA has recently deployed its own tool for submission of many files at once, called Webservices, but to use this option, medical providers must develop their own software interface to SSA’s Web site. Although SSA provides some technical support, some providers may still find this option beyond their technical expertise. As of November 2008, only two medical record providers were using Webservices. SSA officials noted that additional providers have expressed interest in using WebServices but the agency temporarily limited its use to these two because of limits on the system’s capacity that it intends to resolve after a planned upgrade. DDS professional relations officers at a 2007 conference of the National Association of Disability Examiners noted various difficulties they face encouraging providers to use SSA’s Web site for submitting evidence online. In order to use online options for submitting medical records to SSA, some providers with electronic medical record systems may either need to convert files or print and scan them. In some cases, providers may find this too time consuming to be feasible. Although some providers have registered as Web site users, the difficulties encountered were enough to make them stop using it. A DDS professional relations officer said that they were getting so many calls from providers having problems with the Web site that they had to designate someone to handle the calls. On the other hand, the Mississippi DDS had early success encouraging providers to use the Web site by contracting with a former SSA official who provided detailed “start to finish” guidance on how to use the Web site. SSA held conferences in two cities in March 2008 to give its Web site users an opportunity to express their concerns, and made some modifications to the Web site in July 2008, but SSA has conducted only limited study of the problems with electronic submission of medical records or analyzed the barriers various groups of providers face using the site (such as small- and medium-volume users), and they have not developed a strategy for overcoming these barriers. The agency has made progress responding to some user concerns, for example, by enabling claimants’ representatives to view clients’ folders online, but SSA has not developed a strategy to address the concerns of other user groups. SSA’s efforts to realize its electronic submission goal also are hindered by the uneven pace of the medical community’s acceptance of electronic records. Despite a presidential call for widespread adoption of electronic health records by the year 2014, the Robert Wood Johnson Foundation estimated that less than one-fifth of responding U.S. physicians (17 percent) had at least basic electronic health records and only about 4 percent had fully functional electronic records systems. Nationwide, in September 2008, SSA received 52 percent of records for disability claims on paper, 21 percent through online submission, and 27 percent by fax. (See fig. 6.) One large provider accounts for most of the records SSA receives online. In September 2008, 57 percent of online submissions came from this large medical record copy service. We found variation among the DDSs in the percentages of records received online. In September 2008, 13 DDSs received more than 25 percent of records online while another 11 DDSs received less than 10 percent. DDSs varied in the percentage of records received by electronic fax, with 10 DDSs receiving less than 15 percent of records by fax, and 5 DDSs receiving more than 50 percent. Although providers have submitted an increasing share of records via fax and online over the last few years, the growth in nationwide use of online submission options has slowed in recent months. SSA Is Beginning to Transform Its Process with Computer-to-Computer Requests and Receipts of Records in Uniform Formats While encouraging providers to submit medical records electronically speeds the collection of medical evidence, SSA is participating in preliminary tests of new computer processes that are expected to bring substantial additional efficiencies. With these new procedures, SSA computers request and receive electronic medical records directly from providers’ computers—records in uniform formats that SSA’s computer system can search and use to begin analysis of the claimant’s condition. The electronic images of medical records they currently use are not as suited for analysis as are electronic medical records in uniform formats. For example, currently, DDS examiners cannot electronically search a record or file for particular diagnoses and test results. Instead they must review all the medical records—hundreds of pages of records in some cases—in order to find the pertinent evidence. Most surveyed DDS directors (32 of 51) reported that options for submitting medical evidence in these new formats would be of great or very great value. In its strategic plan for fiscal years 2008 to 2013, SSA established a goal to transform its medical evidence collection process by automatically requesting and receiving electronic medical records through a nationwide health information network. This network is expected to enable medical providers to securely exchange electronic medical records in uniform formats. This will enable SSA to automatically search and analyze the records at the start of the disability determination process. Software will flag medical records that contain references to diagnoses and tests specified in SSA’s medical listings, and thus help examiners promptly determine whether claimants have impairments that qualify as disabilities. To help encourage the use of these processes, SSA is working with other agencies and health providers to develop electronic methods to request, receive, and analyze electronic medical records. For example, SSA and a Boston hospital have launched a prototype effort by which SSA electronically queries the hospital’s computer and retrieves the hospital’s electronic medical records for specific claimants. SSA plans to expand the Boston initiative to additional providers in the future. However, industry standards and protocols need to be further developed before this process can be replicated widely. For example, standards have only recently been developed for the document format used in the Boston initiative called the “continuity of care document.” This format is an electronic exchange standard for sharing patient summary information. In addition, challenges remain in electronic authorization procedures designed to protect the privacy of patients’ health records, as we have reported in previous reports and testimonies. Conclusions The collection of medical evidence in the disability determination process poses many challenges. The DDSs are operating in a high-volume environment and must balance reasonable efforts to obtain complete medical information with the need for timely determinations. Medical providers have constraints on their time and resources as well, and typically focus on diagnosis and treatment rather than assessment of functional ability. The difficulties some DDSs have in obtaining requested medical records and ensuring that claimants attend consultative exams suggest opportunities for continued improvement in the medical evidence collection process. Some DDSs have independently developed varied approaches to respond to these challenges; and all DDSs might benefit from learning from one another and testing and adopting some of these approaches, as appropriate. SSA, however, currently lacks some important data necessary to evaluate these approaches and identify promising practices, which might be shared to promote more timely and complete collection of relevant medical evidence by all DDSs. Meanwhile, SSA efforts to improve the use of consultative examinations and the collection of medical records proceed as the medical community undertakes a major transformation from paper to computer records. With a presidential goal of widespread adoption of electronic medical records by 2014, increasing numbers of providers may have certified electronic records systems capable of fulfilling DDS records requests in electronic formats. As a high-volume user of these records, SSA has incentives to keep pace with industry standards. As such, the prospect of electronically requesting and receiving medical records being explored by SSA and a Boston hospital, and in the development of the nationwide health information network, among other projects, holds promise for achieving even greater efficiencies in medical evidence collection for disability cases in the long run. In the near term, SSA has opportunities to realize greater efficiencies in the collection of medical evidence by encouraging providers to submit records online, saving both time and money by dispensing with inefficient copying and scanning. SSA has taken measures to improve its online submission options, but some providers continue to face difficulties using them and utilization remains limited. Reasons for this are unknown, even to SSA. An evaluation that studies the utilization of SSA’s online submission options, identifies barriers to wider usage, and develops strategies to address these barriers, may help SSA identify cost-effective ways to encourage wider use of online submission methods, especially as more providers begin to use electronic medical records. Recommendations for Executive Action To foster timely and effective collection of medical evidence for disability determinations, we recommend that the Commissioner of SSA identify DDS medical evidence collection practices that may be promising, evaluate their effectiveness, and encourage other DDSs to adopt effective practices where appropriate. As a part of these evaluations, the Commissioner should work with the DDSs to find cost-effective ways to gather consistent data on the effectiveness of DDS medical evidence collection activities. Such data should include key indicators, such as the proportion of requests that yield medical records, the timeliness of medical record receipts, and how frequently claimants fail to attend consultative exams. To achieve a more timely and efficient collection of medical records by encouraging medical evidence providers to submit records electronically, until the nationwide health information network is in operation, we recommend that the Commissioner of SSA conduct an evaluation of the limited utilization of its online submission options. This evaluation should include an analysis of the needs of small, medium, and large providers; identify any barriers to expanded use; and develop strategies to address these barriers. Agency Comments We provided a draft of this report to officials at SSA for their review and comment. In its comments, SSA agreed with our findings and recommendations. Specifically, SSA noted the need for consistent nationwide data but indicated that this is complicated by fact that each DDS uses one of 5 separate case processing systems. To address this limitation, SSA plans to include consistent management data in its common disability case processing system, currently in the planning stage with implementation to begin in 2011. The agency also described current and planned activities to identify and address barriers to electronic submission of data. SSA’s comments are reproduced in appendix IV. We are sending copies of this report to the Commissioner of SSA and others who are interested. The report is also available at no charge on GAO’s Web site at http://www.gao.gov. Please contact me on (202) 512-7215 if you or your staffs have any questions about this report. Other major contributors to this report are listed in appendix V. Appendix I: Scope and Methodology To determine how Disability Determination Services (DDS) and the Social Security Administration (SSA) collect medical evidence, we used four primary sources of information: (1) a survey of the 51 DDSs including all 50 states and the District of Columbia; (2) in-depth interviews and site visits with 5 states; (3) a review of 100 randomly selected initial claims files and 50 claim files at the appeals level; and (4) analysis of SSA data concerning disability determinations. To assess progress in moving from paper to electronic collection of medical evidence, we reviewed SSA documents concerning SSA and the health industry’s efforts and analyzed data compiled by SSA’s computer system regarding receipts of evidence and discussed efforts to encourage electronic submission with SSA and DDS officials, as well as several medical providers. GAO Survey of DDS Directors on Collection of Medical Evidence for Initial DDS Disability Decisions Our survey of DDSs addressed the timeliness of provider responses to DDS requests for medical records, practices and challenges associated with collecting medical records, practices and challenges associated with obtaining consultative exams, outreach to the medical provider community, and SSA and DDS initiatives associated with medical evidence collection. We pretested the complete survey questionnaire at four of the five DDSs we visited during our site visits and tested selected questions during our fifth DDS site visit. We revised our questionnaire following these pretests, incorporating suggestions and feedback from DDS and SSA regional office officials who reviewed the draft questionnaire during these pretests. In May 2008, we sent confidential access information to each of the 51 DDS directors in the 50 states and the District of Columbia. We received a response from all 51 of these directors, for a 100 percent response rate. We analyzed the survey responses and present selected results in our report. In a few instances, we include results only from DDSs that submitted complete responses and computed national totals from DDS- supplied information. For example, we limited our analysis of DDS responses to questions about receipt of requested medical records to the 37 DDSs that provided the numbers of requested records received within 10 days, 11 to 20 days, 21 to 30 days, more than 30 days, and the number not received. Several DDSs responded to some, but not all of these questions, and other DDSs did not respond to any of these questions. Some of the DDSs estimated their responses while others indicated they were able to compute the information about medical record requests and receipts from their database. One DDS director indicated that the number of records not received included provider responses indicating that the requested records were not available. Another indicated that the number the DDS provided for records not received included instances in which the DDS received records for which no payment was due. Checking with DDS directors in our site visit states, we determined that some of these DDSs used these same approaches, but others did not. In addition, we enforced skip patterns that were published in the survey. State DDS Site Visits We visited DDS in five states—California, Mississippi, New York, Vermont, and Wyoming—to gain a more detailed understanding of the medical evidence collection process, related challenges, and the availability of relevant data. At each of the DDSs we visited, we typically met with the DDS Director, Professional or Medical Relations Officer, and the Information Technology Specialist(s). SSA regional office representatives joined us for some meetings as well. We also met individually with several experienced claims examiners selected by the DDS directors in each state. In addition to describing their collection practices and challenges, DDS officials provided valuable feedback on the content and organization of our questionnaire on medical evidence collection in advance of its release to DDS directors in all 50 states and the District of Columbia. In California and New York, we visited two of those states’ multiple DDS branch offices: Sacramento and Oakland, California; and Albany and Manhattan, New York. During each of these branch office visits we also spoke with experienced claims examiners. The information we obtained from each DDS we visited provided useful context to DDS operations and detailed examples of DDS responses to challenges, but information from these site visits is not intended to describe the operations of all DDSs. We consulted a variety of factors in determining which DDSs to visit including geographic diversity, size, type of administrative computer processing system used, and SSA-provided performance data. These performance data included productivity, accuracy, percentage of claims with at least one invoiced medical record, percentage of all medical records received electronically, and percentage of claims with at least one consultative exam. We selected DDSs with both high and low indicators on these measures to illustrate examples of states with a variety of different medical evidence collection practices. The information we obtained at our site visits is illustrative and not intended to reflect the experiences of DDSs in other states. Table 4 presents some of the indicators we consulted in selecting the five DDSs to visit. Reviews of Random Samples of Claimants’ Folders To obtain more detailed information about the medical evidence collection process, we reviewed two sets of randomly selected, but not projectable, samples of case files: (1) 100 initial disability claims files—electronic folders containing documentation of the disability determination for individual disability claimants and (2) 50 folders for claims decided at the administrative law judge level (ALJ) or appeal. For results from these reviews, see appendixes II and III. To select these 100 initial disability claims folders, we reviewed all DDS decisions during fiscal year 2007 for Supplemental Security Income (SSI) and Disability Insurance (DI) disability benefits and excluded reconsiderations, continuing disability reviews, reopenings, and informal remands. For administrative purposes, we also excluded records that SSA maintained using paper records, rather than certified electronic folders. In order to avoid overrepresentation of claimants who filed for both SSI and DI simultaneously (30 percent of DDS initial decisions in fiscal year 2007), we eliminated duplicate listings of these claimants in our data set. We then randomly selected 100 cases from among the approximately 2.3 million cases in the selected data set. These folders contained copies of SSA and DDS forms used in the development of the case including documentation for both DI and SSI claims. These documents often included medical evidence received from physicians and other providers, claimant and third-party assessments of the claimant’s functional abilities, reports from providers of consultative exams of the claimant, forms providing evaluations of the evidence by DDS medical consultants, DDS forms for obtaining medical source statements from providers, forms and letters used to request medical and nonmedical evidence, evidence submitted by the claimant or his or her authorized representatives, and documents related to the disability determination such as SSA form 831, and Personal Decision Notices and similar notices for denied claims. Similarly, to select a sample of cases decided by SSA ALJ hearings offices, we obtained from SSA an extract of SSA’s Case Processing and Management System data set managed by SSA’s Office of Disability Adjudication and Review. We selected records for decisions by the ALJ hearing offices during the first 6 months of fiscal year 2008 concerning initial claims for SSI and DI disability benefits that had been denied at the DDS initial level. Some had been appealed to the DDS (a “reconsideration”) or to the federal reviewing official, while others were appealed directly to the SSA ALJ hearing office. We also excluded records for which SSA had paper records, rather than certified electronic folders. We randomly selected 50 of these records. SSA staff prepared a CD for each case folder. These electronic folders provided documents compiled by SSA and the DDS during the initial determination, as well as additional documents compiled subsequently, including those obtained during reconsideration of the initial decision by the DDS, documents provided by authorized representatives of the claimant, copies of medical evidence concerning treatment and examinations after the initial determination, medical source statements, an interrogatory, a deposition, and ALJ decision documents. Analysis of SSA Data To obtain more detailed data concerning DDS collection practices and to examine variations among DDSs, we obtained from SSA and analyzed a variety of computerized data. These included data for initial and reconsideration filings received, decided, and pending at year end; filings approved and denied; filings for which one or more medical evidence of record was purchased; filings for which one or more consultative exam was requested; expenditures for purchase of medical records and consultative exams; errors in DDS initial determinations identified by SSA quality assurance the results of evaluations of medical records collected and consultative exam reports by SSA quality assurance reviewers; and responses to medical records obtained via methods, including paper and faxed submissions, and online submission options such as SSA’s Electronic Records Express Web site. We used these data to summarize and compare how DDSs display these data graphically. We also used these data to provide additional information concerning the initial claim case files described above. To conduct limited tests of the reliability of these data we obtained copies of 831 data and Case Processing Management System data from SSA and compared results provided by SSA with results from our analysis of these data sources. Appendix II: Selected Results from Analysis of 100 Randomly Selected Initial Disability Cases The following tables provide selected findings from our review of 100 randomly selected cases for claimants with initial DDS determinations in fiscal year 2007. Appendix III: Medical Evidence Collection Process at the Administrative Hearing Level The process for collecting medical evidence at the administrative hearing level typically differs from the process at the DDS level. If the claimant for disability benefits is dissatisfied with the DDS’s initial decision, he or she can appeal. In many cases the initial appeal is a request for a reconsideration by the DDS. Then, if is the claimant is not satisfied with the DDS decision, he or she can appeal and request a hearing before an administrative law judge (ALJ), who will review the case in light of the evidence gathered by the DDS as well as additional evidence obtained. The responsibility for providing evidence to support the appeal falls on the claimant. A claimant may be represented by an attorney or other representative, to collect the additional evidence on his or her behalf. If necessary evidence is not provided, the ALJ must attempt to fully and fairly develop the evidence. Most claimants who appeal to an SSA hearings office are represented by attorneys or others who enter into agreements with SSA providing payment to the representative, which may be from a specified proportion of awarded retroactive disability benefits in cases where claimants win their appeal. SSA requires ALJs to conduct a prehearing review of all evidence and determine whether additional development is needed. Claimants’ representatives may submit updated medical records. If the ALJ is unable to obtain adequate evidence, the ALJ also can request consultative exams or tests. Similarly, if additional evidence is needed, the ALJ may have an independent medical expert review the file and answer written interrogatories, or testify at the hearing. Some ALJs ask the DDS to gather additional evidence on their behalf. Others have SSA hearings office staff gather evidence for the hearing. ALJs have additional options to obtain opinion evidence from claimants’ providers, including sending interrogatories or questionnaires, requesting testimony at the hearing, and, under certain circumstances, issuing administrative subpoenas. Claimants’ representatives told us that letters describing the possibility of such subpoenas are sometimes sent, but subpoenas are rare. As part of SSA’s continuing efforts to reduce the backlog of claims at the hearing level, it has implemented the Medical Expert Screening Initiative Business Process. This is a new pre-hearing initiative to identify disability claimants whose impairments are most likely to meet the requirements for disability with a pre-hearing interrogatory sent to medical experts. If the medical expert responses to the interrogatories show that a fully favorable decision may be made on the record, without the need for additional evidence or a hearing, the case is referred to an attorney adjudicator in that hearing office to issue the decision, if warranted. ALJs and DDSs use the same definition of disability, but use different administrative guidance. SSA guidance for DDSs is included in SSA’s Program Operations Manual System. Its counterpart for ALJs is called the Hearings, Appeals, and Litigation Law Manual. To obtain information on how medical evidence is collected at the ALJ hearing level, we reviewed electronic copies of 50 claims that were decided at the appeals level during the first half of fiscal year 2008. Claims were randomly selected from all decided initial disability claims nationwide which had a certified, fully electronic folder. The small sample size means that the information we obtained from these selected cases cannot be considered representative of all cases at the appeals level, but it provides examples of how medical evidence is collected at the appeals level. These included 34 fully favorable decisions, 1 partially favorable decision (a changed date for onset of the claimant’s disability), and 10 unfavorable decisions. In 4 cases, the case was dismissed or the claimant withdrew. The tables below summarize results from our review of these cases: ALJs often gather nonmedical as well as medical evidence to reach a decision. They typically observe the claimant during the hearing, in- person, or by video conference. One ALJ wrote, for example, “Furthermore, the state agency consultants did not adequately consider that the claimant’s statements concerning the intensity, persistence and limiting effects of these symptoms are generally credible.” Hearings also sometimes involve evidence from vocational experts—experts in assessing a claimant’s ability to perform various jobs. In 3 of the 50 cases reviewed, the ALJ cited medical-vocational rules as the basis of their decision. By the time the cases we reviewed were decided by the SSA hearings office, medical evidence had typically been added that was not available at the time of the initial DDS decision. In most of these cases, the claimant’s representative collected the new evidence and submitted it to SSA. Often this included evidence from sources that had not provided medical records at the initial DDS level. In several cases the representative obtained a medical source statement from a source that had not previously submitted one, but had provided medical records. In 12 cases, evidence indicated that the claimant’s condition proved more prolonged than the DDS expected. Appendix IV: Comments from the Social Security Administration Appendix V: GAO Contact and Staff Acknowledgments Staff Acknowledgments In addition to the contact named above, Michael J. Collins, Assistant Director; Benjamin P. Pfeiffer; Susan L. Aschoff; Alexander G. Galuten; Catherine M. Hurley; Karen A. Jarzynka; Katherine N. Laubacher; Jennifer R. Popovic; Suzanne C. Rubins; Meghan H. Squires; Vanessa R. Taylor; Rachael C. Valliere; and Walter K. Vance, made key contributions to this report. Related GAO Products Social Security Disability: Management Controls Needed to Strengthen Demonstration Projects. GAO-07-331. Washington, D.C.: September 26, 2008. Federal Disability Programs: More Strategic Coordination Could Help Overcome Challenges to Needed Transformation. GAO-08-635. Washington, D.C.: May 20, 2008. Social Security Disability: Better Planning, Management, and Evaluation Could Help Address Backlogs. GAO-08-40. Washington, D.C.: December 7, 2007. High Risk Series: An Update. GAO-07-310. Washington, D.C.: January 2007. Disability Programs: SSA Has Taken Steps to Address Conflicting Court Decisions, but Needs to Manage Data Better on the Increasing Number of Court Remands. GAO-07-331. Washington, D.C.: April 5, 2007. Social Security Administration: Agency Is Positioning Itself to Implement Its New Disability Determination Process, but Key Facets Are Still in Development. GAO-06-779T. Washington, D.C.: June 15, 2006. Electronic Disability Claims Processing: SSA Is Proceeding with Its Accelerated Systems Initiative but Needs to Address Operational Issues. GAO-05-97. Washington, D.C.: September 23, 2005. Social Security Administration: More Effort Needed to Assess Consistency of Disability Decisions. GAO-04-656. Washington, D.C.: July 2, 2004. Social Security Disability: Commissioner Proposes Strategy to Improve the Claims Process, but Faces Implementation Challenges. GAO-04-552T. Washington, D.C.: March 29, 2004. Electronic Disability Claims Processing: SSA Needs to Address Risks Associated with Its Accelerated Systems Development Strategy. GAO-04-466. Washington, D.C.: March 26, 2004. Social Security Administration: Strategic Workforce Planning Needed to Address Human Capital Challenges Facing the Disability Determination Services. GAO-04-121. Washington, D.C.: January 27, 2004. SSA Disability Decision Making: Additional Steps Needed to Ensure Accuracy and Fairness of Decisions at the Hearings Level. GAO-04-14. Washington, D.C.: November 12, 2003. Electronic Disability Claims Processing: Social Security Administration’s Accelerated Strategy Faces Significant Risks. GAO-03-984T. Washington D.C.: July 24, 2003. Social Security Disability: Efforts to Improve Claims Process Have Fallen Short and Further Action is Needed. GAO-02-826T. Washington, D.C.: June 11, 2002 Social Security Disability: Disappointing Results from SSA’s Efforts to Improve the Disability Claims Process Warrant Immediate Attention. GAO-02-322. Washington, D.C.: February 27, 2002. SSA Disability Redesign: Actions Needed to Enhance Future Progress. GAO/HEHS-99-25. Washington, D.C.: March 12, 1999.

Summary: The timely collection of relevant medical evidence from providers, such as physicians and psychologists, is key to the Social Security Administration (SSA) process for deciding whether an estimated 2.5 million new claimants each year have impairments that qualify them to receive disability benefits. The initial determinations are generally made by state agencies called Disability Determination Services (DDSs). We evaluated: (1) the challenges, if any, in collecting medical records from the claimants' own providers and ways SSA and the DDSs are responding to these challenges; (2) the challenges, if any, in obtaining high-quality consultative exams and ways SSA and the DDSs are responding to these challenges; and (3) the progress SSA has made in moving from paper to electronic collection of medical evidence. We surveyed 51 DDS directors, visited 5 state DDSs, reviewed sample case files, and interviewed officials with SSA, DDSs, and associations for claimants and providers. Obtaining timely and complete medical records is a challenge to DDSs in promptly deciding disability claims, and DDSs have responded with additional provider contacts and adjustments to their payment procedures. Although DDSs pay most medical providers for medical records and SSA pays the DDSs to cover these expenses, 14 of 51 DDSs reported the percentage of requests for which they did not receive records was 20 percent or more in fiscal year 2007. In response to this challenge, all DDSs conduct follow-up with providers and claimants to urge them to provide records. Over half of the DDSs (34 of 51) have also implemented more timely payments for records and six increased the amount they pay. Although SSA evaluates DDS collection of medical records, it does not compile key data necessary to identify and share promising collection practices. Recruiting and retaining qualified providers is a challenge to obtaining consultative exams needed to supplement insufficient medical records. For example, 41 of 51 DDSs reported routinely asking claimants' own providers to perform these exams; yet 34 reported providers never or almost never agree to do so. DDSs directors in our survey believe that current payment rates account for some of the difficulty recruiting and retaining consultative exam providers. In response to these challenges, 32 DDSs rely on medical providers who specialize in performing disability evaluations, and 20 pay providers for time spent preparing for appointments claimants fail to attend. SSA evaluates evidence from consultative exams, but these evaluations and the data they yield are too limited to identify and share promising DDS practices. SSA has made progress moving to electronic collection of medical records, but faces challenges in fully implementing electronic retrieval and analysis of medical evidence. SSA now uses electronic images instead of paper copies of new claimants' records. Though SSA seeks to obtain all records electronically and provides options for online submission of records, only one large provider accounts for most of the records submitted online, and about half of all records received are on paper. To date, SSA has taken only limited action to identify and analyze the barriers providers face in using current electronic record submission options, and has not developed a strategy to address them. In the long run, SSA is participating in an advanced prototype to collect medical records in formats that can be searched and analyzed by electronically querying a hospital's records database and directly retrieving the claimants' records.

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Summarize: A FORMER Queensland internet king is believed to have been a key figure behind FBI action against three major gambling websites in the United States. Daniel Tzvetkoff, who had been facing 75 years jail in the US, has done a deal with prosecutors which has seen him freed on bail and living in a secret New York location. The Courier-Mail reported today that the deal came after Tzvetkoff - a Brisbane boy wonder, who started a company with school mates at 13 - became embroiled in a massive, $543 million stew of money laundering, bank fraud and conspiracy that could bring down the world of online gambling. Federal prosecutors in New York yesterday charged the founders of the three largest internet poker companies in the US with bank fraud, money laundering and other gambling offenses and are seeking penalties upward of $3 billion. Federal authorities also froze approximately 76 bank accounts in 14 countries that contain proceeds from the alleged offenses. They also shut down five internet domain names used by the three companies to host their games. A total of 11 defendants, including the founders of Poker Stars, Full Tilt Poker and Absolute Poker, were named in the indictment unsealed Friday. The Courier-Mail reported today that two of those companies Full Tilt Poker and PokerStars, had been seeking $100m they believed Tzvetkoff had taken from them. Tzvetkoff was arrested in April last year and charged with money laundering, bank fraud and conspiracy for processing $543m in illegal internet gambling earnings through his British Virgin Islands corporation, Intabill, the trading arm of his now liquidated Brisbane company, BT Projects. He was mysteriously bailed last August, and US authorities are using his inside knowledge of the gambling industry to go after gaming companies. In yesterday's indictment, federal prosecutors explain that poker companies operating offshore cannot accept most forms of payment "in connection with the participation of another person in unlawful internet gambling." Since most banks in the US would not process their payments, the companies circumvented federal law by making payments appear to be transactions for other types of merchandise. In the indictment, federal prosecutors say they arranged for payment processors with bank accounts in the US to receive payments from US gamblers and disguise them as payments for products such as jewelry or golf balls. Of the billions of dollars in payment transactions that the Poker Companies tricked US banks into processing, approximately one-third or more of the funds went directly to the Poker Companies as revenue through a charge players must make on almost every poker hand played online. That scheme worked for a while until some banks caught on. By 2009, they had shut down many fraudulent bank accounts used by the poker companies. Two of the defendants later came up with a scheme to persuade the principals of a few small, struggling banks to process payments in return for multi-million investments. In one case, they persuaded the vice chairman of SunFirst Bank in Saint George, Utah, to process gambling transactions in return for a $10 million investment. "As charged, these defendants concocted an elaborate criminal fraud scheme, alternately tricking some US banks and effectively bribing others to assure the continued flow of billions in illegal gambling profits," said Preet Bharara, US Attorney in Manhattan. "Moreover, as we allege, in their zeal to circumvent the gambling laws, the defendants also engaged in massive money laundering and bank fraud." Read more on Tzvetkoff in today's print edition of The Courier-Mail. The U.S. government disrupted the weekend—and life—plans of Cory Albertson and thousands of others like him who earn much of their living playing poker online. Federal prosecutors have targeted the three largest online poker companies doing business in the U.S., charging their founders with money laundering and bank fraud and seizing five of the companies' domain names. Alexandra Berzon has details. For nearly eight years, Mr. Albertson has camped out every Sunday on his couch with his laptop to play No Limit Hold'Em with thousands of other online players at PokerStars or Full Tilt Poker. He might pocket $500 for the day, or lose money, but sometimes he'd win big, as much as $75,000 at a time, adding a nice sum to his income as a freelance writer in Austin, Texas. The U.S. Justice Department announced Friday it was blocking players in the U.S. from accessing Full Tilt Poker, along with other online poker sites, accusing 11 people of bank fraud and of illegally operating gambling websites. The government seized accounts run by the sites that held money stored by players. The crackdown came after years of tension between the sites and the U.S. government, which long held that online gambling is illegal. The case could test the claim by the poker site operators that operating a poker site online isn't illegal because, they say, as a game that involves skill, poker is not gambling. The government action shined a light on a game that had become a vocation for thousands of Americans and pastime for millions of casual players. Online poker has spawned an industry of celebrity players, bloggers, coaches and television shows sponsored by the sites now charged with criminal activity. "We understood there were issues," said Jonathan Wein, a professional poker player who runs a business teaching poker online. "We never assumed there'd be some type of black-out overnight." Congress passed a law in 2006 that forbid financial institutions from processing financial transactions related to online gambling. That made it much more difficult for websites to accept money from players and pay them back. Many sites left the U.S after the law passed. Others, namely Full Tilt Poker and PokerStars, built lucrative businesses by catering to U.S. players from overseas. PokerStars is based in the Isle of Man, Full Tilt is regulated by Alderney in the U.K.'s Channel Islands and Absolute Poker, another site, is in Costa Rica. The approach seemed to work, allowing the sites to build a market that last year included about 1.8 million people in the U.S. who played poker online for money, according to PokerScout, which tracks online poker site data. Other organizations say there are many more players. The sites saw around $16 billion in wagers from U.S. players last year, with the bulk of that taken in by Full Tilt Poker and PokerStars, according to PokerScout. The indictment last week and accompanying civil complaint alleged that the companies skirted the 2006 ban on electronic transfers related to gambling by working with third parties to create fictitious websites for fake companies to trick banks into thinking that it was not an Internet poker site. One was Green2YourGreen, an apparent environmentally-friendly household products company. In later years the sites invested in small U.S. banks in exchange for their cooperation in processing funds, the government alleges. Enlarge Image Close Agence France-Presse/Getty Images Last year about 1.8 million people in the U.S. played poker online for money, according to PokerScout. Full Tilt said in a statement that it "is, and has always been committed to preserving the integrity of the game and abiding by the law." Representatives for PokerStars and Full Tilt didn't respond to requests for comment. Absolute Poker representatives could not be reached. Regular online players said in interviews that while they were aware that financial transactions had become difficult under U.S. law, they turned a blind eye to the specifics. "All of the fake websites and phony bank accounts—that was something the players assumed was taking place," Mr. Albertson said. "But we're totally detached from that. We didn't know exactly how it works. We just knew it did work." In 2009, the government began seizing bank accounts managed by third-party processors, such as Allied Systems Inc. and Account Services, which held millions of dollars of player money. Poker players say that their money was reimbursed by the sites. Yet since then, cashing out began to take more time and checks were issued under numerous different account names, the players said. In a statement on its website PokerStars said that players would get their money back. Mr. Wein said he had about $15,000 in his poker accounts. More than the fate of that money, he's concerned that poker playing and teaching won't be as lucrative now. "Our entire business plan has changed overnight," he said. Players may move to other sites, although many say they're hesitant to do so. The number of U.S. players using Bodog, a gambling website that wasn't named in the government suit, showed a 21% rise in player numbers on Saturday compared to a week earlier, a gain of around 150 players, according to Dan Stewart, who runs PokerScout. In interviews, several professionals said they may transfer to live games—even though that is likely to bring in less income, in part because the players can't play as many games at one time. Some also said they are considering moving abroad. "Online I can play 500 tournaments a week," Mr. Wein said. "In a casino it might be three to five." Mr. Wein was among the players this weekend who said they'll consider moving abroad so they can continue playing. For Mr. Albertson, the crackdown is likely to bring a new career path—and schedule. "I was joking with my girlfriend, 'I guess now I have to learn how to socialize with people on Sundays,'" he said. Corrections & Amplifications The U.S. Justice Department said it was blocking players in the U.S. from accessing Full Tilt Poker, along with other online poker sites. A previous version didn't specify that the shutdown applied to the U.S. only. Write to Alexandra Berzon at alexandra.berzon@wsj.com

Summary: The online poker world is reeling after this weekend's massive US government crackdown on online poker sites. The Department of Justice indicted the owners of the three largest sites-Full Tilt Poker, PokerStars, and Absolute Poker-for bank fraud, illegal gambling, and money laundering on Friday, shutting down all three sites, the Wall Street Journal reports. The indictment said the defendants used fraudulent methods to trick financial institutions into processing payments on their behalf following a 2006 law that made such payments illegal. It said they sometimes arranged for money from US gamblers to be disguised as payments to hundreds of non-existent online merchants purporting to sell merchandise such as jewelry and golf balls. The government also seized 76 bank accounts, many of which contained players' money. The government knew exactly where to strike, because it persuaded the "boy genius" who helped invent the sites' e-commerce systems to help them, the Courier-Mail reports. Daniel Tzvetkoff had already fallen out with the sites, who were suing him for $100 million, when the government arrested him in April. He was released on bail in August-after a secret meeting with prosecutors, in which he gave them everything they needed to take down the sites. Click for more on the "boy genius."

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Summarize: WASHINGTON — The federal government is preparing for a large-scale cyber attack on government accounts Tuesday as federal officials try to learn the lessons from the Associated Press hacking that sent stocks into a brief but expensive tailspin last month. A senior federal official shared documents with BuzzFeed Monday that show the government is warning agencies that a cyber assault Tuesday could affect agencies across the the federal government. “On 7 May 2013, a group of mostly Middle East- and North Africa-based criminal hackers are preparing to launch a cyber attack campaign known as ‘OpUSA’ against websites of high-profile US Government agencies, financial institutions, and commercial entities,” reads a warning sent across federal agencies earlier this month. “The attacks likely will result in limited disruptions and mostly consist of nuisance-level attacks against publicly accessible webpages and possibly data exploitation. Independent of the success of the attacks, the criminal hackers likely will leverage press coverage and social media to propagate an anti-US message.” The Huffington Post reported Monday that the attacks — prompted by criticisms of U.S. foreign policy — have “an ambitious list of targets, including the websites of the White House, the Defense Department, the FBI, Bank of America and Chase Bank.” Warnings of the attack come amidst criticisms of White House handling of a hacking attack last month, when the AP’s Twitter feed was infiltrated and reported explosions at the White House injured President Obama. That sent stocks into a brief tailspin that worried market observers. In the aftermath of that attack, the senior government official told BuzzFeed government agencies need to prepare to quickly respond to attacks on media organizations. The official criticized the White House for letting the hacked AP tweet go officially unanswered until the White House briefing later in the day. In addition to being prepared for hacks to their own social media and other accounts, the official said, government agencies need to be prepared to quickly dispel false accounts on hacked social media feeds. The documents shared with BuzzFeed Monday show federal agencies readying themselves for Tuesday’s planned attack. It’s not clear what precautions, if any, the White House is taking. A White House official did not immediately respond to requests for comment late Monday night. A collective of hacker groups plans to attack the websites of major government agencies and banks on Tuesday to protest American foreign policy. For weeks, the groups, which include Anonymous, have used social media to publicize their planned operation, dubbed "#OpUSA." In a post on the file-sharing site Pastebin, one member of Anonymous laid out an ambitious list of targets, including the websites of the White House, the Defense Department, the FBI, Bank of America and Chase Bank. “Anonymous will make sure that this May 7th will be a day to remember,” another post from Anonymous said, adding the planned attacks are meant as a response to "multiple war crimes" committed by the United States in Iraq, Afghanistan and Pakistan. In the past, however, Anonymous has hyped plans to launch coordinated attacks but ended up having little impact, security experts say. Last month, Anonymous launched #OpIsrael, which promised to “wipe Israel off the internet.” That operation was "a total failure," Ronen Kenig, director of security solutions for Radware, told The Daily Beast last month. Tuesday's planned operation still has the U.S. government's attention. The Department of Homeland Security issued an alert last week warning about the event that "likely will result in limited disruptions and mostly consist of nuisance-level attacks against publicly accessible webpages." Hackers based in the Middle East and North Africa plan to participate in the attacks targeting U.S. government, financial, and commercial institutions, according to the DHS alert, which was first reported by the security blog Krebs on Security. "Independent of the success of the attacks, the criminal hackers likely will leverage press coverage and social media to propagate an anti-US message," the alert said. Tuesday's operation comes as hackers based in the Middle East have generated increased attention. Since last fall, a group that calls itself the Izz ad-Din al-Qassam Cyber Fighters has claimed responsibility for disrupting the websites of several major U.S. financial institutions, including JPMorgan Chase, Wells Fargo and Bank of America. U.S. officials claim the group is linked to the Iranian government, but have not offered proof of such a connection. In recent weeks, another hacking group that calls itself the Syrian Electronic Army has taken credit for hacking the Twitter accounts of several news agencies, including NPR, Reuters, BBC and Al Jazeera. Security experts say the group appears to have ties to the Syrian government. The group's attack last month on the Twitter account of the Associated Press sent out a fake tweet about an explosion at the White House that injured President Obama. The tweet, which was re-tweeted thousands of times within minutes, caused the Dow Jones Industrial Average to drop sharply before the stock market index quickly recovered. UPDATE: By 4 p.m. Tuesday, the operation appeared to have largely fizzled. The website Hackers News Bulletin claimed to keep a list of more than 600 sites that were defaced in the operation, dubbed #OpUSA. But most of the sites listed -- if they had been brought down -- were largely unknown to the general public. One site, yourchessgames.com, appeared to have been replaced Tuesday with a message from Anonymous. Marty Meyer, president of Corero Network Security, told The Huffington Post that his company had several customers on the hackers' list of purported targets, but "we haven't really seen anything yet." He said #OpUSA appeared to have "no real focus" and doubted the hackers had access to the large botnets, or networks of infected computers, needed to launch large-scale attacks that can bring down major websites. "It's kind of a non-event," Meyer told The Huffington Post.

Summary: Hackers have spent weeks warning of a giant attack on US government agencies and banks-and today is the day, they say. "Anonymous will make sure that this May 7th will be a day to remember," said the hacker group in a post, per the Huffington Post. The attacks are retaliation for US "war crimes" in Afghanistan, Pakistan, and Iraq, the group noted. The government is preparing, but it doesn't seem hugely scared, expecting "limited disruptions" and "nuisance-level attacks against publicly accessible webpages." The hackers are "mostly Middle East- and North Africa-based," according to government documents shown to BuzzFeed. Among the targets of the attack, dubbed #OpUSA, are websites of the White House, Pentagon, FBI, Bank of America, and Chase Bank, HuffPo notes. Major warnings from Anonymous haven't always had big results, according to experts. But "independent of the success of the attacks, the criminal hackers likely will leverage press coverage and social media to propagate an anti-US message," the government documents say.

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Write a title and summarize: Active adult stem cells maintain a bipotential state with progeny able to either self-renew or initiate differentiation depending on extrinsic signals from the surrounding microenvironment. However, the intrinsic gene regulatory networks and chromatin states that allow adult stem cells to make these cell fate choices are not entirely understood. Here we show that the transcription factor DNA Replication-related Element Factor (DREF) regulates adult stem cell maintenance in the Drosophila male germline. A temperature-sensitive allele of DREF described in this study genetically separated a role for DREF in germline stem cell self-renewal from the general roles of DREF in cell proliferation. The DREF temperature-sensitive allele caused defects in germline stem cell self-renewal but allowed viability and division of germline stem cells as well as cell viability, growth and division of somatic cyst stem cells in the testes and cells in the Drosophila eye. Germline stem cells mutant for the temperature sensitive DREF allele exhibited lower activation of a TGF-beta reporter, and their progeny turned on expression of the differentiation factor Bam prematurely. Results of genetic interaction analyses revealed that Mi-2 and Caf1/p55, components of the Nucleosome Remodeling and Deacetylase (NuRD) complex, genetically antagonize the role of DREF in germline stem cell maintenance. Taken together, these data suggest that DREF contributes to intrinsic components of the germline stem cell regulatory network that maintains competence to self-renew. Adult stem cells maintain tissues during the lifetime of an organism by replenishing short-lived differentiated cells such as in the skin, intestinal epithelium and blood. Adult stem cells also give rise to differentiated cells upon injury in tissues such as skeletal muscle and lung. To maintain tissue homeostasis, daughter cells produced by adult stem cell divisions must make the critical cell fate decision between self-renewal and the onset of differentiation. Deviation from the tightly regulated balance between these alternate fates may result in poor tissue maintenance or cancerous growth of poorly differentiated precursor cells[1]. Adult stem cells are thus in a bipotential state, able to self-renew or to initiate differentiation in response to extrinsic signals from the surrounding microenvironment[2,3]. This bipotential state relies on intrinsic transcriptional and chromatin programs that dictate how stem cells respond to external signals from the niche. Here we show that in Drosophila male germline adult stem cells, the transcription factor DNA Replication-Related Element Factor (DREF) and members of the Nucleosome Remodeling and Deacetylase (NuRD) complex, Mi-2 and Chromatin Assembly Factor 1 (Caf1, also known as p55), act antagonistically to regulate the balance between germline stem cell self-renewal and differentiation. In the adult testis, two populations of stem cells, germline stem cells (GSCs) and somatic cyst stem cells (CySCs), reside adjacent to a group of post-mitotic somatic cells called the hub. The hub cells and the CySCs provide a microenvironment for GSC maintenance[4]. Both the germline and the somatic cyst stem cells divide asymmetrically: after division, one daughter remains in contact with the hub and self-renews while the other daughter is displaced away from the hub and initiates differentiation[5,6]. In the germline stem cell lineage, the differentiating daughter, termed the gonialblast, initiates four rounds of transit amplifying mitotic divisions with incomplete cytokinesis. The resulting 16 interconnected germ cells undergo premeiotic S phase in synchrony, become spermatocytes, and commit to terminal differentiation[7]. In the somatic cyst cell lineage, the differentiating daughter cell becomes a post-mitotic cyst cell, two of which enclose each gonialblast and its progeny, providing a supportive microenvironment necessary for the proper differentiation of the germ cells[8–10]. We identified a missense allele of DREF (DREFts) that revealed a role for DREF in the maintenance of Drosophila male GSCs. DREF is known to function in cell growth, cell division, and DNA replication[11–13]. However, its role in these housekeeping processes has masked identification of other biological functions of DREF. The protein encoded by DREFts is able to function in cell division and cell survival but is defective for maintenance of GSCs in the testes. Analysis of mutant germline stem cells demonstrated defects in downstream targets of TGF-beta signaling. Genetic interactions with this allele of DREF suggested that DREF functions antagonistically to the chromatin regulators Caf1/p55 and Mi-2 to maintain GSCs. We propose that DREF may promote expression of self-renewal genes by overcoming transcriptional repression by a Mi-2 containing chromatin-remodeling complex. A temperature-sensitive allele of DREF (DREFts) was discovered in an EMS-mutagenesis screen to identify genes required cell-autonomously for GSC maintenance in the Drosophila male germline. When GSCs homozygous for DREFts and negatively marked for GFP were generated using the FLP/FRT system [14] and grown at 25°C for 3 days post clone induction, 84. 2±3. 0% of the testes scored (n = 49) had at least one marked DREFts GSC adjacent to the hub. This is comparable to 95±3. 0% of control testes (n = 38) with marked GSCs wild-type for DREF adjacent to the hub. However, the percentage of testes with at least one marked homozygous DREFts mutant GSC steadily decreased over time, so that by day 12 post clone induction, only 16. 7±4. 7% of testes (n = 91) contained one or more marked homozygous DREFts mutant GSCs, compared to 82. 0±9. 1% of testes (n = 64) in control flies (Fig 1A) (p<0. 001). Surprisingly, DREFts did not have the same effect on CySC maintenance. The percentage of testes with marked CySCs in DREFts/+ and wild-type controls were comparable at day 3 post clone induction (75. 6% of DREFts/+ (n = 38) to 78. 3% (n = 49) of control testes) and also at day 12 post clone induction (39. 2±14. 5% of DREFts/+ (n = 41) to 44. 3±6. 6% (n = 62) of control testes) (Fig 1B). Complementation analysis indicated that the mutation responsible for the failure to maintain GSCs mapped to the DREF locus. The DREFts allele failed to complement Df (2L) BSC17 [Df (DREF), which deletes the DREF locus], as well as two independently-generated alleles, DREFKG09294 (referred to here as DREFnull) and DREFNP4719 for early germ cell loss. Analysis of testes by phase contrast microscopy revealed that an average of 94. 6± 5. 6% testes (n = 58, p<0. 0001) from newly eclosed DREFts/Df (DREF) males grown at 25°C had late-stage germ cells (elongating spermatids) but lacked early germ cells (spermatogonia and primary spermatocytes), while 0% of testes from sibling DREF mutant/+ males lacked early germ cells (Fig 1C and 1D). The presence of elongating spermatids in testes from newly eclosed DREFts/Df (DREF) males suggests that GSCs and early germ cells were initially present during development but were eventually lost due to differentiation. Immunofluorescence analysis of mutant testes confirmed the absence of GSCs and early germ cells; testes from newly eclosed DREFts/Df (DREF) males grown at 25°C lacked Vasa-positive germ cells at the apical tip (Fig 1F), while testes from sibling controls had an abundance of Vasa-positive germ cells at the apical tip (Fig 1G). DREF function is also required for maintenance of female GSCs/early germ cells. In ovaries isolated from DREFts/Df (DREF) mutant adult females grown at 25°C and examined three days after eclosion, 26. 9% (n = 26) of ovarioles contained developing germ cell cysts and egg chambers but empty germaria (S1 Fig). The loss of early germ cells in DREFts/Df (DREF) males reared at 25°C was rescued by expression of a UAS-DREF cDNA transgene in early germ cells, confirming that the mutation causing GSC loss is in the DREF locus and that DREF function is required in germ cells for GSC maintenance. As assessed by phase contrast microscopy, only 5. 37± 5. 56% (n = 58) of testes from DREFts/Df (DREF) males grown at 25°C contained early germ cells, while 100% (n = 57) of testes from DREFts/Df (DREF) males expressing UAS-DREF cDNA under control of nanos-Gal4-VP16 (Fig 1E) and 93. 3 ± 8. 80% (n = 59) of testes from DREFts/Df (DREF) males expressing UAS-DREF cDNA under control of Vasa-Gal4 (Fig 1E and Table 1) contained early germ cells. Immunofluorescence analysis revealed the presence of GSCs adjacent to the hub in DREFts/Df (DREF) mutant testes expressing UAS-DREF cDNA under control of nanos-Gal4-VP16 (Fig 1H). The GSC loss phenotype of DREFts/DREFnull flies was temperature-dependent. As assayed by phase contrast microscopy, 100 ± 0% (n = 82) of testes isolated from DREFts/DREFnull transheterozygous flies grown at 22°C had early germ cells present on the day of eclosion. However, when DREFts/DREFnull flies were grown at 25°C, only 20. 2 ± 12. 9% (n = 375) of testes scored contained early germ cells on the day of eclosion. DREFts/DREFnull flies grown at 30°C failed to survive to adulthood and died in late third instar larval and/or pupal stages (Table 2). Sequencing of the DREF coding region revealed that the DREFts allele had two amino acid substitutions (Methionine 651 to Leucine and Glycine 652 to Alanine), which occur in a domain that has been shown to be responsible for co-factor binding in Drosophila DREF[15,16]. Germ cells homozygous mutant for DREFts still expressed DREF protein as assayed by immunostaining 3 days and 6 days post clone induction. In contrast, at day 3 post clone induction, DREF protein expression was not detected in DREFnull mutant germ cells by immunofluorescence using anti-DREF antibodies (S2 Fig). Furthermore, GSCs in testes from DREFts/DREFnull versus DREFnull/+ flies grown at 22°C until eclosion then shifted to 30°C for 2 days failed to show significantly different levels of DREF protein (0. 63±0. 15 n = 18 GSCs versus 0. 72±0. 21 n = 24 GSCs, Materials and Methods). The DREFts allele allowed separation of the role of DREF in stem cell maintenance from a general role of DREF in cell survival and proliferation. Male GSCs homozygous mutant for the DREFts allele appeared to be lost because they differentiate more often than self-renew. While homozygous DREFts mutant GSCs were rapidly lost from the apical hub region of the testis at 25°C, their marked clonal progeny appeared to differentiate normally to at least the spermatocyte stage, as assessed by phase contrast microscopy. Cysts of spermatocyte clones homozygous for the DREFts allele examined on day 4 post clone induction contained 16 germ cells per spermatocyte cyst, as expected after 4 rounds of transit amplification divisions, and were comparable in size to neighboring wild-type spermatocytes (Fig 2A, 2A’ and 2C). In contrast, loss of DREF function in germline clones homozygous for the DREFnull allele or due to expression in early gem cells of an RNAi hairpin directed against DREF mRNA under control of nanos-Gal4-VP16 resulted in defects in germ cell survival, growth, proliferation, and/or differentiation. At day 4 post induction of marked clones homozygous for DREFnull, 32. 6% of the testes scored contained no DREFnull clones, 24. 5% had marked GSCs and/or spermatogonia but no late spermatocyte cysts homozygous for DREFnull, and only 42. 9% contained cysts with recognizable spermatocytes at 25°C (Fig 2D). The cysts of DREFnull/DREFnull mutant spermatocytes in the clones appeared smaller in size compared to neighboring DREFnull/+ germ cell cysts (Fig 2B and 2B’). In addition, about 25% of the germ cell cysts that made it to the spermatocyte stage exhibited fewer than 16 cells per cyst (Fig 2C). Together, these observations suggest that lack of DREF function may cause developing germ cell cysts to either die, grow slowly, or fail to initiate the differentiation program. Similarly, knockdown of DREF function in late spermatogonia and spermatocytes by expressing UAS-DREF-RNAi under the control of a Bam-Gal4 driver resulted in extensive cell death and absence of meiotic and post-meiotic stages (S3 Fig). Consistent with the finding that homozygous DREFts germ cells proliferate and differentiate normally, cells homozygous for DREFts in the eye were able to proliferate and differentiate, unlike cells homozygous for DREFnull. Flies with eyes entirely composed of cells homozygous mutant for DREFnull generated using the EGUF-hid method [17] and reared at 25°C had very small eyes (Fig 2G). In contrast, eyes entirely homozygous mutant for DREFts appeared similar in size and morphology to wild type controls, whether grown at 25°C (Fig 2E) or 30°C (Fig 2F). Additionally, eyes in DREFts/ DREFnull transheterozygous flies grown at 25°C were wild type in size and appearance (Fig 2H). The temperature-sensitivity of the DREFts allele allowed analysis of how GSCs are lost when shifted from permissive to non-permissive temperature. GSCs present when DREFts/DREFnull males were grown at 22°C until eclosion were lost within 2–3 days upon shifting the males to 30°C (Fig 1I). On the day of eclosion, DREFts/DREFnull males grown at 22°C had an average of 6. 6± 0. 9 GSCs around the hub (n = 22 testes), compared to 8. 2± 0. 6 GSCs in heterozygous control testes (n = 27 testes). In contrast, testes from DREFts/DREFnull males grown at 22°C then shifted to 30°C for 3 days after eclosion had an average of 0. 8± 0. 7 GSCs (n = 69 testes), while sibling control testes from DREF mutant/+ males had an average of 8. 19±1. 4 GSCs per testis (n = 59 testes) (p<0. 0001) (Fig 1I). The loss of DREF function when DREFts/DREFnull males were shifted to 30°C did not appear to affect the rate of GSC division or survival. The percentage of GSCs in mitosis scored by immunostaining for phosphorylated-Threonine 3 of histone H3 (PH3) was similar in testes isolated from DREFts/ DREFnull transheterozygotes (3. 90 ± 0. 65%, n = 154 GSCs) and sibling control flies (4. 49 ±2. 84%, n = 178 GSCs) that were grown at 22°C, shifted to 30°C at eclosion and then held at 30°C for two days (Fig 3A). Additionally, TUNEL assays failed to detect dying GSCs in testes from either DREFts/ DREFnull transheterozygotes or control flies (n = 83 and n = 94 GSCs, respectively), while in both cases some dying spermatogonial cysts were detected. The loss of GSCs in DREFts/ DREFnull testes did not appear to be due to loss of hub-GSC adhesion. Expression of UAS-E-Cadherin-GFP specifically in early germ cells using the nanos-Gal4-VP16 driver resulted in localization of E-Cadherin-GFP protein to the hub-GSC interface in both DREFts/ DREFnull (Fig 3C–3C’’’) and DREFts/+ (Fig 3D–3D’’’) GSCs in testes isolated from males grown at 22°C until eclosion then shifted to 30°C for two days. Expression of E-Cadherin-GFP using the UAS-GAL4 system in early germ cells did not rescue the loss of GSCs in DREFts/ DREFnull temperature-shifted flies, as testes from DREFts/ DREFnull males shifted to 30°C for two days contained similar numbers of GSCs per testis whether or not they expressed UAS-E-Cadherin-GFP under control of nanos-Gal4-VP16 (average of 0. 9±0. 2 GSCs per testis (n = 52 testes) and 0. 8±0. 7 GSCs per testis (n = 59 testes), respectively). DREFts/ DREFnull germ cells adjacent to the hub also oriented their centrosomes as in wild-type GSCs, where one centrosome is positioned adjacent to the hub-GSC interface throughout the cell cycle, resulting in oriented GSC division[5]. In testes isolated from DREFts/ DREFnull males grown at 22°C then shifted to 30°C for two days after eclosion, an average of 92. 78 ± 3. 76% (n = 201 from 62 testes) of GSCs that remained next to the hub and contained two centrosomes had one centrosome adjacent to the hub-GSC interface, similar to control DREFts/+ GSCs (94. 1 ± 1. 07%, n = 239 GSCs from 30 testes) (Fig 3B). Hub-GSC adhesion and oriented centrosome positioning are two features of GSCs that depend on activation of the JAK-STAT pathway in response to Unpaired (Upd) ligand secreted from the hub[10,18]. Consistent with intact hub-GSC attachment and correct positioning of centrosomes, GSCs in testes from DREFts/ DREFnull males grown at 22°C then shifted to 30°C for two days post-eclosion expressed STAT92E protein, a downstream target of JAK-STAT signaling, at levels comparable to sibling control GSCs (Fig 3E–3E’ and 3F–3F’). Many GSCs homozygous mutant for DREFts showed reduced expression of a reporter of TGF-beta signaling, Dad-LacZ, compared to their DREFts/+ neighbors next to the hub. In wildtype, Dad-LacZ is primarily expressed in GSCs, the gonialblast, and in later stage somatic cyst cells[19]. In many germ cells next to the hub made homozygous for DREFts by FLP induced mitotic recombination, LacZ staining was often drastically reduced compared to neighboring DREFts/+ GSCs (Fig 4A–4A’’’). The effect was variable, however, with some GSCs homozygous for DREFts appearing to have normal levels of LacZ, likely leading to the observed gradual loss of DREFts mutant GSCs. As a population, mutant GSCs showed a 30. 3% reduction (P<0. 05, n = 14 GSCs in 11 testes, Fig 4E) in Dad-LacZ staining intensity relative to control GSCs (n = 17 GSCs in 11 testes) within the same testes as quantified by ImageJ (Materials and Methods). Consistent with a reduced response to TGF-beta signaling, the differentiation marker Bag of Marbles (Bam) was expressed earlier than normal in germ cells in DREFts/DREFnull testes. Bam protein is normally detected by antibody staining in 4- to 16-cell spermatogonial cysts[20]. Likewise, using a reporter line driving GFP-tagged Bam protein expressed from its own promoter and regulatory elements[21], Bam-GFP expression, as detected by anti-GFP immunostaining, was first detected in 4 cell cysts, with very few 2 cell cysts scoring positive. GSCs from DREFts/ DREFnull males grown at 22°C until eclosion then shifted to 30°C for two days did not express Bam-GFP in GSCs adjacent to the hub (n = 36 GSCs from 14 testes), similar to GSCs from sibling controls that were either DREFts/+ or DREFnull /+ (n = 100 GSCs from 12 testes) (Fig 4B–4B’’’). Likewise, gonialblasts, defined as single germ cells away from the hub containing a dot-fusome, from DREFts/DREFnull temperature shifted males also did not express Bam-GFP (n = 23 gonialblasts from 14 testes), similar to the gonialblasts in heterozygous controls, in which Bam-GFP was not detected (n = 31 gonialblasts from 12 testes). However, there was a marked increase in the percentage of Bam-GFP positive two-cell cysts in DREFts/DREFnull mutant testes, where 35. 1% of the two-cell cysts analyzed (n = 37 counted in 14 testes) were positive for Bam-GFP, compared with only 4. 6% of two-cell cysts scored as positive for Bam-GFP in testes from DREFts/+ or DREFnull /+ sibling controls (n = 44 cysts counted in 12 testes) (Fig 4C’–4C’’’ and 4D). Function of DREF appeared to be required for maintenance of germline stem cell state even under the condition of forced ectopic expression of the ligand Upd, which activates the JAK-STAT signal transduction pathway. In control DREFts/+ or Df (DREF) /+ flies, ectopic expression of UAS-Upd in early germ cells under the control of nanos-Gal4-VP16 at 25°C resulted in 100% (n = 68 testes) of testes examined containing an overabundance of GSC-like Vasa-positive cells with dot spectrosomes, as well as many CySC-like cells positive for Zfh-1 (Fig 5A–5A’’’). Under the same conditions, in contrast, only 4. 98±5. 64% (n = 66 testes) of DREFts/Df (DREF) testes ectopically expressing UAS-Upd under control of nanos-Gal4-VP16 exhibited an overabundance of GSC and CySC-like cells. Rather, the vast majority of testes (95. 02%, n = 66) from DREFts/Df (DREF) males carrying nanos-Gal4-VP16; UAS-Upd grown at 25°C had an abundance of CySC-like cells but few or no germ cells as assayed by immunostaining for Vasa (Fig 5B–5B’’’). The abundance of Zfh-1 positive CySC-like cells in many of the DREFts/Df (DREF) testes suggested that sufficient Upd was expressed early, prior to the GSC loss (Fig 5C–5C’’’). The DREFts allele provided a sensitized background in which to screen for genetic interactors important for male GSC differentiation vs. maintenance. When DREFts/ DREFnull flies were raised at 25°C, 79. 8±12. 9% of testes (n = 375) from newly eclosed males had few or no early germ cells and displayed elongating spermatid bundles close to the apical tip (Fig 6A). Strikingly, reducing the gene dosage of either Chromatin assembly factor 1, p55 subunit (Caf-1/p55), a subunit of multiple chromatin-modifying complexes including the NuRD complex, or Mi-2, a subunit of the Nucleosome Remodeling and Deacetylase (NuRD) complex and the dMEC complex, rescued the DREF early germ cell loss phenotype. While only 20. 2±12. 9% (n = 375) of testes from newly eclosed DREFts/DREFnull males had early germ cells (Fig 6A), 93. 9±5. 35% (n = 62) of testes from DREFts/DREFnull; Caf19-2/+ males contained both plentiful early germ cells and abundant spermatocytes as assessed by phase contrast microscopy (Fig 6B). Similarly, 91. 8±7. 5% (n = 76) of testes from DREFts/DREFnull; Df (Mi-2) /+ and 55. 6±4. 0% of testes from DREFts/DREFnull; Mi-24/+ males contained many early germ cells and spermatocytes (Fig 6C). Immunofluorescence analysis revealed that reducing Caf1 or Mi-2 dosage by half in a DREFts/DREFnull background restored the presence of GSCs next to the hub (Fig 6D–6F). The suppression of the DREFts/DREFnull GSC loss phenotype by lowering the dosage of either Mi-2 or Caf1, both of which are components of the NuRD complex, suggests that DREF and the NuRD complex may act antagonistically to influence GSC maintenance. However, lowering the dose of Rpd3 or Mbd-like, two other subunits of the NuRD complex, did not suppress the early germ cell loss phenotype in DREF mutant testes as assessed by phase contrast microscopy (Fig 6G). Similarly, lowering the dose of XNP, a member of the DREF-containing XNP/dATRX repression complex, or Putzig, a member of the DREF-TRF2 complex, did not affect the germ cell loss phenotype, with only 29. 1±10. 9% (n = 74) and 23. 3±10. 4% (n = 41), respectively, of testes scored by phase contrast microscopy containing visible early germ cells (Fig 6G). TRF2, which is male lethal, could not be tested in the same manner. Mi-2 is required cell-autonomously for GSC maintenance in the testis. GSCs made homozygous mutant for either the Mi-24 (frameshift) or the Mi-26 (premature stop codon) allele using the Flp-FRT system were lost over time. At day 3 post clone induction, 65. 9±16. 1% of testes scored (n = 33) for Mi-24 and 70. 7±11. 5% of testes scored (n = 66) for Mi-26 contained marked homozygous mutant GSCs, compared to control clones, for which 82. 5±5. 9% of testes scored (n = 55) contained marked GSCs. By day 8 post clone induction, however, only 14. 3±15. 2% (n = 44) for Mi-24 and 17. 2±7. 9% (n = 70) for Mi-26 of testes scored contained marked homozygous mutant GSCs, while the percentage of control testes with marked GSCs was significantly higher (72. 3±9. 1%, n = 76, p<0. 001) (Fig 7A). Germ cells homozygous mutant for Mi-2 were able to differentiate into spermatocytes. Expression of RNAi directed against Mi-2 using the nanos-Gal4-VP16 driver also resulted in early germ cell loss, confirming a role for Mi-2 in GSC maintenance (Fig 7B and 7C). Similarly, RNAi targeting Caf1 expressed using the nanos-Gal4-VP16 driver also resulted in GSC loss, demonstrating a requirement for Caf1 for GSC maintenance (S4 Fig). Homozygous Mi-24 or Mi-26 mutant GSCs remaining at day 5 post clone induction expressed DREF protein at levels comparable to neighboring Mi-2/+ heterozygous GSCs, as detected by immunostaining (Fig 7D). However, later stage germ cells lacking Mi-2 function demonstrated prolonged DREF expression, visible as persistent high levels of DREF protein in spermatocyte cysts in germline clones homozygous mutant for Mi-2, compared to neighboring Mi-2/+ spermatocytes (Fig 7E–7E’’’). Drosophila DREF was initially isolated based on its ability to bind the DNA-Replication Related Element (DRE), an 8bp sequence 5’TATCGATA’3 located upstream of many genes related to DNA replication. Binding of DREF protein to the DRE has been shown to activate expression of genes regulating cell division, including DNA polymerase, E2F, and Cyclin A[22–24]. In addition, Drosophila DREF has been shown to act downstream of the TOR [13] signaling pathway and Drosophila DREF and its human homolog, hDREF, have also been shown to control cell growth by regulating the expression of ribosomal genes and histone H1[13,25,26]. The DRE bound by DREF is known to be a key cis-regulatory component of a class of core promoters different from the canonical TATA box containing promoters[27]. Binding of DREF protein to the DRE recruits TRF2, a transcription factor related to TATA-box-binding protein (TBP), directing recognition of these alternate core promoters, regulating, for example expression of the proliferating cell nuclear antigen (PCNA) [28]. DREF Protein binds to and potentially regulates 1,961 distinct loci in the genome[29]. For example, DREF has been shown to regulate chromatin by: 1) by activating transcriptional expression of chromatin regulators such as brahma, moira and osa[22,30], Mes4[31], and HP6[32], 2) physically interacting with XNP/dATRX and potentially targeting them to regions in the genome[16], 3) competing with the chromatin insulator Boundary Element Association Factor 32 (BEAF32) for a mutual binding site[29,33], and 4) regulating the HET-A, TART, TAHRE array (HTT) array in Drosophila[34]. Previous reports, and our work here, showed that null alleles of DREF have defects in cell division and cell growth in tissues ranging from the eye[12,22], salivary glands[12], the imaginal wing discs[35], and the testis (this report). The DREFts allele we identified a role for DREF in self-renewal of germ line stem cells, genetically separable from the previously-defined role of DREF in cell proliferation. The DREFts allele did not strongly affect cell viability and division in the eye, and somatic cyst stem cells (CySCs) homozygous mutant for the DREFts allele were able to self-renew and differentiate normally. However, in flies homozygous mutant for the DREFts allele, GSCs were not maintained, although the progeny of mutant GSCs were able to differentiate into spermatocytes. It is possible that the DREFts allele might affect specific physical interactions between DREF and particular binding partner (s) required in GSCs but not in many other cell types, resulting in stem cell loss. Intriguingly, previous research suggests that the domain mutated in DREFts (the CR3 domain) does not contribute to the DNA binding or dimerization functions of DREF, but may play a role in the ability of DREF to bind and interact with different cofactors[36]. Overexpression of the CR3 domain of DREF has been shown to have a dominant-negative effect on DREF function, possibly by competing for normal binding partners of endogenous DREF[36]. In support of this view, DREF has been shown to bind to the chromatin remodeling factor XNP through its CR3 domain[16]. When bound to XNP, DREF can function as a transcriptional repressor, in contrast to its typical role as a transcriptional activator when bound to TRF2[16]. However, XNP showed no genetic interaction with the DREFts/DREFnull mutant phenotype, suggesting that either XNP is not dosage sensitive or that the role of DREF in GSC maintenance is not mediated through the DREF-XNP complex. Although an RNAi screen by Yan et al. [37] showed a requirement for DREF in the female germline, it is important to note that in our hands complete loss of function of DREF (through either RNAi or null alleles) causes severe phenotypes likely due to the role of DREF in housekeeping functions required for cell growth and division, which parallels the multiple, complex defects Yan et al. [37] notes in knockdown of DREF in the female germline. The JAK-STAT signaling pathway plays pivotal roles in regulating the two adult stem cell populations in the testis. In male GSCs, the JAK-STAT signal transduction pathway is required cell autonomously for adhesion to the hub and oriented divisions, but not for self-renewal[18]. Many mutants that result in GSC loss, such as NURF301 [38] have reduced JAK-STAT signaling, possibly resulting in loss of GSC adhesion to the hub and subsequent differentiation. In contrast, DREFts/DREFnull GSCs had normal levels of STAT protein and did not appear to be defective in hub-GSC adhesion, as evidenced by localization of E-Cadherin and proper centrosome orientation, suggesting that they are not likely lost due to defects in JAK-STAT signaling. JAK-STAT activation is also required in CySCs for self-renewal[18,39]. Forced activation of JAK-STAT signaling in the testes, either by expressing constitutively active JAK in CySCs or by forced ectopic expression of the activating ligand Upd in germ cells, results in an apparent failure of CySCs to differentiate[18]. As a consequence of the early CySC-like state, the neighboring germ cells fail to differentiate and the testis is filled with GSC-like and CySC-like cells. This overproliferation of GSC-like cells due to forced activation of the JAK-STAT pathway can mask or override the GSC-loss phenotype in his2Av or GEF26 mutants[40,41]. Although, like his2Av and GEF26 mutant GSCs, DREFts GSCs are lost to differentiation, the outcome of combining DREFts with forced expression of Upd ligand in germ cells was strikingly different, with the DREFts/Df (DREF) germ line stem cell loss phenotype predominating even with forced activation of JAK-STAT signaling due to ectopic expression of Upd. Thus, while his2av and GEF26 may be important for fine-tuning the balance between self-renewal and differentiation, the function of DREF altered by the temperature-sensitive mutation may be intrinsically required for maintaining the GSC state. Genetic interaction studies uncovered a novel role for Caf1 and Mi-2, components of the Nucleosome Remodeling and Deacetylase (NuRD) chromatin-modifying complex in repressing DREF-mediated self-renewal. Reducing the gene dosage of either Caf1 or Mi-2 function by half was able to rescue the GSC-loss phenotype in a DREFts/DREFnull mutant background. Our results are consistent with previous studies indicating an antagonistic relationship between DREF and Mi-2. Reduction of Mi-2 gene dosage by half had been shown previously to enhance defects caused by DREF overexpression in the eye, consistent with Mi-2 antagonizing DREF[42]. Yeast two-hybrid screening identified the human homolog of Mi-2, CHD4, as a binding partner of human DREF and pull-down assays confirmed this association in Drosophila, showing that Mi-2 physically associates with DREF[42]. Mi-2 has been shown to interact with the DNA-binding domain of DREF, thereby inhibiting the ability of DREF to bind DNA in vitro[42]. Additionally, recent work with hDREF has shown that the reciprocal regulation as well: hDREF has been shown to increase SUMOylation of Mi-2 protein, thereby increasing dissociation of Mi-2 from chromatin[43]. Our data also indicated an inhibitory interaction between DREF and CAF1, raising the possibility that Mi-2 might act as a part of the NuRD complex to inhibit DREF function in male germline stem cells. The genetic interactions between Mi-2 or Caf1 and the DREFts allele suggest that Mi-2 and Caf1 can act as repressors of GSC self-renewal. Interestingly, we also found that Mi-2 and Caf1 are required for GSC maintenance in a genetic background wild-type for DREF function. The Mi-2/NuRD complex is known to play broad roles in reorganizing chromatin architecture to promote silencing[44], and Mi-2/NuRD has been shown to localize to hundreds of regions in the genome of Drosophila[42]. One possibility is that complete loss of Mi-2 function may cause general de-repression of genes important for cell-identity, self-renewal, and differentiation. Indeed, loss of Mi-2 in spermatocytes causes activation cryptic promoters at many sites in the genome, leading to massive misexpression[45]. It may be that Mi-2 plays a similar role in restraining misexpression during the early stages of germ cell development as well. Previous studies suggest that Drosophila male GSCs are sensitive to changes in the transcript levels of genes required for self-renewal versus differentiation[41]. One role of DREF in Drosophila male GSCs may be to exclude Mi-2 from promoters of self-renewal genes, thereby allowing higher levels of expression at these loci. Under conditions of reduced DREF function in the DREFts mutant flies, Mi-2 may gain abnormal access to self-renewal genes, dialing down their expression and tilting the balance of GSC fate towards differentiation. We propose that in the context of DREFts/DREFnull background, a half-dose reduction of Mi-2 or CAF1 function is sufficient to allow the partially functional DREF protein expressed in the DREFts mutant to overcome Mi-2-mediated repression of self-renewal genes and tilt the balance back towards GSC maintenance. All crosses were grown at 25°C on standard molasses media unless otherwise stated. DREF mutant alleles used in this study include 1) al1, dpov1, DREFts, b1, pr1, FRT40A/SM6a (derived from an EMS mutagenesis screen), 2) DREFKG09294 (from BDSC); this allele is a P-element insertion into the 5’UTR of DREF and has been previously reported to be a null allele that expresses little to no DREF protein[13], 3) DREFKG09294, FRT40A (from DGRC), 4) Df (2L) BSC17 (referred to as Df (DREF), from BDSC) is a deletion that spans from pelota to DREF, and 5) DREFNP4719 (from DGRC), a P-element insertion in the 5’ UTR of DREF. Other mutant alleles used in this study include 1) Caf19-2, a deletion allele of Caf1 (gift from Joseph Lipsick, Stanford University[46]), 2) Df (3R) BSC471 (referred to as Df (Caf1), from BDSC), 3) Mi-24 and Mi-26 alleles (from BDSC and gift from J. Müller[47]), 4) Df (3L) BSC445 (referred to as Df (Mi-2), from BDSC), 5) Df (3R) BSC471 (referred to as Df (Putzig), from BDSC), 6) Df (3R) XNP1 (referred to as Df (XNP1), from BDSC), 7) Df (3L) Exel7208 (referred to as Df (Rpd3), from BDSC), 8) Df (3R) Exel6153 (referred to as Df (Mbdl), from BDSC) and 9) Nurf3014, a deletion allele of Nurf301 (from BDSC). Other fly stocks used include 1) al1, dpov1, b1, pr1, FRT40A (an isogenized version of FRT40A from BDSC), 2) yw, hs-flp122; FRT40A, Ubi-GFP, 3) eyeless-Gal4, UAS-Flp; GMR-hid, 2LCL FRT40A (17), 3) UAS-DEFL #6–1 [48] 4) bam: : bam-GFP, a transgenic line driving Bam-GFP under the control of bam promoter (a gift from D. McKearin (21) ) 5) UAS-Upd [49], and 6) UAS-DREF[22]. al, dp, DREFts, b, pr, FRT40A, UAS-DREF/SM6a and DREFts, UAS-Upd were generated by recombining DREFts chromosome onto the UAS-DREF or UAS-Upd chromosome, respectively. The following Gal4 drivers were used to drive UAS transgress in a cell-type specific manner, 1) yw; ; nanos-Gal4VP16 (a gift from R. Lehmann[50]), 2) UAS-dicer2; ; nanos-Gal4VP16,3) yw; ; Vasa-Gal4,4) yw; ; Bam-Gal4, UAS-dicer2, (Bam-Gal4 lines was a gift from D. McKearin[21]) and 5) C587-Gal4; tub-Gal80ts; UAS-dicer2 (C587-Gal4 line was a gift from S. Hou). RNAi lines for DREF (BDSC#35962), Caf-1 (BDSC#34069 and VDRC#105838) and Mi-2 (VDRC#107204 and 10766) were used in this study. Temperature shift experiments for germ cell loss analysis in DREF transheterozygotes were performed by growing flies at 22°C until eclosion, and then shifting to 30°C on the day of eclosion. Dissections were performed on day of eclosion, or on one, two, or three days post eclosion. For analysis of DREF function in the eye, clones were generated by crossing DREF alleles on FRT40A chromosomes to eyeless-Gal4, UAS-Flp; GMR-hid, 2LCL FRT40A/SM6a. These crosses were grown at either 25°C, or at 30°C one day after the cross was set up. Testes were dissected in 1X phosphate-buffered saline (PBS) and fixed in 4% paraformaldehyde diluted in PBS for 20 minutes at room temperature, washed twice in PBS with 0. 1% TritonX-100, permeabilized in PBS with 0. 3% TritonX-100 and 0. 6% sodium deoxycholate for 30 minutes and blocked in PBS with 0. 1% TritonX-100 and 3% bovine serum albumin for 30 minutes. Testes were incubated overnight at 4°C in primary antibodies against DREF (mouse, 1: 100; gift from Dr. Andreas Hochheimer[28]), Vasa (goat, 1: 50; Santa Cruz Biotechnology), Zfh-1 (rabbit, 1: 5000; gift from R. Lehman), Traffic Jam (guinea pig, 1: 5000; gift from D. Godt) LI ET AL NAT CELL BIOL 2003, Armadillo (mouse, 1: 10; Developmental Studies Hybridoma Bank (DSHB) ), DE-Cadherin (rat, 1: 10; DSHB), FasIII (mouse, 1: 10; DSHB), alpha-spectrin (mouse, 1: 10; DSHB), Green Fluorescent protein (rabbit 1: 400–1: 1000; Invitrogen and Sheep 1: 1000; Abd-Serotec), gamma-tubulin (mouse, 1: 50; Sigma), phosphor-Histone3 Threonine3 (rabbit, 1: 100; Upstate Biotechnology/Millipore), and STAT92E (rabbit, 1: 100; gift from E. Bach[51]). Testes were incubated in appropriate secondary antibodies were from the Alexa Fluor-conjugated series (1: 500; Molecular Probes) and mounted in VECTASHIELD medium containing DAPI to visualize DNA (Vector Labs). Tunel Assays were performed using the In Situ Cell Death Detection Kit, TMR red by Roche. Immunofluorescence images were taken using the Leica SP2 Confocal Laser scanning microscope. Phase and clonal analysis images were captured using a Zeiss Axioskop microscope and SPOT RT3 camera by Diagnostic Instruments or CoolSNAePz camera by Phomometrics. Images were processed using Adobe Photoshop and Illustrator CS6. Nuclear protein quantification was performed using ImageJ software and comparing the relative levels of the stained protein of interest (standardized to DAPI to control for sample depth) between experimental and control GSCs-. To perform RNAi knockdown in the germline, males from strains containing the RNAi hairpin of interest were crossed to UAS-dicer2; ; nanos-Gal4VP16 virgins and grown at 25°C for 4 days after which the progeny of the cross were shifted to 30°C. Testes were isolated from males of the cross on the day of eclosion and 7 days post eclosion. In other cases, to follow the time course of stem cell loss, the progeny of crosses were grown at 18°C until eclosion, shifted to 30°C on the day of eclosion and males from the cross were dissected at different days post-shift to 30°C. Somatic RNAi knockdown was performed by crossing the RNAi hairpin strains to virgin females containing the somatic lineage driver C587-Gal4; tub-Gal80ts; UAS-dicer2. Crosses were performed at 18°C until eclosion, when adults were shifted to 30°C and dissected 3- and 7-days post temperature shift. Knockdown in transit amplifying cells and later stages was performed by crossing the RNAi hairpin to; ; BamGal4, UAS-dicer2. Crosses were grown at 25°C for 4 days and then shifted to 29°C until eclosion and then they were dissected.

Title: DREF Genetically Counteracts Mi-2 and Caf1 to Regulate Adult Stem Cell Maintenance Summary: Many adult tissues are maintained throughout life by the dual ability of adult stem cells to produce progeny that either self-renew or differentiate to replace specialized cells lost to turnover or damage. Although signals from the surrounding microenvironment have been shown to regulate the choice between self-renewal and onset of differentiation, the intrinsic gene regulatory programs that set up and maintain this bipotential state are not well understood. In this report we describe antagonistic components of an intrinsic stem cell program important for maintaining the balance between self-renewal and differentiation in Drosophila male germline adult stem cell lineage. We identified a temperature-sensitive mutant in the transcription factor DNA Replication-related Element Factor (DREF) gene that disrupts the ability of germline stem cells to self-renew, but not stem cell viability, ability to divide or differentiate under the same conditions. DREF mutant germline stem cells showed defects in the TGF-beta signaling pathway, a pathway that is critical for maintaining the stem cell population. Genetic interaction analyses revealed that Mi-2 and Caf1/p55, components of the Nucleosome Remodeling and Deacetylase complex genetically antagonize the role of DREF in germline stem cell maintenance. We propose that DREF contributes to a transcriptional environment necessary for maintaining a bi-potential stem cell state able to properly respond to extrinsic niche signals.

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Summarize: Please continue to support our quest to locate our beautiful 15 year old daughter, Brianna Herrmann!Your donations can make all the difference! We are using the funds to:1. Work with the right people.2. Gather neccessary supplies.3. Finance the search efforts.4. Offer a larger reward.5. Use the best resources to bring Brianna home ASAP!Brianna Herrmann, (15 y/o), was last seen in San Diego, CA on April 27th, 2015. Brianna is 5'4" tall, 118lbs, has blonde hair and brown eyes. She may be accompanied by Dean Henderson, aka Timothy Dean Rivera (20 y/o). Dean is 5'7" tall, 130lbs, has blonde hair and brown eyes. We really need the public to help locate her and bring her home safely! He preys on younger vulnerable girls, and is preventing Brianna from returning home or contacting her friends and family who love her dearly!If you have any information, please contact The Brianna Herrmann Hotline, (844)-7HELPUS (844-743-5787), which will be monitored 24/7 or call 911.Thank you for any donations to support our search! We feel your support, we see your contributions, and our spirits are lifted.**Please Note: once we bring Brianna home, we plan to donate any leftover donations to help other families find their missing children. This is a horrible experience no parent should ever suffer!** Monday was Rhona Kauffman's birthday, and all she wanted was for her daughter Brianna Herrmann to be brought home safely. "She's being held somewhere and we know she's fighting to get home. It's the worst thing to ever happen to someone, I'm just falling apart," Kauffman told Dateline. "My daughter and I are super close, super close. I have to keep fighting, that's what a mother has to do." According to San Diego Police, Kauffman's 15-year-old daughter Brianna vanished after sneaking away from home in California on April 29th in her mother's car. That vehicle was impounded by Los Angeles police a little over a week later, after being found abandoned. Officials identified the last person seen with the 15-year-old as Timothy 'Dean' Rivera, 19, who police say is possibly selling drugs. Kauffman says her daughter met the teen on the beach in early April. The teen left everything behind, including her wallet and retainer, according to Kauffman. She believes her daughter was lured out of her home and was not planning on being gone long. Herrmann was reportedly last seen with Timothy 'Dean' Rivera, 19, who is described by the San Diego Police Department as 5'7" tall, weighing 130 lbs. with long blond hair. San Diego Police Department There have been several reported sightings of Brianna over the past several weeks; one in Irvine, California, and another in Los Angeles. Kauffman says that her daughter had Snapchatted and texted to a friend saying she was being held captive behind a locked door in a home in Los Angeles several days after she vanished. According to KGTV, police raided the home in May where Brianna was believed to be and found the room she had described to her friend, but she was no longer there. Los Angeles Police did not return Dateline's call for comment. "You don't know if your child is being harmed, you don't know where she is. She tried to get back to us so we're trying everything to get her back," said Kauffman. Officer Humberto Hernandez of the San Diego Police Department told Dateline that they are the lead department on the case, but they could not release anymore information at this time. Family and friends have continued to update the 'HelpFindBriannaHerrmann' Facebook page in order to keep spreading awareness about the teen's disappearance. Kauffman, a lawyer by profession, says she has taken nearly seven weeks off work in order to spend her days searching for Brianna. "I can never give up, I never will. I have to get her back. A mother never gives up." Brianna Herrmann is described as 5'4" tall, weighing 115 pounds, with blonde hair and brown eyes. If you have any information that can help bring Brianna home, please contact the San Diego Police Department at (619) 531-2000. The family is reportedly offering a $10,000 reward for information that helps bring Brianna home safely. SAN DIEGO - A local family says their teenage daughter is being held against her will and San Diego police are not pursuing the case. "I can't function. I can't work, I can't eat, I'm not sleeping. I can't imagine … my daughter and I are so close," said Rhona Kauffman. Kauffman said her 15-year-old daughter Brianna Hermann sneaked out of their La Jolla apartment on April 28. Kauffman told 10News she believes Brianna went to Los Angeles with a 20-year-old man she recently met. While Kauffman acknowledged her daughter did run away, she said she believes Brianna, a freshman at University City High School, is being held against her will. According to Kauffman, Brianna told one of her friends that she was in Los Angeles being held captive behind a locked door with a mattress on the floor. On Tuesday, Los Angeles police raided the home where Brianna was believed to be located but she and the man were not found. Police found everything that Brianna had described to her friend, including the room and the mattress on the floor. Kauffman, a lawyer, tried to describe what the last two weeks have been like: "It's very devastating. It's the most devastating thing you could possibly imagine of anything in your life … it's just not real; it's horrible." Kauffman told 10News that San Diego police will not get involved because they say it is simply a case of a runaway. However, Kauffman believes her daughter's life is in danger, and the family is continuing to spread the word around Los Angeles and San Diego, as well as on social media.

Summary: Brianna Herrmann, 15, has been missing since April 29. That was when she reportedly sneaked out of her San Diego home and vanished-though not entirely without a trace. The car she made off in, her mother's, was found abandoned in early May; potential sightings of her in LA and Irvine have been called in. And there's the ominous Snapchat messages. The teen's mother, Rhona Kauffman, tells NBC News via Dateline that Brianna Snapchatted with a friend soon after she went missing, saying she was being held against her will in an LA home. KGTV last month reported that the LAPD swarmed what they believed to be that home on May 12. They found a room matching the description Brianna had given her friend-it held a mattress on the floor-but she was not there. Neither was the man she's believed to be with: Timothy "Dean" Rivera, 19 or 20, who Brianna met on the beach the month she disappeared. NBC News describes him, by way of police, as a possible drug dealer; the family is more blunt. A GoFundMe page set up to raise funds to assist in the search alleges that Rivera "preys on younger vulnerable girls." Kauffman doesn't think her daughter intended to leave for good, noting she left her wallet and retainer at home, and the Help Find Brianna Herrmann Facebook page says that "Information was received that she has been seen possibly being forced to prostitute herself in the El Sereno area of Los Angeles." A $10,000 reward is being offered to anyone who can locate Brianna. In the meantime, "I have to keep fighting," says Kauffman, a lawyer who has put work on hold for nearly two months to search for her girl. "That's what a mother has to do."

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Summarize: A group of New York City atheists is demanding that the city remove a street sign honoring seven firefighters killed in the Sept. 11, 2001 terrorist attacks because they said the sign violates the separation of church and state. The street, “Seven in Heaven Way,” was officially dedicated last weekend in Brooklyn outside the firehouse where the firefighters once served. The ceremony was attended by dozens of firefighters, city leaders and widows of the fallen men. “There should be no signage or displays of religious nature in the public domain,” said Ken Bronstein, president of New York City Atheists. “It’s really insulting to us.” Bronstein told Fox News Radio that his organization was especially concerned with the use of the word “heaven.” “We’ve concluded as atheists there is no heaven and there’s no hell,” he said. “And it’s a totally religious statement. It’s a question of separation of church and state.” He was nonplussed over how his opposition to the street sign might be perceived – especially since the sign is honoring fallen heroes. “It’s irrelevant who it’s for,” Bronstein said. “We think this is a very bad thing.” David Silverman, president of American Atheists, agreed and called on the city to remove the sign. “It implies that heaven actually exists,” Silverman told Fox News Radio. “People died in 9-11 but they were all people who died, not just Christians. Heaven is a specifically Christian place. For the city to come up and say all those heroes are in heaven now, it’s not appropriate.” “All memorials for fallen heroes should celebrate the diversity of our country and should be secular in nature. These heroes might have been Jews, they might have been atheists, I don’t know but either way it’s wrong for the city to say they’re in heaven. It’s preachy.” City leaders seemed dumbfounded by the atheists’ outrage because no one complained about the sign as it was going through a public approval process. “It’s unfortunate that they didn’t raise this as an issue while it was undergoing its public review either at the community board level or when it came before the city council on their public agenda,” said Craig Hammerman, the district manager for Brooklyn Community Board Six. Hammerman told Fox News Radio that the community was “solidly behind this proposal. Not a single person stood up to speak out against it. I think it’s a little late in the process for someone to be bringing this up now.” The criticism brought condemnation from Bill Donohue, president of the Catholic League. “There’s more than a phobia about Christianity going on here,” Donohue said. “There’s a deep-seated visceral hatred of religion and particularly Christianity. That’s what’s driving this because most people who are not believers wouldn’t blink an eye at this.” Silverman said he would not be surprised if atheists are vilified for their criticism of the street sign – suggesting they were simply being patriotic. “If we’re opposed to this sign, we’re somehow opposed to honoring the heroes,” he said. “The attacks on 9-11 were an attack on America. They were an attack on our Constitution and breaking that Constitution to honor these firefighters is the wrong thing to do. “The patriotic and right thing to do is to obey our own law and to realize that we are a diverse nation, a melting pot full of different views,” Silverman added. The local and national atheist organizations said they’ve offered alternative names that would still honor the firefighters but without any religious affiliation. Bronstein suggested they call the street, “We Remember The Seven – 9-11.” He said that would be “more appropriate.” But the city has no intention of removing the street sign. If that’s the case, Bronstein said he may consider a lawsuit. There's a new street sign hanging on Richards Street in Red Hook that honors seven firefighters from Engine 202 and Ladder 101 who were killed in the 9/11 terrorist attacks. The sign says "Seven in Heaven Way," which is causing some controversy, reports the Brooklyn Paper. After all, some people don't believe in God, or heaven, and, of course, there's that whole "separation of Church and state" thing. On the other side are the people saying that the firefighters are heroes and deserving of a "place like heaven," and isn't this just a nice thing to do, for the love of God? And then there's the point that Ken Bronstein of NYC Atheists makes: "The problem with the sign is that you're assuming that you know what they felt deep down," said Bronstein, pointing out another potential flaw with the street sign. "You're assuming they even believed in heaven." Still, practically speaking, all of the firemen's names (Joseph Gullickson, Brian Cannizzaro, Salvatore Calabro, Thomas Kennedy, Patrick Byrne, Joseph Maffeo, and Terence McShane) would hardly fit on a sign. And there seems to be a historical precedent for the name. As Gothamist reports, "The seven heroes have long been known as the 'Seven in Heaven,' " [City Councilmember Sara González's spokesman Mike] Schweinsburg tells us. "That's something that we didn't have any hand in, it is the way the community and their families chose to remember them. So if that is their desire then we are happy to continue to remember them in the way that their family and fellow firefighters prefer to call them." The Brooklyn Paper points out that other street dedications honor groups of fallen firefighters without getting religious -- "Red Hook Happy Hookers Hook and Ladder," for example. One commenter retorts, "I guess making a reference to hookers is preferable to mentioning heaven." And the end of the day, dear atheists, this may be sort of a no-win. God's country? Red Hook street gets heavenly name [Brooklyn Paper]

Summary: A street sign in Brooklyn honoring seven firefighters who died on 9/11 has gotten the thumbs down from a New York atheist group, reports the Village Voice. The problem? The sign ceremonially renames Richards Street "Seven in Heaven Way," and the NYC Atheists say that any reference to heaven on a government sign violates the separation of church and state. "The problem with the sign is that you're assuming that you know what they felt deep down," says the group's president, who tells Fox News Radio that he might sue if it isn't removed. "You're assuming they even believed in heaven." "The attacks on 9-11 were an attack on America," adds the president of American Atheists, who has called for the sign to be taken down. "They were an attack on our Constitution and breaking that Constitution to honor these firefighters is the wrong thing to do." But some city officials are peeved about the timing of the controversy. "I think it's a little late in the process for someone to be bringing this up now," says one. And a rep for one city councilmember tells Gothamist, "The seven heroes have long been known as the 'Seven in Heaven.' It is the way the community and their families chose to remember them. So if that is their desire then we are happy to continue to remember them in the way that their family and fellow firefighters prefer to call them."

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Summarize: Il principio generale in materia Il legislatore prevede anche un'azione individuale del singolo socio o del terzo quanto questi soggetti ricevono un danno diretto dagli atti colposi o dannosi dell'amministratore, in particolare, l'art. 2395 cc stabilisce che le disposizioni dei precedenti articoli non pregiudicano il diritto al risarcimento del danno spettante al singolo socio o al terzo che sono stati direttamente danneggiati da atti colposi o dolosi degli amministratori. Sulla base di questi principi deve essere risolta la questione relativa all'eventuale risarcimento richiesto da un acquirente di azioni sociali agli amministratori, che sulla base di bilanci apparentemente corretti, (ma che -successivamente- risulteranno redatti in modo non conforme ai principi previsti dal codice), hanno deciso di acquistare delle azioni della società e si trovano, dopo l'acquisto, a dover ridurre e ricostruire il capitale sociale, per far fronte ad una situazione debitoria che non appariva dai bilanci. In questa situazione, l'acquirente di partecipazioni sociali (che dalla posizione di terzo, assume la posizione di socio) per poter essere risarcito dagli amministratori quali oneri deve adempiere? La giurisprudenza sembra seguire la seconda tesi. Infatti, tenendo inevitabilmente fermo il principio indiscusso secondo cui l'accoglimento della azione risarcitoria proposta a norma dell'art.2395 cod.civ. richiede l'accertamento non solo della condotta contra legem ma anche (al pari di ogni altra azione risarcitoria) la allegazione e prova, da parte dell'attore, del danno lamentato e del nesso causale intercorrente tra questo e la condotta stessa, pare evidente che non possa, in diritto, affermarsi che la responsabilità, prevista dalla norma richiamata, degli amministratori di una società nei confronti dei terzi acquirenti di quote di partecipazione della società da essi gestita sussisterebbe per il solo fatto che i bilanci da essi redatti non risultino conformi alle prescrizioni degli artt.2423 e ss. cod. civ. L'applicabilità di questo principio diventa più chiaro se si considera il tipo di danno oggetto della domanda di risarcimento. Del resto, quando il danno di cui è stato chiesto il risarcimento consiste nelle somme spese per l'acquisto delle azioni (oltre che per la successiva ricostituzione del capitale sociale), occorre verificare "se" e "quale" incidenza causale abbia avuto la rappresentazione non veritiera -o comunque non chiara- della situazione patrimoniale e del conto economico contenuta nei bilanci redatti dagli amministratori dell'epoca nel compimento da parte della ricorrente dell'atto dannoso, costituito dall'acquisto per quel corrispettivo di azioni che afferma essersi rivelate prive di valore.

Summary: La Cassazione del 18.2.2016 n. 3186 ha affermato che l'accoglimento della azione risarcitoria proposta ex art. 2395 cc richiede l'accertamento non solo della condotta contra legem, ma anche (al pari di ogni altra azione risarcitoria) la allegazione e prova del danno lamentato e del nesso causale intercorrente tra questo e la condotta stessa; ora pare evidente che non può affermarsi che la responsabilità ex art. 2395 cc degli amministratori di una società nei confronti degli acquirenti di quote della società sussiste per il solo fatto che i bilanci da essi redatti non risultino conformi alle prescrizioni degli art. 2423 cc e ss.

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Write a title and summarize: El electricista jubilado Pierre Le Guennec tiene cara de buen tipo y pinta de persona a la que uno compraría un coche usado. Desde hace una semana se ha convertido en el manitas más famoso y perseguido de Francia: el lunes, por medio de un artículo en Libération, se supo que guardó durante 40 años 271 obras inéditas de Picasso en un rincón del garaje de su casa de Mouans-Sartoux, en el sur de Francia, a veinte kilómetros de Cannes, envueltas en una bolsa de plástico, según él mismo explica, al lado de sus herramientas de electricista y de un montón de cables viejos. Él asegura que se los regaló el pintor en 1973. "Y se conservaron bien", añade, con una sonrisa retraída, "a pesar de los ratones que hay ahí". Según Le Guennec, en 1973, Jacqueline le dio una caja con obras del pintor y le dijo: "Para ti, de parte del maestro" "No me imagino a Picasso regalando a su electricista 'collages' que no hubiera dado ni a Braque", dice Jean Jacques Nauer Le Guennec -gafas con cordones, tirantes, camisa de leñador de las de hace treinta años- es muy tímido, hasta el extremo de que le cuesta explicarse. Habla a trompicones y esconde la cara con las manos en un gesto repetido de impotencia. Cuando se le comenta que los dibujos que él conservó tanto tiempo ocultos valen más de ochenta millones de euros murmura (aparentemente) abrumado por la cifra: "Esto no es posible. Esto me sobrepasa". Para el abogado de los herederos de la familia Picasso, Le Guennec es un pillo mentiroso muy listo con cara de buen hombre que ha conseguido mantener en secreto y escondido un tesoro robado hace 40 años que ahora destapa para dejar una herencia a sus dos hijos y cuya impostura puede acabar con una condena de cárcel; para la abogada Evelyn Rees, de Cannes, sus defendidos, Le Guennec y su animosa y charlatana mujer Danielle, son simplemente una pareja humilde de ancianos que ha vivido siempre del escaso sueldo del marido (algo que corrobora la policía), reconvertidos de golpe en protagonistas de una historia tan inverosímil como cierta, de esas que solo pueden ocurrir en la Provenza, y que arrancó una mañana de 1970. "Ese día, el secretario de Picasso, Miguel algo, me llamó por teléfono para que fuera a arreglar el motor del horno que se les había estropeado en su casa de Mougins, que está cerca de donde yo vivo. Fui y se lo arreglé. Después volví mucho allí, a arreglar luces, enchufes, grifos, a poner un sistema de alarma por toda la casa", explica Le Guennec, muy despacio, mirando al suelo. -Pero cuenta lo del sombrero, hombre, lo del sombrero, le ordena Danielle. "Un día, en el que yo estaba arreglando las luces del jardín, el secretario ese, Miguel, me hizo llamar, y me dijo que me llamaba el maestro. Yo me acerqué. Estaban desayunando en la terraza. Picasso me indicó que me sentara a su lado. Y se fijó en el sombrero de paja que yo tenía. Jacqueline [Roque, última esposa de Picasso] me pidió que se lo regalase. Y se lo di claro. Luego vi que lo había utilizado para un cartel de una exposición en Aviñón". Después, un día no determinado de 1973, meses antes de que falleciera el pintor, cuando Le Guennec se iba para casa después del trabajo, Jacqueline se le acercó: "Venía con una caja de cartón y me dijo: 'Para ti, de parte del maestro'. Vi que eran unos papeles, unos dibujos, pero no le di mucha importancia, lo metí en la camioneta y me volví a casa. Al llegar los envolví bien y los dejé en una estantería del garaje. Para mí no eran cuadros, no eran pinturas, muchos no estaban acabados, eran dibujos, pruebas, a los que no di mucho valor...". La resolutiva Danielle añade: "Tal vez ahora habríamos hecho otra cosa. Pero entonces, éramos jóvenes, no sabíamos. Él tenía 30 años y yo, 27". Guardaron el contenido de la caja, jamás hablaron de él a nadie, pasaron 40 años, y hace meses Pierre decidió desenterrarlo. ¿Por qué ahora? "Porque hace un año me detectaron un cáncer de próstata. Me operaron, toco madera, y estoy bien, pero pensé que si yo moría, mis hijos se iban a preguntar que qué eran esos dibujos, así que decidí contarles la historia y para que quedara claro que eran de Picasso, me dirigí a los herederos". Así, en enero llamó a la sociedad Picasso Administration, en París, y explicó a una secretaria que poseía varias obras del pintor y que deseaba autentificarlas. En esta sociedad están acostumbrados a las llamadas de chiflados o de espabilados que afirman guardar en su casa un cuadro o un dibujo del artista, así que a Le Guennec le dieron la respuesta tipo: "Haga unas fotografías y envíenoslas por correo". El viejo electricista, ayudado por uno de sus hijos, colocó un marco blanco de papel a cada dibujo y se puso manos a la obra: "Mientras las fotografiábamos les íbamos poniendo el título que nos parecía mejor, un poco al tuntún: a una la llamamos Bailarina, a otra Cabeza de mujer..., yo no sé". Envió una treintena de fotografías. Los de Picasso Administration le pidieron más. Obedeció. Y en septiembre, Claude Picasso, uno de los hijos del pintor y el encargado de gestionar la herencia, intrigado por esas fotografías malas en blanco y negro que escondían obras desconocidas, llamó a Le Guennec y le rogó que se acercara a París para estudiarlo todo personalmente. "Metimos en una maletita con ruedas todos los dibujos y nos fuimos en tren a París, Danielle y yo", explica Le Guennec, encogiéndose de hombros. El hijo de Picasso y un colaborador contemplaron estupefactos durante tres horas el maravilloso contenido de la maleta de los dos ancianos: un pequeño cuaderno con un centenar de deliciosos dibujos de Picasso a lápiz y a tinta, de apuntes al natural, de ensayos, de caricaturas; pero también una treintena de litografías (varias idénticas), un retrato a tinta de la primera mujer de Picasso, Olga Koklowa, nueve collages cubistas que por sí solos valen más de cuarenta millones de euros, una decena de bocetos de Las tres gracias, una acuarela de su periodo azul y varios paisajes (muy raros en Picasso), entre otros prodigios. En ningún momento dudaron de su autenticidad. Nadie en el mundo podría haber imitado con tanta perfección tantas técnicas diferentes de Picasso. El valor aproximado de las obras guardadas en el garaje de Le Guennec ronda los ochenta millones de euros, según varios expertos franceses. Anne Baldasari, directora del Museo Picasso de París, en una entrevista concedida el miércoles al periódico Le Figaro, aseguraba: "Las numerosas piezas aparecidas tienen una importancia considerable para aclarar la obra de Picasso en su juventud. Son fondos de su taller personal, de los años 1900-1932". Recuperado de la conmoción, Claude Picasso recomendó a Le Guennec que hiciera fotos en color -y de buena calidad- de las obras a fin de autentificarlas de una vez y le recomendó un fotógrafo parisiense. Y quedaron en hablar. Le Guennec accedió y fue a ver a ese fotógrafo al salir de la entrevista. "Pero cobraba cuarenta euros por foto, así que lo dejamos", explica. Volvieron los dos, Danielle y Pierre, en tren a su casa de la Provenza, con los dibujos otra vez metidos en la maletita de ruedas. Al llegar a casa, eso sí, los guardaron en un arcón donde Le Guennec conserva una colección de armas antiguas. Y se dispusieron a aguardar la llamada de los Picasso. En vez de eso, a la semana se presentaron en la casa varios agentes especializados de la Oficina Central Contra el Tráfico de Bienes Culturales que reclamaron inmediatamente las obras y le informaron de que sobre él pendía una denuncia interpuesta por los herederos de Picasso. Asombrado, asustado, según cuenta, Le Guennec le mostró a la policía el arcón donde guardaba los dibujos. Después, los policías registraron minuciosamente toda la casa, habitación por habitación, el jardín, el famoso garaje. Pero no encontraron nada más. Le Guennec no había distraído ni uno solo de los dibujos que enseñó a Claude Picasso: todo estaba ahí. Los tres (los dibujos, Pierre y Danielle) fueron traslados a la comisaría. Allí, el electricista jubilado se enteró de que los herederos de Picasso le habían denunciado no por robo (delito ya prescrito), sino por apropiarse de un bien robado (delito aún vigente). Arrestado por ladrón, pasó una noche en el calabozo. -A mí me soltaron a las tres horas, especifica Danielle, sonriente. El abogado de Picasso Administration, Jean-Jacques Neuer, desde un despacho de una de las zonas más exclusivas de París, explica las razones que les llevaron a acusar a Le Guennec: "Para nosotros está claro que robó las pinturas. Ninguno de los dibujos está dedicado. Todos pertenecen a un periodo determinado, como si estuvieran archivados en un mismo sitio, en la misma caja. Nadie conoce a este señor Le Guennec de nada, no aparece por ningún lado en ninguna biografía del artista probablemente más estudiado de la historia. No creemos que fuera un amigo de Picasso". Y añade: "Si a ti te regalan unos dibujos de Picasso, los pones en tu casa, los cuelgas en las paredes, los enseñas, no los escondes en el garaje. ¿Por qué los ha ocultado durante cuarenta años? Además, no me imagino a Picasso regalándole a su electricista un lote de dibujos, muchos de ellos inacabados, o dándole unos collages surrealistas que no habría regalado ni a Braque. Todo esto no tiene sentido, es simplemente aberrante". Con todo, la prensa local defiende al electricista y subraya el hecho de que jamás haya intentado vender ningún dibujo bajo cuerda y a escondidas, que no haya intentado escapar después de hablar con Claude Picasso, que ni siquiera ocultó las obras ni apartó ninguna para él después de viajar a París. Los expertos en arte, por el contrario, opinan que Le Guennec se apropió de algo que no le pertenecía, apelando a las mismas razones que Neuer. Hay galeristas de Niza que opinan, sin embargo, que Jaqueline Roque bien pudo darle la caja por error y que eso explicaría el caso. El alcalde de Mouans-Sartoux, André Aschieri, solo recuerda, en una entrevista reciente a Le Figaro, que Pierre ha sido siempre un vecino ejemplar del que jamás se ha conocido un episodio turbio. Y su abogada desde hace 15 días, Evelyn Rees, asegura que los herederos de Picasso tratan de ensuciar una bonita historia de gente honrada que tuvo la suerte de codearse con Picasso porque simplemente vivían a diez minutos en coche. El mismo Le Guennec, con su torpeza al hablar y sus gestos de impotencia, explica inocentemente que él jamás pensó que ese lote de dibujos, muchos inacabados, sin marcos, valieran algo, que jamás imaginó que ese montón de pinturas desordenadas dentro de una caja de cartón pudieran ser consideradas obras maestras, que por eso lo guardó todo en el garaje y que ha sido la amenaza de la muerte después de operarse de cáncer y la necesidad de que sus hijos entendieran qué y de dónde venía eso lo que le impulsó a dirigirse a Claude Picasso. Y no entiende que pueda acabar en la cárcel. Por lo pronto, la policía investiga con los cuadros requisados y custodiados en una comisaría de Nanterre. Después, será el fiscal de la zona el que decida. Lo hará a finales de diciembre. A él le corresponderá dilucidar si Le Guennec es lo que parece, esto es, un jubilado apacible con aspecto de buen vecino al que la suerte le sonrió hace 40 años, o si por el contrario es un gran actor dispuesto a rentabilizar el golpe de su vida. Si el fiscal cree que existen sospechas de delito, el caso continuará en manos de un juez de instrucción. Si no, los 80 millones de euros en pinturas y dibujos volverán a la casa del electricista jubilado de 1.200 euros de pensión. ¿Qué hará entonces con ellos, convenientemente autentificados, tasados ya en una fortuna si eso es lo que decide el juez? Le Guennec se vuelve a ocultar la cabeza con las manos, tartamudea un poco, sonríe (tal vez enigmáticamente, tal vez no) y dice: "No lo sé. Esto me supera". * Este artículo apareció en la edición impresa del Domingo, 5 de diciembre de 2010

Title: De cómo ocultar 40 años 271 'picassos' en un garaje Summary: Pierre Le Guennec, electricista y manitas que hizo chapuzas para el genio malagueño entre 1970 y 1973, relata cómo y por qué conservó escondidos durante 40 años centenares de dibujos, acuarelas, apuntes y 'collages' del pintor, valorados en más de 80 millones de euros.

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Summarize: Overview of the Congressional Review Act (CRA) What Is the CRA? The Congressional Review Act (CRA) is an oversight tool that Congress may use to overturn a rule issued by a federal agency. When Congress passes a law, it often grants rulemaking authority to federal agencies to implement provisions in the law. That delegation of rulemaking authority, and the rules issued by federal agencies under this authority, is a crucial component of the policy process. Congress has an interest in ensuring that, when issuing rules, federal agencies are faithful to congressional intent. To conduct proper oversight of federal agency actions, Congress has a number of tools available, including the CRA. The CRA was enacted in 1996 as part of the Small Business Regulatory Enforcement Fairness Act (SBREFA). Under the CRA, before a rule can take effect, an agency must submit the rule to Congress and the Government Accountability Office (GAO). Upon receipt of the rule by Congress, Members of Congress have a specified time period in which to submit and take action on a joint resolution disapproving the rule. If both houses pass the resolution, it is sent to the President for signature or veto. If the President were to veto the resolution, Congress could vote to override the veto. What Are Advantages of Using the CRA? Procedural The CRA establishes a special set of parliamentary procedures for considering a joint resolution disapproving an agency final rule. Supporters cite two main advantages to these procedures over the regular legislative process. First, when a joint resolution of disapproval meets certain criteria, it cannot be filibustered in the Senate. Specifically, once 20 calendar days have passed after the receipt and publication of the final rule, the Senate committee to which a joint resolution disapproving the rule has been referred can be discharged of further consideration if 30 Senators sign and file a petition. Once the committee is discharged, any Senator can make a nondebatable motion to proceed to consider the disapproval resolution. Should the Senate choose to consider the disapproval resolution, debate on it is limited and a final vote would be all but guaranteed. The second advantage of the CRA process often cited by its supporters is that if a joint resolution of disapproval is enacted, it not only invalidates the rule in question, but in most cases also bars the agency from issuing another rule in "substantially the same form" as the disapproved rule unless authorized to do so in a subsequent law. Failure of a CRA Joint Resolution of Disapproval Could Make a Major Rule Take Effect Faster than Otherwise Allowed Under the CRA In the case of some major rules, use of the CRA mechanism may make the rule go into effect more quickly than it otherwise would. Under the requirements of the CRA, agencies must delay the effective date of major rules by at least 60 days. This is essentially an extension of the Administrative Procedure Act's (APA's) requirement that agencies delay the effective date of rules by at least 30 days. Should either chamber choose to consider a joint resolution disapproving a major rule and then vote to reject it, the rule in question may go into force immediately, notwithstanding any layover period in its effective date established by the CRA. No rule may go into effect, however, until the effective date set by the agency in the rule itself has been reached. This provision of the CRA could be viewed as an advantage for Members who support a particular major rule and want it to take effect as soon as possible. Agency Oversight The CRA provides Congress with a method of conducting oversight of agency rulemaking. Not only can Congress use the CRA to overturn agency rules, but certain provisions of the CRA may help to increase congressional awareness of federal agency actions in general. The requirement for agencies to submit their rules to Congress, and the subsequent referral of each rule to the committee of jurisdiction, functions as a notification mechanism through which committees and Members can be made aware of rulemaking activity in which they may be interested. Although Members are likely to become aware of high-profile rules that are of broad interest and receive national media attention, the referral of each rule upon receipt in Congress provides an additional notification for rules that may be of a more localized or specialized interest to Members. In addition, the threat of submission or passage of a disapproval resolution may provide a mechanism through which a Member can pressure an agency for a particular outcome, either on that particular rule or on another matter. On the other hand, however, the single successful use of the CRA to overturn an agency rule in 2001 (discussed in more detail below) suggests that agencies may not consider use of the CRA to be a credible threat, and Members of Congress may be best served by exploring other options to influence agency actions. Increased Oversight of Independent Regulatory Agencies As discussed more below (see " Presidential Veto/De Facto Supermajority Requirement "), the biggest obstacle to enactment of a CRA resolution is generally considered to be the likelihood that a President would veto a joint resolution disapproving a rule issued by his own Administration. It might be expected, however, that Presidents are more likely to sign a resolution disapproving a rule that has been issued by an independent regulatory agency, a type of agency over which the President has less control. Congress created a number of federal agencies with certain characteristics to make them independent from the President, and, in some cases, from Congress itself. Those agencies are generally referred to as independent regulatory agencies or independent regulatory commissions. The President has limited ability to remove officials from those agencies, for example, and those agencies' budget requests may be submitted directly to Congress without modification by the President. In addition, some agencies may receive their funding outside the annual appropriations process. Most notably for rulemaking purposes, the independent regulatory agencies do not submit their regulations to the Office of Management and Budget (OMB) for review, unlike executive agencies such as Cabinet departments. Therefore, the independent regulatory agencies' regulations are considered to be more removed from presidential control than executive agencies', because the President—through OMB—does not have a direct influence over the content of their rules. As such, the rules issued by those agencies are more likely to be incongruent with the President's policy preferences, so that he may be more likely to sign a resolution disapproving such a rule. As one scholar states, "while still not representing much of a change from the Article I legislative process, the CRA may provide some real power in the case of political review of rulemaking by independent agencies." Drawing Attention to a Rule Another potential advantage of the CRA is that it provides a method for Members of Congress to draw attention to a particular rule or to make clear their position on a rule. The required language of a joint resolution of disapproval, which is stipulated in the CRA, provides for a relatively straightforward process through which a Member can make clear his or her opposition to a rule. In addition, the expedited procedures by which a resolution may reach the Senate floor provide an opportunity for a minority of the Senate to obtain floor consideration. Increased Transparency of Rulemaking Another benefit of the CRA, for Members of Congress as well as for the public, is that it has increased opportunities for transparency in the federal rulemaking process, primarily through a database compiled by GAO. Since the CRA's enactment, GAO has posted the rules agencies submit to GAO under the CRA to a database on its website that is publicly available. The website can be used to search for final rules that have been published by agencies, by elements such as the title, issuing agency, date of publication, type of rule (major or non-major), and effective date. The website also contains GAO's reports on major rules that are required under the CRA and discussed more below. What Are Disadvantages of Using the CRA? Procedural Use of the CRA mechanism also involves several potential procedural disadvantages: First, one might argue that the likelihood of a presidential veto (discussed in detail below) constitutes a de facto supermajority requirement to which most CRA disapproval resolutions are likely to be subject. Second, the CRA does not establish any "fast track" procedures for initial consideration of a disapproval resolution in the House of Representatives. As a result, unless the House majority party is willing to schedule the measure for consideration, it in all likelihood will not be considered. Third, unlike the regular legislative process, the CRA disapproval mechanism is available in the Senate only during certain specific time periods. Fourth, calculating the periods established by the CRA for submitting and acting on a disapproval resolution can be difficult, especially in cases where the act provides for additional submission and action periods in a subsequent session of Congress. Fifth, unlike regular legislation, each CRA disapproval resolution can only be aimed at a single agency final rule in its entirety; multiple disapproval resolutions cannot be "bundled" together and still maintain their privileged parliamentary status. Finally, as is noted above, if either chamber rejects a CRA disapproval resolution on a major rule, it could have the effect of putting a regulation in force sooner than would otherwise be the case. This provision of the CRA could be viewed as a disadvantage for Members who oppose a particular major rule and would prefer as long of a period as possible to elapse before the rule becomes effective. Disapproval of an Entire Rule Unlike under the regular legislative process, the CRA can only be used to invalidate an agency final rule in its entirety; it cannot be used to modify or restructure a rule in order to make it acceptable to Congress. If Congress were to use the regular legislative process instead of the CRA, Congress could invalidate part of a rule or instruct the agency to amend or repeal part of a rule. However, regular legislation would not be eligible for the same expedited procedures in the Senate in the same way a CRA resolution would. It would not be assured of the opportunity for floor consideration and might be subject to filibuster. Presidential Veto/De Facto Supermajority Requirement Perhaps the most widely cited reason why the CRA has been used to overturn only one rule is that a President is generally expected to veto a joint resolution of disapproval attempting to overturn a rule proposed by his own Administration. A joint resolution of disapproval requires the signature of the President to become law—a very unlikely prospect if his own Administration issued the rule. If the President were to veto the measure, Congress could attempt to override the veto. A two-thirds majority of both houses of Congress is required to override a President's veto; this creates a de facto supermajority requirement for a CRA joint resolution to be enacted. During a transition following the inauguration of a new President, however, the CRA is more likely to be used successfully. Because of the structure of the periods during which Congress can take action under the CRA, there may be a period at the beginning of each new Administration during which rules issued near the end of the previous Administration would be eligible for consideration under the CRA. The one instance in which the CRA was used to overturn a rule took place during such a period—the resolution was enacted in the early days of the George W. Bush Administration and overturned a rule that had been issued late in the Clinton Administration. See " How Many Rules Have Been Overturned Using the CRA? " for more information on this instance. How Many Rules Have Been Overturned Using the CRA? To date, the CRA has been used to overturn one rule. In November 2000, the Clinton Administration's Occupational Safety and Health Administration (OSHA) in the Department of Labor (DOL) issued a rule on ergonomics standards. The full congressional consideration period provided for in the CRA did not elapse before the second session of the 106 th Congress adjourned, so additional periods for review became available. The Senate passed the CRA resolution, S.J.Res. 6, on March 6, 2001. The House voted on the Senate resolution and passed it the following day. On March 20, 2001, President George W. Bush signed into law P.L. 107-5, overturning the rule. To date, OSHA has not attempted to re-issue another version of the ergonomics rule. Five CRA joint resolutions of disapproval have been vetoed since the law was enacted, all by President Obama. For a discussion of why the CRA has only been used to overturn one rule, see the section above titled " Presidential Veto/De Facto Supermajority Requirement." Definitions Under the CRA What Is a Rule Under the CRA? The CRA adopts the definition of a "rule" that appears in Section 551 of the Administrative Procedure Act (APA) with three exceptions. Section 551 of the APA defines a rule as the whole or a part of an agency statement of general or particular applicability and future effect designed to implement, interpret, or prescribe law or policy or describing the organization, procedure, or practice requirements of an agency and includes the approval or prescription for the future of rates, wages, corporate or financial structures or reorganizations thereof, prices, facilities, appliances, services or allowances therefore or of valuations, costs, or accounting, or practices bearing on any of the foregoing. The first exception in the CRA definition of a "rule" is for rules of particular applicability, including several of the types of rules specifically included in the APA definition: a rule that "approves or prescribes for the future rates, wages, prices, services, or allowances therefor, corporate or financial structures, reorganizations, mergers, or acquisitions thereof, or accounting practices or disclosures bearing on any of the foregoing." Second, the CRA's definition of a rule excludes "any rule relating to agency management or personnel... " Finally, "any rule of agency organization, procedure, or practice that does not substantially affect the rights or obligations of non-agency parties" is also excluded from the definition of "rule." Notably, the CRA adopts the broadest definition of "rule" contained in the APA, which is broader than the category of rules subject to notice and comment rulemaking. Therefore, some agency actions that are not subject to notice and comment rulemaking under the APA, and thus may not be published in the Federal Register, may still be considered a rule under the CRA. Does the CRA Apply to Interim Final Rules? Yes. Interim final rules are considered to be final rules and, therefore, an interim final rule that satisfies the CRA definition of a "rule" will be subject to the CRA. Interim final rules are used by agencies to promulgate rules without providing the public with notice and an opportunity to comment before publication of the final rule, while reserving the right to modify the rule following a post-promulgation comment period. Agencies must assert a valid "good cause" in order to issue any interim final rule. Interim final rules are considered final rules that carry the force and effect of law. Does the CRA Apply to Proposed Rules? It does not appear that the CRA applies to proposed rules issued by an agency. Arguably a proposed rule does not satisfy the CRA definition of a "rule." A proposed rule is not "designed to implement, interpret, or prescribe law or policy"; instead, it is generally created by the agency as a draft with which to solicit and receive public comments. Additionally, a proposed rule has no "future effect," because a rule subject to a notice of proposed rulemaking may not go into effect until comments are received and considered by the agency and a final rule is published in the Federal Register. Presumably on these grounds, GAO specifically advises agencies not to submit proposed rules to Congress or GAO under the CRA. In 2014, GAO published an opinion discussing the CRA and proposed rules. GAO limited its analysis to three questions regarding GAO's role under the CRA and its precedents analyzing whether specific agency actions are rules under the CRA. It concluded that "the terms of [the] CRA, and its supporting legislative history, clearly do not provide a role for GAO with regard to proposed rules, and do not require agencies to submit proposed rules to GAO." Furthermore, GAO stated that its prior decisions found "that an agency action constituted a rule for CRA purposes... [if] the action imposed requirements that were both certain and final." Since proposed rules "are proposals for future agency action that are subject to change... and do not have a binding effect on the obligations of any party," GAO concluded they are "not a triggering event for CRA purposes." GAO also noted that, because the CRA's expedited procedure for review of agency rules was enacted pursuant to Congress's constitutional authority to establish its own procedural rules, it is for "Congress to decide whether [the] CRA would apply to a resolution disapproving a proposed rule." What Is a Major Rule Under the CRA? The CRA defines a major rule as any rule that the Administrator of the Office of Information and Regulatory Affairs [OIRA] of the Office of Management and Budget [OMB] finds has resulted in or is likely to result in— (A) an annual effect on the economy of $100,000,000 or more; (B) a major increase in costs or prices for consumers, individual industries, Federal, State, or local government agencies, or geographic regions; or (C) significant adverse effects on competition, employment, investment, productivity, innovation, or on the ability of United States-based enterprises to compete with foreign-based enterprises in domestic and export markets. The term does not include any rule promulgated under the Telecommunications Act of 1996 and the amendments made by that Act. A previous CRS report provided information on the number of major rules issued in recent years, and noted that the 100 major rules issued in calendar year 2010 were considered major because of their effect on the economy, measured in other ways than just in costs for compliance. For example, 37 of the rules appeared to be major because they involved transfers of funds from one party to another (most commonly, federal funds to the recipients of those funds, such as payments to Medicare providers). Ten other rules appeared to be major because they were expected to prompt consumer spending, or because they established fees for the reimbursement of federal functions. Thirty-nine rules appeared major because they were expected to result in at least $100 million in annual compliance costs, regulatory benefits, or both. What Happens When a Rule Is Designated as Major? When a rule is designated as major pursuant to the CRA, the act subjects it to two additional requirements. The first is that the Comptroller General is required to prepare and submit to the committee of jurisdiction a report on each major rule within 15 calendar days of its submission or publication date. This report is to contain "an assessment of the agency's compliance with procedural steps" required for the rule, including any cost-benefit analysis or other analysis under certain statutes such as the Regulatory Flexibility Act and the Unfunded Mandates Reform Act. Second, the CRA contains provisions that may delay the effective dates of major rules. Specifically, if the rule is major, the statute provides that it "shall take effect on the latest of" 60 days after the date that the rule is published in the Federal Register or received by Congress, whichever is later; if Congress passes a joint resolution of disapproval and the President vetoes it, the date on which either house of Congress votes and fails to override the veto or 30 session days after the date Congress received the veto, whichever is earlier; or the date the rule would have otherwise taken effect, if not for this provision of the CRA. The delay provided for in the CRA allows Congress additional time to consider whether to overturn a major rule before it goes into effect. If the rule is not major, the CRA states that the rule "shall take effect as otherwise provided by law after submission to Congress." Who Determines Whether a Rule Is Major? Under the CRA, the Administrator of OIRA is responsible for determining whether a rule is major. However, the CRA does not specifically require agencies to submit their rules to OIRA so that such a determination can be made. A former OIRA Administrator, Cass Sunstein, stated that "[o]nce an agency has submitted a rule to Congress and the GAO under the CRA, OMB does not conduct retrospective reviews of their appropriate designation" as major or non-major rules. Executive agencies, excluding independent regulatory agencies, are required to submit "significant regulatory actions" to OIRA for its review, in accordance with Executive Order 12866. As part of that review process, agencies and OIRA make a determination as to whether a rule is "economically significant" as defined under Section 3(f)(1) of Executive Order 12866. The definitions for "economically significant" rule and major rule are not identical, but they are very similar. In most cases, a rule determined to be "economically significant" under the executive order will also be major under the CRA, and vice versa. Independent regulatory agencies do not submit their rules to OIRA for review under Executive Order 12866. However, OIRA is still tasked with determining whether an independent regulatory agency's rule is major. Accordingly, it is not clear whether and how rules issued by the independent regulatory agencies should be designated as major under the CRA. Sally Katzen, who was the OIRA Administrator when the CRA was enacted, stated in testimony to Congress that, Because OIRA does not review the regulations issued by the independent regulatory agencies under Executive Order 12866, we had to design a process for us to determine whether the final rule of an independent regulatory agency is "major" within the meaning of the statute. Therefore, we invited regulatory contacts from the independent regulatory agencies... to a meeting on April 12, 1996, to discuss my April 2 memorandum [on the CRA] and how they could best coordinate with us on our determination of "major." After this meeting, the independent regulatory agencies began sending OIRA summaries of their upcoming final regulations for us to decide whether or not these rules were "major." Initially, there was a flurry of staff discussions; this process for the "independents" has now become routine. More recent accounts suggest, however, that at least some of the independent regulatory agencies no longer appear to be acknowledging a role for OIRA in the determination of rules as major. Rather, these agencies appear to be making the determination themselves. A December 2013 GAO report stated that the independent regulatory agencies were inconsistent in how they determined whether a rule was major, which could "raise the risk of some rules not being properly classified as major, limiting Congress's ability to review these rules before they become effective." Does the CRA Apply to Non-Major Rules? Yes. The CRA can be used to overturn any final rule, regardless of whether the rule is major. Agency Submission of Rules When Does an Agency Have to Submit a Rule to Congress and GAO? The CRA does not specify when an agency must submit a rule. However, a rule cannot become effective until after it is submitted. In practice, agencies generally submit rules around the time the rule is finalized and published. How Do I Check if a Rule Has Been Submitted Under the CRA? Submissions to Congress When final rules are submitted to Congress pursuant to the CRA, notice of each chamber's receipt and referral appears in the respective House and Senate sections of the daily Congressional Record devoted to "Executive Communications." They are also entered into a database which can be searched using the Legislative Information System of the U.S. Congress (LIS). House communications can be accessed at the House LIS Database. Senate communications can be viewed in the Senate LIS Database. Submissions to GAO As mentioned above, GAO has a database on its website that tracks rules submitted to GAO under the CRA. The database can be accessed at http://gao.gov/legal/congressional-review-act/overview. The GAO database also contains links to the reports that GAO produces on major rules. It is important to note that the date of receipt of a final rule listed in the GAO database represents the date that the final rule was received by GAO; this date may or may not be the same date that the rule was received by the House and Senate, the latter being the date used for calculating the various CRA time periods for review and action. See " How Do I Introduce a Joint Resolution of Disapproval? " for a discussion of how "receipt by Congress" is determined for purposes of estimating the time periods governing the CRA disapproval mechanism. What Happens If an Agency Does Not Submit a Rule to Congress? In some instances, an agency has considered an action not to be a rule under the CRA and has declined to submit it to Congress. Although the disapproval procedures established in the CRA seem to be triggered by agency submission of a rule to Congress, it appears that Congress may still be able to utilize the CRA even if an agency fails to submit a rule. In the past, when a Member of Congress has thought an agency action is a rule under the CRA, the Member has sometimes asked GAO for a formal opinion on whether the specific action satisfies the CRA definition of a "rule" such that it would be subject to the CRA's disapproval procedures. GAO has issued 11 opinions of this type at the request of Members of Congress. In seven opinions, GAO has determined that the agency action satisfied the CRA definition of a "rule." After receiving these opinions, some Members have submitted CRA resolutions of disapproval for the "rule" that was never submitted. In four opinions, GAO has determined that the agency action does not satisfy the CRA definition of "rule," either because it falls under one of the exceptions or is outside the scope of the statute altogether. Members have had varying degrees of success in getting resolutions recognized as privileged under the CRA even if the agency never submitted the rule to Congress. It appears from recent practice that, in these cases, the Senate has considered the publication in the Congressional Record of the official GAO opinions discussed above as the trigger date for the initiation period to submit a disapproval resolution and for the action period during which such a resolution qualifies for expedited consideration in the Senate. (For a discussion of these periods and their triggers, see " How Do I Introduce a Joint Resolution of Disapproval? " and " What Are the CRA "Fast Track" Procedures? " below.) It is important to note that it is unlikely that an affected party would be able to challenge in court an agency's failure to submit a rule to Congress pursuant to the CRA, because the statute explicitly states that "no determination, finding, action, or omission under [the CRA] shall be subject to judicial review." See " Is There Judicial Review Under the CRA? " below. Congressional Procedures Under the CRA How Do I Introduce a Joint Resolution of Disapproval? In most respects, submitting (introducing) a CRA joint resolution of disapproval is the same as initiating any other House or Senate bill. There is, however, a very specific time period during which a qualifying joint resolution can be submitted, and its text must read exactly as laid out in the law. The receipt of a final rule by Congress begins a period of 60 "days-of-continuous-session" during which any Member of either chamber may submit a joint resolution disapproving the rule under the CRA. For purposes of the act, a rule is considered to have been "received by Congress" on the later date of its receipt in the Office of the Speaker of the House or its referral to Senate committee. In calculating "days of continuous session" every calendar day is counted, including weekends and holidays, and the count is only paused for periods where either chamber (or both) is gone for more than three days, that is, pursuant to an adjournment resolution. In order to qualify for the special parliamentary procedures of the CRA, a joint disapproval resolution must be submitted during this 60-day period, not before, and not after. Under Section 802(a) of the act, the text of a CRA joint disapproval resolution is also stipulated. It states the matter after the resolving clause must read, "That Congress disapproves the rule submitted by the ____ relating to ____, and such rule shall have no force or effect." (The blank spaces being appropriately filled in). The first blank would identify the agency promulgating the final rule and the second the name of the rule itself. Can a Joint Resolution of Disapproval Contain a Preamble?64 It is unclear. While the CRA procedure does not specifically bar a joint disapproval resolution from having a preamble, including one raises a number of unanswered questions about House and Senate consideration of the measure. For example, does the inclusion of a preamble destroy the privileged status of the measure in the eyes of either chamber? In the Senate, the preamble to a joint resolution is voted on after the passage of the resolution itself, and is separately amendable. Would the consideration of a preamble fall under the "fast track" Senate procedures banning amendments and limiting debate? Because of these and other ambiguities, Members considering including a preamble in a CRA joint disapproval resolution are advised to consult with the House and Senate Parliamentarians to obtain their definitive guidance on the question prior to submission. How Is a Joint Resolution of Disapproval Different from a Bill? Bills and joint resolutions each have traditional uses, but for purposes of the legislative process, the two are generally interchangeable. In order to be enacted, a bill or joint resolution has to pass the House and Senate with precisely identical text and be presented to the President for his signature, enacted over his veto, or become law without his signature. Can a Joint Resolution of Disapproval Be Used to Invalidate Part of a Rule or More than One Rule? No. Each CRA joint resolution of disapproval can only be used to invalidate one final rule in its entirety. What Are the CRA "Fast Track" Procedures? The CRA contains "fast track" procedures (sometimes called "expedited parliamentary procedures") for both committee consideration and floor consideration of a CRA disapproval resolution in the Senate. The CRA does not contain "fast track" procedures for initial consideration in the House. A CRA disapproval resolution would likely be considered in the House under the terms of a special rule reported by the Rules Committee and adopted by the House. The CRA also provides expedited procedures which govern the consideration by either the House or Senate of a disapproval resolution received from the other chamber. What Are the CRA "Fast Track" Procedures for Senate Committee Consideration? Any time after the expiration of a 20-calendar-day period which begins after a final rule is received by Congress and published in the Federal Register, a Senate committee can be discharged from the further consideration of a CRA joint resolution disapproving the rule. This discharge occurs upon the filing on the Senate floor of a petition signed by at least 30 Senators. While the act does not specify the text of a CRA discharge petition, those that have been used in the past resemble a cloture petition. For example, We, the undersigned Senators, in accordance with chapter 8 of title 5, United States Code, hereby direct that the Senate Committee on Commerce, Science, and Transportation be discharged of further consideration of S.J. Res. 6, a resolution on providing for congressional disapproval of a rule submitted by the Federal Communications Commission relating to the matter of preserving the open Internet and broadband industry practices, and, further, that the resolution be immediately placed upon the Legislative Calendar under General Orders. What Are the CRA "Fast Track" Procedures for Senate Floor Consideration? Once a CRA joint resolution of disapproval is reported or discharged from Senate committee, any Senator may make a nondebatable motion to proceed to consider the disapproval resolution. This motion to proceed requires a simple majority for adoption. If the motion to proceed is successful, the CRA disapproval resolution would be subject to up to 10 hours of debate, and then voted upon. A nondebatable motion to limit debate below 10 hours is in order. No amendments are permitted. A CRA disapproval resolution requires a simple majority in order to pass. For How Long Are the "Fast Track" Procedures Available? In order to be eligible for the "fast track" procedures for Senate consideration, that body has to act on a disapproval resolution during a period of 60 days of Senate session which begins when the rule is received by Congress and published in the Federal Register. After that period, the measure would have to be considered under normal Senate rules. There is no deadline on House consideration except the life of the two-year Congress. Do Disapproval Resolutions Have to Be Submitted in Both Chambers of Congress? No. The CRA does not require that "companion" disapproval resolutions be submitted in both the House and Senate. Under certain circumstances, however, doing so may be advisable. Under the terms of the CRA "fast track" procedure, if one chamber receives a disapproval resolution passed by the other chamber, the receiving chamber may take up and debate its own disapproval resolution, but at the point of disposition, is to take the final vote not on its own measure, but on the disapproval resolution received from the other house. This automatic "hookup" provision guarantees that both chambers are acting on the same joint resolution, and as such, it can be sent directly to the President following second-chamber passage. The mechanism also ensures that there will be no need to resolve legislative differences between the chambers even in cases where the House and Senate disapproval resolutions have slightly different texts. If the House passes a joint resolution of disapproval, for example, and messages it to the Senate, the Senate would apparently be able to consider the House measure under the fast track procedures only by first taking up its own disapproval resolution. If there is no Senate companion resolution, taking up the House measure could potentially require unanimous consent. As such, House sponsors who want the Senate to be able to consider the House resolution under the CRA "fast track" procedures should ensure that a companion Senate disapproval resolution is submitted during the 60-day initiation period. If the Senate acts first, the House can take up the measure, should it choose to do so, under its normal parliamentary mechanisms without having a companion resolution submitted in the House. What Happens if Congress Adjourns Before the CRA Initiation or Action Periods Conclude? If, within 60 days of session in the Senate or 60 legislative days in the House after the receipt by Congress of a rule, Congress adjourns its session sine die, the periods to submit and act on a disapproval resolution "reset" in their entirety in the next session of Congress. In the new session, the reset periods begin on the 15 th day of session in the Senate and the 15 th legislative day in the House. If these two dates do not coincide, it appears that both houses would regard the reset period of 60 days of continuous session for submitting a disapproval resolution as beginning on the later of the two, similarly to the way in which the date of initial receipt by Congress is calculated, so that the new initiation period will be the same for both chambers. If the new session is the second session of the same Congress, a disapproval resolution submitted in the first session remains available for expedited action in the Senate during its new action period of 60 days of session. This "carryover" provision is intended to ensure that Congress will have the full periods contemplated by the act to disapprove a rule regardless of when it is received. Is it Possible to Ascertain When the Periods for Submission, Discharge, and Action on a Resolution to Disapprove a Given Rule Begin and End? Yes. CRS can provide congressional clients with unofficial estimates of the periods to submit, discharge, and act on a joint resolution of disapproval under the CRA once a given rule has been received by Congress and published in the Federal Register. It is important to note, however, that CRS estimates are unofficial and nonbinding. The House and Senate Parliamentarians are the sole definitive arbiter of the CRA parliamentary mechanism, including day count calculations, and should be consulted for authoritative guidance on its operation. Effect of a Resolution of Disapproval What Is the Effect of Enacting a CRA Joint Resolution of Disapproval? Enactment of a CRA joint resolution disapproving a rule has two primary effects. First, a rule subject to a disapproval resolution would not take effect. If a rule has previously taken effect, it is not to continue in effect and "shall be treated as though such rule had never taken effect." Second, the agency may not reissue the rule in "substantially the same form" or issue a "new rule that is substantially the same" as the disapproved rule, "unless the reissued or new rule is specifically authorized by a law enacted after the date of the joint resolution disapproving the original rule." When Is a New Rule "Substantially the Same" as a Disapproved Rule? The CRA does not define the meaning or scope of "substantially the same," what criteria should be considered, or who should make such a determination. Since the CRA does not define "substantially the same," sameness could be determined by scope, penalty level, textual similarity, or administrative policy, among other factors. For example, if Congress objected to a specific section of language in a rule that was ultimately disapproved, would a rule that only removed that language be considered "substantially the same" as the original? If the agency reissued a rule in which it changed one standard listed in the original regulation, would that be substantially similar? If it changed the number of categories to which a standard applied would the rule still be "substantially the same"? These questions, for which no definitive answer is available, highlight the ambiguity in the meaning of "substantially the same." The statute is also silent on the question of who would make the determination as to whether an amended rule or new rule is "substantially the same" as a disapproved rule. It appears that Congress could take action if it determined that a reissued or new rule was substantially the same as a disapproved rule, given that any reissued or new rule would also be subject to the CRA. Given that the statute precludes judicial review of any "determination, finding, action, or omission" under the CRA, one could argue that evaluating whether the "substantially the same" prohibition has been violated may be a matter for Congress alone to decide. See " Is There Judicial Review Under the CRA? " below. What Is the Effect of a CRA Joint Resolution Disapproving an Amendment to a Previously Issued Rule? Agencies often promulgate rules that substantively amend or make technical corrections to a previously issued rule. An amendment to a rule, if substantive or even if simply a technical correction, is considered to be a "rule" under the APA and the CRA. If a CRA joint resolution of disapproval were enacted regarding such an amendment, it would prevent the amendment from going into effect or continuing in effect. However, this CRA joint resolution of disapproval would have no effect on the previously existing rule that was being amended. How Does the CRA Affect the Effective Date of a Rule? As the first step in the congressional disapproval process, the CRA generally requires federal agencies to submit their covered rules to both houses of Congress and GAO "before a rule can take effect." Currently, the APA requires that agencies generally wait at least 30 days after issuance in the Federal Register before a rule can become effective. As explained above (see " What Happens When a Rule Is Designated as Major? "), the CRA extends that required period for major rules, providing that major rules "shall take effect on the latest of" three dates: 60 days after the date that the rule is published in the Federal Register or submitted to Congress, whichever is later; if Congress passes a joint resolution of disapproval and the President vetoes it, the date on which either house of Congress votes and fails to override the veto or 30 session days after the date Congress received the veto, whichever is earlier; or the date the rule would have otherwise taken effect, unless a joint resolution of disapproval is enacted. Non-major rules "shall take effect as otherwise provided by law after submission to Congress." For certain types of rules, these effective date requirements may not apply. The CRA contains a provision stating that the following rules will take effect on the date the promulgating agency chooses: (1) any rule that establishes, modifies, opens, closes, or conducts a regulatory program for a commercial, recreational, or subsistence activity related to hunting, fishing, or camping, or (2) any rule which an agency for good cause finds (and incorporates the finding and a brief statement of reasons therefor in the rule issued) that notice and public procedure thereon are impracticable, unnecessary, or contrary to the public interest... What Happens if a Rule that Is Already Effective Is Overturned? If a rule has already taken effect, the CRA provides that the rule shall not continue in effect and "shall be treated as though such rule had never taken effect." Is There Judicial Review Under the CRA? Section 805 of the CRA states that "[n]o determination, finding, action, or omission under this chapter shall be subject to judicial review." Two federal appeals courts and several federal district courts have examined this section and determined that it unambiguously prohibits judicial review of any question arising under the CRA. One court, a federal district court, has reached the contrary conclusion, ruling that it could review a claim based on noncompliance with the CRA. In the first case to consider the CRA's judicial review provision, a federal district court in Texas Savings & Community Bankers Association v. Federal Housing Finance Board rejected the plaintiff's argument that "§ 805 only forecloses review of any 'determination, finding, action, or omission' by Congress." Instead, it concluded that the "[c]ourt must follow the plain English" of the statute, which barred review of actions "' under this chapter'not'by Congress under this chapter.'" In the court's words, "the language could not be plainer" and the alleged failure to comply with the CRA "is not subject to review by this [c]ourt." The D.C. Circuit Court of Appeals, in Montanans for Multiple Use v. Barbouletos, confronted a similar assertion that an agency action should be invalidated because of the agency's failure to comply with the submission requirements in the CRA. The court ruled that the CRA judicial review provision "denies courts the power to void rules on the basis of agency noncompliance with the [CRA]." Therefore, "the language in § 805 is unequivocal and precludes review of this claim... " It appears that only one court, a federal district court in Indiana, has ruled that the Section 805 language is ambiguous and may allow a court to adjudicate claims arising from the CRA. In United States v. Southern Indiana Gas and Electric Company, the court concluded that the statute could be reasonably interpreted two ways. First, the statute could prohibit any judicial review of an agency's compliance with the CRA. This interpretation was adopted in the cases discussed above. Second, the statute could "preclude judicial review of Congress' own determinations, findings, actions, or omissions made under the CRA after a rule has been submitted to it for review." Under this interpretation, the bar on judicial review would not extend to claims challenging an agency's action, such as whether an agency should have submitted a rule to Congress under the CRA. Ultimately, the court rejected the first interpretation because it would allow agencies to "evade the strictures of the CRA by simply not reporting new rules," which it argued was at odds with the statute's purpose to prevent agencies from "essentially legislating without Congressional oversight." It adopted the second interpretation and concluded "that it has jurisdiction to review whether an agency rule is in effect that should have been reported to Congress pursuant to the CRA." This conclusion appears to be a minority view among the federal courts. Concluding Questions What Other Tools Are Available To Congress for Conducting Oversight of Federal Regulations? Although the CRA offers a number of advantages to Congress, as discussed above, Congress also has a number of other tools available to conduct oversight of federal agency rulemaking. These tools include general legislative powers, oversight hearings, meetings with agency officials, and appropriations language. Each of these is briefly discussed below. Every rule issued by a federal agency must be based upon a grant of authority given to that agency by Congress in statute, and it is Congress's prerogative to ensure that agencies issue rules in a manner consistent with congressional intent. As such, Congress can use its legislative power to oversee the issuance and implementation of rules, or even require that an agency repeal a rule. For example, Congress can make a change to the underlying statute authorizing a rule or enact legislation that simply overrides the rule. Such a change could remove or change the agency's authority to issue the rule, or it could prescribe more specifically in law what the rule should contain. The advantage of using the CRA is that the procedures it provides for, particularly in the Senate, can make it easier to pass a joint resolution of disapproval than to pass a regular bill. However, as discussed in detail below, Members must submit and act on a CRA resolution within a particular time period following issuance of a rule, whereas Congress can use its general legislative power to act on a rule at any time. Hearings are another method of conducting oversight of federal rules. Congressional committees can hold oversight hearings at any time that focus on the development or implementation of a particular rule or set of rules that fall under their jurisdiction. Oversight hearings can give Members a chance to ask agency officials questions about rules and communicate their views to agency officials. A Member of Congress also can request a meeting with the rulemaking agency while a rule is under development to communicate his or her views to the agency. In addition, a Member can request to meet with the Office of Information and Regulatory Affairs (OIRA), the entity within OMB that reviews most agency regulations prior to their publication. Such meetings are sometimes referred to as "12866 meetings," a reference to Executive Order 12866, which governs OIRA review of agency rulemaking. During the review process, OIRA can play a significant role in the content of a proposed or final rule. Therefore, Members may want to make their views known to OIRA while the rule is under review. Finally, Congress has frequently used appropriations legislation to restrict an agency's use of funds to promulgate or implement particular regulations. However, unlike CRA joint resolutions of disapproval, provisions of this type do not nullify an existing regulation, nor do they remove the agency's underlying statutory authority to issue a regulation. Therefore, any final rule that has taken effect will continue to be binding law—even if an appropriations restriction prohibits the agency from using funds to enforce the rule. In addition, restrictions on the use of funds in appropriations acts, unless otherwise specified, are binding only for the period of time covered by the measure (i.e., a fiscal year or a portion of a fiscal year). In these instances, any restriction that is not repeated in the next relevant appropriations act or enacted as part of another measure no longer binds the relevant agency or agencies. Has Legislation Been Proposed to Amend the CRA? The Regulations from the Executive In Need of Scrutiny (REINS) Act ( H.R. 427 and S. 226 in the 114 th Congress) is one legislative proposal that would amend the CRA. The REINS Act would keep the current requirements of the CRA in place for non-major rules, but for any rule deemed to be major, it would require Congress to vote to approve the rule before it can take effect. As is currently the case under the CRA for a resolution of disapproval, the REINS Act provides a certain set of procedures under which a resolution of approval would be considered in each chamber. Earlier versions of the REINS Act passed the House in the 113 th and the 112 th Congresses ( H.R. 367 and H.R. 10, respectively). Another legislative proposal that would amend the CRA is H.R. 5982, the Midnight Rules Relief Act. If enacted, H.R. 5982 would make it easier for a new Congress to disapprove multiple rules issued in the final months of an outgoing President's Administration. Currently, as described above, Congress can overturn a single final rule through enactment of a joint resolution of disapproval—a disapproval resolution cannot be used to overturn more than one rule. In addition, if a rule is submitted late enough in a session of Congress, there may be additional time periods for consideration available in the next session. H.R. 5982 would amend the CRA to allow a disapproval resolution to contain more than one rule for those late-issued rules finalized by an outgoing Administration—that is, for rules submitted to Congress during the final 60 days of session in the Senate or 60 legislative days in the House of Representatives before sine die adjournment. Appendix. Government Accountability Office (GAO) Opinions on Whether Certain Agency Actions Are "Rules" Under the CRA

Summary: The Congressional Review Act (CRA) is an oversight tool that Congress may use to overturn a rule issued by a federal agency. The CRA was included as part of the Small Business Regulatory Enforcement Fairness Act (SBREFA), which was signed into law on March 29, 1996. The CRA requires agencies to report on their rulemaking activities to Congress and provides Congress with a special set of procedures under which to consider legislation to overturn those rules. Under the CRA, before a rule can take effect, an agency must submit a report to each house of Congress and the Comptroller General containing a copy of the rule; a concise general statement relating to the rule, including whether it is a major rule; and the proposed effective date of the rule. Upon receipt of the report in Congress, Members of Congress have specified time periods in which to submit and take action on a joint resolution of disapproval. If both houses pass the resolution, it is sent to the President for signature or veto. If the President were to veto the resolution, Congress could vote to override the veto. If a joint resolution of disapproval is submitted within the CRA-specified deadline, passed by Congress, and signed by the President, the CRA states that the "rule shall not take effect (or continue)." That is, the rule would be deemed not to have had any effect at any time. Even provisions that had become effective would be retroactively negated. Furthermore, if a joint resolution of disapproval were enacted, the CRA provides that a rule may not be issued in "substantially the same form" as the disapproved rule unless it is specifically authorized by a subsequent law. The CRA does not define what would constitute a rule that is "substantially the same" as a nullified rule. Additionally, the CRA prohibits judicial review of any "determination, finding, action, or omission under this chapter." This report discusses the most frequently asked questions received by the Congressional Research Service about the CRA. It addresses questions relating to the applicability of the act; the submission requirements with which agencies must comply; the procedural requirements that must be met in order to file and act upon a CRA joint resolution of disapproval; and the legal effect of a successful CRA joint resolution of disapproval. This report also discusses potential advantages and disadvantages of using the CRA to disapprove rules, as well as other options available to Congress to conduct oversight of agency rulemaking. For further questions not addressed here, please contact one of the authors: [author name scrubbed] (questions regarding history of and agency compliance with the CRA); [author name scrubbed] (questions regarding congressional procedures and day counts under the CRA); or [author name scrubbed] (questions regarding legal issues under the CRA).

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Summarize: BACKGROUND OF THE INVENTION 1. Field of Invention The present invention relates to a diffuser for insertion into a suction inlet in a side of a swimming pool or spa. 2. Description of Related Art A popular method for cleaning swimming pools and spas involves the use of a device which automatically moves throughout the pool or spa cleaning the bottom and sides of the pool or spa as it moves. Many popular forms of this pool cleaning device employ water suction as a means for propulsion. The water suction is usually provided by the main pool water pump which is used to circulate the pool water through a filter. The pool cleaning device is usually connected to the pump by a flexible hose, which in turn is connected to a water suction inlet in the side of the pool and below the surface of the water. The suction created by the pump draws water into the pool cleaning device, through the flexible hose, into the water suction inlet and through piping to the pump. As pool pumps operate at high pumping rates, moving great volumes of water in a short period of time, the suction created at the water suction inlet can be very strong. The pool cleaning device is usually left connected to the water suction inlet whenever the pool is not in use and operates whenever the pool pump operates. To avoid possible entanglement of a swimmer with the pool cleaning device and/or flexible hose, the pool cleaning device and flexible hose are usually removed from the pool and disconnected from the water suction inlet whenever the pool is used. However, whenever the pool pump operates with the flexible hose detached from the water suction inlet, the strong suction created by the pool pump at the water suction inlet presents a safety hazard to swimmers. As the water suction inlet is traditionally a hole in the side of the pool of approximately one to two inches in diameter, the high flow rate of the pool pump creates a very strong suction at the water suction inlet. Swimmers, especially small children, have been injured by being pulled toward and held against the water suction inlet due to the powerful suction created by the pool pump. Because the water suction inlet is generally a hole relatively flush with the side of the pool, an area of skin of a swimmer larger than the water suction inlet can create a water-tight seal with the water suction inlet resulting in a very strong vacuum being created within the pipe between the water suction inlet and the pool pump. This vacuum can make it very difficult, or even impossible, for the swimmer to pull away from the water suction inlet until the pool pump is turned off. The resulting injuries can include severe bruises and death due to drowning. It is possible to avoid the above-described danger by turning off the pool pump prior to removal of the flexible hose from the water suction inlet. However, the controls for the pool pump are often located at a remote location from the pool itself and, therefore, swimmers often neglect to turn off the pump prior to swimming. In addition, as all swimmers are not familiar with the operation of pool pump controls, owners of pools are often reluctant to allow swimmers to operate pool pump controls. SUMMARY OF THE INVENTION To solve the above-described pool safety problem, Applicant has invented a suction dispersion device to be inserted into an underwater suction inlet of a pool or spa. The device includes a tubular body having a first tubular portion and a second tubular portion. The first tubular portion has a sealing mechanism for forming a substantially water-tight seal with the suction inlet and the second tubular portion has a submersible length with a perforated periphery and a perforated end. The perforations on the periphery and the end of the submersible length of the second tubular portion disperse the suction force created by the pool pump along the submersible length of the second tubular portion. By perforating the periphery and the end of the second tubular portion, the danger of a swimmer being drawn to and held against the suction inlet by suction force is eliminated. This is because it is very difficult, if not impossible, to cover all of the perforations on the periphery and the end of the submersible length at one time. As a result, when a swimmer comes in contact with the device, only a portion of the perforations are covered and the suction force can draw water through the remaining perforations which are not covered by the swimmer. Since less than all of the perforations are covered at any one time by a swimmer coming in contact with the device, the suction force at the perforations covered by the swimmer is insufficient to injure the swimmer or prevent the swimmer from pulling away from the device. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a side view of one embodiment of the present invention; FIG. 2 is a front view of the device shown in FIG. 1; FIG. 3 is a bottom view of the device shown in FIG. 1; FIG. 4 is a rear view of the device shown in FIG. 1; FIG. 5 is a sectional view along section line V--V of FIG. 1; FIG. 6 is a side view of a second embodiment of the present invention; FIG. 7 is a rear view of the embodiment shown in FIG. 6; FIG. 8 is a partial view of another embodiment of the invention; FIG. 9 is a perspective view of an underwater suction inlet in the side of a pool; FIG. 10 is a perspective view of the device shown in FIG. 1 inserted into the underwater suction inlet of FIG. 9; FIG. 11 is a perspective view of an embodiment of the invention which includes a connection device; FIG. 12 is a side view of the device shown in FIG. 11; FIG. 13 is a sectional view of one embodiment of the connection device shown in FIG. 11; and FIG. 14 is a sectional view of another embodiment of the connection device shown in FIG. 11. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Preferred embodiments of the invention will now be explained with reference to the attached figures. FIG. 1 shows a side view of a first embodiment of the invention wherein the suction dispersion device includes a tubular body 10 having a first tubular portion 12 and a second tubular portion 14. The first tubular portion 12 and the second tubular portion 14 are connected by a connector portion 16 which can be a 90° elbow in a preferred embodiment. The first tubular portion 12 is configured so as to fit into an underwater suction inlet of a pool or spa. As conventional suction inlets are usually round in shape (as shown in FIG. 9), in the embodiment shown in FIGS. 1-5, the first tubular portion 12 is a round tube. The outside diameter D of the first tubular portion 12 is slightly smaller than the inside diameter of the suction inlet so that the first tubular portion 12 slides snugly into the suction inlet and is held in place by frictional forces between the outer surface of the first tubular portion 12 and the inner surface of the suction inlet (as shown in FIG. 10). The second tubular portion 14 has an end 18. The end 18 of the second tubular portion 14 is perforated with at least one end hole 20 so as to allow the flow of water into the end hole 20, through the second tubular portion 14 and into the suction inlet. The second tubular portion 14 has a periphery surface 22 which is perforated by at least one periphery hole 24. The at least one periphery hole 24 allows water to flow into and through the second tubular portion 14 and into the suction inlet. The number and location of periphery holes 24 is set so that it is very difficult for a user of the pool to block all periphery holes 24 and the end hole 20 at one time. For example, multiple periphery holes 24 can be provided such that a first hole and a second hole are spaced apart by at least 21/2 inches, preferably at least 3 inches and more preferably at least 4 inches. As another example, a first one of the periphery holes 24 can be located on a first plane and a second one of the periphery holes 24 can be located on a second plate different from the first plane. By locating the first and second holes on different planes (for example planes perpendicular to one another), the danger of a substantially planar body part (such as a person&#39;s back) being held against the suction dispersion device is reduced or eliminated. Although this embodiment has been described with only one end hole 20, multiple end holes 20 can be provided. By positioning the periphery holes 24 and the end holes 20 as described above, the danger of a person using the pool being drawn to and held against the device is avoided. As a result, the danger associated with an open water suction inlet is eliminated when the device is inserted into the water suction inlet. While the embodiment of the invention shown in FIGS. 1-5 is made from a single piece of bent tubing, the device could also be made from several pieces of straight tubing connected by, for example, 90° elbow tubing. In addition, shapes other than round tubing can be employed as the second tubular portion 14. Also, the first tubular portion 12 can be configured in any shape that will be accepted by the suction inlet. In the embodiment shown in FIGS. 1-5, the end hole 20 has a diameter equal to the inside diameter d of the first tubular portion 12 because the device is made from a uniform diameter piece of tubing. In another embodiment of the invention (FIG. 6), the first tubular portion 12 includes a plurality of flexible fins 26 protruding radially from the first tubular portion 12. The fins 26 are preferably of different sizes and arranged with the smallest fin 28 closest to the end 30 of the first tubular portion 12, as shown in FIG. 6. The fins 26 allow the universal use of the device with suction inlet holes of varying sizes. The fins 26 also allow the formation of a substantially water-tight seal even when irregularities exist in the size and/or shape of the suction inlet or the first tubular portion 12. Adapters having such fins are commercially available. In another embodiment of the invention (FIG. 8), a cap 32 covers the end 18 of the second tubular portion 14. The cap 32 is sufficiently larger than the end 18 so that water can flow around the cap and into the end hole 20 of the second tubular portion 14, as shown by arrows A in FIG. 8. An attachment portion 34 (FIG. 1) also can be fitted to the body 10 of the invention to allow attachment of the invention to the pool by a string, or the like, so as to facilitate retrieval of the invention if it is dropped in the pool. In other embodiments, the suction dispersion device can be used with the flexible hose of the mobile pool cleaner. For example, (FIG. 11) if the suction dispersion device were installed in the suction inlet, the flexible hose could be attached to the first and/or second tubular portions 12, 14 of the tubular body 10 by a connection device 36 to cover the end hole 20 and periphery holes 24. This way, the suction is developed in the flexible hose through the end hole 20 and/or periphery holes 24. When the pool cleaner 60 is removed from the pool, the flexible hose can be disengaged from the suction dispenser device by releasing the connection device 36, thereby exposing the end hole 20 and periphery holes 24 and dispersing the suction force along the submerged length of the second tubular portion. Of course any appropriate type of connection can be used to connect the connection device 36 to the suction dispersion device, such as, for example, threads, a bayonet socket, a clamp or a friction fit. As an example, FIGS. 12 and 13 show threaded portion 40 of the suction dispersion device which engages threads 42 on the inside of connection device 36. In the example of FIGS. 12 and 13, periphery holes 24 are covered by the inside wall 44 of connection device 36 such that all of the suction is developed through the end hole 20. As another example, FIG. 14 shows a connection device 36&#39; which includes an o-ring 46 located in a groove 48 at an upper end of the connection device 36&#39;. The o-ring 46 creates a seal and a friction fit with the periphery surface 22 of the suction dispersion device when the connection device 36&#39; is installed over the suction dispersion device. Suction is developed, and water flows, through the periphery holes 24 and the end hole 20 since the periphery surface 22 is held away from the inside wall 44&#39; of the connection device 36&#39; by the support members 52. Various details of the invention may be changed without departing from its spirit or its scope. Furthermore, the foregoing description of the embodiments according to the present invention is provided for the purpose of illustration only, and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.

Summary: A safety diffuser for use with an underwater suction inlet of a pool or spa eliminates the danger associated with a suction inlet on a side of a pool or spa created by the strong suction produced by the pool pump. By strategically placing holes in a tubular portion of the device, blockage of all the holes by a user of the pool or spa is prevented. As a result, the danger of a user of the pool or spa being drawn to and held against the device or the suction inlet is reduced.

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Summarize: AT&T Inc. (T) is refining its retail strategy with its first flagship store, a location on Chicago’s Michigan Avenue that goes beyond phones and tablets to show services such as fitness applications and “smartcar” features. The 10,000-square-foot (929-square-meter) store, opening Sept. 1 in the shopping mecca known as Chicago’s “Magnificent Mile,” is three times larger than the average of the company’s 2,300 retail outlets. Located across the street from Coach Inc. and Cartier Ltd. stores, it has cement floors, white plastic and reclaimed teak furniture with more than 100 video displays. With the loss of its exclusive agreement to sell Apple Inc. (AAPL)’s iPhone and a saturated wireless market that makes it hard to find new subscribers, Dallas-based AT&T is planning to use its stores to gain an edge against Verizon Wireless, Sprint Nextel Corp. (S) and T-Mobile USA Inc. The move also pits AT&T against the standard-bearer in consumer-electronics retail, Apple itself. “We are very different than Apple,” Paul Roth, AT&T’s president of retail sales and services, said in an interview. “In their stores, the product is the hero. This store is all about the experience.” The second-biggest U.S. wireless carrier is looking for ways to show investors it’s a bargain. Investors are getting a 29 percent discount for AT&T compared to its telecommunications peers on a price-to-earnings basis, up from 18 percent at the end of last year, according to data compiled by Bloomberg. AT&T shares fell 0.4 percent to $36.69 today in New York. No Shadowing Roth’s plan is to blend the hands-on approach of Apple stores with a visually dazzling environment. He’s requiring sales staff to greet visitors within 10 seconds or 10 feet after they’ve entered the store, to make them welcome without shadowing them, he said. Emulating Apple doesn’t guarantee success. Nike Inc. (NKE), Nokia Oyj (NOK1V), Microsoft Corp. and Sony Corp. have each tested the brand- centered retail approach, with mixed results. Nokia, the Espoo, Finland-based mobile-phone maker, has shut stores in New York, Chicago, London and Mexico City in the past three years after starting its own retail chain in 2005. AT&T has tried to give its store a customer-friendly makeover before. In 2007, it opened its first “AT&T Experience” store, a 5,000-square-foot Houston location with sales kiosks and product demonstrations. App Lounge The Chicago flagship goes beyond the Experience concept, which AT&T has dropped. At the front of the new store is an 18- foot wall of video screens and an App Lounge where people can use 55-inch monitors to test apps for Apple products or for Google Inc.’s Android system. The shop’s open layout has a series of “boutiques” where customers can see demonstrations on how to prepare for the Chicago Marathon or examine the texting safety features on a Nissan Leaf. “Customers are overwhelmed by technology,” Roth said. “They want to know less about the device and more about what it can do for them.” The store has 40 employees with as many as 30 on the sales floor at one time, Roth said. There are no cash registers, with staff using tablets or smartphones to make sales. Flagship stores help companies immerse their customers in everything they have to offer, said Michael Cote, a wireless strategist with the Cote Collaborative in Chicago. “These are branding opportunities more than retail outlets,” Cote said. “And what’s important here is that AT&T will be the first carrier to have an ‘experiential’ flagship store on the Magnificent Mile.” Verizon Overhaul Verizon Wireless, which has a store about two blocks away from AT&T on Michigan Avenue, has started an overhaul of its stores to keep up with the trend in retail toward giving customers more access to sample devices. The nation’s largest wireless carrier plans to have 60 stores outfitted this year with a new look featuring white interiors with blond wood, fewer counters separating staff from customers and products displayed on tables instead of walls, said Thomas Pica, a Verizon Wireless spokesman. The Basking Ridge, New Jersey-based company hasn’t designated a flagship store, he said. Sprint has had a flagship site in New York, prominently located on the first floor of the angular Flatiron Building, since 1997. Deutsche Telekom AG (DTE) unit T-Mobile’s flagship is also in New York, near Times Square. The model for success with a self-branded store is Cupertino, California-based Apple, said Lee Peterson, executive vice president of creative services at WD Partners, a retail strategy and design company based in Dublin, Ohio. “There’s no magic bullet,” said Peterson, whose clients include Best Buy Co. and Samsung Electronics Co. “Gimmickry doesn’t work. Lounges don’t work. We try to convince clients that it’s what the salesperson knows about the customer and the product that matters.” Apple, which had 372 stores around the world at the end of June, is preparing to introduce the next version of the iPhone on Sept. 12, two people with knowledge of the company’s plans said last month. To contact the reporters on this story: Scott Moritz in New York at smoritz6@bloomberg.net; Leslie Patton in Chicago at lpatton5@bloomberg.net To contact the editor responsible for this story: Nick Turner at nturner7@bloomberg.net War used to be simple. All you needed was the biggest bomb, and everyone else kept their mouths shut. Then more people figured out how to make that bomb. And then all sorts of other threats–biological agents, computer viruses, and UAVs–complicated the landscape. advertisement advertisement Consider this in the context of AT&T. There was a time when AT&T controlled the world–or at least iPhones. Before too long, however, AT&T had lost its exclusive on Apple’s category-crushing product, and a loosely organized association of Android phones clouded consumer preference again. So what does AT&T do now? They’re no longer the only carrier with the most coveted phone. Their net income is up and customer churn has been low, but its biggest tactical advantage has been squandered. Now it’s time to take this battle to the street. Specifically, Chicago’s busy Michigan Avenue. That’s where, this weekend, following a few years of planning, AT&T is opening its first ever flagship store. There, as 60,000 people per day pass by Cartier, Louis Vuitton, and Coach, they’ll see AT&T’s new 10,000-square-foot retail mecca, a store that AT&T hopes to “bring life to the brand,” according to store manager Christina Cheng. View the Tour Here Upon entering the store, you’ll first see an atrium ringed with LEDs. Employees will be on hand to greet all the customers, I’m told, because AT&T’s focus groups have discovered that it’s personal greetings that make customers feel welcome–not architectural bells and whistles. Even customers carrying phones from Verizon and T-Mobile can play with a nearby touchscreen table loaded with AT&T’s favorite apps. Just click a category, preview the page, and then download it on your smartphone through Bluetooth, QR code, or a simple URL. advertisement Tucked in a corner nearby, a stage backed by a small tower of LCDs allows customers to play head-to-head, Kinect-style motion games. Does this have much of anything to do with AT&T itself? Not really, but it supports “a vibe of exploration” Cheng tells me. This stage will double as a place for both product announcements and presentations from local app developers. That area is just an iPhone’s throw from a (shorter) electronics table featuring apps and gadgets for kids. The App Bar is in the same vicinity, staffed by App Tenders. Unlike Apple’s Genius Bar–the clear line of inspiration here–these staffers don’t handle any serious problems. Rather, they suggest apps based on your tastes, “like your local barista would recommend something for you,” Cheng says. Again, it reinforces the casualness of the store–it’s so casual, in fact, that it doesn’t even have a checkout counter. Employees ring up customers at mobile terminals. The deeper diagnostic work is tucked in the back, a series of cozy tables for one-on-one conversations, all wrapped in a studio space filled with large splash walls of Chicago designers who’ve designed limited edition, custom cases only available at AT&T’s flagship. It’d be easy to simply label the whole experience an Apple Store clone. And indeed, you do feel Cupertino’s influences, from the App Bar to the expansive open tables full of electronics. But if the Apple Store feels like a modern museum that you’re free to touch, AT&T’s flagship feels more like a rich person’s basement loaded with toys. The store is one wood-burning oven away from doubling as a high-end pizza and wine bar. I’m also reminded a bit of REI as I walk past the Lifestyle Boutiques–tables dedicated to particular interests, like health and fitness, productivity, and photography/sharing. Cheng tells me that she’s staffing these tables with knowledgeable experts (much like the staff at REI always seems to be scraping the mud off their boots before walking into work). A former photojournalist will introduce shoppers to their photography peripherals. A certified personal trainer will be discussing Fitbits and tablet connectivity. Across the store, AT&T has set up its Experience Platform, which is pretty much a big budget CES booth come to life. Each space represents part of a consumer’s life, from a Nissan Leaf parked in the corner, which shoppers can enter and play with in-car phone connectivity, to a model kitchen outfitted with AT&T’s beta home automation software, to a four-couched living room set up, filled with Xbox 360s and AT&T U-verse. advertisement “If you don’t have this area, [our services are] just a list,” Cheng explains. “For this much a month you can do this, or for this much a month you can do that.’” Instead, shoppers can actually sit on a couch, try out fiber-optic cable and beam content to sample phones and tablets that they’re simply handed, completely untethered, to test out and try new techniques. To the skeptic, it’s a lot of empty demo space in a premium retail strip that rents for $450 a square foot. “Our main focus is not sales,” Cheng explains. “Our traditional metrics may not work for here, but we’ll be successful in other ways.” She may be right. It’s in the Experience Platform–this floor space-swallowing digital mise en scene–that you really see AT&T’s plan with its flagship, to sell their current and future services, not as a promise of another new iPhone and faster data, but as platform-agnostic interconnectivity. It’s driving to work. It’s making dinner. It’s digital idealism free from the bounds of any phone, but very closely tied to AT&T itself. So imagine my surprise when I’ve circled the mega boutique store and notice, for the first time, all of AT&T’s actual phones are on display. They’re sitting on a series of tables, splitting the grand room right down the middle–positioned in an obvious yet surely overlooked spot, the physical and metaphorical backbone of the store. Check out more images of AT&T’s Chicago flagship store here.

Summary: AT&T is revamping its retail strategy in grand style, with a new 10,000-square-foot flagship store on Chicago's "Magnificent Mile" that will show off not just phones and tablets, but fitness applications and even "smartcar" features, Bloomberg reports. Apple comparisons are inevitable, but "we are very different," one executive says. "In their stores, the product is the hero. This store is all about the experience." That includes a sales staff that's Apple-level attentive: Customers are greeted within 10 seconds of entering the store's LED-lit atrium. There's an "App Lounge" where customers can try out Android and iOS apps on giant monitors, and an "App-Bar" where an "App-Tender" will recommend apps to you "like your local barista," the manager tells Mark Wilson of Fast Company. The vibe is so casual that there aren't even cash registers; employees ring you up via mobile terminals. "If the Apple Store feels like a modern museum that you're free to touch," Wilson writes, "AT&T's flagship feels more like a rich person's basement loaded with toys."

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Summarize: A Republican state senator from Oklahoma City introduced a bill Tuesday that would ban the use of aborted human fetuses in food, despite conceding that he's unaware of any company using such a practice. Freshman Sen. Ralph Shortey said his own Internet research led him to believe such a ban is necessary and prompted him to offer the bill aimed at raising "public awareness" and giving an "ultimatum to companies" that might consider such a policy. Shortey said he discovered suggestions online that some companies use embryonic stem cells to develop artificial flavors, but added that he is unaware of any Oklahoma companies doing such research. In an e-mail to The Associated Press, U.S. Food and Drug Administration spokeswoman Pat El-Hinnawy said: "FDA is not aware of this particular concern." The executive director of the anti-abortion group Oklahomans for Life, which has successfully pushed some of the strictest anti-abortion laws in the country through the state's GOP-controlled Legislature, also said he had never heard of human fetuses being used in food research. "I don't know anything about that," said Tony Lauinger. Shortey's bill would prohibit the manufacture or sale of any food in which aborted fetuses were used to develop any of the ingredients. Meanwhile, the bill has caused a stir among Oklahoma lawmakers, many decrying the proposed legislation. Self-described "pro-life" Sen. Brian Crain, the chairman of the Senate Human Services Committee to which Shortey's bill likely would be assigned, said Tuesday other issues are more deserving of the Legislature's attention. "We've got too many challenges facing Oklahomans today. We don't need to go looking for possible challenges that may come about sometime in the future," said Crain, R-Tulsa. "If it can be demonstrated that this is a challenge facing our food supply, then I think we need to act quickly, but there's been no demonstration that this is going on. "I'd hate to think we're going to spend our time coming up with possibilities of things we need to stop." First elected in 2010 to a heavily Hispanic district on the city's south side, Shortey has grabbed headlines with other bills he's introduced that have not become law. He sponsored a measure last year to crack down on illegal immigrants by authorizing law enforcement to seize their homes and vehicles, and to deny Oklahoma citizenship to babies born to illegal immigrants. He also offered an amendment to a bill that would have allowed legislators to carry firearms anywhere in the state, including the floor of the House and Senate. This year, Shortey has introduced a bill seeking a public vote on amending the Oklahoma Constitution to abolish the Court of Criminal Appeals. ___ Sean Murphy can be reached at http://www.twitter.com/apseanmurphy OKLAHOMA CITY - A state lawmaker said Tuesday he wants a serious discussion on his bill that would make it illegal in the state to manufacture or knowingly sell food or any other product intended for human consumption that contains aborted human fetuses. Sen. Ralph Shorty said he is not aware of any company in Oklahoma or anywhere else that is using practices featured in a 1973 science-fiction movie. In “Soylent Green,” small green wafers were said to contain high-energy plankton but were actually made from human corpses. “People are thinking that this has to do with fetuses being chopped up and put in our burritos,” said Shortey, R-Oklahoma City, who was elected in 2010. “That's not the case. It's beyond that. “There are companies that are using embryonic stem cells to research and basically cause a chemical reaction to determine whether or not something tastes good or not,” he said. “As a pro-life advocate, it kind of disturbed me that we would use aborted embryos or aborted human fetuses to extract stem cells and use them for research to basically make things taste better.” Shortey said he filed the bill after reading last fall that an anti-abortion group, Children of God for Life, had called on the public in March 2010 to boycott products of major food companies that partnered with a biotech company that produces artificial flavor enhancers, unless the company stopped using aborted fetal cells to test their products. The company has denied the allegation. A representative of the San Diego-based company did not return a telephone call or email request for comment Tuesday. “The technology and the research capabilities are available,” he said. “They're used in some things. Whether or not they use human cells or animal cells, it's hard to tell because companies are under no obligation to give that information unless their shareholders request it. “I'm not pointing fingers at any particular company,” Shortey said. “What I'm saying is in Oklahoma if you're a company just don't do this. There are plenty of other alternatives for developing food; you don't need to use aborted human fetuses or stem cells to do that.” Shortey, who opposes the use of embryonic stem cells for research, said he filed the measure, Senate Bill 1418, as a public awareness effort. It is not an attempt to ban stem cell research in the state. “The people that seem to be negative about this bill are the ones that support embryonic stem cells because they think I'm trying to do something with that here,” he said. “If I wanted to outlaw embryonic stem cell research, I would just come out and do it.” Ryan Kiesel, executive director of the American Civil Liberties Union of Oklahoma, said his group has concerns about the legislation. “From what I can tell, Sen. Shortey has authored this legislation based upon some rumors that he's heard about this but with no evidence that it's actually occurring,” said Kiesel, a former state legislator. “Rumor doesn't make for the best public policy.” Shortey said more work will be done on the bill, which is only one page and does not include any criminal penalties, he said. “It's akin to back in the 1960s and '70s... you had these companies that were using animals in pretty extreme ways doing testing on them and things like that,” he said. “Nobody believed it, they weren't admitting to it.... It's kind of like this case. If you've got a company that is using these types of unethical research techniques, they're not going to admit to it because it's a public-relations nightmare. “What we're saying is that if a company chooses to do this unethically, then not only will be they doing it unethically but they'll also be breaking the law at the same time,” Shortey said. “I want to start a discussion with my colleagues and I want it to be a serious discussion.” He said he expects his measure will get a committee hearing. Senate President Pro Tem Brian Bingman said it will up to the appropriate committee chairman to determine whether the measure will get a hearing. Bills still are being assigned. “Hopefully, at the end of the day the Legislature as a body does the right thing,” said Bingman, R-Sapulpa. “That's part of the process that we come up and look at both sides of the issue. You can't control what a guy does when he files legislation. It's all a process and at the end of the day you want to look at the final bills that are actually passed and signed by the governor.” Shortey said he was surprised SB 1418 has drawn so much attention. He's also filed legislation, Senate Joint Resolution 83, which seeks sending to a vote of the people a proposal to abolish the state Court of Criminal Appeals. Last year he filed a measure which, in response to doubts about President Barack Obama's citizenship, would have required presidential candidates to provide birth certificates in order to be on the state's presidential preference primary ballot. He also filed bills that would have denied Oklahoma citizenship to babies born to illegal immigrants and would have allowed police not only to question people about their immigration status but also to confiscate property, including homes and vehicles, belonging to those in the country illegally. All three failed to advance. Shortey said his measure could evolve into one that would outlaw embryonic stem cell research in the state. A similar measure failed to advance last year in the Legislature. “I'm a firm believer of pro-life principles and I think life begins at conception,” he said. “It's abhorrent that we don't protect that life... and it's disgraceful that we first allow the life to be taken and then when the life is taken we just disregard the body in whatever form it's in and allow it to be used to profit a company.” Kiesel said that debate could harm the medical research industry in the state. “Anytime that we see politicians in Oklahoma making an effort to criminalize scientific research, it does a disturbance to the entire scientific community and it does a disturbance to the health care options that might be available to Oklahomans,” he said. “We know for a fact that there is a world of potential medical breakthrough that can come through the use of stem cell research, including embryonic stem cell research. What kind of message does that send to the scientific community that we're in Oklahoma seeing again an effort to criminalize medical research? We're doing this at a time when we're trying to attract top-tiered doctors, physicians and medical researchers to our state.” Related to this story

Summary: Oklahoma Sen. Ralph Shortey is on a mission. He's introduced a bill banning any food products "which contains aborted human fetuses in the ingredients." Is this a going problem in Oklahoma, you ask? Well no, but Shortey read about it once on the Internet, he tells the AP, and the bill is intended to raise "public awareness" of the issue. He insists the bill is serious, and says it's being misunderstood. "People are thinking that this has to do with fetuses being chopped up and put in our burritos," he tells the Daily Oklahoman. "It's beyond that." According to that thing Shortey read online that one time, some companies are using embryonic stem cells to test their products for tastiness. The FDA says it "is not aware of this particular concern," and the bill appears to have little chance of passage. The chairman of the committee it would likely head to says Oklahoma has more pressing concerns.

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Summarize: Introduction This report provides an overview of selected campaign finance policy issues that have received recent legislative attention, or have otherwise been prominent, and which could receive attention during the 111 th Congress. Specifically, the report emphasizes nine issues: (1) bundling; (2) campaign travel aboard private aircraft; (3) electronic filing of Senate campaign finance reports; (4) the Federal Election Commission (FEC); (5) hybrid political advertising; (6) joint fundraising committees; (7) public financing of presidential campaigns; (8) 527 organizations; and (9) the related topic of restricting campaign activity among certain state election officials. The report includes a brief overview of each issue followed by a discussion of recent legislation (if any) and policy considerations. Legislative or regulatory activity, developments during recent election cycles, or a combination of all those factors suggest that each issue will remain a topic of debate during the 111 th Congress. This report is not intended to provide an exhaustive discussion of each topic. In some cases (noted throughout the report) other CRS products provide additional detail. The topics addressed in this report are typically considered separately, suggesting targeted legislation if Congress chooses to revisit the issues. The 111 th Congress could also consider broad legislation addressing one or more campaign finance issues. However Congress decides to proceed, the debate will likely be shaped by questions of (1) amounts and sources of money; (2) transparency; and (3) scope of regulation. As the final section of this report discusses, these factors unify the seemingly disparate policy issues discussed in the report and are common themes in the debate over campaign finance policy. Campaign Finance Activity in the 110th Congress: A Brief Review During the 110 th Congress, approximately 50 legislative measures affecting federal campaign finance policy were introduced. Two became law. Most significantly, the Honest Leadership and Open Government Act (HLOGA; P.L. 110-81 ) restricted campaign travel aboard private aircraft and required political committees to report additional information to the FEC about certain contributions bundled by lobbyists. In addition, late in the second session of the 110 th Congress, the FEC's Administrative Fine Program, which had been scheduled to expire, was extended until 2013 ( P.L. 110-433 ). Other issues received hearings or floor votes but did not become law. These included House passage of legislation affecting campaign payments to candidate families ( H.R. 2630, Schiff); disbursement of campaign funds by non-treasurers ( H.R. 3032, Jones (NC)); and funding for certain criminal enforcement of the Bipartisan Campaign Reform Act ( H.R. 3093, the relevant provision was an amendment sponsored by Representative Pence); A Committee on House Administration, Subcommittee on Elections, hearing on automated political telephone calls; Senate Rules and Administration Committee hearings on public financing of congressional campaigns ( S. 1285, Durbin); coordinated party expenditures ( S. 1091, Corker); electronic filing of Senate campaign finance reports ( S. 223, Feingold); FEC nominations; and automated political telephone calls ( S. 2624, Feinstein). Citizens United v. Federal Election Commission: Shaping Debate for the Second Session Perhaps the most prominent policy concern for the second session of the 111 th Congress has been developments surrounding a recent Supreme Court ruling. On January 21, 2010, the Court issued a 5-4 decision in Citizens United v. Federal Election Commission. A legal analysis of the case is beyond the scope of this report and, indeed, the precise implications of the case remain to be seen. Additional discussion of various policy and legal issues appears in other CRS products. In essence, however, the opinion invalidated aspects of the Bipartisan Campaign Reform Act's (BCRA) electioneering communication provision, which had prohibited corporations and unions from using their treasury funds to air broadcast ads referring to clearly identified federal candidates within 60 days of a general election or 30 days of a primary election or caucus. Perhaps more notably, the decision also overturned the Supreme Court's 1990 ruling in Austin v. Michigan Chamber of Commerce, which had upheld restrictions on corporate-funded independent expenditures. ( Citizens United appears not to affect the ban on corporate or union contributions to political candidates.) As a consequence of Citizens United, corporations—and presumably unions—now appear to be free to use their treasury funds to air political advertisements explicitly calling for election or defeat of federal (or state) candidates. Previously, such advertising would generally have had to be financed through voluntary contributions raised by political action committees (PACs) affiliated with unions or corporations. Unlimited, albeit independent, expenditures by corporations and unions has spurred legislative action in Congress, although no post- Citizens United measures have become law. Possible policy responses for those favoring additional regulation include enacting public campaign financing legislation, altering contribution limits, pursuing shareholder protection initiatives, easing restrictions on coordinated party expenditures, or amending the Constitution, among others. By contrast, those who believe that Citizens United correctly strengthens corporate speech rights may prefer the status quo, in which case no legislative action may be necessary. Thus far, most congressional attention responding to the ruling has focused on the DISCLOSE Act ( H.R. 5175 ; S. 3295 ; S. 3628 ). The House of Representatives passed H.R. 5175, with amendments, on June 24, 2010, by a 219-206 vote. By a 57-41 vote, the Senate declined to invoke cloture on companion bill S. 3628 on July 27, 2010. A second cloture vote failed (59-39) on September 23, 2010. The bill remains on the calendar. On a related note, on July 29, 2010, the Committee on Financial Services ordered reported H.R. 4790. The bill would require additional disclosure of political expenditures to corporate shareholders and is designed as a partial response to Citizens United. Other Emerging Campaign Finance Policy Issues Some of the issues considered during the 110 th Congress might be—or have been—addressed again during the 111 th Congress. Others became prominent during recent election cycles, especially 2008, and appear to be ongoing. The following discussion provides additional detail about selected issues that may continue to be on the legislative or oversight agenda. Authority to Disburse Campaign Funds The Federal Election Campaign Act (FECA) assigns campaign treasurers with primary responsibility for filing FEC reports and ensuring that political committees comply with the act. Treasurers—not candidates—are legally responsible for disbursing campaign funds. In fact, FECA does not specify a role for candidates in campaign financial decisions. As a practical matter, however, candidates may exert substantial informal influence over campaign spending. In recent Congresses, some Members have expressed concern about how campaign funds would be spent in the event a candidate died. On March 25, 2009, the House Committee on Administration reported H.R. 749 (Jones, NC) by voice vote and without amendment. The bill would permit candidates to designate to the FEC an individual to direct campaign spending following the candidate's death. That designation would supersede the treasurer's normal spending responsibilities, but would not affect the treasurer's reporting or other responsibilities. A backup could also be identified if the designee died, became incapacitated, or were unable or unwilling to carry out his or her responsibilities. The bill also permits candidates to specify their wishes about how funds would be disbursed. On April 22, 2009, H.R. 749 passed the House by voice vote and under suspension of the rules. The measure was subject to only brief debate and received bipartisan support. H.R. 749 is virtually identical to H.R. 3032, also sponsored by Representative Jones, and which the House passed on July 15, 2008, under suspension of the rules and by voice vote. The Senate took no action on the bill during the 110 th Congress, nor has it done so thus far during the 111 th Congress. Policy Considerations H.R. 749, and its predecessor ( H.R. 3032 ) have received bipartisan support amid candidates' desires to influence their campaign spending and make their wishes clear. To that end, H.R. 749 could alleviate the potential for asset disputes following candidate deaths. That outcome, however, depends on designees adhering to candidate wishes, and assumes that designees would be more faithful to candidate wishes than would be treasurers. H.R. 749 could create different levels of candidate authority over spending in life than in death. Specifically, although H.R. 749 would provide a mechanism for circumventing the treasurer after a candidate dies, the bill would not provide additional remedies for such action while the candidate is living. This may be a minor distinction due to candidates' de facto influence over their campaigns, despite FECA's general silence on the issue. Nonetheless, if Congress chose to enact H.R. 749 and felt it were important to create parity in candidates' abilities to direct campaign spending, it could amend FECA to create a clearer candidate role over campaign funds regardless of whether the candidate is living or dead. Congress might also provide explicit permission in FECA for candidates to hire and fire campaign treasurers. Bundling Bundling is a fundraising practice in which an intermediary either receives contributions and passes them on to a campaign or is credited with soliciting contributions that go directly to a campaign. Lobbyists often serve as bundlers. Bundling has been prominent in recent years both because of the additional disclosure required in HLOGA and because of the role bundling played in the 2008 presidential elections. Bundling opponents contend the practice allows individuals to circumvent FECA by delivering larger contributions than they could on their own, even though those contributions are funded by multiple sources. Critics also point to anecdotal evidence suggesting that some contributions routed through bundlers might have been coerced or come from impermissible sources. Nonetheless, bundling is not prohibited by FECA or FEC regulations; it is also a common fundraising practice. The FEC unanimously approved rules implementing HLOGA's bundling provisions on December 18, 2008. An "explanation and justification" (E&J) statement approved in February 2009 provided additional guidance and clarified the commission's decision-making process. HLOGA's major requirement regarding bundling, and the major requirement in the new bundling rules, is that political committees report contributions "reasonably known" to be bundled if at least two of those contributions aggregated at least $15,000 ($16,000 as adjusted for inflation in 2010) during specified reporting periods. Only contributions bundled by registered lobbyists must be included in bundling disclosure reports. Committees are to determine whether bundlers are registered lobbyists by consulting the websites of the Clerk of the House, Secretary of the Senate, or FEC (in the case of PACs maintained or controlled by registered lobbyists). The commission noted in the new rules that other sources of knowledge about lobbyists' bundling activities could also trigger reporting requirements. (As discussed in the next section, however, credit plays a more prominent role in bundling disclosure than does knowledge.) Two aspects of the new bundling rules have generated some controversy. The first concerns whether political committees "credit" particular lobbyists with raising bundled contributions. Under the new rules, political committees are required to report contributions as being bundled only if the committee has awarded (through external recognition or internal records) credit to a particular lobbyist or lobbyists for having bundled the contributions. As the commission noted in the E&J, a lobbyist merely claiming to have bundled contributions does not necessarily warrant disclosure, nor does committee knowledge of a lobbyist being a bundler if the committee has not credited that person with bundling for the committee. According to the commission, "[M]ere knowledge [of bundling], in and of itself, is not enough. Rather, it is necessary for a reporting committee to credit through'records, designations, or other means of recognizing that a certain amount of money has been raised' before reporting is required." The second area of contention, related to the first, concerns how credit is awarded for jointly hosted fundraising events. Under the new rules, all hosts of joint fundraising events would have to be listed in bundling disclosure reports only if those hosts were registered lobbyists and were credited by the campaign with raising bundled contributions that met the $16,000 threshold. As the FEC stated in the E&J, for example, an event co-hosted by three lobbyists that generated $20,000 would require bundling disclosure attributing the entire amount to only the one lobbyist the committee credited with having been responsible for raising the funds (assuming the committee did not award credit to the other two). In cases in which more than one lobbyist is credited with raising funds, the committee must report the share raised by and credited to each individual. Some groups have criticized both these components of the rules, suggesting that they could permit political committees to avoid disclosing bundling activities simply because they do not award tangible credit for doing so. The joint-fundraiser provisions, they say, also could allow committees to avoid disclosing the roles of some bundlers through manipulation of crediting arrangements. The FEC, however, contends that awarding credit is the "focus of HLOGA Section 204" [the bundling provision] and that the rules are consistent with the law's legislative history. Policy Considerations If Congress chooses to revisit bundling policy, two perspectives could be relevant. The first emphasizes reporting information about bundling. The second emphasizes further regulating bundling practices. From the reporting (disclosure) perspective, a key question is whether campaigns should continue to be permitted to provide information only about bundling by registered lobbyists. If so, existing requirements could be sufficient, provided that Congress is satisfied with the reporting criteria established in HLOGA and FEC regulations. Congress may also wish to monitor continued FEC implementation of the HLOGA requirements and the effectiveness of the new reporting process, which took effect during the spring and summer of 2009. If it chose to do so, Congress could also amend Section 204 of HLOGA to require different disclosure than is articulated in the new bundling rules. From a broader perspective, Congress may wish to increase transparency about bundling overall, including by non-lobbyists. A relatively straightforward way to do so could be to extend the existing disclosure requirements to cover bundling by anyone, regardless of profession. During the 110 th Congress, S. 2030 (Obama) essentially proposed such an approach; the bill did not advance beyond committee referral. If Congress adopted the view that bundling should be discouraged or reduced, additional regulation could be necessary. For example, limits could be applied to the amount or number of contributions arranged by a single bundler. Bundling could also be banned altogether. Depending on specifics, however, a ban could prohibit even basic fundraising involving multiple contributors. For those who believe that bundling circumvents FECA, additional restrictions or disclosure requirements could enhance transparency, limit the prevalence of bundling, or both. On the other hand, those restrictions could increase compliance burdens for the regulated community. Finally, those who view bundling as an efficient and effective fundraising practice may object to further regulation. Campaign Travel Aboard Private Aircraft In addition to the bundling restrictions discussed above (and other issues), HLOGA restricts campaign travel on private, non-commercial aircraft (e.g., charter jets). Before HLOGA became law, under 2003 FEC regulations political committees were permitted to reimburse those providing private aircraft at the rate of first-class travel as long as commensurate first-class commercial service were available for the route flown. Reimbursement at non-discounted coach or charter rates was required if commensurate first-class service were unavailable on the route. By contrast, under HLOGA, Senators, candidates, and campaign staff may continue to travel on private aircraft only if they reimburse the entity providing the aircraft for the "pro rata share of the fair market value" for rental or charter of a comparable aircraft (e.g., the charter rate). The latter rates would typically be well above the old first-class rate that applied to most flights before HLOGA took effect. Unlike their Senate counterparts, House Members, candidates, and campaign staff are "substantially banned" from flying aboard private, non-commercial aircraft, as HLOGA precludes reimbursements for such flights. Although the FEC adopted rules to implement HLOGA's air-travel provisions in December 2007, a required explanation and justification statement was not adopted before the commission lost its policymaking quorum in January 2008. Consequently, the air-travel rules were never published in the Federal Register and never took effect. Additional nominees were confirmed to the commission in June 2008, bringing the agency back to full policymaking strength. However, the commission did not finalize the HLOGA travel regulations until November 2009. Under the rules adopted by the FEC on December 14, 2007—but never finalized—Senate, presidential, and vice-presidential campaign travel aboard private aircraft was required to be reimbursed at the "pro-rata share" of the charter rate. These requirements also would have applied to travel on behalf of PACs (including leadership PACs ) and party committees. In essence, this meant that presidential, vice-presidential, or Senate campaign travel occurring aboard charter aircraft would have had to be paid for based on charter rates. HLOGA essentially banned reimbursement for House campaign travel aboard private aircraft, as was evident in the 2007 rules. On November 19, 2009, the commission revisited the travel rules at an open meeting. During the meeting, commissioners debated congressional intent in the relevant section (601) of HLOGA and potential interpretations of the statute. A motion to approve an explanation and justification (E&J) statement supporting the December 2007 rules failed by a 3-3 deadlocked vote along partisan lines. Immediately afterward, alternative rules and an accompanying E&J were approved by a 4-2 vote in which Chairman Walther (I) joined Republican Commissioners Hunter, McGahn, and Petersen to constitute a majority. Consequently, the new rules and E&J superseded the never-finalized 2007 rules. A detailed discussion of the lengthy and complex new rules is beyond the scope of this report. Essentially, however, the 2009 rules distinguish between restrictions on campaign travel and travel on behalf of PACs or political parties. The rules also require charter-rate reimbursement in some circumstances but permit reimbursement at coach, first-class, or charter rates (depending on the route flown) in others. Specifically, the new rules require that candidate -oriented travel for presidential, vice-presidential, and Senate travel be reimbursed at the charter rate. By contrast, travel on behalf of party committees or leadership PACs may be reimbursed based on the 2003 regulations (often the first-class rate). House campaign travel—including for House-oriented leadership PACs—aboard private aircraft remains, essentially, prohibited, although travel on behalf of House party committees could be reimbursed at the 2003 rates. Policy Considerations Controversy has emerged over the degree to which the November 2009 rules reflect congressional intent as enacted in HLOGA. Some opponents of the new rules suggest that Congress clearly intended for charter-rate reimbursement to apply to all campaign-related travel, even if parties or PACs pay for the flights. They also argue that the rules could provide cover to avoid the more expensive charter-rate reimbursement simply by classifying travel as on behalf of PACs or parties rather than individual Senate campaigns. Defenders of the new rules, however, suggest that Congress required charter-rate reimbursement only for presidential, vice-presidential, or Senate candidate travel and that it would be improper for the FEC to require PACs or parties to reimburse at the charter rate (unless no commercial service were available). If Congress objects to the new rules, as at least one Senator has, oversight or legislation could be employed. For example, the charter rate could be applied to all campaign travel regardless of whether the travelers are doing so for candidates, parties, or PACs. In addition, Congress could clarify that restrictions on reimbursement by House leadership PACs are also intended to apply to Senate leadership PACs. Congress could also essentially ban Senate campaign travel aboard private aircraft, as is already the case for House campaign travel. As an alternative (or addition) to legislation, Congress could choose to monitor implementation of the new rules to determine whether travel reported as PAC and party travel actually primarily benefits those entities, or whether it appears to subsidize Senate campaigns. Finally, as is often the case with FEC rulemakings, Congress or others could pursue litigation to revisit the rules. By contrast, however, those who believe that the new rules accurately reflect congressional intent or are otherwise acceptable would likely prefer the status quo, in which case little or no congressional action is necessary. Electronic Filing of Senate Campaign Finance Reports Unlike all other federal political committees (except those raising or spending less than $50,000 annually), Senate campaign committees, party committees, and PACs are not required to file campaign finance reports electronically. Senate reports are also unique because they are filed with the Secretary of the Senate rather than directly with the FEC. In the 110 th Congress, the Senate Committee on Rules and Administration reported S. 223 (Feingold), which would have extended electronic filing to Senate reports. The bill was never considered on the Senate floor, despite attempts to bring it up under unanimous consent. Despite the lack of success in the 110 th Congress, electronic filing remains a widely popular policy proposal. In the 111 th Congress, Senator Feingold has introduced S. 482. That bill is substantially similar to S. 223 from the 110 th Congress. Senator Feingold has also introduced S. 1858, which would amend FECA to both require electronic filing and reporting directly to the FEC. The Senate versions of the DISCLOSE Act ( S. 3295 and S. 3628 ) also contain electronic filing provisions. Policy Considerations Two major policy questions surround electronic filling. Both are straightforward. First, should Senate campaign finance reports be filed electronically? Second, if so, where should those reports be filed? The primary arguments in favor of electronic filing concern efficiency and expense. Currently, a contractor converts the paper reports filed with the Secretary into electronic format. The FEC then makes the reports publicly available on the Internet. The conversion process can take weeks or months at a reported cost of $250,000 annually. As a result, House campaign finance data filed electronically (and directly with the FEC) are routinely available well before Senate data. Various Members of Congress, campaign finance groups, and media organizations have supported electronic filing. Both the FEC and the Secretary of the Senate have stated publicly that their offices are, or can be, prepared to administer electronic filing. Electronic filing could eliminate the conversion process and make public disclosure of the data much faster. Electronic filing could, therefore, improve transparency and reduce costs. Requiring electronic filing of Senate reports would also place the same filing responsibilities on Senate committees that currently exist for House candidate committees, party committees, and PACs. As a result, uniform filing standards would apply to all political committees. There is little, if any, notable opposition to electronic filing itself. However, some Members have called for addressing other campaign finance disclosure issues alongside electronic filing. For example, attempts in the 110 th Congress to bring up S. 223 were unsuccessful amid a dispute over whether the bill would be amended to require groups filing ethics complaints to disclose their donors. Similarly, at a March 2007 Senate Rules and Administration Committee hearing on S. 223, Senator Stevens emphasized the need to also consider disclosure requirements for 527 organizations. Filing location has been a secondary issue of debate. Senate reports are currently filed with the Secretary of the Senate rather than with the FEC. Bypassing filing with the Secretary of the Senate could make reports more readily accessible to the public and could reduce delay or costs associated with transmitting the reports to the FEC. If campaign finance reports are considered Senate documents, however, some may object to their being filed with the FEC. During the 110 th Congress, Senator Feinstein reported at a markup of S. 223 that Senator Byrd raised concerns about the possibility of filing directly with the FEC because he viewed filing with the Secretary as a matter of Senate prerogative. Federal Election Commission Issues The 1974 FECA amendments established the FEC, which enforces civil compliance with campaign finance law. The commission also facilitates disclosure of federal campaign finance data and administers the presidential public financing program. Six presidentially appointed commissioners lead the agency; the Senate may confirm or reject nominations to the FEC. The 110 th Congress enacted one bill affecting the agency's functioning. P.L. 110-433, which President George W. Bush signed in October 2008, extended authority for the FEC's Administrative Fine Program (AFP) until 2013. (The program had been set to expire at the end of 2008.) The AFP sets standard penalties for routine financial-reporting violations and requires fewer resources than the commission's full enforcement process, which can involve protracted negotiations, litigation, or both. During the 111 th Congress, the FEC has had and will have responsibility for implementing any changes to campaign finance law that Congress enacts or judicial rulings that affect campaign finance law or regulation. Internal commission issues, including "deadlocked" votes—those which fail to achieve at least a four vote majority for or against an action—are also potentially noteworthy. As noted elsewhere in this report, commission rulemakings, particularly on campaign travel aboard private aircraft, could also receive congressional consideration. Policy Considerations Perhaps the most fundamental policy question surrounding the FEC is the status of the agency itself. Questions about the commission's structure and effectiveness have long been a topic of debate. In the 111 th Congress, for example, S. 1648 (Feingold) would replace the FEC with a proposed Federal Election Administration (FEA). Major provisions of the bill would establish a three-member governing body with enhanced enforcement powers. Two similar bills, H.R. 421 (Meehan) and S. 478 (McCain), were introduced in the 110 th Congress. Neither bill advanced beyond committee referral. Other FEC issues would not necessarily warrant legislative action, but could be relevant for oversight or appropriations matters. In particular, Congress may wish to monitor the agency as the FEC continues to recover from a six-month loss of its policymaking quorum. Between January and June 2008, only two commissioners remained in office due to a nominations dispute. As a result, the commission was unable to approve (among other things) agency rules and enforcement actions. As noted previously, loss of the commission's operating quorum continues to be relevant for issues left unresolved from the period, such as, until recently, the HLOGA travel rules. Commission enforcement and operations could also be of interest to Congress. Some Members of Congress have also expressed concern about deadlocked votes at the commission (which can, but do not necessarily, affect enforcement issues). In January 2009, the FEC held two days of hearings on various operations issues. At these wide-ranging sessions, a variety of election lawyers and interest-group representatives both praised and criticized the FEC's procedures and transparency. The agency is also currently reconsidering its Internet presence, including how various constituencies are served through the FEC website. The commission held July and August 2009 hearings on the topic. The commission will also have responsibility for implementing regulatory changes resulting from litigation such as Citizens United. Finally, nominations to the FEC, subject to Senate advice and consent, have received legislative attention during the 111 th Congress. On April 30, 2009, the terms of two commissioners expired. The term of a third commissioner had already expired. As Table 1 shows, the term of Commissioner Ellen Weintraub expired in 2007. She remains at the agency in holdover status. The terms of Commissioners Donald McGahn and Steven Walther expired on April 30, 2009; they may also continue to serve in holdover status. A commissioner may remain in office after the expiration of his or term unless or until (1) the President nominates, and the Senate confirms, a replacement; or (2) the President, as conditions permit, makes a recess appointment to the position. On May 1, 2009, President Obama announced his intention to nominate Service Employees International Union (SEIU) associate general counsel John J. Sullivan to the commission. (Sullivan would have replaced Commissioner Weintraub.) The Senate Rules and Administration Committee held a brief hearing on Sullivan's nomination on June 10, 2009. Various campaign finance interest groups took opposing positions on the Sullivan nomination. In particular, groups such as the Campaign Legal Center and the Center for Competitive Politics reportedly disagreed about the extent to which Sullivan's positions—as expressed while representing the SEIU before the FEC—would have affected his ability to enforce FECA and FEC regulations, particularly regarding political advertising. At the June 10, 2009, Senate Rules and Administration Committee hearing, Sullivan noted that his SEIU work reflected advocacy on behalf of his client, not necessarily his personal willingness to enforce law or regulation. Three Senators who attended the hearing (Chairman Schumer, Ranking Member Bennett, and Senator Chambliss) expressed support for Sullivan's nomination and noted that they expected him to be confirmed. The committee favorably reported the nomination by voice vote on June 11, 2009. However, the nomination then received no additional action in the Senate. President Obama withdrew the nomination in August 2010. As of this writing, no replacement has been nominated. Hybrid Advertising Hybrid advertising references a clearly identified candidate and makes generic references to other candidates of a political party (e.g., "John Doe and our Democratic team"). Hybrid ads are of potential legislative concern because of a cost-sharing practice associated with the ads. With traditional advertising, the sponsoring entity typically covers all costs. With hybrid advertising, the party and the candidate's campaign committee share costs. An FEC rulemaking on the issue has been open since May 2007. Policy Considerations The controversy over hybrid advertising concerns whether the method of paying for those advertisements undermines FECA. Those calling for additional regulation of hybrid ads have suggested that cost-sharing represents a "loophole" that permits parties to improperly subsidize campaign spending. This is particularly noteworthy for publicly financed presidential campaigns, which must agree to limit their spending as a condition of receiving public funds. Cost-sharing might also be viewed as way of circumventing limits on coordinated party expenditures. Those who object to current cost-sharing practices allege that shared costs primarily benefit only the named candidate yet allow that candidate's campaign committee to pay for only a portion (e.g., 50%) of the advertising. Some groups have urged the FEC to adopt regulations attributing 100% of the cost to the named candidate. If Congress determines that additional regulation of hybrid advertising is necessary, it could wait for the FEC's ongoing rulemaking to proceed. However, it is unclear if or when the agency will issue new rules. Alternatively, Congress could legislate particular cost-sharing requirements. Doing so could close the arguable loophole surrounding hybrid ads, but would also involve legislating in a technical area more typically left to the FEC. Congress could also choose to make no changes if it determines that hybrid ads do not circumvent FECA or that additional regulation is unnecessary. Those opposed to additional restrictions suggest that existing FEC regulations provide sufficient guidance on various cost-sharing arrangements, including hybrid advertising. Additional restrictions, including legislation, could also minimize parties' flexibility to allocate costs according to individual circumstances. That flexibility was a central concern for various party representatives who testified at a July 2007 FEC hearing. Finally, cost-sharing associated with hybrid ads could also be viewed as the continuation of a long tradition of various contacts between parties and campaigns during campaigns. Therefore, some may fear that additional restrictions on hybrid advertising could threaten the relationship between parties and candidates. Joint Fundraising Committees Joint fundraising committees were particularly active in the 2008 presidential race, but also supported House and Senate contests. Joint committees are of potential legislative concern because some observers contend that they facilitate large contributions that would otherwise be impermissible under FECA. FECA limits contributions from individuals as shown in Table 2. In 2007-2008, individuals could contribute no more than $4,600 to a candidate campaign ($2,300 for the primary campaign and another $2,300 for the general-election campaign). As the table shows, individuals could also donate up to $28,500 annually to national party committees and up to $10,000 annually to state or local party committees. During the 2008 cycle, joint fundraising committees affiliated with the Democratic and Republican presidential campaigns collected contributions that exceeded the limits discussed above. In some cases, the committees (often called "victory funds") reportedly received contributions of $70,000 or more from a single source. Joint committees then distributed those contributions, in permissible amounts (i.e., consistent with the individual contribution limits), to other political committees. Recipients included each party's presidential campaign, their legal and accounting compliance committees, national party committees, and party committees in targeted states. Policy Considerations As Congress considers whether or how to restrict joint fundraising committees, a key question is whether the House and Senate believe joint committees circumvent FECA. Some joint committees represent an "extra" way to support candidates above the individual contribution limits. A coalition of interest groups has urged the 111 th Congress to ban joint fundraising committees. If Congress chooses to restrict joint committees, at least four options exist. First, joint committees could be prohibited. Second, candidate participation in joint fundraising could be restricted. Third, Congress could restrict joint committees' abilities to transfer funds to other recipients. Fourth, FECA or FEC regulations on coordination could be amended to encompass joint fundraising. If joint fundraising committees were prohibited or restricted, those who wanted to support more than one political committee would have to contribute directly to those committees, within the limits established in FECA. Applying the coordination restrictions to joint committees could limit the amount of permissible transfers among committees. Any of these options could make it more difficult for individuals to make contributions to a single source in the hopes of benefitting multiple recipients. Conversely, Congress could choose to maintain the status quo if it determines that joint committees do not violate the spirit of FECA. In turn, this conclusion depends on whether one believes that joint committees are a backdoor method of supporting individual candidates or whether joint committees support a variety of party-building activities, as existing FECA provisions and FEC regulations appear to assume. Some also contend that joint committees represent an efficient way to funnel large aggregate contributions, in permissible amounts, to targeted states and political committees. No legislative action is necessary to maintain the status quo. Public Financing of Congressional Campaigns72 Despite introduction of congressional public financing legislation in virtually every Congress since the 1950s, House and Senate campaigns have always been privately financed. The 1980s and early 1990s were the most intensive period of congressional activity on public financing of House and Senate campaigns. Congressional public financing legislation has only passed both chambers and been reconciled in conference once, during the 102 nd Congress (1991-1992). President George H.W. Bush vetoed the legislation ( S. 3 ), which would have provided additional funds to those facing certain high-spending opponents, in addition to matching funds and broadcast and postal benefits in certain cases. Momentum for congressional public financing legislation subsided by the mid-1990s and early 2000s. The issue has received renewed attention in recent Congresses. Five congressional public financing bills were introduced in the 110 th Congress: H.R. 1614 (Tierney), H.R. 2817 (Obey), H.R. 7022 (Larson), S. 936 (Durbin), and S. 1285 (Durbin). All five bills proposed to publicly fund House or Senate campaigns. All focused on providing grants and other benefits designed to cover all costs of participating candidates. None of the bills advanced out of committee, although the Senate Rules and Administration Committee held a hearing on various congressional public financing issues, including S. 1285, in June 2007. Five congressional public financing bills have been introduced in the 111 th Congress. The first bill introduced, H.R. 158 (Obey), would essentially mandate public financing during House general elections by prohibiting candidate spending other than from a proposed public financing fund. In exchange, candidates would receive grants designed to cover full campaign costs. Second, H.R. 2056 (Tierney) proposes a "clean money, clean elections" model, in which participants would receive a combination of grants and matching funds in exchange for limiting campaign spending. Three other bills, H.R. 6116 (Larson), H.R. 1826 (Larson), and S. 752 (Durbin), propose voluntary public financing that provides a base subsidy, matching funds, and, except for H.R. 6116, broadcast vouches. Unlike most public financing proposals, however, the three bills would not impose spending limits on participants, provided that their private fundraising were limited to $100 contributions (per election) from individuals. The Committee on House Administration held a July 28, 2009, hearing on H.R. 1826. H.R. 6116, introduced in September 2010, is apparently intended to supersede H.R. 1826. The committee ordered H.R. 6116 reported on September 23, 2010. Policy Considerations The debate over public financing of congressional campaigns is more than 50 years old. In brief, supporters say that public financing can reduce the threat of political corruption, enhance electoral competition, and allow candidates to focus on issues rather than raising money. On the other hand, opponents suggest that private financing is sufficient, particularly in an era when public funds are needed for various other government services. Some public financing opponents believe that government-funded campaign subsides amount to "welfare for politicians." The spending limits that also often accompany public financing proposals also raise constitutional concerns for those who criticize public financing proposals. In addition to those perennial issues, one of the most significant questions surrounding public financing proposals is how to design a program that provides enough benefits to allow participants to mount robust campaigns. The level of benefits and spending limits offered in exchange for participation in public financing is particularly important. The three companion bills, H.R. 6116, H.R. 1826, and S. 752 contain a familiar combination of grants and other benefits for participating candidates. Unlike most other proposals, however, the bills would not limit participants' expenditures, provided that their spending were limited to allocations from proposed public financing funds or private fundraising of no more than $100 per individual contributor, per election. These "small dollar" contributions would also be eligible for federal matching funds. Regardless of the chosen approach, public financing would not altogether eliminate private money in politics. Virtually all proposals require some private fundraising to establish viability, albeit far less than under private financing. In addition, some observers fear that public financing creates opportunities for more financial influence from less accountable sources, such as independent expenditures and election-related "issue advocacy" by interest groups. Public financing systems generally do not regulate fundraising or spending outside candidate campaigns, although legislation could address such issues. Public Financing of Presidential Campaigns 76 Perhaps the most prominent campaign finance issue during the 2008 election cycle was the status of the presidential public financing system. Even before the 2008 campaigns began in earnest, the cycle was widely perceived as the last in which the current public financing system could survive without major reform. The program suffers from low taxpayer participation, resulting in funding shortfalls during recent elections. As the program's financial resources and public participation generally declined in recent elections, so did participation by major candidates. In 2008, eight candidates received PECF matching funds during the primaries. Senator McCain, the Republican nominee, received public funds during the general-election campaign. Senator Obama, the Democratic nominee, became the first major-party nominee since the program's inception to completely decline public funds. Some observers have suggested that Senator Obama's decision to opt out of public financing, combined with the other challenges discussed above, marks the death knell of the program. Others contend that the public financing program can work well again if reformed. Policy Considerations Until the 2000 election, the public financing program was the major funding source in presidential campaigns, particularly for the general election. Nonetheless, as noted above, public financing has become less appealing to candidates in recent elections. Other developments, such as joint fundraising committees allegedly threaten the program's intended emphasis on limiting private fundraising in exchange for public funds. Maintaining the status quo would leave the public financing program unchanged. If that approach is taken, however, there is widespread agreement that the most competitive candidates will continue to forgo public funds. As a result, the program could be in danger of providing funding only for those candidates with a limited chance of success. As the preceding discussion suggests, a fundamental policy question is what role—if any—Congress wants public financing to play in presidential campaigns. If that role is to be a prominent one, there is broad agreement that the program needs to be at least partially revamped. Making the program more attractive to competitive candidates, particularly through increased spending limits, is a major focus of several reform proposals. Such efforts will not come without costs. An infusion of funds, through an increased checkoff designation, other revenue sources, increased taxpayer participation, or a combination of all three, would likely be necessary. Public financing can also be controversial along ideological lines, which suggests that strong political will and coalition-building will be necessary if changes to the program are to be enacted. In the aftermath of the 2008 election cycle, the related issue of small contributions has also been a prominent topic of debate. Although publicly financed general-election candidates must agree to forgo private fundraising for their campaigns, public financing is designed to supplement small, private contributions during the primary campaign. Currently, the Presidential Election Campaign Fund (PECF) provides a 100% match of individual primary contributions up to $250. Providing additional matching funds have been a major component of recent reform proposals. Two bills to revamp the presidential public financing system were introduced in late July 2010. Neither H.R. 6061 (Price, NC) nor S. 3681 (Feingold) have been the subject of additional action. Those bills took root in similar proposals offered during the previous Congress. During the 110 th Congress, four bills ( H.R. 776 (Meehan), H.R. 4294 (Price, NC), S. 436 (Feingold), and S. 2412 (Feingold)) that proposed to restructure the PECF would have matched small contributions at 400% or 500% rather than the current 100%. In addition, the maximum matching contribution would have been lowered to $200 from the current $250. Increasing the match rate from the current 100% to 400% or 500% could increase the effect of small contributions. It could also provide substantially greater resources to publicly financed candidates. However, this approach assumes that sufficient funds would be available in the PECF to cover the additional match. In fact, sufficient funds have been unavailable during portions of recent election cycles. Nonetheless, proposals to reform the public financing program typically include revisions to funding mechanisms. Congress could also renew the focus on small contributions by permitting publicly financed campaigns to spend larger (or unlimited) amounts of funds raised through small contributions. This approach might or might not include matching funds. The effect could be to encourage candidates to focus their efforts on small contributions, while still providing government assistance for some campaign needs. However, focusing on small contributions would not necessarily contain campaign costs (another program goal), particularly for those candidates who were able to raise and spend virtually unlimited amounts. In fact, if spending limits were eliminated, public financing could become an additional, but potentially unnecessary, funding source for those already able to raise substantial private funds. Finally, public financing could be repealed. This approach would largely or entirely (depending on specifics) eliminate taxpayer funds in presidential campaigns. In the 110 th Congress, two bills ( H.R. 72 (Bartlett), H.R. 484 (Doolittle)) would have repealed parts of the program or the entire program. Neither bill advanced beyond committee referral. In the 111 th Congress, Representative Cole has H.R. 2992 introduced legislation to repeal public financing for presidential nominating conventions. 527 Organizations FECA focuses largely on political committees, which include candidate committees, party committees, and PACs. In recent years, "527" organizations have shaped some elections even though they are not typically considered to be political committees. America Coming Together and Swift Boat Veterans for Truth, for example, were prominent (and controversial) in 2004. Much of the concern surrounding 527s has involved the argument that millions of dollars from these organizations affect federal elections without necessarily being regulated by FECA. The precise nature of 527s' financial impact is open to debate, as various research organizations and interest groups classify individual groups' activities differently and rely on different data. Nonetheless, and despite differing data and interpretations of those data, research has consistently shown decreased activity among 527s during the 2008 cycle compared with the 2004 cycle. Table 3 displays financial summaries from two prominent sources, CQ MoneyLine (a commercial tracking service) and the Center for Responsive Politics (CRP). Both sources show that 527s' receipts and expenditures during the 2008 cycle were far below those of the 2004 cycle. Policy Considerations The 527 issue can be considered from both financial and regulatory perspectives. Financially, 527s remain a significant force surrounding some targeted races. 527s also continue to command substantial financial resources overall. Nonetheless, 527s' decreased financial activity suggests that the issue might not receive as much policy attention as 527s have in recent years. Even with decreased financial activity, however, the matter of regulating 527s continues to be controversial. Indeed, the major policy question surrounding 527s is whether all such organizations should be regulated as political committees under FECA. Thus far, the FEC has made case-by-case determinations of whether 527s' activities required them to register as political committees. Particularly after the 2004 elections, the FEC assessed major fines against some 527s for failing to register as political committees. However, because fines were not assessed until well after the election and represented a small portion of the organizations' operating budgets, some critics contended that the penalties and current regulation of 527s were insufficient. Controversy over FEC enforcement regarding 527s continues today. Against this backdrop, some have suggested that all 527s should be required to register with the FEC as political committees. In the 110 th Congress, H.R. 420 (Meehan) and S. 463 (McCain) would have amended FECA to treat 527s as political committees, with some exceptions. Requiring 527s to register as political committees would make those organizations subject to contribution limits and other requirements in FECA, just as all political committees are today. Those advocating additional regulation of 527s generally suggest that these groups' activities clearly influence federal elections and, therefore, should be captured by FECA. Others, however, contend that placing additional regulations on 527s is unnecessary and could stifle the groups' political speech. Activity on Legislation Related to Campaign Finance: Restricting Campaign Activity by Certain State Election Officials Election administration is not necessarily related to campaign finance policy. Some legislation, however, can affect both policy areas. Although devoted primarily to election administration, H.R. 512 proposes to amend FECA. Therefore, the FEC would implement the measure if it became law. As passed by the House (296-129) on September 29, 2010, H.R. 512 (Davis, CA) would prohibit "chief State election administration officials" (e.g., Secretaries of State) from "tak[ing] an active part" in managing or otherwise being involved in federal election campaigns if the official "has supervisory authority" for administering the relevant election. Among other restrictions, the bill would prohibit a chief election official from "serving as a member" of a federal candidate's principal (authorized) campaign committee or engaging in fundraising for their campaigns. The bill would provide an exemption for involvement in a family member's federal campaign. Policy Considerations As H.R. 512's findings section suggests, the bill could reduce the potential for conflicts of interest among officials who are involved in both campaigning for, and supervising the elections of, federal candidates. At a June 10 markup of the bill, some Members expressed concern that H.R. 512 appeared to presume that election officials could not objectively separate campaign activities and election-administration duties, and might unnecessarily limit election officials' political activities. Representative Lungren, ranking member of the Committee on House Administration, reiterated those themes during floor debate. By contrast, Representative Susan Davis countered that the measure was reasonably limited to thwarting potential corruption and designed to enhance integrity in the electoral process. As Congress considers H.R. 512, at least two points, in addition to those discussed above, could be relevant. First, if Congress is primarily concerned about real or potential conflicts of interest among a state's chief election-administration officials, the language proposed in H.R. 512 could be sufficient. The bill does not, however, propose to regulate conduct by other election officials. Second, the scope of at least one element of the bill is potentially unclear. As noted above, H.R. 512, would prohibit a chief state election-administration officer from "serving as a member of an authorized committee of a candidate for Federal office." In a practical sense, this language suggests that affected election-administration officials would be prohibited from active involvement in a federal candidate's campaign. The term "member," however, is not defined in FECA or in FEC regulations. Although the term "political committee" might connote membership, those involved in campaign management are also not typically referred to as committee members, which suggests potential ambiguity about which campaign roles the bill intends to regulate. If a more precise meaning of "member" were a concern, Congress could amend the bill to more explicitly identify particular campaign roles or duties. The FEC could also clarify the scope of that portion of the language through a rulemaking if H.R. 512 becomes law. Overarching Policy Concerns and Concluding Comments For some, a steady increase in money flowing through the 2008 and 2010 election cycles suggests that the campaign finance system is in need of significant reform. Others contend that the primary focus should not be on the amount of money in politics, but on the way in which that money is regulated. For many, existing regulation is already too cumbersome. Both election cycles will undoubtedly inform deliberations about how, if at all, to examine campaign finance policy during the 111 th Congress. Some of the issues discussed in this report are closely tied to recent elections. Others have been prominent for several election cycles and have received congressional attention in the past. All the issues discussed in this report are essentially technical questions about how to regulate a particular facet of campaigns. Reaching consensus on these points can be difficult. There are, however, common themes that tend to organize the debate over campaign finance policy. Even when Members of Congress disagree about particular approaches, these themes can serve as useful starting points for considering policy options and debate. Amounts and Sources of Money Whether there is "too much" money in American elections is a hotly debated topic. For some, the billions of dollars involved in federal campaigns signal potential corruption. The "money chase" of campaigns also allegedly prevents candidates and officeholders from concentrating on serving their constituents. Others counter that fundraising is an important test of a candidate's political viability and that the amount of money spent on American elections is far less than the amount spent on consumer goods. It is unlikely that this ideologically charged debate will be resolved in the foreseeable future. Even if the debate over amounts money is not resolved, sources of funds could be ripe for legislation or oversight. The debate over 527s demonstrates that some entities' financial activities remain contentious. Similarly, the debate over public financing can be viewed as an attempt to steer candidates toward lower campaign spending with incentives (or requirements) to limit private fundraising. Bundling, hybrid advertising, and joint fundraising also raise policy questions about whether these funding sources should be further regulated. Transparency Transparency is typically accomplished through disclosure. Most of that information is then made publicly available. The details of which activities should be disclosed, and in which amounts, are sometimes controversial, but disclosure is generally accepted as a hallmark of campaign finance policy. The debate over electronic filing of Senate campaign finance reports has the most obvious connections to transparency. For some, the current form of paper filing is wasteful and causes unnecessary delay in providing information to the public. For others, broader disclosure concerns should also be addressed if Senate electronic filing is reconsidered. Senate prerogative may also be a concern. Other recent issues may also be considered from a transparency perspective. In particular, new disclosure requirements related to bundling—enacted in the 110 th Congress and potentially subject to expansion or revision during the 111 th Congress—represent an effort to provide more information about how some large contributions are raised. On the other hand, those efforts may cause an additional compliance burden or inhibit some donors from participating (at least as they otherwise would). Scope of Regulation Perhaps the most fundamental questions in campaign finance policy is which behaviors should be subject to FECA or FEC regulations, and to what extent. As Congress decides how or whether to address campaign finance issues in the 111 th Congress, these questions are again likely to be at the forefront of debate. All the policy issues addressed in this report could involve placing new requirements on members of the regulated community. Among the issues discussed in this report, debate has essentially focused on whether bundling, electronic filing, hybrid advertising, joint fundraising, recent developments in presidential public financing, and 527s undermine various requirements in FECA. More generally, the FEC itself may be reevaluated if Congress determines that its structure or effectiveness is insufficient for current needs. If Congress decides to address these or other campaign finance issues, a key question will be whether they are to be considered alone or jointly. All the issues discussed in this report could be self-contained. Some of the issues are also interactive. This is particularly true for presidential campaign financing, which has clear connections to public financing, bundling, hybrid advertising, and joint fundraising.

Summary: This report provides an overview of selected campaign finance policy issues that may receive, or have received, attention during the 111th Congress. Congress continues to consider the Supreme Court's January 21, 2010, ruling in Citizens United v. Federal Election Commission. The decision has shaped much of the legislative debate on campaign finance issues during the second session of the 111th Congress. Thus far, most congressional attention responding to the ruling has focused on the DISCLOSE Act (H.R. 5175; S. 3295; S. 3628). H.R. 5175 passed the House on June 29, 2010. On a related note, on July 29, 2010, the Committee on Financial Services ordered reported H.R. 4790. The bill would require additional disclosure of political expenditures to corporate shareholders and is designed as a partial response to Citizens United. Other than attention to Citizens United, four aspects of campaign finance policy have been subject to major actions thus far during the 111th Congress. First, in April 2009, the House passed legislation (H.R. 749) concerning authority to disburse campaign funds after a candidate's death. Second, on June 10, 2009, the Committee on House Administration favorably reported H.R. 512 (Davis, CA). The bill would amend the Federal Election Campaign Act (FECA) to restrict certain state election officials from involvement in others' campaigns. Third, on July 28, 2009, the Committee on House Administration held a hearing on H.R. 1826, a bill that would publicly finance House campaigns. The committee ordered reported a successor bill, H.R. 6116, on September 23, 2010. Finally, the Senate considered the nomination of John J. Sullivan to be a member of the Federal Election Commission for much of the 111th Congress. However, the President withdrew the nomination on August 5, 2010. Questions about the health of the presidential public financing system were especially prominent during the 2008 election cycle. Two bills to revamp the presidential public financing system were introduced in late July 2010. Neither H.R. 6061 nor S. 3681 have been the subject of additional action. Also in the 111th Congress, Representative Cole has introduced legislation (H.R. 2992) to repeal public financing for presidential nominating conventions. Legislation on public financing of congressional campaigns was introduced in early 2009 (H.R. 158, H.R. 1826, H.R. 2056, S. 751, and S. 752). H.R. 6116, apparently intended to supersede H.R. 1826, was introduced in September 2010 and, as noted above, was ordered reported. Recent election cycles also witnessed new or expanded techniques for raising and spending money, such as bundling, joint fundraising committees, and hybrid advertising. Remaining issues from the 110th Congress, such as electronic filing of Senate campaign finance reports (S. 482 and S. 1858 in the 111th Congress), may also receive renewed scrutiny. Other issues, such as 527 organizations, may also be addressed. Congressional oversight of the FEC could also be on the legislative agenda. Some of the issues discussed in this report have only recently received substantial attention. Others have long been controversial. All appear likely to remain prominent policy issues. Whether Congress decides to pursue these or other campaign finance issues, common questions about the role of money in politics, transparency, and the need for additional regulation are likely to shape the debate. The text of this report was last updated November 3, 2010. It will not be updated but remains relevant for historical reference. For more recent discussion, see CRS Report R41542, The State of Campaign Finance Policy: Recent Developments and Issues for Congress, by [author name scrubbed].

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Summarize: There is always after the death of anyone a kind of stupefaction; so difficult is it to grasp this advent of nothingness and to resign ourselves to believe in it. But still, when he saw that she did not move, Charles threw himself upon her, crying-- "Farewell! farewell!" Homais and Canivet dragged him from the room. "Restrain yourself!" "Yes." said he, struggling, "I'll be quiet. I'll not do anything. But leave me alone. I want to see her. She is my wife!" And he wept. "Cry," said the chemist; "let nature take her course; that will solace you." Weaker than a child, Charles let himself be led downstairs into the sitting-room, and Monsieur Homais soon went home. On the Place he was accosted by the blind man, who, having dragged himself as far as Yonville, in the hope of getting the antiphlogistic pomade, was asking every passer-by where the druggist lived. "There now! as if I hadn't got other fish to fry. Well, so much the worse; you must come later on." And he entered the shop hurriedly. He had to write two letters, to prepare a soothing potion for Bovary, to invent some lie that would conceal the poisoning, and work it up into an article for the "Fanal," without counting the people who were waiting to get the news from him; and when the Yonvillers had all heard his story of the arsenic that she had mistaken for sugar in making a vanilla cream. Homais once more returned to Bovary's. He found him alone (Monsieur Canivet had left), sitting in an arm-chair near the window, staring with an idiotic look at the flags of the floor. "Now," said the chemist, "you ought yourself to fix the hour for the ceremony." "Why? What ceremony?" Then, in a stammering, frightened voice, "Oh, no! not that. No! I want to see her here." Homais, to keep himself in countenance, took up a water-bottle on the whatnot to water the geraniums. "Ah! thanks," said Charles; "you are good." But he did not finish, choking beneath the crowd of memories that this action of the druggist recalled to him. Then to distract him, Homais thought fit to talk a little horticulture: plants wanted humidity. Charles bowed his head in sign of approbation. "Besides, the fine days will soon be here again." "Ah!" said Bovary. The druggist, at his wit's end, began softly to draw aside the small window-curtain. "Hallo! there's Monsieur Tuvache passing." Charles repeated like a machine--- "Monsieur Tuvache passing!" Homais did not dare to speak to him again about the funeral arrangements; it was the priest who succeeded in reconciling him to them. He shut himself up in his consulting-room, took a pen, and after sobbing for some time, wrote-- "I wish her to be buried in her wedding-dress, with white shoes, and a wreath. Her hair is to be spread out over her shoulders. Three coffins, one of oak, one of mahogany, one of lead. Let no one say anything to me. I shall have strength. Over all there is to be placed a large piece of green velvet. This is my wish; see that it is done." The two men were much surprised at Bovary's romantic ideas. The chemist at once went to him and said-- "This velvet seems to me a superfetation. Besides, the expense--" "What's that to you?" cried Charles. "Leave me! You did not love her. Go!" The priest took him by the arm for a turn in the garden. He discoursed on the vanity of earthly things. God was very great, was very good: one must submit to his decrees without a murmur; nay, must even thank him. Charles burst out into blasphemies: "I hate your God!" "The spirit of rebellion is still upon you," sighed the ecclesiastic. Bovary was far away. He was walking with great strides along by the wall, near the espalier, and he ground his teeth; he raised to heaven looks of malediction, but not so much as a leaf stirred. A fine rain was falling: Charles, whose chest was bare, at last began to shiver; he went in and sat down in the kitchen. At six o'clock a noise like a clatter of old iron was heard on the Place; it was the "Hirondelle" coming in, and he remained with his forehead against the windowpane, watching all the passengers get out, one after the other. Felicite put down a mattress for him in the drawing-room. He threw himself upon it and fell asleep. Although a philosopher, Monsieur Homais respected the dead. So bearing no grudge to poor Charles, he came back again in the evening to sit up with the body; bringing with him three volumes and a pocket-book for taking notes. Monsieur Bournisien was there, and two large candles were burning at the head of the bed, that had been taken out of the alcove. The druggist, on whom the silence weighed, was not long before he began formulating some regrets about this "unfortunate young woman." and the priest replied that there was nothing to do now but pray for her. "Yet," Homais went on, "one of two things; either she died in a state of grace (as the Church has it), and then she has no need of our prayers; or else she departed impertinent (that is, I believe, the ecclesiastical expression), and then--" Bournisien interrupted him, replying testily that it was none the less necessary to pray. "But," objected the chemist, "since God knows all our needs, what can be the good of prayer?" "What!" cried the ecclesiastic, "prayer! Why, aren't you a Christian?" "Excuse me," said Homais; "I admire Christianity. To begin with, it enfranchised the slaves, introduced into the world a morality--" "That isn't the question. All the texts-" "Oh! oh! As to texts, look at history; it, is known that all the texts have been falsified by the Jesuits." Charles came in, and advancing towards the bed, slowly drew the curtains. Emma's head was turned towards her right shoulder, the corner of her mouth, which was open, seemed like a black hole at the lower part of her face; her two thumbs were bent into the palms of her hands; a kind of white dust besprinkled her lashes, and her eyes were beginning to disappear in that viscous pallor that looks like a thin web, as if spiders had spun it over. The sheet sunk in from her breast to her knees, and then rose at the tips of her toes, and it seemed to Charles that infinite masses, an enormous load, were weighing upon her. The church clock struck two. They could hear the loud murmur of the river flowing in the darkness at the foot of the terrace. Monsieur Bournisien from time to time blew his nose noisily, and Homais' pen was scratching over the paper. "Come, my good friend," he said, "withdraw; this spectacle is tearing you to pieces." Charles once gone, the chemist and the cure recommenced their discussions. "Read Voltaire," said the one, "read D'Holbach, read the 'Encyclopaedia'!" "Read the 'Letters of some Portuguese Jews,'" said the other; "read 'The Meaning of Christianity,' by Nicolas, formerly a magistrate." They grew warm, they grew red, they both talked at once without listening to each other. Bournisien was scandalized at such audacity; Homais marvelled at such stupidity; and they were on the point of insulting one another when Charles suddenly reappeared. A fascination drew him. He was continually coming upstairs. He stood opposite her, the better to see her, and he lost himself in a contemplation so deep that it was no longer painful. He recalled stories of catalepsy, the marvels of magnetism, and he said to himself that by willing it with all his force he might perhaps succeed in reviving her. Once he even bent towards he, and cried in a low voice, "Emma! Emma!" His strong breathing made the flames of the candles tremble against the wall. At daybreak Madame Bovary senior arrived. Charles as he embraced her burst into another flood of tears. She tried, as the chemist had done, to make some remarks to him on the expenses of the funeral. He became so angry that she was silent, and he even commissioned her to go to town at once and buy what was necessary. Charles remained alone the whole afternoon; they had taken Berthe to Madame Homais'; Felicite was in the room upstairs with Madame Lefrancois. In the evening he had some visitors. He rose, pressed their hands, unable to speak. Then they sat down near one another, and formed a large semicircle in front of the fire. With lowered faces, and swinging one leg crossed over the other knee, they uttered deep sighs at intervals; each one was inordinately bored, and yet none would be the first to go. Homais, when he returned at nine o'clock (for the last two days only Homais seemed to have been on the Place), was laden with a stock of camphor, of benzine, and aromatic herbs. He also carried a large jar full of chlorine water, to keep off all miasmata. Just then the servant, Madame Lefrancois, and Madame Bovary senior were busy about Emma, finishing dressing her, and they were drawing down the long stiff veil that covered her to her satin shoes. Felicite was sobbing--"Ah! my poor mistress! my poor mistress!" "Look at her," said the landlady, sighing; "how pretty she still is! Now, couldn't you swear she was going to get up in a minute?" Then they bent over her to put on her wreath. They had to raise the head a little, and a rush of black liquid issued, as if she were vomiting, from her mouth. "Oh, goodness! The dress; take care!" cried Madame Lefrancois. "Now, just come and help," she said to the chemist. "Perhaps you're afraid?" "I afraid?" replied he, shrugging his shoulders. "I dare say! I've seen all sorts of things at the hospital when I was studying pharmacy. We used to make punch in the dissecting room! Nothingness does not terrify a philosopher; and, as I often say, I even intend to leave my body to the hospitals, in order, later on, to serve science." The cure on his arrival inquired how Monsieur Bovary was, and, on the reply of the druggist, went on--"The blow, you see, is still too recent." Then Homais congratulated him on not being exposed, like other people, to the loss of a beloved companion; whence there followed a discussion on the celibacy of priests. "For," said the chemist, "it is unnatural that a man should do without women! There have been crimes--" "But, good heaven!" cried the ecclesiastic, "how do you expect an individual who is married to keep the secrets of the confessional, for example?" Homais fell foul of the confessional. Bournisien defended it; he enlarged on the acts of restitution that it brought about. He cited various anecdotes about thieves who had suddenly become honest. Military men on approaching the tribunal of penitence had felt the scales fall from their eyes. At Fribourg there was a minister-- His companion was asleep. Then he felt somewhat stifled by the over-heavy atmosphere of the room; he opened the window; this awoke the chemist. "Come, take a pinch of snuff," he said to him. "Take it; it'll relieve you." A continual barking was heard in the distance. "Do you hear that dog howling?" said the chemist. "They smell the dead," replied the priest. "It's like bees; they leave their hives on the decease of any person." Homais made no remark upon these prejudices, for he had again dropped asleep. Monsieur Bournisien, stronger than he, went on moving his lips gently for some time, then insensibly his chin sank down, he let fall his big black boot, and began to snore. They sat opposite one another, with protruding stomachs, puffed-up faces, and frowning looks, after so much disagreement uniting at last in the same human weakness, and they moved no more than the corpse by their side, that seemed to be sleeping. Charles coming in did not wake them. It was the last time; he came to bid her farewell. The aromatic herbs were still smoking, and spirals of bluish vapour blended at the window-sash with the fog that was coming in. There were few stars, and the night was warm. The wax of the candles fell in great drops upon the sheets of the bed. Charles watched them burn, tiring his eyes against the glare of their yellow flame. The watering on the satin gown shimmered white as moonlight. Emma was lost beneath it; and it seemed to him that, spreading beyond her own self, she blended confusedly with everything around her--the silence, the night, the passing wind, the damp odours rising from the ground. Then suddenly he saw her in the garden at Tostes, on a bench against the thorn hedge, or else at Rouen in the streets, on the threshold of their house, in the yard at Bertaux. He again heard the laughter of the happy boys beneath the apple-trees: the room was filled with the perfume of her hair; and her dress rustled in his arms with a noise like electricity. The dress was still the same. For a long while he thus recalled all his lost joys, her attitudes, her movements, the sound of her voice. Upon one fit of despair followed another, and even others, inexhaustible as the waves of an overflowing sea. A terrible curiosity seized him. Slowly, with the tips of his fingers, palpitating, he lifted her veil. But he uttered a cry of horror that awoke the other two. They dragged him down into the sitting-room. Then Felicite came up to say that he wanted some of her hair. "Cut some off," replied the druggist. And as she did not dare to, he himself stepped forward, scissors in hand. He trembled so that he pierced the skin of the temple in several places. At last, stiffening himself against emotion, Homais gave two or three great cuts at random that left white patches amongst that beautiful black hair. The chemist and the cure plunged anew into their occupations, not without sleeping from time to time, of which they accused each other reciprocally at each fresh awakening. Then Monsieur Bournisien sprinkled the room with holy water and Homais threw a little chlorine water on the floor. Felicite had taken care to put on the chest of drawers, for each of them, a bottle of brandy, some cheese, and a large roll. And the druggist, who could not hold out any longer, about four in the morning sighed-- "My word! I should like to take some sustenance." The priest did not need any persuading; he went out to go and say mass, came back, and then they ate and hobnobbed, giggling a little without knowing why, stimulated by that vague gaiety that comes upon us after times of sadness, and at the last glass the priest said to the druggist, as he clapped him on the shoulder-- "We shall end by understanding one another." In the passage downstairs they met the undertaker's men, who were coming in. Then Charles for two hours had to suffer the torture of hearing the hammer resound against the wood. Next day they lowered her into her oak coffin, that was fitted into the other two; but as the bier was too large, they had to fill up the gaps with the wool of a mattress. At last, when the three lids had been planed down, nailed, soldered, it was placed outside in front of the door; the house was thrown open, and the people of Yonville began to flock round. Old Rouault arrived, and fainted on the Place when he saw the black cloth!

Summary: She arrives to find Charles worried for her safety and depressed about their financial ruin. Ignoring his questions she writes a letter, seals it and, telling him not to read it until the following day, lies down upon her bed and waits to die. She vomits, feels chills and experiences sharp pains. Charles pleads with her to tell him what she's eaten and seeing the love in his eyes she finally points to the letter. When Charles reads that she has poisoned herself he becomes wild with anguish. He sends for Homais who arrives to find Bovary out of his mind with worry. Homais writes letters to Monsieur Cavinet and Doctor Lariviere. Emma calls for her little girl who is frightened by the sight of her sick mother. Cavinet arrives and Charles begs him to save his wife. He prescribes an emetic and soon she is vomiting blood. Soon the celebrated Doctor Lariviere arrives and seeing Emma pulls Charles aside tells him that nothing can be done. Not wishing to see Emma die, Cavinet and Lariviere leave the room and Homais hurries after them in order to invite them to lunch. Before he can leave the town Lariviere is forced to suffer through a meal with Homais and then he is besieged by the townspeople and their complaints of illness. Homais and Cavinet, seeing the priest enter the Bovary house, return to witness the end. In her delirium Emma is pleased to see the priest and implants a passionate kiss on the crucifix. The abbs performs communion and Emma's face acquires a peaceful countenance. Suddenly she begins to breathe rapidly in the throes of death. As she suffers Emma hears the sound of the beggar from Rouen, who has come to Yonville seeking Homais' cure, singing a song that ends with the couplet:. The wind blew very hard that day. And snatched her petticoat away. Emma sits upright and calls out "The blind man. before collapsing dead.

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Summarize: More than 100,000 Chinese have signed a petition on a White House website urging the US to deport the chief suspect in a 19-year-old case of poisoning. Chinese citizens dubious about their country’s legal system are seeking justice in an unusual place for the victim of an alleged attempted murder in China. They are taking the case to the White House. More than 100,000 people have signed a petition on a White House website urging the US to deport the chief suspect in a 19-year-old unsolved case of poisoning that continues to excite strong emotions here. Adding piquancy to the case: The suspect is very well-connected politically in China. In 1994, a chemistry student at one of China’s top universities, Tsinghua, called Zhu Ling was poisoned with Thallium, a chemical often used in rat poison. She did not die, but was left nearly blind, paralyzed, and brain-damaged, needing constant care from her increasingly aged parents. Her fate has not been forgotten, says Wu Hongfei, a former journalist who has followed Ms. Zhu’s case closely, partly because she was pretty and smart and partly because Tsinghua is so prestigious. But the main reason, says Ms. Wu, is that the only real suspect in the case “had close ties to high ranking officials.” Sun Wei, Zhu’s roommate at Tsinghua, was investigated by the police at the time of the incident, but was never charged, though reports at the time said she had access to Thallium. The police said there was not enough evidence to pursue the case; many ordinary citizens believe that evidence was covered up because Ms. Sun’s father's cousin had been deputy mayor of Beijing and her grandfather was reputedly a friend of then President Jiang Zemin. “Because of her family background … she avoided punishment,” complained one netizen, posting as “@Jinse Guniang” on Sina Weibo, a Twitter-like social media platform. Sun changed her name and is believed to now be living in the United States. The case has erupted again into the public consciousness in the wake of last month’s arrest of a student for fatally poisoning his roommate at another prestigious university, Fudan, in Shanghai. The suspect in that case has confessed to putting poison in his dorm-mate’s water dispenser, saying he did it for a joke. Zhu's case continues to rankle. On Monday, after just three days on the White House website, the petition concerning Sun had drawn more than the 100,000 signatures required for the US administration to offer a response. On Sina Weibo, terms relating to the case accounted for three of the top five search words. Journalist Wu has little hope that the White House petition will do any good. Dissident artist Ai Weiwei “attracted a lot of international attention but he is still not allowed to leave China,” she points out. But as public pressure mounts at home, the authorities appear to be listening. Over the weekend, social media posts including such words as “Thallium” or “Zhu Ling” were being scrubbed from the Internet by Chinese censors, apparently afraid of criticism of the Chinese judicial system. By Monday, the censors had lifted their search blocks. And even the state owned media have joined in the chorus of demands. The online version of Peoples’ Daily, organ of the ruling Communist Party and Xinhua, the official news agency, shared a headline: “China, Ruled by Law, Should Seek Justice.” At long last, the victim of that unsolved poisoning seems to have friends in high places, too. Bei, who later went on to start a software development company, for the first time realized that the Internet was going to be a game-changer. “Before that you could not imagine there are nearly, I think, 200 doctors all over the world who can join together to diagnose this girl, and make the right diagnosis, and give treatment advice. It’s impossible to imagine, it’s like a dream,” he told me. Unfortunately, this story has far from a happy ending. Over the years there has been intense netizen speculation that Sun Wei, Zhu’s roommate, was saved from prosecution by her family connections. Sun Wei was reportedly the only person in Zhu's circle with access to thallium. (Sun Wei denies this.) One theory is that she was motivated by jealousy. Online bulletin board sites were flooded with rumors, accusations of guilt and attempts to even hunt down Sun Wei. We may never know what really happened. But as a satisfying verdict was never reached in Chinese courts, someone appearing to be Sun Wei ended up testifying in the court of online opinion. The pressure grew so fierce that in 2005, Sun Wei issued a statement on the popular Tianya bulletin board site. “I am innocent,” she wrote. “I am also a victim of the Zhu Ling case.” She claimed that she had been questioned by police and subsequently cleared of suspicion. Sun Wei even went as far as to scold Chinese netizens for their behavior: “On the Internet, even though everyone is just a virtual ID, one should still be rational and objective, and responsible for his own words and actions.” Netizens, of course, were far from convinced. Now many believe that Sun Wei has left China, and is residing in the United States. There is even a petition on the White House Web site demanding the deportation of Sun Wei. It already has thousands of signatures. And now, making matters worse, netizens suspect that weibo is covering something up. As of May 4, when you searched for Zhu Ling’s name on Sina weibo you learn that according to Chinese law, the results cannot be displayed. Even “thallium” has become a sensitive word, as are other words connected to the case. This level of Zhu Ling-related censorship is new. Zhu Ling’s story has been floating around the Internet for years, and has even been covered by Chinese state media. But now censors are getting worried, in large part because at the end of the day, people are not simply angry about one unsolved crime. Rather, anger over this case reflects a widespread lack of trust in China’s rule of law. As long as the truth of Zhu Ling’s case hasn’t come to light and nobody has been brought to justice, one netizen wrote, “the Chinese dream can only be the powerful officials’ dream.” Weibo censorship has only made people more angry and suspicious. One netizen wrote, “A lot of information about Zhu Ling has been censored. So we can then see that Sun Wei is the murderer.” Another said, “You can delete Weibo and the two characters for Zhu Ling. Can you [also] delete the truth?” One person encouraged microbloggers to continue inundating weibo with comments related to the crime. That way, short of Sina shutting down weibo itself, it would be impossible to erase the people’s pursuit of justice. Of course, it would be far better if this pursuit took place through the actual legal system, rather than on the Internet. The silver lining is that intense interest on weibo is yet another sign of increasing rights awareness among ordinary Chinese, as well as a collective desire for a fairer system. From the beginning of the Zhu Ling drama, the Internet has helped ordinary citizens form networks to solve problems. It helped to save Zhu Ling’s life, and now it is ensuring that her case is not forgotten. Nor is this online activism in pursuit of an abstract notion of justice. If we don’t stand up for Zhu Ling, people reason, who will stand up for me? That's why so many people remain fascinated by Zhu Ling's case. Bei Zhicheng puts it best: “Many of our generation have successful careers and comfortable lives,” he said. "Zhu Ling should have been one of us.” Ting Zhao contributed research to this article. Emily Parker is a senior fellow and digital diplomacy advisor at The New America Foundation, where she is writing a book about the Internet and democracy.

Summary: An unsolved poisoning case has enthralled China, 19 years after the fact, and now more than 112,000 people have signed a petition asking the White House to investigate and deport a former suspect who is said to have moved to the US. Zhu Ling was a chemistry student at a top Chinese university when she was poisoned with Thallium in 1994, the Christian Science Monitor explains. She survived, but is now almost blind, paralyzed, and suffering from brain damage. Her case attracted quite a bit of attention at the time owing to the fact that she was young, smart, and attractive; it was never solved, and now a recent, similar poisoning has re-ignited interest. Police investigated Zhu's roommate, Sun Wei, who was said to have access to Thallium, but she was never charged due to a lack of evidence. Many speculated, however, that evidence was actually covered up because Sun's family was politically connected. She changed her name and is thought to live in the US now; in 2005, she even issued a statement declaring her innocence, the New Republic adds. The case was brought back to the forefront of public attention last month, when a student was arrested for fatally poisoning his university roommate. A journalist who has followed the case doubts the petition will do any good, but the Chinese government has definitely taken notice: Censors were briefly removing social media posts about the case, but now even state media are calling for further investigation.

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Summarize: Updated 1:02 p.m. Eastern Time President Obama on Friday pointed to polls to argue that his proposal of a "balanced approach" on a debt deal - one that includes revenue increases as well as spending cuts - is what the American people want. "My Republican friends have said that they're not willing to do revenues, and they have repeated that on several occasions," he told reporters at a news conference at the White House. "My hope, though, is that they're listening not just to lobbyists or special interests here in Washington, but they're also listening to the American people. Because it turns out, poll after poll, many done by your organizations, show that it's not just Democrats who think we need to take a balanced approach, it's Republicans as well." A Gallup poll released Wednesday found that only 20 percent of Americans support a deal that only includes spending cuts, something Republicans have insisted on. Another 30 percent wanted a deal that was "mostly" spending cuts, and 32 percent wanted a deal split equally between spending cuts and tax increases. Eleven percent favored a deal that was mostly or all tax increases. "The clear majority of Republican voters think that any deficit reduction package should have a balanced approach and should include some revenues," Mr. Obama said. "That's not just Democrats. That's the majority of Republicans." (That Gallup poll found that only one in four Republicans favor a deal that is only spending cuts.) President Obama makes an opening statement on the ongoing budget negotiations before his press conference. / AP Photo/Pablo Martinez Monsivais The president reiterated his desire to see lawmakers "do something big," saying, "We have a chance to stabilize America's finances for a decade, for 15 years or 20 years, if we're willing to seize the moment." An agreement to do so requires "shared sacrifice," he said, including cuts to defense spending, dealing with entitlement spending (including Medicare), and revenue increases. He said he is still pushing for "a big deal" -- he has set $4 trillion as a benchmark in the past -- but also seemed to acknowledge that a smaller (if still "ambitious") deal of around $2 trillion is now more likely. He said he has told congressional leaders that "If we can't do the biggest deal possible, then let's still be ambitious, let's still try to at least get a downpayment on deficit reduction." He said he indicated that that is something "we can actually accomplish without huge changes in revenue or significant changes in entitlements, but we could still send a signal that we are serious about this problem." The president said he wants congressional lawmakers to come back to him within 24-36 hours with a plan, saying that "if they show me a serious plan, I'm ready to move, even it requires some tough decisions on my part." A plan that includes spending cuts in excess of $2 trillion but is "not asking anything from the wealthiest among us or from closing corporate loopholes -- that doesn't seem like a serious plan to me," he added. Mr. Obama's comments follow an appearance Friday morning by House Speaker John Boehner, who says Republicans are leading where the president is not. House Republicans plan a vote next week would raise the debt ceiling in conjunction with passage of a balanced budget amendment, despite the fact that such an amendment has virtually no chance of passage. (Mr. Obama said Friday that "we don't need" a balanced budget amendment.) Obama: We don't need a balanced budget amendment Boehner said in response to Mr. Obama's comments that "President Obama has been talking tough about cutting spending, but his deeds aren't matching his words." "While Republicans have focused on the big problems we face, this White House has focused on protecting the status quo," he said. "The same holds true for entitlement spending, where the White House has been talking in terms of nickels and dimes at a time when trillions of dollars in serious reforms are needed to preserve the programs and put them on a sustainable path." At a closed-door meeting Thursday, Mr. Obama told lawmakers "it's decision time" for a deal, a Democratic official familiar with the talks said. That meeting, which came after a contentious session Wednesday, was described as "very cordial" - though a breakthrough remained elusive. Boehner: Obama has no debt plan. Republicans do Obama presses on debt deal: "It's decision time" Boehner says too many people trying to make deal The Obama administration and many economists, including Federal Reserve Board Chairman Ben Bernanke, have warned of economic catastrophe if the United States does not raise the amount it is legally allowed to borrow -- now $14.3 trillion -- by August 2. Yet lawmakers remain far apart on a deal. Republicans, who control the House of Representatives, have said they will only vote to increase the debt limit in exchange for a deficit-reduction package larger than the amount of the increase. Democrats are in favor of such a package, but there is a major point of contention between the parties: Republicans want the deal to include only spending cuts, while Democrats say it must also include revenue increases as well. If the debt ceiling is not increased by August 2, the administration says, the United States will no longer to be able to pay its obligations, potentially resulting in default to creditors, the suspension of Social Security checks and other benefits, an increase in interest rates and a host of other extremely serious and negative economic consequences. Administration officials have suggested a deal must be in place by roughly July 22 in order to get a deal through Congress in time. "This is not some abstract issue," Mr. Obama said Friday. "These are obligations that the United States has taken on in the past. The Congress has run up the credit card, and we now have an obligation to pay our bills. If we do not, it could have a whole set of adverse consequences. We could end up with a situation, for example, where interest rates rise for everybody all throughout the country -- effectively, a tax increase on everybody -- because suddenly, whether you're using your credit card, you're trying to get a loan for a car or a student loan, businesses that are trying to make payroll, all of them could end up being impacted as a consequence of a default." On Wednesday, ratings agency Moody's put the United States' Aaa bond rating under review for possible downgrade as the deadline approaches, and Standard and Poor's quickly followed suit with its own warning of a possible downgrade; on Thursday, Geithner said bluntly, "we're running out of time." There has been growing momentum around Senate Minority Leader Mitch McConnell's "back-up plan" to effectively hand responsibility for raising the debt ceiling over to Mr. Obama. That would allow Republicans not to have to vote to raise the debt ceiling, but it could also mean no spending cuts in conjunction with the debt ceiling increase. That prospect angers fiscal conservatives. "This proposal is a dereliction of duty by Senator McConnell and everything that's wrong with Washington," Club for Growth President Chris Chocola said Friday of the plan. "It's nothing more than a legislative maneuver by so-called Republicans to avoid responsibility for America's spending problem." Mr. Obama described the McConnell plan as "the least attractive option" Friday, saying that "if we take that approach, this issue is going to continue to plague us for months and years to come." Asked for specifics about what he was considering as part of a debt deal, Mr. Obama said "we've said that we are willing to look at" raising the retirement age and means testing Social Security of Medicare. He said that while he sees those two programs "as the most important social safety nets that we have," by "making some modest modifications in those entitlements can save you trillions of dollars." More coverage of the debt limit from CBS MoneyWatch.com: Jobs: The elephant being ignored in deficit talks? Did Republicans just force the Fed into QE3? Twenty percent favor deficit reduction by cutting spending only PRINCETON, NJ -- Americans' preferences for deficit reduction clearly favor spending cuts to tax increases, but most Americans favor a mix of the two approaches. Twenty percent favor an approach that relies only on spending cuts and 4% favor an approach that uses tax increases alone. These results are based on a July 7-10 Gallup poll, conducted as government leaders from both parties continued negotiating an agreement to raise the federal debt limit. Both Republicans and Democrats appear willing to raise the debt limit, provided the government outlines plans to significantly reduce federal deficits in the future. The parties generally agree on making deep spending cuts, but do not agree on whether tax increases should be included to help reach their target goals for deficit reduction. Many Republicans in Congress oppose any such tax increases; thus, the legislation may not pass if tax hikes are included. Americans do not necessarily share this view, with 20% saying deficit reduction should come only through spending cuts. That percentage is a little higher, 26%, among those who identify as Republicans. Republicans do, however, tilt heavily in favor of reducing the deficit primarily if not exclusively with spending cuts (67%) as opposed to tax increases (3%). Fifty-one percent of independents share that preference. Democrats are most inclined to want equal amounts of spending cuts and tax increases (42%), though more favor a tilt toward spending cuts (33%) than tax increases (20%). The question does not make clear what types of tax increases Americans might be willing to accept, or whether those saying deficit reduction should come "mostly" from spending cuts would prefer that the proportion of spending cuts be closer to 51% or 99%. The public has been willing to endorse higher taxes on wealthy Americans in recent months, in terms of allowing Bush-era income tax cuts to expire and as a means of keeping Social Security solvent. Spending a Key Worry for Americans on Debt Limit Increase Gallup finds about 6 in 10 Americans paying close attention to the debate about raising the debt limit. When the same poll asked for their general position on raising the limit, without providing reasons for doing so or not doing so, Americans were more likely to oppose an increase than favor one. The 42% who are opposed to doing so generally find fault with the government's spending patterns when asked in an open-ended format to explain their views. The most common reasons given for opposing an increased debt limit are that the U.S. already has too much debt and cannot afford more, that the government needs to control its spending, and that it needs to do a better job of budgeting and living within its means. Another common response is that raising the debt limit does not implicitly address the government's debt problem, and that government would likely just keep raising the limit in the future. The smaller proportion of Americans who favor an increase to the debt limit, 22%, are most likely to believe the United States has little choice in the matter -- in other words, the action may be undesirable but is necessary. Most commonly, proponents say they favor increasing the limit to avoid an economic catastrophe, which some experts including Treasury Secretary Tim Geithner predict will occur if the government is no longer able to borrow money. The other most common reasons for favoring a higher debt limit are that the U.S. cannot default on its debt, that the country simply has "no choice" in the matter, and to avoid a disruption of government services and benefits. Responses on both sides to a large degree reflect the arguments political leaders are making. Two of the most common, and arguably the dominant themes of the open-ended responses, are concerns about the effect that not raising the debt limit will have on the economy versus concerns that raising it will not sufficiently address government spending. In the same poll, Gallup asked Americans which of these two risks concerned them more, and the public expressed greater concern about raising the debt ceiling without a plan for major cuts in future government spending (51%) than about the potential harm to the economy if the debt ceiling is not raised (32%). Read the verbatim responses. Implications Government spending seems to be the primary worry for Americans when their opinions are probed about raising the debt limit. Government leaders appear to be listening, as party leaders are proposing major cuts in future government spending as a way to persuade members of Congress to vote for an increase in the nation's debt limit. In terms of deficit reduction, Americans seem to generally back an approach that relies more on spending cuts than tax increases. A key question to be answered in the days ahead is whether an agreement to raise the debt ceiling will include any tax increases. This is something many Republican members of Congress oppose, but most Americans do not seem to share this view.

Summary: President Obama got combative in his press conference today, saying Republicans' refusal to raise revenues in a debt ceiling deal is out of touch. "My hope, though, is that they're listening not just to lobbyists or special interests here in Washington, but they're also listening to the American people," he said, according to CBS. "Because it turns out, poll after poll, many done by your organizations, show that it's not just Democrats who think we need to take a balanced approach, it's Republicans as well." Obama was referring in part to a Wednesday Gallup poll showing that a mere 20% of Americans thought a deal should include only spending cuts, with the rest favoring some tax increases. "That's not just Democrats. That's the majority of Republicans," Obama said. Indeed, even among Republicans, only 26% supported a cuts-only deal. Obama also reiterated his determination to "do something big," and "stabilize America's finances for a decade, for 15 or 20 years."

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Summarize: BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] This invention relates to florfenicol-containing formulations having improved aqueous solubility. In particular, the invention relates to forming florfenicol complexes with cyclodextrins to improve its aqueous solubility. [0003] 2. Description of Related Art [0004] Florfenicol is a broad spectrum antibiotic, structurally related to thiomphenicol and chloramphenicol developed as a veterinary treatment for use in cattle, swine, poultry, and fish. [0005] Nuflor® Drinking Water Concentrate is a product of Schering-Plough designed to be an oral solution containing 23 mg/ml of florfenicol. This product was developed as an additive for drinking water systems for swine and poultry. When dosed at a concentration of 400 mg/gal (˜0.1 mg/ml) in the drinking water, the product minimizes mortality due to E. coli airsacculitis in broiler chickens and minimizes respiratory diseases in swine associated with Actinobacillus pleuropneumonia, P. multocida, Mycoplasma, Salmonella cholera suis and Streptococcus suis Type II. [0006] One challenge associated with the Nuflor® product is the relatively low solubility of florfenicol in water. Typically, the product is either added directly to the bulk drinking water source or the product is added into the bulk drinking water source through a proportioner mixing tank system. These methods require the formulation to be soluble not only at the efficacious concentration of 400 mg/gal (˜0.1 mg/mL) in the bulk drinking water, but also at a concentration of ˜13.5 mg/mL to allow the use of a typical proportioner mixing ratio of 1:128 (1 oz. to 1 gallon). The solubility of florfenicol in water (1.23 mg/ml) allows for direct addition into the bulk drinking water with minimal problems; however, the required concentration for the proportioner systems is ten times greater. Therefore, efforts have been made to improve the aqueous solubility of florfenicol. [0007] Cyclodextrins are a group of cyclic oligomers containing α-D-glucopyranose units linked with α-1-4 bonds. There are three well known naturally occurring CDs: α, β and γ, which are composed of six, seven or eight glucopyranose units, respectively ( FIG. 1 ). In addition, modified CDs, such as HP-beta cyclodextrin and sulfoalkylether-cyclodextrin, which have the flexibility and ability to incorporate a variety of molecular frames are also known. Thanks to their peculiar structure, CDs are known to exhibit complex formation. Complex formation is defined as a reversible entrapment of a guest molecule into a host cavity to yield a new entity, i.e., the inclusion complex. [0008] Cyclodextrins are used in pharmaceutical formulations because of their ability to increase the apparent solubility, stability and bioavailability of various medicinal agents by forming non-covalent inclusion complexes. Complexation with cyclodextrins is a useful way to enhance the solubility of poorly water soluble pharmaceutical compounds. Cyclodextrins are capable of forming inclusion complexes with organic and inorganic molecules in aqueous solutions acting as a host. The formation of inclusion complexes between the host cyclodextrin and the guest molecule is generally a function of the dimension of the cyclodextrin cavity and the dimension of the guest molecule. Natural cyclodextrins are somewhat limited in terms of size and shape, and modified cyclodextrins have therefore been employed to overcome the restrictions associated with natural cyclodextrins. SUMMARY OF THE INVENTION [0009] The compositions of the invention are typically in the form of soluble powders, soluble granules, or lyophilized powders/cakes which are ready for reconstitution in a solvent. Other potential formulations include but are not limited to ready to use solutions, capsules, and tablets as well as other formulations useful for topical use. [0010] In accordance therewith, one aspect of the invention provides compositions that contain: [0011] a) from about 2.5 to about 35 wt % of florfenicol or a pharmaceutically acceptable salt thereof; [0012] b) from about 0.5 to about 20 wt % of a cyclodextrin; and [0013] c) from about 20 to about 95 wt % of water, a solvent and/or a mixture thereof. [0014] The compositions can be in the form of an intimate complex of the florfenicol and the cyclodextrin by removing the water and/or solvent to form the complex. [0015] The combination of the organic solvent and cyclodextrin has a significant effect in improving the solubility of florfenicol in water. Such synergism reduces the amount of solvent necessary to achieve the required concentration of the drug in solution and to maintain the drug in solution over time. This creates many advantages for practical use in the field, such as in automated proportioner mixing tank systems for animal drinking water systems. It also potentially provides a user-friendly florfenicol concentrate solution, thereby avoiding the use of high amounts of solvents and large volume containers which are difficult to handle and properly dispose. Furthermore, the combined action of cyclodextrin and the organic solvent in enhancing the florfenicol solubility may be used to reduce the amount of cyclodextrin in the formulation, thus limiting the overall cost of the product. [0016] In addition, complex formation between the drug florfenicol and natural and/or modified cyclodextrins in water has been shown using solubility studies ( FIG. 5 and FIG. 6 ) to have a calculated binding constant that is relatively high. This provides an advantage for the formulation of the drug florfenicol with cyclodextrin in water by enhancing its solubility, and providing a toll to reach the desired concentration in water without the co-aid of an organic solvent. DESCRIPTION OF THE DRAWINGS [0017] FIG. 1 is a graphic representation of the chemical structure of α, β and γ cyclodextrin. [0018] FIG. 2 is an illustration of the physical structure of cyclodextrin. [0019] FIG. 3 is a graphic representation of the chemical structure of SBE- and HP-β-CD. [0020] FIG. 4 is a graphic representation of the chemical structure of florfenicol. [0021] FIG. 5 is a phase solubility diagram for florfenicol in β cyclodextrin. [0022] FIG. 6 is a phase solubility diagram for florfenicol in γ cyclodextrin. [0023] FIG. 7 is a phase solubility diagram for florfenicol in HP-β cyclodextrin. [0024] FIG. 8 is a phase solubility diagram for florfenicol in Captisol (a type of sulfoalkylether cyclodextrin). DETAILED DESCRIPTION OF THE INVENTION [0025] The invention provides compositions containing florfenicol or a pharmaceutically acceptable salt thereof for use in animal drinking water systems. In some preferred aspects of the invention, the florfenicol is present in an aqueous formulation, a solvent formulation, an aqueous/solvent formulation, a powder, granules or a lyophilized power/cake. Other formulations include ready to use solutions, capsules, tablets, as well as other formulations for topical use. Each of the above formulations can be added directly to the drinking water system to reach the antibiotic therapeutic dose with a fast solubility rate profile. [0026] One of the key components of the formulations of the invention is the drug florfenicol. Florfenicol can be prepared as a free base or in its salt form and also in any of its derivative forms such us phosphate derivatives and any florfenicol pro-drugs. Florfenicol is not hygroscopic, so its incorporation in a formulation does not cause instability due to water absorption. Florfenicol is also known as [R-(R*,S*)]2,2-Dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]-ethyl]acetamide (see FIG. 4 ). Processes for the manufacture of this preferred antibiotic, and intermediates useful in such processes, are described in U.S. Pat. Nos. 4,311,857; 4,582,918; 4,973,750; 4,876,352; 5,227,494; 4,743,700; 5,567,844; 5,105,009; 5,382,673; 5,352,832; and 5,663,361. Another preferred antibiotic is thiamphenicol. Pharmaceutically acceptable salts of the foregoing are also contemplated for addition to the formulations described herein. [0027] In some aspects of the invention, the amount of florfenicol included in the compositions may range from about 2.5 to about 35 wt %. In preferred aspects, the amount of florfenicol is from about 15 to about 25 wt %, while in more preferred aspects, the amount is from about 20 to about 25 wt %. [0028] The compositions of the invention preferably contain a cyclodextrin. The cyclodextrin can be a natural cyclodextrin, a modified cyclodextrin or a mixture thereof. A non-limiting list of natural cyclodextrins is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin and mixtures thereof. Modified cyclodextrins can include, for example, HP-beta cyclodextrin, sulfoalkyl-cyclodextrin, methylated cyclodextrin, ethylated cyclodextrin, and mixtures thereof. [0029] The amount of cyclodextrin included in the compositions of the invention is from about 0.5 to about 20 wt % of the composition. Preferably, the amount is from about 0.5 to about 15 wt %, and more preferably from about 5 to about 10 wt % of the composition. [0030] The compositions of the invention also preferably include water, a solvent, or a mixture thereof. The synergistic combination of a solvent and cyclodextrin significantly improves the solubility of florfenicol in water. Such synergism reduces the amount of solvent necessary to achieve the required concentration of the drug in solution and to maintain the drug in solution over time. As a result, it becomes easier to administer the drug through automated proportioner mixing tank systems for animal drinking water. In addition, a user-friendly florfenicol concentrate solution is achieved, thereby avoiding the use of high amounts of solvents and large volume containers which are difficult to handle and properly dispose. Furthermore, the combined action of cyclodextrin and the solvent in enhancing the florfenicol solubility may be used to reduce the amount of cyclodextrin in the formulation, thus limiting the overall cost of the product. [0031] Non-limiting examples of solvents include polyethylene glycol 300, polyethylene glycol 400, propylene glycol, 2-pyrol, n-methylpyrol, and mixtures thereof. [0032] The water is typically present in an amount of from about 20 to about 95 wt % of the composition. In a preferred embodiment, the water is present in an amount of from about 40 to about 80 wt % of the composition, and more preferably from about 5 to about 10 wt % of the composition. [0033] Typically, the solvent is present in an amount of from about 20 to about 95 wt % of the composition. Preferably, the solvent is present in an amount of from about 40 to about 80 wt % of the composition, and more preferably from about 5 to about 10 wt % of the composition. [0034] When the compositions of the invention contain a mixture of water and a solvent, the solvent:water ratio is typically in the range of from about 1 to about 10. Preferably, the ratio is from about 1 to about 5, and more preferably from about 1 to about 3. [0035] Conventional excipients, such as colorings, fillers, diluents, surfactants, sweeteners, flavorings, preservatives, antioxidants, stabilizers, as well as other ancillary pharmaceutically acceptable ingredients and the like and mixtures thereof may be added to the formulations. For example, the formulations can also contains additional common excipients such us binders, lubricants, diluents, surfactants, solvents and mixtures thereof. One preferred diluent is lactose anhydrous. Other diluents that are suitable include without limitation microcrystalline cellulose, sorbitol, starch and calcium phosphate. The amount of diluent can range from about 0% by wt. to about 40% by wt. One preferred lubricant is magnesium stearate but other suitable lubricants can include, without limitation, calcium phosphate and/or calcium phosphate di-basic. The amount of lubricant can range from about 0% by wt. to about 5% by wt. One preferred surfactant is Tween80 but other suitable surfactants can include without limitation sodium lauryl sulfate. The amount of surfactant can range from about 0% by wt. to about 10% by wt. One preferred binder is polyvinylpyrrolidone (PVP) 30 in a range of between 2 and 20% by wt in aqueous or alcoholic solution. A non-limiting list of suitable alternatives may include polyvinylpyrrolidone 90, starch, methylcellulose, sodium carboxymethylcellulose, polyacrilamide and polyvinyl alcohols. [0036] Other optional inert ingredients may be added to the present composition, as desired. Such ingredients include preservatives, antioxidants, stabilizers, colorings, sweeteners and flavorings. Exemplary preservatives include methyl p-hydroxybenzoate (methylparaben) and propyl p-hydroxybenzoate (propylparaben). Exemplary antioxidants include butylated hydroxyanisole and sodium monothioglycerol. Preferred stabilizers for use in the present invention include, for example, BHT or citric acid. A particularly preferred stabilizer to prevent degradation of any of the active ingredients in the formulations of the present invention is BHT in a concentration between 0.01% (w/w) and 0.05% (w/w). Other suitable stabilizers include, for example fumaric acid, malic acid, and tartaric acid. When a suitable acid is used as preservative it can be added in addition to or as part of the acid component, according with the stoichiometric ratio between acid and basic component in the effervescent formulation. [0037] Exemplary sweeteners are mannitol, lactose, sucrose and dextrose. [0038] In still further aspects of the invention, the compounds can contain a second pharmaceutically active composition that does not interfere or otherwise hamper the effectiveness of the florfenicol. It will be appreciated that other active ingredients may be combined with the formulations of the present invention. Such ingredients may include, for example, anti-inflammatory agents such as corticosteroids, NSAIDS, such as flunixin, COX-inhibitors and other analgesics, antiparasitic compounds such as, for example, an avermectin compound such as ivermectin, doramectin, milbemycin, selamectin, emamectin, eprinomectin, and moxidectin, and/or optionally a flukicide. It may also be preferred to employ a second antibiotic in the formulation. Preferred antibiotics may include tetracyclines. Particularly preferred is chlorotetracycline and oxytetracycline. Other preferred additional antibiotics include betalactams, such as penicillins, cephalosporins, e.g., penicillin, amoxicillin, or a combination of amoxicillin with clavulanic acid or other beta lactamase inhibitors, ceftiofur, cefquinome, etc. Also preferred antibiotics include fluoroquinolones, such as, for example, enrofloxacin, danofloxacin, difloxacin, orbifloxacin and marbofloxacin, and macrolide antibiotics such as tilmicosin, tulathromycin, erythromycin, azithromycin and pharmaceutically-acceptable salts there of and the like. Alternatively, one could include insect growth regulators in combination with the formulations of the present invention. [0039] In another aspect of the invention, there are provided methods of treating or preventing diseases and florfenicol-susceptible conditions. The methods include introducing a sufficient amount of the composition described herein into water, and administering the resultant solution to a subject in need thereof, as part of the liquid to be ingested by the subject, e.g., the formulation may be added into its drinking water system to administer the treatment and therapeutic dose to livestock. [0040] The amount administered is a therapeutically or prophylactically-effective amount of the florfenicol solution resulting from the introduction of the compound into water. In most aspects of this embodiment, the amount of compound added to water is an amount that is sufficient to bring the concentration of florfenicol in the drinking water to from about 0.01 mg/mL to about 0.2 mg/mL. Preferably the concentration will be about 0.1±0.09 mg/mL in the bulk drinking water, and a concentration of about 13.5±0.1 mg/mL when the aqueous solutions are used in a typical proportioner mixing ratio of 1:128 gallons. Depending upon the condition being treated and the type, size, weight, etc. of the animal being treated, it is contemplated that suitable periods of treatment will range from about 1 to about 5 days or longer if needed using the novel compounds in drinking water at the concentrations mentioned above. As will be appreciated by those of ordinary skill, the animals will drink the treated water ad libitum. It is nonetheless contemplated that sufficient amounts of the florfenicol will be administered to the animals in need thereof when it is available for drinking for the periods mentioned above. [0041] The compounds of the present invention may, if desired, be presented in a pack or dispenser device, such as an FDA approved kit, which may contain one or more unit dosage forms containing the compound in the form of compressed tablets, granules or a lyophilized powder/cake containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack may also consist of a soluble biodegradable pouch ready to use, sealed in a metal plastic foil. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accompanied by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or of human or veterinary administration. Such notice, for example, may be of the labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert. Compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Thus, the kit can be used in connection with the treating or preventing of a bacterial infection or other disease in a subject in need thereof and include a sufficient amount of the compound described herein and instructions for introducing the compound into drinking water to be given to the subject in need thereof. EXAMPLES [0042] The following examples are provided to illustrate certain embodiments of this invention and are not intended, nor are they to be construed, to limit its scope in any manner whatsoever. [0043] Phase solubility analysis is one of the methods used to determine a drug:CD binding constant and its consequences on the drug solubility have been extensively described in the literature by Higuchi and Connors. In such experiments, the solubility of a substance (S) is monitored with increases in the concentration of a ligand (L) (cyclodextrin in this case). The experiments are conducted in a series of tubes or vials containing the same volume of ligand solutions with increasing concentrations, except that one tube contains the solvent only. To each tube is added a known amount of the substance or drug, and the samples are equilibrated at constant temperature. The solution phase is then analyzed for the total substance concentration. If a soluble complex forms, the substance concentration should vary with increasing ligand concentration. The solubility behavior can be determined using a phase diagram by plotting the total substance concentration versus the total ligand concentration. [0044] Florfenicol solubility in mixed solvents, such as water/PEG-300, and florfenicol complexes with beta cyclodextrin were evaluated by solubility studies using High Performance Liquid Chromatography (HPLC). The HPLC system consisted of a Waters Alliance Separation Module equipped with a Waters 2996 Photodiode Array Detector interfaced with Millennium Chromatography manager data software. The HPLC mobile phase consisted of acetonitrile and a 0.1% phosphoric acid aqueous solution (30:70 v/v). A Phenomenx®, Luna C8 5 micron column was used. The flow rate was 1.0 mL/min and the detection wavelength was 260 nm. Binding constants were calculated using the Higuchi Connors method from solubility study plots. The solubility of florfenicol in aqueous CD/PEG-300 systems was also investigated with the same technique. [0045] In a first set of experiments, phase solubility studies were conducted for FFC in natural and modified cyclodextrins. The results of these studies are reported in Tables I, II, III, IV and V below, and the phase solubility diagrams are reported in FIGS. 5, 6, 7 and 8. [0000] TABLE I Experimental water solubility for drug FFC: Solubility of FFC, mg/mL Standard 1 1.91 Standard 2 1.90 Standard 3 1.95 The calculated FFC Solubility S 0 was 4.90E-07 M. [0000] TABLE II FFC Solubility in Beta CD Complex: Beta-CD, M Average FFC, mg/mL STDEV FFC, M 0.05 15.59 0.66 4.04E−05 0.02 9.79 0.02 2.54E−05 0.01 5.91 0.17 1.53E−05 0.006 4.03 0.01 1.045E−05 The calculated binding constant for FFC:CD complex was 1429.57 M −1. [0000] TABLE III FFC Solubility in Gamma CD Complex: Gamma-CD, M Average FFC, mg/mL STDEV FFC, M 0.11 10.77 0.30 2.79E−05 0.06 8.20 0.45 2.12E−05 0.03 5.24 0.26 1.36E−05 0.014 3.70 0.01 9.60E−06 0.007 2.51 0.46 6.51E−6 The calculated binding constant for FFC:Gamma-CD Complex was 612.43 M −1. [0000] TABLE IV FFC Solubility in Hp-beta CD Complex: HP-Beta-CD, M Average FFC, mg/mL STDEV FFC, M 0.09 17.43 0.64 4.52E−05 0.05 9.76 0.49 2.53E−05 0.02 7.00 0.01 1.82E−05 0.012 4.88 0.27 1.26E−5 0.006 3.72 0.023 9.62E−6 The calculated binding constant for FFC:HP-CD complex was 816.652 M −1. [0000] TABLE V FFC Solubility in Captisol ® Complex: Captisol ®, M Average FFC, mg/mL STDEV FFC, M 0.10 19.18 0.73 4.97E−05 0.05 13.17 0.21 3.41E−05 0.03 7.98 0.23 2.07−05 0.013 5.11 0.03 1.32E−5 0.006 4.92 0.31 9.28E−6 The calculated binding constant for FFC:Captisol® complex was 1020.92 M −1. [0046] In a second set of experiments, the effects of different percentages of PEG-300 when used as a co-solvent were investigated in a FFC-cyclodextrin complex system. [0047] The results obtained for the FEC-CD complex in the presence of different percentages of PEG-300 and different molar concentrations of cyclodextrin are reported in Tables VI and VII below. [0000] TABLE VI Effect of different percentage of PEG-300 on a FFC: 10 mM Beta-CD system: Beta-CD: PEG-300 System Solubility of FFC, mg/mL 10 mM beta/3% PEG-300 7.51 10 mM beta/10% PEG-300 6.31 10 mM beta/50% PEG-300 12.28 [0000] TABLE VII Effect of different percentage of PEG-300 on a FFC: 50 mM Beta-CD system: Beta-CD: PEG-300 System Solubility of FFC, mg/mL 50 mM beta/20% PEG-300 10.57 50 mM beta/30% PEG-300 14.36 50 mM beta/50% PEG-300 15.50 [0048] Based on the solubility results obtained for FFC, it was demonstrated that complexation with cyclodextrin is an alternative to the use of high percentage organic solvents for the formulation of a concentrated solution of florfenicol (and related-structure antibiotics) to be used in drinking water systems. Furthermore, when PEG-300 was used as co-solvent for a FFC:cyclodextrin complex, the solubility of FFC was greatly increased. [0049] The complex formation between cyclodextrin and a drug such as florfenicol may be achieved using different techniques. In one technique, the complex can be formed in a water solution. For instance, a saturated water solution of the drug is added to 10% cyclodextrin and incubated for 24 hours. The excess drug is removed and the solvent may be added at this point. In a second technique, the complex is formed by a “paste technique” using a minimal amount of solvent, and the paste of cyclodextrin and the drug is at added to the formulation. In a third technique, the cyclodextrin/drug complex is formed directly in the solvent under continuous agitation. [0050] Non-limiting examples of possible formulations for use in drinking water systems are: Example 1 [0051] [0000] Component % (w/w) Florfenicol 1.5% HP-Beta CD 10% Water q.s [0052] The formulation reported in Example 1 was a clear solution, or in alternative, it could be lyophilized to be presented as a powder to be reconstituted in water. Example 2 [0053] [0000] Component % (w/w) Florfenicol 4.5% HP-Beta CD 30% Water q.s [0054] The formulation reported in Example 2 was a clear solution, or in alternative, it could be lyophilized to be presented as a powder to be reconstituted in water. Example 3 [0055] [0000] Component % (w/w) Florfenicol 2% Beta CD 20% PEG-300 30% Water q.s [0056] The formulation reported in Example 3 was a clear solution, or in alternative, it could be lyophilized to be presented as a powder to be reconstituted in water. [0057] With FFC:CD complexation, it is possible to achieve desirable FFC solubility, to have the desired concentration in the automated proportioner mixing tank system, and to maintain the drug in solution over time. Furthermore, samples containing multiple solubilizing agents, such as beta-CD and PEG-300, show a significant increase in FCC solubility in water. The synergism of cyclodextrin solutions with PEG-300 reduced the amount of solvent (polyethylene glycol) necessary to achieve the required concentration in the automated proportioner mixing tank system. The synergistic combination of cyclodextrin with PEG-300 also provides a user-friendly FFC concentrate solution, thereby avoiding the use of high amounts of solvents and large volume containers which are difficult to handle and dispose of properly. [0058] Although certain presently preferred embodiments of the invention have been described herein, it will be apparent to those skilled in the art to which the invention pertains that variations and modifications of the described embodiments may be made without departing from the spirit and scope of the invention. [0059] Accordingly, it is intended that the invention be limited only to the extent required by the appended claims and the applicable rules of law.

Summary: The relatively low solubility of florfenicol (FEC) in water (1.3 mg/mL) limits its use in medicated drinking water systems for treatment of pulmonary disease of swine and poultry. Current formulations use a high volume organic solvent to reach the required FFC concentration of 13.5 mg/mL in an automated proportioner mixing tank system, with practical disadvantages for the users in the field. This invention relates to the effects of complex formation with natural and modified cyclodextrins on the aqueous solubility of FFC and antibiotics of related structure. Furthermore, this invention relates to the effects of polyethylene glycol (PEG-300) as a co-solvent in an FFC-cyclodextrin system to achieve the required FFC dose in the mixing tank system and to avoid high volumes of the organic solvent.

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Summarize: VIII.--The Adventure of the Six Napoleons. IT was no very unusual thing for Mr. Lestrade, of Scotland Yard, to look in upon us of an evening, and his visits were welcome to Sherlock Holmes, for they enabled him to keep in touch with all that was going on at the police head-quarters. In return for the news which Lestrade would bring, Holmes was always ready to listen with attention to the details of any case upon which the detective was engaged, and was able occasionally, without any active interference, to give some hint or suggestion drawn from his own vast knowledge and experience. On this particular evening Lestrade had spoken of the weather and the newspapers. Then he had fallen silent, puffing thoughtfully at his cigar. Holmes looked keenly at him. "Anything remarkable on hand?" he asked. "Oh, no, Mr. Holmes, nothing very particular." "Then tell me about it." Lestrade laughed. "Well, Mr. Holmes, there is no use denying that there IS something on my mind. And yet it is such an absurd business that I hesitated to bother you about it. On the other hand, although it is trivial, it is undoubtedly queer, and I know that you have a taste for all that is out of the common. But in my opinion it comes more in Dr. Watson's line than ours." "Disease?" said I. "Madness, anyhow. And a queer madness too! You wouldn't think there was anyone living at this time of day who had such a hatred of Napoleon the First that he would break any image of him that he could see." Holmes sank back in his chair. "That's no business of mine," said he. "Exactly. That's what I said. But then, when the man commits burglary in order to break images which are not his own, that brings it away from the doctor and on to the policeman." Holmes sat up again. "Burglary! This is more interesting. Let me hear the details." Lestrade took out his official note-book and refreshed his memory from its pages. "The first case reported was four days ago," said he. "It was at the shop of Morse Hudson, who has a place for the sale of pictures and statues in the Kennington Road. The assistant had left the front shop for an instant when he heard a crash, and hurrying in he found a plaster bust of Napoleon, which stood with several other works of art upon the counter, lying shivered into fragments. He rushed out into the road, but, although several passers-by declared that they had noticed a man run out of the shop, he could neither see anyone nor could he find any means of identifying the rascal. It seemed to be one of those senseless acts of Hooliganism which occur from time to time, and it was reported to the constable on the beat as such. The plaster cast was not worth more than a few shillings, and the whole affair appeared to be too childish for any particular investigation. "The second case, however, was more serious and also more singular. It occurred only last night. "In Kennington Road, and within a few hundred yards of Morse Hudson's shop, there lives a well-known medical practitioner, named Dr. Barnicot, who has one of the largest practices upon the south side of the Thames. His residence and principal consulting-room is at Kennington Road, but he has a branch surgery and dispensary at Lower Brixton Road, two miles away. This Dr. Barnicot is an enthusiastic admirer of Napoleon, and his house is full of books, pictures, and relics of the French Emperor. Some little time ago he purchased from Morse Hudson two duplicate plaster casts of the famous head of Napoleon by the French sculptor, Devine. One of these he placed in his hall in the house at Kennington Road, and the other on the mantelpiece of the surgery at Lower Brixton. Well, when Dr. Barnicot came down this morning he was astonished to find that his house had been burgled during the night, but that nothing had been taken save the plaster head from the hall. It had been carried out and had been dashed savagely against the garden wall, under which its splintered fragments were discovered." Holmes rubbed his hands. "This is certainly very novel," said he. "I thought it would please you. But I have not got to the end yet. Dr. Barnicot was due at his surgery at twelve o'clock, and you can imagine his amazement when, on arriving there, he found that the window had been opened in the night, and that the broken pieces of his second bust were strewn all over the room. It had been smashed to atoms where it stood. In neither case were there any signs which could give us a clue as to the criminal or lunatic who had done the mischief. Now, Mr. Holmes, you have got the facts." "They are singular, not to say grotesque," said Holmes. "May I ask whether the two busts smashed in Dr. Barnicot's rooms were the exact duplicates of the one which was destroyed in Morse Hudson's shop?" "They were taken from the same mould." "Such a fact must tell against the theory that the man who breaks them is influenced by any general hatred of Napoleon. Considering how many hundreds of statues of the great Emperor must exist in London, it is too much to suppose such a coincidence as that a promiscuous iconoclast should chance to begin upon three specimens of the same bust." "Well, I thought as you do," said Lestrade. "On the other hand, this Morse Hudson is the purveyor of busts in that part of London, and these three were the only ones which had been in his shop for years. So, although, as you say, there are many hundreds of statues in London, it is very probable that these three were the only ones in that district. Therefore, a local fanatic would begin with them. What do you think, Dr. Watson?" "There are no limits to the possibilities of monomania," I answered. "There is the condition which the modern French psychologists have called the 'idee fixe,' which may be trifling in character, and accompanied by complete sanity in every other way. A man who had read deeply about Napoleon, or who had possibly received some hereditary family injury through the great war, might conceivably form such an 'idee fixe' and under its influence be capable of any fantastic outrage." "That won't do, my dear Watson," said Holmes, shaking his head; "for no amount of 'idee fixe' would enable your interesting monomaniac to find out where these busts were situated." "Well, how do YOU explain it?" "I don't attempt to do so. I would only observe that there is a certain method in the gentleman's eccentric proceedings. For example, in Dr. Barnicot's hall, where a sound might arouse the family, the bust was taken outside before being broken, whereas in the surgery, where there was less danger of an alarm, it was smashed where it stood. The affair seems absurdly trifling, and yet I dare call nothing trivial when I reflect that some of my most classic cases have had the least promising commencement. You will remember, Watson, how the dreadful business of the Abernetty family was first brought to my notice by the depth which the parsley had sunk into the butter upon a hot day. I can't afford, therefore, to smile at your three broken busts, Lestrade, and I shall be very much obliged to you if you will let me hear of any fresh developments of so singular a chain of events." The development for which my friend had asked came in a quicker and an infinitely more tragic form than he could have imagined. I was still dressing in my bedroom next morning when there was a tap at the door and Holmes entered, a telegram in his hand. He read it aloud:-- "Come instantly, 131, Pitt Street, Kensington.--Lestrade." "What is it, then?" I asked. "Don't know--may be anything. But I suspect it is the sequel of the story of the statues. In that case our friend, the image-breaker, has begun operations in another quarter of London. There's coffee on the table, Watson, and I have a cab at the door." In half an hour we had reached Pitt Street, a quiet little backwater just beside one of the briskest currents of London life. No. 131 was one of a row, all flat-chested, respectable, and most unromantic dwellings. As we drove up we found the railings in front of the house lined by a curious crowd. Holmes whistled. "By George! it's attempted murder at the least. Nothing less will hold the London message-boy. There's a deed of violence indicated in that fellow's round shoulders and outstretched neck. What's this, Watson? The top steps swilled down and the other ones dry. Footsteps enough, anyhow! Well, well, there's Lestrade at the front window, and we shall soon know all about it." The official received us with a very grave face and showed us into a sitting-room, where an exceedingly unkempt and agitated elderly man, clad in a flannel dressing-gown, was pacing up and down. He was introduced to us as the owner of the house--Mr. Horace Harker, of the Central Press Syndicate. "It's the Napoleon bust business again," said Lestrade. "You seemed interested last night, Mr. Holmes, so I thought perhaps you would be glad to be present now that the affair has taken a very much graver turn." "What has it turned to, then?" "To murder. Mr. Harker, will you tell these gentlemen exactly what has occurred?" The man in the dressing-gown turned upon us with a most melancholy face. "It's an extraordinary thing," said he, "that all my life I have been collecting other people's news, and now that a real piece of news has come my own way I am so confused and bothered that I can't put two words together. If I had come in here as a journalist I should have interviewed myself and had two columns in every evening paper. As it is I am giving away valuable copy by telling my story over and over to a string of different people, and I can make no use of it myself. However, I've heard your name, Mr. Sherlock Holmes, and if you'll only explain this queer business I shall be paid for my trouble in telling you the story." Holmes sat down and listened. "It all seems to centre round that bust of Napoleon which I bought for this very room about four months ago. I picked it up cheap from Harding Brothers, two doors from the High Street Station. A great deal of my journalistic work is done at night, and I often write until the early morning. So it was to-day. I was sitting in my den, which is at the back of the top of the house, about three o'clock, when I was convinced that I heard some sounds downstairs. I listened, but they were not repeated, and I concluded that they came from outside. Then suddenly, about five minutes later, there came a most horrible yell--the most dreadful sound, Mr. Holmes, that ever I heard. It will ring in my ears as long as I live. I sat frozen with horror for a minute or two. Then I seized the poker and went downstairs. When I entered this room I found the window wide open, and I at once observed that the bust was gone from the mantelpiece. Why any burglar should take such a thing passes my understanding, for it was only a plaster cast and of no real value whatever. "You can see for yourself that anyone going out through that open window could reach the front doorstep by taking a long stride. This was clearly what the burglar had done, so I went round and opened the door. Stepping out into the dark I nearly fell over a dead man who was lying there. I ran back for a light, and there was the poor fellow, a great gash in his throat and the whole place swimming in blood. He lay on his back, his knees drawn up, and his mouth horribly open. I shall see him in my dreams. I had just time to blow on my police-whistle, and then I must have fainted, for I knew nothing more until I found the policeman standing over me in the hall." "Well, who was the murdered man?" asked Holmes. "There's nothing to show who he was," said Lestrade. "You shall see the body at the mortuary, but we have made nothing of it up to now. He is a tall man, sunburned, very powerful, not more than thirty. He is poorly dressed, and yet does not appear to be a labourer. A horn-handled clasp knife was lying in a pool of blood beside him. Whether it was the weapon which did the deed, or whether it belonged to the dead man, I do not know. There was no name on his clothing, and nothing in his pockets save an apple, some string, a shilling map of London, and a photograph. Here it is." It was evidently taken by a snap-shot from a small camera. It represented an alert, sharp-featured simian man with thick eyebrows, and a very peculiar projection of the lower part of the face like the muzzle of a baboon. "And what became of the bust?" asked Holmes, after a careful study of this picture. "We had news of it just before you came. It has been found in the front garden of an empty house in Campden House Road. It was broken into fragments. I am going round now to see it. Will you come?" "Certainly. I must just take one look round." He examined the carpet and the window. "The fellow had either very long legs or was a most active man," said he. "With an area beneath, it was no mean feat to reach that window-ledge and open that window. Getting back was comparatively simple. Are you coming with us to see the remains of your bust, Mr. Harker?" The disconsolate journalist had seated himself at a writing-table. "I must try and make something of it," said he, "though I have no doubt that the first editions of the evening papers are out already with full details. It's like my luck! You remember when the stand fell at Doncaster? Well, I was the only journalist in the stand, and my journal the only one that had no account of it, for I was too shaken to write it. And now I'll be too late with a murder done on my own doorstep." As we left the room we heard his pen travelling shrilly over the foolscap. The spot where the fragments of the bust had been found was only a few hundred yards away. For the first time our eyes rested upon this presentment of the great Emperor, which seemed to raise such frantic and destructive hatred in the mind of the unknown. It lay scattered in splintered shards upon the grass. Holmes picked up several of them and examined them carefully. I was convinced from his intent face and his purposeful manner that at last he was upon a clue. "Well?" asked Lestrade. Holmes shrugged his shoulders. "We have a long way to go yet," said he. "And yet--and yet--well, we have some suggestive facts to act upon. The possession of this trifling bust was worth more in the eyes of this strange criminal than a human life. That is one point. Then there is the singular fact that he did not break it in the house, or immediately outside the house, if to break it was his sole object." "He was rattled and bustled by meeting this other fellow. He hardly knew what he was doing." "Well, that's likely enough. But I wish to call your attention very particularly to the position of this house in the garden of which the bust was destroyed." Lestrade looked about him. "It was an empty house, and so he knew that he would not be disturbed in the garden." "Yes, but there is another empty house farther up the street which he must have passed before he came to this one. Why did he not break it there, since it is evident that every yard that he carried it increased the risk of someone meeting him?" "I give it up," said Lestrade. Holmes pointed to the street lamp above our heads. "He could see what he was doing here and he could not there. That was his reason." "By Jove! that's true," said the detective. "Now that I come to think of it, Dr. Barnicot's bust was broken not far from his red lamp. Well, Mr. Holmes, what are we to do with that fact?" "To remember it--to docket it. We may come on something later which will bear upon it. What steps do you propose to take now, Lestrade?" "The most practical way of getting at it, in my opinion, is to identify the dead man. There should be no difficulty about that. When we have found who he is and who his associates are, we should have a good start in learning what he was doing in Pitt Street last night, and who it was who met him and killed him on the doorstep of Mr. Horace Harker. Don't you think so?" "No doubt; and yet it is not quite the way in which I should approach the case." "What would you do, then?" "Oh, you must not let me influence you in any way! I suggest that you go on your line and I on mine. We can compare notes afterwards, and each will supplement the other." "Very good," said Lestrade. "If you are going back to Pitt Street you might see Mr. Horace Harker. Tell him from me that I have quite made up my mind, and that it is certain that a dangerous homicidal lunatic with Napoleonic delusions was in his house last night. It will be useful for his article." Lestrade stared. "You don't seriously believe that?" Holmes smiled. "Don't I? Well, perhaps I don't. But I am sure that it will interest Mr. Horace Harker and the subscribers of the Central Press Syndicate. Now, Watson, I think that we shall find that we have a long and rather complex day's work before us. I should be glad, Lestrade, if you could make it convenient to meet us at Baker Street at six o'clock this evening. Until then I should like to keep this photograph found in the dead man's pocket. It is possible that I may have to ask your company and assistance upon a small expedition which will have be undertaken to-night, if my chain of reasoning should prove to be correct. Until then, good-bye and good luck!" Sherlock Holmes and I walked together to the High Street, where he stopped at the shop of Harding Brothers, whence the bust had been purchased. A young assistant informed us that Mr. Harding would be absent until after noon, and that he was himself a newcomer who could give us no information. Holmes's face showed his disappointment and annoyance. "Well, well, we can't expect to have it all our own way, Watson," he said, at last. "We must come back in the afternoon if Mr. Harding will not be here until then. I am, as you have no doubt surmised, endeavouring to trace these busts to their source, in order to find if there is not something peculiar which may account for their remarkable fate. Let us make for Mr. Morse Hudson, of the Kennington Road, and see if he can throw any light upon the problem." A drive of an hour brought us to the picture-dealer's establishment. He was a small, stout man with a red face and a peppery manner. "Yes, sir. On my very counter, sir," said he. "What we pay rates and taxes for I don't know, when any ruffian can come in and break one's goods. Yes, sir, it was I who sold Dr. Barnicot his two statues. Disgraceful, sir! A Nihilist plot, that's what I make it. No one but an Anarchist would go about breaking statues. Red republicans, that's what I call 'em. Who did I get the statues from? I don't see what that has to do with it. Well, if you really want to know, I got them from Gelder and Co., in Church Street, Stepney. They are a well-known house in the trade, and have been this twenty years. How many had I? Three--two and one are three--two of Dr. Barnicot's and one smashed in broad daylight on my own counter. Do I know that photograph? No, I don't. Yes, I do, though. Why, it's Beppo. He was a kind of Italian piece-work man, who made himself useful in the shop. He could carve a bit and gild and frame, and do odd jobs. The fellow left me last week, and I've heard nothing of him since. No, I don't know where he came from nor where he went to. I have nothing against him while he was here. He was gone two days before the bust was smashed." "Well, that's all we could reasonably expect to get from Morse Hudson," said Holmes, as we emerged from the shop. "We have this Beppo as a common factor, both in Kennington and in Kensington, so that is worth a ten-mile drive. Now, Watson, let us make for Gelder and Co., of Stepney, the source and origin of busts. I shall be surprised if we don't get some help down there." In rapid succession we passed through the fringe of fashionable London, hotel London, theatrical London, literary London, commercial London, and, finally, maritime London, till we came to a riverside city of a hundred thousand souls, where the tenement houses swelter and reek with the outcasts of Europe. Here, in a broad thoroughfare, once the abode of wealthy City merchants, we found the sculpture works for which we searched. Outside was a considerable yard full of monumental masonry. Inside was a large room in which fifty workers were carving or moulding. The manager, a big blond German, received us civilly, and gave a clear answer to all Holmes's questions. A reference to his books showed that hundreds of casts had been taken from a marble copy of Devine's head of Napoleon, but that the three which had been sent to Morse Hudson a year or so before had been half of a batch of six, the other three being sent to Harding Brothers, of Kensington. There was no reason why those six should be different to any of the other casts. He could suggest no possible cause why anyone should wish to destroy them--in fact, he laughed at the idea. Their wholesale price was six shillings, but the retailer would get twelve or more. The cast was taken in two moulds from each side of the face, and then these two profiles of plaster of Paris were joined together to make the complete bust. The work was usually done by Italians in the room we were in. When finished the busts were put on a table in the passage to dry, and afterwards stored. That was all he could tell us. But the production of the photograph had a remarkable effect upon the manager. His face flushed with anger, and his brows knotted over his blue Teutonic eyes. "Ah, the rascal!" he cried. "Yes, indeed, I know him very well. This has always been a respectable establishment, and the only time that we have ever had the police in it was over this very fellow. It was more than a year ago now. He knifed another Italian in the street, and then he came to the works with the police on his heels, and he was taken here. Beppo was his name--his second name I never knew. Serve me right for engaging a man with such a face. But he was a good workman, one of the best." "What did he get?" "The man lived and he got off with a year. I have no doubt he is out now; but he has not dared to show his nose here. We have a cousin of his here, and I dare say he could tell you where he is." "No, no," cried Holmes, "not a word to the cousin--not a word, I beg you. The matter is very important, and the farther I go with it the more important it seems to grow. When you referred in your ledger to the sale of those casts I observed that the date was June 3rd of last year. Could you give me the date when Beppo was arrested?" "I could tell you roughly by the pay-list," the manager answered. "Yes," he continued, after some turning over of pages, "he was paid last on May 20th." "Thank you," said Holmes. "I don't think that I need intrude upon your time and patience any more." With a last word of caution that he should say nothing as to our researches we turned our faces westward once more. The afternoon was far advanced before we were able to snatch a hasty luncheon at a restaurant. A news-bill at the entrance announced "Kensington Outrage. Murder by a Madman," and the contents of the paper showed that Mr. Horace Harker had got his account into print after all. Two columns were occupied with a highly sensational and flowery rendering of the whole incident. Holmes propped it against the cruet-stand and read it while he ate. Once or twice he chuckled. "This is all right, Watson," said he. "Listen to this: 'It is satisfactory to know that there can be no difference of opinion upon this case, since Mr. Lestrade, one of the most experienced members of the official force, and Mr. Sherlock Holmes, the well-known consulting expert, have each come to the conclusion that the grotesque series of incidents, which have ended in so tragic a fashion, arise from lunacy rather than from deliberate crime. No explanation save mental aberration can cover the facts.' The Press, Watson, is a most valuable institution if you only know how to use it. And now, if you have quite finished, we will hark back to Kensington and see what the manager of Harding Brothers has to say to the matter." The founder of that great emporium proved to be a brisk, crisp little person, very dapper and quick, with a clear head and a ready tongue. "Yes, sir, I have already read the account in the evening papers. Mr. Horace Harker is a customer of ours. We supplied him with the bust some months ago. We ordered three busts of that sort from Gelder and Co., of Stepney. They are all sold now. To whom? Oh, I dare say by consulting our sales book we could very easily tell you. Yes, we have the entries here. One to Mr. Harker, you see, and one to Mr. Josiah Brown, of Laburnum Lodge, Laburnum Vale, Chiswick, and one to Mr. Sandeford, of Lower Grove Road, Reading. No, I have never seen this face which you show me in the photograph. You would hardly forget it, would you, sir, for I've seldom seen an uglier. Have we any Italians on the staff? Yes, sir, we have several among our workpeople and cleaners. I dare say they might get a peep at that sales book if they wanted to. There is no particular reason for keeping a watch upon that book. Well, well, it's a very strange business, and I hope that you'll let me know if anything comes of your inquiries." Holmes had taken several notes during Mr. Harding's evidence, and I could see that he was thoroughly satisfied by the turn which affairs were taking. He made no remark, however, save that, unless we hurried, we should be late for our appointment with Lestrade. Sure enough, when we reached Baker Street the detective was already there, and we found him pacing up and down in a fever of impatience. His look of importance showed that his day's work had not been in vain. "Well?" he asked. "What luck, Mr. Holmes?" "We have had a very busy day, and not entirely a wasted one," my friend explained. "We have seen both the retailers and also the wholesale manufacturers. I can trace each of the busts now from the beginning." "The busts!" cried Lestrade. "Well, well, you have your own methods, Mr. Sherlock Holmes, and it is not for me to say a word against them, but I think I have done a better day's work than you. I have identified the dead man." "You don't say so?" "And found a cause for the crime." "Splendid!" "We have an inspector who makes a specialty of Saffron Hill and the Italian quarter. Well, this dead man had some Catholic emblem round his neck, and that, along with his colour, made me think he was from the South. Inspector Hill knew him the moment he caught sight of him. His name is Pietro Venucci, from Naples, and he is one of the greatest cut-throats in London. He is connected with the Mafia, which, as you know, is a secret political society, enforcing its decrees by murder. Now you see how the affair begins to clear up. The other fellow is probably an Italian also, and a member of the Mafia. He has broken the rules in some fashion. Pietro is set upon his track. Probably the photograph we found in his pocket is the man himself, so that he may not knife the wrong person. He dogs the fellow, he sees him enter a house, he waits outside for him, and in the scuffle he receives his own death-wound. How is that, Mr. Sherlock Holmes?" Holmes clapped his hands approvingly. "Excellent, Lestrade, excellent!" he cried. "But I didn't quite follow your explanation of the destruction of the busts." "The busts! You never can get those busts out of your head. After all, that is nothing; petty larceny, six months at the most. It is the murder that we are really investigating, and I tell you that I am gathering all the threads into my hands." "And the next stage?" "Is a very simple one. I shall go down with Hill to the Italian quarter, find the man whose photograph we have got, and arrest him on the charge of murder. Will you come with us?" "I think not. I fancy we can attain our end in a simpler way. I can't say for certain, because it all depends--well, it all depends upon a factor which is completely outside our control. But I have great hopes--in fact, the betting is exactly two to one--that if you will come with us to-night I shall be able to help you to lay him by the heels." "In the Italian quarter?" "No; I fancy Chiswick is an address which is more likely to find him. If you will come with me to Chiswick to-night, Lestrade, I'll promise to go to the Italian quarter with you to-morrow, and no harm will be done by the delay. And now I think that a few hours' sleep would do us all good, for I do not propose to leave before eleven o'clock, and it is unlikely that we shall be back before morning. You'll dine with us, Lestrade, and then you are welcome to the sofa until it is time for us to start. In the meantime, Watson, I should be glad if you would ring for an express messenger, for I have a letter to send, and it is important that it should go at once." Holmes spent the evening in rummaging among the files of the old daily papers with which one of our lumber-rooms was packed. When at last he descended it was with triumph in his eyes, but he said nothing to either of us as to the result of his researches. For my own part, I had followed step by step the methods by which he had traced the various windings of this complex case, and, though I could not yet perceive the goal which we would reach, I understood clearly that Holmes expected this grotesque criminal to make an attempt upon the two remaining busts, one of which, I remembered, was at Chiswick. No doubt the object of our journey was to catch him in the very act, and I could not but admire the cunning with which my friend had inserted a wrong clue in the evening paper, so as to give the fellow the idea that he could continue his scheme with impunity. I was not surprised when Holmes suggested that I should take my revolver with me. He had himself picked up the loaded hunting-crop which was his favourite weapon. A four-wheeler was at the door at eleven, and in it we drove to a spot at the other side of Hammersmith Bridge. Here the cabman was directed to wait. A short walk brought us to a secluded road fringed with pleasant houses, each standing in its own grounds. In the light of a street lamp we read "Laburnum Villa" upon the gate-post of one of them. The occupants had evidently retired to rest, for all was dark save for a fanlight over the hall door, which shed a single blurred circle on to the garden path. The wooden fence which separated the grounds from the road threw a dense black shadow upon the inner side, and here it was that we crouched. "I fear that you'll have a long wait," Holmes whispered. "We may thank our stars that it is not raining. I don't think we can even venture to smoke to pass the time. However, it's a two to one chance that we get something to pay us for our trouble." It proved, however, that our vigil was not to be so long as Holmes had led us to fear, and it ended in a very sudden and singular fashion. In an instant, without the least sound to warn us of his coming, the garden gate swung open, and a lithe, dark figure, as swift and active as an ape, rushed up the garden path. We saw it whisk past the light thrown from over the door and disappear against the black shadow of the house. There was a long pause, during which we held our breath, and then a very gentle creaking sound came to our ears. The window was being opened. The noise ceased, and again there was a long silence. The fellow was making his way into the house. We saw the sudden flash of a dark lantern inside the room. What he sought was evidently not there, for again we saw the flash through another blind, and then through another. "Let us get to the open window. We will nab him as he climbs out," Lestrade whispered. But before we could move the man had emerged again. As he came out into the glimmering patch of light we saw that he carried something white under his arm. He looked stealthily all round him. The silence of the deserted street reassured him. Turning his back upon us he laid down his burden, and the next instant there was the sound of a sharp tap, followed by a clatter and rattle. The man was so intent upon what he was doing that he never heard our steps as we stole across the grass plot. With the bound of a tiger Holmes was on his back, and an instant later Lestrade and I had him by either wrist and the handcuffs had been fastened. As we turned him over I saw a hideous, sallow face, with writhing, furious features, glaring up at us, and I knew that it was indeed the man of the photograph whom we had secured. But it was not our prisoner to whom Holmes was giving his attention. Squatted on the doorstep, he was engaged in most carefully examining that which the man had brought from the house. It was a bust of Napoleon like the one which we had seen that morning, and it had been broken into similar fragments. Carefully Holmes held each separate shard to the light, but in no way did it differ from any other shattered piece of plaster. He had just completed his examination when the hall lights flew up, the door opened, and the owner of the house, a jovial, rotund figure in shirt and trousers, presented himself. "Mr. Josiah Brown, I suppose?" said Holmes. "Yes, sir; and you, no doubt, are Mr. Sherlock Holmes? I had the note which you sent by the express messenger, and I did exactly what you told me. We locked every door on the inside and awaited developments. Well, I'm very glad to see that you have got the rascal. I hope, gentlemen, that you will come in and have some refreshment." However, Lestrade was anxious to get his man into safe quarters, so within a few minutes our cab had been summoned and we were all four upon our way to London. Not a word would our captive say; but he glared at us from the shadow of his matted hair, and once, when my hand seemed within his reach, he snapped at it like a hungry wolf. We stayed long enough at the police-station to learn that a search of his clothing revealed nothing save a few shillings and a long sheath knife, the handle of which bore copious traces of recent blood. "That's all right," said Lestrade, as we parted. "Hill knows all these gentry, and he will give a name to him. You'll find that my theory of the Mafia will work out all right. But I'm sure I am exceedingly obliged to you, Mr. Holmes, for the workmanlike way in which you laid hands upon him. I don't quite understand it all yet." "I fear it is rather too late an hour for explanations," said Holmes. "Besides, there are one or two details which are not finished off, and it is one of those cases which are worth working out to the very end. If you will come round once more to my rooms at six o'clock to-morrow I think I shall be able to show you that even now you have not grasped the entire meaning of this business, which presents some features which make it absolutely original in the history of crime. If ever I permit you to chronicle any more of my little problems, Watson, I foresee that you will enliven your pages by an account of the singular adventure of the Napoleonic busts." When we met again next evening Lestrade was furnished with much information concerning our prisoner. His name, it appeared, was Beppo, second name unknown. He was a well-known ne'er-do-well among the Italian colony. He had once been a skilful sculptor and had earned an honest living, but he had taken to evil courses and had twice already been in gaol--once for a petty theft and once, as we had already heard, for stabbing a fellow-countryman. He could talk English perfectly well. His reasons for destroying the busts were still unknown, and he refused to answer any questions upon the subject; but the police had discovered that these same busts might very well have been made by his own hands, since he was engaged in this class of work at the establishment of Gelder and Co. To all this information, much of which we already knew, Holmes listened with polite attention; but I, who knew him so well, could clearly see that his thoughts were elsewhere, and I detected a mixture of mingled uneasiness and expectation beneath that mask which he was wont to assume. At last he started in his chair and his eyes brightened. There had been a ring at the bell. A minute later we heard steps upon the stairs, and an elderly, red-faced man with grizzled side-whiskers was ushered in. In his right hand he carried an old-fashioned carpet-bag, which he placed upon the table. "Is Mr. Sherlock Holmes here?" My friend bowed and smiled. "Mr. Sandeford, of Reading, I suppose?" said he. "Yes, sir, I fear that I am a little late; but the trains were awkward. You wrote to me about a bust that is in my possession." "Exactly." "I have your letter here. You said, 'I desire to possess a copy of Devine's Napoleon, and am prepared to pay you ten pounds for the one which is in your possession.' Is that right?" "Certainly." "I was very much surprised at your letter, for I could not imagine how you knew that I owned such a thing." "Of course you must have been surprised, but the explanation is very simple. Mr. Harding, of Harding Brothers, said that they had sold you their last copy, and he gave me your address." "Oh, that was it, was it? Did he tell you what I paid for it?" "No, he did not." "Well, I am an honest man, though not a very rich one. I only gave fifteen shillings for the bust, and I think you ought to know that before I take ten pounds from you." "I am sure the scruple does you honour, Mr. Sandeford. But I have named that price, so I intend to stick to it." "Well, it is very handsome of you, Mr. Holmes. I brought the bust up with me, as you asked me to do. Here it is!" He opened his bag, and at last we saw placed upon our table a complete specimen of that bust which we had already seen more than once in fragments. Holmes took a paper from his pocket and laid a ten-pound note upon the table. "You will kindly sign that paper, Mr. Sandeford, in the presence of these witnesses. It is simply to say that you transfer every possible right that you ever had in the bust to me. I am a methodical man, you see, and you never know what turn events might take afterwards. Thank you, Mr. Sandeford; here is your money, and I wish you a very good evening." When our visitor had disappeared Sherlock Holmes's movements were such as to rivet our attention. He began by taking a clean white cloth from a drawer and laying it over the table. Then he placed his newly-acquired bust in the centre of the cloth. Finally, he picked up his hunting-crop and struck Napoleon a sharp blow on the top of the head. The figure broke into fragments, and Holmes bent eagerly over the shattered remains. Next instant, with a loud shout of triumph, he held up one splinter, in which a round, dark object was fixed like a plum in a pudding. "Gentlemen," he cried, "let me introduce you to the famous black pearl of the Borgias." Lestrade and I sat silent for a moment, and then, with a spontaneous impulse, we both broke out clapping as at the well-wrought crisis of a play. A flush of colour sprang to Holmes's pale cheeks, and he bowed to us like the master dramatist who receives the homage of his audience. It was at such moments that for an instant he ceased to be a reasoning machine, and betrayed his human love for admiration and applause. The same singularly proud and reserved nature which turned away with disdain from popular notoriety was capable of being moved to its depths by spontaneous wonder and praise from a friend. "Yes, gentlemen," said he, "it is the most famous pearl now existing in the world, and it has been my good fortune, by a connected chain of inductive reasoning, to trace it from the Prince of Colonna's bedroom at the Dacre Hotel, where it was lost, to the interior of this, the last of the six busts of Napoleon which were manufactured by Gelder and Co., of Stepney. You will remember, Lestrade, the sensation caused by the disappearance of this valuable jewel, and the vain efforts of the London police to recover it. I was myself consulted upon the case; but I was unable to throw any light upon it. Suspicion fell upon the maid of the Princess, who was an Italian, and it was proved that she had a brother in London, but we failed to trace any connection between them. The maid's name was Lucretia Venucci, and there is no doubt in my mind that this Pietro who was murdered two nights ago was the brother. I have been looking up the dates in the old files of the paper, and I find that the disappearance of the pearl was exactly two days before the arrest of Beppo for some crime of violence, an event which took place in the factory of Gelder and Co., at the very moment when these busts were being made. Now you clearly see the sequence of events, though you see them, of course, in the inverse order to the way in which they presented themselves to me. Beppo had the pearl in his possession. He may have stolen it from Pietro, he may have been Pietro's confederate, he may have been the go-between of Pietro and his sister. It is of no consequence to us which is the correct solution. "The main fact is that he HAD the pearl, and at that moment, when it was on his person, he was pursued by the police. He made for the factory in which he worked, and he knew that he had only a few minutes in which to conceal this enormously valuable prize, which would otherwise be found on him when he was searched. Six plaster casts of Napoleon were drying in the passage. One of them was still soft. In an instant Beppo, a skilful workman, made a small hole in the wet plaster, dropped in the pearl, and with a few touches covered over the aperture once more. It was an admirable hiding-place. No one could possibly find it. But Beppo was condemned to a year's imprisonment, and in the meanwhile his six busts were scattered over London. He could not tell which contained his treasure. Only by breaking them could he see. Even shaking would tell him nothing, for as the plaster was wet it was probable that the pearl would adhere to it--as, in fact, it has done. Beppo did not despair, and he conducted his search with considerable ingenuity and perseverance. Through a cousin who works with Gelder he found out the retail firms who had bought the busts. He managed to find employment with Morse Hudson, and in that way tracked down three of them. The pearl was not there. Then, with the help of some Italian EMPLOYEE, he succeeded in finding out where the other three busts had gone. The first was at Harker's. There he was dogged by his confederate, who held Beppo responsible for the loss of the pearl, and he stabbed him in the scuffle which followed." "If he was his confederate why should he carry his photograph?" I asked. "As a means of tracing him if he wished to inquire about him from any third person. That was the obvious reason. Well, after the murder I calculated that Beppo would probably hurry rather than delay his movements. He would fear that the police would read his secret, and so he hastened on before they should get ahead of him. Of course, I could not say that he had not found the pearl in Harker's bust. I had not even concluded for certain that it was the pearl; but it was evident to me that he was looking for something, since he carried the bust past the other houses in order to break it in the garden which had a lamp overlooking it. Since Harker's bust was one in three the chances were exactly as I told you, two to one against the pearl being inside it. There remained two busts, and it was obvious that he would go for the London one first. I warned the inmates of the house, so as to avoid a second tragedy, and we went down with the happiest results. By that time, of course, I knew for certain that it was the Borgia pearl that we were after. The name of the murdered man linked the one event with the other. There only remained a single bust--the Reading one--and the pearl must be there. I bought it in your presence from the owner--and there it lies." We sat in silence for a moment. "Well," said Lestrade, "I've seen you handle a good many cases, Mr. Holmes, but I don't know that I ever knew a more workmanlike one than that. We're not jealous of you at Scotland Yard. No, sir, we are very proud of you, and if you come down to-morrow there's not a man, from the oldest inspector to the youngest constable, who wouldn't be glad to shake you by the hand." "Thank you!" said Holmes. "Thank you!" and as he turned away it seemed to me that he was more nearly moved by the softer human emotions than I had ever seen him. A moment later he was the cold and practical thinker once more. "Put the pearl in the safe, Watson," said he, "and get out the papers of the Conk-Singleton forgery case. Good-bye, Lestrade. If any little problem comes your way I shall be happy, if I can, to give you a hint or two as to its solution." ***** THE STRAND MAGAZINE Vol. 27 JUNE, 1904 THE RETURN OF SHERLOCK HOLMES. By ARTHUR CONAN DOYLE.

Summary: Inspector Lestrade is back yet again. He is chilling at Baker Street and he is distracted. Lestrade has a case that seems really stupid and weird, but it's bothering him. Holmes tells him to spill it. Lestrade tells us that a guy named Morse Hudson, who ran the 1890s version of Pier One, had someone smash a bust of Napoleon in his shop and run off. Lestrade at first thought that this was "hooliganism." But then a man named Mr. Barnicot had the same thing happen to him. He used to be the proud owner of two discount busts of Napoleon bought from Morse Hudson. But some person recently broke in to Barnicot's home and office and broke his Napoleon busts. Tragic. All three Napoleon busts were made from the same mould. Lestrade is wondering if some crazy person has some sort of Napoleon obsession. Dr. Watson helpfully notes that there are lots of mental disorders, so who knows. Thanks for that tip, Watson. Holmes finds this all shifty, and says to keep him updated since seemingly dumb cases often turn out to be major ones. The next morning Holmes barges in on Watson and shows him a telegram from Lestrade telling them to come to an address. They do so and find a dead body. The dead body is outside the house of journalist Horace Harker, who had his Napoleon bust stolen last night. Holmes and Watson go to talk to the upset Harker. Harker is partially upset because he is too upset to write, and his newspaper will miss out on his eyewitness inside scoop. Harker gives them a quick run-down of events and notes that he bought his Napoleon bust from the Harding Brothers store and not Morse Hudson. Shop rivalry. The dynamic duo goes back outside to chat with Lestrade. There's no identification on the body, but he was carrying a picture of a man that Watson describes as "ape-like." The cops have also found a smashed Napoleon bust nearby under a street-lamp. Holmes theorizes that this person is breaking these busts for a deliberate purpose and not just to satisfy a Napoleon vendetta or something. Watson and Holmes leave to go talk to the people at the Harding Brothers' shop and at Morse Hudson's shop. Morse is able to identify the man in the photograph found on the dead body as Beppo, an Italian workman who did stuff like carving and framing at Gelder and Co. Then Holmes and Watson head to Gelder and Co., which is where the Napoleon busts were made originally. Beppo's former boss at Gelder and Co. tells about what a punk he was and how he got arrested on the job after fleeing the cops. Beppo had knifed another Italian in the street. He was a good worker until that incident though. The ex-boss also gives Holmes more info on the Napoleon busts. There were six total made from the same mold. Later Holmes and Watson see a hilarious account in the newspaper about a homicidal nut with a Napoleon complex running around London. They go back to the Harding Brothers shop and find out who owns the other two Napoleon busts. Holmes contacts both men. Lestrade comes back and fills them in on his day's work. Lestrade found out the identity of the dead body: Pietro Venucci. He's an Italian with mafia connections. Lestrade wants to go hunt for Beppo in the Italian Quarter but Holmes says they can let Beppo come to them. So Lestrade, Holmes, and Watson go stake-out the house of Josiah Brown. Eventually Beppo shows up to steal Josiah's Napoleon bust. Beppo is caught and arrested. Beppo smashes the bust before he's caught, depriving Josiah of some nice decoration in his home. Then Bepo is hauled off to jail, and Lestrade goes back to Baker Street with the dynamic duo. A Mr. Sandeford comes by to sell Holmes his Napoleon bust. He can't figure why Holmes is willing to pay so much for it, but Holmes convinces him it's cool and shoves him out the door. Then Holmes breaks the statue open and reveals a black pearl hidden inside. Holmes explains that this is a famous pearl that was stolen years ago. Holmes couldn't solve the case until now. Pietro had a sister, Lucretia, who stole the pearl. He doesn't know if Beppo was in on the scam or if he robbed Pietro, but Beppo hid the pearl in one of the Napoleon busts as the plaster was drying. But then he was arrested and had to wait until he got out of jail to find the pearl.

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Write a title and summarize: of Disapproval.-- (1) Joint resolution of disapproval defined.--In this subsection, the term ``joint resolution of disapproval'' means a joint resolution of either House of Congress the sole matter after the resolving clause of which is as follows: ``That Congress disapproves of the action proposed by the President in the report submitted to Congress under section 3(a) of the No Russian Diplomatic Access to Compounds Here in America Act on ____.'', with the blank space being filled with the appropriate date. (2) Effect of enactment.--Notwithstanding any other provision of law, the President may not take any action to waive, suspend, reduce, provide relief from, or otherwise limit the application of paragraph (1) or (2) of section 2(a), if a joint resolution of disapproval is enacted in accordance with this subsection. (3) Introduction.--During the 120-calendar-day period provided for under subsection (b)(1), a joint resolution of disapproval may be introduced-- (A) in the House of Representatives, by the majority leader or the minority leader; and (B) in the Senate, by the majority leader (or the majority leader's designee) or the minority leader (or the minority leader's designee). (4) Floor consideration in house of representatives.-- (A) Reporting and discharge.--If a committee of the House of Representatives to which a joint resolution of disapproval has been referred has not reported the resolution within 10 legislative days after the date of referral, that committee shall be discharged from further consideration thereof. (B) Proceeding to consideration.--Beginning on the third legislative day after each committee to which a joint resolution of disapproval has been referred reports it to the House or has been discharged from further consideration thereof, it shall be in order to move to proceed to consider the resolution in the House. All points of order against the motion are waived. Such a motion shall not be in order after the House has disposed of a motion to proceed on the resolution. The previous question shall be considered as ordered on the motion to its adoption without intervening motion. The motion shall not be debatable. A motion to reconsider the vote by which the motion is disposed of shall not be in order. (C) Consideration.--The joint resolution of disapproval shall be considered as read. All points of order against the resolution and against its consideration are waived. The previous question shall be considered as ordered on the resolution to final passage without intervening motion except two hours of debate equally divided and controlled by the sponsor of the resolution (or a designee) and an opponent. A motion to reconsider the vote on passage of the resolution shall not be in order. (5) Consideration in the senate.-- (A) Committee referral.--A joint resolution of disapproval introduced in the Senate shall be referred to the Committee on Foreign Relations. (B) Reporting and discharge.--If the Committee on Foreign Relations has not reported a joint resolution of disapproval within 10 session days after the date of referral of the resolution, that committee shall be discharged from further consideration of the resolution and the resolution shall be placed on the appropriate calendar. (C) Proceeding to consideration.--Notwithstanding Rule XXII of the Standing Rules of the Senate, it is in order at any time after the Committee on Foreign Relations reports the joint resolution of disapproval to the Senate or has been discharged from its consideration (even though a previous motion to the same effect has been disagreed to) to move to proceed to the consideration of the resolution, and all points of order against the resolution (and against consideration of the resolution) are waived. The motion to proceed is not debatable. The motion is not subject to a motion to postpone. A motion to reconsider the vote by which the motion is agreed to or disagreed to shall not be in order. If a motion to proceed to the consideration of the resolution is agreed to, the resolution shall remain the unfinished business until disposed of. (D) Debate.--Debate on the joint resolution of disapproval, and on all debatable motions and appeals in connection therewith, shall be limited to not more than 10 hours, which shall be divided equally between the majority and minority leaders or their designees. A motion to further limit debate is in order and not debatable. An amendment to, or a motion to postpone, or a motion to proceed to the consideration of other business, or a motion to recommit the resolution is not in order. (E) Vote on passage.--The vote on passage shall occur immediately following the conclusion of the debate on the joint resolution of disapproval and a single quorum call at the conclusion of the debate, if requested in accordance with the rules of the Senate. (F) Rulings of the chair on procedure.--Appeals from the decisions of the Chair relating to the application of the rules of the Senate, as the case may be, to the procedure relating to the joint resolution of disapproval shall be decided without debate. (G) Consideration of veto messages.--Debate in the Senate of any veto message with respect to the joint resolution of disapproval, including all debatable motions and appeals in connection with the resolution, shall be limited to 10 hours, to be equally divided between, and controlled by, the majority leader and the minority leader or their designees. (6) Rules relating to senate and house of representatives.-- (A) Coordination with action by other house.--If, before the passage by one House of a joint resolution of disapproval of that House, that House receives a joint resolution of disapproval from the other House, the following procedures shall apply: (i) The joint resolution of disapproval of the other House shall not be referred to a committee. (ii) With respect to the joint resolution of disapproval of the House receiving the joint resolution of disapproval from the other House-- (I) the procedure in that House shall be the same as if no joint resolution of disapproval had been received from the other House; but (II) the vote on passage shall be on the joint resolution of disapproval of the other House. (B) Treatment of a resolution of other house.--If one House fails to introduce a joint resolution of disapproval, the joint resolution of disapproval of the other House shall be entitled to expedited floor procedures under this subsection. (C) Treatment of house resolution in senate.--If, following passage of the joint resolution of disapproval in the Senate, the Senate then receives a joint resolution of disapproval from the House of Representatives, the joint resolution of disapproval of the House shall not be debatable. (D) Application to revenue measures.--The provisions of this paragraph shall not apply in the House of Representatives to a joint resolution of disapproval that is a revenue measure. (7) Rules of house of representatives and senate.--This subsection is enacted by Congress-- (A) as an exercise of the rulemaking power of the Senate and the House of Representatives, respectively, and as such is deemed a part of the rules of each House, respectively, but applicable only with respect to the procedure to be followed in that House in the case of a joint resolution of disapproval, and supersedes other rules only to the extent that it is inconsistent with such rules; and (B) with full recognition of the constitutional right of either House to change the rules (so far as relating to the procedure of that House) at any time, in the same manner, and to the same extent as in the case of any other rule of that House. (d) Appropriate Congressional Committees and Leadership Defined.-- In this section, the term ``appropriate congressional committees and leadership'' means-- (1) the Committee on Finance, the Committee on Banking, Housing, and Urban Affairs, the Select Committee on Intelligence, the Committee on Foreign Relations, and the majority and minority leaders of the Senate; and (2) the Committee on Ways and Means, the Committee on Financial Services, the Permanent Select Committee on Intelligence, the Committee on Foreign Affairs, and the Speaker, the majority leader, and the minority leader of the House of Representatives.

Title: No Russian Diplomatic Access to Compounds Here in America Act Summary: No Russian Diplomatic Access to Compounds Here in America Act or No Russian DACHA Act This bill prohibits the President from allowing access by the government of the Russian Federation or its personnel to Russian-owned diplomatic facilities and properties at Pioneer Point in Centreville, Maryland, and in Upper Brookville, New York. Before taking any action to waive or otherwise limit the application of such prohibition, the President must submit to specified congressional committees and the majority and minority leaders of the House of Representatives and the Senate a report that describes the proposed action and certifies that the Russian government: (1) did not use such facilities and properties for intelligence-related purposes, and (2) has ceased the harassment of U.S. government diplomatic personnel in Russia. The bill provides for a period of congressional review of such report and certification and prohibits the President from taking any such action if Congress passes a joint resolution disapproving it.

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Summarize: By. Harriet Arkell. A university student has told how he became a 'human fireball' after a doorman deliberately set fire to his fancy dress sheep costume. Sean Collins, 22, whose home-made costume was covered with cotton wool balls, was at a Preston nightclub for a friend's 21st birthday when his costume caught fire in what he assumed was an accident. Engulfed in flames, it took him ten seconds to rip the burning costume off, during which Mr Collins suffered horrific burns to his hands and arms. Before and after: Sean Colins, 22, suffered horrific burns after his sheep costume was set alight in a club. The University of Central Lancashire student was at the Evoque nightclub in Preston when he was set alight. Mr Collins, from Sunderland, may need two more years of treatment and suffers from anxiety and depression. He was rushed to hospital where medics said he had sustained 12 per cent burns to his body and needed several skin grafts and extensive hospital treatment. The forensic science and criminal investigation student at the University of Central Lancashire in Preston said: 'I became a human fireball instantly. I could feel this intense pain which I can't even begin to describe.' He later discovered that his injuries had been caused by a doorman at the Evoque nightclub, whom he'd never met, holding his cigarette lighter to the costume. Yesterday the bouncer, father of two Thomas McGuiness, 24, from Chorley, Lancashire, was jailed for 18 months at Preston Crown Court after admitting unlawful wounding. Before jailing McGuiness, Judge Michael Leeming, QC, murmured 'horrific' and there were gasps in the courtroom as CCTV footage of the moment Sean's costume was set alight was played. Hanifa Patel, prosecuting, said Mr Collins, of Sunderland, Tyne and Wear, who had made his outfit out of cotton wool balls and hairspray to keep them in place, was having a cigarette with friends when 'All of a sudden his costume ended up alight.' Bouncer Thomas McGuiness, 24, left, was jailed after admitting unlawfully wounding Mr Collins, right. She added: 'When officers arrived at the scene the victim was being treated for his injuries and the defendant was present. 'He was standing very close and trying to see what was happening. He then commented: "It was my fault. I was talking to my girlfriend having a cigarette and as I was waving my hand my cigarette caught him and he set alight. "'I'm an off-duty doorman and work at Evoque if you need to speak to me."' Miss Patel said that Mr Collins' injuries after the incident on January 17 meant he had missed two months of the final year of his course at UCLan and had had to give up his part-time job in the kitchen at McDonald's. Adrian Williams, defending, said: 'This was an incredibly stupid prank, not a deliberate assault on Mr Collins. 'This defendant was shocked by the consequences of his actions, he did not foresee them at all but he is responsible for them.' Mr Collins said: 'I remember standing having a cigarette with two of my mates - the next minute I was on fire. Engulfed in flames: The student became a 'human fireball' in seconds and said the pain was 'intense' 'I literally just burst into flames and I remember feeling shock and panic. I could feel this intense pain which I can't even begin to describe. 'It had taken me about 12 hours to make the costume and I became a human fireball instantly. I panicked and ran around trying to get the suit off. 'The whole thing was on fire and I knew I just had to get it off. My friends tried to help me and it took about ten seconds in total. 'Afterwards I ran into the street and sank to the pavement in shock.' Mr Collins was transferred from the Royal Preston Hospital for further care at South Manchester University Hospital where he underwent several skin graft operations. He may need a further two years of treatment, and has been left suffering anxiety and depression. He said: 'I was dealing with it pretty well for the first few days when I was in hospital because I thought it was an accident - I really thought someone had caught me with a cigarette. But then when the police came to see me and told me it wasn't an accident, it really affected me. 'I was devastated that someone could do something like that, especially to someone they'd never met. 'It was completely unprovoked.' He added: 'I suppose in some ways I'm lucky it wasn't worse but my head is all over the place now.' Mr Collins said he was'majorly disappointed' with the sentence, and added: 'I feel like what he's done hasn't been taken seriously. If I hadn't managed to get the suit off I could have died, but he'll be out before too long.'

Summary: Sean Collins, 22, spent 12 hours making outfit of cotton wool and hairspray. He attended a friend's 21st birthday party at Evoque nightclub in Preston. Student, from Sunderland, was with friends when his costume caught fire. Said: 'I became a human fireball instantly - I can't begin to describe the pain' He suffered 12 per cent burns and needed several skin grafts in hospital. Yesterday club doorman Thomas McGuiness, 24, was jailed for 18 months. Father of two from Chorley had set Mr Collins' costume alight with lighter. The bouncer admitted unlawful wounding but said it was an accident. Gasps from courtroom as footage of incident played to Preston Crown Court.

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Summarize: FIELD OF THE INVENTION This invention relates generally to a pad system, and more specifically to a removable and modular pad system usable in a variety of environments such as military, police, recreational shooting, recreational outdoor activities, construction, and home improvement. BACKGROUND OF THE INVENTION Conventional knee pads are available in two types: soft shell and hard shell. Volleyball players, for example, use soft knee pads that attach with elastic straps. Hard shell knee pads generally include a soft inner pad fixed to a hard outer pad of material having a higher density (i.e., the hard shell). Like the soft shell knee pads, the most hard shell knee pads are attachable to the wearer using elastic straps. If the straps are permanently attached to the knee pad system then it is worn by sliding it over the foot and up to the knee. Otherwise, the straps may be attached using clips, buckles or a hook-and-loop fastening system (e.g., a VELCRO® fastening system). The pads may be worn under or over pants. After so much movement like walking or running, the strap-style knee pads often begin to fall or at least move with respect to the knee, thus requiring effort to pull the knee pad back up or to adequately reposition it. In some environments such as a military combat situation, a soldier&#39;s split second movement to pull up his knee pad could give away his position or provoke even harsher consequences. In other, less dangerous, environments the pulling up or repositioning of strap-style knee pads can just be irritating. Protective pads that are not in the proper place may also not provide adequate protection. The pads and straps can also bind or chafe the knee or leg making the pads uncomfortable to wear. One type of knee pad system provides for the knee pad to be sewn into the apparel, which essentially results in a non-removable knee pad. One drawback of such a permanent assembly is that in many activities the wearer may perspire, which in turn generates moisture that is absorbed by the knee pad. The moist knee pad may then become heavier and less comfortable. Closed-cell pads have been developed for use with pants and may be insertable into a knee pocket in the pants. However, these pads do not prevent excessive wear on the outer layer of the pants and may even accelerate the wear of the pant knees. These same basic considerations apply to elbow pads, hip pads, and other protective pads. SUMMARY OF THE INVENTION The present invention relates to a padding system that may advantageously provide the benefits of being modular in terms of size and shape, easily removable and replaceable, comfortable and secure all while maintaining an aesthetically, orderly, or neat and trim look. These advantages, and in particular the latter advantage, make the padding system beneficial to and desirable for military and police units. In one embodiment, the padding system is a knee pad system having an inner knee pad and an outer shell fastened to one another through openings provided in a trouser fabric located between the inner knee pad and the outer shell. The inner knee pad may be received in a pocket coupled to the trouser fabric. In accordance with an aspect of the invention, a padding system includes an inner pad; a fastening assembly; and an outer shell removably attachable to one of an apparel item or the inner pad by way of the fastening device. In accordance with another aspect of the invention, a padding system for an apparel item includes a pocket coupled to a surface of the apparel item; an inner pad receivable in the pocket; and an outer shell removably attachable to the inner pad by way of openings provided in either the apparel item or the pocket. In accordance with yet another aspect of the invention, a pair of trousers includes a knee portion coupled to the trousers; a pocket coupled to the knee portion; an inner knee pad receivable in the pocket; and an outer shell removably attachable to the inner knee pad by way of openings provided in one of the knee portion or the pocket. In accordance with yet another aspect of the invention, a method for coupling a padding system to an apparel item includes the steps of (1) sliding an inner pad into a pocket coupled to the apparel item, the inner pad having a fastening device; (2) arranging the inner pad in the pocket to align the fastening device with an opening formed in either one of the pocket or the apparel item; and (3) coupling an outer shell to the inner pad using a complementary fastening device that is engageable with the fastening device of the inner pad. BRIEF DESCRIPTION OF THE DRAWINGS Preferred and alternative embodiments of the present invention are described in detail below with reference to the following drawings: FIG. 1 is a front perspective view of a padding system according to an embodiment of the present invention; FIG. 2 a cross-sectional view of the padding system of FIG. 1 taken along line 2 - 2 of FIG. 1 according to an embodiment of the present invention; FIG. 3 is a rear plan view of an outer shell of the padding system of FIG. 1 according to an embodiment of the present invention; FIG. 4 is a front plan view of an inner pad of the padding system of FIG. 1 according to an embodiment of the present invention; FIG. 5 is a front plan view of an the outer shell of FIG. 3 attached to the inner pad of the FIG. 4 without any apparel material therebetween according to an embodiment of the present invention; FIG. 6 is a front plan view of a knee portion of a trouser leg having openings that permit the outer to be coupled to the inner pad of the padding system according to an embodiment of the present invention; FIG. 7 is a front perspective view of an apparel item with a pocket having an opening configured to receive an inner pad according to an embodiment of the present invention; FIG. 8 is a cross-sectional view of a padding system with an inner pad received in an inner pocket and an outer shell coupled to the inner pad according to another embodiment of the present invention; FIG. 9 is a cross-sectional view of a padding system with an inner pad received in a pocket and an outer shell coupled to an apparel item according to another embodiment of the present invention; FIG. 10 is a cross-sectional view of a padding system having an inner pad received in a pocket and coupled to an apparel item and an outer shell also coupled to the apparel item according to another embodiment of the present invention; and FIG. 11 is a cross-sectional view of a padding system with an inner pad not received in a pocket, but coupled to an apparel item, and an outer shell also coupled to the apparel item according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT As will be described in further detail below, an embodiment of the present invention includes a padding system having an outer shell coupled to an inner pad that is received in a pocket coupled to an article of apparel, such as a trouser leg or a shirt sleeve, which may be made from a natural cloth, synthetic, laminate or other type of material. The pocket may extend inwardly or outwardly from a portion of the apparel. Thus, either the pocket or the trouser leg includes openings that permit fasteners on the outer shell to be coupled to fasteners on the inner pad. In at least one embodiment, these openings are covered by the outer shell when attached to the inner pad, which in turn provides a clean, aesthetic appearance. Alternatively, the fasteners may not extend through openings, but be secured with magnets or to the apparel directly with other fasteners, while still generally aligning the shell over the pad. The pad may fit snuggly within the pocket created in the apparel for it, while the shell is securable to the outer layer of the apparel to be positioned directly over the pad. Alternatively, the pad may simply be disposed inside the apparel with the shell on the outside, without the pad being secured within a pocket. The securement of the shell to the pad situates the pad in this embodiment. This system and its various alternate embodiments may be applied to a knee pad, an elbow pad, a hip pad, or other protective gear used in conjunction with apparel. For purposes of brevity and clarity, the description here will focus on a knee pad embodiment as set forth below. FIG. 1 shows a portion of a pair of trousers 100 having a trouser leg 102 with a trouser knee portion 104 integrally formed therewith or attached thereto. A knee pad system 105 is attached to the knee portion 104. The illustrated embodiment shows an outer shell 106 having fasteners 108, which take the form of snaps in this embodiment. The knee portion 104 is configured with an opening 107 configured to receive an inner pad (not shown), as will be described in greater detail below. However, the fasteners 108 may take other forms such as, but not limited to, hook and loop fasteners or clips. The trousers may otherwise be referred to as or take the form of fatigues, slacks, jeans, denims, dungarees, overalls, corduroys, or chaps. Fatigues may have different names depending on the type of service or unit, for example the U.S. Army calls them army combat uniforms (ACUs). As mentioned above, the padding system may be used with apparel on other parts of the body as well, such as elbows or hips. The double-dashed lines in FIG. 1 show stitching on the trousers 100. FIG. 2 shows the outer shell 106 fastened to an inner pad 110, which in turn is received in a space 112 formed by a pocket 114 coupled to the knee portion 104. The inner pocket 114 may be stitched to or otherwise attached to the knee portion 104. The inner pocket 114 is defined by an interfacing pocket portion 113 and a region 115 of the knee portion 104 that cooperate to form the space 112. In the illustrated embodiment, the pocket 114 is formed on or attached to an exterior surface of the trousers 100. Therefore, the inner pad 110 contacts both the interfacing pocket portion 113 and the region 115, which is not visible when the outer shell 106 is removed. The region 115 includes a surface 117 in contact with the wearer; whereas the interfacing pocket portion 113 is trapped between the outer shell 106 and the inner pad 110. The pocket opening is provided near a lower section of the knee portion 104 such that the inner pad 110 is inserted into the pocket opening 107 by pushing it upwards into the pocket 114. FIGS. 3 and 4 show the outer shell 106 and inner pad 110. Referring specifically to FIG. 3, the outer shell 106 includes an inner surface 116 and an approximate hourglass shape or periphery contour 118. In the illustrated embodiment, the snap fasteners 108 are arranged adjacent the rounded corners of the contour 118, but could be arranged in a variety of configurations. Likewise, the outer shell 106 could have different shapes and/or periphery contours other than the approximate hourglass shape. Further, the snap fasteners 108 take the form of female snap fasteners, but could also take the form of male snap fasteners. The inner surface 116 includes a convex configuration for nesting with the inner pad 110 as best shown in FIG. 5. The outer shell 106 is preferably made from a hard or semi-rigid plastic material, but may be made from a variety of materials, whether rigid or flexible. Briefly referring to FIG. 4, the inner pad 110 includes complementary fasteners 120, which in the illustrated embodiment take the form of male snap fasteners, but could also take the form of female snap fasteners. The inner pad 110 also includes an outer surface 122 and an approximate hourglass shape 124, but less pronounced than that of the outer shell 106. The outer surface 122 is concave and configured to nest with the inner surface 116 of the outer shell 106. The inner pad 110 is made from open or closed cell foam, but closed cell foam is preferable for preventing unwanted moisture absorption. The inner 110 may be made from other flexible materials that are easily bendable, yet spring back to their shape 124 when inserted into the pocket 114 ( FIG. 2 ). FIG. 6 shows the knee portion 104 with openings 126 for the outer shell 108, which in turn is shown in dashed lines as merely projected onto the knee portion 104 for illustrative reference purposes. In the illustrated embodiment, the openings 126 are sized to closely receive the mating fasteners 108 ( FIG. 3) and 120 ( FIG. 4 ), respectively. Preferably, when the outer shell 106 is coupled to the inner pad 110, the openings 126 are covered by the outer shell 106. FIG. 7 shows the inner pad 110 being inserted into the pocket 114 through the pocket opening 107. Preferably, the inner pad 110 is rolled, folded, or partially folded to fit within the pocket 114 because a maximum width of the inner pad 110 exceeds a width of the pocket opening 107. Once in the pocket 114, the inner pad 110 springs back to its unrolled or unfolded shape and may be maneuvered by hand to align with the openings 126. FIG. 8 shows a trouser leg 200 having a knee portion 204 and a padding system 205. Similar or identical features will retain the same reference numerals as the previous embodiment and merely be incremented by one hundred, but will not be described again in detail. An outer shell 206 is fastened to an inner pad 210 with fasteners 208. A pocket 214 extends inward from the knee portion 204 instead of outward as illustrated in FIG. 2. The pocket 214 includes a pocket opening 207 near a bottom region of the knee portion 204. The pocket opening 207 may be closed with hook and loop fasteners, snaps, or buttons to better secure the pad and prevent debris or dirt from entering the pocket 214. The opening 207 may take the form of a flap that covers the ingress region of the pocket 214. Moreover, other fastening, closing, and covering systems may be employed. FIG. 9 shows a trouser leg 300 with a knee portion 304 and a padding system 305. Again, similar or identical features will retain the same reference numerals as the previous embodiment and merely be incremented by one hundred, but will not be described again in detail. In the illustrated embodiment, an outer shell 306 is coupled directly to the knee portion 304 with a fastener system 330. Thus, the outer shell 306 may have fasteners 332 that take the form of male snaps whereas the knee portion 304 may have crimped on fasteners 334 that take the form of female snaps. However, other types of fastener systems 330, such as hook and loop fastener systems, may be employed. The inner pad 310 is received into a pocket 314 in a folded manner and then expands within the pocket 314 to prevent it from falling out. It is appreciated that a pocket opening 307 may be located on the side or top of the pocket 314. FIG. 10 shows a slightly different embodiment of a trouser leg 400 with a knee portion 404 and a padding system 405. Again, similar or identical features will retain the same reference numerals as the previous embodiment and merely be incremented by one hundred, but will not be described again in detail. In the illustrated embodiment, an outer shell 406 is coupled directly to the knee portion 404 with a first fastener system 430. In addition, an inner pad 410 is coupled to the knee portion 404 with a second fastener system 436, which may also be attached to the pocket 414. Alternatively, the pocket 414 may extend outward from the knee portion 404 and both the outer shell 406 and inner pad 410 may be fastened to the pocket 314. FIG. 11 shows yet another embodiment of a trouser leg 500 with a knee portion 504. In the illustrated embodiment, an outer shell 506 is attached directly to the knee portion 504 and an inner pad 510 is attached directly to the knee portion 504, but not located in any type of a pocket. The outer shell 506 and inner pad 510 may be attached with first and second fastener systems 530, 534, respectively or may be attached directly to each other through openings (not shown) in the knee portion 504. While the preferred embodiments of the invention have been illustrated and described, as noted above, many changes can be made without departing from the spirit and scope of the invention, such as which way the pockets extend, how the shell and pad are coupled to the apparel and coupled together, whether a pocket is provided and what type of fastener systems may be utilized. Accordingly, the scope of the invention is not limited by the disclosure of the preferred embodiment. Instead, the invention should be determined by reference to the claims that follow.

Summary: A padding system may be advantageously modular in terms of size and shape, easily removable and replaceable, and comfortable and secure while maintaining an aesthetically neat and trim look. In one embodiment, the padding system includes an inner pad coupled to an outer shell with a portion of an apparel article positioned between, The apparel may include openings to allow a direct connection between the inner pad and outer shell or fasteners may be attached to the apparel for removably engaging with one or both of the inner pad and outer shell. The inner pad may be received in a pocket, which may extend inward or outward.

big_patent

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Write a title and summarize: SECTION 1. SHORT TITLE. This Act may be cited as the ``Higher Education Affordability Act of 2010''. SEC. 2. CONSOLIDATION OF EDUCATION TAX INCENTIVES INTO HIGHER EDUCATION TAX CREDIT. (a) In General.--Section 25A of the Internal Revenue Code of 1986 (relating to Hope and Lifetime Learning credits) is amended to read as follows: ``SEC. 25A. HIGHER EDUCATION TAX CREDIT. ``(a) Allowance of Credit.--In the case of an individual, there shall be allowed as a credit against the tax imposed by this chapter for the taxable year an amount equal so much of the higher education expenses paid by the taxpayer during the taxable year (for education furnished during any academic period beginning in such taxable year with respect to each student for whom an election is in effect under this section for any taxable year) as does not exceed $3,000. ``(b) Limitations.-- ``(1) Lifetime credit limitation.--The amount of the credit allowed under subsection (a) for any taxable year with respect to any student shall not exceed the excess of-- ``(A) $15,000, over ``(B) the aggregate credit allowed under subsection (a) with respect to such individual for all prior taxable years. ``(2) Credit limitation based on modified adjusted gross income.-- ``(A) In general.--The amount which would (but for this paragraph) be taken into account under subsection (a) for the taxable year shall be reduced (but not below $500) by the amount determined under subparagraph (B). ``(B) Amount of reduction.--The amount determined under this subparagraph is the amount which bears the same ratio to the amount which would be so taken into account as-- ``(i) the excess of-- ``(I) the taxpayer's modified adjusted gross income for such taxable year, over ``(II) the applicable amount under subparagraph (D), bears to ``(ii) $24,000 ($48,000 in the case of a joint return). ``(C) Modified adjusted gross income.--The term `modified adjusted gross income' means the adjusted gross income of the taxpayer for the taxable year increased by any amount excluded from gross income under section 911, 931, or 933. ``(D) Applicable amount.--The applicable amount under this subparagraph is-- ``(i) in the case of a joint return, 200 percent of the dollar amount in effect under clause (ii) for the taxable year, and ``(ii) in any other case, $80,000. ``(3) Limitation based on amount of tax.--In the case of a taxable year to which section 26(a)(2) does not apply, the credit allowed under subsection (a) for the taxable year shall not exceed the excess of-- ``(A) the sum of the regular tax liability (as defined in section 26(b)) plus the tax imposed by section 55, over ``(B) the sum of the credits allowable under this subpart (other than this section and section 23) and section 27 for the taxable year. ``(c) Definitions.--For purposes of this subsection-- ``(1) Higher education expense.--The term `higher education expense' means any expense of a type which is taken into account in determining the cost of attendance (as defined in section 472 of the Higher Education Act of 1965, as in effect on the date of the enactment of this section) of a student who is-- ``(A) the taxpayer, ``(B) the taxpayer's spouse, or ``(C) any dependent of the taxpayer with respect to whom the taxpayer is allowed a deduction under section 151, at an eligible educational institution with respect to the attendance of such student at such institution for the academic period for which the credit under this section is being determined. ``(2) Eligible educational institution.--The term `eligible educational institution' means an institution-- ``(A) which is described in section 481 of the Higher Education Act of 1965, as in effect on the date of the enactment of the Taxpayer Relief Act of 1997, and ``(B) which is eligible to participate in a program under title IV of such Act. ``(d) Special Rules.-- ``(1) Identification requirement.--No credit shall be allowed under subsection (a) to a taxpayer with respect to any individual unless the taxpayer includes the name and taxpayer identification number of such student on the return of tax for the taxable year. ``(2) Adjustment for certain scholarships.--The amount of higher education expenses otherwise taken into account under subsection (a) with respect to an individual for an academic period shall be reduced (before the application of subsections (a) and (b)) by the sum of any amounts paid for the benefit of such individual which are allocable to such period as-- ``(A) a qualified scholarship which is excludable from gross income under section 117, ``(B) an educational assistance allowance under chapter 30, 31, 32, 34, or 35 of title 38, United States Code, or under chapter 1606 of title 10, United States Code, and ``(C) a payment (other than a gift, bequest, devise, or inheritance within the meaning of section 102(a)) for such student's educational expenses, or attributable to such individual's enrollment at an eligible educational institution, which is excludable from gross income under any law of the United States. ``(3) Treatment of expenses paid by dependent.--If a deduction under section 151 with respect to an individual is allowed to another taxpayer for a taxable year beginning in the calendar year in which such individual's taxable year begins-- ``(A) no credit shall be allowed under subsection (a) to such individual for such individual's taxable year, and ``(B) higher education expenses paid by such individual during such individual's taxable year shall be treated for purposes of this section as paid by such other taxpayer. ``(4) Treatment of certain prepayments.--If higher education expense is paid by the taxpayer during a taxable year for an academic period which begins during the first 3 months following such taxable year, such academic period shall be treated for purposes of this section as beginning during such taxable year. ``(5) Denial of double benefit.--No credit shall be allowed under this section for any expense for which deduction is allowed under any other provision of this chapter. ``(6) No credit for married individuals filing separate returns.--If the taxpayer is a married individual (within the meaning of section 7703), this section shall apply only if the taxpayer and the taxpayer's spouse file a joint return for the taxable year. ``(7) Nonresident aliens.--If the taxpayer is a nonresident alien individual for any portion of the taxable year, this section shall apply only if such individual is treated as a resident alien of the United States for purposes of this chapter by reason of an election under subsection (g) or (h) of section 6013. ``(e) Portion of Credit Refundable.--The aggregate credits allowed to a taxpayer under subpart C shall be increased by 20 percent of the portion of the amount of the credit which would have been allowed to the taxpayer under this section without regard to this subsection and the limitation under section 26(a)(2) or subsection (b)(4), as the case may be. The amount of the credit allowed under this subsection shall not be treated as a credit allowed under this subpart and shall reduce the amount of credit otherwise allowable under subsection (a) without regard to section 26(a)(2) or subsection (b)(3), as the case may be. ``(f) Election Not To Have Section Apply.--A taxpayer may elect not to have this section apply with respect to the higher education expenses of an individual for any taxable year. ``(g) Inflation Adjustment.-- ``(1) In general.--In the case of a taxable year beginning after 2011, the $3,000 and $15,000 amount in subsections (a) and (b)(1), respectively, shall each be increased by an amount equal to-- ``(A) such dollar amount, multiplied by ``(B) the cost-of-living adjustment determined under section 1(f)(3) for the calendar year in which the taxable year begins, determined by substituting `calendar year 2010' for `calendar year 1992' in subparagraph (B) thereof. ``(2) Rounding.--If any amount as adjusted under subparagraph (A) is not a multiple of $1,000, such amount shall be rounded to the next lowest multiple of $1,000. ``(h) Regulations.--The Secretary may prescribe such regulations as may be necessary or appropriate to carry out this section, including regulations providing for a recapture of the credit allowed under this section in cases where there is a refund in a subsequent taxable year of any expense which was taken into account in determining the amount of such credit.''. (b) Elimination of 529 Plan Reduction for Education Credit.--Clause (v) of section 529(c)(3)(B) of such Code is amended by striking ``shall be reduced'' and all that follows through the period at the end and inserting the following ``shall be reduced as provided in section 25A(g)(2).''. (c) Conforming Amendments.-- (1) Subparagraph (B) of section 24(b)(3) of such Code is amended by striking ``25A(i)'' and inserting ``25A''. (2) Clause (ii) of section 25(e)(1)(C) of such Code is amended by striking ``2A(i)'' inserting ``25A''. (3) Paragraph (2) of section 25B(g) of such Code is amended by striking ``25A(i)'' and inserting ``25A''. (4) Paragraph (2) of section 1400C(d) of such Code is amended by striking ``25A(i)'' and inserting ``25A''. (5) Section 62(a) of such Code is amended by striking paragraph (18). (6) Subparagraph (A) of section 86(b)(2) of such Code is amended by striking ``, 222''. (7) Subparagraph (B) of section 72(t)(7) of such Code is amended by striking ``section 25A(g)(2)'' and inserting ``section 25A(d)(2)''. (8) Subparagraph (A) of section 135(c)(4) of such Code is amended by striking ``, 222''. (9) Subparagraph (A) of section 137(b)(3) of such Code is amended by striking ``, 222''. (10) Subparagraph (A) of section 199(d)(2) of such Code is amended by striking ``, 222''. (11) Clause (ii) of section 219(g)(3)(A) of such Code is amended by striking ``, 222''. (12) Clause (i) of section 221(b)(2)(C) of such Code is amended by striking ``, 222''. (13) Clause (iii) of section 469(i)(3)(F) of such Code is amended by striking ``221, and 222'' and inserting ``and 221''. (14) Subsection (d) of section 221 of such Code is amended-- (A) by striking ``section 25A(g)(2)'' in paragraph (2)(B) and inserting ``section 25A(d)(2)'', and (B) by striking ``section 25A(f)(2)'' in the second sentence of paragraph (2) and inserting ``section 25A(c)(2)''. (15) Paragraph (3) of section 221(d) of such Code is amended to read as follows: ``(3) Eligible student.--The term `eligible student' means, with respect to any academic period, a student who-- ``(A) meets the requirements of section 484(a)(1) of the Higher Education Act of 1965 (20 U.S.C. 1091(a)(1)), as in effect on the date of the enactment of the Taxpayer Relief Act of 1997, and ``(B) is carrying at least \1/2\ the normal full- time workload for the course of study the student is pursuing.''. (16) Subclause (I) of section 529(c)(3)(B)(v) of such Code, as amended by this Act, is amended by striking ``section 25A(g)(2)'' and inserting ``25A(d)(2)''. (17) Clause (i) of section 529(e)(3)(B) of such Code is amended by striking ``section 25A(b)(3)'' and inserting ``section 221(d)(3)''. (18) Subclause (I) of section 530(d)(2)(C)(i) of such Code is amended by striking ``section 25A(g)(2)'' and inserting ``section 25A(d)(2)''. (19) Clause (iii) of section 530(d)(4)(B) of such Code is amended by striking ``section 25A(g)(2)'' and inserting ``25A(d)(2)''. (20) Section 1400O of such Code is amended by adding at the end the following flush sentence: ``For purposes of this section, any reference to section 25A shall be treated as a reference to such section as in effect on the day before the date of the enactment of this sentence.''. (21) Subsection (e) of section 6050S of such Code is amended by striking ``subsection (g)(2)'' and inserting ``subsection (d)(2)''. (22) Subparagraph (J) of section 6213(g)(2) of such Code is amended by striking ``section 25A(g)(1) (relating to higher education tuition and related expenses)'' and inserting ``section 25A(d)(1) (relating to higher education tax credit)''. (23) Paragraph (2) of section 1324(b) of title 31, United States Code, is amended by inserting ``, 25A,'' after ``section 35''. (d) Effective Date.--The amendments made by this section shall apply to expenses paid after December 31, 2010, for education furnished in academic periods beginning after such date.

Title: To amend the Internal Revenue Code of 1986 to consolidate education tax benefits into one credit against income tax for higher education expenses Summary: Higher Education Affordability Act of 2010 - Amends the Internal Revenue Code to replace the Hope and lifetime learning tax credits with a partially refundable $3,000 tax credit for the higher education expenses of a taxpayer, the taxpayer's spouse, or any dependent at an institution of higher education.

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Summarize: Katy Perry might be young in love these days, but at one point she was even younger and maybe even more in love! An auction site has gotten ahold of a love letter that Perry wrote in 1995 to a lucky boy named Christopher Villar. Based on the letter, it seems the not-yet-famous performer met him at camp and continued to see him at evangelical rallies their families attended. The full-page note seems to be in response to a letter Villar had sent to her. Despite being only 11-years-old, the “Dark Horse” singer was certain she really liked this boy, as her postscript says, “I like you a lot! Write back a.s.a.p.” PHOTOS: Katy Perry and Her Fab Fashion The pop sensation even accessorized her letter with Lisa Frank-style stickers to give it a little extra pop! The starting price for the one-of-a-kind love letter is $300 and is expected to sell for $600-$800. Would you bid on a Katy Perry love letter? Sound off in the comments below! The NFL has reportedly short-listed the three acts for the 2015 game, but there's a catch. You can't buy the kind of exposure the Super Bowl halftime show brings -- or can you? Is Katy Perry Playing the Super Bowl? 5 Reasons Behind the Theory According to a report Tuesday (Aug. 19) in the Wall Street Journal, the NFL has narrowed down its 2015 Super Bowl halftime performer wish list to Rihanna, Coldplay and Katy Perry. But the league thinks the music superstars should pay them for the opportunity to perform at the highest-rated TV event of the year, not the other way around. The report says the NFL was met with a "chilly reception" from the acts' reps, so it remains to be seen whether any of the three will pony up for the performance (or if the NFL will back down on the idea altogether). But if it truly comes down to this trifecta, who are you rooting for? Cue the "Firework"s: Katy Perry has officially signed on to perform during the halftime show for Super Bowl XLIX on February 1st, Billboard reports. The multi-platinum pop star had been in the running alongside Rihanna and Coldplay, according to The Wall Street Journal. Related 18 Things You Learn Following Katy Perry Around From hating fame to dreaming of an acoustic record, here's what didn't fit into her third Rolling Stone cover story WSJ also reported that some artists were asked if they would agree to a "pay to play" deal by making a financial contribution to the NFL in exchange for the major national exposure granted from such a high-profile gig. But sources indicated that the proposition "got a chilly reception from the candidates' representatives." Perry joked about the Super Bowl negotiations this past Saturday during a recent appearance on ESPN's College GameDay. "We have had some conversations, and I would be honored, of course," she said. "But I have let them know that I'm not the kind of girl who would pay to play the Super Bowl. The ball is in their field." A representative for Perry was not immediately available for comment. The NFL's "pay to play" plan hasn't gone over too well with agents, either. "Obviously it is a marketing boon to play halftime for the Super Bowl," David T. Viecelli, agent for Arcade Fire, Mumford & Sons and St. Vincent, told Rolling Stone. "But I hope that everybody tells them to go get stuffed." The league rarely pays artists who perform during the halftime show, though they do typically cover travel and production expenses, which can reach as high as $1 million. In recent years, the halftime show has continued to grow in popularity — this year's performance with Bruno Mars and the Red Hot Chili Peppers brought in a record 115.3 million viewers, while only 112.2 million watched the actual game. Katy Perry will perform at this year's Super Bowl halftime show, sources have confirmed with Billboard. Perry's performance has been speculated since August after the National Football League had reportedly shortlisted her along with Coldplay and Rihanna, who saw the use of her song "Run This Town" with Jay-Z axed in a segment during the wake of the Ray Rice scandal. Super Bowl Halftime Pay-to-Play Reports: Grammys Producer Ken Ehrlich Weighs In The news of those three contenders also came with word the league was asking those artists under consideration to pay to play, since last year's broadcast drew a record-setting 111.5 million viewers and previous performers have all seen significant boosts in sales, touring and public profile. In response, appearing on ESPN's College Game Day this past Saturday, Perry said, "I'm not the kind of girl who would pay to play the Super Bowl." With previous speculation, Billboard reported a number of good reasons for Perry to play the big stage, including her current hits, her (mostly) family-friendly catalog, and her international popularity (her 58.1 million Twitter followers make her the most popular presence on the social site). The NFL has declined to comment.

Summary: Billboard last night broke the news that, based on sources, the 2015 Super Bowl halftime performer will be neither Rihanna nor Coldplay but... Katy Perry. Which is interesting, because when she appeared on ESPN's College GameDay on Saturday, as Rolling Stone notes, Perry talked about the fact that the NFL was reportedly planning to ask performers to pay the league for the privilege of playing the show. "We have had some conversations, and I would be honored, of course," she said at the time. "But I have let them know that I'm not the kind of girl who would pay to play the Super Bowl. The ball is in their field."

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Summarize: Palmer United's Jacqui Lambie wants members of radical Islamic groups to be stripped of their right to vote and deported in a bid to combat home-grown terrorists. Prime Minister Tony Abbott is 'turning a blind eye' to the real threat of terrorists in our own backyard, as he sends our troops to fight them overseas, Senator Lambie says. If Islamic leaders who preach violence and allegiance to anti-democratic foreign powers are not allowed to stand for the Australian parliament, the next step should be introducing laws that mean such leaders are stripped of their citizenship and their right to vote, she said. Scroll down for video. Jacquie Lambie delivering a speech at Parliament House in Canberra. '(How many of them) enjoy Australian social services payments, entitlements and democratic freedoms?' Senator Lambie said. 'If you're going to carry on with that sort of rot, the first thing we should ensure is that they don't receive any government funds or entitlements, don't have the right to vote and are deported.' 'Our taxes should be exclusively reserved for people who love Australia with no formal or informal allegiances to foreign religious leaders and anti-democratic laws, she said. Lambie is also running a campaign to 'ban the burqa.' Last month, Lambie made the following statements in the wake of the nation wide terror raids. Lambie (left) went head-to-head with Maha Abdo from the Muslim Women's Association (right) on Channel Seven's morning show Sunrise. When Lambie shared an image on her Facebook of Malalai Kaka, an Afghanistan's policewoman who the Taliban murdered in her car in 2008, she went under intense fire. 'Now we're at war with the sharia extremists and Australia has been placed on a heightened terrorism alert - we can't have anyone hiding their identity in public. It now becomes an important national security issue,' Lambie said. 'I call for an immediate and complete ban on the wearing of burkas in public. 'The burkas are obviously designed by men who have an obsessive need to have extreme control and power over women. 'Why have the feminists turned a blind eye to this and other abhorrent cultural practices happening in Australia like female genital mutilation?' Last month, she shared an image on her Facebook of Malalai Kaka, an Afghanistan's policewoman who the Taliban murdered in her car in 2008. The image featured the words 'For security reasons it's now time to ban the burqa.' Lambie went under intense fire for the post, and was accused of being ignorant by opposition leader Bill Shorten. Earlier this month, Lambie went head-to-head with Maha Abdo from the Muslim Women's Association on Channel Seven's morning show Sunrise. During the debate, she told Abdo, 'You have beautiful faces and it would be nice to be able see them.'

Summary: Senator Lacquie Lambie wants members of radical Islamic groups to be stripped of their right to vote. She says Prime Minister Tony Abbott is 'turning a blind eye' to the real threat of terrorists. 'The first thing we should ensure is that they don't receive any government funds or entitlements, don't have the right to vote and are deported' It come after a spate of controversial Muslim comments from Ms Lambie.

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Summarize: STATEMENT OF PRIORITY [0001] This is a non-provisional application claiming priority to U.S. Provisional Application No. 62/295,964, filed on 16 Feb. 2016, and entitled “Automatic Air Backup System.” The entirety of the provisional disclosure is incorporated herein by reference. FIELD OF THE APPLICATION [0002] The present application relates, generally, to a backup system for providing a logging unit or other field environment which is required to be at overpressure with a backup air supply, and a method of automatically switching between the two to avoid interruption. BACKGROUND [0003] On rigs and other well drilling sites, logging units often contain sensitive electronic equipment which record data from the drilling of a well, equipment which must be protected from contamination from the outside environment. Consequently, these units are often kept at a positive air pressure differential, or overpressure, from the ambient air pressure located outside the logging unit. This air is usually supplied from the ambient atmosphere around the rig itself, utilizing pumps and filters to supply the logging unit with overpressure. [0004] Most logging units respond to interruptions in air supply, whether from mechanical or human error, by preemptively shutting down the logging equipment and only restarting once the unit has again reached overpressure. Since it may take anywhere from 45 minutes to an hour for overpressure to be reestablished, such errors may result in the loss of several thousand feet worth of drilling logs. [0005] A need therefore exists for a backup unit which can supply air at overpressure in the absence of a connection between the outside air supply and the pumps. A need additionally exists for a backup unit which can automatically switch between the two air supplies without the need for a manual intervention. DRAWINGS [0006] FIG. 1A depicts a perspective view of an embodiment of the backup unit. [0007] FIG. 1B depicts a top (plan) view of an embodiment of the backup unit. [0008] FIG. 1C depicts a front view of an embodiment of the backup unit. [0009] FIG. 1D depicts a side view of an embodiment of the backup unit. [0010] FIG. 1E depicts a rear view of an embodiment of the backup unit. [0011] FIG. 2A depicts a front view of the valve system housing. [0012] FIG. 2B depicts a perspective view of the valve system within the housing. [0013] FIG. 2C depicts a cross-sectional view of the valve system within the housing. [0014] FIG. 2D depicts a flow diagram illustrating connections within the valve system. [0015] FIG. 3A depicts a side view of the valve system in isolation. [0016] FIG. 3B depicts a perspective view of the valve system in isolation. SUMMARY OF THE INVENTION [0017] Embodiments usable within the scope of the present disclosure include a system capable of automatically switching the logging unit environment to a backup air supply system through the use of a valve assembly comprising an external port operatively connected to a standard ambient air supply (e.g., a pump and filter), a backup port operatively connected to a plurality of air tanks mounted in a frame, and an output port operatively connected to both inputs by means of a shuttle valve. Two reset valves control the relative pressures of the standard air supply and the backup air supply; in normal operation, the first reset valve allows the external air supply to circulate through the valve assembly and out the shuttle valve. In the event the external air supply is interrupted, the valves reverse and the first reset valve closes; the second reset valve then opens and allows the backup air tanks to supply air. These pressures may be monitored and controlled by indicator lights, pressure gauges, and regulators. [0018] In an embodiment of a method of use within the scope of the present disclosure, the logging unit is operatively connected to an external pressure source and a backup pressure source. The backup pressure source is kept at a lower pressure than the external pressure source such that when the external pressure source is active, the backup control valve is closed and the external air is allowed through the shuttle valve. When the external pressure source is interrupted or reduced to a pressure less than the backup pressure, the control valves switch and the backup control valve opens while the external control valve closes, allowing backup air to continue being supplied through the shuttle valve. DETAILED DESCRIPTION OF THE INVENTION [0019] Before describing selected embodiments of the present disclosure in detail, it is to be understood that the present invention is not limited to the particular embodiments described herein. The disclosure and description herein is illustrative and explanatory of one or more presently preferred embodiments and variations thereof, and it will be appreciated by those skilled in the art that various changes in the design, organization, order of operation, means of operation, equipment structures and location, methodology, and use of mechanical equivalents may be made without departing from the spirit of the invention. [0020] As well, it should be understood that the drawings are intended to illustrate and plainly disclose presently preferred embodiments to one of skill in the art, but are not intended to be manufacturing level drawings or renditions of final products and may include simplified conceptual views as desired for easier and quicker understanding or explanation. As well, the relative size and arrangement of the components may differ from that shown and still operate within the spirit of the invention. [0021] Moreover, it will be understood that various directions such as “upper,” “lower,” “bottom,” “top,” “left,” “right,” and so forth are made only with respect to explanation in conjunction with the drawings, and that the components may be oriented differently, for instance, during transportation and manufacturing as well as operation. Because many varying and different embodiments may be made within the scope of the concepts herein taught, and because many modifications may be made in the embodiments described herein, it is to be understood that the details herein are to be interpreted as illustrative and non-limiting. [0022] Disclosed is an apparatus and method for providing a backup air supply to a logging unit which can automatically switch between external air and stored air. The apparatus can comprise a frame with a plurality of air cylinders for storing the backup air, as well as a front housing/display with an internal valve assembly, status lights, and gauges for measuring the level of overpressure. [0023] Turning first to FIGS. 1A-1E, an embodiment of the backup unit 10 is depicted in perspective, top, front, side, and rear views, respectively. Backup unit 10 comprises a plurality of air tanks 12 a, 12 b mounted inside a frame 14. While the depicted embodiment comprises two tanks, it can be appreciated that other embodiments may utilize a single tank or three or more tanks without departing from the scope of this disclosure. In a preferred embodiment, the tanks are pressurized at 17,000 kPa (2500 psi) and regulated down to 550 kPa (80 psi) by an external regulator (not shown). [0024] As shown, frame 14 can comprise a forklift slot 16 and lifting lugs 18 on the top of the frame. The depicted embodiment is roughly 1.78 meters (70 inches) in height and 0.58 meters (23 inches) in width and depth, although it can be appreciated that other embodiments may comprise different dimensions without departing from the scope of this disclosure. [0025] As shown, air tanks 12 a, 12 b can be mounted through yoke piece 15 and can comprise at least one manual valve 20, which are optionally enclosed by valve cover 22 (usually in the course of shipping to/from the worksite.) Valve 20 is always open in normal operation and can be regulated at 550 kPa (80 psi) by an external regulator (not shown). The automatic switching capability will be described in greater detail further herein. Tanks 12 a, 12 b are operatively connected to a valve assembly 100, which can be located within a detachable housing 101, which may be mounted in frame 14 or stored at a distance from air tanks 12 a, 12 b. Once depleted, tanks 12 a, 12 b are typically shipped off-site for refilling. [0026] Turning now to FIG. 2A, an embodiment of the valve assembly 100 is shown in greater detail from the outside, which can include detachable housing 101, pressure gauge 110, indicator lights 112 and 114 indicating airflow coming from ambient air or backup air, respectively, and four side ports (i.e., external air port 120, backup air port 122, output port 124, and drain port 126 ). [0027] Turning now to FIGS. 2B, 2C, and 2D, the internal view of valve assembly 100, with housing 101 open, shows the key components in greater detail. These components include valve mount 102, auto reset valves 104, 108, shuttle valve 105, T-connections 106, 107, and regulator 109 (labeled in FIG. 3A ). FIG. 2D is a duplicate drawing of FIG. 2C showing the various flow paths through the valve assembly 100, with some numbering eliminated for clarity. In FIG. 2D, the solid line represents air received from external air port 120, the dashed line represents air received from backup air port 122, the dotted/dashed line represents air being moved into the ambient environment through output port 124, and the dotted line represents fluid drained to drain port 126. [0028] With reference to these figures, the fluid connections are now described in greater detail. Air from the ambient environment can be taken in by regulator 109, through external air port 120, which can feed through a first auto reset valve 108. Auto reset valve 108 may comprise a pressure sensor 111, through which air port 120 can be directly fed into the top side of. This fluid is communicated at a first pressure, which in an embodiment may be 760 kPa (110 psi), but could be greater or lesser without departing from the scope of this disclosure. [0029] Regulator 109 can be looped with auto reset valve 108 and may act to reduce the fluid to a second pressure, which in an embodiment may be 550 kPa (80 psi), but could be greater or lesser without departing from the scope of this disclosure provided the second pressure is less than the first pressure. Condensation from regulator 109 can be drained through drain port 126. After exiting auto reset valve 108, the external air can be fed to T-connection 107, which operatively connects both shuttle valve 105 and the topside of second auto reset valve 104. The top side of second auto reset valve 104 can be further coupled to indicator light 112. [0030] Meanwhile, air from tanks 12 a and/or 12 b (not visible in this drawing) can be delivered through backup air port 122, from manual valve 20 (depicted in FIGS. 1A-1E ) and through an external regulator (not shown). Backup air port 122 can connect firstly to second auto reset valve 104 and, if the system is shifted to backup air, through T-connection 106, which in turn connects indicator light 114 and shuttle valve 105 from the opposite direction, represented by the arrow pointing left to right, at a third pressure which is less than the first pressure. [0031] Second auto reset valve 104 can be configured to isolate the top side (fluidly coupled to external air port 120 through T-connection 107 ) and the bottom side (fluidly coupled to backup air port 122 through T-connection 106 ) from each other during normal operation. [0032] In normal operation, the first pressure will be greater than the second and third pressure, and the system will operate with the first auto reset valve 108 open and the second auto reset valve 104 closed, thus, blocking the air originating from backup air port 122, from going through to T-connection 106 and delivering as output air, sourced from external air port 120, through the regulator 109, first auto reset valve 108, and T-connection 107 (which lights indicator 112 ). Output is represented by the arrow pointing up to down, which leads to output port 124. Output is also in fluid communication with pressure gauge 110. Output can include reducer 115, which lessens the diameter of the connection as it exits shuttle valve 105 towards output port 124. [0033] However, in the event of interruption of the external air supply to external air port 120, the pressure sensor 111 in the first auto reset valve will detect the interruption, and the auto reset valves 104, 108 will trip and reverse, closing the first reset valve 108 and opening the second auto reset valve 104, allowing air from backup air port 122 to go through the T-connection 106, tripping light indicator 114, and going through to the shuttle valve 105 to output port 124. Reducer 115 ensures this process is not instantaneous by allowing gradual pressure bleed-off from the external air, while shuttle valve 105 and the lessening pressure of the external air supply during bleed-off ensure that there is no backwards flow during this process. [0034] FIGS. 3A-3B depict an embodiment of the invention, with numbered features identical to FIGS. 2B-2C, where the housing is absent and the connections between the valves are shown in greater detail. [0035] Various embodiments, usable within the scope of the present disclosure, have been described with emphasis and these embodiments can be practiced separately or in various combinations thereof. In addition, it should be understood that within the scope of the appended claims, the present invention can be practiced other than as specifically described herein.

Summary: A system and method for maintaining overpressure in a logging unit or other pressurized space through interruptions is disclosed. A backup air supply comprising tanks mounted to a frame is operatively connected to the ambient environment of the logging unit through a valve assembly which also connects a conventional pressure setup (e.g., pumps and filters from the external environment). The valve assembly comprises two auto valves, a shuttle valve, and a pressure sensor that allow the logging unit to switch from the conventional external air supply to the tanks when the pressure detected from the conventional air supply falls below a predetermined level. The valve assembly is independently housed and may be mounted or detached from the frame housing the backup tanks.

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Summarize: By Brad Segall and Jan Carabeo NORRISTOWN, Pa. (CBS) — Prosecutors in Montgomery County, Pa. say they’ve taken down an intricate drug distribution network that targeted students at high schools and colleges throughout the Main Line and was being run by two graduates of a prestigious private school. Prosecutors say the criminal enterprise was known as the “Main Line Takeover Project,” and they say the ringleaders had eyes on becoming the major marijuana distributors in the area. According to officials, 25-year-old Neil Scott and 18-year-old Timothy Brooks were running the operation and grooming others to help distribute their product at high schools and colleges. “Scott and Brooks employed students from five local high schools and three colleges as what they called ‘subdealers’ to distribute cocaine, marijuana, hash oil, (and) Ecstasy,” says Montgomery County DA Risa Ferman, “and they used connections in their community to target dealers who would then carry on their business.” Law enforcement started this four-month investigation in January after receiving tips from confidential informants. Prosecutors say Scott had bulk marijuana shipped from California to his Haverford apartment, the base of his illegal drug operation. Prosecutors say he also used his parents’ home in Paoli and Brooks’ home in Villanova to conduct business. It was Brooks, authorities say, who supervised sub-dealers who sold marijuana at local high schools. PHOTOS: Suspects In Main Line Drug Ring —- She says the subdealers were urged to meet quotas and to offer incentives to buyers to increase profits. The schools were Harriton, Lower Merion, Radnor, and Conestoga High Schools, the Haverford School, and Gettysburg, Lafayette, and Haverford Colleges. Scott and Brooks were graduates of the Haverford School. In all, eleven people have been charged. The investigation is continuing. Prosecutors say the ring leaders are facing some serious time behind bars. PHOTOS: Summer's Hottest Concerts VIDEO: Latest News & Weather AUDIO: Podcasts & Shows NEWS: Top Headlines PHOTOS: View The Best Galleries They called the operation the “main line take over project.” In terms of intricacy and ambition, it appears more suited for the business pages than the crime blotter. But its objective, according to authorities in Montgomery County, Pa., couldn’t have been more simple: saturate eastern Pennsylvania schools in drugs, expand the clientele base and always keep supply pumping. Authorities say at the top of the operation’s 11-person apparatus were 18-year-old Timothy Brooks and 25-year-old Neil Scott. Both of them, as well as some of their alleged employees, attended the Haverford School, an all-boys preparatory school that costs $35,000 per year and is nestled inside Philadelphia’s affluent “Main Line.” From within those communities, the young men allegedly hatched a nation-wide drug smuggling operation that began in California and returned to eight wealthy high schools and colleges in greater Philadelphia. On Monday, following a four-month investigation, 11 members of the group were arrested on charges of corrupt organization, intent to deliver a controlled substance, criminal conspiracy and dealing in proceeds of unlawful activity. The Montgomery County District Attorney’s Office says the operation worked like this: Scott, an unshaven 2008 graduate of Haverford School, had the drugs shipped to his Haverford apartment. He then used that house, or his parents’ place, or Brooks’s tree-lined Villanova home to conduct “drug business.” Prosecutors say the youths ran marijuana, cocaine, hash oil and ecstasy down the organization’s ranks to nine subsidiary dealers stationed at five high schools and three colleges. Each dealer allegedly had a quota: moving at least one pound of marijuana per week. Police say Brooks, who Scott allegedly coached on drug economics, was a driving supervisor. Prosecutors say he wanted them to “efficiently distribute drugs.” He allegedly even added incentives, including lowering the purchase price for marijuana “to increase their profit margin.” He allegedly wanted supply high. “Brooks instructed the high school sub-dealers to make certain there was always a constant supply of marijuana in their assigned schools,” investigators charge. “Brooks said this was important to him because he remembered not always being able to buy marijuana when he was in high school.” Brooks’s high school experience comes into sharper focus on social media. On Facebook, he and the accused sub-dealers’ play lacrosse, pose for family photos, hug cats, fence, and wear lots of button downs. In all, they look like everyday, if wealthy, teens and twentysomethings — perhaps characters out of “The Social Network,” the movie about Mark Zuckerberg and Facebook’s birth. Not the sort to be caught with what investigators say they found: eight pounds of marijuana, 23 grams of cocaine, 11 grams of ecstasy, three grams of hash oil, $11,000 in cash, two AR-15 rifles, one handgun and loads of ammo. And it’s that contrast that has shocked some in the Haverford community. “This is a huge story because of the prestige of the schools involved,” one of Brooks’ friends, who requested anonymity, told the Washington Post. “It’s not like this is the first time there has been a drug bust. It’s the uniqueness of the perpetrators.” From the outside, Brooks, a square-jawed and gregarious teen, appeared to have a lot going for him. He excelled at Lacrosse, and adopted the nonchalant disposition of the disinterested jock – “@cant_readbrooks” is his Twitter handle. After graduating from Haverford School in 2013, he netted a scholarship to play Lacrosse at the University of Richmond. “Richmond has everything I wanted,” he told Phillylacrosse.com in early 2013. “The school has a great academic reputation, is in a perfect region, and the campus is awesome.” He had planned to study business. But shortly after the lacrosse season started that year, his friend told the Washington Post he suffered a “career-ending” shoulder injury. “The shoulder injury put him down the wrong path,” said the friend, who visited with Brooks at a January party after Brooks had learned prosecutors were investigating him. “His friends were off at college and he was chilling at home and got bored. The idle mind is a dangerous one.” Though some of Brooks’ friends suspected he was in trouble, few had any idea the extent. “I knew he was into some sketchy stuff,” the friend said. “But I had no idea he was a drug kingpin.” The texts between the friends appeared to be about the dearth of good marijuana back when they were Main Line prep school students - and how their fledgling drug business could take off. Timothy C. Brooks asked Neil K. Scott if he had ever envisioned such success. "Only dreamed of it," Scott allegedly wrote in reply. "There is a much bigger market than just a lb each at each of these schools." Scott, 25, of Haverford, and Brooks, 18, of Villanova, were accused Monday of being the leaders of a drug trafficking ring that sought to corner the trade across some of the western suburbs' most prominent public schools. Brooks even branded the effort, allegedly describing it as "the main line take over project." Authorities said the pair enlisted student dealers and customers at their alma mater, the Haverford School, and at Lower Merion, Harriton, Conestoga, and Radnor High Schools - all considered among the state's elite. The network also allegedly sold drugs at a few colleges. Investigators said the pair demanded that their dealers move at least a pound of marijuana a week, and offered them incentives, such as discounts on drugs and the ability to buy on credit. "It was a business - an illegal business, but they were using very traditional business practices," Montgomery County District Attorney Risa Vetri Ferman said during a news conference announcing the arrests. Six other men and one woman were charged in the ring, as well as two juveniles - 17-year-olds from Radnor and Lower Merion High Schools. The charges - including conspiracy, drug distribution and sales - could land them in prison for years. The defendants appeared before a district judge in Lower Merion on Monday. Most were released on bail. Scott had been jailed since March 1, with bail set at $1 million cash. Both he and Brooks played lacrosse at the Haverford School as students and later coached there. Scott briefly attended Connecticut College and in 2010, authorities said, moved to San Diego, where he worked at a medical marijuana dispensary. He returned to Pennsylvania in October because his girlfriend ended their relationship, and ultimately moved into a Haverford apartment, police said. By December, Scott had spent all his money and decided "to sell marijuana because he noticed the marijuana being sold on the Main Line was of poor quality," according to an affidavit filed with the charges. Brooks attended the University of Richmond on a lacrosse scholarship but withdrew after a semester. He told investigators he started selling the drugs because he was having problems at home and wanted to move from his parents' house, court records said. Besides marijuana, authorities said, the pair also peddled cocaine, hash oil, and ecstasy. Lower Merion Police Superintendent Michael McGrath said authorities launched their investigation in January after confidential informants - current or former students at the schools - told police about drug dealing. Assisting were investigators from Delaware, Chester, Northampton, and Adams Counties and Philadelphia. Informants eventually made "controlled buys" for police, who then got warrants to search the suspects' homes. There, police said, they found marijuana and cocaine, $11,035 in cash, and weapons including a loaded AR-15 assault rifle and a loaded 9mm semiautomatic pistol. Also seized were cell phones used by Scott and Brooks. Their texts suggest Scott was the veteran and Brooks his aspiring protégé. "Idk [I don't know] what you make a week but I want to make 2 if I do this," Brooks wrote Scott, according to the affidavit. Police said "2" refers to $2,000 a week. Later, Brooks allegedly wrote to Scott: "Every Nug on the mainline is about to come from you and me." Nug is street slang for a marijuana plant's bud portion, police said. News of the arrests spread quickly through the high schools on Monday. "It is crazy to think people around here can get guns and drugs like that and not be caught before they did," said George Walker, a senior at Radnor High School. At the Haverford School, parent Daria Pew said she was glad the arrests occurred. "I'm glad they are getting to the bottom and discovering what is going on for the sake of the kids at the school," said Pew, of Bryn Mawr, and the mother of an 11th grader. The school's headmaster, John Nagl, said an assistant district attorney had alerted him Sunday night of the pending announcement. "This is obviously deeply distressing," added Nagl, who said he did not know the alleged ringleaders. "We prepare boys for life. This is not the kind of life we prepare them for." A spokesman for the Lower Merion School District said officials there were disheartened by the allegations. "But Lower Merion and the Main Line are not immune to these kinds of issues," spokesman Doug Young said. Richard Gusick, curriculum director for the Tredyffrin/Easttown School District, which includes Conestoga High School, said officials just learned Monday of the charges, but had been aware of efforts to investigate drugs in the schools. "As always, we stand ready to assist law enforcement officials any way we can if and when they request our involvement," he said. Also charged in the case, authorities said, were Daniel R. McGrath, 18, of Glenolden, a current student at the Haverford School; John C. Rosemann, 20, of Connecticut, who was at Lafayette College; Christian S. Euler, 23, of Villanova, a student at Lafayette; Garrett M. Johnson, 18, a Haverford College student from New York; Reid Cohen, an 18-year-old Haverford College student from Englewood Cliffs, N.J.; and Willow L. Orr, 22, and Domenic V. Curcio, 29, both of Philadelphia. District Judge Kathleen Valentine set their preliminary hearings for May 6. One of the defendants gulped and looked as though he were trying to choke back tears as Valentine spoke. None of the defendants or their parents wanted to comment. Greg Pagano, the attorney for Brooks, said his client "regrettably lost his way" after sustaining a serious injury. Pagano did not elaborate on the injury, but said he was suffering from depression when he and Scott became a team. "He was at a very susceptible point in his life," Pagano said of Brooks. Brooks, Pagano said, "is willing to accept responsibility for what he did in this case." Brooks' parents were set to post a portion of his $250,000 bail. Outside the courtroom, Brooks' father told his son's attorney that "I have to go to the bank." Scott was arrested in the drug case while being on probation for unrelated charges. cdavis@phillynews.com 610-313-8109 @carolyntweets Inquirer staff writers Kathy Boccella and Laura McCrystal contributed to this article.

Summary: After a four-month investigation, authorities yesterday busted 11 alleged members of a drug ring-a drug ring notable because some of its members were students and alums of pricey prep schools living in the leafy, affluent "Main Line" suburbs outside Philadelphia. Their goal, police say, was to keep five elite high schools and three colleges in Montgomery County, Pa., constantly stocked with drugs-they allegedly called it the "Main Line Takeover Project," CBS Philly reports. One of the alleged ringleaders, 18-year-old Timothy Brooks, "said this was important to him because he remembered not always being able to buy marijuana when he was in high school," according to investigators. Brooks graduated from the Haverford School, a $35,000-per-year, all-boys prep school, in 2013; his alleged co-ringleader, 25-year-old Neil Scott, was a 2008 grad of the school. Police say Scott had drugs shipped from California to his Haverford apartment; he sometimes also used his parents' Paoli house or Brooks' parents' house in wealthy Villanova to deal the drugs. The nine dealers, ages 17 to 29, who allegedly worked beneath Brooks and Scott were told to move at least one pound of marijuana per week, police say, and the DA says the pair "were using very traditional business practices," including discount incentives and lines of credit, to push their product, according to the Philadelphia Inquirer. They also allegedly moved cocaine, hash oil, and ecstasy. Police seized a stash of those drugs, plus $11,000 in cash, two AR-15 rifles, one handgun, and a lot of ammo. "This is a huge story because of the prestige of the schools involved," one of Brooks' friends tells the Washington Post. "I knew he was into some sketchy stuff, but I had no idea he was a drug kingpin."

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Summarize: I missed the latest Saturday Night Live, but by the next morning I had received an email from a concerned citizen about the content of its "cold open," in which Fred Armisen, as President Barack Obama, is assailed by Will Forte's Hu Jintao over America owing China money. The emailer was angry at Saturday Night Live for reinforcing flawed media narratives to the effect that the stimulus package has not created any jobs and that health care reform will not save any money -- and overall getting facts wrong. "This is really the wrong time for SNL to be getting basic facts so sorely wrong." WATCH the sketch in question: Does anyone actually expect Saturday Night Live to get its facts straight? Well, yes! Very recently, the show ran another sketch that featured Armisen as Obama running down a list of achievements -- and finding that none had been accomplished. This actually led to CNN factchecking the show: CNN's judgment was subsequently skewered by The Daily Show: Now, I am basically of the mind that holding Saturday Night Live up to some high level of fact-check scrutiny is more than a little absurd. The traction point of this Saturday's cold open was simply that lots of people joke about China holding so much of our debt. The writers basically take this fundamentally oversimplified idea to give the Jintao character room to complain about how America is spending money to ameliorate social problems and bail out banks while China has an outstanding IOU. I suppose that Armisen could have launched into a lengthy analysis of how the stimulus package is rolling out, or delivered a treatise on how reforming health care could keep people out of crippling debt, allowing them to purchase more Chinese exports, but doing so would commit the comedy crime of "negating the premise" -- the premise being that America is literally screwing China. This whole sketch is nothing more than a vehicle for the comedians to make a broad anal sex joke. They even follow the "rule of three," to maximize it's accessibility. All of which is true, I suppose. But it's worth pointing out that the sort of comedy Cobb makes is a unique animal. Cobb's Public Service Administration produces hilarious satire, but it's comedy that hinges on being well informed about a topic. For instance, their take on Dana Milbank and Chris Cillizza's "Mouthpiece Theatre" is fantastic, but wouldn't work with an audience unfamiliar with the two reporters' callow belief that their journalistic perch makes them funny, or the Washington Post's struggles with creating a web-based brand identity. I suspect this joke would not play well on NBC's affiliate in Des Moines: On top of that, Cobb often lends his considerable talents to advocacy. His comedic premises account for facts because he is in the business of "making the case" for things. That's what's on display in this spot for Health Care For America Now, sending up the way insurance companies arbitrarily change the rules on their consumers: Of course, the mass consumption version of this comedic ethos is seen on Comedy Central's The Daily Show and The Colbert Report, both of which do a great job of informing their viewers because their stock in trade is penetrating and demystifying media narratives and laying them bare. Everything I've read from SNL writers describing how their comedic sausage gets made indicates that they do not feel any sort of higher obligation to "making the case" for one particular point of view. Similarly, they don't often apply themselves to decoding media narratives -- because that would get in the way of the anal sex jokes. We could argue whether SNL is passing on the chance to create a better or more trenchant or more "dangerous" brand of sketch comedy, but I think what's unavoidable is that Saturday Night Live has its own unique set of priorities, and they include preparing a show that puts their guest host to his or her best use and putting the talents of their own character-driven comedians on display. (I think if we were to fact-check Kristen Wiig's "Penelope" character, many of her claims would not hold up to scrutiny. Still, LET'S NOT GET WOLF BLITZER INVOLVED, OKAY?) Nevertheless, I think that going forward, we're going to see the factcheck fetish continue to be applied to Saturday Night Live. There are two things that are driving this. First and foremost, legitimate news organizations are, more and more, repurposing SNL's content as a cheap way to kill a few minutes every hour. For example, ABC News's This Week devotes a whole portion of its weekly broadcast to the antics of late-night comedians. By the end of today, MSNBC might well show that cold open three or four times, unless their prudishness gets the better of them. No one intends SNL's content to stand in as the literal truth, but as long as comedy is appearing on the same platform as news, people are going to treat it as fair game for high levels of scrutiny. The other reason new outlets are likely to fact-check comedy shows is that it makes them look tough, at a time when the public does not have a lot of faith that they are capable of holding anyone accountable anymore. Organizations such as Politifact and FactCheck.org have risen to fill that gap. And now, we're often treated to the spectacle of news organizations citing these outside political factcheckers, which always makes me wonder what's wrong with their own stable of journalists! Watching a spokesman for Politifact come on teevee to talk about what's true and what's not is a lot like walking into a Starbucks and finding out that they've outsourced the boiling of water to a contractor. That might be a pretty good premise for a joke actually, but I'm not sure it would play all that well at 11:30pm, live from New York. [Would you like to follow me on Twitter? Because why not? Also, please send tips to tv@huffingtonpost.com -- learn more about our media monitoring project here.] I’ll be honest: I didn’t watch Saturday Night Live this past weekend. But it doesn’t seem like I missed too much. Since Obama’s campaign took his off, and certainly since his presidency began, SNL has been a reliable source of right-wing, anti-Obama talking points. This weekend’s opening skit was no exception, lambasting Obama’s stimulus program, his deficit-spending, his deference to world leaders, etc. Most imaginatively, the skit seemed to blame America’s debt to China on Obama himself, which is a laughable proposition–unlike the rest of the skit, which you can see here. SNL’s anti-Obama tidings have been visible for some time. Perhaps they started during the primaries, when the show attacked the media for being favorable to Obama at the expense of Hillary; certainly the show’s general outlook toward the president were clear when Fred Armisen, the guy the show pays to play Obama in blackface, announced in character that the president had accomplished “nothing.” (Tell that to those who think the guy has brought socialism to the United States.) What about Tina Fey, you say? Sure, she struck gold with her Sarah Palin impression. But Palin’s ineptitude went far beyond ideology; she was obviously incapable of governing and thus deserving of mockery by many Americans. Recent polls have been clear–few people like Palin. Obama, meanwhile, is still liked by many Americans. His numbers aren’t at their honeymoon peak, but they’re certainly still strong and steady. And so SNL can hardly be said to represent the zeitgeist. Perhaps that’s because the show, fat and rich in its old age, reflects the politics of its executive producer, Lorne Michaels, who maxed out to McCain in 08. Granted, he also gave to Obama–but not until the general election. His heart was with McCain from the beginning–he was a donor way back in 2000, too–and seems like it still might be. Or perhaps the Obama fatigue that has occurred is hard to mine for comedy. Better to stick to the easy yet facile right wing arguments–we owe the Chinese money!–than engage with anything a bit complicated. Whatever the case, SNL is now an anti-Obama conservative comedy show. It’s certainly better than Fox’s ill-fated attempt to make a right-wing Daily Show. But conservative is what it is.

Summary: Saturday's SNL cold opener-which poked fun at Obama's deficit spending-conclusively marked the show as an "occasionally humorous right-wing propaganda organ," writes Ethan Porter of True/Slant. SNL's been obviously anti-Obama since the primaries, pausing only to mock Sarah Palin, who's far less popular than Obama. "The show, fat and rich in its old age, reflects the politics of its executive producer, Lorne Michaels, who maxed out to McCain in 08." Even CNN recently took issue with a recent SNL jab at Obama, going so far as to fact-check it. But Jason Linkins of the Huffington Post thinks everyone ought to calm down. Unlike, say, the Daily Show, SNL isn't in the business of advocating for causes. This latest sketch was "nothing more than a vehicle for comedians to make a broad anal sex joke."

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Summarize: RELATED APPLICATIONS This application is a continuation in part of U.S. patent application Ser. No. 07/254,044 filed Oct. 6, 1988, now abandoned. BACKGROUND OF INVENTION This sport of ice fishing has commonly used a wide variety of fishing rigs which do not need constant attention in order to permit ice fisherman to watch their fishing rigs from the comfort of ice shelters some distance from the rigs. In general, these fishing rigs provide a signal which is activated when a fish strikes the line and causes the fishing reel to rotate. A variety of systems have been developed that permit a flag or some other signal to be displayed when a fish strikes. The most pertinent art known to the applicant include U.S. Pat. Nos. 4,566,216; 3,645,029; 3,641,693; 4,285,154; 4,030,223; 4,021,958; 3,888,035; and 4,120,111. Of these, perhaps the most relevant to the present invention are U.S. Pat. Nos. 3,645,029 and 4,566,216. U.S. Pat. No. 4,566,216 generally discloses an ice fishing rig in which a signal is positioned within a tubular pole with the signal normally covered by a screen. The screen is released and falls by the force of gravity through a leverage system activated when the fish strikes the line. U.S. Pat. No. 3,645,029, on the other hand, describes an ice fishing rig in which a signal is raised under the force of mechanical spring mechanisms that are released when a fish strikes the line. Both of these rigs rely upon a mechanical actuation of the signaling devices. In the first, a leverage system is operable only under the force of a fish pulling the line. The second system is dependent upon the force of the pull by the fish and is severely limited by ambient problems and conditions of freezing. For example, the rotating and movable components may freeze, thus making the system entirely inoperable. The second reference, U.S. Pat. No. 3,645,029, has similar mechanical movement limitations. In that system, the restraining means, comprising magnetic components, must be stronger than the spring mechanism which propels the signal upwardly. In addition, freezing water inside the tube may make the system inoperable. Serious limitations also exist in respect to the strengths of the magnet and the relationship of the spring mechanism. SUMMARY OF THE INVENTION The purpose of this invention is to provide an improved ice fishing rig that avoids deficiencies existent in currently available rigs. More specifically, the present invention is intended to provide an ice fishing rig in which the operable components are not likely to freeze during use and will, accordingly, operate with certainty at all times. A further object of the present invention is to provide an ice fishing rig which is light in weight, simple in construction, easy to repair, simple to use, and inexpensive to manufacture. A further object of this invention is to provide an ice fishing rig in which the signaling component comprises a colored or distinctive float that is moved to a signaling position without the requirement of mechanical actuation. A further object of this invention is to provide an ice fishing rig in which the signaling device may be readily reset to its initial position without adjustment of mechanical devices and by merely rotating a single component. One further object of the present invention is to provide an ice fishing rig in which the signaling device is contained within a tubular structure and is not exposed to ambient conditions and in particular, may not be affected by winds, rain, or other weather conditions. Another object of this invention is to provide a means by which the position of the tubular pole may be adjusted with respect to the level or thickness of the ice. Accordingly, the present invention provides an ice fishing rig consisting, in substance, of a crossbar member adapted to extend over a hole formed in ice on a body of water. A tubular pole is supported on the crossbar member with one end of the tubular pole projected into the water and the other above the ice. The tubular pole contains a fluid having a freezing point below zero centigrade in which a float, preferably distinctively colored, is free to float. A fishing reel secured to one end of the tubular pole carries a magnet with a complimentary magnet secured to the float. When aligned, the magnetic components on the reel and on the float attract one another and secure the float to the one end of the tubular pole. When a fish strikes the line and the reel rotates, magnetic components are misaligned and the float is released to rise in the antifreeze fluid to the top thereby signaling a fish has struck the line. DETAILED DESCRIPTION OF DRAWINGS FIG. 1 is a perspective view of the ice fishing rig of the present invention positioned in an ice hole; FIG. 2 is a cross sectional view of the ice fishing rig of the present invention; FIG. 3 is a side view of the ice fishing rig of the present invention; FIG. 4 is a detailed view of the reel of the ice fishing rig of the present invention; and FIG. 5 shows an alternate embodiment of the end braces of the present invention. DETAILED DESCRIPTION OF INVENTION The ice fishing rig generally shown in the drawings includes as its principle component a crossbar member or assembly 1 which is interengaged with a tubular pole 2 by pivoting means 3 which supports the tubular pole 2 for rotation in respect to the crossbar assembly 1. A fishing reel 4 is rotatably supported on its axis on one end of the tubular pole 2 by suitable means, such as an axle 5. A float 6 preferably colored is positioned within the tubular pole 2 and is free to float in a fluid 7 which has a freezing point below zero degrees centigrade, and preferably at least 20 to 30 degrees below zero centigrade. The reel 4 and float 6 each carry one of the components 9 and 10 forming a magnetic means. The components 9 and 10 are secured respectively to the inside of reel 4 and the side or bottom of float 6 in positions for mutual alignment with one another, so that when aligned and adjacent to one another the float 6 will remain secured at the one end of the transparent tubular pole 2, as illustrated in FIG. 2. Preferably, the component 10 is secured to the end of the float 6 so that inadvertent rotation of the float 6 within the tube 2 will not result in variations in the magnetic attraction between component 9 and 10. Alternately, inadvertent rotation of the float 6 within tubular pole 2 may be avoided by making the tubular pole other than circular in cross section with the float 2 having a corresponding configuration. The tubular pole 2 is preferably made of a transparent plastic material. A typical configuration for the unit contemplates tubular pole 2 may be one inch to one and a half inches in diameter and having a length of two to four feet. The tube is sealed at one end 12 and at the other end 14 by suitable means which may comprise a plug or a heat sealed segment of the tube itself. Prior to sealing the tube the float 6 and the fluid 7 are positioned in the tube. The fluid 7 is preferably an antifreeze material with a freezing point sufficiently low as not to freeze during any normal usage conditions. Typically, the antifreeze should be fluid at temperatures of at least 20 to 50 degrees below zero centigrade. Conventional automotive antifreeze material may accordingly be used. The antifreeze however should not be opaque. The float 6 may be formed of any suitable material which is not reactive with the antifreeze and will readily float in it. Thus, for example, a cellular foam plastic material may be utilized. The float 6 should be vividly colored for easy observation through the tubular pole 2. If desired, a luminescent paint may be applied to the surface of the float 6. The magnetic means consisting of the magnets 9 and 10 may be conventionally formed of standard magnets with poles oriented to attract one another. In some instances for ease in orienting and securing the float more than one magnet component 9 may be used on the inner surface of the reel 4. As previously discussed, the magnet 10 is preferably secured to and across the bottom of float 6. The reel 4 may comprise a conventional fish reel having an axle 5 that projects through the reel and rotatably supports it at end 14 of the tubular pole 2. The axle 5 may comprise a shaft locked by suitable means to the end 14 of the tubular pole 2 for easy rotation. The reel 4 contains a lenth of fish line 18 with appropriate gear at its end, including for example, a hook 20 and/or weight 21. FIG. 4 shows a detailed view of the reel. The reel comprises a pair of parallel side walls 72 and 74, with each having a plurality of arcuate inwardly extending flanges 76. Each side wall further includes an axle-accepting flange 78 having a hole 79 therethrough for accepting the axle 5 when the reel is assembled. When assembled, flanges 76 on side wall 70 mate with flanges 76 on side wall 74 and the axle is inserted through hole 79. The reel 4 may be also be provided with a handle 24 for reeling in the line 18. Preferably the handle 24 should be relatively small so as not to prevent significant resistance to rotation when the reel is in the water. The magnet component 9 associated with the reel is positioned within a sleeve 70 disposed close to the periphery of the reel. As a result of the placement of the magnet component 9 close to the periphery of the reel, the magnet component 9 will move a greater distance from the magnet component 10 for a given rotation of the reel 4 than a magnet positioned closer to the axle 5. Therefore, a lesser rotation of the reel will release the float 6 than if the magnet was positioned closer to the center of the reel. The crossbar assembly 1 is designed to support the tubular pole over a hole in the ice as illustrated in FIG. 1. As illustrated, the opposite ends 30 and 31 of the crossbar assembly 1 are supported over a hole 32 in the ice 33 with one end 12 of the tubular pole extending above the ice and the other end 14 of the tubular pole in the water. The means 3 supported the pole on the crossbar assembly preferably comprises a pivotable assembly which includes a block 36 having a hole shaped and sized to receive the pole 2, with the medial portion of the pole 2 snugly fitting through a hole 38 in the block 36. The pole 2 is secured against movement through the hole 38 by a set screw 40 which extends through the block 36 and contacts pole 2. The pole 2 may be adjusted in the hole 38 by loosening the set screw 40 and sliding the tube longitudinally in the hole 38 to a position in which desired lengths of the pole extend on either side of the block 36. In order to prevent inadvertent loss of the pole 2 from the rig in the event set screw 40 is not properly secured, the end 12 of the pole 2 may be formed with a plug 44 having a diameter greater than the diameter of the hole 38. In such event, the plug 44 must be inserted or secured after the pole 2 is assembled in the block 36, or alternately, the reel assembly 4 must be secured after the tube is secured in block 36. The crossbar assembly 1 preferably comprises a pair of elongated rods 46 and 48 that extend parallel to one another on either side of the pole 2. These rods may be formed of any suitable material and are secured in fixed relation to one another at their ends 30 and 31 by end braces 50 and 52. The rods 46 and 48 and cross braces 50 and 52 may be formed of any suitable material. If desired and primarily for appearance reasons the end braces 50 and 52 may be made of the same material as tubular pole 2 but need not be filled with a fluid. Thus, for example, the crossbar assembly 1 and tube 2 may all be made of a polycarbonate tubing. In a preferred embodiment, the cross-connectors 54 and 56 of end braces 50 and 52 may be offset from the ends of elongated rods 46 and 48 and further may be arcuately curved, with each end brace curved in opposite directions, as shown in FIG. 5 which illustrates an end view of end brace 50 The arcuate curve of end brace 52 is curved in the opposite direction. Thusly, the arcuate and offset braces 50 and 52 provide a recess that will permit the pole 2 to lie flat and coplanar with the rods 46 and 48 when the tubular pole 2 is pivoted into parallel alignment with the rods 46 and 48 for storage. The block 36 is secured for pivotable rotation between rods 46 and 48, preferably at the center of the crossbar assembly 1. A pair of pins 40 and 58 provide pivoting support for the block 36. As shown in FIG. 3, pin 40 extends completely through block 36 and also acts as the set screw. In alternate embodiments, a separate setting screw 40 may be included, in which case both pins would extend only partially through block 36 while the setting screw would extend completely through block 36 to contact pole 2 to hold it in place. In use, a fisherman will ordinarily pivot the tubular pole 2 from storage position in which its parallel end coplanar with rods 46 and 48 to the position illustrated in FIG. 1. The reel 4 will be unwound a suitable length and the hook suitably baited. The float 6 will be positioned at the bottom or other end of tubular pole 2 with the magnetic components 9 and 10 aligned and attracting one another to secure the float 6 at the other end of the tubular pole 2. The crossbar assembly is positioned with the ends 30 and 31 supported on the ice 33 and the one end of the tubular pole visible above the ice. When a fish strikes the line 18 and causes the reel to move, the magnetic alignment of magnets 9 and 10 is disturbed and the float 6 rises in the tubular pole 2 to the one end 12. When the line is to be reset, the procedure described above is repeated.

Summary: An ice-fishing rig with a signaling device which is magnetically restrained until released by movement of the fishing reel. A pair of magnetically interactive and aligned components, secured one each to the signaling device and reel, restrain the signaling device until a fish pulls on the line and the magnetic alignment is broken, releasing the signaling device. The signaling device comprises a colored float in as transparent vertical tube which is pivotally secured to the center of crossbar member. The tube is filled with an antifreeze to permit movement of the float in cold weather. The tube is pivoted to a position essentially parallel to the crossbar members for easy storage and handling.

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Summarize: Paris police are holding three Al-Jazeera reporters for allegedly flying a drone, days after the machines sparked a terror alert in the city. Journalists from the Qatar-funded news network were arrested in a park in the French capital from where they were illegally operating a drone, a judicial source told AFP. The arrests come after drones were on Monday seen buzzing the Eiffel Tower, Bastille Square and the U.S. embassy, then on to the Place de la Concorde and the Invalides military museum, where Napoleon is buried. Fear: Drones were spotted flying near the Invalides military museum, where Napoleon Bonaparte is buried. French security sources where unable to catch the drones, which are typically fitted with cameras and can be used for target surveillance to assess security and any spikes in pedestrian footfall ahead of a planned attack. The Al-Jazeera reporters arrested today, aged 70, 54 and 36, were arrested yesterday afternoon after police saw a drone flying in the Bois de Boulogne woods in western Paris, said Paris prosecutors' spokeswoman Agnes Thibault-Lecuivre. She said it was unclear what the trio were trying to accomplish. A judicial source earlier told AFP: 'The first was piloting the drone, the second was filming and the third was watching.' Responding to an Associated Press request for comment, Doha-based Al-Jazeera said: 'Three Al-Jazeera English journalists have been held by police in Paris while filming a report on the city's recent mystery drones. 'We will comment further when more information is available.' The journalists can be held for a maximum of 24 hours under French law. Flying drones without a license in France is illegal and carries a maximum one-year prison sentence and a 75,000 euros ($85,000) fine. Alert: Paris is on alert for a new terror attack after 'at least' five drones were spotted illegally flying around city landmarks, including the the U.S. embassy building (pictured) Tension: Drones were also seen flying around the world-famous Eiffel Tower. New threat: French law bans small, civilian drones from areas such as nuclear facilities, which are protected by a no-fly zone that spans a 1.6-mile radius and a height of 1,000 metres. The above drone crashed on the grass near the White House in the United States last month. A map showing where the drones have been sighted in Paris. There is so far no suggestion the Al-Jazeera journalists are linked this week's night-time drone sightings over Paris, including on Monday and Tuesday nights. Police sighted one or more drones in five instances buzzing in the Paris sky in the night of Tuesday to Wednesday - from 11.30pm to 2am. An unidentified flying object was first seen Tuesday night near the Gare de l'Est train station, with sightings continuing in sequence for over two hours over the Paris Opera, then on to the Tuileries gardens, past the Eiffel Tower and then south past Paris' Montparnasse Tower, according to Thibault-Lecuivre. An inquiry was launched after drones, which are banned over Paris, were also spotted Monday night - beginning over the U.S. Embassy at around midnight on Monday. Between then and 6am the Eiffel Tower, Bastille Square, the Place de la Concorde and the Invalides military museum 'were also flown over', a security source said. 'It could be a coordinated action but we don't know for now,' the source, who asked not to be identified, added. 'We did everything to try and catch the operators but they were not found,' another source close to the investigation said. France has experienced a series of mysterious drone appearances in the last few months. On January 20, a pilotless aircraft briefly went over the presidential palace in Paris, while around 20 drones were earlier seen flying above nuclear power plants. However until Tuesday 'there have never been so many drones appearing in one night,' the security source said. Location: At some point between midnight and 6am on Monday, drone aircraft were spotted flying near Bastille Square. Tourist hotspot: The first drone sighting in the French capital was around midnight on Monday. Shortly after an unmanned aircraft was seen flying near the Place de la Concorde. The emergence of drones comes amid warnings by terrorist groups that they will attack the city, following January shootings which left a total of 20 dead, including three terrorists. ‘They could be seen throughout the night, but nobody knows who were operating them,’ said a police source in the capital. A specialist police aviation unit tried to establish who was at the controls, but there have been no arrests. There have been other mysterious drone flights across Paris, but this is the first time that such a concentrated number have been seen above so many potentially vulnerable targets. The US embassy has been threatened by numerous groups in the past, from Al-Qaeda to Algeria’s Armed Islamic Group. French law bans small, civilian drones from areas such as nuclear facilities, which are protected by a no-fly zone that spans a 1.6-mile radius and a height of 1,000 metres. Experts say that the small unmanned craft would not pose a threat if crashed into a hardened nuclear facility. Fightback: Earlier this month France unveiled its latest weapon against the growing menace of rogue drones buzzing through their nation's skies: another drone, with a net. Caught: In a demonstration in La Queue-en-Brie, east of Paris, the mesh-wielding flying machine was shown snaring a DJI Phantom 2 drone - the same brand as one which crashed onto the White House lawn last month. France has barred six 'would-be jihadists' from leaving the country after discovering their plans to travel to Syria and join the Islamic State terror group. It the first such travel ban under a new law aimed at preventing French Islamic radicals travelling to the vast swathes of Syria and Iraq currently under the control of Sunni extremists. French interior minister Bernard Cazeneuve says some 40 other French citizens will face travel bans in the coming weeks. He did not reveal the identity of the six people whose passports have already been confiscated. The bans are the first since a sweeping anti-terrorism law passed in France last year. The government is especially worried since attacks in Paris last month killed 20 people, including three gunmen claiming ties to Islamic extremists in Syria and Yemen. An Interior Ministry official says the passports and ID cards of the six have been declared invalid for six months - a measure that can be extended for up to two years. The news comes just days after Cazeneuve said he asked Google, Facebook and Twitter to work directly with French officials during investigations and to immediately remove terrorist propaganda when authorities alert them to it. Earlier this month France unveiled its latest weapon against the growing menace of rogue drones buzzing through their nation's skies: another drone, with a net. In a demonstration flight in La Queue-en-Brie, east of Paris, the mesh-wielding flying machine was shown snaring a DJI Phantom 2 drone - the same brand as one which crashed onto the White House lawn last month. The U.S. Secret Service was sent scrambling by the unexpected intrusion, but France has already faced dozens of drone overflights over sensitive sites. Mystery drones have buzzed nuclear plants, military installations and even the presidential palace in recent months, as fears run high of terror attacks linked to the Islamic State terror group. Concerned at the new technology, officials have asked scientists and companies to develop ways to monitor and detect intruding drones and their remote-control pilots; analyse and track their flight paths; and ultimately neutralise the drones, either temporarily or permanently, with the least collateral damage possible. Last October it emerged that holidaymakers who are planning to fly a camera-equipped drone in Paris’ tourist zones risk spending time in jail and being slapped with a hefty fine. An Israeli tourist found out the hard way this week when he was arrested in front of Notre Dame Cathedral while flying a drone above some of Paris’ top attractions

Summary: The reporters were allegedly operating the drone from a suburban park. There is no suggestion they were involved in a recent spate of sightings. Unmanned aircraft on Monday flew over tourist hotspots in French capital. Appeared in 'at least' five locations in the city in early hours of Monday. Security officials were unable to catch the operators of the drone aircraft. Civilian drones are thought a serious security risk and are banned in Paris.

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Summarize: Crawl of outlinks from wikipedia.org started March, 2016. These files are currently not publicly accessible. Properties of this collection. It has been several years since the last time we did this. For this collection, several things were done: 1. Turned off duplicate detection. This collection will be complete, as there is a good chance we will share the data, and sharing data with pointers to random other collections, is a complex problem. 2. For the first time, did all the different wikis. The original runs were just against the enwiki. This one, the seed list was built from all 865 collections. This post has been corrected. See the note below for details. A vast building in McAllen, Texas, was once home to a Wal-Mart -- but no longer. When the discount superstore moved to a larger location, it left behind a vast empty building. The community took advantage of the space and converted the warehouse-like building into a public library. The size of more than two football fields, the McAllen Public Library is the largest single-story library in the country, the website PSFK writes. Its conversion from vast warehouse space to functioning library has recently made it the winner of the 2012 Library Interior Design Competition by the International Interior Design Assn. Adriana Ramirez, who teaches creative writing at the University of Pittsburgh, grew up in McAllen. "The old library on Main Street was not beautiful," she told Jacket Copy. "It was packed with books and seemed too small for the people it serviced. Of course, that was part of the charm -- always waiting your turn for the computer and spending a good amount of time finding a corner where you could read uninterrupted. The new library solves all that." McAllen is near the southernmost tip of Texas, on the Mexico border. "In a city like McAllen, with cartel violence across the river (less than 10 miles away from the library), I think it's amazing that the city is devoting resources to a) not only saving a large and conspicuous piece of property from decline and vandalism, but b) diverting those resources into youth and the public trust," Ramirez writes. "It's easy to fall into drugs, drinking, and violence when you live on the border. It's not really easy to find a place to hang out when you're 14 that's not the mall, the movies, or Mexico. And a giant library -- a cool-looking open space devoted to entertaining the imagination? Well, I think that's the best counter-move against violence imaginable. And you don't even have to wait for a computer now." The new McAllen Public Library opened in December 2011; after it had been open for just a month, new user registration increased by 23%.

Summary: When McAllen, Texas, found itself with an abandoned Walmart on its hands, it didn't just bring in another store: It used the building to create a new library. And that library just so happens to be the largest single-story library in the country-and the winner of the International Interior Design Association's 2012 Library Interior Design Competition. PSFK has a number of pictures of the exceptional space, which includes a striking entrance, cheerful orange highlights, hip ceiling elements, and a special lounge for teens. The McAllen Public Library now clocks in at 124,500 square feet, or about 2½ football fields, and has seen new-user registration increase 23% in the first month after opening. "In a city like McAllen, with cartel violence across the river"-the town is on the Mexico border- "I think it's amazing that the city is devoting resources to a) not only saving a large and conspicuous piece of property from decline and vandalism, but b) diverting those resources into youth and the public trust," a McAllen native tells the Los Angeles Times. "It's easy to fall into drugs, drinking, and violence when you live on the border. It's not really easy to find a place to hang out when you're 14 that's not the mall, the movies, or Mexico."

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Write a title and summarize: Bacterial capsular polysaccharides are virulence factors and are considered T cell–independent antigens. However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4+ T cells in a major histocompatibility complex (MHC) class II–dependent manner. The mechanism of carbohydrate presentation to CD4+ T cells is unknown. We show in live murine dendritic cells (DCs) that Sp1 translocates from lysosomal compartments to the plasma membrane in MHCII-positive tubules. Sp1 cell surface presentation results in reduction of self-peptide presentation without alteration of the MHCII self peptide repertoire. In DM-deficient mice, retrograde transport of Sp1/MHCII complexes resulting in T cell–dependent immune responses to the polysaccharide in vitro and in vivo is significantly reduced. The results demonstrate the capacity of a bacterial capsular polysaccharide antigen to use DC tubules as a vehicle for its transport as an MHCII/saccharide complex to the cell surface for the induction of T cell activation. Furthermore, retrograde transport requires the functional role of DM in self peptide–carbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens. The immune response to polysaccharide antigens is considered T cell–independent [1]. However, emerging evidence suggests that bacterial polysaccharides from Streptococcus pneumoniae, Bacteroides fragilis, and Staphylococcus aureus activate CD4+ T cells in vivo and in vitro due to their zwitterionic charge motif within each repeating unit [2,3]. Nuclear magnetic resonance (NMR) structural studies of zwitterionic polysaccharides (ZPSs) such as the capsular polysaccharides PS A2 from B. fragilis and Sp1 from S. pneumoniae serotype 1 reveal the formation of extended right-handed helices with repeated 20 Å negatively charged grooves and positive charges located on the outer surfaces of the lateral boundaries [4,5]. A minimum molecular weight of ZPS >5 kDa and ≤17 kDa is required for the elucidation of antigenicity [6]. ZPSs induce CD4+ T cell activation in the presence of B cells, monocytes, and dendritic cells (DCs) [7] and have been demonstrated to correct systemic T cell deficiencies [8]. Animals lacking αβCD4+ T cells fail to develop abscesses in response to ZPS [9]. We and others have shown that T cell activation by the ZPS requires the costimulatory molecules B7–2, CD40, and the major histocompatibility complex (MHC) class II protein HLA-DR [7,10,11]. ZPSs locate in endosomal compartments and co-immunoprecipitate with HLA-DR [7,12]. These studies indicate similarities between ZPS and peptide antigen presentation to CD4+ T cells by antigen-presenting cells (APCs). Antigen processing and presentation to CD4+ T cells by the MHCII endocytic pathway has been considered strictly limited to protein antigens [13]. A complex set of interlinked factors, including the local pH, is likely to influence the activity of the processing enzymes. The endosomal pH in APCs is regulated by proinflammatory and anti-inflammatory cytokines [14] and microbial products such as bacterial lipopolysaccharide (LPS) [15]. LPS triggers enhanced vacuolar proton ATPase function in immature DCs (iDCs), lower endosomal or lysosomal pH, and more efficient antigen processing and a rapid and transient boost of MHCII synthesis [15,16]. Another important event in antigen processing and presentation is the removal of class II invariant chain (CLIP) occupying the peptide binding groove by the MHCII homolog DM (HLA-DM in humans and H2-M in mice). DM further stabilizes the empty MHCII molecule and assists in peptide selection [17–19]. In the absence of DM, peptide editing fails, leading to the appearance of weakly bound peptides, including CLIP [20]. CLIP also qualifies as an endogenous regulator in DCs in priming of T helper cells by antagonizing the polarization towards the TH1 phenotype [21]. Recent studies show that LPS challenge induces tubules from lysosomes, which transport MHCII to the cell surface [22–24]. In the case of protein-loaded lysosomes, protein is transported in the MHCII tubules to the cell surface for presentation of the peptide, formation of biological interaction with T cells, and induction of T cell–dependent immune responses [24,25]. Although lysosomal compartments contain abundant glycosidases that act on sugar linkages, presumably with high specificity, they are considered the end stations for carbohydrates. MHCII tubules formed after LPS challenge in iDCs do not transport carbohydrates such as dextran from lysosomes to the cell membrane [24]. However, Cobb et al. recently showed that a nitric oxide–dependent processing mechanism of the ZPS PS A1 in early endosomes, resulting in the generation of low molecular weight, antigenic fragments [12]. This finding indicates that antigen processing is not limited to proteins only. Our recent observation that blockade of endo/lysosomal acidification inhibits carbohydrate-induced T cell activation [11] suggests that intravesicular acidic pH and DM activity [26] are required for polysaccharide binding to MHCII in lysosomal compartments and/or retrograde transport of carbohydrate/MHCII complexes. Here, we report the mechanism of retrograde transport of the bacterial capsular polysaccharide Sp1 from S. pneumoniae in live cells and the essential role of DM in this process. Sp1 traffics through endosomal compartments to acidic lysosomes and is transported in MHCII-positive tubules for presentation to the cell surface and engagement of T cells. We show that the DM molecule is required for the retrograde transport and the cellular immune responses in vitro and in vivo. The data close a gap in our understanding of the new paradigm of MHCII presentation of bacterial carbohydrate antigens. Sp1 induces T cell activation in the presence of B cells, monocytes, and DCs [7]. In an experimental model of abscess formation, besides macrophages [27], CD11c-positive DCs play an important role. They migrate into the peritoneal cavity upon Sp1 challenge and are retrieved in the abscess capsule (Figure 1). Live cell imaging showed that in iDCs, part of Sp1 is internalized into early endosomes as indicated by partial co-localization with Rab5 and BCECF-dextran (dextran-2′, 7′-bis- (2-carboxyethyl) -5- (and-6) -carboxyfluorescein) (Figure 2A and 2B). Co-localization of Sp1 with Rab7 and dextran, markers for late endosomes and lysosomes, and with LysoTracker, an acidotropic marker for lysosomes, demonstrated that Sp1-containing compartments fuse with late endosomes and lysosomes (Figure 2C–2E). Sp1 co-localized with ovalbumin, a conventional protein antigen processed and presented by the MHCII pathway (Figure 2F). In order to test whether Sp1 is internalized and represented by recycling receptors, we performed live cell imaging with Rab11b-EGFP fusion protein, a marker for recycling endosomal compartments. Co-localization of Sp1 with Rab11b was not observed during an observation interval of 5 min to 24 h in the absence and presence of LPS treatment (Figure 2G). These results demonstrate that after internalization, Sp1 gains access to endocytic compartments where antigenic epitopes are loaded to MHCII molecules. As presentation of Sp1 by recycling receptors is largely excluded, the question arises whether and how Sp1 is transported to the cell surface. Lysosomes constitute the terminal compartment of the endocytic pathway where exogenous components are generally degraded. Recent studies with green fluorescent protein (GFP) –tagged MHCII have shown that after LPS stimulation of iDCs, MHCII molecules are transported via tubules that originate from lysosomes to the plasma membrane [22–24]. We transfected iDCs of C57BL/6 wild-type (WT) mice with MHCII-GFP (I-Eα-EGFP) to investigate the presentation mechanism of Sp1. Flow cytometry analysis revealed that surface expression of assembled I-A and I-E molecules in transfected DCs was similar to I-A surface expression in non-transfected cells (Figure S1). Thus, MHCII-GFP was fully functional and appeared to exhibit the same general pattern of intracellular transport as endogenous MHCII in iDCs and mature DCs (mDCs). In iDCs, MHCII-GFP co-localized extensively with Sp1-Alexa 594 in lysosomes (Figure 3A). No MHCII-GFP was found on the cell surface. Within 4 h after LPS stimulation, numerous extensive tubules extended from the perinuclear area, which were intensely labeled for both MHCII and Sp1 (Figure 3B; see also Video S1). All tubules were yellow, indicating that Sp1 is exclusively transported in MHCII-positive tubules. The observation that lysosomes can form dynamic and motile MHCII/Sp1-containing tubules does not prove that these structures mediate the transfer of MHCII/Sp1 complexes to the cell membrane. To determine directly whether these tubules not only move to the periphery but also actually reach the plasma membrane, we imaged Sp1 transport in DCs using combined epifluorescence (EPI) and total internal reflectance fluorescence microscopy (TIR-FM) [28]. We observed Sp1-Alexa 594–containing tubules exiting lysosomes and associating with the plasma membrane (Figure 3C; see also Video S2). With time, as the tubule approached the membrane, the red-colored EPI signal decreased while the bright yellow TIR-FM signal increased. After 4 h of LPS stimulation of Sp1-biotin–treated DCs, we detected significant amounts of Sp1 on the APC surface by fluorescence-activated cell sorting (FACS) analysis (Figure 3D), demonstrating that MHCII/Sp1 fuses with the cell membrane for cell surface presentation of Sp1. Concomitantly, Sp1-treated DCs induced engagement with CD4+ T cells, while LPS stimulation of DCs in the absence of Sp1 did not induce conjugate formation with T cells (Figure 4A and 4B). Analysis of CD69, the early activation marker, showed that although the majority of naïve CD4+ T cells form transient interactions with Sp1-pulsed DCs, a maximum 8% of naïve T cells are activated by Sp1-treated DCs at 10 h of incubation (Figure 4C), indicating proper cell surface T cell stimulatory function of MHCII/Sp1 complexes. The proposed functions of CLIP are that of a precursor peptide to be exchanged for foreign antigenic peptides, and of a regulator in priming TH cells by antagonizing the polarization towards the TH1 phenotype [21]. It was shown that regardless of the presence and type of protein antigen provided to mDCs and loaded onto MHCII, the number of surface CLIP/MHCII complexes remained unchanged [21]. Here, in contrast to ovalbumin as a control antigen, the incubation of maturing DCs with Sp1 resulted in a 57% decrease in Δ-CLIP surface expression (Figure 5A), whereas HLA-DR expression remained unaltered. The ratio of the mean fluorescence intensities (MFIs) of CLIP/MHCII for iDCs, mDCs, and ovalbumin-treated DCs was 0. 5, and 0. 3 for Sp1-treated DCs. This observation suggests that CLIP is displaced when Sp1 is present and that reduced CLIP surface presentation modulates Sp1-mediated T cell immune responses. To investigate whether Sp1 treatment also affects presentation of self peptides other than CLIP, we performed matrix-assisted laser desorption and ionization mass spectrometry (MALDI-MS) of MHCII precipitates from T2. DR4. DM transfectants. The composition of the self-peptide repertoire with CLIP as the major representative remained unaltered when we compared MALDI-MS spectra obtained in the absence and presence of Sp1 (Figure 5B). In summary, Sp1 provided to DCs and loaded onto MHCII leads to a reduction in the number of surface self-peptide/MHCII complexes with CLIP/MHCII as the principal subset. Sp1 is a highly charged molecule and might be exchanged for peptides in an antigen site due to its stronger electrostatic forces. However, it is possible that DM as a catalyzer of peptide exchange and editor of peptide/MHCII binding might also be required for carbohydrate/peptide exchange. To assess the catalytic activity of DM, we first investigated whether DM is required for T cell–dependent immune responses to Sp1 in vivo. In an experimental model for abscess formation, unlike WT mice, animals lacking DM are not able to form abscesses in response to Sp1 (Figure 6A). Twenty-four hours before challenge, CD4+ T cells from WT mice were adoptively transferred to DM−/− mice per intravenous route to compensate for the 3- to 4-fold reduction of mature CD4+ T lymphocytes and for the diminished T cell repertoire selection of DM−/− mice [29]. Analysis of the cells migrating into the peritoneal cavity 24 h after polysaccharide challenge showed that the total number of cells did not differ in WT and DM−/− mice (Figure 6B, left panel). In both groups, about 40% of influx cells were macrophages (not shown). In contrast to WT mice, the peritoneal influx of CD4+ T cells was significantly reduced in DM−/− mice (Figure 6B, right panel). Adoptive intraperitoneal transfer of Sp1-pulsed APCs from WT mice fully reconstituted the CD4+ influx in DM−/− mice. Analysis of the peritoneal lavage did not reveal a CD4+ T cell influx to the APC transfer alone. These findings indicate that the CD4+ T cell influx in response to Sp1 depends on DM expression in peritoneal APCs. We investigated the role of DM in the retrograde transport of Sp1 in DCs and in the initiation of T cell–dependent immune responses in vitro. We transfected iDCs of DM−/− mice of the H-2b haplotype with I-Eα-EGFP. The dependency of I-A molecules on DM to function in antigen presentation has been characterized extensively in the DM−/− mouse strain used [29–31]. It also has been shown that I-E is dependent on DM for peptide loading, as evidenced by the abundance of CLIP occupying the MHCII groove in DM−/− mice [32]. Flow cytometry analysis revealed that after LPS stimulation of DM−/− iDCs, assembled I-E and I-A molecules appeared at the cell surface with similar quantities and kinetics as in WT DCs (Figure S2). In DM−/− iDCs, MHCII co-localized extensively with Sp1 in lysosomes (Figure 7A). Within 4 h of stimulation with LPS, tubules extended from the perinuclear area, which were intensely labeled for MHCII-GFP and were devoid of Sp1-Alexa 594 (Figure 7B). At this time point and within the next 6 h, all tubules were green, indicating that Sp1-Alexa 594 is not transported in tubules with MHCII-GFP in DCs lacking DM. To provide functional evidence for the requirement of DM for Sp1 presentation in DCs, we examined the effect of the absence of DM on APC/T-cell engagement in vitro. iDCs from DM−/− and WT mice were pulsed with Sp1-Alexa 594 in the presence or absence of LPS for different time intervals. Pulsed DCs were incubated with carboxyfluorescein succinimidyl ester (CFSE) –labeled CD4+ T cells from WT mice and examined for DC/T-cell conjugate formation by fluorescent microscopy. After the addition of LPS, WT DCs showed a significant increase of APC/T-cell conjugates, which peaked at 4 h to 10 h (Figure 7C). In contrast to WT DCs, DM−/− DCs pulsed with Sp1-Alexa 594 did not induce significant conjugate formation with CD4+ T cells. The new paradigm of MHCII-restricted presentation of carbohydrates leaves open obvious questions regarding the precise mechanism of bacterial capsular carbohydrate interactions with MHCII molecules. Here we provide evidence that internalization of polysaccharides is followed by intracellular transport and presentation on the cell surface by newly synthesized MHCII molecules. We show that in DCs, Sp1 migrates in tubules as carbohydrate/MHCII complexes to the cell surface to induce T cell–dependent immune responses in vitro and in vivo. Sp1/MHCII retrograde transport requires the editor protein DM. Intracellular tracking of Sp1 reveals partial co-localization with BCECF-dextran and Rab5, markers for early endosomes, that might reflect different pathways for Sp1-containing pinocytic and endocytic vesicles [33] or an intermediate status during fast maturation of Sp1-containing vesicles into late endosomes and lysosomes. In early endosomes, Sp1 could be subjected to oxidation by free radicals as was shown for PS A1 [12]. There is an increasing acidification of Sp1-containing intracellular compartments. We previously demonstrated that Sp1-induced T cell activation depends on the acidic lysosomal pH and that Sp1 induces maturation of human monocyte-derived DCs [11]. Besides proteases, lysosomes also contain abundant glycosidases, such as fucosidases and galactosidases [34]. At a later stage of the endocytic pathway at an optimal acidic pH of maturing DCs [15], glycosidases may trim Sp1 to smaller molecular sizes, forming conformations that facilitate Sp1 anchoring and binding to MHCII and promote optimal generation of T cell epitopes. In contrast to non-charged dextrans, Sp1 is transported from lysosomes to the cell surface in MHCII-positive tubules like conventional protein antigens HEL and Ova [24,25]. Confocal, EPI/TIR fluorescence microscopy, and FACS analyses demonstrate time-dependent retrograde transport and cell surface presentation of Sp1 on maturing DCs, indicating fusion of Sp1-carrying tubules with the plasma membrane for formation of an immunological synapse required for proper activation of T cells. Presentation of Sp1 on the DC surface results in conjugate formation with a considerable number of T cells from non-Sp1–primed naïve mice. Although mDCs are known to attract and cluster with naïve T cells [35], it is possible that T cells from non–germ-free animals that are colonized with the ubiquitous gut organism B. fragilis are primed by the ZPS from B. fragilis and cross-react with Sp1 [36]. Indeed, about 8% of the naïve CD4+ T cells become activated by Sp1-treated DCs. The drastically different immunogenic properties of Sp1 are brought about by specific biochemical characteristics by which Sp1 distinguishes itself from other carbohydrates such as dextrans. At an acidic lysosomal pH similar to the Sp1 isoelectric point of 3. 5 (unpublished observation), an optimal equilibrium of positively charged free amino groups and negatively charged carboxyl groups is available and provides a large number of binding sites to associate with MHCII molecules. The high density of alternating opposite charges is exposed on the outmost surface of the molecule. Maximum binding would be achieved via abundant electrostatic interactions supplemented by the potential for numerous hydrogen bonds to hydrophilic hydroxyls and van der Waals interactions. The proper balance of TH1 and TH2 immunologic responses is critical to maintain balance in the immune system' s task to fight microbial antigens. It has been shown that increased representation of CLIP/MHCII complexes antagonize polarization of T cells towards the TH1 phenotype [21]. Here, we show reduction of CLIP cell surface presentation in mDCs possibly caused by antigenic exchange of CLIP with Sp1 and/or modulation of MHCII/self-peptide retrograde transport by Sp1. Inhibition of presentation of CLIP/MHCII in Sp1-treated mDCs might contribute to the establishment of a TH1/TH2 balance towards the TH1 phenotype as has been described for the ZPS of the symbiotic intestinal bacteria B. fragilis [8]. It might also be responsible for low Sp1-specific antibody production (unpublished data) and might modulate the immune response to ZPS during abscess formation and adhesion. Beyond the functional role of DM in peptide exchange, our data suggest an extension to antigenic exchange with carbohydrates. Three functions have been described for DM: 1) to catalyze the removal of CLIP or non-CLIP peptides and their exchange by heterogeneous peptides [17–19]; 2) to serve as a molecular chaperone, preventing non-specific aggregation of the temporarily empty αβ dimers following CLIP release [37]; and 3) to function as a peptide editor, positively selecting peptides that can stably bind to a particular class II allele [18,38]. Besides facilitating Sp1 binding through catalytic release of CLIP and other peptides, DM might select those Sp1 length variants for binding that form the most stable complexes due to their optimal structural and electrostatic features. Although in DM-deficient DCs accumulation of Sp1 in endocytic compartments, retrograde transport, and surface expression of MHCII complexed with either CLIP or self peptides is normal, they are inefficient in transporting Sp1 from endocytic compartments to the cell surface and initiating conjugate formation with naïve CD4+ T cells. So far, it is not possible to rule out internalization and presentation of ZPS by recycling MHCII or presentation similar to superantigens [7,12]. Recycling MHCII binds to peptides in early endosomes and traffics between early endosomes and cell membrane. Indeed, Sp1 partially co-internalizes with transferrin (not shown), a marker for recycling receptor-mediated endocytosis. However, Sp1 is directed from early endosomal compartments to late endosomes and lysosomes, where it co-localizes with newly synthesized MHCII and does not locate in recycling endocytic Rab11b-positive compartments. Furthermore, the dependency of Sp1 biological activity on DM and on the retrograde tubular transport of MHCII clearly argues against a presentation mechanism similar to superantigens and by recycling MHCII molecules. Taking the results together, we show that bacterial polysaccharide–induced APC/T-cell conjugate formation and T cell–dependent immune responses depend on retrograde transport via MHCII tubules and the functional role of DM. S. pneumoniae type 1 capsular polysaccharide complex was obtained from the American Type Culture Collection (http: //www. atcc. org) and further purified to obtain homogeneity as described previously [11]. High-resolution (500 MHz) proton NMR spectroscopy [5] revealed that Sp1 was free of contaminating protein and nucleic acids. Endotoxin was not detectable in Sp1 by the limulus test with sensitivity of <8 pg LPS/mg Sp1. As control antigens, ovalbumin–fluorescein isothiocyanate (FITC), ovalbumin–Alexa Fluor 594, dextran–Alexa Fluor 488, and dextran–Texas Red Molecular Probes were used (http: //probes. invitrogen. com). For intracellular tracking, BCECF-dextran, LysoTracker Red DND-99, dextran–Alexa Fluor 488, and ovalbumin-FITC were obtained from Molecular Probes. Sp1 is a linear polymer of an average molecular size of 90 kDa corresponding to 167 trisaccharide repeating units with a respective molecular size of 537 Da. Each repeating unit of Sp1 contains one positively and two negatively charged groups with galacturonic acid (GalA, residues a and c) and 2-acetamido-4-amino-2,4, 6-trideoxygalactose (Aat, residue b) with a sequence of →3) -α-D-GalA (a) - (1→3) -α-D-Aat (b) - (1→4) -α-D-GalA (c) - (1→ [5,39]. The adjacent hydroxyl groups on residue c (molecular weight 175) were oxidized by sodium m-periodate (Sigma, http: //www. sigmaaldrich. com) treatment in molar ratios ranging from 1: 0. 1 to 1: 0. 5 for 90 min at room temperature in the dark to create highly reactive aldehyde functional groups [40]. The reaction was stopped by addition of ethylene glycol (Sigma). After gel filtration chromatography with a PD-10 column (Amersham, http: //www. amersham. com), Sp1 was labeled by formation of covalent hydrazone linkages between aldehydes and EZ-Link Biotin-Hydrazide (Pierce, http: //www. piercenet. com), Alexa Fluor 488 hydrazide, and Alexa Fluor 594 hydrazide (Molecular Probes) following the instructions of the manufacturer. After reduction of residual aldehydes of biotinylated Sp1 (Sp1-biotin), Alexa Fluor 488–labeled Sp1 (Sp1-Alexa 488), and Alexa Fluor 594–labeled Sp1 (Sp1-Alexa 594) by base treatment at pH 9. 0 for 60 min, the glycoconjugate was separated from unbound labeling agents by three consecutive runs on PD-10 columns. The degree of biotinylation was determined with the ImmunoPure 2- (4′-hydroxyazobenzene benzoic acid) (HABA) and ImmunoPure Avidin (Pierce) reagents, following the instructions of the manufacturer. This method allows the calculation of mol biotin per mol Sp1 and number of biotin molecules per repeating units. Labeled Sp1 carried a biotin molecule on every 20th repeating unit (Sp1-biotin), which corresponds to one label per 11-kDa fragment by 1H NMR spectroscopy and showed the same chemical shifts as native Sp1 (Figure S3A and S3B). The additional signals obtained for Sp1-biotin originated from EZ-Link Biotin-Hydrazide (Figure S3B, upper spectrum). All mice challenged with Sp1-biotin developed intraabdominal abscesses to the same degree as native Sp1 (Figure S3C). Sp1 labeled with Alexa Fluor hydrazide 488 (Sp1-Alexa 488) or Alexa Fluor hydrazide 594 (Sp1-Alexa 594) preserved its intact structure and in vivo immune responses (not shown). These controls demonstrated that the biological activity of labeled Sp1 used in our studies is indistinguishable from that of unlabeled Sp1. NMR spectra were obtained from a sample of 2 mg of purified Sp1, Sp1-biotin, or Sp1-Alexa 488, which was exchanged with 2H2O once and redissolved in 0. 7 ml of 2H2O as described previously [5]. NMR experiments were performed on a Bruker DRX 500 instrument (Bruker, http: //www. bruker. de) with a proton resonance frequency of 500. 13 MHz. The 1H spectra were recorded at 80 °C in 2H2O using presaturation to suppress the water signal. Chemical shifts were referenced in relation to 1H2HO resonance at 4. 36 ppm. Animal experiments were performed in accordance with the guidelines of German animal protection legislation (license number 50. 203. 2-K 16,3/02). In abscess induction studies, B6129SF2/J (WT) and H2-Dmatm1Luc (DM−/−) [29] obtained from Charles River Laboratories (http: //www. criver. com) were injected intraperitoneally with Sp1 (100 μg of Sp1 in PBS mixed with sterile cecal content adjuvant [SCCA]; 1: 1 v/v, 0. 2 ml total volume) [9]. Then, 24 h before challenge, 2 × 107 CD4+ T cells (>95% purity) from WT mice were adoptively transferred to DM−/− mice per intravenous route. Six days after challenge, mice were macroscopically examined for the presence of abscesses within the peritoneal cavity by two double-blinded examiners. Abscesses were isolated and their diameter was measured. The cellular influx into the peritoneal cavity was assessed at 24 h following challenge with Sp1. As in abscess induction studies, 2 × 107 CD4+ T cells from C57BL/6 (WT) mice obtained from Charles River Laboratories were adoptively transferred to DM−/− mice per intravenous route 24 h before challenge. WT mice were challenged intraperitoneally with Sp1. DM−/− mice were either challenged intraperitoneally with Sp1, Sp1 plus 2 × 107 WT APCs, or 2 × 107 WT APCs alone. APCs were purified from the peritoneal lavage followed by CD4+ T cell depletion (<0. 05% CD4+ T cells) of WT mice challenged 24 h before adoptive transfer. Mice underwent peritoneal lavage with 4 ml of ice-cold PBS. A total cell count was performed by trypan blue staining with a hemocytometer. Each sample was then analyzed by flow cytometry for different cell types. The absolute number of each respective cell type present was calculated by taking its respective frequency and multiplying it by the total number of cells per ml lavage obtained from each mouse. In each experiment, four to six mice per group were tested. The experiment was performed three times in an independent manner. Frozen sections of abscesses were fixed in cold acetone for 10 min followed by blocking of endogenous peroxidase with peroxidase blocking solution (DAKO, http: //www. dako. com) for 10 min at room temperature. The CD11c antibody (N418, supernatant; 1: 100 diluted) was then overlayed and the slides incubated in a humid chamber for 45 min. With TRIS washes between every step, a biotinylated link antibody (Becton Dickinson, http: //www. bdbiosciences. com) was applied for 45 min followed by a streptavidin-alkaline phosphatase (DAKO) for 10 min. After another wash, the substrate (Vector NovaRed; Vector Laboratories, http: //www. vectorlabs. com) was added and the slides were incubated in the dark for 20 min. After a TRIS wash, the slides were counter stained, mounted, and viewed using a Zeiss Axiophot microscope with photographic capabilities (http: //www. zeiss. com). DCs were generated from mouse bone marrow by adapting a previously described method [41]. In brief, bone marrow cells from H2-Dmatm1Luc [29] (DM−/−) and C57BL/6 (WT) mice that have a mutation that abolishes production of the MHCII I-Eα chain [31,42] were cultured in RPMI supplemented with 5% FBS, 500–1,000 U recombinant mouse granulocyte/macrophage-colony stimulating factor (GM-CSF), 20 μg per ml gentamicin, and 50 μM 2-mercaptoethanol (DC medium). DC medium was exchanged in two-day intervals. DCs were isolated by magnetic cell sorting with a CD11c-specific monoclonal antibody (mAb) (Miltenyi Biotec, http: //www. miltenyibiotec. com). CD11c-positive iDCs were imaged on days 4 and 5 of culture. mDCs were generated by adding LPS O26: B6 (100 ng/ml) (Sigma) to disaggregated and replated cultures. Infection of proliferating precursors with retrovirus containing I-Eα-EGFP was performed on day 2 by adapting a method described previously by Chow and coworkers [24]. I-Eα-EGFP, kindly provided by I. Mellman, was cloned into LZRS-pBMN using EcoRI sites. This viral vector was transfected into ΦNX-ecotropic cells using calcium chloride. Virus was collected in DC medium for 24 h, supplemented with polybrene and HEPES, and added to the DC culture for infection. Cells were spun at 32 °C, 2,500 rpm for 2 h. Virus was removed and fresh medium added. Expression was assayed 48 h after infection. Localization of Sp1 in recycling, early, and late endosomes was performed by adenoviral infection of live dendritic cells with Rab11b-EGFP, Rab5-GFP, and Rab7-GFP–containing mammalian expression plasmids [43]. DNA fragments containing Rab fusion protein constructs and CMV promoter were amplified in the double digested promoter-less transfer vector pEntry148AU-MCS. For packaging into adenovirus particles, constructs were recombined into pAd/PL-DEST vector (Invitrogen, http: //www. invitrogen. com). Adenoviral stocks were produced in 293A cells after transfection with plasmid DNA and Lipofectamine. Infection of DCs with Rab5-EGFP, Rab7-EGFP, and Rab11b-EGFP was performed on day 4. iDCs were spun at 2,500 rpm at 37 °C for 120 min in virus-containing medium supplemented with 10 mM HEPES. After replacement with DC medium, expression was checked by fluorescence microscopy after 24 h. Transfection efficiency was 50% to 70%. Human DCs were differentiated from peripheral blood mononuclear cells as described [44]. Monocytes were isolated from peripheral blood mononuclear cells by positive selection by anti-CD14 magnetic beads (Miltenyi Biotec) and cultured in complete RPMI medium containing 50 ng/ml GM-CSF and 3 ng/ml IL-4. Maturation was induced at day 4 by the addition of LPS from Salmonella abortus equi (1 μg/ml) (Sigma). Staining of surface molecules was performed using PE- or FITC-conjugated anti-CD4 (clone L3T4), anti-CD11c (clone Hl3), anti-CD69 (clone HI. 2F3), anti-I-Eαβ (clone 14. 4. 4S), anti-I-Aβ (clone AF6–120. 1), anti-HLA-DR/CLIP complex (clone Cer. CLIP), and anti-HLA-DR (clone L243) (BD Pharmingen, http: //www. bdbiosciences. com). For Sp1 surface presentation studies, iDCs were incubated for 30 min at 37 °C without or with Sp1-biotin (200 μg/ml), washed, and incubated for 30 min to 8 h at 37 °C in LPS-containing medium (100 ng/ml) before staining with streptavidin-FITC (Sigma) for 30 min and washing. Cells prepared for flow cytometry were analyzed—after gating for viable cells by forward and side scatter and by propidium iodide staining—by FACScan (Becton Dickinson) using CELLQuest software (Becton Dickinson). The results were expressed as MFI, or as percentage (%) of fluorescence-labeled APCs of the whole APC population. To investigate intracellular trafficking of Sp1, live cell imaging was performed. Cells were plated for 30 min on poly-d-lysine–pre-coated number 1. 5 coverslips attached to 35-mm dishes (MatTek, http: //www. mattek. com), and fresh medium was added. To study mechanisms of internalization of Sp1, cells were incubated with competitors or chemical inhibitors for 30 min at 4 °C or 37 °C before Sp1 treatment. To monitor Sp1, APCs were loaded with markers for cellular compartments before or at the same time point of Sp1 addition. Cells were washed before and after Sp1 treatment three times in ice-cold medium. Inverted fluorescent microscopy was performed on an Olympus IX81 microscope (http: //www. olympus-europe. com/microscopes/index. htm). Temperature control at 37 °C was achieved with a heating dish. Acquisition was performed using AnalySIS Imaging System software (Olympus, http: //www. olympus. de). Confocal microscopy was done on a PerkinElmer UltraView LCI spinning disc system (http: //las. perkinelmer. com) equipped with a suitable multi-band beamsplitter and a MellesGriot Omnichrome 643-RYB-A02 ArKr gas laser (http: //www. mellesgriot. com) providing 488-nm and 568-nm lines for excitation. A Nikon Plan Fluor ×100 1. 3NA oil immersion objective (http: //www. nikon. com) and 525/50 and 607/45 emitter filters were used for GFP, FITC, Alexa 488, and Alexa 594, and Texas Red stains, respectively. Multi-color TIR-FM and EPI was performed on an Olympus Biosystems Cell-R system equipped with a stabilized Xenon arc lamp and dual coupling for Coherent Sapphire 488–20 and Compass 250M-50 diode lasers (http: //www. coherent. com) providing 488 nm and 532 nm excitation light, respectively. On confocal microscopy, EPI, and TIR-FM systems, environmental condition was controlled by a custom incubator (EMBL GP 168) that provides a 37 °C and 5% CO2 atmosphere. Images were exported to TIFF images, processed using Adobe Photoshop version 6. 0 (http: //www. adobe. com), and converted into QuickTime movies using Graphic Converter version 3. 8 (Softguide, http: //www. softguide. de). Investigation of DC/T-cell conjugate formation was performed as previously described [45]. In brief, DCs from C57BL/6 WT and DM−/− mice were loaded with Sp1-Alexa 594 for 30 min or left untreated and washed. DCs (0. 5 × 105/ml) were then treated with LPS (100 ng/ml) for different time intervals, washed, and mixed with CFSE-labeled CD4+ T cells (1. 5 × 105) from C57BL/6 WT mice. Cells were centrifuged for 5 min at 50g to increase cell interactions, and incubated at 37 °C for 20 min. The cells were gently transferred to poly-d-lysine–pre-coated number dishes. After incubation at 37 °C for 30 min, T-cell–DC conjugates were subjected to imaging by fluorescent microscopy. CFSE-labeled T cells were distinguished from GFP-labeled DCs by morphology. Three independent experiments were performed and the number of CFSE-positive CD4+ T cells interacting with 100 Sp1-Alexa 594–positive DC was counted in a blinded manner as previously described [22]. For the investigation of WT CD4+ T cell activation induced by Sp1-treated DCs, the same protocol as for DC/T-cell conjugate formation was applied with some modifications. DCs were treated with 100 μg/ml Sp1 for 45 min or left non-treated. Analysis of the expression of CD69, the early activation marker on CD4+ T cells, was performed by flow cytometry at different time points after addition of T cells to DCs. T2. DR4. DM transfectants, expressing the MHCII molecules HLA-DR4 and DM, respectively, were maintained in RPMI 1640 supplemented with 10% FCS. T2 is a BxT cell hybrid with a large deletion in the MHCII locus and does not express endogenous MHCII proteins. Cells at a density of 6 × 105 cells/ml were treated with Sp1 (200 ug/ml) for 20 h, washed with PBS, and lysed (6 × 106/ml) at 4 °C in lysis buffer of 20 mM and 5 mM MgCl containing 1% Triton X-100 and protease inhibitors. The cells were precipitated with mAb L243 (recognizing antigen/HLA-DR complexes) conjugated to sepharose beads. Peptides were eluted with 0. 1% trifluor-acetic acid. MALDI-MS analysis was done as described [21] on a Reflex III mass spectrometer (Bruker). Comparison of groups with regard to abscess formation was made by chi-square analysis. Results of the various groups in peritoneal cellular influx and APC/T-cell engagement assays were compared by Student' s t test.

Title: Transport of Streptococcus pneumoniae Capsular Polysaccharide in MHC Class II Tubules Summary: Microorganisms are comprised of proteins, carbohydrates, lipids, and nucleic acids. Current immunologic paradigms state that activation of T lymphocytes required for humoral and cellular immune responses resulting in immunologic memory to the pathogens is solely brought about by proteinaceous antigens, processed and degraded to small peptides, loaded onto major histocompatibility complex (MHC) molecules, and transported as MHC/peptide complexes to the cell surface, where the MHC/peptide complex is recognized by the T cell antigen receptor. The findings of the present study elucidate the mechanism of MHC class II (MHCII) -dependent presentation of the bacterial capsular polysaccharide of Streptococcus pneumoniae serotype 1 (Sp1) that results in effective T cell activation. Sp1 is transported in MHCII-positive tubules from lysosomal compartments to the plasma membrane for presentation. In the absence of the DM molecule, known as an editor and catalyst of self and foreign peptide exchange, retrograde transport of carbohydrate/MHCII complexes resulting in dendritic cell engagement with T cells in vitro and T cell-dependent immune responses to the polysaccharide in vivo fail. The results suggest a fundamental shift in the immunologic paradigm, offering previously unrecognized opportunities for the design of new classes of vaccines against infectious diseases.

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Summarize: Sir John Betjeman may have rhapsodised. about playing tennis with Joan Hunter Dunn, who had ‘the speed of a. swallow, the grace of a boy’. But the modern tennis heroine has rather. more weapons in her arsenal — and we are not just talking about ability. on the court. Eugenie Bouchard, 20 years old and. Canadian, is gloriously blonde with perfectly regular, brilliantly white. film-star teeth, a pair of oiled thighs that could crack walnuts, half a. million fans on Facebook — and a Twitter profile which ranges from the. flirtatious to the, frankly, provocative. Indeed,. the new face of women’s tennis - who will be fighting to be crowned. Wimbledon champion on Saturday — likes to post pictures of herself. lounging seductively in bikinis and pouting in fancy dress. VIDEO Scroll down to watch Stunning Eugenie Bouchard dazzle in Sportsmail photo shoot. Rising star: Eugenie Bouchard prepares at the All England Club for her Wimbledon final clash on Saturday. Fierce: While much focus is on Bouchard's appearance, she is a determined competitor and hugely talented. She is as much the queen of the selfie. as the queen of the court. Canny, money-making and with an ambition and. drive which make the rest of the tennis crowd - no offence Maria. Sharapova - look like a bunch of shuffling amateurs. Her. smitten fans, known as the Genie Army, follow her around the globe and,. in a mawkish display of puppy love, throw teddy bears on to the court,. some with proposals of marriage attached. Adorable. though she may be, Eugenie can also be utterly ruthless - in a charming. way - when it comes to fulfilling her role as champ-in-waiting. For example, she was once best friends. with British tennis hope Laura Robson, who is also 20. They met aged. nine and were inseparable for a decade. They. were once so close that Canadian Bouchard stayed with Robson at her. family home near the All England Club when they played there. As. teenagers they dined together every night during overseas tournaments. and two years ago made a video featuring tennis stars - including. Sharapova - performing Gangnam Style dance moves. But there has been an acrimonious. falling out. Asked on Friday if they were still close, Bouchard. responded bluntly: ‘No. I don’t think so,’ adding ‘I’m sure you guys can. figure out that one... I’ll leave it at that.’ The. rift is believed to be over Nick Saviano, the leading coach who runs. the Florida tennis academy where they first met. While the pair. previously shared his services, he now coaches Bouchard exclusively. Falling out: Bouchard (right) and Britain's Laura Robson (left) used to be inseparable but are no long close. Their. friendship has deteriorated further during the past year as Bouchard. accelerated ahead of her former friend. She has climbed into the tennis. top ranks, while Robson peaked when she reached the fourth round of last. year’s Wimbledon, then missed this year’s championships with a wrist. injury. She now languishes at 91 in the world rankings. Tennis insiders say the girls no. longer speak, let alone post pictures of themselves together on social. networking sites as they once did so regularly. Before the French Open,. Bouchard said she didn’t have a best friend: ‘I don’t think the tennis. tour is the place to have friends. For me it’s all competition.’ Where. her twin sister Beatrice is concerned, Eugenie says they are. ‘opposites’ and ‘very different’. Beatrice, she adds, ‘retired from. tennis aged six’, and they see little of each other as Eugenie. criss-crosses the globe in search of sporting glory. Beatrice, a student, is the older by. six minutes. Speaking to reporters, she claimed to have a telepathic. link with Eugenie and broke into a broad smile over her sister’s. achievements. ‘Every day I am just in awe,’ she said. ‘I have seen. everything she has missed out on in childhood and teenage years. She has. sacrificed a lot to get where she is today.’ Eugenie. has self-belief and focus by the bucketload. When she met tennis legend. Chris Evert at an event in Singapore in January, she was far from. over-awed. BFFs no more: When asked if she was close with Robson anymore, Bouchard said: 'No. I don't think so. I'm sure you guys can figure out that one... I'll leave it at that' Tight bond: As teenagers Bouchard would stay at Robson's house when she played at Wimbledon. Evert tweeted: ‘@GenieBouchard has informed me that there are more cameras focused on her...’ By. the end of the day they were apparently friends, and Evert wrote: ‘Ok,. spent the whole day with @GenieBouchard. Impressions: genuine, mature,. determined, and really funny!!!’ Or, as she told a reporter that day, more bluntly: ‘She is as tough as nails.’ So. who is Eugenie? Born on February 25, 1994, in Montreal, she is the. product of a wealthy suburban upbringing. Her father Michel Bouchard,. known as Mike, is an investment banker, and mum Julie LeClair is a great. fan of the Royal Family — which is why she called her twin girls. Eugenie and Beatrice. ‘When. I was young my mum gave me a magazine with the two Princesses in it and. I still keep it on my bedside table,’ Bouchard says. Her younger brother is named. William after Prince William and the eldest of the siblings is. Charlotte, after Princess Charlotte Casiraghi of Monaco. Home was in the posh suburb of Westmount - in the same street as former Canadian Prime Minister Brian Mulroney. The children were introduced to tennis. at a young age, but Eugenie, then aged five, detested the ‘childish’ games involving hula hoops and balloons that were supposed to interest. them in the sport. Acrimonious: The rift between Bouchard and Robson is reportedly over coach Nick Saviano choosing to work with the Canadian exclusively. Confronting: Bouchard remonstrates with the chair umpire during her semi-final victory at Wimbledon. ‘All of the kids, including my sister,. loved the games, except me,’ she told the Canadian Globe and Mail. newspaper. ‘I hated them, I just wanted to hit more balls and actually. play tennis. ‘Eventually, I. started playing three times a week, then took private lessons and played. my first tournament aged eight. I loved it right away.’ Extraordinarily,. this was when she decided that tennis was to be her life. ‘Nine is very. young to decide what you want to do in life, but that is pretty much. when I decided,’ she said. When she was 12, Eugenie had the chance to move to Florida to train with coach Nick Saviano at his academy. The. whole family relocated to Florida from Montreal — and moved back a few. years later, after Tennis Canada agreed to pay for an exclusive trainer. for her in Montreal. She continues to train with Saviano in Florida for. part of the year, and spends the rest of it on the tour, going home to. Montreal for visits when she can. Mike Bouchard — like the parents of. champs Andre Agassi and Steffi Graff — has taken a hands-on approach to. building his daughter’s sporting career, sometimes with excessive zeal. Bouchard. tried to claim thousands that he personally spent on his daughter’s. dream in 2004, 2005 and 2006 as business losses against tax — but. Canada’s tax service disallowed it. An. embarrassing episode perhaps, but Eugenie continued her march to tennis. glory. She won Junior Wimbledon in 2012 and last year was named WTA. tennis newcomer of the year. She reached the semis of the 2014. Australian Open in January and the 2014 French Open. Moving on: Bouchard defeated Simona Halep in straight set to win her place in Saturday's Championship decider. Clash: The 13th seed (left) faces sixth seed and 2011 winner Petra Kvitova (right) on Centre Court. Her. prize money to date stands at £1 million — her greater earnings come. from endorsements, which so far include Nike and Coke, and she has been. in Vogue and other fashion magazines. She is now being courted by watch. manufacturers, jewellery designers, clothes labels and banks. Sharapova,. the best financially rewarded female athlete on the planet, netted. £15 million last year with her deals with Tiffany, Omega, et al. Fancy dress: Eugenie (right) with twin sister Beatrice. Eugenie’s agent, Sam Duvall, is tipping her to become the most famous player in the world. ‘She’s got the personality, she’s got the game, she’s got the looks,’ he said. ‘She speaks two languages [French and English] and the crossover appeal is great. Aussie fans love her, French fans love her.’ ‘She understands that the better she plays tennis, the more money, the more marketable and the more famous she will be. But it’s all centred on the tennis.’ Nigel Currie, of sports agency Brand Rapport, agrees that Bouchard could unseat the glorious Sharapova as the game’s top earner. Her use of social media already sets her apart and makes her all the more valuable as a commodity. She is, online at least, an unabashed flirt — posting a selfie with the actor Owen Wilson earlier this year; a picture of herself on her birthday, lying on her bed surrounded by flowers and birthday wishes; and one on Valentine’s day with a hand-drawn card: ‘From me, to me.’ All of which makes her fans love her even more. She is, though, apparently quietly going out with American ice hockey player Alex Galchenyuk, who plays for a Canadian team. Before that she was dating Australian tennis star Bernard Tomic. She faces No 6 seed Petra Kvitova as Canada’s first Grand Slam singles finalist at Wimbledon, and is brimming with confidence. ‘It’s not a surprise to me. I expect to be in these finals. I totally feel like I belong. I want to make my own history.’ As well as her own millions

Summary: Canadian Bouchard, 20, will contest the Wimbledon final on Saturday. She meets Petra Kvitova on Centre Court at the All England Club. Bouchard used to be close friends with Britain's Laura Robson. The pair had fell out, reportedly about their former coach Nick Saviano. Friendship deteriorated as Bouchard flew up the rankings ahead of Robson. Bouchard said: 'I don't think the tennis tour is the place to have friends'

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Summarize: TECHNICAL FIELD This invention relates to a pharmaceutical composition of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole having analgesic activity in mammals, and to a method of use of the composition to alleviate pain in mammals. BACKGROUND OF THE INVENTION More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages thereby diminishing the expected side effects and toxicity that would result from the otherwise required higher dosages. U.S. Pat. No. 3,393,197, issued to Pachter and Matossian on July 16, 1968, discloses N-substituted-14-hydroxydihydronormorphines, including the N-cyclobutylmethyl derivative, commonly called nalbuphine: ##STR1## Pachter and Matossian and others, such as H. W. Elliott, et al., J. Med. (Basel), 1, 74-89 (1970); H. Blumberg, et al., Pharmacologist, 10, 189 (Fall 1968); P. Roberts, Drugs of the Future, 2, 613-5 (1977), disclose the use of nalbuphine as an analgesic for the control of moderate to severe pain. U.S. Pat. No. 4,237,140, issued to J. R. Dudzinski on Dec. 2, 1980, describes an analgesic mixture of nalbuphine and acetaminophen. U.S. Pat. No. 4,282,215, issued to J. R. Dudzinski and W. K. Schmidt on Aug. 4, 1981, describes an analgesic mixture of nalbuphine and aspirin. U.S. Pat. No. 4,190,666 issued to S. C. Cherkofsky and T. R. Sharpe on Feb. 26, 1980, discloses the compound 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole ##STR2## its synthesis, and its use as an analgesic. SUMMARY OF THE INVENTION It has now been found that combinations of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole provide unexpectedly enhanced analgesic activity. Specifically, a pharmaceutical composition comprising a combination of synergistically effective analgesic amounts of nalbuphine, or a pharmaceutically suitable salt thereof, and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, or a pharmaceutically suitable salt thereof, has been found to provide enhanced pain relief in mammals. Another aspect of the invention comprises the method of alleviating pain in a mammal by administering an effective analgesic amount of the composition described above to a mammal. BRIEF DESCRIPTION OF THE DRAWING FIGS. 1 and 2 are isobologram plots characterizing the effective pain relieving doses which produce analgetic responses in one half the mice subjected to the phenyl-p-benzoquinone induced writhing test at various dose ratios of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole studied at two different times. DETAILED DESCRIPTION OF THE INVENTION Nalbuphine, which has the chemical name (-)-17-(cyclobutylmethyl)-4,5α-epoxymorphinan-3,6α,14-triol, and its preparation are described in U.S. Pat. No. 3,393,197, the disclosure of which is hereby incorporated by reference. 4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole and its preparation are described in U.S. Pat. No. 4,190,666, the disclosure of which is hereby incorporated by reference. When the terms nalbuphine or 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole are used herein, it is to be understood that any of the pharmaceutically suitable salts thereof which have analgesic properties in man and other mammals are included by the term. For nalbuphine, such salts include the hydrochloride, hydrobromide, hydroiodide, sulfate, bisulfate, nitrate, citrate, tartrate, bitartrate, phosphate, malate, maleate, fumarate, succinate, acetate and pamoate, while for 4,5-bis-(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, pharmaceutically suitable salts would include those of calcium, potassium, and sodium. In the composition of the invention, nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole are combined and have been utilized at dose ratios based on weight of nalbuphine to 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole of from 1:0.000245 to 1:0.107 in mice subjected to the phenyl-p-benzoquinone induced writhing test to establish analgetic effectiveness. The phenyl-p-benzoquinone induced writhing test in mice [H. Blumberg et al., Proc. Soc. Exp. Biol. Med., 118, 763-766 (1965)] is a standard procedure for detecting and comparing the analgetic activity of different classes of analgesic drugs with a good correlation with human analgetic activity. Data for the mouse, as presented in the isobologram, can be translated to other species where the orally effective analgesic dose of the individual compounds is known or can be estimated. The method simply consists of reading the % ED50 DOSE for each dose ratio on the best fit regression analysis curve from the mouse isobologram, multiplying each component by its effective species dose, and then forming the ratio of the amount of nalbuphine to 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1 H-imidazole. This basic correlation for analgesic properties enables estimation of the range of human effectiveness. [E. W. Pelikan, The Pharmacologist, 1, 73 (1959). ] Application of an equieffective dose substitution model and a curvilinear regression analysis utilizing all the data for the individual compounds and various dose ratios for the combinations establishes the existence of unexpectedly enhanced analgetic activity of combinations of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, i.e., the resulting activity is greater than the activity expected from the sum of the activities of the individual components. The composition of the invention presents the opportunity of obtaining relief from pain with reduced dosages of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, thereby diminishing the side effects and toxicity which would result from the otherwise required amounts of the individual drug components. Dosage Forms The combination of analgetic agents of the invention can be administered to treat pain by any means that produces contact of the active agent with the agent&#39;s site of action in the body of a mammal. The composition of the invention can be administered by any conventional means available for use in conjunction with pharmaceuticals. It can be administered alone, but is generally administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice. The dosage administered will, of course, vary depending upon known factors such as the pharmacodynamic characteristics of the particular agent, and its mode and route of administration; age, health, and weight of the recipient; nature and extent of symptoms, kind of concurrent treatment, frequency of treatment, and the effect desired. Usually a daily dosage can be such that the active ingredient is administered at a daily dosage of from about 0.25 to 7.50 milligrams per kilogram (mg/kg) of body weight of nalbuphine and from about 0.1 to 2.0 mg/kg of 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole. Ordinarily, administration of the composition of the invention in divided doses 2-5 times a day or in a sustained release form is effective to obtain desired results. Dosage forms (compositions) suitable for internal administration contain a total of from about 15 milligrams to about 600 milligrams of active ingredients per unit. In these pharmaceutical compositions the active ingredients will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition. The active ingredients can be administered orally in solid dosage forms, such as capsules, tablets, and powders, or in liquid dosage forms, such as elixirs, syrups, and suspensions. Gelatin capsules contain the active ingredients and powdered carriers, such as lactose, sucrose, mannitol, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance. Suitable pharmaceutical carriers are described in Remington&#39;s Pharmaceutical Sciences, A. Osol, a standard reference text in this field. Useful pharmaceutical dosage-forms for administration of the composition of the invention can be illustrated by the following examples: EXAMPLE 1 Nalbuphine/4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole Tablets (30/1.5 mg) ______________________________________Formula mg/Tablet______________________________________Nalbuphine HCl 30.04,5-Bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H--imidazole 1.5Microcrystalline Cellulose 200.0Starch, modified 16.0Magnesium Stearate 2.5 250.0______________________________________ EXAMPLE 2 Nalbuphine/4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole Tablets (30/7 mg) ______________________________________Formula mg/Tablet______________________________________Nalbuphine HCl 30.04,5-Bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H--imidazole 7.0Microcrystalline Cellulose 200.0Starch, modified 10.5Magnesium Stearate 2.5 250.0______________________________________ EXAMPLE 3 Nalbuphine/4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole Tablets (15/30 mg) ______________________________________Formula mg/Tablet______________________________________Nalbuphine HCl 15.04,5-Bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H--imidazole 30.0Microcrystalline Cellulose 180.0Starch, modified 22.5Magnesium Stearate 2.5 250.0______________________________________ EXAMPLE 4 Nalbuphine/4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole Capsules (30/1.5 mg) ______________________________________Formula mg/Capsule______________________________________Nalbuphine HCl 30.04,5-Bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H--imidazole 1.5Microcrystalline Cellulose 280.0Starch, modified 30.5Starch 8.0 350.0______________________________________ EXAMPLE 5 Nalbuphine/4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl-1H-imidazole Capsules (30/7 mg) ______________________________________Formula mg/Capsule______________________________________Nalbuphine HCl 30.04,5-Bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H--imidazole 7.0Microcrystalline Cellulose 280.0Starch, modified 25.0Starch 8.0 350.0______________________________________ EXAMPLE 6 Nalbuphine/4,5-Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole Capsules (15/30 mg) ______________________________________Formula mg/Capsule______________________________________Nalbuphine HCl 15.04,5-Bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H--imidazole 30.0Microcrystalline Cellulose 270.0Starch, modified 27.0Starch 8.0 350.0______________________________________ Test Methods The unexpectedly enhanced analgetic activity obtained in the method of the invention is evidenced by tests conducted on mice. Male CF 1 mice obtained from Charles River Breeding Laboratories, fasted for 16-22 hours and weighing 18-22 g at the time of testing are used throughout. All mice are dosed sequentially by the oral route with suspensions of 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole and/or of nalbuphine hydrochloride. A dosing volume of 10 ml/kg is used for each sequential solution or suspension. It will be appreciated by those skilled in the art that the enhanced activity will be obtained whether the 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole and nalbuphine are administered simultaneously as a mixture or sequentially as the two individual components. All doses are coded and the test is performed under a code not known to the observer. A stock suspension of 4,5-bis(4-methoxyphenyl)-2-trifluoromethylsulfonyl)-1H-imidazole is prepared by mixing 8.0 mg 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole with 80 ml of an aqueous vehicle containing 2% by volume of Tween 80®, a pharmacological dispersant manufactured by Fisher Scientific Company and containing 100% polysorbate 80, and 1% by weight of Methocel® MC powder, a suspending agent manufactured by DOW Chemical Company and containing 100% methylcellulose, in distilled water. The mixture is sonicated at 150 watts for 1-2 minutes with an ultrasound system, then shaken for two hours at 280 oscillations/minute with 15-20 gm of glass beads. The resultant suspension contains 0.1 mg/ml of 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole; all dosing suspensions are prepared by dilution of the stock suspension with the Methocel®/Tween 80® vehicle; the vehicle control is Methocel®/Tween 80®. All suspensions are prepared fresh daily. Stock solutions of nalbuphine HCl are prepared by dissolving dry nalbuphine hydrochloride powder with distilled water. All dosing solutions are prepared by dilution of the stock solution with distilled water; the vehicle control is distilled water. As indicated above, the standard procedure based upon the prevention of phenyl-p-benzoquinone induced writhing in mice is utilized to detect and quantify the analgetic activity of compositions containing nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole. Mice, intubated with various doses of nalbuphine hydrochloride, 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, combined doses of nalbuphine hydrochloride and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, or vehicle, are injected intraperitoneally with a challenge dose of phenyl-p-benzoquinone 5 minutes prior to the designated observation period. The phenyl-p-benzoquinone is prepared as an 0.1 mg/ml solution in 5% by volume of ethanol in water; the writhing dose is 1.25 mg/kg injected in a volume of 0.25 ml/20 g. For scoring purposes a &#34;writhe&#34; is indicated by whole body stretching or contraction of the abdomen; mice are observed 10 minutes for the presence or absence of writhing beginning 5 minutes after receiving the phenyl-p-benzoquinone dose. Each mouse is used only once, then discarded. The alleviation of pain is quantified by determining the dosage at which 50% of the mice in a test group exhibit an analgesic response for the composition being tested. This dosage as described herein is referred to as the ED50. All ED50 values and their 95% confidence limits are determined numerically by the computer-assisted methods of Finney. [D. J. Finney, &#34;Probit Analysis,&#34; Third Edition, Cambridge University Press, Cambridge, England, 1971]. In order to study the interaction between nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole, 5 or 6 precise dosage ratios of nalbuphine hydrochloride and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole were selected. Four or five coded doses of each selected combination are studied for analgesic effectiveness at 40 or 80 minutes using an experimental design which permits coding and complete randomization of the separate dosage forms tested. Altogether 35 or 40 separate dosage forms are used and each form is represented in each experimental session. The experiments are continued by running experimental sessions with an equal number of mice per group being tested until the total number, N, of mice tested per group is 30. The nature of the analgetic interaction (addition, synergism, or antagonism) is determined by graphing the results in a Loewe isobologram [S. Loewe, Pharm. Rev. 9:237-242 (1957)]. The isobologram is a quantitative method for measuring interactions between drugs where dose-effect relationships are depicted in a multi-dimensional array with lines connecting dose pairs that are equieffective in relationship to a common pharmacological endpoint. In this instance, the antiphenylquinone writhing test is used to estimate a common level of analgesic activity (ED50 dose) for the two component drugs separately and for each fixed dose-ratio combination. In the isobolographic figure, areas of dose addition, synergism, and/or antagonism are clearly defined by reference to the theoretical &#34;ED50 Addition Line.&#34; According to Loewe&#39;s isobolographic theory, ED50&#39;s falling under the curve (between the ED50 Addition Line and the origin) would represent unexpectedly enhanced analgetic activity and combination ED50&#39;s located above the line would represent unexpectedly diminished analgetic activity. Most importantly, the isobolographic technique permits a full range of doses and dose combinations to be examined where the proportion of the first drug to the second actually varies from 0 to infinity, and to determine, by virtue of the graphical display, whether any one or more of the paired drug combinations displays unique pharmacological properties in comparison to the entire body of data generated. The isobologram is also valuable for organizing the data in a form which is easily amenable to statistical assessment of observed differences. The synergistic interaction of nalbuphine hydrochloride and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole on phenyl-p-benzoquinone induced writhing in mice is demonstrated by the data in Tables I and II for data at 40 and 80 minutes, respectively, and in FIGS. 1 and 2, the Loewe isobolograms. In the isobolograms, the analgetic effect of nalbuphine alone is presented in the ordinate, and that of 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole alone is on the abscissa. The dotted lines radiating from the origin represent the exact fixed dosage ratios based on the weight of nalbuphine HCl:4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole in the ranges of 1:0.00143 to 1:0.107 (FIG. 1) and 1:0.000245 to 1:0.00612 (FIG. 2). ED50 values are marked on the ordinate and abscissa, representing nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole alone, and on the dotted radial lines, representing the compositions of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole at the fixed dosage ratios. The arrows extending above and below each ED50 point represent the 95% confidence limits of the ED50&#39;s. As drawn in FIG. 1, the solid diagonal line joining the ED50 values of the two drugs given separately represents the &#34;ED50 Addition Line,&#34; the theoretical line for simple additivity of drug effects which would be observed in the absence of a synergistic response. The drawing clearly shows that in the method of the invention, all of the tested fixed ratio compositons give unexpectedly enhanced analgetic activity since the ED50 values for each of these ratios fall below the line of simple additivity. Similar data are presented in FIG. 2, which again clearly demonstrates unexpectedly enhanced analgetic activity. By utilizing an equieffective dose substitution model and a statistical regression analysis of all of the data, one can obtain a more reliable assessment of the existence of a synergistic property, in this case unexpectedly enhanced analgetic activity. The effects of two compounds are additive if the response to a dose of the two in combination does not change when a portion of one is removed from the mixture and replaced by an equipotent portion of the other. If such substitution increases the response, the mixing together of the compounds is said to potentiate their effects and synergism exists. Consider ED50 doses of mixtures of X units of compound B with Y units of compound A, whose ED50 doses are β and α, respectively. Given the hypothesis of additivity, all doses of mixtures satisfying the straight line relation, ##EQU1## will be ED50 doses. To test the hypothesis of additivity, ED50 doses of mixtures are estimated through probit analysis of data from experiments run at various ratios of A to B. Linear and curvilinear regression models are fitted to the data to estimate the amounts of A in respective ED50 doses, given the amount of B, (or, conversely, the amount of B, given A). If a curvilinear regression fit the data significantly better than a straight line regression, the hypothesis of additivity is refuted and synergism exists for the two compounds for the property of interest. Values of Y calculated from the straight line of Equation 1, and values of Y calculated from the curvilinear regression are plotted against X on an ED50 isobologram to describe the synergism. It is convenient to standardize the units of dose such that 100 units of either compound alone is its respective estimated ED50 dose. The additivity hypothesis, then, will be represented by a straight line from 100 on the Y-axis to 100 on the X-axis on the isobologram, and Equation (1) becomes: Y=100-X. The isobolographic Figures show the straight line additivity hypothesis for nalbuphine HCl and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole 40 and 80 minutes post oral dosing in the mouse antiphenylquinone writhing test. Data were standardized to the ED50 doses of nalbuphine HCl (28.9 or 141 mg/kg) and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole (0.161 or 0.135 mg/kg). Synergism is demonstrated by the regression fitted to ED50 dose levels estimated by probit analysis. Its curvilinearity is statistically significant. The regression is fitted to the data by the method of least squares. Residual squared deviations about the line of best fit are minimized in directions along lines from the origin through respective data points on the isobologram, these lines making angles with X-axis, tan -1 (Y/X). This is accomplished by a transformation prior to the regression analysis. Its inverse is applied to transform the coordinates of the regression curve back to the X,Y coordinates of the isobologram. Let D r be an ED50 dose of a mixture of A and B, where r is the fraction of compound B in the mixture; i.e. ##EQU2## It follows from Equation 1 that ##EQU3## From the additivity hypothesis, the logarithms of the ED50 doses at various mixture ratios are a straight line function of (Log D r ). To test the hypothesis, polynominal regressions, as follows, are fitted to ED50 estimates from experimental data obtained at various mixture ratios: ##EQU4## The additivity hypothesis is refuted if a polynomial of degree higher than one fit the data significantly better than a straight line, ##EQU5## Since X and Y are uniquely determined by F r and r, the coordinates of the regression are transformed readily to the coordinates of the isobologram. If data are scaled to ED50 dose levels of 100 standard dose units, Equation (2) becomes F.sub.s =log 100=2. (2.1) The additivity hypothesis implies that F s is independent of r s, and may be tested by analysis of the regression model ##EQU6## the subscripts, s, indicating that the data are scaled. A statistically significant regression will refute the hypothesis. The method of least squares utilizes jointly the information contained in all of the separate data points. Statistical significance of the curvilinearity of the regression model establishes the existence of synergism (or antagonism) of the compounds in the biological system studied. The parameters in the model describe its intensity over the range of mixture ratios, from 0 to 1, the nature of which is seen readily when the regression is plotted on the isobologram. This method was used to determine the best-fitting ED50 regression line through the seven (7) or eight (8) ED50 data points representing equivalent levels of analgetic activity for each of the five (5) or six (6) dose-ratios for nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole given in Tables I and II. As shown in both of the isobologram plots, FIGS. 1 and 2, the calculated quadratic polynomial &#34;ED50 Regression Line&#34; fits the data significantly better than the straight &#34;ED50 Addition Line&#34; as established by Fisher&#39;s F test, statistically significant at p≦0.05 to compare the goodness of fit between the straight line and curvilinear regressions. Thus, consistent with Loewe&#39;s isobolographic model, the hypothesis of analgetic additivity is refuted and analgetic synergism is established for all combinations of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole. By substitution of the expected analgetic activity of nalbuphine alone and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole alone from test results in other warm blooded mammals, it is possible to use the isobologram in conjunction with the correlation method discussed above to predict the equivalent range of maximum potentiating dosages for man. Thus utilizing the data of the present invention and the equivalent ratios in man, it is predicted that nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole would demonstrate analgetic potentiation over a range of doses exceeding 1:0.000245 to 1:4.6. As described above, all tests of statistical significance establishing the best fit regression equation for the experimental data and its difference from the ED50 Addition Line were carried out using stringent 95% confidence limits. The use of less stringent limits merely reinforces the conclusions. It will be apparent that the instant specification and examples are set forth by way of illustration and not limitation, and that various modifications and changes may be made without departing from the spirit and scope of the present invention. TABLE I__________________________________________________________________________ORAL NALBUPHINE/CII* COMBINATIONS IN THEMOUSE ANTIPHENYLQUINONE WRITHING TEST40 MIN (N = 30 Mice/Dose) ED50 AT 40 MINDRUG COMBINATIONS DRUG DOSE (mg/kg) (95% Confidence Limits)Nalbuphine HCL: Nalbuphine % MICE NalbuphineCII* HCL CII* BLOCKED HCl CII*__________________________________________________________________________Control (0:0) 0 0 6.7% -- --Nalbuphine 5.85 0 16.7% 28.9 0.0Only (1:0) 11.7 0 30.0% (18.7-41.7) 23.4 0 43.3% 46.8 0 70.0% 93.6 0 83.3%1:0.00143 3.5 0.005 3.3% 14.2 0.012 7 0.01 30.0% (10.3-18.9) (0.014-0.026) 14 0.02 50.0% 28 0.04 80.0%1:0.0043 2.44 0.0104 6.7% 10.9 0.045 4.88 0.0208 13.3% (8.62-13.2) (0.036-0.055) 9.75 0.0417 40.0% 19.5 0.0833 90.0% 39 0.167 100.0%1:0.0107 1.95 0.0208 6.7% 7.22 0.074 3.9 0.0416 20.0% (5.61-8.76) (0.058-0.090) 7.8 0.0833 56.7% 15.6 0.167 93.3% 31.2 0.333 100.0%1:0.0214 1.46 0.032 6.7% 3.81 0.079 2.93 0.064 30.0% (3.11-4.50) (0.064-0.093) 5.85 0.125 86.7% 11.7 0.250 100.0% 23.4 0.500 100.0%1:0.0427 0.975 0.0417 6.7% 2.33 0.097 1.95 0.0833 43.3% (1.82-2.80) (0.075-0.116) 3.9 0.167 83.3% 7.8 0.333 100.0% 15.6 0.667 100.0%1:0.107 0.488 0.521 13.3% 1.10 0.114 0.975 0.104 50.0% (0.04-2.49) (0.004-0.259) 1.95 0.208 80.0% 3.9 0.417 100.0% 7.8 0.833 96.7%CII* 0 0.063 10.0% 0.0 0.161Only (0:1) 0 0.125 46.7% (0.120-0.204) 0 0.250 73.3% 0 0.500 93.3%__________________________________________________________________________ *CII = 4,5Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H--imidazole TABLE II__________________________________________________________________________ORAL NALBUPHINE/CII* COMBINATIONS IN THEMOUSE ANTIPHENYLQUINONE WRITHING TEST80 Min (N = 30 Mice/Dose) ED50 AT 80 MINDRUG COMBINATIONS DRUG DOSE (mg/kg) (95% Confidence Limits)Nalbuphine HCl: Nalbuphine % MICE NalbuphineCII* HCl CII* BLOCKED HCl CII*__________________________________________________________________________Control (0:0) 0 0 3.3% -- --Nalbuphine 24.5 0 6.7% 141 0.0Only (1:0) 49 0 26.7% (101-198) 98 0 40.0% 196 0 56.7% 392 0 83.3%1:0.000245 20.4 0.005 13.3% 50.2 0.012 40.8 0.01 40.0% (38.3-62.9) (0.009-0.015) 81.7 0.02 76.7% 163 0.04 90.0% 327 0.08 96.7%1:0.000612 16.3 0.01 13.3% 44.3 0.027 32.7 0.02 26.7% (34.2-54.1) (0.021-0.033) 65.3 0.04 80.0% 131 0.08 96.7% 261 0.16 100.0%1:0.00122 12.3 0.015 10.0% 31.4 0.038 24.5 0.03 30.0% (25.3-37.1) (0.031-0.045) 49 0.06 86.7% 98 0.12 100.0% 196 0.24 100.0%1:0.00245 8.17 0.02 6.7% 22.3 0.055 16.3 0.04 30.0% (17.4-25.8) (0.043-0.063) 32.7 0.08 80.0% 65.3 0.16 100.0% 131 0.32 100.0%1:0.00612 4.08 0.025 10.0% 12.7 0.078 8.17 0.05 30.0% (9.71-15.8) (0.059-0.097) 16.3 0.10 63.3% 32.7 0.20 90.0% 65.3 0.40 100.0%CII* 0 0.03 13.3% 0.0 0.135Only (0:1) 0 0.06 26.7% (0.093-0.223) 0 0.12 56.7% 0 0.24 63.3%__________________________________________________________________________ *CII = 4,5Bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H--imidazole

Summary: Pharmaceutical compositions of nalbuphine and 4,5-bis(4-methoxyphenyl)-2-(trifluoromethylsulfonyl)-1H-imidazole have been found to exhibit unexpectedly enhanced analgesic activity by applying an analysis model which considers data characterizing the analgesic effect of both the pure components as well as the fixed dose ratio combinations. This synergism enables the use of lower doses of either or both drugs with a concomitant reduction in risk of possible side effects.

big_patent

en

Summarize: RELATED APPLICATION [0001] This application is a division of co-pending application Ser. No. 10/818,972 filed Apr. 5, 2004 in the names of Davis, John M., et al. titled Lane Maintenance Machine Having Reciprocating Cleaning Liquid Dispensing Head. TECHNICAL FIELD [0002] The present invention relates to bowling lane maintenance machines and, more particularly, to the cleaning mechanism of such machines used to remove dirt, grime and old lane dressing from the surface of the lane before re-applying conditioning dressing thereto. BACKGROUND AND SUMMARY [0003] Lane maintenance machines that travel up and down the length of a bowling lane removing surface grime and old lane dressing are well known in the art. Some of such machines are combination units which clean the lane in the front half of the machine and apply a fresh film of lane dressing to the lane in the rear half. Other machines are essentially single purpose machines capable of only cleaning the lane or applying the lane dressing. Typically, in machines having a cleaning function, a cleaning liquid is applied and then quickly removed through the use of a vacuum squeegee pickup head and sometimes also a wiping cloth immediately ahead of the squeegee. [0004] Typically, the cleaning liquid is applied using fixed position, pressurized spray nozzles that atomize the liquid and spray it onto the lane surface ahead of the machine. Examples of that type of cleaning system are disclosed in prior U.S. Pat. Nos. 5,729,855 and 6,615,434 owned by the assignee of the present invention. While pressurized, fixed position spray nozzle systems have performed well over the years, they also have certain drawbacks. [0005] For example, the pressurized spray nozzles sometimes drip between spray pulses and at other times, necessitating contrivances to catch and contain such drips. Furthermore, overspray can be a problem wherein the airborne spray droplets are carried by air currents onto adjacent gutters and other structure that must be separately cleaned and maintained from time-to-time. In some establishments having significant air currents, the overspray may even carry into adjacent lanes that have just been cleaned and conditioned. [0006] The present invention provides a solution to problems associated with conventional, fixed position pressurized spray systems. In the present invention, instead of relying only on one or more pressurized nozzles to spray cleaning liquid into the air and allow it to settle onto the lane surface in front of the machine, at least one reciprocating dispensing head is positioned close to the lane surface and travels back and forth across the path of travel of the machine while dispensing a highly controlled volume of cleaning liquid directly onto the surface. The position of the dispensing head as it moves across the width of the lane can be accurately coordinated with the position of the machine along the length of the lane to precisely start and stop liquid flow and produce a predetermined pattern of applied liquid. Board-by-board precision is achievable with this type of system. [0007] Preferably, a positive displacement pump such as a peristaltic pump is utilized to supply cleaning liquid to the dispensing head in successive uniform increments, producing a precisely metered quantity of the liquid. In one form of the invention, the cleaning liquid is not atomized, but rather issues from the dispensing head in a coherent stream to produce a bead of cleaning liquid on the lane surface. In another form of the invention, each increment of liquid is atomized or diffused into small droplets at the point of discharge to cover a larger surface area of the lane. BRIEF DESCRIPTION OF THE DRAWINGS [0008] FIG. 1 is a left front perspective view of a maintenance machine embodying the principles of the present invention with its top cover removed to reveal internal details of construction; [0009] FIG. 2 is a right rear perspective view of the machine; [0010] FIG. 3 is a right front perspective illustration of the cleaning system of the machine and its relationship to certain other components; [0011] FIG. 4 is a left rear perspective illustration of the cleaning system and related components; and [0012] FIG. 5 is a right side elevational view of the machine with the near sidewall thereof removed to reveal internal details of construction. DETAILED DESCRIPTION [0013] The present invention is susceptible of embodiment in many different forms. While the drawings illustrate and the specification describes certain preferred embodiments of the invention, it is to be understood that such disclosure is by way of example only. There is no intent to limit the principles of the present invention to the particular disclosed embodiments. [0014] The machine 10 illustrated in the drawings is similar in many respects to the machine disclosed in U.S. Pat. No. 5,729,855. Accordingly, the &#39;855 patent is incorporated herein by reference. In view of the full disclosure in the &#39;855 patent of the construction and operation of the lane machine, the construction and operation of the machine 10 will be described only generally herein. [0015] The machine 10 has a cleaning system denoted broadly by the numeral 12 and located generally in the front of the machine. A dressing application system is denoted broadly by the numeral 14 and located generally in the rear portion of the machine. These two systems perform their functions as the machine travels up and down the lane through the provision of lane-engaging drive wheels 16 and 18 fixed to a transverse shaft 20 that is powered by a drive motor 22 and a chain and sprocket assembly 24. [0016] The dressing application system 14 includes an applicator roll 26 disposed for engaging the lane surface, a reciprocating dressing dispensing head 28 that travels back and forth across the width of the lane above roll 26, and a brush assembly 30 between roll 26 and dispensing head 28 for receiving dressing from head 28 and delivering it to roll 26. Details of the construction and manner of use of brush assembly 30 are disclosed in co-pending application Ser. No. 10/791,413 filed Mar. 2, 2004, and titled “Strip Brush Bowling Lane Dressing Application Mechanism”, which is incorporated herein by reference. Dressing application system 14 additionally includes a reservoir 32 and a positive displacement pump (not shown) for supplying dressing from reservoir 32 to dispensing head 28. [0017] Dressing dispensing head 28 is mounted for reciprocation along a transverse guide track 34 extending between the sidewalls of the machine. An endless drive belt 36 is secured to head 28 and has its opposite ends looped around a pair of pulleys 38 and 40, the pulley 40 being operably coupled with a reversible motor 42 to provide driving power to belt 36 and thus propel dispensing head 28 along track 34. A pair of sensors 44 and 46 adjacent opposite ends of the path of reciprocal travel of dispensing head 28 are operable to sense the presence of dispensing head 28 as it reaches one limit of its path of travel so as to signal the motor 42 to reverse directions and drive dispensing head 28 in the opposite direction along track 34. [0018] The pulley 38 is fixed to a long fore-and-aft extending shaft 48 disposed just outboard of the right sidewall of the machine. Near its rear end, just forwardly of pulley 38, shaft 48 is provided with a notched wheel 50 whose rotation is sensed by a sensor 52. An output from sensor 52 may be sent to the control system of the machine (not shown) for the purpose of determining the precise location of the dressing dispensing head 28 across the width of the machine and the bowling lane. Such location is coordinated with a particular lane dressing pattern that has been programmed into the control system of the machine so that dressing dispensing head 28 may be actuated to precisely dispense dressing at predetermined locations along its path of reciprocation. Distance down the lane is determined by a pair of lane-engaging wheels 53 ( FIGS. 3, 4 and 5 ) located just in front of the rear wall of the machine. Wheels 53 are fixed to a common cross shaft 54 that rotates a notched wheel 55 ( FIG. 4 ) via a chain drive 56 ( FIG. 3 ). The number of revolutions of notched wheel 55 is detected by a sensor 57 ( FIG. 4 ) that sends a signal to the control system of the machine. [0019] The cleaning system 12 includes one or more cleaning liquid dispensing heads 58 that reciprocate across the path of travel of the machine as it moves along the lane. While system 12 may also include one or more pressurized spray nozzles as in conventional machines, in a preferred embodiment no such conventional spray nozzles are utilized. In the particular embodiment disclosed herein, only a single dispensing head 58 is utilized, such head 58 traveling essentially the full transverse width of the machine to the same extent as the dressing dispensing head 28. [0020] Dispensing head 58 includes a vertically disposed, depending discharge tube 60 provided with a tip 62 that is located close to the lane surface. In one form of the invention, tip 62 is not in the nature of an atomizing nozzle but is instead configured and arranged to emit liquid in a fairly coherent stream so that a bead of cleaning liquid is laid down on the lane surface. One suitable tip 62 for carrying out this particular non-atomizing function is available from the Value Plastics Company of Fort Collins, Colo. as part number VPS5401001N. Other types of tips (not shown) that atomize, breakup or diffuse liquid supplied to the tip may also be utilized where broader surface area coverage by the cleaning liquid is desired. In either case, tip 62 is preferably provided with an internal check valve (not shown). [0021] Cleaning system 12 further includes a guide track 64 attached to the front wall of machine 10 that slidably supports dispensing head 58 for its reciprocal movement. Track 64 extends across substantially the entire width of machine 10 to the same extent as the track 34 associated with dressing dispensing head 28. An endless drive belt 66 is attached to dispensing head 58 for providing reciprocal drive thereto, the belt 66 at its opposite ends being looped around a pair of pulley wheels 68 and 70 respectively. [0022] Although pulley 68 may be driven in a number of different ways, including by its own separate drive motor, in a preferred form of the invention pulley 68 is fixed to the forwardmost end of shaft 48 from pulley 38 so that both dispensing heads 28 and 58 are driven by the same reversible motor 42. Consequently, both dressing dispensing head 28 and cleaning liquid dispensing head 58 are reciprocated simultaneously by motor 42 when the latter is actuated. However, it will be noted that dressing dispensing head 28 and cleaning liquid dispensing head 58 reciprocate in mutually opposite directions due to the fact that dressing dispensing head 28 is secured to the upper run 36 a of its drive belt 36 while cleaning liquid dispensing head 58 is secured to the lower run 66 b of its drive belt 66. [0023] Cleaning system 12 further includes a cleaning solution reservoir 72 at the rear of machine 10. A supply line 74 leading from reservoir 72 is coupled in flow communication with a peristaltic pump 76 driven by a chain and sprocket assembly 78 operably coupled with the drive shaft 20 of lane drive wheels 16 and 18. When drive wheels 16 and 18 are turning, pump 76 is operating. It will be appreciated, however, that pump 76 could be driven by its own separate drive motor. An outlet line 80 from pump 76 leads to an inlet port of a solenoid-controlled valve 82 whose operation is controlled by the control system of machine 10. A supply line 84 leading from one outlet port of valve 82 communicates the valve 82 with discharge tube 60 of dispensing head 58, while a return line 86 communicates another outlet port of valve 82 with reservoir 72. Thus, depending upon the position of control valve 82, cleaning liquid may either be pumped to dispensing head 58 from reservoir 72 or by-passed back to reservoir 72 via return line 86. Because pump 76 is preferably a peristaltic pump, it supplies liquid to dispensing head 58 in constant volume slugs or squirts that enable the cleaning liquid to be very precisely and accurately metered onto the lane surface. Furthermore, it permits the supply of liquid to dispensing head 58 to be essentially instantaneously stopped and started, which, in conjunction with control valve 82, affords precise, board-by-board control over the pattern of cleaning liquid applied to the lane surface by dispensing head 58. [0024] Cleaning system 12 additionally includes a wiping assembly 88 immediately behind cleaning liquid dispensing head 58. Assembly 88 includes a web 90 of soft material such as duster cloth looped around a lower compressible back-up member 92 in the nature of a roller that extends across the full width of the machine. Cloth 90 is stored on a roll 94 and is paid out at intervals selected by the operator and taken up by a takeup roll 96. Wiping assembly 88 is similar in principle to the corresponding wiping assembly disclosed in U.S. Pat. No. 6,615,434, which patent is hereby incorporated by reference into the present specification. [0025] A further component of cleaning system 12 comprises a vacuum pickup head 98 located behind wiping assembly 88. Vacuum pickup head 98 extends essentially the full width of machine 10 and includes a pair of flexible, squeegee-type blades 100 and 102 that assist in picking up the thin film of cleaning liquid left on the lane surface after the wiping assembly 88 has acted upon the liquid. A large vacuum hose 104 leads from pickup head 98 to a holding tank 106 for storing liquid picked up by head 98. Vacuum pressure within holding tank 106 is obtained by means of a suction fan (not shown) coupled with tank 106. [0000] Operation [0026] In use, machine 10 is energized and controlled through the use of a user interface panel 108 located adjacent the right rear corner of the machine. Using interface panel 108, any one of a number of different patterns may be selected for applying cleaning liquid to the lane surface and for the application of dressing. Details of the oil pattern application using the dressing dispensing head 28 are described in the incorporated U.S. Pat. No. 5,729,855. [0027] With respect to cleaning operations, as machine 10 travels along the lane surface the cleaning liquid dispensing head 58 reciprocates back and forth along its track 64 across the full width of the lane. Depending upon the distance down the lane as detected by the lane distance sensor 57 and the position of the dispensing head 58 across the width of the lane as detected by the transverse position sensor 52, control valve 82 allows cleaning liquid from constantly operating pump 76 to be squirted onto the lane surface through the outlet tube 60 and tip 62 of dispensing head 58. Although it is contemplated that dispensing head 58 may dispense cleaning liquid to the lane across the full width of the lane, it is also within the scope of the present invention to have cleaning liquid applied on a board-by-board basis for selective stripping or cleaning of the lane surface. The check valve (not shown) within tube 60 or tip 62 instantly closes the discharge path for cleaning liquid from head 58 when control valve 82 is shifted to a non-dispensing position. The check valve thus prevents leakage from dispensing head 58 during periods of non-use and provides a sharp demarcation between the presence and absence of cleaning liquid on the lane surface. [0028] Cleaning liquid deposited by head 58 is immediately wiped into a thin film by cloth 90 looped around the backup roll 92 of wiping mechanism 88. While much of the liquid and oil and dirt are removed by cloth 90, a thin film remains, and this is engaged by the squeegees 100 and 102 of vacuum pickup head 98. Pickup head 98 thus lifts all remaining moisture, oil and grime from the lane surface and deposits it in the holding tank 106. Finally, as the rear of the machine passes over the cleaned region, the lane dressing is applied by applicator roll 26 in the pattern selected by the operator. [0029] The inventor(s) hereby state(s) his/their intent to rely on the Doctrine of Equivalents to determine and assess the reasonably fair scope of his/their invention as pertains to any apparatus not materially departing from but outside the literal scope of the invention as set out in the following claims.

Summary: A lane maintenance machine has a cleaning system that includes at least one cleaning liquid dispensing head which reciprocates back and forth transversely of the lane as the machine travels along the length of the lane. In a preferred embodiment the dispensing head emits successive squirts of liquid from a positive displacement pump, such as a peristaltic pump. The positive displacement pump provides accurate, precise metering of the cleaning liquid and affords board-by-board control of the dispensing action. A wiping assembly immediately behind the cleaning liquid dispensing head provides a web of cloth-like material looped under a compressible backup roller to wipe the applied liquid into a thin film and to pick up a measure of the liquid along with oil and dirt. A vacuum squeegee pickup head trailing the wiping assembly lifts the remaining film of cleaning liquid completely off the lane surface, whereupon lane dressing is applied at the rear of the machine utilizing a dressing dispensing head that, like the cleaning liquid dispensing head, reciprocates transversely of the lane to dispense dressing in a pattern preselected by the operator.

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Write a title and summarize: Les parlementaires béninois ont voté contre la levée de l'immunité parlementaire de Barthélémy Kassa, jeudi 20 août 2015 Kassa Ces derniers temps, Barthélémy Kassa faisait profil bas. Yeux légèrement enfoncés, visage mafflu avec l’embonpoint qui va avec, il forçait son sourire depuis qu’une commission spéciale du Parlement béninois avait été mise en place, le 10 août, pour étudier la levée de son immunité, demandée par la présidence sous la pression des Pays-Bas, appuyée par le procureur général. L’ancien ministre de l’énergie et de l’eau, élu au Parlement aux législatives d’avril 2015, va désormais pouvoir se montrer plus serein. Jeudi 20 août en fin de journée, 45 députés sur 83 ont refusé la levée de son immunité après avoir repoussé l’échéance lundi 17 août en n’allant pas s’asseoir dans l’hémicycle. M. Kassa devait être entendu — les Pays-Bas l’exigeaient avant toute reprise de la coopération avec le Bénin — par la Haute Cour de justice (l’instance chargée de juger les personnalités au sommet de l’Etat) pour examiner son éventuelle implication, ainsi que celle de plusieurs fonctionnaires et hommes d’affaires, dans le détournement de 4 millions d’euros d’aide publique néerlandaise au détriment d’un programme d’aménagement hydraulique. Ce pilier du camp présidentiel est soupçonné d’avoir couvert un vaste réseau de fraude au sein de son ministère. Lire aussi Corruption au Bénin : les députés du pouvoir aux abonnés absents Durant la période d’incertitude, Barthélémy Kassa, pourtant connu pour s’exhiber devant les caméras de télévision et y chanter les louanges du président Boni Yayi, fuyait les médias. Nos demandes d’entretien étaient restées lettre morte et c’est par hasard que nous l’avions croisé, jeudi 6 août, à l’Assemblée nationale. « Je sais que vous cherchez à me voir. Mais le moment n’est pas propice pour une entrevue », avait-il lâché avant de s’éclipser. « Une richesse insolente » Ce n’est un secret pour personne, Barthélémy Kassa est riche et puissant. On lui prête une fortune à dix chiffres, bien que personne n’en connaisse le montant exact. Ce qui est certain, c’est que son influence dépasse la sphère du parti au pouvoir et s’étend à l’opposition. Le vote du Parlement de jeudi en sa faveur a fait le plein des voix du clan présidentiel (41 voix) tout en réussissant à rallier quatre députés de l’opposition, pourtant majoritaire à l’Assemblée. Victor Topanou, ancien secrétaire général du gouvernement, puis garde des sceaux, a côtoyé M. Kassa au gouvernement entre 2006 et 2010. Il garde le souvenir d’un homme « très exubérant et d’une turbulence excessive. Il avait tendance à afficher une certaine arrogance et une richesse insolente ». Victor Topanou dit s’être souvent interrogé sur l’origine de la fortune de Barthélémy Kassa, entré au gouvernement en 2008 comme ministre des recherches pétrolières et minières. « Je trouvais suspect qu’un professeur assistant à l’université qui n’a pas d’à-côtés ni un passé d’opérateur économique puisse offrir un amphithéâtre à l’université d’Abomey-Calavi [la plus grande université du Bénin]. Je ne parlerai pas du luxe de ses maisons. Cela fait beaucoup, même pour un ministre du gouvernement dont le salaire mensuel est connu [deux millions de francs CFA, soit 3 000 euros]. » Barthélémy Kassa vit à Abomey-Calavi, au nord de Cotonou, dans un grand domaine d’où émergent à l’abri des regards indiscrets trois villas de haut standing. Toujours à Cotonou, il posséderait au moins une autre maison et, proche de l’hôtel Azalai, un immeuble. Il aligne une dizaine de voitures, avec une préférence pour les grosses cylindrées, dont une Acura MDX. Mais, ce 6 août, à l’Assemblée nationale, un concessionnaire était venu livrer des véhicules de fonction aux nouveaux élus. Le choix de Barthélémy Kassa s’est porté sur une plus modeste Kia 4 × 4 Sportage. « Un jour, en conseil des ministres, se souvient Victor Topanou, Barthélémy Kassa lance : “Topanou, c’est le théoricien, mais quand il faut agir, on ne le voit pas!” Comme pour dire qu’il a de l’argent et pas moi. » Pour les proches de M. Kassa, la lecture de Victor Topanou est celle d’un intellectuel aigri. « Kassa fonce tête baissée. Il est courageux et n’a jamais peur », affirme l’un de ses proches collaborateurs au ministère. Fauteur de trouble en périodes électorales Agronome de formation et professeur assistant à l’université, Barthélémy Kassa commence sa carrière politique entre 2003 et 2004, lorsqu’il entre au Parlement en tant que suppléant de Daniel Tawema, l’un de ses mentors et cacique du régime Mathieu Kérékou, appelé au gouvernement. Bien qu’il manque de peu sa réélection à l’hémicycle en 2007, il est en 2008, l’un des représentants des Forces Cauris pour un Bénin émergent (FCBE), le parti au pouvoir, au sein de la Commission électorale nationale autonome (CENA), chargée de conduire les élections municipales, communales et locales. Il y affiche une certaine impudence. « La tâche n’a pas été de tout repos avec les représentants de la mouvance présidentielle », se rappelle Pascal Todjinou, président à l’époque de la CENA et représentant reconnu de la société civile. « Nous avons dû reprendre trois fois de suite l’élection du bureau, parce que les membres de la mouvance, en particulier M. Kassa, formaient à chaque fois recours devant la cour suprême. Toujours dans le but de saccager les travaux », se rappelle M. Todjinou. Pis, l’homme serait allé jusqu’à soustraire des documents pour faire invalider des décisions de plénière qui n’étaient pas favorables au parti présidentiel. Barthélémy Kassa avait été contraint à démissionner de son poste de ministre de l'eau et de l'énergie au Bénin, après des accusations de détournement de 4 millions d’euros d’aide publique néerlandaise au détriment d’un programme d’aménagement hydraulique. Kassa « C’est son côté délinquant », sourit un membre de la CENA chargé de coordonner les élections législatives de 2007. Qui poursuit : « Lors des législatives en 2007, il a tenté de soudoyer les agents de bureau de sa région d’origine, Materi [600 km au nord-ouest de Cotonou], souvent sur un ton badin, afin de tripatouiller les résultats des urnes. » Laudateur du chef de l’Etat Outsider élu en 2006, c’est à partir de l’année suivante que le président Thomas Boni Yayi affermit son pouvoir, renforcé par les élections municipales et communales de 2008. « Et pour remercier Barthélémy Kassa pour son activisme pendant ces périodes électorales, estime Victor Topanou, le président lui fait de la place dans son gouvernement, en octobre 2008. » Barthélémy Kassa commence ainsi, avec le portefeuille des mines et des recherches pétrolières, son ascension au sein du régime. Laudateur invétéré du chef de l’Etat, celui que les médias locaux surnomment « le ministre du ciel et de la terre » s’impose comme un pilier du gouvernement. L’une de ses phrases de l’époque est restée dans les esprits : « Quand Yayi dit d’aller à gauche, on va à gauche ; quand Yayi dit d’aller à droite, on va à droite. Quand Yayi dit : “ couchez-vous pour que je passe ”, on se couche. C’est ça la fidélité. » Il est sorti du gouvernement après les législatives de 2011, où il réussit, cette fois, à être élu. Mais Barthélémy kassa se voit confier une nouvelle fois le ministère de l’énergie et de l’eau, en plus du département des mines, en 2013. Il y reste jusqu’à sa démission forcée après l’éclatement du scandale du détournement de fonds hollandais, en mai 2015. Une image de philanthrope Au sein de ce ministère s’exécutent des projets d’exploration pétrolière, de construction de centrales thermiques, ainsi que le programme pluriannuel d’appui au secteur eau et assainissement (PPEA), financé par les Pays-Bas. C’est dans ce cadre qu’un vaste réseau de prévaricateurs a été mis en place, soustrayant 4 millions d’euros aux 66 du programme. L’audit du cabinet Kroll, mandaté après l’éclatement du scandale, note qu’« aucun flux financier au profit du ministre Kassa n’a été relevé ». Pour un cadre de l’administration publique, au fait des procédures de passation de marchés publics, cela ne veut rien dire : « les ministres prennent toujours leur commission en espèces », dit-il. Le rapport Kroll révélait aussi le détournement de cinq autres milliards de francs CFA (environ 7 millions d’euros) dans d’autres ministères. Fort de son statut de ministre de l’énergie et de l’eau, il facilite l’accès à l’énergie et à l’eau potable dans sa commune rurale d’origine, Matéri, l’une des plus pauvres du Bénin. Cela concourt à le rendre très populaire sur ses terres. « Avant l’arrivée du ministre Kassa, il n’y avait rien ici. Ses actions ont développé la commune de Matéri. Et quand les étrangers viennent du Burkina, ils constatent un véritable changement », témoigne un habitant de Matéri. Barthélémy Kassa se forge aussi une image de philanthrope en prenant en charge les frais d’université d’étudiants de sa localité et en les hébergeant gracieusement. A Matéri, où l’ancien ministre possède plusieurs biens immobiliers (une visite des lieux avec des habitants permet d’en compter cinq), et envisagerait de construire un vaste complexe hôtelier, le taux de scolarité et de réussite scolaire est très bas. « Les étudiants, une fois le bac obtenu, n’ont souvent personne à Cotonou, où se trouvent les meilleurs lieux de formation, et n’ont pas les moyens de les intégrer. Barthélémy Kassa nous aide à financer nos études », confie un étudiant ayant bénéficié de ses largesses. Mutisme des parlementaires A l’Assemblée nationale, la forte pression des Pays-Bas a donné lieu à la mise en place d’une commission spéciale pour étudier la demande de la levée d’immunité parlementaire du ministre Kassa. C’était sans compter la grande influence de l’homme qui aurait financé les campagnes électorales de certains de ses collègues députés. « La levée de l’immunité parlementaire requiert les deux tiers des députés. Mais au regard de la configuration politique dans l’hémicycle, ce n’est pas gagné d’avance, estimait avant le vote Wilfried Léandre Houngbédji, journaliste et analyste politique. Il va falloir miser sur la bonne volonté politique du gouvernement et de son chef pour instruire les 33 députés FCBE de voter dans ce sens, et espérer que les élus d’opposition votent favorablement aussi.» C’est raté. Des députés du parti au pouvoir et de l’opposition contactés par Le Monde Afrique avant le vote avaient refusé de s’exprimer, à l’instar de Candide Azannaï, pourtant acerbe envers le parti au pouvoir et son mode de gouvernance. « Je ne suis pas disposé à répondre à vos questions. Je vous souhaite du courage pour la suite de votre travail », avait-il lâché avant de raccrocher. Barthélémy Kassa avait laissé penser que s’il devait couler, il ne coulerait pas seul. Entendu par la commission le 10 août, il aurait refusé d’être le seul à parler, déclarant qu’il n’était pas « celui qui signait les décaissements qui vont au Trésor public. C’était le ministre de l’économie et des finances, Komi Koutché. » Cette commission parlementaire de dix membres avait émis un avis neutre sur la demande de la levée d’immunité du député estimant, contrairement aux Pays-Bas, qu’il n’y a pas suffisamment d’éléments de preuve qui engageaient la responsabilité pénale de l’ancien ministre. Le résultat du vote au Parlement laisse de fait de nombreuses questions ouvertes. Le président Boni Yayi a-t-il encouragé les siens à protéger son « ministre du ciel et de la terre »? Comment va réagir le premier ministre, le béninois-français Lionel Zinsou, qui prône un comportement irréprochable des élus et des hauts fonctionnaires? Et surtout, comment vont riposter les Pays-Bas, dont les programmes de développement, toujours interrompus, sont essentiels pour l’accès à l’eau potable au Bénin et pour la protection de Cotonou contre les inondations? La suite au prochain épisode.

Title: Bénin: Barthélémy Kassa, l'opportuniste exubérant du système Boni Yayi Summary: Surprise: le Parlement béninois a refusé de lever l'immunité de l'un des siens, soupçonné de détournements de fonds néerlandais et affichant une richesse insolente. Le coup est dur pour les Pays-Bas, qui exigeaient sa traduction en justice. Qui est Barthélémy Kassa, l'auteur de ce coup de maître?

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Write a title and summarize: Melioidosis is a frequently fatal disease requiring specific treatment. The yield of Burkholderia pseudomallei from sites with a normal flora is increased by culture using selective, differential media such as Ashdown’s agar and selective broth. However, since melioidosis mainly affects people in resource-poor countries, the cost effectiveness of selective culture has been questioned. We therefore retrospectively evaluated this in two laboratories in southeast Asia. The results of all cultures in the microbiology laboratories of Mahosot Hospital, Vientiane, Laos and Angkor Hospital for Children, Siem Reap, Cambodia, in 2017 were reviewed. We identified patients with melioidosis who were only diagnosed as a result of culture of non-sterile sites and established the total number of such samples cultured using selective media and the associated costs in each laboratory. We then conducted a rudimentary cost-effectiveness analysis by determining the incremental cost-effectiveness ratio (ICER) per DALY averted and compared this against the 2017 GDP per capita in each country. Overall, 29 patients in Vientiane and 9 in Siem Reap (20% and 16. 9% of all culture-positive patients respectively) would not have been diagnosed without the use of selective media, the majority of whom (18 and 8 respectively) were diagnosed by throat swab culture. The cost per additional patient detected by selective culture was approximately $100 in Vientiane and $39 in Siem Reap. Despite the different patient populations (all ages in Vientiane vs. only children in Siem Reap) and testing strategies (all samples in Vientiane vs. based on clinical suspicion in Siem Reap), selective B. pseudomallei culture proved highly cost effective in both settings, with an ICER of ~$170 and ~$28 in Vientiane and Siem Reap, respectively. Selective culture for B. pseudomallei should be considered by all laboratories in melioidosis-endemic areas. However, the appropriate strategy for implementation should be decided locally. Burkholderia pseudomallei is the causative agent of melioidosis, an important but under-recognised public health problem throughout the tropics [1]. It grows readily in clinical samples from normally sterile sites, such as blood cultures, aseptically aspirated pus from abscesses or body fluids. In sites with a normal flora, where it may be overgrown by other bacteria, the yield of culture can be improved by using selective differential media, such as Ashdown’s agar and broth, that suppress the growth of other organisms and encourage the formation of characteristic colonies [2,3]. We have used these media routinely in our laboratories in melioidosis-endemic areas for more than 30 years, and have shown that they increase the number of cases of melioidosis diagnosed [3–11]. However, we have been fortunate to have research funding to support the associated costs of additional media, which would not be available to the majority of laboratories in endemic areas that have to make difficult decisions about the allocation of more limited resources. Melioidosis is unevenly distributed across endemic areas and others have questioned whether the routine use of selective media is cost effective [12,13]. We therefore decided to review the cost-effectiveness of our current approach during 2017 in two different settings that used different strategies for the deployment of selective media for B. pseudomallei culture. The testing strategies in the 2 hospitals were different. In Vientiane, all throat swabs, pus and wound swabs, sputum and endotracheal aspirates, and urine samples received were cultured using selective media for B. pseudomallei. Throat swabs, which were sent specifically for B. pseudomallei culture from patients in whom melioidosis was suspected, were routinely cultured using selective media alone (one ASH plate and one SB) since previous experience has shown us that B. pseudomallei is rarely present in large numbers in such samples and is difficult to detect amongst the large numbers of colonies of other species that are invariably present on non-selective media [3]. Pus and wound swabs, sputum and endotracheal aspirates were cultured on ASH and SB in addition to non-selective media. The centrifuged deposit of urine samples was cultured on half an ASH plate in addition to routine semi-quantitative culture on chromogenic agar. All SB were subcultured onto half an ASH plate. In Siem Reap, selective media were used only when the responsible clinician indicated a suspicion of melioidosis on the request form. Laboratory methods were similar to those used in Vientiane except that whole ASH plates were used for urine culture (half for neat urine and half for the centrifuged deposit) and SB subculture. The consumable costs per Ashdown’s plate and broth were calculated for the additional selective media based on the prices of the ingredients in Thailand, where both laboratories purchase consumables and which was considered representative of melioidosis-endemic areas in Asia. These equated to 10 baht (approx. $0. 31) per ASH and 8 baht (approx. $0. 25) per SB. In both laboratories, colonies suspected of being B. pseudomallei were screened by Gram stain, oxidase test and latex agglutination. Routine confirmation of identity was by API 20NE (bioMérieux, Basingstoke, UK). We performed a rudimentary cost-effectiveness analysis as an indication as to whether the incremental costs of selective media would represent a judicious use of scarce resources in the two settings. The approach is similar to that used in a previous cost-effectiveness analysis of candidate melioidosis vaccines [14]. We considered the total additional costs for consumables for selective media and applied an additional 30 minutes of a microbiologist’s time per sample, costed at $2. 90 per hour based on accounting records at the Cambodia site. We used an estimated 3% mortality rate in non-bacteraemic melioidosis patients when identified and treated, based on the literature [15] and our own data (mortality in non-bacteraemic cases 3. 95% in Vientiane and 0. 7% in Siem Reap), as compared with a mortality rate of 9% when undetected, based on the reported mortality before the introduction of modern treatment regimens [16]. We assumed that each death averted was associated with 66 Disability-Adjusted Life Years (DALYs) in Siem Reap, a paediatric hospital where the mean patient age was 5. 7 years, and 37 DALYs in Vientiane where the mean patient age was 38. 5 years, using the country-specific estimated life expectancy of individuals at this age [17]. The incremental cost-effectiveness ratio (ICER) per DALY averted was calculated by dividing the incremental costs of consumables and labour divided by the total number of DALYs averted (Eq 1). The ICER was compared against the Laos and Cambodia 2017 GDP per capita ($2,457 and $1,384, respectively) to determine whether the use of selective media would be cost-effective. All samples were submitted primarily for the purposes of routine diagnosis. In addition, many of the patients were included in studies of the aetiology of fever. In Cambodia the study was approved by the AHC Institutional Review Board (AHC IRB, 979–14) and the Oxford Tropical Research Ethics Committee (OxTREC 550–14). In Laos the study was approved by the Oxford Tropical Research Ethics Committee (OxTREC 006–07) and the Lao National Ethics Committee for Health Research (028–17). For these studies, patients or their parents or guardians provided written informed consent. During 2017,145 patients with culture-positive melioidosis were diagnosed in Vientiane, of whom 64 (44. 1%) were only diagnosed by culture of 82 non-sterile sites. In Siem Reap, there were 53 cases of culture-positive melioidosis of whom 45 (84. 9%) were only diagnosed by culture of 46 non-sterile sites (one patient was positive in superficial swab specimens from two anatomical sites). The breakdown of the positive samples and the media which were positive is shown in Table 1 and full results for individual culture-positive patients are given in S1 Table. Eighteen patients in Vientiane and eight in Siem Reap were diagnosed by throat swab culture only, but most of these were positive on direct plating on ASH and only one positive throat swab in Vientiane and three in Siem Reap were detected by SB enrichment alone. The majority of pus samples and wound swabs were positive on non-selective media, with an additional four (9. 1% of positives) detected through the use of ASH in Vientiane (with growth of small numbers of B. pseudomallei on ASH but no growth on non-selective plates) and none in Siem Reap, but the only additional yield from the use of SB for pus and wound swabs was from a single specimen in Siem Reap. Two of the specimens positive on ASH but not on non-selective media were swabs rather than pus and one was taken after several weeks of treatment. The numbers of positive sputum and endotracheal aspirates and urine samples were small and confined to Vientiane. More than half of the positive respiratory samples were only positive using selective media. Two patients in Vientiane were only diagnosed with melioidosis as a result of culture of a centrifuged deposit of urine on ASH. Overall, in Vientiane 27 patients (18. 6% of all culture-positive patients) would not have been diagnosed without the use of ASH, the majority of whom were only positive on throat swab culture, and an additional two (1. 4%) would not have been diagnosed without the use of SB. In Siem Reap, five (9. 4%) would not have been diagnosed without the use of ASH and four (7. 5%) would not have been diagnosed without the use of SB. During 2017 the Vientiane laboratory processed 2,130 throat swabs, 1,796 urines, 728 pus or wound swabs, 350 deep pus, 346 sputum and 142 ET aspirates. Table 2 shows the estimated consumable costs of the selective media used in processing these samples and the cost of detecting an additional case of melioidosis by using either ASH or SB on each sample type. The total consumable cost of using these additional selective media throughout the year was $2,921. 02, meaning that the total consumables costs of each of the 29 additional cases detected using our current approach was almost exactly $100. The cost per additional positive sample detected varied considerably, from approximately $25 for an ASH plate on a throat swab to nearly $200 or more for the use of SB on each sample type. In Siem Reap, 416 samples were cultured during the year using selective media on the basis of clinical request at a consumables cost of $349. 60, and this resulted in the diagnosis of nine cases of melioidosis that would not have been confirmed had selective media not been used, meaning that the consumable cost of selective culture per additional case detected was only approximately $39. The cost per additional positive detected was approximately $7. 60 for culture of a throat swab on ASH and ranged between approximately $23 and $150 for the additional use of SB. The additional 29 cases detected in Vientiane would corresponed with 64. 4 DALYs averted, at a total cost of ~$10,966 including both consumables and labour, with an ICER of ~$170 per DALY averted. In Cambodia where only 416 samples were cultured with selective media the total cost was ~$903; the additional 9 detected cases would correspond with 31. 9 DALYs averted and an ICER of ~$28; in both settings the use of selective media would therefore appear to be higly cost-effective, with an ICER well below the GDP per capita in their respective settings. The additional yield from using selective media for culture of sites with a normal flora to detect patients with melioidosis is well established [3–9]. Overall the use of selective media in this study was responsible for the diagnosis of 20% of all the cases of melioidosis in Vientiane and 16. 9% of the cases in Siem Reap, considerably more than in our previous study conducted in northeast Thailand nearly 30 years ago (3. 5%) [3]. Since selective media only were used for throat swabs, it is not possible to compare the relative yields of selective and non-selective media, although in our previous studies B. pseudomallei grew on non-selective media from only 9 of 118 culture-positive throat throat swabs [3]. However, the relative benefit of using selective media will depend on several factors such as the local incidence of melioidosis, local clinical practice, the laboratory testing strategy adopted, and the cost of the media themselves. Understanding the local costs and benefits of different approaches is clearly of importance to laboratory managers in melioidosis-endemic areas who have to make decisions about the most effective way to deploy scarce resources in order to bring about the greatest benefit to patients. This question came up repeatedly during a recent workshop on melioidosis in Cambodia [18], prompting us to undertake the current analysis. While further context-specific analyses are advised, our findings from two different settings indicate that more extensive use of selective media than is commonly practiced in many endemic areas is likely to be highly cost-effective. There has been one previous attempt to estimate the cost-effectiveness of selective culture for melioidosis diagnosis [13]. This study, which took place in Kuala Lumpur, Malaysia, an area of relatively low melioidosis incidence, and predominantly entailed respiratory samples, estimated the costs to detect one additional culture and patient as $25 and $75, respectively. Another study in Kampong Cham Provincial Hospital, Cambodia found that only one additional B. pseudomallei positive sample was identified amongst 241 sputum samples cultured using SB and ASH. Clearly the local incidence of melioidosis is likely to be one of the factors with the greatest impact on the cost effectiveness of selective culture. However, the testing strategy adopted (e. g. using selective culture on all samples of particular types as opposed to culturing only those from patients in whom clinicians indicate a suspicion of melioidosis) will also have a major impact on cost-effectiveness. Overall, in our study the costs of selective media per additional case detected varied considerably between the two laboratories as a result of the difference in screening strategy. In Vientiane, the cost of selective media using the current approach was approximately $380 per additional case diagnosed (including both consumables and labour) as opposed to only $100 in Siem Reap. The relative benefits of adding SB enrichment also varied between the sites, with only 2 of 39 samples that were positive by selective culture alone in Vientiane being detected through broth enrichment as opposed to 4 of 9 in Siem Reap. Clearly there are differences between the patient populations in the two centres, with patients in Vientiane being from all age groups whereas only children were included in Siem Reap, which might have affected the quality of the samples collected. While this emphasises the fact that decisions about the most appropriate culture strategy needs to be decided at a local level, the very low ICERs imply that more extensive use of selective media could cost-effectively yield additional gains. This is particularly likely in Cambodia, where the use of selective media was restricted to patients in whom the clinician suspected melioidosis. Assuming a willingness to pay $1,384 per DALY averted (the Cambodia GDP per capita), spending up to $50 per patient on selective media cultures in other patients would remain cost-effective even if the prevalence of undetected cases in these patients was as low as 1%. In both sites, culture of a throat swab on ASH was confirmed as an effective strategy for detecting patients with melioidosis who were not diagnosed in other ways. In Vientiane, the majority of throat swabs are submitted specifically for the investigation of melioidosis. This does not reflect the presence of pharyngitis in most of these patients, but is likely mainly to represent contamination of the throat by lower respiratory tract secretions. It is not common practice in Laos for clinicians to send sputum for bacteriological culture. Had this been the case, the additional benefit from culture of throat swabs is likely to have been less. However, culture of sputum and ET aspirates on ASH was also relatively cost-effective in Vientiane. The additional benefit from using ASH for culture of pus/wound swabs and urine samples was less than that for throat swabs, and therefore correspondingly less cost-effective, but both methods did detect some patients with melioidosis who would not have been diagnosed in other ways. The use of ASH for culture of pus from previously undrained abscesses is unlikely to be worthwhile, as in melioidosis this is likely to grow pure B. pseudomallei, although occasional dual infections (e. g. with Staphylococcus aureus) can occur. However, the use of ASH is more likely to be of benefit in superficial wound swabs and abscesses that have already ruptured, as these may be colonised with a range of flora that could outgrow B. pseudomallei on non-selective media, or in patients on treatment. We consider that the culture of the centrifuged deposit of a urine sample on ASH is also worthwhile in all patients suspected of having melioidosis, as in some patients this may be the only positive sample, and the number of organisms present is often well below the threshold for ‘significant bacteriuria’ with other pathogens, even in patients with prostatic involvement [6]. There are several approaches that might be used to reduce the costs associated with selective culture to detect B. pseudomallei. These include the omission of SB enrichment for some or all samples, the use of half rather than whole plates, the use of cheaper media, and the testing of only selected specimens rather than all specimens of a particular type. Several other media have been recommended for the selective isolation of B. pseudomallei from clinical samples [7,19–23]. Our study has focused only on the use of ASH and SB, which were the media in use in our laboratories during 2017. Studies comparing B. pseudomallei selective media on clinical samples are relatively rare and further comparative evaluations of different formulations would be useful, although it is unlikely that any other media would be significantly cheaper than ASH and SB. One issue of particular concern is that ASH relies on gentamicin to suppress Gram negative organisms and as the prevalence of antimicrobial resistance increases it may become less effective and new formulations may become necessary [23]. The use of half plates is worthy of consideration, although this can make colonies of B. pseudomallei more difficult to pick out from other local flora. In conclusion, this analysis has caused us to review our own approach to the use of selective media for the diagnosis of melioidosis. In any patients with suspected melioidosis we recommend that, in addition to blood culture, a throat swab, or a good quality sputum sample if available, should be sent specifically for culture on ASH and in SB, and a centrifuged deposit of urine should also be cultured on ASH. In areas of high melioidosis incidence, we also recommend the use of ASH and SB for any sputum and endotracheal aspirates received from patients with pneumonia. However, we do not consider that the routine use of selective media for culture of pus samples and wound swabs is warranted unless the request form specifically requests investigation for melioidosis. Others must decide on the appropriate way to deploy selective media according to their local epidemiology, clinical practice and available resources.

Title: The cost-effectiveness of the use of selective media for the diagnosis of melioidosis in different settings Summary: Melioidosis is a frequently fatal disease caused by a soil bacterium called Burkholderia pseudomallei, that is widespread in the rural tropics. Because staff are often not familiar with it and because it may be hidden if it is outgrown by other bacteria, special culture media can help laboratories diagnose the disease. However, this costs more money so it is not always done even in areas where the disease is known to be present. We have looked at the results of a year's bacterial cultures in two different laboratories in southeast Asia to identify how many patients were only identified using these special culture techniques, how much it cost, and whether the investment was considered worthwhile in terms of the gain in healthy life years in these patients who might otherwise have died had the disease not been diagnosed. Even though the laboratories adopted very different strategies for using the special media and served very different populations, in both places the use of the special techniques was very cost effective in terms not just of lives saved, but on purely financial grounds when compared with the GDP of each country.

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Write a title and summarize: SECTION 1. SHORT TITLE. This Act may be cited as the ``High-Tech Port Security Act of 2003''. SEC. 2. DEFINITIONS. In this Act: (1) Captain-of-the-port.--The term ``Captain-of-the-Port'', with respect to a port, means the individual designated by the Commandant of the Coast Guard as the Captain-of-the-Port at that port. (2) Container.--The term ``container'' means a cargo container designed or used for the international transportation of merchandise by vessel. (3) Blast-resistant container.--The term ``blast-resistant container'' means a container that incorporates blast-resistant technology and has been certified as a blast-resistant container by the Secretary pursuant to section 101. (4) Regulated container.--The term ``regulated container'' means a container that is manufactured after the date that is 15 months after the date the Secretary prescribes regulations under section 101. (5) Secretary.--The term ``Secretary'' means the Secretary of the Department of Homeland Security. (6) Vessel.--The term ``vessel'' has the meaning given that term in section 401 of the Tariff Act of 1930 (19 U.S.C. 1401). TITLE I--PORT SECURITY AND SAFE CARGO SEC. 101. BLAST-RESISTANT CONTAINERS. (a) Regulations.--Not later than 90 days after the date of the enactment of this Act, the Secretary shall prescribe regulations-- (1) establishing standards for the certification of blast- resistant containers; (2) establishing the procedure by which interested parties may apply for such certification, including the submittal of prototypes and cost estimates; and (3) requiring that, effective on and after the date that is 15 months after the date such regulations are prescribed by the Secretary, no vessel carrying 1 or more regulated containers and seeking to enter the United States shall be allowed such entry unless all such regulated containers are certified blast- resistant containers pursuant to the standards and procedures described in this section. (b) Certification.--The Secretary shall evaluate each application for certification submitted pursuant to the regulations described in paragraphs (1) and (2) of subsection (a), and shall notify each applicant whether such container is certified as blast-resistant-- (1) not later than the date that is 90 days after the application is submitted, if such application is submitted not later than the date that is 90 days after the Secretary prescribes such regulations under subsection (a); or (2) not later than such other date as may be established by the Secretary pursuant to such regulations, if such application is submitted after the date that is 90 days after the date the regulations are prescribed. (c) Deadline.-- (1) Generally.--Not later than 15 months after the date the Secretary prescribes regulations under subsection (a), the Secretary shall deny entry of a vessel into the United States if any of the regulated containers carried by such vessel are not certified under subsections (a) and (b). (2) Extension of deadline.--The Secretary may extend the deadline under paragraph (1) for up to 1 year if the Secretary-- (A) determines that none of the prototypes with respect to which applications have been submitted prior to such deadline are economically feasible; and (B) submits a report (which may be in classified form) to the Committee on Commerce, Science, and Transportation of the Senate and the Committee on Transportation and Infrastructure of the House of Representatives describing-- (i) the reasons for such extension; and (ii) such steps as the Secretary deems necessary or appropriate to ensure that economically feasible prototypes exist prior to the extended deadline. SEC. 102. SCREENING PRIOR TO DEPARTURE FROM PORT. (a) Regulations.--Not later than 90 days after the date of the enactment of this Act, the Secretary shall prescribe regulations-- (1) establishing standards for the certification of equipment designed to screen a container carried by a vessel entering the United States for radioactive and explosive materials before the container leaves the port; (2) establishing the procedure by which interested parties may apply for such certification, including the submittal of prototypes and cost estimates; and (3) requiring that, effective on and after the date that is 15 months after the date such regulations are prescribed by the Secretary, every container carried by a vessel entering the United States shall be screened for radioactive and explosive materials before the container leaves the port. (b) Certification.--The Secretary shall evaluate each application for certification submitted pursuant to the regulations described in paragraphs (1) and (2) of subsection (a), and shall notify each applicant whether the screening equipment is certified for purposes of screening containers for radioactive and explosive materials-- (1) not later than the date that is 90 days after the application is submitted, if such application is submitted not later than the date that is 90 days after the Secretary prescribes such regulations under subsection (a); or (2) not later than such other date as may be established by the Secretary pursuant to such regulations, if such application is submitted after the date that is 90 days after the date the regulations are prescribed. (c) Screening Equipment Deployment.-- (1) Twenty largest ports.--The Secretary shall take all necessary action, including providing grants to ports, to ensure that, not later than 15 months after the date the Secretary prescribes regulations under subsection (a), the 20 largest ports in the United States, as determined by the Secretary under section 201(a)(1), and any other United States ports determined by the Secretary to be highly vulnerable, have deployed screening equipment certified under subsections (a) and (b). (2) Other ports.--The Secretary shall take all necessary action to ensure that every other port in the United States deploys such certified screening equipment as soon as practicable. (d) Mandatory Screening Deadline.--Not later than the date that is 15 months after the date the Secretary prescribes regulations under subsection (a), the Secretary shall require that any container carried by a vessel entering any of the 20 largest ports in the United States, and any other United States port determined by the Secretary to be highly vulnerable, shall be screened for radioactive and explosive materials before the container leaves the port. TITLE II--PROTECTION OF LARGEST PORTS SEC. 201. COMMAND AND CONTROL CENTERS. (a) Establishment of Command and Control Centers.--Not later than 90 days after the date of the enactment of this Act, the Secretary shall-- (1) identify the 20 largest ports in the United States, as measured by the number of containers processed annually at each port; and (2) in coordination with the Captain-of-the-Port and other officials responsible for security matters at each such port, develop a plan to establish a command and control center for the purpose of coordinating, monitoring, and managing all of the security operations at the port. (b) Grants.-- (1) In general.--The Secretary shall establish a grant program for providing funds to port authorities, facility operators, and State and local agencies to develop and implement the command and control centers under subsection (a)(2). (2) Application.--Each entity seeking a grant under this subsection shall submit an application to the Secretary at such time, in such manner, and accompanied by such information as the Secretary may reasonably require. TITLE III--AUTHORIZATION OF APPROPRIATIONS SEC. 301. AUTHORIZATION OF APPROPRIATIONS. There is authorized to be appropriated to the Secretary $100,000,000 for the purpose of carrying out this Act.

Title: A bill to protect United States ports, and for other purposes Summary: High-Tech Port Security Act of 2003 - Instructs the Secretary of the Department of Homeland Security to prescribe regulations: (1) establishing certification standards and procedures for blast-resistant containers; and (2) prohibiting entry into the United States of any vessel carrying regulated containers after such regulations are prescribed unless they are all certified blast-resistant. Directs the Secretary to: (1) establish standards for the certification of equipment designed to screen a container carried by a vessel entering the United States for radioactive and explosive materials before the container leaves the port; (2) take action to ensure that the twenty largest domestic ports (and any others determined highly vulnerable) have deployed such certified screening equipment; and (3) establish command and control centers at the twenty largest domestic ports.

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Summarize: AUSTIN (KXAN) — A husband and wife accused of running a prostitution ring posing as a massage parlor in northwest Austin were revealed after hundreds of condoms clogged part of their sewage system. On Feb. 7, a detective was assigned to investigate Jade Massage Therapy, at 11416 N. Farm to Market 620 — near Anderson Mill Road — after getting a tip from the property’s management company about possible prostitution at the massage parlor. It was the second such tip the Austin Police Department had received in the last three months. The company said they had recently taken over the property and became aware of the problem when an industrial waste disposal unit connecting the property to the city sewer became clogged and destroyed by the condoms, according to a police affidavit. Several tenants had already contacted the company, concerned that prostitution was taking place at Jade Massage. Investigators found that husband and wife Joseph Emery, 54, and Juan Wang, 49, were listed as the tenants for the business. Police found that just two days before, on Feb. 5, Wang was stopped during security screening at Austin-Bergstrom International Airport after a number of small duct-taped bundles of cash were found in her carry-on luggage, totaling $30,000. Wang told an officer she was on her way to China for a medical procedure and needed the money to pay for it. She said the money was from Jade Massage, where she claimed to make $20,000 a year. When the officer pointed out that she was carrying more than a year’s worth of income, police say Wang became “visibly nervous” and had difficulty answering any more questions. She then told officers that her husband does their taxes. Police contacted Emery who said his wife keeps the money under a mattress at home and that it comes from their business. Wang was then allowed to continue on her way to China with the $30,000. Detectives found that there were numerous advertisements for Jade Massage on backpage.com, a website police say is often used by people selling sexual services. On March 7 and 15, detectives stopped men coming out of Jade Massage. The two men admitted to receiving sexual services in exchange for cash. Police say the clients who frequented the massage parlor would tip between $40-$120 on top of a standard $60 massage charge. Police executed search warrants on both the business and the couple’s home on Alameda Trace Circle in northwest Austin on March 22. Wang was found inside the business with a completely naked man. A second naked man was found in another room with a female masseuse. A third woman was also found inside the business. Detectives say that in businesses associated with human trafficking, the prostitutes are also made to live inside the business. At their home, more than $60,000 in cash was found inside a safe. Wang told officers that she would find women to work for her through a friend, but claimed to be unable to remember the friend’s name. She also claimed to be unable to name any woman, other than one of the women present during the search warrant, who had worked for her in the past year. Both Wang and Emery, when interviewed by police, initially claimed that the other was in charge of the business and their cash. Wang and Emery have been charged with both engaging in organized criminal activity and money laundering. Emery’s bond was set at $53,000 and Wang’s at $45,000. Neither were listed as currently held in the Travis County Jail. 'Hundreds of condoms' destroy pipe, police raid Texas massage parlor A husband and wife accused of operating an Austin prostitution ring are facing felony charges following an investigation that began when police discovered a waste pipe connected to the business was clogged with "hundreds of condoms," according to records. Juan Wang and her husband, Joseph Emery, the owners of Jade Massage Therapy LLC, each face a charge of engaging in organized criminal activity. Neither suspect was listed as an inmate at the Travis County Jail on Tuesday afternoon. The investigation into the massage parlor began Feb. 7, when the property manager for the Jade Massage location in the 11400 block of North Ranch Road called police to express her suspicion that prostitution was happening at the business. RELATED: SAPD: Armed assailant robbed man of pickup truck at North Side car wash She "became aware of a problem when an industrial waste disposal unit connecting the property to city sewer services became clogged and destroyed by hundreds of condoms," affidavits for Wang and Emery state. The property manager's tip was the second complaint of possible prostitution at Jade Massage that police had received in three months. After the discovery of the destroyed pipes, police searched Backpage.com, which often solicits prostitution services, for advertisements for the business. They found several. Advertisements for Jade Massage were posted on Backpage.com as often as two to three times per day, the affidavits state. RELATED: Pot found in truck that hit church bus near Leakey, DPS says In the following weeks, police staked out Jade Massage's second location in the 9100 block of Anderson Mill Road. Officers pulled over a couple of suspected john's who had gone into the massage parlor, who allegedly both admitted that they had paid for sexual services during their time inside. On March 22, members of the Austin Police Department Human Trafficking Unit and members of the Criminal Conspiracy Unit executed search warrants at the Alameda Trace Circle location. Inside, Wang was found inside a room with a nude man, and another woman was found inside a different room with another nude male, the affidavit states. Police simultaneously executed a search warrant at Wang and Emery's home and discovered over $65,000 in a safe. RELATED: Boarded-up East Side home goes up in flames, arson investigators on scene Further investigation into the couple revealed Wang had been stopped Feb. 5 at Austin Bergstrom International Airport by a TSA agent who found $30,000 in "duct taped bundles" of cash in her possession. She claimed the money was earned from her massage business and that she was taking it with her to China to pay for a medical procedure. She was allowed to pass through with the money, but only after the agent called Emery to verify her story. Both Wang and Emery would later tell police that they didn't know the names of their employees, who were all located and recruited by a "friend." Ledgers for Jade Massage showed no payments to the women, but they did show that Jade Massage's customers, almost all of whom were men, regularly tipped between $40 and $120 on top of a $60 charge. cdowns@mysa.com Twitter: @calebjdowns

Summary: Neighbors of Jade Massage Therapy in Austin, Texas, had their suspicions about the place, but it was a property manager's unusual find that helped bring about prostitution charges-a broken pipe linking the business to the sewer had been clogged by hundreds of used condoms, reports MySanAntonio. "It's not the normal... lead you would get on a place committing criminal activity, but it happened," an officer tells the Austin American-Statesman. "I was like, 'You've got to be kidding me.'" It wasn't the only find to raise suspicion. Two days before authorities learned of the pipe on Feb. 7, parlor owner Juan Wang had been stopped at an airport with $30,000 in cash, according to an arrest affidavit. A "visibly nervous" Wang told authorities she had saved the money for a procedure in China, though she said she made only $20,000 a year. She then provided a phone number that was linked to a Backpage.com account advertising sexual services at Jade Massage, the affidavit says. Men later admitted paying for sexual services there, per KXAN, and during a search on March 22, Wang and another woman were each found in a room with a naked man, police say. Ledgers revealed that clients left tips of 200% or so on a $60 massage. Wang and her husband, Joseph Emery-who allegedly told police they didn't know the names of their employees-face charges of engaging in organized criminal activity and money laundering.

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Write a title and summarize: SECTION 1. SHORT TITLE. This Act may be cited as the ``Middle Class Tax Cut Act of 2011''. TITLE I--PAYROLL TAX RELIEF SEC. 101. TEMPORARY PAYROLL TAX CUT FOR EMPLOYERS, EMPLOYEES AND THE SELF-EMPLOYED. (a) Wages.--Notwithstanding any other provision of law-- (1) with respect to remuneration received during the payroll tax holiday period, the rate of tax under 3101(a) of the Internal Revenue Code of 1986 shall be 3.1 percent (including for purposes of determining the applicable percentage under sections 3201(a) and 3211(a) of such Code), and (2) with respect to remuneration paid during the payroll tax holiday period, the rate of tax under 3111(a) of such Code shall be 3.1 percent (including for purposes of determining the applicable percentage under sections 3221(a) and 3211(a) of such Code). (3) Subsection (a)(2) shall only apply to-- (A) employees performing services in a trade or business of a qualified employer, or (B) in the case of a qualified employer exempt from tax under section 501(a), in furtherance of the activities related to the purpose or function constituting the basis of the employer's exemption under section 501. (4) Subsection (a)(2) shall apply only to the first $5 million of remuneration or compensation paid by a qualified employer subject to section 3111(a) or a corresponding amount of compensation subject to 3221(a). (b) Self-Employment Taxes.-- (1) In general.--Notwithstanding any other provision of law, with respect to any taxable year which begins in the payroll tax holiday period, the rate of tax under section 1401(a) of the Internal Revenue Code of 1986 shall be-- (A) 6.2 percent on the portion of net earnings from self-employment subject to 1401(a) during the payroll tax period that does not exceed the amount of the excess of $5 million over total remuneration, if any, subject to section 3111(a) paid during the payroll tax holiday period to employees of the self-employed person, and (B) 9.3 percent for any portion of net earnings from self-employment not subject to subsection (b)(1)(A). (2) Coordination with deductions for employment taxes.--For purposes of the Internal Revenue Code of 1986, in the case of any taxable year which begins in the payroll tax holiday period-- (A) Deduction in computing net earnings from self- employment.--The deduction allowed under section 1402(a)(12) of such Code shall be the sum of (i) 4.55 percent times the amount of the taxpayer's net earnings from self-employment for the taxable year subject to paragraph (b)(1)(A) of this section, plus (ii) 7.65 percent of the taxpayer's net earnings from self- employment in excess of that amount. (B) Individual deduction.--The deduction under section 164(f) of such Code shall be equal to the sum of (i) one-half of the taxes imposed by section 1401 (after the application of this section) with respect to the taxpayer's net earnings from self-employment for the taxable year subject to paragraph (b)(1)(A) of this section plus (ii) 62.7 percent of the taxes imposed by section 1401 (after the application of this section) with respect to the excess. (c) Regulatory Authority.--The Secretary may prescribe any such regulations or other guidance necessary or appropriate to carry out this section, including the allocation of the excess of $5 million over total remuneration subject to section 3111(a) paid during the payroll tax holiday period among related taxpayers treated as a single qualified employer. (d) Definitions.-- (1) Payroll tax holiday period.--The term ``payroll tax holiday period'' means calendar year 2012. (2) Qualified employer.--For purposes of this paragraph, (A) In general.--The term ``qualified employer'' means any employer other than the United States, any State or possession of the United States, or any political subdivision thereof, or any instrumentality of the foregoing. (B) Treatment of employees of post-secondary educational institutions.--Notwithstanding paragraph (A), the term ``qualified employer'' includes any employer which is a public institution of higher education (as defined in section 101 of the Higher Education Act of 1965). (3) Aggregation rules.--For purposes of this subsection rules similar to sections 414(b), 414(c), 414(m) and 414(o) shall apply to determine when multiple entities shall be treated as a single employer, and rules with respect to predecessor and successor employers may be applied, in such manner as may be prescribed by the Secretary. (e) Transfers of Funds.-- (1) Transfers to federal old-age and survivors insurance trust fund.--There are hereby appropriated to the Federal Old- Age and Survivors Trust Fund and the Federal Disability Insurance Trust Fund established under section 201 of the Social Security Act (42 U.S.C. 401) amounts equal to the reduction in revenues to the Treasury by reason of the application of subsections (a) and (b) to employers other than those described in (e)(2). Amounts appropriated by the preceding sentence shall be transferred from the general fund at such times and in such manner as to replicate to the extent possible the transfers which would have occurred to such Trust Fund had such amendments not been enacted. (2) Transfers to social security equivalent benefit account.--There are hereby appropriated to the Social Security Equivalent Benefit Account established under section 15A(a) of the Railroad Retirement Act of 1974 (45 U.S.C. 231n-1(a)) amounts equal to the reduction in revenues to the Treasury by reason of the application of subsection (a) to employers subject to the Railroad Retirement Tax. Amounts appropriated by the preceding sentence shall be transferred from the general fund at such times and in such manner as to replicate to the extent possible the transfers which would have occurred to such Account had such amendments not been enacted. (f) Coordination With Other Federal Laws.--For purposes of applying any provision of Federal law other than the provisions of the Internal Revenue Code of 1986, the rate of tax in effect under section 3101(a) of such Code shall be determined without regard to the reduction in such rate under this section. SEC. 102. TEMPORARY TAX CREDIT FOR INCREASED PAYROLL. (a) In General.--Notwithstanding any other provision of law, each qualified employer shall be allowed, with respect to wages for services performed for such qualified employer, a payroll increase credit determined as follows: (1) With respect to the period from October 1, 2011 through December 31, 2011, 6.2 percent of the excess, if any, (but not more than $12.5 million of the excess) of the wages subject to tax under section 3111(a) of the Internal Revenue Code of 1986 for such period over such wages for the corresponding period of 2010. (2) With respect to the period from January 1, 2012 through December 31, 2012, (A) 6.2 percent of the excess, if any, (but not more than $50 million of the excess) of the wages subject to tax under section 3111(a) of the Internal Revenue Code of 1986 for such period over such wages for calendar year 2011, minus (B) 3.1 percent of the excess (if any) of-- (i) the lesser of $5,000,000 or such wages for calendar year 2012, over (ii) such wages for calendar year 2011. (3) In the case of a qualified employer for which the wages subject to tax under section 3111(a) of the Internal Revenue Code of 1986 (a) were zero for the corresponding period of 2010 referred to in subsection (a)(1), the amount of such wages shall be deemed to be 80 percent of the amount of wages taken into account for the period from October 1, 2011 through December 31, 2011 and (b) were zero for the calendar year 2011 referred to in subsection (a)(2), then the amount of such wages shall be deemed to be 80 percent of the amount of wages taken into account for 2012. (4) This subsection (a) shall only apply with respect to the wages of employees performing services in a trade or business of a qualified employer or, in the case of a qualified employer exempt from tax under section 501(a) of the Internal Revenue Code of 1986, in furtherance of the activities related to the purpose or function constituting the basis of the employer's exemption under section 501. (b) Qualified Employers.--For purposes of this section-- (1) In general.--The term ``qualified employer'' means any employer other than the United States, any State or possession of the United States, or any political subdivision thereof, or any instrumentality of the foregoing. (2) Treatment of employees of post-secondary educational institutions.--Notwithstanding subparagraph (1), the term ``qualified employer'' includes any employer which is a public institution of higher education (as defined in section 101 of the Higher Education Act of 1965). (c) Aggregation Rules.--For purposes of this subsection rules similar to sections 414(b), 414(c), 414(m) and 414(o) of the Internal Revenue Code of 1986 shall apply to determine when multiple entities shall be treated as a single employer, and rules with respect to predecessor and successor employers may be applied, in such manner as may be prescribed by the Secretary. (d) Application of Credits.--The payroll increase credit shall be treated as a credit allowable under Subtitle C of the Internal Revenue Code of 1986 under rules prescribed by the Secretary of the Treasury, provided that the amount so treated for the period described in subsection (a)(1) or subsection (a)(2) shall not exceed the amount of tax imposed on the qualified employer under section 3111(a) of such Code for the relevant period. Any income tax deduction by a qualified employer for amounts paid under section 3111(a) of such Code or similar Railroad Retirement Tax provisions shall be reduced by the amounts so credited. (e) Transfers to Federal Old-Age and Survivors Insurance Trust Fund.--There are hereby appropriated to the Federal Old-Age and Survivors Trust Fund and the Federal Disability Insurance Trust Fund established under section 201 of the Social Security Act (42 U.S.C. 401) amounts equal to the reduction in revenues to the Treasury by reason of the amendments made by subsection (d). Amounts appropriated by the preceding sentence shall be transferred from the general fund at such times and in such manner as to replicate to the extent possible the transfers which would have occurred to such Trust Fund had such amendments not been enacted. (f) Application to Railroad Retirement Taxes.--For purposes of qualified employers that are employers under section 3231(a) of the Internal Revenue Code of 1986, subsections (a)(1) and (a)(2) of this section shall apply by substituting section 3221 for section 3111, and substituting the term ``compensation'' for ``wages'' as appropriate. TITLE II--SURTAX ON MILLIONAIRES SEC. 201. SURTAX ON MILLIONAIRES. (a) In General.--Subchapter A of chapter 1 of the Internal Revenue Code of 1986 is amended by adding at the end the following new part: ``PART VIII--SURTAX ON MILLIONAIRES ``Sec. 59B. Surtax on millionaires. ``SEC. 59B. SURTAX ON MILLIONAIRES. ``(a) General Rule.--In the case of a taxpayer other than a corporation for any taxable year beginning after 2012, there is hereby imposed (in addition to any other tax imposed by this subtitle) a tax equal to 3.25 percent of so much of the modified adjusted gross income of the taxpayer for such taxable year as exceeds $1,000,000 ($500,000, in the case of a married individual filing a separate return). ``(b) Inflation Adjustment.-- ``(1) In general.--In the case of any taxable year beginning after 2013, each dollar amount under subsection (a) shall be increased by an amount equal to-- ``(A) such dollar amount, multiplied by ``(B) the cost-of-living adjustment determined under section 1(f)(3) for the calendar year in which the taxable year begins, determined by substituting `calendar year 2011' for `calendar year 1992' in subparagraph (B) thereof. ``(2) Rounding.--If any amount as adjusted under paragraph (1) is not a multiple of $10,000, such amount shall be rounded to the next highest multiple of $10,000. ``(c) Modified Adjusted Gross Income.--For purposes of this section, the term `modified adjusted gross income' means adjusted gross income reduced by any deduction (not taken into account in determining adjusted gross income) allowed for investment interest (as defined in section 163(d)). In the case of an estate or trust, adjusted gross income shall be determined as provided in section 67(e). ``(d) Special Rules.-- ``(1) Nonresident alien.--In the case of a nonresident alien individual, only amounts taken into account in connection with the tax imposed under section 871(b) shall be taken into account under this section. ``(2) Citizens and residents living abroad.--The dollar amount in effect under subsection (a) shall be decreased by the excess of-- ``(A) the amounts excluded from the taxpayer's gross income under section 911, over ``(B) the amounts of any deductions or exclusions disallowed under section 911(d)(6) with respect to the amounts described in subparagraph (A). ``(3) Charitable trusts.--Subsection (a) shall not apply to a trust all the unexpired interests in which are devoted to one or more of the purposes described in section 170(c)(2)(B). ``(4) Not treated as tax imposed by this chapter for certain purposes.--The tax imposed under this section shall not be treated as tax imposed by this chapter for purposes of determining the amount of any credit under this chapter or for purposes of section 55.''. (b) Clerical Amendment.--The table of parts for subchapter A of chapter 1 of the Internal Revenue Code of 1986 is amended by adding at the end the following new item: ``part viii. surtax on millionaires.''. (c) Section 15 Not to Apply.--The amendment made by subsection (a) shall not be treated as a change in a rate of tax for purposes of section 15 of the Internal Revenue Code of 1986. (d) Effective Date.--The amendments made by this section shall apply to taxable years beginning after December 31, 2012.

Title: A bill to create jobs by providing payroll tax relief for middle class families and businesses, and for other purposes Summary: Middle Class Tax Cut Act of 2011 - Reduces employment tax rates in calendar year 2012 (payroll tax holiday period) for both employers and employees to 3.1%. Limits the reduction for employers to the first $5 million of wages paid by the employer in 2012. Reduces the tax rate on the first $5 million of net earning of a self-employed taxpayer. Allows nongovernmental employers a tax credit for payroll increases in the last quarter of 2011 and in 2012. Appropriates funds to the social security trust funds to compensate for any revenue loss to such funds from the reduction in rates and the tax credit allowed by this Act. Amends the Internal Revenue Code to impose on individual taxpayers in taxable years beginning after 2012 an additional tax equal to 3.25% of so much of their modified adjusted gross income as exceeds $1 million. Defines "modified adjusted gross income" as adjusted gross income reduced by any deduction allowed for investment interest. Provides for an inflation adjustment to the $1 million threshold amount for taxable years beginning after 2013.

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Write a title and summarize: Extraparenchymal neurocysticercosis (ExPNCC), an infection caused by Taenia solium cysticerci that mainly occurs in the ventricular compartment (Ve) or the basal subarachnoid space (SAb), is more severe but less frequent and much less studied than parenchymal neurocysticercosis (ParNCC). Demographic, clinical, radiological, and lumbar cerebrospinal fluid features of patients affected by ExPNCC are herein described and compared with those of ParNCC patients. 429 patients with a confirmed diagnosis of neurocysticercosis, attending the Instituto Nacional de Neurología y Neurocirugía, a tertiary reference center in Mexico City, from 2000 through 2014, were included. Demographic information, signs and symptoms, radiological patterns, and lumbar cerebrospinal fluid (CSF) laboratory values were retrieved from medical records for all patients. Data were statistically analyzed to assess potential differences depending on cyst location and to determine the effects of age and sex on the disease presentation. In total, 238 ExPNCC and 191 ParNCC patients were included. With respect to parenchymal cysts, extraparenchymal parasites were diagnosed at an older age (P = 0. 002), chiefly caused intracranial hypertension (P < 0. 0001), were more frequently multiple and vesicular (P < 0. 0001), and CSF from these patients showed higher protein concentration and cell count (P < 0. 0001). SAb patients were diagnosed at an older age than Ve patients, and showed more frequently seizures, vesicular cysticerci, and higher CSF cellularity. Gender and age modulated some traits of the disease. This study evidenced clear clinical, radiological, and inflammatory differences between ExPNCC and ParNCC, and between SAb and Ve patients, and demonstrated that parasite location determines different pathological entities. Neurocysticercosis (NCC) is caused by the establishment of the larval stage of Taenia solium in the central nervous system. NCC is still endemic in a significant portion of low-income countries in Asia, Africa, and Latin America. The recent but highly noticeable emergence of human NCC in the USA and to a lesser extent in some European countries has fostered a growing medical concern about this neglected parasitic disease [1,2]. One of the most evident traits of NCC is a great clinical heterogeneity [3,4]. Several elements are relevant in this observation, like patient-related factors (age, sex, genetic background) and disease-related issues (number, stage, and location of parasites) [5,6]. With respect to parasite location in the central nervous system, most cysts are located in the parenchyma or in the sulci of the subarachnoid space of the convexity (ParNCC). While these parasites are actually lodged in two different compartments, they are generally grouped together as they share common characteristics in term of symptoms, diagnosis, treatment, and prognosis, and because sometimes it is difficult to differentiate them by neuroradiological studies. ParNCC has been extensively studied: Its main symptom is epilepsy [7,8]; the parasite can be easily recognized by neuroradiological studies [9], and cysticidal treatment clearly improves most patients [10,11]. On the contrary, much less is known about extraparenchymal NCC (ExPNCC), occurring when cysticerci are lodged in the subarachnoid space of the basal cisterns, Sylvian fissure, and spinal medulla or in the ventricular system; such lack of information is probably due to a lower prevalence and the higher difficulties for its diagnosis [12,13]. Although reviews and case reports of ExPNCC have been published [14–22], large series of patients are scarce. Some of them were conducted before MRI was extensively used [23,24], and thus fail to describe it thoroughly. Other papers are mainly focused on treatment [25,26], and the most recent one, describing all NCC cases diagnosed in one hospital at the United States between 1997 and 2005, only reports 35 ExPNCC cases [27]. The appearance of parasites in this location, especially in the subarachnoid space, is frequently different from ParNCC. They generally appear like a cluster of grapes, and thus were termed racemose cysts. They occur when cysts are lodged in a place that allows for unusual growth, and arise from the segmentation of cysticercus cellulosae following the development of interconnected new cysts, which generally lack of a scolex [28]. They are larger than parenchymal cysts and are identified on magnetic resonance imaging (MRI) as multiple cystic lesions [29]. Considering this context, the aim of this study was to describe the demographic, clinical, radiological, and lumbar CSF features of ExPNCC patients and to compare them with ParNCC cases. This study was conducted in accordance with local clinical research regulations and was approved by the Institutional Review Board and Ethical Committee of the Instituto Nacional de Neurología y Neurocirugía (Mexico City). All patients (parents or guardians in the case of children) gave written informed consent, and all analyzed data were anonymized. In total, 429 Mexican patients who attended for the first time the INNN Neurocysticercosis Clinic in Mexico City from 2000 through 2014 were included in this study. Patients attending the Clinic before 2007 were retrospectively included by retrieving information from each patient’s clinical and radiological records. From 2007 onwards, patients were included prospectively. NCC diagnosis was based on pathology results (50 patients, 11. 6%), imaging findings (only cranial computed tomography in 16 patients, all of them with calcified disease only, showing no symptoms suggesting extraparenchymal locations, and both computed tomography and magnetic resonance imaging in all others), clinical and lumbar CSF features, as well as the response to specific treatment. Response to specific treatment was defined as the occurrence of any change in size (decrease) or intensity (increase) in one or more parasites, 4 to 6 months after treatment. All patients included were regarded as ParNCC or ExPNCC, considering the latest diagnosis criteria [30]. Patients were divided into three groups depending on parasite location, according to imaging studies: Par (parenchyma or subarachnoid sulci of the convexity), ExP (subarachnoid space of the Sylvian fissure, basal cisterns, medulla, and ventricles), and mixed (Mx, parenchymal and extraparenchymal). Examples of parenchymal, subarachnoid, and ventricular parasites are shown in Figs 1,2 and 3, respectively. Parasite degenerating stages were defined according to the classical scale, as published elsewhere [30]. Racemose parasites were defined as multiple vesicular parasites without scolex located in one same extraparenchymal region. All patients included were diagnosed in the INNN and had not received specific NCC treatment before. All patient features herein reported (clinical, radiological, and inflammatory) are pre-treatment. The assessed variables were: age at diagnosis, sex, area of provenance, symptoms, lumbar CSF characteristics, and the number and degenerative stage of cysts. The presence of specific antibodies and of the HP10 antigen in lumbar CSF and serum was assayed by ELISA in a subset of patients, using previously published protocols [31,32]. Data were processed in Excel (Microsoft, Redmond, VA) and SPSS 15. 0 (SPSS Inc., Chicago, IL), and reported as proportion or mean ± standard deviation. Statistical comparisons between variables were performed using either parametrical or non-parametrical tests, depending on data distribution. Categorical variables were compared by the chi-squared test with Yates correction or Fisher’s exact test, while mean comparison was made using Student’s t-test, ANOVA (with Bonferroni or Tamhane post-hoc test when appropriate), or Mann-Whitney test. Correlations between numeric variables were assessed using the Pearson coefficient of correlation and checking for outliers and leverage. Normality was checked using the Kolmogorov-Smirnov test. Dichotomous dependent variables were analyzed using logistic regression to take into account the possible effects of confounding variables. For the same purpose, continuous dependent variables were analyzed using multifactorial analysis of variance, including covariables. Variance homogeneity was tested using Levene’s test; Welch correction was used when variances were not statistically similar. Differences were regarded as statistically significant when P-value was less than 0. 05. Of the total 429 patients included, 125 showed extraparenchymally-located parasites (ExP), 191 showed parenchymally-located parasites (Par), and 113 showed cysts in both compartments (ExP+Par: Mx). Most patients (359,83. 7%) were from urban areas, defined as having a population of more than 2500 inhabitants (National Institute of Statistics, INEGI, Mexico). The number of patients diagnosed by year varied from 14 (in 2000) to 46 (in 2008), with no significant trend in the period of inclusion (R = 0. 46, P = 0. 44) (Fig 4). The main characteristics of the patients included in the three groups are shown in Table 1. Table 1 (P2) shows that ExPMx patients are diagnosed at an older age than Par patients, and also exhibited intracranial hypertension, inflammatory CSF and racemose cysts in a significantly higher frequency. Similar results were obtained in a multivariate analysis, controlling for gender and age. ICH (OR: 27. 1, CI95%: 14. 2–51. 9, P < 0. 0001), the presence of antibodies and antigens (OR: 20. 6, CI95%: 9. 56–44. 3, P < 0. 0001, and OR: 6. 2, CI95%: 2. 15–17. 9, P = 0. 001, respectively), higher CSF cellularity and protein concentration (P < 0. 0001), and the presence of vesicular cysts, racemose cysts, and multiple degenerating cysts (OR: 15. 86, CI95%: 9. 38–26. 8, P < 0. 0001; OR: 6. 0, CI95%: 3. 3–10. 9, P < 0. 0001; OR: 5. 00, CI95%: 2. 0–10. 4, P < 0. 0001, respectively) were more frequently observed in ExPMx than in Par patients, while seizures were associated with the Par group (OR: 10. 39, CI95%: 6. 5–16. 6, P < 0. 001). Male ExPMx patients were diagnosed at an older age than female patients (43. 5 ± 13. 0 vs. 39. 9 ± 12. 6, P = 0. 03); degenerating cysticerci were more frequent in females than in males (36,31. 6% vs. 22,17. 9%, P = 0. 01); CSF cellularity was higher in females (105. 3 ± 359. 4 vs. 95. 7 ± 149. 2, P = 0. 05), and CSF protein concentration was higher in males (236. 9 ± 677. 2 vs. 108. 6 ± 230. 3, P = 0. 001). Vesicular cysticerci were observed at an older age than other parasite stages (42. 2 ± 12. 6 years vs. 37. 5 ± 15. 2 years), although the difference was at the limit of statistical significance (P = 0. 06). Additionally, protein concentration increased with age (P < 0. 05), and this result persisted when controlling for gender (R = 0. 14; P = 0. 04). Neither gender nor age modulated the clinical presentation of ExPMx patients. Regarding clinical features, males showed higher seizure frequency (P = 0. 004), while females showed a higher ICH frequency (P = 0. 03); headache was associated with an older age (41. 4 ± 12. 6 vs. 36. 3 ± 12. 7, P = 0. 01), while seizures correlated with a younger age (42. 2 ± 12. 0 vs. 36. 4 ± 12. 8 years, P = 0. 009). Multivariate analysis only confirmed that seizures were associated with male gender (OR: 3. 39; CI95%: 1. 6–7. 3). With regard to parasite degenerative stage, uni- and multivariate analysis showed that vesicular parasites were more frequent in males (OR: 2. 23; CI95%: 1. 2–4. 1), while patients lodging only calcified parasites at diagnosis time were more frequently female (OR: 2. 0; CI95%: 1. 1–3. 6). No other differences between genders or associated with age were observed, particularly with respect to CSF characteristics. Two main groups of ExPMxNCC patients can be distinguished: those lodging cysticerci in the ventricles (Ve) and those with parasites in the basal subarachnoid cisterns (SAb). Comparing these two groups by univariate analysis after excluding those patients showing parasites in both compartments (Table 3), age at diagnosis was significantly earlier in Ve patients. Seizures, CSF inflammatory parameters, multiple vesicular parasites, and the presence of specific antibody and antigens were more frequent in SAb patients, while the presence of single degenerating parasites was more frequent in Ve patients. In multivariate analysis controlling for age and gender, the association of the following variables with Sab location persisted: seizures (OR: 4. 33, CI95%: 1. 63–11. 52, P = 0. 003), CSF cellularity (P = 0. 002) and CSF protein concentration (P = 0. 008), antibody presence (OR: 7. 39, CI95%: 1. 28–42. 64, P = 0. 025), and antigen presence (OR: 8. 04, CI95%: 2. 57–25. 14, P < 0. 0001), presence of vesicular cysts (OR: 18. 44, CI95%; 3. 95–85. 99, P < 0. 0001), and presence of racemose cysts (OR: 25. 89, CI95%: 8. 3–80. 2, P < 0. 0001). Differences in clinical features, cyst degenerating stage, and CSF inflammatory characteristics were evaluated in patients with positive and negative antigen detection. While no differences in the evaluated variables were found in both groups, a tendency (P = 0. 07) to higher CSF protein concentration was noted in HP10-negative SAb patients. The demographic, clinical, radiological, and inflammatory status at diagnosis time of 238 ExPNCC was herein compared with that of 191 ParNCC patients. This study represents the first extended patient series with confirmed ExPNCC, the less frequent but also the most severe NCC form. With respect to demographic variables, male/female ratio was not statistically different between ParNCC and ExPNCC patients, nor between SAb and Ve patients. On the other hand, patients with ExPNCC were diagnosed at a significantly older age than patients with parenchymal cysts; among ExPNCC patients, age at diagnosis was significantly older in patients with subarachnoid than ventricular parasites. In this respect, it is interesting to note that age at diagnosis of Par patients was similar to Ve patients. This may be due to the fact that subarachnoid parasites must reach larger sizes than parenchymal and ventricular ones before causing symptoms. Indeed, parasites in the subarachnoid compartment have no contact with cerebral structures when their size is small due to the wide space available in the subarachnoid cisterns. Symptoms will only be evident when cysts reach such a size that they obstruct CSF flow or have a mass effect affecting cerebral structures; additionally, when cysts have contact with arachnoid/ependymal tissues or blood vessels, they cause signs related with arachnoiditis/ependymitis or vasculitis. So, latency period between infection and symptoms appearance is probably much longer in patients with subarachnoid parasites than in other locations. Most patients came from urban areas, as reported in previous studies [33]. Some considerations should be made to correctly interpret this finding. First, we defined rurality as proposed by the Mexican Institute of Statistic and Geography (INEGI), official organism that regards communities of less than 2500 inhabitants as rural. We are conscious that, in the context of this study, such definition could be improved. Particularly, it is very likely that in some communities classified as “urban” (having more than 2500 inhabitants), conditions that favor the parasite life cycle are still prevalent. Another point to consider is, as we have commented before, the time between infection and diagnosis, which can be very long (years). While progress has not reached all Mexican territory, a progressive improvement in the socioeconomic status in some regions has allowed us to prevent the completion of T. solium life cycle in those settings. It is possible that some patients were infected years before, when their living area was more rural than today. Finally, the role of migration from rural to urban areas could be involved as well. Currently, most Mexicans (77. 8%) live in urban settings [34] in contrast with the situation in the 1960s, where about one-half of the population (50. 7%) lived in this condition. It is possible that patients were infected while living in rural areas but were diagnosed later, after migrating to an urban center. The significantly higher proportion of rural patients in the mixed (parenchymal and extraparenchymal) group is probably a consequence of a higher infectious pressure and the ensuing higher infectious burden, resulting in cyst establishment in different compartments of the central nervous system. With respect to clinical presentation, our results confirmed that parasite location (ExP vs. Par) in fact determine two entirely different diseases. Intracranial hypertension is the most frequent symptom in ExPNCC patients, affecting more than 64% of them. In contrast, only a small minority (6. 3%) of Par patients exhibited this symptom. The association of ICH with higher CSF protein concentration but not with parasite multiplicity in the Par group points to the probable participation of associated arachnoiditis (related with the previous presence of cysts in the SAb compartment, already degenerated at the diagnosis time) rather than of encephalitis in its onset. On the other hand, seizures were the most frequent symptom in ParNCC patients (77%), while only 25. 6% of ExP cases showed this condition. Interestingly, although clinical features of subarachnoid and ventricular forms of the disease were similar, seizures were significantly more frequent when parasites were located in the subarachnoid space (P = 0. 04). This result was not related with the higher frequency of parenchymal parasites in SAb patients, since Par parasites were present in 52. 4% and 49. 1% of Ve and SAb parasites, respectively (P = 0. 75). The reason of these differences is not known, but it is feasible that the higher CSF inflammatory response observed in SAb patients may favor vasculitis, resulting in parenchymal vascular insults and triggering seizures [35]. With respect to this point, it is interesting to note that some authors reported an increase in the frequency of hippocampal sclerosis in ParNCC, and it is likely that inflammation-mediated damage of hippocampal neurons is involved in this finding [36]. The distribution of parasite degenerating stages showed some dependence on location. Parasites were mostly vesicular in ExPNCC patients, while the most frequent stage in ParNCC cases was calcification. Similarly, while vesicular cysts were the most frequent degenerating stage in SAb and IV locations (ExPNCC cases), the proportion of vesicular parasites was significantly higher in SAb than in IV parasites. Interestingly, the higher frequency of vesicular parasites was associated with more severe CSF inflammatory parameters. This association was clear in ExP parasites (compared with Par ones) and in subarachnoid parasites (compared with ventricular ones). So, it seems that the local inflammatory reaction was not associated with parasite death in extraparenchymal locations. This scenario is very different from the case of Par parasites, where the local inflammatory reaction is clearly associated with parasite degeneration. In these cases, a close contact between the parasite, brain immune cells and blood vessels, and the disruption of the blood-brain-barrier allowing the arrival of peripheral immune cells, participate in the success of the immune response [37]. Another factor that could be involved in the varying effectivity of the immune response depending on the compartment where it occurs is the presence of regulatory cells in CSF [38]. These cells could play a role in regulating the immune response, decreasing its effectivity in this compartment and favoring parasite survival. The apparent higher effectivity of the immune response in the ventricular compartment with respect to the subarachnoid space could be related with the more restricted space available for a ventricular parasite, which rapidly contacts ependymal cells. Indeed, an experimental study using the related parasite Mesocestoides corti showed that ependymal cells actively express immune mediators in experimental NCC, and that ependyma is a prominent source of leukocyte infiltration into the ventricles [39]. While sex and age did not modulate the clinical presentation of ExPMxNCC patients, the only significant result of multivariate analysis in ParNCC cases was a higher frequency of seizures in male patients. Similar results were found in other studies [40,41], but the explanation is not clear. The influence of these demographic variables on radiological and inflammatory features of NCC was more evident. Indeed, vesicular parasites were significantly more frequent in male Par patients, whereas calcified cysts were the most frequent presentation in female patients. In ExPMx patients, females showed more degenerating parasites and a higher CSF cellularity, while CSF protein concentration was higher in males and in older patients. Altogether, these findings point to a higher intensity and immediacy of the inflammatory reaction in females, as reflected by the increase in CSF cellularity and by a higher frequency of degenerating and calcified parasites. In males, on the other side, the increase in protein concentration probably indicates a more chronic evolution; this possibility is supported by the positive correlation between CSF protein concentration and age. These findings are probably related with immune-endocrine interactions not completely understood yet [4,42,43]. Finally, it is relevant to mention that although parasite location (parenchymal or extraparenchymal) determine two clearly different clinical diseases, there is a significant heterogeneity in the intensity of the associated inflammatory reaction and the radiological characteristics within each group. This is particularly evident in the ExP group. CSF was normal in some patients, while an intense inflammatory reaction was observed in others. At a radiological level, although most parasites were racemose, about 20% of patients presented a single parasite. The consequences of this variability are not completely understood, but it could be involved in the heterogeneity of the response to treatment and in the varying success of such treatment, as previous studies indicate [44,45]. Further analysis is required to better understand this aspect. In conclusion, this study strongly supports the relevance of parasite location to define the pathology associated to NCC. Therefore, cyst location should be one of the main factors to be considered when approaching a NCC patient.

Title: Extraparenchymal neurocysticercosis: Demographic, clinicoradiological, and inflammatory features Summary: Neurocysticercosis (NCC) is caused by the establishment of Taenia solium larvae in the human central nervous system. While NCC diagnosis, treatment, and prevention have clearly improved in the last 40 years, the disease still causes significant morbidity and mortality in endemic regions of Latin America, Asia, and Africa. Herein we described demographic, clinical, radiological, and cerebrospinal fluid features of a large series of NCC patients, and evaluated the relevance of parasite location on disease presentation. 191 patients with parenchymal parasites, 125 patients with extraparenchymal cysts, and 113 patients lodging parasites in both locations were included. Our results clearly demonstrated that differences in parasite location actually determines distinct diseases, with wide variations in severity. This is particularly evident when comparing parenchymal with extraparenchymal patients and ventricular with subarachnoid patients. Gender and age also modulate some characteristics of the disease. In conclusion, parasite location is one of the most important features of the disease, which must be considered when approaching an NCC patient.

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Write a title and summarize: SECTION 1. SHORT TITLE. This Act may be cited as the ``Health Equity and Access under the Law for Immigrant Women and Families Act of 2014'' or as the ``HEAL Immigrant Women and Families Act of 2014''. SEC. 2. FINDINGS. Congress finds as follows: (1) Insurance coverage reduces harmful health disparities by alleviating cost barriers to and increasing utilization of basic preventive health services, especially among low-income and underserved populations, and especially among women. (2) Based solely on their immigration status, many immigrants and their families face legal restrictions on their ability to obtain health insurance coverage through Medicaid, CHIP, and Health Insurance Exchanges. (3) Lack of health insurance contributes to persistent disparities in the prevention, diagnosis, and treatment of negative health outcomes borne by immigrants and their families. (4) Immigrant women are disproportionately of reproductive age, low-income, and lacking health insurance coverage. Legal barriers to affordable health insurance coverage therefore particularly exacerbate their risk of negative sexual, reproductive, and maternal health outcomes, with lasting health and economic consequences for immigrant women, their families, and society as a whole. (5) Denying coverage or imposing waiting periods for coverage unfairly hinders the ability of immigrants to take responsibility for their own health and economic well-being and that of their families. To fully and productively participate in society, access to health care is fundamental, which for women includes access to the services necessary to plan whether and when to have a child. (6) The population of immigrant families in the United States is expected to continue to grow. Indeed one in five children in the United States is part of an immigrant family. It is therefore in the nation's shared public health and economic interest to remove legal barriers to affordable health insurance coverage based on immigration status. SEC. 3. REMOVING BARRIERS TO HEALTH COVERAGE FOR LAWFULLY PRESENT INDIVIDUALS. (a) Medicaid.--Section 1903(v)(4) of the Social Security Act (42 U.S.C. 1396b(v)(4)) is amended-- (1) by amending subparagraph (A) to read as follows: ``(A) Notwithstanding sections 401(a), 402(b), 403, and 421 of the Personal Responsibility and Work Opportunity Reconciliation Act of 1996, payment shall be made under this section for care and services that are furnished to aliens, including those described in paragraph (1), if they otherwise meet the eligibility requirements for medical assistance under the State plan approved under this title (other than the requirement of the receipt of aid or assistance under title IV, supplemental security income benefits under title XVI, or a State supplementary payment), and are lawfully present in the United States.''; (2) in subparagraph (B)-- (A) by striking ``a State that has elected to provide medical assistance to a category of aliens under subparagraph (A)'' and inserting ``aliens provided medical assistance pursuant to subparagraph (A)''; and (B) by striking ``to such category'' and inserting ``to such alien''; and (3) in subparagraph (C)-- (A) by striking ``an election by the State under subparagraph (A)'' and inserting ``the application of subparagraph (A)''; (B) by inserting ``or be lawfully present'' after ``lawfully reside''; and (C) by inserting ``or present'' after ``lawfully residing'' each place it appears. (b) CHIP.--Subparagraph (J) of section 2107(e)(1) of the Social Security Act (42 U.S.C. 1397gg(e)(1)) is amended to read as follows: ``(J) Paragraph (4) of section 1903(v) (relating to lawfully present individuals).''. (c) Effective Date.-- (1) In general.--Except as provided in paragraph (2), the amendments made by this section shall take effect on the date of the enactment of this Act and shall apply to services furnished on or after the date that is 90 days after such date of the enactment. (2) Exception if state legislation required.--In the case of a State plan for medical assistance under title XIX, or a State child health plan under title XXI, of the Social Security Act which the Secretary of Health and Human Services determines requires State legislation (other than legislation appropriating funds) in order for the plan to meet the additional requirements imposed by the amendments made by this section, the respective State plan shall not be regarded as failing to comply with the requirements of such title solely on the basis of its failure to meet these additional requirements before the first day of the first calendar quarter beginning after the close of the first regular session of the State legislature that begins after the date of the enactment of this Act. For purposes of the previous sentence, in the case of a State that has a 2-year legislative session, each year of such session shall be deemed to be a separate regular session of the State legislature. SEC. 4. REMOVING BARRIERS TO HEALTH COVERAGE FOR INDIVIDUALS GRANTED DEFERRED ACTION FOR CHILDHOOD ARRIVALS. (a) In General.--For the purposes of eligibility under any of the provisions referred to in subsection (b), individuals granted deferred action under the Deferred Action for Childhood Arrivals process of the Department of Homeland Security, as described in the memorandum of the Secretary of Homeland Security on June 15, 2012, shall be considered lawfully present in the United States. (b) Provisions Described.--The provisions described in this subsection are the following: (1) Exchange eligibility.--Section 1311 of the Patient Protection and Affordable Care Act (42 U.S.C. 18031). (2) Reduced cost-sharing eligibility.--Section 1402 of the Patient Protection and Affordable Care Act (42 U.S.C. 18071). (3) Premium subsidy eligibility.--Section 36B of the Internal Revenue Code of 1986. (4) Medicaid and chip eligibility.--Titles XIX and XXI of the Social Security Act, including under section 1903(v) of such Act (42 U.S.C. 1396b(v)). (c) Effective Date.-- (1) In general.--Subsection (a) shall take effect on the date of the enactment of this Act. (2) Transition through special enrollment period.--In the case of an individual described in subsection (a) who, before the first day of the first annual open enrollment period under subparagraph (B) of section 1311(c)(6) of the Patient Protection and Affordable Care Act (42 U.S.C. 18031(c)(6)) beginning after the date of the enactment of this Act, is granted deferred action described in subsection (a) and who, as a result of such subsection, qualifies for a subsidy described in paragraph (2) or (3) of such subsection, the Secretary of Health and Human Services shall establish a special enrollment period under section 1311(c)(6)(C) of such Act during which such individual may enroll in qualified health plans through Exchanges under title I of such Act and qualify for such a subsidy. For such an individual who has been granted deferred action as of the date of the enactment of this Act, such special enrollment period shall begin not later than 90 days after such date of enactment. Nothing in this paragraph shall be construed as affecting the authority of the Secretary to establish additional special enrollment periods under section 1311(c)(6)(C) of the Patient Protection and Affordable Care Act (42 U.S.C. 18031(c)(6)(C)).

Title: HEAL Immigrant Women and Families Act of 2014 Summary: Health Equity and Access under the Law for Immigrant Women and Families Act of 2014 or the HEAL Immigrant Women and Families Act of 2014 - Amends titles XIX (Medicaid) and XXI (Children's Health Insurance) (CHIP) of the Social Security Act to extend Medicaid and CHIP coverage to aliens lawfully present in the United States. Makes individuals granted deferred action under the Deferred Action for Childhood Arrivals process eligible for: (1) health care exchanges and reduced cost sharing under the Patient Protection and Affordable Care Act, (2) premium subsidies under the Internal Revenue Code, and (3) Medicaid and CHIP.

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Summarize: Background H.R. 6 was introduced by the House Democratic Leadership to revise certain tax and royalty policies for oil and natural gas and use the resulting revenue to support a reserve for energy efficiency and renewable energy. The bill is one of several introduced on behalf of the Democratic Leadership in the House as part of its "100 hours" package of legislative initiatives conducted early in the 110 th Congress. Title I proposes to reduce certain oil and natural gas tax subsidies to create a revenue stream to support energy efficiency and renewable energy. Title II would modify certain aspects of royalty relief for offshore oil and natural gas development to create a second stream of revenue to support energy efficiency and renewable energy. Strategic Energy Efficiency and Renewables Reserve Title III of H.R. 6 creates a budget procedure for the creation and use of a Strategic Energy Efficiency and Renewable Energy Reserve, under which additional spending for energy efficiency and renewable energy programs can be accommodated without violating enforcement procedures in the Congressional Budget Act of 1974, as amended. Bill Purpose and Permitted Reserve Uses The stated purpose of the bill is to "reduce our nation's dependency on foreign oil" by investing in renewable energy and energy efficiency. Specifically, Section 301 (a) of the bill would make the revenue in the Reserve available to "offset the cost of subsequent legislation" that may be introduced "(1) to accelerate the use of domestic renewable energy resources and alternative fuels, (2) to promote the utilization of energy-efficient products and practices and conservation, and (3) to increase research, development, and deployment of clean renewable energy and efficiency technologies." Budget Adjustment Procedure for Uses of the Reserve The budget adjustment procedure for use of the Reserve is set out in Section 301 (b). The procedure is similar to reserve fund procedures included in annual budget resolutions. It would require the chairman of the House or Senate Budget Committee, as appropriate, to adjust certain spending levels in the budget resolution, and the committee spending allocations made thereunder, to accommodate a spending increase (beyond FY2007 levels) in a reported bill, an amendment thereto, or a conference report thereon that would address the three allowed uses of the Reserve noted above. The adjustments for increased spending for a fiscal year could not exceed the amount of increased receipts for that fiscal year, as estimated by the Congressional Budget Office, attributable to H.R. 6. Initial Revenue Estimates for the Reserve According to the Congressional Budget Office (CBO), the proposed repeal of selected tax incentives for oil and natural gas would make about $7.7 billion available over 10 years, 2008 through 2017. The proposed changes to the royalty system for oil and natural gas are estimated to generate an additional $6.3 billion. This would yield a combined total of $14 billion for the Reserve over a 10-year period. The CBO estimates show that the total annual revenue flow would vary annually over the 10-year period, ranging from a low of about $900 million to a high of about $1.8 billion per year. H.R. 6 Action H.R. 6 came to the House floor for debate on January 18, 2007. In the floor debate, opponents argued that the reduction in oil and natural gas incentives would dampen production, cause job losses, and lead to higher prices for gasoline and other fuels. Opponents also complained that the proposal for the Reserve does not identify specific policies and programs that would receive funding. Proponents of the bill countered that record profits show that the oil and natural gas incentives were not needed. They also contended that the language that would create the Reserve would allow it to be used to support a variety of R&D, deployment, tax incentives, and other measures for renewables and energy efficiency, and that the specifics would evolve as legislative proposals come forth for to draw resources from the Reserve. The bill passed the House on January 18 by a vote of 264-163. Related Action on the Budget Resolution In general, the budget resolution would revise the congressional budget for FY2007. It would also establish the budget for FY2008 and set budgetary levels for FY2009 through FY2012. In particular, the House resolution ( H.Con.Res. 99 ) would create a single deficit-neutral reserve fund for energy efficiency and renewable energy that is virtually identical to the reserve described in H.R. 6. In contrast, the Senate resolution ( S.Con.Res. 21 ) would create three reserve funds, which identify more specific efficiency and renewables measures and would allow support for "responsible development" of oil and natural gas. House Version of the Budget Resolution (H.Con.Res. 99) On March 28, the House passed H.Con.Res. 99 by a vote of 216-210. For FY2007, it would allow for additional funding for energy (Function 270) above the President's request that "could be used for research, development, and deployment of renewable and alternative energy." Section 207 would create a deficit-neutral reserve fund that fulfills the purposes of H.R. 6 to "facilitate the development of conservation and energy efficiency technologies, clean domestic renewable energy resources, and alternative fuels that will reduce our reliance on foreign oil." Senate Version of the Budget Resolution (S.Con.Res. 21) On March 23, the Senate passed S.Con.Res. 21, its version of the budget resolution. In parallel to the House resolution, Section 307 of S.Con.Res. 21 would create a deficit-neutral reserve fund that could be used for renewable energy, energy efficiency, and "responsible development" of oil and natural gas. In addition, Section 332 would create a deficit-neutral reserve fund for extension through 2015 of certain energy tax incentives, including the renewable energy electricity production tax credit (PTC), Clean Renewable Energy Bonds, and provisions for energy efficient buildings, products, and power plants. Further, Section 338 would create a deficit-neutral reserve fund for manufacturing initiatives that could include tax and research and development (R&D) measures that support alternative fuels, automotive and energy technologies, and the infrastructure to support those technologies.

Summary: H.R. 6 would use revenue from certain oil and natural gas policy revisions to create an Energy Efficiency and Renewables Reserve. The actual uses of the Reserve would be determined by ensuing legislation. A variety of tax, spending, or regulatory bills could draw funding from the Reserve to support liquid fuels or electricity policies. The House budget resolution (H.Con.Res. 99) would create a deficit-neutral reserve fund nearly identical to that proposed in H.R. 6. The Senate budget resolution (S.Con.Res. 21) would create three reserve funds with purposes related to those in H.R. 6. However, the Senate version has more specifics about efficiency and renewables measures, and it would allow reserve fund use for "responsible development" of oil and natural gas.

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Summarize: WASHINGTON (Reuters) - U.S. President Donald Trump shook up his foreign policy team again on Thursday, replacing H.R. McMaster as national security adviser with John Bolton, a hawk who has advocated using military force against North Korea and Iran. The move, announced in a tweet and a White House statement, came little more than a week after Trump fired Rex Tillerson as secretary of state and nominated Central Intelligence Agency Director Mike Pompeo to replace him. The shake-up shows Trump, in office for 14 months, surrounding himself with advisers more likely to agree with his views and taking his foreign policy in a more hawkish direction. What it means for a prospective summit meeting between Trump and North Korean leader Kim Jong Un is unclear. The meeting is supposed to happen by the end of May, but an exact time and place have yet to be settled on. Bolton’s appointment could doom the already endangered Iran nuclear deal. It could also lead to friction with Trump on how tough to be on Russia, with the president still holding out hope for improved ties with Russian President Vladimir Putin. The news of Bolton’s appointment followed a meeting he had with Trump in the Oval Office. Even Bolton was caught by surprise. “I didn’t really expect an announcement this afternoon, but it’s obviously a great honor,” he told Fox News after the announcement. “I’m still getting used to it.” Bolton, 69, is a Fox News analyst who contemplated a run for the Republican presidential nomination in 2016. He is a familiar figure in Washington, with a walrus-like moustache and hard-charging views on many global challenges. Some members of Congress immediately questioned his selection for the critical position in the White House. “This is not a wise choice. Mr. Bolton does not have the temperament or judgment to be an effective national security adviser,” Democratic Senator Jack Reed said in a statement. Bolton tweeted on Jan. 11 that time was running out on stopping North Korea’s nuclear weapons program. He said: “We’ve got to look at the very unattractive choice of using military force to deny them that capability.” At a time when Trump has threatened to withdraw the United States from the 2015 Iran nuclear deal, unless Europe agrees to change it, Bolton has tweeted that the deal “needs to be abrogated.” He has also called for “effective countermeasures to the cyber war that Russia is engaging.” ‘STRONG SIGNAL’ Elliott Abrams, a senior foreign policy aide to former Republican President George W. Bush, praised Trump’s choice, saying Bolton “proved when we were both in the Bush administration that he is an excellent and forceful bureaucrat.” Whether Bolton, who was U.S. ambassador to the United Nations for Bush, will be able to swallow his own views has been debated by foreign policy experts since he appeared on Trump’s radar. His hiring does not require U.S. Senate confirmation. Bolton said in the Fox News interview that his past statements on various issues were behind him and he would be an honest broker ensuring the president sees all the options available to him. “The important thing is what the president says and the advice I give him,” he said. Still, analysts said Bolton’s views would be influential. “Bolton has long been an advocate for pre-emptive military action against North Korea, and his appointment as National Security Adviser is a strong signal that President Trump remains open to these options,” said Abraham Denmark, deputy assistant secretary of defense for East Asia under former President Barack Obama. FILE PHOTO -- Former U.S. Ambassador to the United Nations John Bolton (L) speaks in Oxon Hill, Maryland, U.S. February 24, 2017, and White House National Security Advisor H.R. McMaster joins the daily briefing in Washington, U.S. July 31, 2017, in this combination photograph. REUTERS/Joshua Roberts, Jonathan Ernst/File Photo “We should also expect an even more confrontational approach to China - a trade war may just be the beginning of a broader geopolitical competition,” he said. Bonnie Glaser, Asia expert at the Center for Strategic and International Studies think tank in Washington, said: “Bolton has long supported regime change in North Korea and closer ties with Taiwan. Fasten your seat belts.” As the State Department’s top arms control official under Bush, Bolton was a leading advocate of the 2003 invasion of Iraq - which was later found to have been based on bogus and exaggerated intelligence about President Saddam Hussein’s weapons of mass destruction and ties to terrorism. ‘MUTUALLY AGREED’ McMaster, hired early in Trump’s presidency to replace scandal-tarred Michael Flynn as national security adviser, had widely been expected to leave soon. Trump found McMaster’s style grating. The two had frequently clashed in meetings and Trump had been looking for a replacement, advisers said. The White House said Trump and McMaster had “mutually agreed” that he would leave. “I am very thankful for the service of General H.R. McMaster who has done an outstanding job & will always remain my friend,” Trump’s tweet said. “The two have been discussing this for some time. The timeline was expedited as they both felt it was important to have the new team in place, instead of constant speculation. This was not related to any one moment or incident, rather it was the result of ongoing conversations between the two,” a senior White House official said. The announcement came a day after Trump was angered by a leak of information from his presidential briefing papers that said he was advised specifically not to congratulate Putin on his disputed election victory. Trump told reporters he had congratulated Putin. McMaster, 55, is to stay on until mid-April. He said in a statement he was also requesting retirement from the U.S. Army, in which he holds the rank of three-star general. White House Chief of Staff John Kelly had been hoping to entice McMaster into another military assignment in order to qualify as a four-star general. Slideshow (7 Images) Tweet with a location You can add location information to your Tweets, such as your city or precise location, from the web and via third-party applications. You always have the option to delete your Tweet location history. Learn more President Donald Trump finally jettisoned National Security Adviser H.R. McMaster on Thursday afternoon. His replacement is John Bolton, the former ambassador to the United Nations in the Bush administration — and one of the most radically hawkish voices in American foreign policy. Bolton has said the United States should declare war on both North Korea and Iran. He was credibly accused of manipulating US intelligence on weapons of mass destruction prior to the Iraq War and of abusive treatment of his subordinates. He once “joked�? about knocking 10 stories off the UN building in New York. That means his new appointment to be the most important national security official in the White House has significant — and frightening — implications for Trump’s approach to the world. Bolton’s new job was announced on Thursday evening, when the president tweeted that McMaster planned to resign and Bolton would replace him. “I am pleased to announce that, effective 4/9/18, [John Bolton] will be my new National Security Advisor,�? Trump wrote. Bolton had been rumored to be the frontrunner for the job for months, but that doesn’t make the pick any less jarring. His track record in government, connections to anti-Muslim groups, and stated views in op-eds and public speeches all suggest that he will push Trump to take extremely dangerous positions on issues like North Korea, Iran, and ISIS. “I operate on the assumption that John Bolton should be kept as far away from the levers of foreign policy as possible,�? says Christopher Preble, the vice president for defense and foreign policy studies at the libertarian Cato Institute. “I think I would rest easy if he was dog catcher in Stone Mountain, Georgia. But maybe not.�? Bolton’s elevation illustrates the degree to whichTrump is influenced by the conservative infotainment sphere, most notably Fox News — where Bolton has long been an on-air fixture. He was, prior to this appointment, a marginal figure in Washington foreign policy circles since his departure from the Bush administration. But he got himself one of the top jobs in the country because of his savvy work in the world of conservative media and advocacy groups. As a result, American foreign policy may be soon be shaped by someone who seems to truly believe that war is the answer to the world’s most pressing problems. John Bolton’s early career shows why he’s a dangerous choice for national security adviser Bolton is, somewhat ironically, a quintessential creature of the Washington swamp. After graduating Yale Law School in 1974, where he had become friends with future Supreme Court Justice Clarence Thomas, he went into private practice in Washington. He made a name for himself working in conservative politics, becoming vice president of the right-wing American Enterprise Institute and serving in midlevel roles in the Reagan and George H.W. Bush administrations. But it wasn’t until the George W. Bush administration that Bolton rose to greater prominence. In May 2001, Bush appointed him to be undersecretary of state for arms control, basically the top diplomat focusing on weapons of mass destruction. This position became fairly important in the runup to the Iraq War, as the Bush administration’s case against Saddam Hussein focused on his alleged nuclear, chemical, and biological weapons. Bolton took the hardest of possible lines. He forcefully argued that Iraq had WMDs — “we are confident that Saddam Hussein has hidden weapons of mass destruction,�? as he put in one 2002 speech. After Bush’s 2002 State of the Union speech connecting North Korea, Iraq, and Iran as an “axis of evil,�? Bolton insisted that this wasn’t just rhetoric — that there was ‘’a hard connection between these regimes — an ‘axis’ along which flow dangerous weapons and dangerous technology.’’ He was involved in shaping US intelligence in the runup to the war — and not in a good way. In 2002, Bolton’s staff prepared a speech alleging that Cuba had an active biological weapons program. This wasn’t true, and the State Department’s lead bioweapons analyst at the time would not sign off on the claim. Per the analyst’s sworn testimony to Congress, Bolton then called the analyst into his office, screamed at him, and then sent for his boss. In this conversation, per the Washington Post’s David Ignatius, he derisively referred to the analyst as a “munchkin�? and attempted to get him transferred to a different department. This was cruel and unprofessional, but also dangerous. Carl Ford, then the assistant secretary of state for intelligence and research, testified that Bolton’s assault on the analyst had a “chilling effect�? throughout the department, freezing out dissent on proliferation issues beyond Cuba. John Prados, a fellow at George Washington University’s National Security Archives, came to an even broader conclusion in a study of declassified Bush administration documents: Bolton bears a significant amount of blame for the politicized intelligence used to justify the decision to attack Iraq. “Although Bolton’s actions did not concern Iraq directly, they came to a high point during the summer of 2002 — the exact moment when Iraq intelligence issues were on the front burner — and they aimed at offices which played a central role in producing Iraq intelligence,�? Prados writes. “Analysts working on Iraq intelligence could not be blamed for concluding that their own careers might be in jeopardy if they supplied answers other than what the Bush administration wanted to hear.�? None of this got Bolton fired. In fact, it got him promoted: In March 2005, President Bush nominated him to be US ambassador to the UN, one of the most important diplomatic positions in the entire government. Bolton’s Senate confirmation hearing turned into a vicious fight, largely over his role in shaping the faulty prewar intelligence about Iraq. But his management style, as exemplified by the munchkin incident, also became a huge issue. When Ford was called to testify before the Senate Foreign Relations Committee, he bluntly said Bolton’s personality should disqualify him from holding high office. Ford called him a “bully�? who “kisses up and punches down,�? among other things. “I’m as conservative as John Bolton is,�? Ford told the committee. “But the fact is that the collateral damage and the personal hurt that he causes is not worth the price that had to be paid.�? Multiple people who had worked with Bolton came out of the woodwork to speak to these issues. Perhaps the most harrowing such account came in an open letter written by a former federal contractor named Melody Townsel, recalling a time that she raised issues surrounding the use of funds in a contract Bolton was working on. He didn’t take it well: Mr. Bolton proceeded to chase me through the halls of a Russian hotel — throwing things at me, shoving threatening letters under my door and, generally, behaving like a madman. For nearly two weeks, while I awaited fresh direction from my company and from US AID, John Bolton hounded me in such an appalling way that I eventually retreated to my hotel room and stayed there. Mr. Bolton, of course, then routinely visited me there to pound on the door and shout threats. All in all, according to then-Sen. Joe Biden, the ranking Democrat on the Senate Foreign Relations Committee at the time, testimony from at least five people confirmed multiple instances of Bolton behaving abusively toward subordinates and retaliating against intelligence professionals who challenged his policy positions. For these reasons, Bolton could not be confirmed by the Senate — which was, at the time, controlled by Republicans. Bolton’s Iraq-era activities are extraordinarily relevant for understanding what he’ll push for as Trump’s national security adviser (a position that doesn’t require Senate confirmation). Technically, his primary job will be running the National Security Council, which exists to coordinate and synthesize the sometimes conflicting policy proposals that emerge from the Pentagon, State Department, and other agencies. He will present the president with strategic assessments of high-level officials like the secretaries of defense and state, offer his own thinking, and then communicate Trump’s ultimate decision to the agencies and work to ensure it’s implemented. Put another way, his job is to manage the information that comes to the president and then present a clear-eyed and accurate assessment of what’s happening and how to respond to it. Yet Bolton’s history suggests a long and storied history of cherry-picking intelligence to support his preferred hawkish policies. “Bolton is so much of an ideologue,�? says Mieke Eoyang, vice president for foreign policy at the center-left think Third Way, “that I don’t think he would accurately portray consequences [of policy options] to the president.�? His reported history of berating and undermining anyone who attempted to challenge him is likely to further stifle dissent. He’ll have more power over the White House national security staff as national security adviser than anyone other than the president, giving him unprecedented ability to act as a “bully,�? in Ford’s words. It’s very plausible that Bolton will accelerate the brain drain from the federal government that already seems to be taking shape — not just in the White House but across the various departments that make foreign policy. “Bolton hates the State Department. He portrays US diplomats as closet Democrats and appeasers,�? Richard Gowan, a professor at Columbia University who has studied Bolton’s career, recalls. “As NSA, he would almost certainly encourage the hollowing out of State Trump and [former Secretary of State Rex] Tillerson have begun.�? John Bolton represents the Fox News-ification of foreign policy Ultimately, Bolton did get the UN ambassador position — though without the Senate’s permission. In August 2005, President Bush appointed him to the post while the Senate was out of session (a so-called “recess appointment�?). Bolton’s year and a half at the UN was characterized by showy condemnations of the organization, which infuriated American allies, but he had little influence on the UN or the overall arc of Bush’s second-term foreign policy. “Bolton raised hell at the UN, but his actual power was quite limited,�? Gowan recalls. “Condi Rice and the mainstream conservatives in the second Bush administration often ignored him. He is quite open about this in his memoirs from that period, which are fun.�? In December 2006, Bolton called it quits, returning to civilian life. He became a fixture on Fox News and conservative talk radio, where his confirmation fight and anti-UN rhetoric was hailed as a sign of his willingness to speak truth to power. He was so prominent in these spheres, mostly through his contract as a Fox contributor, that he considered running for president in both 2012 and 2016. Bolton was particularly popular among a small but influential group of hardline anti-Islam activists, the “counter-jihad�? movement, who believed the US government was being infiltrated by Islamists and that Islamic law was quietly taking over the US legal system. Bolton wrote the foreword to a book by two of the most prominent counter-jihadists, Pamela Geller and Robert Spencer, in 2010. In 2016, Bolton spoke at a conference held by the American Freedom Alliance, considered a “hate group�? by the Southern Poverty Law Center, titled “Can Islam and the West Coexist?�? His speech contained a “joke�? whose punchline was that President Obama was a Muslim. In his many media appearances and public appearances, Bolton never wavered from the kind of hawkish policy views he established during the Bush administration. In a 2015 New York Times op-ed, Bolton advocated for a US and/or Israeli airstrike on Iranian nuclear facilities. “Time is terribly short, but a strike can still succeed,�? he wrote. “Such action should be combined with vigorous American support for Iran’s opposition, aimed at regime change in Tehran.�? Since Trump took office, Bolton has put the media savvy and experience with the conservative movement he’s developed to good use — using various levers to influence the president. In just the first months of 2018, Bolton has appeared on Fox News roughly 20 times. He has used those appearances to sell his policy preferences, warning against diplomacy with North Korea and encouraging Jordan to annex the West Bank (much of which remains under Israeli occupation despite the fact that the vast majority of its citizens are Palestinian). During the early Trump administration, then-White House senior strategist Steve Bannon approached Bolton as part of a plan to get around Cabinet members, like Secretary of Defense Jim Mattis, who opposed withdrawal from the Iran nuclear deal. Bolton drafted a five-page memo detailing his proposal for tearing up the deal, which he then published in National Review after Bannon departed the White House. And in February 2018, he published an op-ed in the Wall Street Journal arguing that the US needed to solve the nuclear standoff with North Korea by force. “Pre-emption opponents argue that action is not justified because Pyongyang does not constitute an ‘imminent threat.’ They are wrong,�? Bolton wrote. “It is perfectly legitimate for the United States to respond to the current ‘necessity’ posed by North Korea’s nuclear weapons by striking first.�? Bolton’s record in the Bush administration and general hawkishness made him a marginal figure in Washington foreign policy conversations. So after leaving, he cannily aligned himself with Fox News and other influential groups on the right, like the counter-jihadists, who saw him as an experienced and credible commentator. This led not only to television news and book contracts but to platforms through which he could potentially influence actual Republican elected officials. This reached a kind of apogee with President Trump. Trump sees the world through a televisual lens; he seems to get more information from Fox News than from his daily intelligence briefings. The president values the advice of people he sees on the TV and other friendly media outlets. Bolton is not seen as a relic of the hated Bush administration; he’s seen as an authoritative and expert Fox voice. According to Bolton’s National Review piece, Trump once told him to “come in and see me any time�? in the White House. Now, of course, Bolton will have a permanent home in the White House. The reason he didn’t have an administration sooner, according to some press accounts, is aesthetic. In December 2016, the Washington Post reported that Bolton was eliminated from the running for secretary of state because Trump — I swear I’m not making this up — didn’t like his mustache. “Donald was not going to like that mustache,�? one Trump associate told the Post. “I can’t think of anyone that’s really close to Donald that has a beard that he likes.�? Perhaps because of the mustache, Trump hadn’t taken Bolton’s policy advice to heart in his first year in office. There’s no war with North Korea, and the Iran deal remains (largely) intact. But now Bolton is national security adviser, with direct access to the president and tremendous influence over a vast and powerful national security bureaucracy. And many foreign policy experts are deeply concerned about what that means. “The United States has not hit rock bottom in our international relations,�? says Eoyang. “[With Bolton], we could go lower.�?

Summary: President Trump is getting his third national security adviser in the first 14 months of his presidency, Reuters reports. Current national security adviser Lt. Gen. HR McMaster is resigning, to be replaced by John Bolton on April 9. "I am very thankful for the service of General H.R. McMaster who has done an outstanding job & will always remain my friend," Trump tweeted Thursday. McMaster, who replaced Michael Flynn as national security adviser, is also resigning from the military, the New York Times reports. While McMaster and Trump butted heads both publicly and privately during his tenure at the White House, officials say McMaster's resignation is amicable and has been in the works for weeks. Officials say Trump wanted to finish a shakeup of his national security team before a planned meeting with North Korea's Kim Jong-un. McMaster's replacement was US ambassador to the UN under the second Bush administration and is "one of the most radically hawkish voices in American foreign policy," according to a Vox explainer on Bolton. The incoming national security adviser has said the US should declare war on both North Korea and Iran. Bolton, notably, has also been a longtime contributor on Fox News. In the past, he's been accused of abusing his subordinates and manipulating US intelligence ahead of the Iraq War and has connections to anti-Muslim groups. His appointment to national security adviser was met with concern from some areas. "I operate on the assumption that John Bolton should be kept as far away from the levers of foreign policy as possible," says the vice president for defense and foreign policy studies at the libertarian Cato Institute.

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Summarize: FIELD OF THE INVENTION The present invention relates to apparatuses and methods for retaining fishing hooks and, more particularly, to embodiments of fishing hook retaining apparatuses and methods that permit the retention of a hook while protecting a fly located thereon. BACKGROUND OF THE INVENTION A common problem encountered by fishermen of all skill levels relates to the storage of hooks. There is a need for a convenient means for storing hooks that are not being used, whether on a long-term basis between fishing outings, or during a particular fishing outing when a different hook is being utilized or during a break in fishing. Storage, to be effective and safe, should secure the hook in a place where neither its barb nor point is at significant risk of coming into contact with the hand or other body portion of the fisherman or bystander. In the area of fly fishing, the problem is made more complicated by the fact that care needs to be taken to not damage a fly during the storage of a hook that is still coupled to a fly. Flies can be delicate and expensive, and the mishandling of a fly can harm it and reduce its effectiveness. There is a need therefore for a fishing hook retaining apparatus and method that facilitates the storage of a hook when not in use, in a manner that is protective of the fly. The present invention satisfies these needs and provides other, related, advantages. SUMMARY OF THE INVENTION In accordance with one embodiment of the present invention, a fishing hook retaining apparatus is provided. The apparatus comprises, in combination: a sleeve having an interior of sufficient size to secure therein a barb and a point of at least one fish hook; wherein an underside of the sleeve is shaped to conform to a shaft of a fishing pole; means for securing the sleeve to the shaft; a channel in an upper surface of the sleeve, extending from a front edge of the sleeve part of the distance toward a rear edge of the sleeve. In accordance with another embodiment of the present invention, fishing hook retaining apparatus is provided. The apparatus comprises, in combination: a sleeve having an interior of sufficient size to secure therein a barb and a point of at least one fish hook; wherein an underside of the sleeve is shaped to conform to a shaft of a fishing pole; means for securing the sleeve to the shaft; a channel in an upper surface of the sleeve, extending from a front edge of the sleeve part of the distance toward a rear edge of the sleeve; wherein an interior of the sleeve is divided into a first side and a second side; a magnet secured in the interior of the sleeve within the first side. In accordance with another embodiment of the present invention, fishing hook retaining apparatus is provided. The apparatus comprises, in combination: a base; opposing sides projecting upward at a substantially ninety degree angle from the base; a bar interposed between the opposing sides; wherein the opposing sides are angled from a first end to a second end thereof, so that the bar is coupled at substantially the highest point of opposing sides. In accordance with a further embodiment of the present invention, a method for retaining a fishing hook is provided. The method comprises: securing a fishing hook retaining apparatus to a shaft of a fishing pole; wherein the fishing hook retaining apparatus comprises, in combination: a sleeve having an interior of sufficient size to secure therein a barb and a point of at least one fish hook; wherein an underside of the sleeve is shaped to conform to a shaft of a fishing pole; means for securing the sleeve to the shaft; a channel in an upper surface of the sleeve, extending from a front edge of the sleeve part of the distance toward a rear edge of the sleeve; wherein an interior of the sleeve is divided into a first side and a second side; and a magnet secured in the interior of the sleeve within the first side; inserting the fish hook into an open end of the channel so that barb and the point are inside the sleeve; and inserting at least the point portion of the fish hook into the interior of the sleeve; positioning the fish hook so that at least a portion thereof is brought into contact with the magnet. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of a fishing hook retaining apparatus consistent with an embodiment of the present invention. FIG. 2 is a top view of the fishing hook retaining apparatus of FIG. 1. FIG. 3 is a bottom view of the fishing hook retaining apparatus of FIG. 1. FIG. 4 is a side, cross-sectional view of the fishing hook retaining apparatus of FIG. 1. FIG. 5 is a front view of the fishing hook retaining apparatus of FIG. 1. FIG. 6 is a rear view of the fishing hook retaining apparatus of FIG. 1. FIG. 7 is a first side view of the fishing hook retaining apparatus of FIG. 1. FIG. 8 is a second side view of the fishing hook retaining apparatus of FIG. 1. FIG. 9 is a perspective view of the fishing hook retaining apparatus of FIG. 1, with a hook therein and in position on a shaft of a fishing pole. FIG. 10 is a front view of the fishing hook retaining apparatus of FIG. 1, with a hook therein and in position on a shaft of a fishing pole. FIG. 11 is a front view of a fishing hook retaining apparatus, consistent with another embodiment of the present invention. FIG. 12 is a rear view of the fishing hook retaining apparatus of FIG. 11. FIG. 13 is a top view of a fishing hook retaining apparatus, consistent with another embodiment of the present invention. FIG. 14 is a side view of the fishing hook retaining apparatus of FIG. 13. FIG. 15 is a side, cross-sectional view of a fishing hook retaining apparatus, consistent with another embodiment of the present invention. FIG. 16 is a side view of the fishing hook retaining apparatus of FIG. 15. FIG. 17 is a top view of the fishing hook retaining apparatus of FIG. 15. FIG. 18 is a front view of the fishing hook retaining apparatus of FIG. 15. FIG. 19 is a front view of a fishing hook retaining apparatus consistent with another embodiment of the present invention. FIG. 20 is a rear view of the fishing hook retaining apparatus of FIG. 19. FIG. 21 is a top view a fishing hook retaining apparatus consistent with another embodiment of the present invention. FIG. 22 is a cross-sectional side view of the fishing hook retaining apparatus of FIG. 21. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring first to FIGS. 1–10, a fishing hook retaining apparatus 10 (“apparatus 10 ”) consistent with an embodiment of the present invention is shown. In this embodiment, the apparatus 10 defines a sleeve 12. The underside 14 of the sleeve 12 is preferably shaped to conform to a fishing pole shaft 15. Projecting from each side of sleeve 12, substantially perpendicular thereto, may be securing members 16. As best seen in FIGS. 5–6, an upper surface 17 of each securing member 16 is preferably angled in an upward direction outward from the sleeve 12. The upward angling of the upper surface 17 is intended to facilitate, as described in more detail below, the securing of the apparatus 10 to the shaft 15 with an O-ring 19 (see FIGS. 9–10 ) or other fastener. As also seen in these drawing figures, a lower surface 21 of the securing member is preferably angled in a downward direction outward from the sleeve 12. The downward angling of the lower surface 21 is intended to further conform the lower surface generally of the apparatus 10 to the shape of the shaft 15 to which the apparatus 10 is being secured. It should be noted that where sufficient gripping force can be achieved with a particular O-ring or other fastener, it may be unnecessary to provide an upward angling of the upper surface 17, and/or to provide a downward angling of the lower surface 21. It is preferred to provide a channel 20 in an upper surface of the sleeve 12, extending from a front edge 24 of sleeve 12 part of the distance toward rear edge 26 of the sleeve 12. Preferably, as shown in FIGS. 1, 2, 4, and 7 – 8, the channel 20 terminates before the rear edge 26, so that, as will be described more fully below, it will not be possible to pull a hook 13 all of the way through sleeve 12. As best seen in FIGS. 1–2, it is preferred that channel 20 have a substantially V-shape, so that the channel 20 narrows from its opening to its close. This tends to promote the positioning of the hook 13 relative to the magnet 32, as herein described in greater detail below, while also making insertion of the hook 13 into the channel 20 relatively easier for the user. Turning now to a description of the interior of the sleeve 12, it is preferred that the interior be divided into a first side and a second side. Preferably, the first side is utilized to secure at least one magnet 32 therein. The second side is utilized to permit the insertion of some portion of a hook 13 therein, including, preferably, the hook point 13 a and barb 13 b. To facilitate a clear division of the interior of the sleeve 12 as herein described, and to promote ready securing of the magnet 32 in the first side, it may be desired to provide an upward projecting ridge 36 along a bottom interior length of the sleeve 12, and a downward projecting ridge 38 along a top interior length of the sleeve 12. As best seen in FIGS. 4–6 and 9 – 10, the magnet 32 may be secured in the first side by inserting it therein, so that a first side of the magnet 32 contacts an interior side of the sleeve 12, and a second side of the magnet 32 contacts each of ridges 36 and 38. It may be sufficient to press fit a magnet 32 into position, or it may be preferred to provide glue or other securing means to more securely retain it into position for use. As shown by way of example in FIG. 3, in one embodiment, it may be desired to provide a molded, angled portion 39 proximate the opening of the sleeve 12, against which an end of the magnet 32 would abut. This would further facilitate insertion of the hook 13 by facilitating its entry into the sleeve 12, and would prevent the hook 13 from being magnetically coupled to the magnet 32 until the hook 13 is in position within the interior of the sleeve 12. It is preferred that the apparatus 10, other than the magnet 32, be a one-piece assembly. In particular, it is preferred that it be formed from a single piece of molded plastic, though other materials may be substituted as desired. It should be noted that it may be desired to provide an apparatus having substantially the features of apparatus 10, without providing a magnet 32 therein. In such a configuration, securing of the hook 13 would be accomplished by, for example, the placement of tension on fishing line coupled between the hook 13 and a fishing reel. It should be noted that one or more than one apparatuses 10 may be positioned along a shaft 15, as desired. The apparatuses 10 may be positioned above the shaft or below the shaft, proximate the handgrip or remote from it—as desired. Referring now to FIGS. 11–14, a fishing hook retaining apparatus 40 (“apparatus 40 ”) consistent with another embodiment of the present invention is shown. In this embodiment, the apparatus 40 preferably comprises many of the features identified above with respect to the embodiment of FIGS. 1–10, which are shown in FIGS. 11–14 using the same reference numbers as used above. The embodiment of FIGS. 11–14 is distinguished from the embodiment of FIGS. 1–10 by the elimination of the outwardly projecting securing members 16. In their stead, coupling of the apparatus 40 is accomplished by other means. For example, as shown in FIG. 13, a base 42 may be provided, extending beyond a front and rear end of the apparatus 40, which base 42 may be coupled to a fishing pole shaft (not shown) by any desired means, such as the retention of ends of the base 42 below a ring or other grasping means, the gluing of the base 42 to the fishing pole shaft, or otherwise. The advantage of apparatus 40 as compared to apparatus 10 is the elimination of the O-ring, and the provision of a more permanent, more secure connection between the apparatus and the fishing pole shaft that does not require securing members 16. Other than with respect to the coupling thereof to the fishing pole shaft, the apparatus 40 functions like the apparatus 10 with respect to the insertion and storage of hooks therein. Referring now to FIGS. 15–18, a fishing hook retaining apparatus 50 (“apparatus 50 ”) consistent with another embodiment of the present invention is shown. In this embodiment, the apparatus 50 preferably comprises a base 52, opposing sides 54 projecting upward at a substantially ninety degree angle from the base 52, and a bar 56 interposed between the opposing sides 54. As best seen in FIGS. 15–16, it is preferred that the opposing sides 54 be angled from a first end to a second end thereof, so that the bar 56 is coupled proximate the highest point of opposing sides 54. This permits ready insertion of the hook 13, with the point 13 a clearing the shaft 15 when in position. As noted above with respect to the base 42 of the embodiment of FIGS. 10–14, the base 52 may be coupled to a fishing pole shaft 15 by any desired means, such as the retention of ends of the base 52 below a ring or other grasping means, the gluing of the base 42 to the fishing pole shaft, or otherwise. The apparatus 50 may be positioned along the shaft 15 as desired. In one embodiment, the apparatus 50 may be positioned proximate the handgrip, in the region where a keeper ring might otherwise be located. The size of the apparatus 50 components can be varied as desired, taking into account the size of the hook 13 and/or shaft 15 with which it is to be used. A width of about 0.3″ would be satisfactory for many uses, and a length of a top portion thereof of about 0.6″ would similarly be suitable for certain uses. However, these dimensions can be varied. Referring now to FIGS. 19–22, a fishing hook retaining apparatus 60 (“apparatus 60 ”) consistent with another embodiment of the present invention is shown. In this embodiment, the apparatus 60 preferably comprises many of the features identified above with respect to the embodiment of FIGS. 1–10, which are shown in FIGS. 19–22 using the same reference numbers as used above. The embodiment of FIGS. 19–22 is distinguished from the embodiment of FIGS. 1–10 by the elimination of the outwardly projecting securing members 16, and the integration of the apparatus 60 into the shaft 15. In this manner, the apparatus 60 will not protrude, or at least the amount of protrusion can be reduced, as compared to the apparatuses 10, 40 and 50 described above. This can serve to limit any interference that the apparatus 60 might otherwise cause with fishing activities. As best seen in FIG. 22, it may be desired to slightly recess a top portion of the sleeve 12, creating a slight stop 62 at either or both ends thereof, to further reduce the profile thereof. The size of the apparatus 10, 40, 50 and/or 60 components can be varied as desired, taking into account the size of the hook 13 and/or shaft 15 with which it is to be used. A width for the sleeve 12 of between about 0.2 and 0.25″ would be satisfactory for many uses, and a length of the sleeve 12 of about 0.6″ would similarly be suitable for certain uses. A sleeve height of between about 0.2 and 0.25″ would similarly be suitable for certain uses. However, these dimensions can be varied as desired without departing from the spirit or scope of the present invention. It should be understood that the invention is not necessarily limited to the specific arrangement, materials and components shown and described above, but may be susceptible to numerous variations within the scope of the invention. It will be understood that the above description of the preferred embodiments of the present invention are susceptible to various modifications, changes and adaptations, and the same are intended to be comprehended within the meaning and range of equivalents of the appended claims.

Summary: A fishing hook retaining apparatus and method, utilizing a retaining apparatus secured to a shaft of a fishing pole. In one embodiment, the apparatus is a sleeve having a magnet in an interior portion thereof, and a channel extending part of the way through an upper portion thereof. A hook is retained therein by the passage of a portion thereof through the channel, and the contacting of the hook with the magnet. The apparatus may be secured to the shaft, in one embodiment, with an O-ring that is looped over two opposing securing members, and about the shaft of the pole. In another embodiment, the apparatus comprises two upwardly angled opposing sides, with a bar interposed therebetween. In a third embodiment, the apparatus comprises a base having retention ends which couple the apparatus to the shaft of the pole. In yet another embodiment, the apparatus is integral with the shaft of the pole.

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Summarize: An Iranian strategic expert has warned that one of President Obama's daughters will be kidnapped and raped if America attacks Syria. Alireza Forghani, also the former governor of southern Iran’s Kish Province, warned of mass abductions and killings of American citizens worldwide in the event the Obama administration launches a military strike in Syria. 'Hopefully Obama will be pigheaded enough to attack Syria, and then we will see the … loss of U.S. interests [through terrorist attacks],' he threatened. 'In just 21 hours [after the attack on Syria], a family member of every U.S. minister [department secretary], U.S. ambassadors, U.S. military commanders around the world will be abducted. And then 18 hours later, videos of their amputation will be spread [around the world]' he said reported The Daily Caller. The threat comes amid reports today that the U.S has intercepted an order from an Iranian official instructing militants in Iraq to attack U.S. interests in Baghdad if the attack goes ahead. Claims: The U.S has intercepted an order from an Iranian official instructing militants in Iraq to attack U.S. interests in Baghdad in the event the Obama administration launches a military strike in Syria, it was reported today. The American embassy in Baghdad was a likely target, according to unnamed U.S. officials quoted by the Wall Street Journal. The Journal said the officials did not describe the range of potential targets indicated by the intelligence. In addition, the State Department issued a warning on Thursday telling U.S. citizens to avoid all but 'essential' travel to Iraq. President Barack Obama has asked the U.S. Congress to back his plan for limited strikes in response to a chemical weapons attack on civilians that the United States blames on Syrian President Bashar al-Assad's forces. The Journal reported that the Iranian. message was intercepted in recent days and came from the head of the. Revolutionary Guards' Qods Force. Target: The American embassy in Baghdad was a likely target, according to unnamed U.S. officials quoted. Scrutiny: Iraqi security forces stand guard in Baghdad today. In addition, the State Department issued a warning on Thursday telling U.S. citizens to avoid all but 'essential' travel to Iraq. The newspaper said the message went to Iranian-supported Shi'ite militia groups in Iraq. The Journal reported that the message informed Shi'ite groups to be prepared to respond with force after any U.S. military strike on Syria. 'Travel within Iraq remains dangerous given the security situation,' according to the State Department's warning, which replaced an earlier one 'to update information on security incidents and to remind U.S. citizens of ongoing security concerns in Iraq, including kidnapping and terrorist violence.' Group photo: Russia's President Vladimir Putin, center front, stands with G-20 leaders during a group photo outside of the Konstantin Palace. Sunshine smiles : President Putin, left, President Obama and German Chancellor Angela Merkel and PM David Cameron as they pose for the family photo. The department said that numerous insurgent groups, including al Qaeda's Iraq affiliate, remain active and 'terrorist activity and sectarian violence persist in many areas of the country at levels unseen since 2008.' It added: 'The ability of the embassy to respond to situations in which U.S. citizens face difficulty, including arrests, is extremely limited.' The State Department declined immediate comment. The CIA declined comment. The US and France are so far the only nations attending the G20 to have backed the use of military force against the Assad regime, with Russia and China insisting that any action in the absence of UN Security Council approval would be illegal. Italian Prime Minister Enrico Letta - who also attended this morning's aid meeting - said in a tweet last night that 'the G20 has just now finished the dinner session, at which the divisions about Syria were confirmed'. Man on a mission: Obama has expanded a list of targets in Syria as he struggles to gather international support for military action. President Barack Obama, left, listens as Russian President Vladimir Putin, right, speaks during the start of the G-20 Working Session. US frustrations over Russia's stance were reflected in comments by the American envoy to the UN, Samantha Power, who told a New York news conference: 'Even in the wake of the flagrant shattering of the international norm against chemical weapons use, Russia continues to hold the (Security) Council hostage and shirk its international responsibilities. 'What we have learned, what the Syrian people have learned, is that the Security Council the world needs to deal with this crisis is not the Security Council we have.' The US Government accuses Assad's forces of killing 1,429 people in a poison-gas attack in a suburb of the Syrian capital, Damascus, on August 21. Britain announced yesterday that scientists at the Porton Down research laboratories have found traces of the nerve gas sarin on cloth and soil samples retrieved from the site of the attack. Meanwhile, there were signs that Mr Obama may struggle to secure support in Congress for his proposal of 'limited and proportionate' military action against Assad. A poll commissioned by the BBC and ABC News suggested more than one-third of Congress members were undecided whether or not to back military action, while a majority of those who had made a decision said they would vote against the President. The survey found that 226 members of the House of Representatives said they would oppose or were likely to oppose military action, against 45 who were certain or likely to support it and 189 who were undecided or did not respond. Some 17 members of the Senate were certain or likely to oppose Mr Obama's plans, against 23 certain or likely to back him and 60 whose position was undecided or unknown

Summary: Threats made by Alireza Forghani, former governor of Iran's Kish Province. Unnamed U.S. officials: American embassy in Baghdad is a likely target. Officials did not describe range of potential targets indicated. State Department: U.S. citizens to avoid all but 'essential' travel to Iraq. Iranian message was intercepted in recent days. It came from the head of the Revolutionary Guards' Qods Force.

cnn_dailymail

en

Write a title and summarize: Grönland (grönländisch Kalaallit Nunaat, deutsch,Land der Kalaallit', dänisch Gronland, deutsch,Grünland') ist ein autonomer Bestandteil des Königreichs Dänemark. Der größte Teil der Landesfläche besteht aus der größten Insel der Erde, gelegen im Nordatlantik bzw. Arktischen Ozean. Grönland wird geografisch zu Nordamerika und geologisch zu dessen arktischer Teilregion gezählt. Grönland verfügt über die nördlichste Landfläche der Erde und ist nur spärlich besiedelt. Die gesamte Bevölkerung lebt an der Küste, vor allem im Westen des Landes. Bis 1953 eine dänische Kolonie, genießt Grönland seit 1979 Autonomie, seit 2009 in verstärkter Form. == Name Der Name Grönland ist die deutsche Schreibung des dänischen Gronland, das wörtlich übersetzt "Grünland" bedeutet. Dieser Name stammt vom altnordischen Grnland. Erik der Rote hatte das Land bei seiner Ankunft in Südgrönland so genannt. Es wird davon ausgegangen, dass der Name einerseits wegen des wärmeren Klimas eher zutreffend war als heute, andererseits soll es sich um einen Werbetrick gehandelt haben, um Siedler ab dem Jahr 985 n. Chr. anzulocken. Die grönländischsprachige Eigenbezeichnung ist Kalaallit Nunaat, was eine Ableitung von der Volksbezeichnung der Kalaallit (Sg. Kalaaleq) darstellt. Es ist weitgehend akzeptiert, dass es sich hierbei um eine Entlehnung aus dem altnordischen skrlingr handelt, das an die grönländische Phonotaktik angepasst wurde. Der Begriff wurde in der Wikingerzeit genutzt, um die in Grönland und Kanada lebenden Inuit zu bezeichnen. Im Labrador-Dialekt des Inuktitut findet sich gleichermaßen der Begriff karaaliq zur Bezeichnung eines Grönländers, der bereits im 18. Jahrhundert belegt ist. Auch im Grönländischen war im 18. Jahrhundert noch die Form mit r belegt, das aber in Lehnwörtern üblicherweise zu l wurde. == Geografie === Landschaftsformung ==== Allgemeines Grönland reicht von 59° 46' nördlicher Breite am Kap Farvel bis 83° 40' nördlicher Breite an der Kaffeklubben-Insel beim Kap Morris Jesup und ist 2670 km lang. Die Breite beträgt maximal 1050 km vom Kap Alexander im Westen bis Nordostrundingen im Osten. Grönlands Nordküste ist mit 740 km Abstand die dem Nordpol am nächsten gelegene größere zusammenhängende Landmasse. Im Norden der Insel liegt der vereiste Arktische Ozean mit seinen Randmeeren Lincolnsee und Wandelsee. Im Osten grenzt sie an die Grönlandsee und an die Irmingersee, im Westen an die Davisstraße und die Baffin Bay, alles Randmeere des Atlantiks. Im Nordwesten geht Grönland in die sehr zerklüftete und weitläufige Inselwelt der Königin-Elisabeth-Inseln über. Dort ist Grönland durch die Naresstraße, die die Baffin Bay mit der Lincolnsee verbindet und bereits zum Arktischen Ozean gehört, von der Ellesmere-Insel (Teil der Königin-Elisabeth-Inseln) getrennt. Das gesamte grönländische Inland ist von einem Eisschild bedeckt, das auf einem teils unter dem Meeresspiegel liegenden Becken ruht. Er macht vier Fünftel der Landesfläche aus. Die eisfreien Küstenbereiche machen eine Fläche aus, die etwas größer als die Fläche Deutschlands ist. Auf Weltkarten wird Grönland oft stark verzerrt dargestellt. Da es nicht möglich ist, die Oberfläche der kugelförmigen Erde ohne Verzerrungen auf eine flache Karte abzubilden, kann eine Weltkarte nicht zugleich längentreu, flächentreu und winkeltreu sein. In der winkeltreuen klassischen Mercatorprojektion erscheint die Insel Grönland (2,2 Mio. km^2) infolge hoher geografischer Breite überaus groß dargestellt, verglichen etwa mit Kontinenten wie Afrika (30 Mio. km^2) oder Australien (8,6 Mio. km^2). ==== Küstengeografie Der eisfreie Küstenstreifen hat verschiedene Breiten, teilweise reicht das Inlandseis bis direkt an die Küste heran. Die Küste ist vor allem im Westen und Osten von mehreren tausend Fjorden, Buchten und Meerengen zerschnitten, durch die der Hauptinsel ebenso viele Inseln und Schären vorgelagert sind. Dadurch beträgt die grönländische Küstenlänge etwa 39.000 km. Der Norden und Nordwesten Grönlands um den Distrikt Qaanaaq ist geprägt von bis zu 100 km breiten Gletschern wie dem Humboldt-Gletscher und massiven eisfreien Küstenbereichen, denen nur wenige Inseln vorgelagert sind. Südlicher liegt die Melville-Bucht und südlich davon der Distrikt Upernavik, wo das gesamte Festland vom Inlandeis bedeckt ist. Ihm vorgelagert liegen hunderte mehrheitlich kleine Inseln. Südlich davon im Distrikt Uummannaq und der Diskobucht ist die Küste von wenigen größeren Inseln, wobei der eisfreie Küstenstreifen hier eine Breite von durchschnittlich etwa 20 km erreicht. Im zentralen Westgrönland erreicht dieser Längen von bis zu knapp 200 km, der von ebenso langen Fjorden und hunderten kleiner vorgelagerter Inseln geprägt ist. Nach Süden hin verringert sich die Breite auf etwa 50 km. Südgrönland ist noch etwas stärker von Fjorden zerfurcht. Hier liegt die Breite bei etwa 70 bis 120 km. Die grönländische Ostküste hat kaum eisfreie Bereiche und nur wenige kleinere Inseln. Im Nordosten erreicht der Küstenstreifen wieder Breiten von bis zu 200 km und ist von langen Fjorden und großen Inseln geprägt. Die grönländischen Fjorde gehören zu den größten und tiefsten der Welt. Der Kangertittivaq in Ostgrönland ist mit einer Länge von 300 km, einer Breite von 40 km und einer Tiefe von bis zu 1450 m der größte der Welt. Am Ende der Fjorde befinden sich häufig vom Inlandeis kommende Gletscher, die wie der Jakobshavn Isbr gewaltige Mengen Eis ins Meer kalben lassen. Die Küste ist in leicht gewelltes Hochland mit sehr hohen Bergen und Gebirgen, von denen der im Watkins-Gebirge im Osten der Insel gelegene Gunnbjorns Fjeld mit 3694 m der höchste ist. Die größte Nebeninsel Grönlands ist die Diskoinsel in der Diskobucht in Westgrönland. ==== Inlandsgeografie Das grönländische Inland ist vollständig von Eis bedeckt. Der bis zu 3400 m mächtige, durchschnittlich 2000 m starke grönländische Eisschild bewegt sich an den Küsten zum Meer und lässt oft Eisberge von mehreren Kilometern Länge entstehen. Er ist der zweitgrößte Eisschild des Planeten, nur übertroffen vom stellenweise mehr als 4700 m dicken antarktischen Eisschild. Die Vereisung setzte vor etwa 2,7 Millionen Jahren ein. Damals setzte durch die Schließung der Landenge von Panama eine neue Phase des känozoischen Eiszeitalters ein, die Gebirge im Osten der Insel waren hoch genug gehoben worden und die Insel in ausreichende Polnähe geraten, um die bis heute anhaltende Vergletscherung auszulösen. Das Festland unter dem Inlandeis liegt bedingt durch den Druck des Eisschilds teilweise unter dem Meeresspiegel. In ihm befindet sich auch der 2013 entdeckte Grand Canyon von Grönland, der mit mindestens 750 km Länge, 10 km Breite und 800 m Tiefe größer als der Grand Canyon im Westen der USA ist. Durch die globale Erwärmung ist das grönländische Inlandeis einem kontinuierlichen Abschmelzprozess ausgesetzt. Zwischen 2011 und 2014 verlor der Eisschild auf Grönland im Schnitt etwa 269 Mrd. Tonnen (ca. 293 km^3) Eis pro Jahr. Der Massenverlust hat sich seit den 1980er Jahren versechsfacht. Würde das gesamte Inlandeis Grönlands (2,85 Mio. km^3) schmelzen, würde der Meeresspiegel weltweit um 7,4 Meter steigen. Von der Eislast befreit würde die Insel in ihren Zentralbereichen, die heute teilweise unter den Meeresspiegel gedrückt werden, um rund 800 Meter aufsteigen (postglaziale Landhebung). === Geologie Die Insel war Bestandteil des sehr alten präkambrischen Kontinents Laurentia, dessen östlicher Kern den Grönland-Schild bildet, während er an den weniger exponierten Küstenstreifen in eine Tafel übergeht. In diesen eisfreien Küstenstreifen treten präkambrisch gebildete, metamorph überprägte und mittlerweile glazial geformte Sedimente auf, welche sich in Teilen der Insel bis ins Känozoikum und Mesozoikum fortsetzen. In Ost- und Westgrönland gibt es Relikte von Flutbasalten. Erwähnenswerte Gesteinsprovinzen liegen an der Südwestküste bei Qeqertarsuatsiaat vor (metamorphe Magmatite, Ultramafite und Anorthosite). Östlich von Nuuk finden sich in der über drei Milliarden Jahre alten Isukasia-Bändereisenerz-Region die ältesten Gesteine der Welt, darunter Grönlandit (ein Gestein vorwiegend aus Hornblende und Hypersthen), entstanden vor 3,8 Milliarden Jahren, sowie Nuummit. Neben der Isukasia-Eisenerz-Region gibt es auf Grönland an der Westküste noch zwei weitere bedeutende Bändereisenerz-Vorkommen bei Qaanaaq und der Talsenke Itilliarsuk östlich von Qeqertaq. In Südgrönland besteht der Illimaussaq Alkaline Complex aus Pegmatiten wie Nephelin-Pegmatit, Syeniten (namentlich Kakortokit oder Naujait) sowie Sodalithit (Sodalith-Foyait). Bei Ivittuut, wo früher Kryolith abgebaut wurde, kommt der fluoridführende Pegmatit vor. Nördlich von Igaliku finden sich die Gardar-Alkali-Pegmatit-Intrusionen aus Augit-Syenit, Gabbro etc. Im Westen und Südwesten gibt es paläozoische Carbonatitkomplexe bei Kangerlussuaq (Gardiner-Komplex) und Safartoq sowie basische und ultrabasische Eruptivgesteine bei Uiffaq auf der Diskoinsel, wo bis zu 25 t schwere gediegene Eisenmassen in den Basalten vorkommen. === Klima ==== Heutiges Klima Die Klimaverhältnisse unterscheiden sich innerhalb Grönlands stark. In den Küstenbereichen herrscht ein subpolares Klima, im Norden und im Inland hingegen polares Klima. Das Klima ist stark von den Jahreszeiten abhängig. Entlang der Küste unterscheiden sich die Temperaturverhältnisse im Sommer im Norden Grönlands nur wenig von denen im Süden, was durch die konstante Sonneneinstrahlung der Mitternachtssonne begründet ist. Im Winter sinkt die Temperatur aufgrund der fehlenden Sonne hingegen umso stärker im Norden. Neben der Sonneneinstrahlung hat auch die von den Eisverhältnissen abhängige Wassertemperatur einen großen Einfluss auf die Temperatur. An der Westküste wird das Klima durch den Grönlandstrom gemildert, den hier der Nordatlantische Strom und der Golfstrom mit relativ warmem Wasser versorgen. Rund 100 km von der Küste entfernt ist das Klima deutlich kontinental geprägt, ähnlich dem Klima Sibiriens oder Mittelalaskas. Auf dem Inlandseis wurden bis zu rund -70 °C gemessen, während in Maniitsoq im Juli 2013 25,9 °C erreicht wurden. Die Jahresdurchschnittstemperatur liegt in Grönland üblicherweise unter dem Gefrierpunkt, nur in Südgrönland leicht darüber. In den Küstenbereichen entspricht die Niederschlagsmenge etwa der Oslos. In den kontinentalen Inlandsbereichen und in Nordgrönland fällt hingegen deutlich weniger Niederschlag, sodass diese Gebiete als Kältewüsten klassifiziert werden können. Auch in Kangerlussuaq, das als einziger Ort Grönlands mehr als 100 km vom Ozean entfernt liegt, fällt nur ein Fünftel der Niederschlagsmenge der Küstenstädte. Wegen der Temperaturen fällt der Niederschlag häufig als Schnee, im Sommer jedoch als Regen. Schnee im Sommer ist möglich, Regen im Winter jedoch selten. Die Windverhältnisse sind deutlich variabler als in Europa. An der grönländischen Küste ist es häufig windstill, aber Föhnwinde und katabatische Winde strömen häufig plötzlich von den Gebirgen hinab und sorgen so für starke Stürme. Der bekannteste von ihnen ist der Piteraq, der in Ostgrönland auftritt und dort in bewohnten Bereichen für starke Zerstörungen sorgen kann. Meist gibt es leichte Winde, die tageszeitenabhängig fjordauf- oder -abwärts wehen. ==== Historische Klimaentwicklungen In den Bohrkernen von Material unter dem mehr als 2000 Meter dicken Eis wurden DNA-Spuren von Kiefern, Eiben und Erlen sowie von Schmetterlingen und anderen Insekten gefunden, die ein Alter zwischen 450.000 und 800.000 Jahren aufzuweisen scheinen, wegen Messunsicherheiten aber auch nur etwa 120.000 Jahre alt sein könnten. Die Forscher um Martin Sharp (University of Alberta, Kanada) vermuten daher, dass Grönland vor der Vergletscherung während der Riß-Kaltzeit ein "grünes Land" mit deutlich wärmerem Klima als heute war. Die Besiedelung Grönlands im Mittelalter durch die Grnlendingar und die Thule-Kultur geht zeitlich mit der Mittelalterlichen Warmzeit einher. Während der Kleinen Eiszeit in der zweiten Hälfte des 2. Jahrtausends sank die Temperatur hingegen wieder. Um 1890 begann die Temperatur wieder zu steigen und erreichte einen Höhepunkt in den 1930er und 1940er Jahren. Das Klima wurde dabei allgemein deutlich maritimer, also mit geringeren Temperaturschwankungen im Laufe des Jahres. Anschließend blieb die Temperatur gleich und sank leicht, ab den 1950er Jahren wieder stärker. Diese Klimaänderung hatte großen Einfluss auf die grönländischen Eisverhältnisse und damit auch auf die wirtschaftliche Grundlage, weg vom Robbenfang hin zur Fischerei. Durch die größtenteils menschlich verursachte globale Erwärmung steht das Ökosystem Grönlands vor schweren Veränderungen. 2015 zeigte die Arktis erste Zeichen von irreversiblen Veränderungen; unter anderem könnte ein Temperaturanstieg zwischen 1 °C und 4 °C das fast vollständige Abschmelzen des grönländischen Eises auslösen. Das Risiko, das sich durch die Aktivierung weiterer Kippelemente ergibt, ist dabei von der Höhe des Temperaturanstieges abhängig und ist bei einer stärkeren Erwärmung umso größer. Seit 1990 hat sich die Durchschnittstemperatur im Sommer um 1,8 °C und im Winter um 3 °C erhöht. Durch vermehrte Regenereignisse wird das Abschmelzen der grönländischen Gletscher weiter beschleunigt, und die Bewölkung verhindert, dass viel Wärme entweichen kann. === Flora und Fauna ==== Flora Grönlands Inland ist ein vegetationsfreier Eisschild. Die Küstengebiete lassen sich hingegen aufgrund der klimatischen Verhältnisse in drei verschiedene Biome aufteilen, die jedoch allesamt durch das Fehlen von eigentlichen Wäldern charakterisiert sind. Auf Grönland wachsen rund 3500 Arten von Moosen, Flechten, Pilzen und Algen. Dazu kommen etwa 500 Arten höherer Pflanzen. Zu diesen gehören Farne, Bärlapppflanzen, Wacholder und zahlreiche Bedecktsamer wie Hahnenfußgewächse, Rosengewächse, Steinbrechgewächse, Kreuzblütler, Nelkengewächse, Heidekrautgewächse, Nachtschattengewächse, Korbblütler, Binsengewächse, Sauergrasgewächse und Süßgräser. Fossilien weisen darauf hin, dass vor 55 Millionen Jahren Wälder überwiegend aus Mammutbäumen und Laubbäumen existierten. Vor vor 900.000 bis 450.000 Jahren war Grönland bewaldet, unter anderem mit Erlen, Fichten, Kiefern und Eiben. Der Klimawandel führt derzeit dazu, dass die Pflanzen eher blühen können. ==== Fauna Grönlands Fauna ist gut erforscht. Archäologische Untersuchungen ermöglichen Erkenntnisse zu früher in Grönland lebenden Tieren. Dazu kommen Beschreibungen der Tierwelt aus schriftlichen Quellen, begonnen bei altnordischer Literatur in Form des Konungs skuggsja (um 1230) und später wissenschaftlichen Beschreibungen von Hans Egede, seinen Söhnen Poul und Niels Egede sowie Otto Fabricius. Später wurden zahlreiche Expeditionen zur Erforschung der grönländischen Fauna durchgeführt. Auf dem grönländischen Land und im Meer leben zahlreiche Säugetiere, Vögel, Fische und Insekten, während Reptilien und Amphibien nicht vorkommen. Die grönländische Landfauna ist in zwei geografische Zonen geteilt, die durch die Melville-Bucht und den Kangertittivaq getrennt werden. In Grönland gibt es nur wenige Arten von Landsäugetieren. In der südlichen Zone kommen Rentiere, Schneehasen und Polarfüchse vor. Wilde Rentiere leben vor allem im zentralen Westgrönland um Sisimiut und Maniitsoq. Schneehasen und Polarfüchse leben auch in der nördlichen Zone. Ausschließlich in der nördlichen Zone leben Moschusochsen und Hermeline sowie der Nördliche Halsbandlemming, dessen Bestand die Vorkommen seiner Fressfeinde stark beeinflussen kann. Durch die Ankunft von Polarwölfen in Nordostgrönland starben um 1900 die Rentiere dort aus. Später verschwand auch der Polarwolf wieder. Im 20. Jahrhundert wurden europäische Rentiere sowie Moschusochsen zur Fleischproduktion in Westgrönland angesiedelt. Der Eisbär lebt ebenfalls hauptsächlich in der nördlichen Zone, bewegt sich auf Treibeis aber regelmäßig in die bewohnten Gebiete West- und Ostgrönlands, wo er eine Gefahr für Menschen, aber auch eine Nahrungsquelle darstellt. In den Gewässern vor Grönlands Küste leben zahlreiche Walarten: Grönlandwale, Zwergwale, Buckelwale, Grindwale, Schweinswale, Schwertwale, Blauwale, Finnwale, Narwale und Weißwale. Neben den Walen gibt es sechs Robbenarten, von denen die Ringelrobbe die verbreitetste ist. Daneben gibt es Bartrobben, Walrösser, Sattelrobben, Klappmützen und wenige Seehunde. Die Inuit zählen auch den Eisbär zu den Meeressäugern, weil dieser wesentliche Zeit seines Lebens auf dem Meer, insbesondere auf dem Pack- und Treibeis, verbringt. Die grönländische Vogelwelt lässt sich ebenfalls in Land- und Seevögel unterteilen. Unter den an Land lebenden Vögeln sind in der südlichen Zone folgende von größerer Bedeutung: Alpenschneehühner, Kolkraben, Schneeammern, Spornammern, Steinschmätzer, Birkenzeisige und Polar-Birkenzeisige leben in ganz Westgrönland. Dazu kommen mehrere Vogelarten, die nur regional vorkommen: Wacholderdrosseln in Südwestgrönland, Strandpieper in Nordwestgrönland und Wiesenpieper nur im Südosten. Des Weiteren gibt es mehrere Raubvögel: Im Westen und Südwesten leben Seeadler, dazu kommen Wanderfalken und Jagdfalken. Zu den Küsten- und Ufervögeln gehören Meerstrandläufer, Odinshühnchen, Thorshühnchen, Mittelsäger, Eistaucher, Sterntaucher, Eisenten, Stockenten, Kragenenten und Blässgänse. In der nördlichen Zone leben Schneeeulen, Gerfalken, Falkenraubmöwen, Schneehühner, Schneegänse, Ringelgänse, Weißwangengänse, Kurzschnabelgänse, Regenpfeifer, Steinwälzer, Knuttstrandläufer, Alpenstrandläufer und Sanderlinge. Seevögel leben häufig an den grönländischen Vogelfelsen. Zu ihnen gehören Eiderenten, Prachteiderenten, Trottellummen und Krabbentaucher, die eine große Rolle spielen. Dazu kommen kleinere Kolonien von Papageitauchern, Tordalken, Kormoranen und Gryllteisten. In Grönland gibt es zudem zahlreiche Möwenarten, wie die Dreizehenmöwe, Eismöwe, Polarmöwe, Mantelmöwe, Schmarotzerraubmöwe, Falkenraubmöwe, Küstenseeschwalbe sowie die selteneren Schwalbenmöwe, Elfenbeinmöwe und Rosenmöwe. Weitere vor der Küste lebende Vögel sind der Eissturmvogel und der Große Sturmtaucher. Die Gewässer in und um Grönland werden von zahlreichen Fischarten bevölkert. In den Flüssen und Seen leben Seesaiblinge, Dreistachlige Stichlinge und Lachse. Die Fischerei stellt wegen der zahlreichen Speisefische einen wichtigen Wirtschaftszweig dar. Im Meer leben Rotbarsche, Gestreifter Seewolf, Schwarzer Heilbutt, Heilbutt, Lachse, Lodden, Grönlandhaie, Seehasen, Atlantischer Hering, Doggerscharben, Vahls Wolfsfisch, Polardorsch, Groppen, Rochen, Uuaq, Lumbe, Rundnasen-Grenadier, Blaulenge, Schellfische und Köhler. Unter den Garnelen spielt die Eismeergarnele die größte Rolle. Daneben kommen Krabben, Tintenfische und Mies- und Kammmuscheln vor. Auf Grönland leben etwa 700 bis 800 Insektenarten und Spinnentiere. Zu diesen gehören vor allem Stech- und Kriebelmücken, Gnitten, Schmeißfliegen, Schmetterlinge (Spanner, Wickler und Eulenfalter), Marienkäfer, Wolfsspinnen und Kreuzspinnen. Dazu kommen Schnecken und Regenwürmer. === Siedlungsgeografie ==== Verwaltungsgliederung Grönland ist in fünf (bis 2018 vier) Kommunen aufgeteilt, die im Zuge einer Kommunalreform im Jahr 2009 gebildet wurden. Die Qaasuitsup Kommunia wurde 2018 in die Avannaata Kommunia und die Kommune Qeqertalik aufgespalten. Neben den fünf Kommunen gibt es mit dem unbewohnten Nordost-Grönland-Nationalpark und der Thule Air Base (Pituffik) zwei gemeindefreie Gebiete. Die fünf Kommunen sind folgende (Einwohnerzahlen vom 1. Januar 2021): Historisch war Westgrönland bis 1950 in eine im Laufe der Zeit variierende Zahl an Koloniedistrikten aufgeteilt, zuletzt elf. Diese verteilten sich auf die zwei Inspektorate Nordgrönland und Südgrönland. Die Koloniedistrikte waren seit 1911 in gut 60 Gemeinden unterteilt. 1950 wurden festgelegt, dass Grönland aus drei Landesteilen besteht: Westgrönland (Kitaa), das aus den beiden bisherigen Inspektoraten bestand, und die beiden administrativ eingegliederten Landesteile Ostgrönland (Tunu) und Nordgrönland (Avanersuaq). Von da an bestand Grönland aus 19 und später 18 Gemeinden, die größtenteils deckungsgleich mit den vorherigen Koloniedistrikten waren. Die 18 Gemeinden wurden 2009 zu den vier Kommunen zusammengelegt. Die bisherigen Gemeinden bestehen darunter als Distrikte weiter, dienen aber eher statistischen und kulturellen als administrativen Abgrenzungszwecken. ==== Ortschaften Die Inuit lebten früher halbnomadisch, lebten also immer an dem Ort, wo man Nahrung finden konnte, und zogen dann zum nächsten Wohnplatz weiter. Durch die Kolonialisierung wurden an manchen Orten Handels- und Missionsstationen mit Infrastruktur errichtet. Zuerst entstanden Kolonien, die für ein bestimmtes Gebiet (die Koloniedistrikte) zuständig waren, ab etwa 1800 wurden auch Udsteder gegründet, die einer Kolonie untergeordnet waren und als lokales Zentren innerhalb des Distrikts dienten. Zahlreiche Wohnplätze erhielten nie eine Infrastruktur und wurden regelmäßig besiedelt und verlassen. Anfang des 20. Jahrhunderts nahm die Mobilität ab und die Wohnplätze wurden dauerhafter besiedelt. In der Mitte des 20. Jahrhunderts wurden fast alle Wohnplätze aufgegeben und die Bevölkerung zog in die ehemaligen Udsteder und Kolonien, die zu Dörfern und Städten wurden. Nur eine Handvoll Wohnplätze überlebten diese Phase und wurden dann ebenfalls als Dörfer klassifiziert. Heute gibt es in Grönland 17 Städte, 55 Dörfer, rund 30 südgrönländische Schäfersiedlungen und einige bewohnte Stationen verschiedener Art. Die Städte dienen als Lokalzentrum für die umliegenden Dörfer. Die meisten Orte liegen an der Westküste der Insel. Dazu kommen sieben Orte an der Ostküste. Die 17 grönländischen Städte sind auf der nebenstehenden Karte verzeichnet. Mittlerweile lebt ein Drittel der grönländischen Bevölkerung in der Hauptstadt Nuuk (rund 18800) Einwohner. Die nächstgrößere Stadt ist Sisimiut mit etwa 5600 Einwohnern. Sechs Städte haben mindestens 2000 Einwohner, weitere sieben zwischen 1000 und 2000 Einwohner. Vier Städte haben unter 1000 Einwohner. Die kleinste Stadt ist Ittoqqortoormiit mit etwa 360 Einwohnern. Mit jeweils rund 450 Einwohnern sind die beiden Dörfer Kangerlussuaq und Kullorsuaq größer als Ittoqqortoormiit. Die übrigen Dörfer haben maximal 300 Einwohner, die kleinsten nur rund 20 Einwohner. == Bevölkerung === Zusammensetzung Grönland hat etwa 56.000 Einwohner. Von diesen sind etwa 89 % in Grönland geboren und 11 % außerhalb. Knapp 98 % der Bevölkerung haben die dänische Staatsbürgerschaft. Da weder in Grönland noch in Dänemark der ethnische Hintergrund untersucht wird, können nur Umfragen und Schätzungen zur ethnischen Bevölkerungsstruktur abgegeben werden. Üblicherweise ist das Grönländischsein eine Frage der Selbstidentifikation. Eine Studie von 2019 hat ergeben, dass etwa 92 % der grönländischen Bevölkerung sich als Grönländer identifizieren, was gut 51.300 Personen entspricht. Die übrige Bevölkerung von rund 5000 Personen besteht aus dänischen Staatsbürgern nichtgrönländischer Identität und Ausländern. Letztere machen rund 1350 Personen aus. Von diesen sind rund 30 % Philippiner, 17 % Thailänder und 9 % Isländer. Weitere signifikante Minderheiten (mindestens 50 Personen) sind Schweden, Norweger, Polen, Deutsche, Chinesen und US-Amerikaner. === Ethnien Als Grönländer werden im rechtlichen Sinne alle dänischen Staatsbürger mit Wohnsitz in Grönland bezeichnet, ungeachtet ihrer Ethnizität. Im ethnischen Sinn gilt als Kalaallit (Sg. Kalaaleq) hingegen nur der Teil der Bevölkerung, der Inuit-Vorfahren hat und in der Regel Grönländisch (Kalaallisut) spricht. Ein Teil dieser Gruppe unterhält seinen Wohnsitz in Dänemark. Ethnologisch lassen sich die Kalaallit in drei Gruppen unterteilen, die sich in Herkunft, Geschichte und Sprache unterscheiden. Auch hier wird keine Statistik geführt, sodass Zahlen nur geschätzt werden können: Die Kujataamiut in Südgrönland gehören zu den Kitaamiut, haben sich aber im 19. Jahrhundert durch Zuwanderung mit den Tunumiit vermischt. Wegen der unterschiedlichen Geschichte bezeichnen sich beispielsweise manche Inughuit nicht als Kalaallit, um ihre eigene Ethnizität hervorzuheben. Der größte Teil der grönländischen Bevölkerung, vor allem die Kitaamiut, ist gemischtethnisch und stammt teils von den Inuit der Thule-Kultur, die nach dem Jahr 1000 von Norden kommend die grönländische Küste besiedelten, teils von den dänischen, in selteneren Fällen norwegischen, isländischen und schwedischen Kolonialangestellten ab, die vom 18. bis zum 20. Jahrhundert in Grönland dienten. 80 % der Grönländer haben heutzutage auch europäische Vorfahren, wobei der europäische Genanteil durchschnittlich 31 % der DNA ausmacht. Lediglich die Tunumiit und Inughuit haben wesentlich weniger europäische Genanteile, weil ihre Gebiete erst um 1900 kolonialisiert wurden. Die Nachnamen der grönländischen Bevölkerung sind teils während der Missionierung neu gebildete Patronyme zu dänischen (Petersen, Olsen, Jensen, Nielsen, Hansen) oder biblischen Namen (Jeremiassen, Petrussen, Filemonsen, Isaksen, Tobiassen), teils die Nachnamen der europäischen Stammväter. Durch das häufige Vorkommen deutscher Nachnamen in Dänemark sind auch viele der Nachnamen in Grönland deutschen Ursprungs (Heilmann, Kleist, Kreutzmann, Fleischer, Chemnitz). Die Grönländer sind nicht zu verwechseln mit Grnlendingar, den skandinavischen Siedlern, die vom 10. bis zum 15. Jahrhundert in Westgrönland lebten. === Sprachen Einzige offizielle Amtssprache in Grönland ist die grönländische Sprache (Kalaallisut). Daneben ist Dänisch Verkehrssprache, das in der Schule erste Fremdsprache ist. Es gibt keine offizielle Statistik zur Sprachsituation in Grönland, allerdings hat das Sprachsekretariat Oqaasileriffik eine Schätzung abgegeben, dass in der Bevölkerung etwa 50 % nur schlecht Dänisch sprechen, 20 % zweisprachig sind und Grönländisch bevorzugen, 20 % zweisprachig sind und Dänisch bevorzugen und 10 % nur Dänisch sprechen. Andere Untersuchungen geben einen weitaus höheren Anteil an Zweisprachigkeit an. In der Dekolonisationsphase von etwa 1950 bis 1980 wurde Dänisch gegenüber Grönländisch in der Schule bevorzugt, sodass vor allem die Generation, die in dieser Zeit zur Schule ging und zudem die größte in Grönland ist, am besten Dänisch spricht. Zudem ist Dänisch in den Städten weiter verbreitet als in den Dörfern und in Nuuk. Gymnasial- und Universitätsbildung findet auf Dänisch statt, womit Sprachkenntnisse eine Voraussetzung für eine weiterführende Ausbildung sind. Auch am Arbeitsplatz und in der Verwaltung überwiegt die dänische Sprache. Unter der nichtgrönländischen Bevölkerung in Grönland ist die Kenntnis der grönländischen Sprache kaum existent. Die grönländische Sprache ist in sich dialektal stark zersplittert. Teilweise kann man Personen anhand ihres Dialekts nach ihrem Herkunftsort zuordnen. Generell wird die grönländische Sprache gemäß der ethnischen Gruppen in Kitaamiusut (Westgrönländisch), Tunumiisut (Ostgrönländisch) und Inuktun (Nordgrönländisch) unterteilt. Kitaamiusut lässt sich weiter unterteilen, wobei die nördlichen und südlichen Dialekte starke ostgrönländische Sprachkontakteinflüsse aufweisen. === Religion Die traditionelle Religion der Inuit wurde im Zuge der Missionierung ab dem 18. Jahrhundert vom Christentum abgelöst. Ursprünglich gab es zwei parallele Missionierungsprozesse in Grönland, bei denen ein Teil der westgrönländischen Bevölkerung von der Dänischen Mission geprägt wurde, ein anderer von der Herrnhuter Brüdergemeine. 1900 wurden die Mitglieder der letzteren in die dänische Mission überführt. In Ost- und Nordgrönland wurden 1921 bzw. 1934 die letzten "Heiden" missioniert. Heute gehören 95 % der grönländischen Volkskirche an, die ein Teil der dänischen Volkskirche ist. Andere Religionen spielen kaum eine Rolle. Seit 1958 gibt es eine katholische Gemeinde mit rund 300 Mitgliedern in Nuuk, der hauptsächlich philippinische Einwanderer angehören. Insgesamt geben 98,5 % der Bevölkerung an, Christen zu sein. Auch wenn Grönländer keiner schamanistischen Religion mehr angehören, sind die Inuit-Mythen kulturell aber noch bewusst. Knapp die Hälfte der Bevölkerung glaubt an Geister. == Geschichte === Besiedlung Um 3000 v. Chr. wanderten die Vorfahren der ersten Inuit über die Beringstraße aus Asien nach Alaska. Um 2500 v. Chr. begannen die ersten Einwanderungen von Prä-Dorset-Eskimos (Paläo-Eskimos) nach Grönland (unter anderem Menschen der Saqqaq-Kultur). Bereits aus dieser Zeit sind Jagdplätze zum Beispiel in der Disko-Bucht und bei Qaja in der Nähe des Jakobshavn-Isfjords nachgewiesen. Diese Erstbesiedler starben wieder aus, aber von 500 v. Chr. bis 1000 n. Chr. siedelten Angehörige der Dorset-Kultur (Neo-Eskimos) in Grönland. Um 875 entdeckte der Norweger Gunnbjorn die Insel und nannte sie Gunnbjornland. 982 musste Erik der Rote aus Island fliehen und landete schließlich im Südwesten Grönlands. Er gab der Insel ihren Namen Grnland (altnordisch für "Grünland"), was wahrscheinlich darauf zurückzuführen ist, dass aufgrund der mittelalterlichen Warmzeit im Küstengebiet eine üppigere Vegetation entstehen konnte, aber möglicherweise auch nur ein Euphemismus war, um potentielle Siedler zu motivieren. Die in Grönland siedelnden Wikinger wurden daher Grnlendingar genannt. Mit Erik begann daher die vielversprechende Landnahme. Mit seinen Gefolgsleuten besiedelte er ab 986 die Gegend um Brattahli. 986 erreichten nur 14 von 25 isländischen Auswandererschiffen mit 700 Menschen an Bord Grönland. Aus der Zeit um 1000 sind im Süden Wohn- und Kirchenruinen nordländischer Siedler erhalten. === Christianisierung und Nordmännerbesiedlung 1000 kehrte Leif Eriksson, der Sohn Eriks des Roten, von Norwegen, wo er Christ wurde, mit einem Missionar nach Grönland zurück. Die grönländischen Wikinger wurden Christen und errichteten die erste Kirche. Eriksson entdeckte in dieser Zeit dann, von Grönland kommend, das nordamerikanische Festland (Vinland). Die Handelsbeziehungen mit Vinland dauerten bis ins 14. Jahrhundert. Ebenfalls in dieser Zeit wanderten aus Alaska und Nordkanada Inuit der Thule-Kultur ein und verdrängten die bisher dort lebenden Dorset-Inuit. 1076 gab Adam von Bremen in seiner Geschichte des Erzbistums Hamburg den ersten schriftlichen Nachweis über die Besiedlung und Christianisierung Grönlands, das bei ihm Gronland heißt. Grönland gehörte damals kirchlich administrativ zum Erzbistum Hamburg-Bremen. Um 1124 bis 1126 wurde Grönland eine eigene Diözese, deren Bischofssitz in Gardar, dem heutigen Igaliku, mit der Kathedrale von Garar lag. 1350 berichtete der isländische Kirchenmann Ivar Bardarsson, dass die westliche Siedlung aufgegeben sei. Eine schwedisch-norwegische Expedition unter Paul Knudson (1355-1364) fand dort keine Grnlendingar mehr vor. Von 1408 stammt die letzte schriftliche Aufzeichnung der Nordmänner aus der östlichen Siedlung, die von einer Hochzeit in der Kirche von Hvalsey berichtete. Die Kontakte mit Norwegen und Island rissen ab. Spätestens um 1550 erlosch die letzte nordische Siedlung in Grönland. Neuere genetische Untersuchungen sowohl an heutigen Inuit als auch an archäologischen Überresten der Grnlendingar scheinen eine Vermischung der beiden Gruppen auszuschließen, das heißt, die Grnlendingar sind wahrscheinlich ausgestorben. Bis heute gibt es für das Verschwinden der Nordmännersiedlungen keine allgemein akzeptierte Erklärung. Vermutlich wirkten verschiedene Einflüsse, wie das Ende der mittelalterlichen Warmzeit sowie die Ausbreitung der Thule-Inuit in die Gebiete der Grnlendingar-Siedlungen zusammen. Verschiedene in der Forschung vertretene Ansätze werden im Artikel Grnlendingar vorgestellt. === Rolle der Norweger und Dänen Nachdem der Kontakt Europas mit den Siedlern auf Grönland 1408 abgerissen war, blieb die Insel wegen ihrer Unwirtlichkeit 300 Jahre lang wenig beachtet. Der englische Seefahrer John Davis landete 1585 auf der Suche nach der Nordwest-Passage als erster Neuentdecker Grönlands, das er Land of Desolation nannte, in der Nähe des heutigen Nuuk. Er umschiffte die Südspitze der Insel und gab dem Kap Farvel seinen Namen. Unter Christian IV. gab es 1605, 1606 und 1607 drei Grönlandexpeditionen. Bei der ersten empfahl Steuermann James Hall, der wahrscheinlich ebenfalls bei John Davis gefahren war, die von John Davis genommene neue Route zwischen den Orkney- und Shetlandinseln. 1721 wurde Grönland vom Norweger Hans Egede für Dänemark-Norwegen in Besitz genommen. Er gründete die Kolonie Haabets, die 1728 nach Nuuk versetzt und in Godthaab umgetauft wurde. Hans Egede und seine Söhne Poul Egede und Niels Egede missionierten die Inuit und handelten mit ihnen. Ein zweiter Stützpunkt in Nipisat wurde 1724 begründet, aber bis 1731 zweimal von holländischen Walfängern zerstört. Ab 1733 wurde auch die Herrnhuter Brüdergemeine in Grönland tätig. 1734 wurde die Kolonie Christianshaab in Qasigiannguit gegründet. 1741 folgten Jakobshavn in Ilulissat und Claushavn in Ilimanaq, 1742 Frederikshaab in Paamiut. Nach der Gründung weiterer Kolonien, wurden ab etwa 1770 auch kleinere Handelsstützpunkte gegründet, die später als Udsteder bezeichnet wurden. 1776 bekam Den Kongelige Gronlandske Handel (KGH) das Handelsmonopol über Grönland und verwaltete die Kolonie fortan. Im 18. und 19. Jahrhundert wurde Grönland immer wieder von niederländischen, dänisch-norwegischen, deutschen und anderen Walfängern besucht. Dabei kam es immer wieder zu gewalttätigen Konflikten mit den Einheimischen. Die Grönlandfahrt trug wesentlich zur wirtschaftlichen Entwicklung Flensburgs bei, das damals zweitgrößter Hafen im dänischen Gesamtstaat war. 1814 wurde im Kieler Frieden die dänisch-norwegische Personalunion aufgelöst, Grönland fiel an Dänemark. Ab 1862 wurden die Einheimischen formal in die lokale Verwaltung sozialer Angelegenheiten miteinbezogen, indem die Forstanderskaber gegründet wurden. 1911 wurden die Kolonialdistrikte in Gemeinden unterteilt und in jeder Gemeinde ein Gemeinderat eingeführt. Zugleich wurden die Forstanderskaber durch Gronlands Landsrad abgelöst, ein beratendes Parlament mit eingeschränkter Entscheidungsgewalt, das zweigeteilt für Nord- und Südgrönland zuständig war. Ab 1925 wurde das Land von der Gronlands Styrelse regiert, deren Direktor dem dänischen Staatsministerium unterstand. Auch die grönländische Kolonialgeschichte war nicht frei von verschiedenen Konflikten und Protesten der indigenen Bevölkerung. === 20. und 21. Jahrhundert Im Ersten Weltkrieg blieb Dänemark (und damit auch Grönland) neutral. 1921 erklärte Dänemark seine Oberhoheit über Grönland. Auf norwegischer Seite behauptete man, dass gemäß dem Frieden von Kiel die dänische Hoheit nur für die wirtschaftlich erschlossenen Gebiete in Westgrönland gelte. Dennoch erkannte Norwegen die dänischen Ansprüche zunächst an. Als Dänemark allerdings Ostgrönland für Nicht-Dänen schloss, erhob sich erneut norwegischer Protest. 1930 begannen norwegische Fischer mit dem Wohlwollen ihrer Regierung mit der Besetzung der Ostküste Grönlands, sodass 1931 eine Teilung der Insel drohte (Eirik Raudes Land). 1933 gab Norwegen nach einem Schiedsspruch des Ständigen Internationalen Gerichtshofes in Den Haag seine Ansprüche auf Grönland endgültig zugunsten Dänemarks auf. Im Zweiten Weltkrieg wurde Dänemark am 9. April 1940 im Rahmen der Operation Weserübung von der Wehrmacht besetzt und blieb bis zum Kriegsende unter deutscher Besatzung. Grönland war von diesem Zeitpunkt an allerdings durch die britische Seevormacht von Dänemark abgeschnitten. Die dänischen Beamten vor Ort übernahmen die Staatsgewalt. Einen Tag nach der deutschen Besetzung erklärte der dänische Gesandte in den Vereinigten Staaten, Henrik Kauffmann, dass er keine Weisungen aus Kopenhagen mehr entgegennehmen werde. Washington betrachtete ihn dennoch weiterhin als den bevollmächtigten dänischen Botschafter und ging mit ihm am 9. April 1941 einen Vertrag ein, der die Errichtung von US-amerikanischen Basen in Grönland garantierte, nachdem deutsche Kriegsschiffe vor Grönland aufgetaucht waren. Daraufhin diente Grönland vor allem als Basis für atlantiküberwachende Flugzeuge auf der Suche nach deutschen U-Booten und wurde als Basis und Auftankstation für eigene Seemissionen benutzt. Es gab darüber hinaus auch deutsche Versuche, die Insel zur Errichtung von Wetterstationen der Wehrmacht in der Arktis mit dem Unternehmen Holzauge, Unternehmen Bassgeiger, Unternehmen Edelweiß und Unternehmen Zugvogel zu nutzen. Als Gegenmaßnahme wurde die Sirius-Patrouille aufgestellt. Nach dem Krieg unterbreitete die Truman-Administration Dänemark ein Kaufangebot für Grönland für 100 Mio. US$ in Gold, das von der dänischen Regierung jedoch abgelehnt wurde. Mit dem Vertrag vom 27. April 1951 wurde Grönland in ein gemeinsames dänisch-amerikanisches Verteidigungsgebiet unter NATO-Regie umgewandelt. Die Vereinigten Staaten erbauten ab 1952 größere Luftstützpunkte wie die Thule Air Base, denn im Kalten Krieg spielte die Nähe zur Sowjetunion quer über den Nordpol für Bomber und Aufklärungsflugzeuge, die entlang einer Orthodrome in die Sowjetunion fliegen konnten, eine wichtige Rolle. 1953 wurden die Inuit aus Thule nach Qaanaaq zwangsumgesiedelt. 1950 erlosch das dänische Handelsmonopol. Grönland wurde damit für den Freihandel geöffnet. Der KGH verlor auch seine administrative Gewalt. Verwaltungschef wurde ein von Dänemark ernannter Landeshauptmann, und es gab einen demokratisch gewählten Landrat (landsrad), der allerdings nur beratende Funktion hatte. Der Aufbau der Infrastruktur wurde nun durch die Gronlands Tekniske Forvaltning (GTO) übernommen (bis 1987). Neue technische Möglichkeiten wie Flugzeuge, Hubschrauber, Eisbrecher, Trawler usw. ermöglichten die Schaffung einer Versorgungslage auf sehr hohem Niveau. Mit dem Inkrafttreten des neuen dänischen Grundgesetzes am 5. Juni 1953 war Grönland keine Kolonie mehr. Das Land wurde nach dänischem Vorbild in drei Verwaltungsbezirke (dänisch amter) mit insgesamt 18 Kommunen eingeteilt. Ab 1953 entsandte Grönland auch zwei demokratisch gewählte Abgeordnete ins dänische Folketing, erstmals nach der Wahl am 22. September 1953. Am 30. August 1955 wurde in Kopenhagen ein spezielles Grönlandministerium eingerichtet, das bis 1987 existierte. Erster Grönlandminister war Johannes Kjrbol, letzter Minister für Grönland war Tom Hoyem. Die formale Entkolonialisierung und die wirtschaftliche Öffnung blieben nicht ohne Folgen für die traditionelle Jägergesellschaft der Inuit, sodass viele auch von einer "kulturellen Kolonialisierung" sprachen, vor der die Inuit zu Zeiten der Isolation weitgehend geschützt waren. In den ersten Jahrzehnten nach dem Zweiten Weltkrieg wurde die Jägergesellschaft schlagartig ins Industriezeitalter versetzt. Die Umwälzungen schufen unmittelbar bessere Lebensbedingungen und Ausbildungsmöglichkeiten nach dänischen Standards, sie führten jedoch auch zu einer tiefgreifenden nationalen Identitätskrise. Alkoholismus und Kriminalität wurden zu ernsthaften gesellschaftlichen Problemen. Seit dem Beginn der 1960er Jahre wurde die Nationalbewegung mit ihrer Forderung nach Selbstverwaltung immer stärker; sie richtete sich gegen ein Gesetz, in dem Dänen bei gleicher Arbeit ein höherer Lohn zustehen sollte als den geborenen Grönländern. Nach dem Beitritt Dänemarks (mit Grönland) zur Europäischen Wirtschaftsgemeinschaft 1973 verschärfte sich der Protest erneut, denn bei der entsprechenden dänischen Volksabstimmung am 2. Oktober 1972 stimmten lediglich 3905 Grönländer für den Beitritt, während 9386 dagegen stimmten. In der Folge wurde 1975 eine paritätisch besetzte grönländisch-dänische Kommission gebildet, die ein Autonomiegesetz nach dem Vorbild der Färöer ausarbeiten sollte. Im Ergebnis der Verhandlungen der Kommission wurde 1978 ein entsprechendes Gesetz vom Folketing verabschiedet. Bei der darauf folgenden Volksabstimmung in Grönland am 17. Januar 1979 sprach sich die große Mehrzahl der Grönländer für dieses Autonomiegesetz (hjemmestyreloven) aus. Am 1. Mai 1979 erlangte Grönland schließlich seine Selbstverwaltung sowie die innere Autonomie mit eigenem Parlament und eigener Regierung. Erster Ministerpräsident war Jonathan Motzfeldt. Seitdem besteht Grönland als "Nation innerhalb des Königreichs Dänemark". Aufgrund der Zugehörigkeit zu Dänemark war Grönland weiterhin Mitglied der Europäischen Wirtschaftsgemeinschaft. Das hatte zur Folge, dass europäische Hochseeflotten in den Gewässern Grönlands fischen und europäische Konzerne auf Grönland nach Bodenschätzen suchen konnten. Dagegen entwickelte sich eine Volksbewegung mit dem Ziel, die Mitgliedschaft in der Europäischen Wirtschaftsgemeinschaft zu beenden. Am 23. Februar 1982 gab es eine Volksabstimmung über den Austritt aus der Europäischen Wirtschaftsgemeinschaft, der am 1. Januar 1985 vollzogen wurde, in erster Linie wegen der Überfischung grönländischer Gewässer durch damals westdeutsche Fangflotten. Grönland genießt in der EU allerdings weiterhin den Status eines "assoziierten überseeischen Landes" mit den Vorteilen einer Zollunion (vgl. Art. 188 EG-Vertrag). Dennoch gehört Grönland seit seinem Austritt aus der Europäischen Wirtschaftsgemeinschaft nicht mehr zum Zollgebiet der Union, welches durch eine Bestimmung in einer Verordnung festgelegt wird. Nach dem Ende des Kalten Krieges verblasste die militärische Bedeutung Grönlands, allerdings gibt es Bemühungen seitens der Vereinigten Staaten, auf Grönland Bodenstationen für den geplanten US-Atomraketenabfangschild errichten zu dürfen. Im Jahr 2007 erlangte Grönland, das jahrzehntelang von den Medien nicht beachtet worden war, im Zuge der globalen Erwärmung ungewöhnlich viel Aufmerksamkeit. Dazu trug auch der spontane Besuch der deutschen Bundeskanzlerin Angela Merkel bei. Grönland ist innenpolitisch vollständig unabhängig, wird in allen außen- und verteidigungspolitischen Angelegenheiten jedoch von Dänemark vertreten. Am 25. November 2008 fand eine Volksabstimmung statt, mit der die Ersetzung des seit 1979 geltenden Autonomiestatuts durch eine Selbstverwaltungsordnung erreicht wurde. Sie wurde am 21. Juni 2009 umgesetzt. Besonders von Hans Enoksen wird gefordert und in Aussicht gestellt, dass Grönland 2021 zum 300. Jahrestag der Ankunft Egedes die vollständige Unabhängigkeit erlangt. Im August 2019, etwa einen Monat vor einem geplanten Staatsbesuch von US-Präsident Donald Trump in Dänemark, wurden Überlegungen bekannt, nach denen dieser wie schon 1946 Harry Truman erwäge, Dänemark die Insel Grönland abzukaufen. Der Präsident beschrieb dieses Szenario als "im Wesentlichen ein großes Immobiliengeschäft" (essentially a large real estate deal). Die Regierung Grönlands erklärte in Reaktion darauf, dass die Insel nicht zum Verkauf stünde. Die dänische Ministerpräsidentin Mette Frederiksen nannte die Idee "absurd". Grönland sei "nicht dänisch, sondern grönländisch" und stünde nicht zum Verkauf. Präsident Trump sagte daraufhin am 21. August 2019 seinen geplanten Staatsbesuch ab. Das Interesse Trumps an Grönland scheint trotzdem nicht abgeklungen zu sein. Im Februar 2020 wurde bekannt, dass mit einem Aufwand von 587.000 Dollar ein amerikanisches Konsulat in Nuuk errichtet werden soll, obwohl die Zahl der Amerikaner, die sich dort aufhalten, gering ist. Zusätzlich stellte die US-Regierung im April 2020 ein "Hilfspaket" für Grönland über ca. 11 Mio. EUR in Aussicht für Investitionen in den Bereichen Tourismus, Rohstoffe und Englischunterricht. == Politik === Allgemeines Grönland ist ebenso wie die Färöer ein autonomer Bestandteil des Königreich Dänemarks und bildet zusammen mit den anderen beiden Ländern die Rigsfllesskab ("Reichsgemeinschaft"). Die grönländische Verfassung ist das 1953 beschlossene dänische Grundgesetz (Danmarks Riges Grundlov), was in dessen §1 festgeschrieben ist. Grönland ist laut §1 des Selvstyregesetzes (Gesetz Nr. 473) eine Demokratie mit einer dreigeteilten Staatsgewalt. Die seit 2009 gültige Regierungsform heißt Selvstyre ("Selbstverwaltung") und ersetzte die ab 1979 gültige Hjemmestyre ("Heimverwaltung"). Beide Autonomiestufen haben die Möglichkeit geschaffen, dass Grönland den Großteil der Regierungsaufgaben vom dänischen Staat übernehmen kann (vgl. §2 des Selvstyregesetzes). Ausgeschlossen sind davon die Verteidigungspolitik und die Außenpolitik. Laut §8 obliegt die Entscheidung über die grönländische Unabhängigkeit einzig der grönländischen Bevölkerung im Rahmen einer Volksabstimmung. Grönlands Staatsoberhaupt ist als Teil der Rigsfllesskab die dänische Königin Margrethe II. Sie wird von Reichsombudsfrau Mikaela Engell vertreten. Das Amt des Reichsombudsmanns entstand 1979 aus dem des Landshovdings, dessen Vorgänger für die Verwaltung des kolonialen Grönlands zuständig waren. Der Reichsombudsmann dient als Bindeglied zwischen der grönländischen Autonomieregierung und dem dänischen Staat und nimmt vor allem organisatorische und koordinatorische Aufgaben wahr. === Exekutive Die grönländische Exekutive ist das Naalakkersuisut, die Regierung. Sie besteht aus meist etwa sieben bis zehn Ministern, die offiziell den Titel Naalakkersuisoq ("Der schafft, was Folge zu leisten ist") tragen. Der Name Naalakkersuisut ist das entsprechende Pluralwort. Unter ihnen ist der Regierungschef, der den offiziellen Titel Naalakkersuisut Siulittaasuat ("Vorsitzender des Naalakkersuisut") trägt. Aktueller Regierungschef seit dem 23. April 2021 ist Mute B. Egede, der das Kabinett Egede anführt. Der gesetzliche Rahmen für das Naalakkersuisut wird in Kapitel 3 des Gesetzes über Inatsisartut und Naalakkersuisut (Gesetz Nr. 26/2010) geregelt. Die Regierung wird vom Parlament gewählt und kontrolliert. Die Minister sind häufig, aber nicht zwangsläufig Mitglieder des Parlaments. Es ist üblich, dass diese mit Ausnahme des Regierungschefs während der Tätigkeit als Minister von den Parlamentsaufgaben beurlaubt sind. === Legislative Die grönländische Legislative ist das Inatsisartut ("Die Befehlenden"), das Parlament. Es besteht aus 31 Abgeordneten (Inatsisartunut Ilaasortat "Mitglieder des Inatsisartut"), die maximal alle vier Jahre neu gewählt werden. Dem Parlament steht ein Parlamentspräsidium aus dem Parlamentspräsidenten und vier Parlamentsvizepräsidenten vor. Aktueller Parlamentspräsident seit dem 23. April 2021 ist Hans Enoksen, der dem 14. Inatsisartut vorsteht. Der gesetzliche Rahmen für das Inatsisartut wird in Kapitel 2 des Gesetzes über Inatsisartut und Naalakkersuisut (Gesetz Nr. 26/2010) geregelt. Das Parlament ist für die Gesetzgebung zuständig, genehmigt den jährlichen Haushaltsplan und ist für die Kontrolle der Regierung zuständig. Das Inatsisartut wählt einen Ombudsmann, der für die Kontrolle der Verwaltungsaufgaben von Regierung und Kommunen zuständig ist. Neben dem eigenen Parlament entsendet Grönland wie die Färöer gemäß §28 des dänischen Grundgesetzes auch zwei Abgeordnete ins Folketing, die die grönländischen Interessen in dänischen Parlamentsangelegenheiten wahrnehmen sollen. === Judikative Die grönländische Judikative ist ein Teil des dänischen Rechtssystems. Höchste grönländische Instanz ist Gronlands Landsret ("Grönlands Landesgericht"), dem vier Kreisgerichte und das Retten i Gronland ("Gericht in Grönland") unterstellt sind. Die Kreisgerichte dienen als Strafgerichte und Familiengerichte, während das Retten i Gronland als Zivilgericht und Insolvenzgericht fungiert. Dem Landsret ist das Hojesteret als oberste Instanz übergeordnet, das in besonderen Fällen angerufen werden kann. === Außen- und Verteidigungspolitik Die Außen- und Verteidigungspolitik Grönlands obliegt dem dänischen Staat. Dennoch verfügt Grönland über einen Außenminister und ein Mitspracherecht in allen Angelegenheiten, die Grönland selbst betreffen. Grönland verfügt als Teil der Rigsfllesskab über keine Botschaften in anderen Ländern. Allerdings hat das Land einen diplomatischen Vertreter in Dänemark, in Island, in den Vereinigten Staaten und bei der Europäischen Union. In Grönland gibt es ein isländisches und ein US-amerikanischen Konsulat sowie mehrere Honorarkonsulate. Grönland ist weder Teil der Europäischen Union noch des Schengen-Raums. Die grönländische Mitgliedschaft in der Europäischen Union wurde 1982 durch ein Referendum beendet. Grönland arbeitet mit Island und den Färöern im Westnordischen Rat zusammen (seit 1985/1997). Weiterhin ist es als Teil der dänischen Delegation seit 1983 Mitglied im Nordischen Rat. Am 5. September 2007 wurde das landsdokument beschlossen, das den Autonomiegebieten land, den Färöern und Grönland die gleichwertige Mitgliedschaft im Nordischen Rat ermöglicht. Die Landesverteidigung obliegt dem dänischen Militär und wird von dessen Arktisk Kommando (zuvor von der Vorgängerorganisation Gronlands Kommando) übernommen. == Wirtschaft Das grönländische Bruttoinlandsprodukt betrug 2015 etwa 2,5 Mrd. US-Dollar, was pro Kopf etwa 41.800 US-Dollar entspricht. Nach letzterem Wert befindet sich Grönland etwa auf einer Stufe mit Italien oder Japan und 28 % hinter dem Mutterland Dänemark. Grönlands Arbeitslosenquote erreichte 2014 den Höchststand von 10,3 %, sank bis 2019 aber auf 5,1 %. Grönlands Handelsdefizit erreichte 2011 2,71 Mrd. Dänische Kronen (507 Mio. US-Dollar), lag 2020 aber nur noch bei 533 Mio. Dänischen Kronen (81,7 Mio. US-Dollar). Die grönländische Wirtschaft ist stark vom jährlichen inflationsregulierten Bloktilskud ("Blockzuschuss") abhängig, durch den Grönland 2020 3911,3 Mio. Dänische Kronen (599 Mio. US-Dollar) vom dänischen Staat erhielt. Ein Großteil des Außenhandels läuft über Dänemark. 2003 wurden 95 % der Produkte nach Dänemark exportiert und 60 % aus Dänemark importiert. Die grönländische Wirtschaft ist wenig diversifiziert. Nach Wirtschaftssektoren machte der Primäre Sektor 2015 12 % in Städten und 32 % in Dörfern aus. Der Sekundäre Sektor machte 9 % in Städten und 2 % in Dörfern aus. Der Tertiäre Sektor lässt sich in Dienstleistungen (37 % in Städten, 34 % in Dörfern) und Öffentliche Verwaltung aufteilen (40 % in Städten, 32 % in Dörfern). Der Primäre Sektor besteht aus Fischerei, Jagd, Landwirtschaft und Bergbau. Erstere macht dabei 93 % der Beschäftigten aus. === Jagd, Fischerei und Landwirtschaft Die Jagd war früher die einzige Möglichkeit für das Überleben der Inuit. Zu den traditionellen Beutetieren gehören Robben, Wale, Eisbären, Rentiere, Füchse, Hasen und Vögel. Die Jagd ist weiterhin ein bedeutender Teil der grönländischen Kultur und dient vor allem in den Dörfern sowie besonders in Nord- und Ostgrönland als wichtiger Teil der Versorgung. Die Jagd ist auf Grundlage biologischer Expertise durch Jagdquoten gesetzlich reguliert, um eine nachhaltige Ressourcennutzung zu gewährleisten. Die Fischerei wurde von den Inuit traditionell weniger getätigt. Während die Kolonialwirtschaft die ersten knapp 200 Jahre auf Basis der Jagd fungiert hatte, fasste die Fischereiwirtschaft erst zu Beginn des 20. Jahrhunderts Fuß in Grönland. Besonders die Fischerei nach Dorsch war bedeutend und konnte ab den 1930er Jahren die rückläufigen Robbenbestände wirtschaftlich aufwiegen. Die Dorschfischerei führte zu Wohlstand in Grönland, brach aber um 1970 zusammen. Damit begann die Phase der Krabbenfischerei, die bis heute andauert und die Hauptgrundlage für den grönländischen Export bildet. Dazu macht die Heilbuttfischerei einen bedeutenden Teil der Fischereiwirtschaft aus. Die Fischerei macht heute 95 % der Exporte Grönlands aus, was die wirtschaftlichte Lage extrem abhängig von Fischereibeständen und -preisen macht. In Südgrönland wird Landwirtschaft betrieben. Im 18. Jahrhundert begann Anders Olsen mit der Rinderhaltung in Igaliku. Zu Beginn des 20. Jahrhunderts leitete Jens Chemnitz die moderne Phase der grönländischen Tierhaltung ein, als er in Narsarmijit begann, Schafe zu halten. In den folgenden Jahrzehnten breitete sich die Schafhaltung über ganz Südgrönland aus und erreichte 1966 mit 48.000 Tieren einen Höchststand, bevor ein besonders harter Winter die Bestände mehr als halbierte. Die Tiere werden in den Schäfersiedlungen, einzeln stehenden Bauernhöfen vor allem im Distrikt Narsaq gehalten. Etwa 20.000 Lämmer werden pro Jahr in Grönland geschlachtet. Daneben gibt es heute 300 Rinder in Grönland, die vier Bauern gehören. Zwei Rentierzüchter halten etwa 1600 Rentiere. Seit etwa 2000 werden in Grönland in kleinem Rahmen Kartoffeln und anderes Gemüse angebaut. Durchschnittlich kommen pro Jahr etwa 100 Tonnen Kartoffeln in den Handel, die von rund fünf bis sechs Bauern angebaut werden. Zu den übrigen Anbauprodukten gehören Mairüben, Rhabarber, Kohl, Radieschen und Salat. Eine entscheidende Rolle in der grönländischen Agrarwirtschaft spielt die Versuchsstation in Upernaviarsuk. Zum aktuellen Zeitpunkt ist die Landwirtschaft in Grönland jedoch ein Verlustgeschäft. === Bergbau Grönland ist reich an Rohstoffen. An der Küste befinden sich unter anderem größere Vorkommen von Gold, Platin, Kupfer, Zink, Nickel, Molybdän und Eisen. In Grönland finden sich auch Vorkommen von Rubinen und Diamanten. Bereits im 1782 wurde im kolonialen Grönland erstmals Bergbau betrieben, als an der Diskobucht mit dem Kohlebergbau begonnen wurde (Ritenbenk Kulbrud), welcher aber eher der lokalen Versorgung diente. Mitte des 19. Jahrhunderts begann der industrielle Bergbau in Grönland mit Grafitabbau in Nordgrönland und Kupferbergbau in Südgrönland. Fast zeitgleich eröffnete die Kryolithmine in Ivittuut, die 130 Jahre aktiv war. Der Kohlebergbau wurde ab etwa 1900 industrialisiert, zuerst in Qaarsuarsuk, dann in Qullissat. Qullissat wurde im 20. Jahrhunderts zu einer der bedeutendsten Städte des Landes, bis sie in den 1970er Jahren, als die Vorkommen aufgebraucht waren, gegen den Willen der Bevölkerung aufgegeben wurde. In den 1970er und 1980er Jahren war die Blei- und Zinkmine in Maamorilik von Bedeutung, wo zuvor bereits Marmor abgebaut worden war. Seit der Jahrtausendwende gibt es mehrere Versuche in Nalunaq Gold abzubauen. Seit 1969 wird vor der grönländischen Küste nach Erdöl gesucht. Die entdeckten Vorkommen wurden aber bisher jedes Mal als unrentabel eingestuft. Bei Narsaq befinden sich bedeutende Vorkommen von Uran und Seltenen Erden am Berg Kuannersuit. Diese haben vor allem seit 2010 mehrfach zu politischen Debatten und Problemen geführt. Die Vorkommen sind so groß, dass erwartet wird, dass sie die Dominanz Chinas auf dem Weltmarkt brechen könnten und die wirtschaftliche und finanzielle Situation Grönlands verbessern könnte. Der potentielle Abbau war während der Regierungszeit von Kuupik Kleist (Inuit Ataqatigiit) interessant geworden, wurde aber durch die Nulltoleranzpolitik verhindert, dass in Grönland keine radioaktiven Stoffe wie Uran abgebaut werden dürfen. 2013 übernahm die Siumut wieder die Macht und schaffte das Abbauverbot mit knapper Mehrheit ab. Daraufhin formierte sich ein Widerstand in der Bevölkerung, die mit Umweltzerstörung durch die Minenaktivität rechnen, vor allem durch die radioaktive Verunreinigung von Gewässern in dem Gebiet, das als einziges in Grönland landwirtschaftlich nutzbar ist. 2021 verlor die Siumut erneut die Macht an die Inuit Ataqatigiit, die versprochen hatte, das Kuannersuit-Projekt zu stoppen. === Tourismus Der Tourismus spielt eine bedeutende Rolle in der grönländischen Wirtschaft. Das staatliche Tourismusunternehmen Visit Greenland wirbt in Grönland beispielsweise mit der arktischen Natur mit Eisbergen, Polarlichtern und der Tierwelt. Es werden Wander- und Skitouren, Bergbesteigungen sowie Kajak- und Hundeschlittentouren angeboten. Daneben wird mit der grönländischen Kultur geworben, die in den Städten und traditionelleren Dörfern erlebt werden kann. Die Zahl an ausländischen Flugpassagieren, die in Grönland landen, ist zwischen 2015 und 2019 leicht gestiegen und beträgt etwa 60.000 Personen, was etwas mehr sind, als Grönland Einwohner hat. Von diesen wohnt knapp die Hälfte in Dänemark, bedeutende Herkunftsländer von Touristen sind daneben vor allem Deutschland, die USA und Kanada. Etwa 260.000 Übernachtungen in grönländischen Hotels gab es 2019, die sich etwa zu gleichen Teilen auf Grönländer und Ausländer verteilten. Hochsaison für den Tourismus sind die Sommermonate Juli und August. Der bedeutendste Tourismuszweig in Grönland ist die Kreuzfahrtschifffahrt, die besonders seit der Senkung der Kreuzfahrtgebühren 2016 stark an Bedeutung gewinnt und sich von 2016 bis 2019 beinahe verdoppelt hat. Von den knapp 50.000 Kreuzfahrttouristen stammen knapp die Hälfte aus Deutschland und den Vereinigten Staaten. Bedeutendste Anlaufhäfen sind Qaqortoq, Nuuk, Ilulissat, Nanortalik und Sisimiut. Probleme für den Tourismus bieten in Grönland die hohen Flugpreise und mangelnde Übernachtungsmöglichkeiten. Mit dem Ilulissat-Eisfjord (seit 2004), der südgrönländischen Kulturlandschaft Kujataa (seit 2017) und der Kulturlandschaft Aasivissuit - Nipisat (seit 2018) hat Grönland drei UNESCO-Welterbestätten. In Grönland befinden sich rund 20 Museen. == Verkehr Eine wesentliche Rolle spielt neben der Schifffahrt vor allem der Flugverkehr. Der größte Flughafen ist Kangerlussuaq (Sondre Stromfjord). Internationale Flüge führen hauptsächlich nach Kopenhagen in Dänemark. Sowohl Air Greenland als auch Air Iceland bieten Routen vom Flughafen Keflavik in Island zu mehreren Zielen in Grönland. Weitere Flughäfen befinden sich in Narsarsuaq (bei Narsaq, Anbindungen an Island und Dänemark), Nuuk (Anbindung an Island), Kulusuk (bei Tasiilaq, Anbindung an Island), und Nerlerit Inaat bei Ittoqqortoormiit (Scoresbysund, Anbindungen an Island). == Gesellschaft === Bildung An der Universität von Grönland in Nuuk, "Ilisimatusarfik", studieren etwa 150 Studenten, davon wenige Ausländer. In den Studienfächern Verwaltung, Kultur- und Sozialgeschichte Grönlands sowie Grönländische Sprach-, Literatur- und Medienstudien können Bachelor- und Master-Abschlüsse erworben werden. Außerdem gibt es das Studienfach Theologie. Unterrichtet wird größtenteils auf Dänisch, in einigen Kursen auch auf Grönländisch. In Nuuk befindet sich die 1956 gegründete Landesbibliothek Nunatta Atuagaateqarfia. Sie fiel 1968 einem Brand zum Opfer, wurde aber 1976 in einem neuen Gebäude wiedereröffnet. Seit 1980 fungiert sie als grönländische Nationalbibliothek. Ihre Groenlandica-Sammlung wurde 2008 auf den neuen Campus Ilimmarfik der Universität ausgelagert. Mit Knud Rasmussen hatte Grönland Anfang des 20. Jahrhunderts seinen eigenen Polarforscher, der von Thule ausgehend sieben Expeditionen unternahm. === Soziale Probleme Laut einer dänischen Reportage soll ein Drittel der Mädchen bis 15 Jahre bereits sexuell missbraucht worden sein und Grönland eine der höchsten Suizidraten der Welt haben, dies vor allem bei Kindern und Jugendlichen. Danach hatte der Suizid, ebenso wie der sexuelle Umgang miteinander, in der Historie (siehe Absatz über die anderen Kulturen im Artikel Suizid und Suizid in Grönland) in der Inuitgesellschaft einen anderen Stellenwert als in der christlichen Kultur. Alkoholmissbrauch ist in Grönland eine weitverbreitete Krankheitsursache. Die meisten Straftaten wie Körperverletzungs- und Tötungsdelikte werden unter Einfluss von Alkohol begangen. Der Unterschied zwischen Arm und Reich sei größer als in den Vereinigten Staaten. Die Schulbildung sei schlecht, es gebe hohe Abbruchquoten. Nur zwei Prozent der Schüler erreichen einen Universitätsabschluss, viele Studenten denken darüber nach, Grönland zu verlassen. Das Land sei von einem sozialen Zusammenbruch bedroht. Die durchschnittliche Lebenserwartung bei der Geburt betrug 2016 nur 72,4 Jahre (Frauen: 75,2 Jahre/ Männer: 69,7 Jahre). Damit belegte Grönland in der Rangliste aller Staaten und Territorien der Welt lediglich den 144. Platz. Seit 2009 steht Grönland zum ersten Mal auf der Liste der Länder, die die UN-Kinderrechtskonvention missachten. Nach Angaben der UNICEF leidet jedes sechste grönländische Kind an Unterernährung und geht hungrig in die Schule oder zu Bett. Mit 2,01 Kindern pro Frau war Grönland gleichzeitig das Territorium von Dänemark mit der höchsten Geburtenrate. == Kultur === Bildende Kunst Die Inuit haben ihre eigene kunsthandwerkliche Tradition; beispielsweise schnitzen sie den Tupilak. Dieses Kalaallisut-Wort bedeutet Seele oder Geist eines Verstorbenen und umschreibt heute eine meist nicht mehr als 20 Zentimeter große, überwiegend aus Walross-Elfenbein geschnitzte Kunstfigur mit verschiedenartiger, ungewöhnlicher Gestalt. Diese Skulptur stellt eigentlich ein mythisches oder spirituelles Wesen dar; gewöhnlich ist sie aber wegen ihres für westliche Sehgewohnheiten grotesken Aussehens zum reinen Sammelobjekt geworden. Moderne Kunsthandwerker nutzen jedoch nach wie vor einheimische Materialien wie Moschusochsen- und Schafwolle, Robbenfell, Muscheln, Speckstein, Rentiergeweihe oder Schmucksteine. Die Geschichte der grönländischen Malerei begann mit Aron von Kangeq, der Mitte des 19. Jahrhunderts die alten grönländischen Sagen und Mythen in seinen Zeichnungen und Aquarellen darstellte. Im 20. Jahrhundert entwickelte sich die Landschafts- und Tiermalerei sowie die Druckgrafik und Buchillustrationen mit teils expressiver Farbgebung. Vor allem durch ihre Landschaftsbilder wurden Kiistat Lund und Buuti Pedersen auch im Ausland bekannt. Anne-Birthe Hove wählte Themen aus dem grönländischen Sozialleben. Ein Museum für bildende Kunst gibt es in Nuuk, das Nuuk-Kunstmuseum. === Musik Die Trommel ist das traditionelle Instrument Grönlands. Mit ihr wurden die traditionellen Trommeltänze durchgeführt. Dazu wurde eine runde Trommel (Qilaat) in Form eines mit einer Eisbärenblase, Eisbärenmagen oder einem Walrossmagen bezogenen Rahmens aus Treibholz oder Walrossrippen benutzt. Getrommelt wurde nicht auf die Membran, sondern mit einem Stock von unten auf den Rahmen. Dazu wurden einfache Melodien gesungen. Der Trommeltanz erfüllte früher zwei Funktionen: Die Trommel wurde einerseits benutzt, um in langen, dunklen Winternächten die Angst zu vertreiben. Dazu schnitt der Trommeltänzer Grimassen und versuchte, die Anderen zum Lachen zu bringen, bis jegliche Angst vergessen war. Auch Streitigkeiten wurden mit der Trommel ausgetragen. Hatte jemand sich falsch benommen, wurde er mit der Trommel herausgefordert. Man hat sich an bestimmten, kraftvollen Plätzen getroffen und dort im Wechsel die Trommel gespielt und dazu gesungen. Dabei versuchte man, den Anderen so lächerlich wie möglich zu machen. Die Zuschauer drückten durch ihr Lachen aus, wer der Gewinner und wer somit der Schuldige ist. Die Trommel konnte auch von Schamanen für rituellen Geisterbeschwörungen eingesetzt werden. Nach der Ankunft der Missionare im 18. Jahrhundert wurde der (heute auch noch bei den kanadischen Inuit beliebte) Trommeltanz als heidnisch-schamanistisch verboten und durch mehrstimmigen Gesang weltlicher und Kirchenlieder verdrängt. Dieser Chorgesang ist heute für seinen besonderen Klang bekannt. Die Kirchenlieder sind aufgrund des Einflusses der Herrnhuter Brüdergemeine teils deutschen Ursprungs. Skandinavische, deutsche und schottische Walfänger brachten die Fidel, das Akkordeon und die Polka (Kalattuut) nach Grönland, wo sie heute zu komplizierten Tanzschritten gespielt werden. Grönland hat auch eine bemerkenswert moderne Musikkultur. Die erste Band, die grönländisch sang, war in den 1970er Jahren die Gruppe Sume (grönländisch wo?). Wichtigste Bands sind Nanook, Chilly Friday, Disko Democratic Republic und Siissisoq (Rock) sowie Nuuk Posse (Hip-Hop), die auch den Trommeltanz verwenden. Bekanntester Liedermacher ist Angu Motzfeldt. International bekannt wurde auch der Sänger und Schauspieler Rasmus Lyberth. In Grönland erscheinen jedes Jahr 10 bis 15 CDs mit Auflagen bis zu 5000 Stück. === Medien Kalaallit Nunaata Radioa betreibt auf Grönland je einen Fernseh- und einen Radiosender. Außerdem gibt es einen zusätzlichen 100-Watt-Hörfunksender in Nuuk, der das Programm von Danmarks Radio (DR P1) ausstrahlt, wo es von 90 Prozent der dänischsprachigen Minderheit gehört werden kann. Trotz der geringen Bevölkerungsdichte gibt es in Grönland ein reichhaltiges Medienangebot. Zum grönländischen Radio- und Fernsehverband STTK gehören insgesamt neun Radio- und elf Fernsehstationen. Beispielsweise verweist Nuuk TV darauf, mit fast 4000 Haushalten fast 75 Prozent aller Haushalte in der Hauptstadt mit 23 Fernseh- und acht Radiokanälen digital verschlüsselt erreichen zu können. Das private lokale Fernsehhauptprogramm sendet darüber hinaus unverschlüsselt digital und analog für die Region Nuuk. Seit 2009 wird eine grönländische Filmindustrie aufgebaut, die auch international einige Aufmerksamkeit erzielte. === Weihnachtsmann von Grönland Nach Angaben der Dänischen Botschaft in Deutschland erreichen jedes Jahr tausende Briefe das Weihnachtspostamt des Weihnachtsmanns in Grönland, weil viele Kinder auf der Welt glauben, der Weihnachtsmann wohne dort. Im Sommer kann man sein Haus besichtigen. Es liegt einen kleinen Spaziergang außerhalb der Ortschaft Uummannaq, unterhalb des markanten Robbenherzberges. === Sport Trotz der Anbindung an Dänemark gibt es eine Grönländische Fußballnationalmannschaft. Grönland ist aber bisher nicht Mitglied der FIFA. Ein Beitritt wird zwar angestrebt, CONCACAF, UEFA und FIFA sperren sich allerdings dagegen. Jahrelang wurde als Grund das Fehlen von Naturrasenplätzen angegeben. Seitdem auf Kunstrasen gespielt werden darf, wird als Grund angegeben, dass die FIFA nur noch souveräne Staaten als Mitglieder akzeptiert (jedoch wurde 2016 mit der Gibraltar Football Association dennoch ein neuer Verband aus einem nicht-souveränen Gebiet in die FIFA aufgenommen). Etliche abhängige Überseegebiete, darunter die Färöische Fußballnationalmannschaft, fallen aber nicht unter diese Regel. Die Grönländische Männer-Handballnationalmannschaft erreichte über die kontinentalamerikanische Qualifikation die Handball-Weltmeisterschaften 2001 in Frankreich, 2003 in Portugal und 2007 in Deutschland. Das Wort "Kajak" ist dem Inuktitut entnommen. Die Inuit bezeichnen mit "Qajaq" ein Boot, das ursprünglich aus Walknochen, später aus Holzverstrebungen konstruiert und mit Robbenhaut bespannt wurde. Anders als der Umiak, das Frauenboot, war der Kajak sehr schmal und dem Körper der ihn nutzenden Person so genau angepasst, dass der Unterkörper wassergeschützt blieb und dem Insassen die sogenannte Eskimorolle ermöglichte. Der Kajak wurde schon von den Menschen der Thulekultur im Sommer für Jagd und Fischfang genutzt. Auch nachdem Kanus mit Außenbordmotoren und sogar Jachten sich in der Arktis durchgesetzt und die traditionellen Kajaks und Umiaks weitgehend verdrängt haben, werden in entlegenen Regionen wie Qaanaaq, Ittoqqortoormiit oder in einzelnen Ansiedlungen der Kommune Upernavik aus Traditionsgründen noch immer auch Kajaks verwendet. == Literatur == Einzelnachweise 70-40Koordinaten: 70° 0' N, 40° 0' W

Title: Grönland Summary: Grönland ist die grösste Insel der Erde. Sie ist über zwei Millionen Quadratkilometer gross, das ist etwa halb so gross wie die Europäische Union. Grönland liegt weit im Norden, östlich von Nordamerika. Es gehört zur Arktis und liegt überwiegend nördlich des Polarkreises. Darum ist es dort sehr kalt, und der grösste Teil der Insel ist von Schnee und Eis bedeckt. Man nennt das die kalt-gemässigte Zone. Der Boden bleibt das ganze Jahr über gefroren, es ist also Permafrostboden. Nur im Sommer wird es manchmal bis zu Null Grad Celsius "warm". Dennoch gibt es ausser Insekten auch Säugetiere auf Grönland, wie Eisbären, Rentiere und Moschusochsen. Im Wasser vor der Küste leben nicht nur viele verschiedene Fische, sondern auch Wale und Robben. Die Hauptstadt heisst Nuuk und liegt im Süden der Insel. Dort leben etwa 15.000 Menschen, ganz Grönland hat etwa 55.000 Einwohner. Die meisten Einwohner Grönlands gehören zu den Inuit, einer Gruppe von Eskimos. Ihre Vorfahren stammen wohl aus Asien. Die übrigen Einwohner kommen aus Dänemark und anderen Ländern Europas. Zwei Drittel der Einwohner gehören zur lutherischen Kirche. Der Name Grönland, also "grünes Land", stammt von den Wikingern, welche um das Jahr 1000 auf die Insel kamen. Davor hatten sie schon das benachbarte Island besiedelt. Die norwegischen Siedler hielten sich im Süden auf in einer Gegend, in der zu dieser Zeit ein eher angenehmes Klima herrschte. Nachdem es um das Jahr 1400 kälter wurde, sind die Nachfahren der Wikinger irgendwann ausgestorben. Um das Jahr 1700 schickte Dänemark, das damals auch über Norwegen und Island herrschte, Walfänger nach Grönland. In der Kolonialzeit wurden auch Handelsniederlassungen gegründet, in denen Dänen und Inuit zusammenlebten. Diese grönländischen Orte trugen einst alle einen dänischen Namen. Später wurden sie auf Grönländisch umbenannt. Denn seit dem Jahr 1979 dürfen die Einwohner der Insel über sich selbst bestimmen. Allerdings ist Grönland immer noch ein Teil des Königreichs Dänemark. Man bezahlt auch mit der dänischen Währung, die Krone heisst. Zur Europäischen Union aber gehört Grönland nicht. Die USA haben einen Platz mit dem Flughafen Thule, wo etwa 250 Soldaten leben. Von dort aus wollten die Amerikaner besonders im Kalten Krieg das Gebiet um den Nordpol kontrollieren.

klexikon_de

de

Summarize: SUMMARY OF THE INVENTION The present invention is directed to a hanger particularly suited for pictures and the like, and more specifically to a picture hanger which is self adjusting to insure that the picture hangs straight at all times. Pictures or other wall hangers are conventionally mounted on the wall by placing a tack, nail or screw in each upper corner of the picture, tightly stringing a wire between the screws, and hanging the picture by the wire on a nail or screw driven into the wall. Inevitably, after a period of time, the wire will slip on the nail or screw in the wall, with the result that the picture hangs crookedly. The present invention is directed to a simple device for preventing this from happening. The device includes a wall mount member which is fixedly attached to the vertical wall surface upon which the picture is to be placed, and a picture mount member which is fixedly attached to the rear surface of the picture along its vertical center line. When the members are connected together in one way, they are permitted to rotate with respect to each other until the picture hangs straight. Even if the picture is displaced from this position, it will automatically tend to return to its straight hanging position. When the members are connected together in a second way, rotation between them is prevented so that the picture is fixed in the straight hanging position. In either event, the members may be easily disengaged from each other so that the picture can be removed from the wall. The wall mount member also includes an alignment feature for initially attaching it to the wall surface to assure that the picture will hang in a straight line. As will become apparent from the detailed description which follows, the device may be easily and inexpensively fabricated from molded plastic or the like. BRIEF DESCRIPTION OF THE DRAWING FIG. 1 is a rear elevation view of the wall mount member associated with the self-adjusting hanger of the present invention. FIG. 2 is a side elevation cross sectional view of the wall mount member of FIG. 1. FIG. 3 is a front elevation view of the picture mount member associated with the self-adjusting hanger of the present invention. FIG. 4 is a side elevation cross sectional view of the picture mount member of FIG. 3. FIG. 5 is a front elevational view of the assembled self-adjusting hanger of the present invention viewed from the picture mounting surface. DETAILED DESCRIPTION The self-adjusting hanger of the present invention is illustrated generally at 1 in FIG. 5, and comprises a wall mount member 2 illustrated in FIG. 1 and FIG. 2, and a picture mount member 3 illustrated in FIG. 3 and FIG. 4. As will be described in more detail hereinafter, wall mount member 2 is fixedly mounted to a vertical wall surface 4, while picture mount member 3 is fixedly mounted to the rear surface 5 of a picture or the like (not shown), preferably along the vertical center line of the picture. Wall mount member 2 is formed by a circular disk 6 having a pair of diametrically opposed mounting holes 7 spaced inwardly from the peripherial edge of the disk. As best shown in FIG. 1, a pair of V-shaped notches 8 is provided along the vertical center line 9 of disk 6, the function of which will be described hereinafter. The central portion of disk 6 is provided with a hub 10 having a mounting hole 11 extending therethrough along the central axis of disk 6. One major surface of disk 6 is provided with an outwardly extending circular rib 12 which is spaced beyond mounting holes 7. It will be observed that circular rib 12 is of sufficient height to form a smooth cylindrical outer surface 13. Surface 13 is provided with an outwardly extending key portion 14 of generally rectangular cross section which is oriented along a line extending between notches 8. Wall mount member 2 is attached to the vertical wall surface 4 such that a vertical line passes through notches 8. This may be accomplished by first securing the wall mount member to the wall by a nail or screw inserted through mounting hole 10 to a sufficient depth to hold the wall mount member in place, while still permitting the member to be rotated. A string with a weight at one end forming a plumb line may then be suspended near the wall mount member or hooked over the upper notch, and the member rotated until a line passing through notches 8 lies parallel to the vertically hanging string. In this regard, other indicia may be substituted for notches 8. It will be understood that wall mount member may be oriented so that key portion 14 lies above or beneath mounting hole 11. Once the wall mount member 2 is properly oriented, it may be permanently secured in position to the wall surface by additional screws or nails inserted in mounting holes 7. In any event, as best seen in FIG. 2, wall mount member 2 is attached so that circular rib 12 abuts the wall surface, thereby forming a space between the outer flange-like periphery of disk 6 and wall surface 4. It will be further observed that notches 8 may be used to align the wall mount member 2 and hence the associated picture at a particular desired angle. This feature may be desirable in modern picture groupings where the pictures are intentionally hung askew. The construction of picture mount member 3 is illustrated in FIGS. 3 and 4. This member is formed by a rectangular-shaped relatively thin plate 15 having a centrally located semi-circular cut-out 16 of just slightly greater diameter than the outer diameter of circular rib 12. As best shown in FIG. 3, the upper portion of cut-out 16 is provided with a rectangular-shaped notch 17 dimensioned to be slightly greater than key portion 14 of wall mount member 2. The side and top peripheral edges of rectangular-shaped plate 15 are provided with an inwardly directed flange 18 having a height just slightly greater than the thickness of disk 6. Picture mount member 3 is provided with a plurality of mounting holes 19 for attaching the wall mount member to the rear surface or frame of a picture or the like by nails, screws, etc. In addition, the member is provided with a pair of larger mounting holes 20 located in the upper corners of rectangular-shaped plate 15 which are dimensioned to accept screws for attaching the wall mount member to the track of certain extruded metal type frames. In general, picture mount member 3 will be mounted with the orientation illustrated in FIG. 3 such that the center line 9a of the picture or picture frame bisects notch 17. A vertical guide line 17a may be placed at the midpoint of notch 17 to assist in properly positioning the picture mount member to insure that the picture mount member will be attached to the picture or frame at a point lying along a vertical line passing through the center of gravity of the picture. After the wall and picture mount members have been fixedly attached to their respective mounting surfaces, they may be connected together as illustrated in FIG. 5 by merely lowering the picture mount member 3 over the wall mount member 2 so that the upper portion of circular rib 12 enters semi-circular cut-out 16. If the wall mount member has been oriented so that key portion 14 is at the top as illustrated in FIG. 1, the key portion will mate with notch 17 preventing relative rotational movement between the wall and picture mount members. If key portion 14 is oriented at the bottom of wall mount member 2 as illustrated at 14a in dashed lines in FIG. 5, the uppermost part of cylindrical surface 13 will make rolling contact with the inner surface associated with semi-circular cut-out 16. Inasmuch as the wall and picture mount members are now free to pivot in rolling contact with respect to each other, the picture attached to the picture mount member will seek a position where a line drawn through the center of gravity of the picture will pass through mounting hole 11. Since the picture mount member 3 has been mounted so that the line 9a passing through the center of gravity also passes through the central part of the mount member, the line passing through the center of gravity of the picture will also coincide with the vertical center line 9 of the wall mount member. Consequently, the picture will seek and maintain a true vertical position. It will be understood that each of the components comprising the self-adjusting hanger of the present invention may be constructed of any suitable material, and in particular a molded plastic material. Furthermore, wall mount member 2 and picture mount member 3 may each be molded of unitary construction. It will be further understood that various changes in the details, materials, steps and arrangements of parts, which have been herein described and illustrated in order the explain the nature of the invention, may be made by those skilled in the art within the principle and scope of the invention as expressed in the appended claims.

Summary: A self-adjusting picture hanger having a wall mount member fixedly attached to the wall which rotatably coacts with a picture mount member secured to the rear of the picture. In one orientation, the members are free to rotate with each other so that the picture seeks and maintains a true vertical position. In a second orientation, a key on the wall mount member engages a notch on the picture mount member to fix the picture in a vertical position. The wall mount member is provided with notches which accept a plumb line for easily orienting the wall mount member.

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Summarize: CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 11/414,456, filed on Apr. 28, 2006, which is a continuation of U.S. patent application Ser. No. 11/033,547, filed on Jan. 10, 2005, now U.S. Pat. No. 7,060,259, which is a continuation of U.S. patent application Ser. No. 10/361,451, filed on Feb. 10, 2003, now U.S. Pat. No. 6,899,867, which is a continuation of U.S. patent application Ser. No. 09/842,514, filed on Apr. 26, 2001, now U.S. Pat. No. 6,541,015, which is a divisional of U.S. patent application Ser. No. 09/469,418, filed on Dec. 23, 1999, now U.S. Pat. No. 6,413,507, all of which are herein incorporated by reference in their entireties. FIELD OF THE INVENTION [0002] This invention relates to hydrolyzable derivatives of poly(ethylene glycol) useful as prodrugs and as degradable components of cross-linked polymers. BACKGROUND OF THE INVENTION [0003] Covalent attachment of the hydrophilic polymer, poly(ethylene glycol), commonly referred as PEG, to biologically active agents and surfaces has important applications in biotechnology and medicine. [0004] PEG is generally soluble in water and many organic solvents. PEG is also substantially non-toxic and normally does not illicit any significant immune response in animals. When PEG is chemically attached to a water insoluble compound, the resulting conjugate generally is soluble in water as well as many organic solvents. When the agent to which PEG is attached is biologically active, such as a drug, the activity of the agent can be retained after the attachment of PEG, and the conjugate generally displays altered pharmacokinetics. [0005] The prodrug approach, in which drugs are released by degradation of more complex agents (prodrugs) under physiological conditions, is a powerful component of drug delivery. See R. B. Greenwald, Exp. Opin. Ther. Patents, 7(6):601-609 (1997). Prodrugs can, for example, be formed by bonding PEG to drugs using linkages which are degradable under physiological conditions. [0006] However, not all linkages are readily degradable and useful in prodrug applications. In general, ester linkages, formed by condensation reactions between PEG carboxylic acids or activated PEG carboxylic acids and alcohol groups on drugs, hydrolyze under physiological conditions to release the drug. For example, in PCT Publication No. WO 96/23794, it is disclosed that paclitaxel can be linked to PEG using ester linkages and the linked paclitaxel can be released in serum by hydrolysis. Antimalarial activity of dihydroartemisinin bonded to PEG through a hydrolyzable ester linkage has also been demonstrated. Bentley et al., Polymer Preprints, 38(1):584 (1997). [0007] Conventional amide and carbamate linkages, formed with amine groups on drugs, generally are stable and do not hydrolyze to release a free drug within a sufficiently short time that is required in practical applications. See, e.g., Zalipsky, Advanced Drug Delivery Reviews, 16:157-182 (1995); Zalipsky, et al., Eur. Polym. J., 19:1177-1183 (1983). For example, it has been demonstrated that carbamate linkages between PEG and a protein in a conjugate are stable under a variety of physiological conditions. Larwood and Szoka, J. Labeled Compd. Radiopharm. 21:603 (1984). Many useful drugs including peptides, proteins, and small agents having amine groups have been bonded to PEG through non-hydrolyzable amide and carbamate linkages. PEG can also be bonded to amine groups on drugs through reductive amination with PEG aldehydes and the resulting amine linkage is non-degradable in vivo. [0008] Because many drugs such as proteins have amine groups that are readily available for reaction to form linkages, it is desirable to make such linkages hydrolytically degradable so that free proteins or other amine-containing agents can be released from the prodrugs at a controlled rate in vivo. Imines, or Schiff bases, offer a possible approach since they hydrolyze to generate the free amine and an aldehyde: [0000] RCH═NR′+H 2 O RCH═O+R′NH 2 [0000] where R′ is a drug or other agent bearing an amino group. This approach has been used in attaching doxorubicin to PEG with release of the drug occurring by hydrolysis of the imine linkage. Ouchi et al. Polymer Preprints, 38(1):582-3 (1997). Since the formation of imines is reversible in water, these compounds are best prepared in organic solvents. Many proteins, peptides, and other agents are thus not amenable to the imine prodrug approach because of their poor solubility or instability in organic solvents. [0009] Conjugates can be prepared by linking an amine-containing drug, through a non-hydrolyzable amide or carbamate linkage, to a PEG molecule having hydrolytically degradable linkages in the PEG backbone. The amine-containing drug is releasable upon the degradation of the PEG backbone. However, the released drug usually has a fragment attached through an amide or carbamate linkage, and the native or parent drug is not released. [0010] U.S. Pat. No. 4,935,465 discloses a water-soluble prodrug in which neighboring group participation by a carboxyl group aids in the hydrolysis of an amide, thus releasing the drug. PEG was a component of a bovine serum albumin (BSA) prodrug disclosed in that patent: [0000] [0011] U.S. Pat. No. 5,561,119 and European Patent No. 595133-A disclose a doxorubicin prodrug as shown below, which utilizes a benzylglucuronyl carbamate linkage. A second component, glucuronidase, must be added in order to cleave the glucuronic acid and liberate doxorubicin and a nitrobenzoquinone methide. [0000] [0012] In yet another approach as disclosed in U.S. Pat. No. 5,413,992, a prodrug of daunamycin shown below, liberates the native drug by an enzyme-induced elimination initiated by abstraction of a proton adjacent to the sulfone group. [0000] [0013] In addition, U.S. Pat. No. 4,760,057 describes enzymatic hydrolysis of a prodrug containing a carbamate linkage: [0000] RR′NCO 2 CR 1 R 2 O 2 CR 3 [0000] where RR′N represents the secondary amine on a drug moiety, and R 1-3 are various moieties such as hydrogen, alkyls, or cycloalkyls. Such prodrugs are hydrolyzed by esterases to generate RR′NCO 2 CR 1 R 2 OH which then decomposes to liberate the drug agent. [0014] Greenwald et al. J. Med. Chem., 42:3657-3667 (1997) discloses prodrugs having a drug linked, through a carbamate linkage to a PEG derivative. 1, 4 or 1,6 elimination reaction is required to release the free drug. The prodrug is structurally complex and toxic quinone methide intermediates may be liberated along the free drug. [0015] Thus, the prodrugs in the prior art generally have drawbacks that limit their practical applications. The requirement for enzyme digestion makes the prodrugs unsuitable or at least less useful for in vivo use. In addition, the generation of toxic intermediates can be associated with the release of free drugs. Thus, there remains a need for prodrugs having improved characteristics. SUMMARY OF THE INVENTION [0016] The invention provides a water soluble prodrug in which a biologically active agent is linked to a water soluble non-immunogenic polymer by a hydrolyzable carbamate bond. The biologically active agent can be readily released by the hydrolysis of the carbamate bond in vivo without the need for adding enzymes or catalytic materials. Generally, the biologically active agent is released, upon hydrolysis, into its parent state, i.e., without any additional moieties attached thereto. In addition, because a water soluble, non-peptidic polymer is used, even a substantially insoluble biologically active agent can be readily delivered in the prodrug in vivo. [0017] Thus, in accordance with the present invention, a prodrug is provided having the formula: [0000] [0000] wherein POLY is a water soluble and non-peptidic polymer, L is a linking group, Ar is an aromatic group, and Y is a biologically active agent. [0018] The water soluble non-immunogenic polymer can have a capping group selected from the group consisting of OH, alkoxy, and [0000] [0000] wherein L′ is a linking group, Ar′ is an aromatic group, and Y′ is a biologically active agent. Preferably, POLY is a poly(ethylene glycol) or a derivative thereof having a molecular weight of from about 200 to about 100,000 Daltons. [0019] In accordance with another embodiment of the invention, a compound is provided having the formula: [0000] [0000] in which POLY is a water soluble, non-peptidic polymer, L is a linking group, Ar is an aromatic group, and X is an activating group capable of reacting with an amino group of a biologically active agent to form a carbamate linkage. [0020] Optionally, POLY can have a capping group selected from the group consisting of OH, alkoxy, and [0000] [0000] wherein L′ is a linking group, Ar′ is an aromatic group, and X′ is an activating group capable of reacting with an amino group of a biologically active agent to form a carbamate linkage. Preferably, POLY is a poly(ethylene glycol) or a derivative thereof having a molecular weight of from about 200 to about 100,000 Dalton. [0021] In another embodiment of this invention, a prodrug is provided having the formula: [0000] Y—Ar—O 2 C—NH—POLY [0000] where Y is a biologically active agent having an aromatic group, Ar is the aromatic group of the biologically active agent Y, such as a substituted benzene or other aromatic such as a substituted naphthalene or heterocylic moiety, and POLY is a water soluble, non-peptidic polymer, preferably poly(ethylene glycol) in any of its form. Hydrolysis of this derivative yields the parent drug Y—ArOH, and POLY-NH 2 and CO 2. [0022] In accordance with yet another embodiment of the present invention, a hydrolytically degradable hydrogel is provided. The hydrogel comprises a backbone bonded to a crosslinking agent through a hydrolyzable carbamate linkage. Typically, a suitable backbone can be any compound having an amino group, preferably at least two amino groups. Examples of such backbones include, but are not limited to, proteins, peptides, aminocarbohydrates, aminolipids, poly(vinylamine), polylysine, poly(ethylene glycol) amines, pharmaceutical agents having an amino group, etc. The crosslinking agent is selected from the group consisting of: [0000] [0000] wherein POLY is a non-peptidic, water soluble polymer, L and L′ are linking groups, Ar and Ar′ are aromatic groups, Z is a central branch core, n is from 2 to about 100, and X and X′ are activating groups capable of reacting with the amino groups in the backbone to form hydrolyzable carbamate linkages. Preferably, POLY is a poly(ethylene glycol) or derivative thereof having a molecular weight of from about 200 to about 100,000. [0023] The foregoing and other features and advantages of the invention, and the manner in which the same are accomplished, will be more readily apparent upon consideration of the following detailed description of the invention in conjunction with the claims and the drawings. DESCRIPTION OF THE DRAWINGS [0024] FIG. 1 is a CE graph showing the hydrolysis of mPEG-lysozyme conjugate prepared with N-mPEG benzamide-m-succimidyl carbonate. At time zero, a small amount of free lysozyme was mixed with mono, di, and tri PEGylated lysozyme (Curve A). After hydrolysis for 10 days at pH 7 and 37° C., more than 85% of free lysozyme was released (Curve B). Peaks I, II, III, and IV represent free lysozyme, mono-PEGylated lysozyme, di-PEGylated lysozyme and tri-PEGylated lysozyme, respectively. DETAILED DESCRIPTION OF THE INVENTION [0025] As used herein, the term “prodrug” means a chemical derivative of a biologically active agent which can release or liberate the parent biologically active agent under defined conditions. By converting a parent biologically active agent into a prodrug, the solubility and immunogenicity of the agent can be modified. In addition, by controlling the rate of release of the agent from the prodrug, temporal control of the agent&#39;s action in vivo can be achieved. [0026] The term “biologically active agent” when used herein means any substances which can affect any physical or biochemical properties of a biological organism including but not limited to viruses, bacteria, fungi, plants, animals and humans. In particular, as used herein, biologically active agent includes any substance intended for the diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals, or to otherwise enhance physical or mental well being of humans or animals. Examples of biologically active agents include, but are not limited to, organic and inorganic compounds, proteins, peptides, lipids, polysaccharides, nucleotides, DNAs, RNAs, other polymers, and derivatives thereof. Examples of biologically active agents also include, e.g., antibiotics, fungicides, anti-viral agents, anti-inflammatory agents, anti-tumor agents, cardiovascular agents, anti-anxiety agents, hormones, growth factors, steroidal agents, and the like. [0027] A prodrug of this invention has the formula: [0000] [0000] wherein: [0028] POLY is a substantially non-immunogenic water soluble polymer; [0029] L is a covalent linkage, preferably a hydrolytically stable linkage; [0030] Ar is an aromatic group; and [0031] Y is a biologically active agent. [0032] As used herein, the terms “group,” “functional group,” “active moiety,” “reactive site,” reactive groups” and “reactive moiety” are all somewhat synonymous in the chemical arts and are used in the art and herein to refer to distinct, definable portions or units of a agent and to units that perform some function or activity and are reactive with other agents or portions of agents. [0033] The term “linking group” is used to refer to groups that normally are formed as the result of a chemical reaction and typically involve covalent bonding. [0034] In the prodrug of this invention, the substantially water soluble non-immunogenic polymer POLY is preferably poly(ethylene glycol) (PEG). However, it should be understood that other related polymers are also suitable for use in the practice of this invention and that the use of the term PEG or poly(ethylene glycol) is intended to be inclusive and not exclusive in this respect. [0035] Poly(ethylene glycol) or PEG is useful in biological applications because it has properties that are highly desirable and is generally approved for biological or biotechnical applications. PEG typically is colorless, odorless, soluble in water, stable to heat, inert to many chemical agents, does not hydrolyze or deteriorate, and is generally nontoxic. Poly(ethylene glycol) is considered to be biocompatible, which is to say that PEG is capable of coexistence with living tissues or organisms without causing harm. More specifically, PEG normally does not tend to produce an immune response in the body. When attached to an agent having some desirable function in the body, the PEG tends to mask the agent and can reduce any immune response so that an organism can tolerate the presence of the agent. Accordingly, the prodrug of the invention typically is substantially non-toxic and does not tend to produce substantial immune response or cause clotting or other undesirable effects. PEG having the formula —(CH 2 CH 2 O) n —CH 2 CH 2 —, where n is from about 8 to about 4000, is one useful polymer in the practice of the invention. Preferably PEG having a molecular weight of from about 200 to about 100,000 Da is used as POLY. [0036] In its most common form, PEG is a linear polymer having a hydroxyl group at each terminus: [0000] HO—CH 2 —CH 2 O(CH 2 CH 2 O)CH 2 CH 2 —OH [0037] PEG is commonly used as methoxy-PEG, or mPEG in brief, in which one terminus is the relatively inert methoxy group, while the other terminus is a hydroxyl group that is subject to ready chemical modification: [0000] CH 3 O—(CH 2 CH 2 O) n —CH 2 CH 2 —OH [0038] Branched PEGs are also in common use. The branched PEGs can be represented as R(—PEG-OH) n, in which R represents a central core agent such as pentaerythritol or glycerol, and m represents the number of arms. The number of arms m can range from three to a hundred or more. The hydroxyl groups are subject to ready chemical modification. [0039] Another branched form of PEG can be represented as (CH 3 O-PEG-) p R—Z, where p equals 2 or 3, R represents a central core such as lysine or glycerol, and Z represents a group such as carboxyl that is subject to ready chemical activation. This type of PEG has a single terminus that is subject to ready chemical modification. [0040] Yet another branched form, the pendant PEG, has reactive groups, such as carboxyls, along the PEG backbone rather than at the end of PEG chains. [0041] Forked PEG represented by the formula PEG(-LCHX 2 ) n is another form of branched PEG, where L is a linking group and X is an activated terminal group. [0042] In addition, the polymers can also be prepared to have weak or degradable linkages in the backbone. For example, PEG having hydrolytically unstable ester linkages in the polymer backbone can be prepared. The ester linkages are susceptible to hydrolysis which results in cleavage of the polymer into fragments of lower molecular weight: [0043] It is understood by those skilled in the art that the term poly(ethylene glycol) or PEG represents or includes all the above forms. [0044] Other polymers than PEG are also suitable for the present invention. These other polymers include, but are not limited to, other poly(alkylene oxides) such as poly(propylene glycol) (“PPG”), copolymers of ethylene glycol and propylene glycol and the like; poly(oxyethylated polyols) such as poly(oxyethylated glycerol), poly(oxyethylated sorbitol), and poly(oxyethylated glucose); poly(vinyl alcohol) (“PVA”); dextran; carbohydrate-based polymers and the like. The polymers can be homopolymers or random or block copolymers and terpolymers based on the monomers of the above polymers, straight chain or branched. [0045] Specific examples of suitable additional polymers include, but are not limited to, poly(oxazoline), difunctional poly(acryloylmorpholine) (“PAcM”), and poly(vinylpyrrolidone) (“PVP”). PVP and poly(oxazoline) are well known polymers in the art and their preparation should be readily apparent to the skilled artisan. PAcM and its synthesis and use are described in U.S. Pat. Nos. 5,629,384 and 5,631,322, the contents of which are incorporated herein by reference in their entirety. [0046] Although the molecular weight of POLY can vary, it is typically in the range of from about 100 to about 100,000, preferably from about 2,000 to about 80,000. [0047] Those of ordinary skill in the art will recognize that the foregoing list for substantially water soluble non-immunogenic polymer POLY is by no means exhaustive and is merely illustrative, and that all polymeric materials having the qualities described above are contemplated. [0048] The polymer POLY can have a terminal capping group distal to the biologically active agent Y. Examples of the capping group include, but are not limited to, OH, alkoxy, and [0000] [0000] wherein L′ is a hydrolytically stable linkage, Ar′ is an aromatic group, and Y′ is a biologically active agent. L′, Ar′, and Y′ can be same or different from L, Ar, and Y respectively. [0049] The aromatic groups Ar and Ar′ in the prodrug can be any aryl groups in any chemically arranged forms. For example, phenyl, substituted phenyl, biphenyl, substituted biphenyl, polycyclic aryls, substituted polycyclic aryls, heterocyclic aryls, substituted heterocylic aryls, and derivatives thereof can all be used. The substitutions on the aromatic ring(s) of Ar and Ar′ can be at any position relative to L or L′. Examples of suitable substitution moieties include, but are not limited to, halogen, alkyls, alkoxy, hydroxy, carboalkoxy and carboxamide. It should be understood that these additional groups bonded to the aromatic group may affect the hydrolysis rate of the carbamate linkage between Ar and Y, and/or Ar′ and Y′. Thus, different substitution moieties can be chosen to control the release rate of the biologically active agent Y and Y′. Preferably Ar and Ar′ are benzenes or substituted benzenes. [0050] The linking groups L and L′ link the aromatic groups Ar and Ar′, respectively, to the non-immunogenic polymer POLY. Typically they are formed by reacting a terminal group of POLY with a reactive moiety on a ring of the aromatic group Ar or Ar′. L and L′ can be any covalent linkages. In particular, L and L′ can include covalent bonds such as ethers, amines, imines, imides, amides, carbamides, esters, thioesters, carbonates and ureas. For example, L and L′ can be selected from moieties such as —O—, —NR— where R is H, a C 1-6 alkyl or substituted alkyl, —CO 2 —, —O 2 C—, —O 2 CO—, —CONH—, —NHCO—, —S—, —SO—, —SO 2 —, etc. Preferably L and L′ are —O—, or —NHCO—. [0051] The carbamate linkages between Ar and Y, and Ar′ and Y′ are hydrolyzable in vivo at a desirable rate. Typically, when a prodrug of this invention is delivered into the body, the prodrug is first delivered to the desired tissue or organ through a selected route, e.g., blood circulation. The parent biologically active agent is released by hydrolysis. Once the parent agent is released, the rest of the components of the prodrug are subsequently eliminated by biodegradation or excretion. To achieve the optimal result, the linkages L and L′ typically are more stable than the hydrolyzable carbamate linkage. Preferably, L and L′ are hydrolytically stable linkages. In addition, the prodrug circulation lifetime should be longer than the time required for hydrolysis of the carbamate linkage. [0052] In the prodrug of this invention, the release rate of the parent biologically active agent from the prodrug can be modified in a number ways. It has been found that the rate of hydrolytic degradation of the carbamate linkage is affected by the position of the attachment of the L or L′, as defined above, to the aromatic ring relative to the position of the carbamate linkage attachment. That is, the carbamate hydrolysis rates vary, in the case of benzene derivatives, between ortho, meta, and para placement of L or L′. The rate of hydrolysis of the carbamate linkage is also affected by the nature of L and L′, for example an ether linkage is more stable than an amide linkage. Moreover, additional moieties bonded to the aromatic group may affect the hydrolysis rate of the carbamate linkage. Thus, different substitution moieties can be chosen to control the release rate of the biologically active agent Y and Y′. [0053] In one preferred embodiment, the prodrug of this invention has the formula: [0000] [0000] wherein: [0054] L is —O— or —NHCO—; [0055] Y is a biologically active agent; [0056] POLY is poly(ethylene glycol) having a capping group selected from the group consisting of —OH, C 1-4 alkyl, and [0000] [0000] wherein Y′ and L′ are as described above. [0057] Thus, the hydrolysis of the carbamate linkage in the prodrug can be illustrated as follows: [0000] [0058] Although, the present invention is especially suited for delivering biologically active agents that are water insoluble and/or immunogenic, this invention can be used for virtually any biologically active agents. However, as is clear below in the description of the synthesis of the prodrug, the biologically active agent to be converted to the prodrug of this invention must have an amino group or a moiety that can be converted to an amino group. Suitable biologically active agents include, but are not limited to, proteins, enzymes, peptides, aminolipids, polysaccharides having an amino group, amino-oligonucleotides, and pharmaceutical agents having an amino group. [0059] Generally the method of synthesizing a prodrug of this invention includes the following steps: first, an activated water soluble and non-peptidic polymer is provided. The activated polymer typically has a reactive terminal moiety. For example, the activated polymer can be POLY-NH 2, H 2 N—POLY-NH 2, POLY-O—SO 2 —CH 3, or CH 3 —SO 2 —O—POLY-O—SO 2 —CH 3, and the like. An aryl compound having two reactive substitution groups linked to the aromatic ring is also provided. The aryl compound can be, e.g., hydroxybenzoic acid or benzyloxyphenol. One of the two reactive groups on the aromatic ring can react with the reactive terminal moiety of the activated polymer to form the linkage L. The other reactive group of the aryl compound either itself can react with an amino group of a biological active agent to form a hydrolyzable carbamate linkage, or can be converted into a reactive group which can react with an amino group of a biological active agent to form a hydrolyzable carbamate linkage. Thus, a compound is provided having the formula: [0000] [0000] wherein POLY, L, and Ar are as described in regard to the prodrug of this invention, and wherein X is an activating group capable of reacting with an amino group of a biologically active agent to form a hydrolyzable carbamate linkage. [0060] Preferably, L is —O— or —NHCO—, Ar is a substituted or unsubstituted benzene moiety, X is chlorine, bromine, N-succinimidyloxy, or 1-benzotriazolyloxy, and POLY is poly(ethylene glycol) or a derivative thereof with a molecular weight of from about 200 to about 100,000 Dalton and having a capping group selected from the group consisting of —OH, C 1-4 alkyl, and [0000] [0000] where L′ is —O— or —NHCO—, Ar′ is a substituted or unsubstituted benzene moiety, and X′ is chlorine, bromine, N-succinimidyloxy, or 1-benzotriazolyloxy. [0061] In another embodiment of this invention, a prodrug is provided having the formula: [0000] Y—Ar—O 2 C—NH—POLY [0000] where Y is a biologically active agent having an aromatic group, Ar is the aromatic group of the biologically active agent Y, such as a substituted benzene or other aromatic such as a substituted naphthalene or heterocylic moiety, and POLY is a water soluble, non-peptidic polymer as described above, preferably poly(ethylene glycol) in any of its form. Hydrolysis of this derivative yields the parent drug Y—ArOH, and POLY-NH 2 and CO 2. [0062] In accordance with another aspect of this invention, a hydrolytically degradable hydrogel is provided. The hydrogel comprises a backbone bonded to a crosslinking agent through a hydrolyzable carbamate linkage. [0063] Typically, the backbone of the hydrogel is a biocompatible macromolecule. The backbone has an amino group available to react with the crosslinking agent to form a hydrolyzable carbamate linkage. Preferably, the backbone has at least two of such amino groups. Examples of such backbones include, but are not limited to, proteins, modified proteins such as glycoproteins, phosphorylated proteins, acylated proteins, and chemically modified proteins, peptides, aminocarbohydrates, glycosaminoglycans, aminolipids, poly(vinylamine), polylysine, poly(ethylene glycol) amines, pharmaceutical agents having at least two amino groups, etc. Specific examples of the backbone include, but are not limited to, fibrin, fibrinogen, thrombin, albumins, globulins, collagen, fibronectin, chitosan and the like. In addition, the backbone may also be microorganisms such as viral particles, bacterial cells, or animal or human cells. [0064] The crosslinking agent can be the difunctional polymer described above having the formula: [0000] [0000] wherein POLY, POLY′, L, L′, X, X′, Ar, and Ar′ are as described above. Alternatively, the crosslinking agent can also be a branched water-soluble substantially non-immunogenic polymer having the formula: [0000] [0000] wherein POLY, L, L′, Ar, Ar′, X and X′ are as described above. Z is a central branch core moiety. n represents the number of arms and is from 2 to about 100. In particular, the central branch core moiety can be derived from the amino acid lysine, or polyols such as glycerol, pentaerythritol and sorbitol. Branched PEGs are known in the art. Suitable branched PEGs can be prepared in accordance with U.S. Pat. No. 5,932,462, which is incorporated herein in their entirety by reference. These branched PEGs can then be modified in accordance with the present teachings. For example, a four-arm, branched PEG prepared from pentaerythritol is shown below: [0000] C(CH 2 —OH) 4 +n C 2 H 4 O-6C[CH 2 O—(CH 2 CH 2 O) n —CH 2 CH 2 —OH] 4 [0065] This branched PEG can then be further modified to form the branched crosslinking agent by the method as described above in the context of synthesizing a prodrug. [0066] In a preferred embodiment, the crosslinking agent has the formula: [0000] [0000] wherein X and L are as described above. Thus, the crosslinking of a backbone having multiple amino groups by this crosslinking agent in the process for foaming a hydrogel can be illustrated as follows: [0000] [0000] where the zig-zag notation represents a backbone having amine groups and where L is as described above. [0067] As will be apparent, the carbamate linkages between the backbones and the crosslinking agents formed from the crosslinking reactions are hydrolyzable. Thus, the hydrogel of this invention can gradually break down or degrade in the body as a result of the hydrolysis of the carbamate linkages. Therefore, the hydrogel of this invention can be used as a carrier for delivery of biologically active agents and other suitable biomedical applications. For example, the hydrogel can carry therapeutic drugs and can be implanted or injected in the target area of the body. The hydrogel may also carry other agents such as nutrients or labeling agents for imaging analysis. [0068] In the various applications of the hydrogel of this invention, the biologically active agents to be delivered can be used as the backbone, or part of the backbone of the hydrogel. Alternatively, biologically active agents can be in the form of a prodrug as described above and covalently linked to the hydrogel as illustrated: [0000] [0000] wherein L is a linkage as described above, Y is a biologically active agent to be delivered in the hydrogel. Typically, in this case, Y has an amino group which can react and form a carbamate linkage as described above. Also, biologically active agents or other substances to be delivered can also be loaded into the hydrogel during the synthesis of the hydrogel, or afterwards, e.g., by diffusion into the cavity or matrix of the hydrogel without being covalently bonded to the hydrogel structure, that is, the backbone or crosslinking agent of the hydrogel. [0069] Because the crosslinking agents in the hydrogel are water soluble and substantially non-immunogenic, the hydrogel can be substantially water soluble and non-immunogenic as well. In addition, because of the interconnection by a large number of hydrolytically degradable carbamate linkages, typically the degradation or breakdown of the hydrogel in the body is gradual in nature. Thus, it is particularly useful for sustained release of a biologically active agent or other substances in the body. [0070] The present invention is further illustrated in the following examples which are given to illustrate the invention, but should not be considered in limitation of the invention. EXAMPLES Example 1 Synthesis of N-mPEG benzamide-m-succinimidyl carbonate (1) [0071] [0072] mPEG amine 5000 (1.5 g, 0.3 mmole), 3-hydroxybenzoic acid (44 mg, 0.315 mmole) and dicyclohexylcarbodiimide (DCC, 84 mg) were dissolved in 20 ml of anhydrous THF. The solution was stirred at room temperature overnight. The solvent was condensed to half on a rotary evaporator and the residue was precipitated into 150 ml of ethyl ether. The precipitate was collected by filtration and dried in vacuo. Yield 1.5 g (100%). 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 6.90 (m, aromatic), 7.22 (m, aromatic), 8.37 (t, PEG-N H CO—), 9.62 (s, —C 6 H 6 —O H ). [0073] The above product (1 gram) and disuccinimidyl carbonate (DSC, 200 mg) were dissolved in 8 ml of acetonitrile. To the solution was added 200 ul of pyridine. The solution was stirred under nitrogen overnight and the solvent was removed under reduced pressure. The resulting solid was redissolved in 10 ml of dry chloroform and the insoluble solid was removed by filtration. The solution was then precipitated into 150 ml of dry ethyl ether and the precipitate collected by filtration and dried in vacuo. Yield 0.95 g (95%). 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 7.58 (m, aromatic), 7.83 (m, aromatic), 8.64 (t, PEG-NHCO—). Example 2 Synthesis of N-mPEG-benzamide-p-succinimidyl carbonate (2) [0074] [0075] mPEG amine 5000 (3 g, 0.6 mmole), 4-hydroxybenzoic acid (87 mg, 0.62 mmole) and dicyclohexylcarbodiimide (DCC, 160 mg) were dissolved in 20 ml anhydrous THF. The solution was stirred at room temperature overnight. The solvent was condensed to half on a rotary evaporator and the residue was precipitated into 150 ml of ethyl ether. The precipitate was collected by filtration and dried in vacuo. Yield 3 g (100%). 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 6.78 (d, aromatic), 7.70 (d, aromatic), 8.23 (t, PEG-N H CO—), 9.94 (s, —C 6 H 6 —O H ). [0076] The above product (1.5 gram) and disuccinimidyl carbonate (DSC, 300 mg) were dissolved in 12 ml of acetonitrile. To the solution was added 300 ul of pyridine. The solution was stirred under nitrogen overnight and the solvent was removed under reduced pressure. The resulting solid was redissolved in 10 ml of dry chloroform and the insoluble solid was removed by filtration. The solution was then precipitated into 150 ml of dry ethyl ether. The precipitate was collected by filtration and dried in vacuo. Yield 1.42 g (95%). 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 7.49 (d, aromatic), 7.95 (d, aromatic), 8.60 (t, PEG-NHCO—). Example 3 Synthesis of mPEG phenyl ether-p-succinimidyl carbonate (3) [0077] [0078] mPEG mesylate 5000 (5 g, 1 mmole) in 60 ml of toluene was azeotropically distilled under nitrogen. After two hours, the solution was cooled to room temperature. [0079] 4-benzyloxyphenol (0.44 g, 2.2 mmole) was added to a mixture of 0.46 ml of sodium methoxide (2 mmole, 25% in methanol) and 25 ml of dry methanol. The mixture was slowly stirred under nitrogen for 20 minutes. Methanol was then gradually distilled off until about 5 ml of solution was left. 50 ml of dry toluene was added and the solution was distilled under nitrogen. The azeotropic distillation was not stopped until all methanol was removed. The mixture was cooled to room temperature. The freshly azeotropically dried mPEG mesylate from the previous step was added and the mixture was refluxed under nitrogen overnight. The reaction mixture was cooled to room temperature, toluene was distilled off, and methylene chloride was added. The solid was removed by filtration and the filtrate was washed with 10% sodium bicarbonate containing 10% sodium chloride aqueous solution and then dried over sodium sulfate. The dry methylene chloride solution was filtered, condensed on a rotary evaporator and precipitated into 100 ml of ether. The product was collected by filtration and dried in vacuum. Yield 4.5 g (90%). NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 4.00 (t, —PEGOCH 2 C H 2 OC 6 H 4 O—), 5.02 (s, —PEGOC 6 H 4 OC H 2 C 6 H 5 ), 6.90 (d+d, —PEGOC 6 H 4 O—), 7.35 (m, —PEGOC 6 H 4 OCH 2 C 6 H 5 ). [0080] mPEG-p-(benzyloxy)-phenyl ether (4.5 g, 0.9 mmole) was dissolved in 1,4-dioxane (40 ml), and then hydrogenated with H 2 (2 atm pressure) and 1.5 gram Pd/C (10%) overnight. The catalyst was removed by filtration and the product precipitated into ethyl ether after most solvent was distilled off on a rotary evaporator. Yield: 3.7 gram (82%). 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 3.96 (t, —PEGOCH 2 C H 2 OC 6 H 4 OH), 6.70 (d+d, —PEGOC 6 H 4 O—), 8.89 (s, —OH). [0081] mPEG phenyl ether-p-phenyl alcohol (1.2 g) and disuccimidyl carbonate (DSC, 210 mg) were dissolved into 15 ml of acetonitrile. To the solution was added 0.12 ml of pyridine. The solution was stirred under nitrogen overnight and the solvent was removed under reduced pressure. The resulting solid was redissolved in 10 ml of dry chloroform and the insoluble solid was removed by filtration. The solution was then precipitated into 150 ml of dry ethyl ether. The precipitate was collected by filtration and dried in vacuo. Yield 1.15 gram. (96%). 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG), 7.49 (d, aromatic), 7.95 (d, aromatic), 8.60 (t, PEG-N H CO—). Example 4 Preparation of mPEG-NH—COO-Drug [0082] [0083] 20 mg of the above drug was azeotropically dried in pyridine and methoxy-PEG isocyanate (177 mg, 5000 Dalton) was then added. The solution was stirred at room temperature overnight and the solvent was removed under reduced pressure to yield a residual syrup. To this was added 100 ml of ether and the resulting precipitate was collected by filtration and dried in vacuo. PEG conjugation was demonstrated to be 60% by 1 H NMR and GPC. Example 5 Synthesis of mPEG phenyl ether-p-mexiletine carbamate [0084] [0085] mPEG phenyl ether-p-succinimidyl carbonate (300 mg, 5000 Dalton), and mexiletine hydrochloride (16 mg), TEA (200 were disclosed in 8 ml of anhydrous methylene chloride. The solution was stirred overnight. The solvent was condensed on a rotary evaporator and 100 ml of isopropyl alcohol was added to the residual syrup. The resulting precipitate was collected by filtration, washed with 20 ml of ether, and dried in vacuo. 1 H NMR (DMSO-d 6 ): δ 3.5 (br m, PEG) 2.23 (s, CH3—), 6.9 (M, aromatic H), 1.23 (d, —CH2—CH(CH3)-). Conjugation was shown to be greater than 90% by GPC. Example 6 Modification of Lysozyme with the PEG Derivatives in Examples 1-3 [0086] 5-25 mg of each of the PEG derivatives prepared in Examples 1-3 was mixed with 1 ml of lysozyme solution at pH 7 (5 mg/ml in 0.1 M phosphate buffer). The solution was gently shaken for 5 hours at room temperature, and then stored at +4° C. for future analysis. PEGylation was monitored by capillary electrophoresis. Example 7 Monitoring Hydrolysis of the PEG Conjugate of Lysozyme by Capillary Electrophoresis [0087] The conjugates prepared as described above were placed at 37° C. and at room temperature and hydrolysis was monitored by capillary electrophoresis (CE). The CE graphs are shown in FIG. 1. [0088] CE conditions: A solution of 25 mM phosphate buffer, containing 0.1 mg/ml PEO 600K, pH 2.7 was flushed through the capillary for approximately 15-20 min. A voltage of 15 kV was applied until a smooth baseline was obtained. The 25 mM phosphate buffer solution was again flushed through for approximately 5 min and the capillary was then ready for sample injection. The sample, which was adjusted to pH 2 by a phosphate buffer (0.1 M, pH 2), was injected hydrostatically for about 10 at a height of approximately 6 inches. A voltage of 15 kV was applied throughout the run with a current between 24 and 30 μA. The protein and PEG-protein conjugate were detected by a UV monitor at 214 nm. The CE instrument consists of a high-voltage power supply (Spellman CZE1000R), a fused silica capillary (75 μm i.d., 360 μm o.d., Polymicro Technologies, Phoenix, Ariz.) and a linear 200 UV/VIS monitor supplied with a deuterium lamp and a capillary flow cell. The total length of the capillary was 64.5 cm, with a 1 cm optical window at 40 cm from the anode. UV data was retrieved and stored using LabVIEW version 4.0.1 software (National Instruments). Example 8 Analysis of Hydrolysis Product by MALDI-TOF [0089] The hydrolysis product from each conjugate was examined by MALDI-TOF to determine if there was any dimerization caused by reactions between hydrolysis intermediates. Free lysozyme was used as control. No dimerization was observed. Experiment 9 Bioactivity Measurement of Reversible Lysozyme Conjugate [0090] Bioactivity of free lysozyme, PEG conjugates of lysozyme and lysozyme recovered from hydrolysis of the conjugates were measured by an assay from the standard protocol of Sigma for hen&#39;s egg white (HEW) lysozyme EC.3.2.1.17. A solution containing the unmodified or PEG-modified lysozyme was diluted to 5.5 μg/ml in a 66 mM sodium phosphate buffer (pH 6.24). A suspension of 1.5 mg Micrococcus lysodeikticus in 10 ml of 66 mM phosphate buffer (pH 6.24) was allowed to equilibrate at room temperature until the absorbance at 450 nm was constant. Then 0.1 ml of a lysozyme solution was placed in a 1 cm light path quatz cuvette containing 2.5 ml of the substrate suspension. The decrease in the absorbance at 450 nm was recorded and the activity was determined from the maximum linear rate. Eighty-two percent of lysozyme bioactivity was recovered from the m-PEG-lysozyme conjugate, while the mPEG lysozyme had undetectable bioactivity prior to hydrolysis. Example 10 Preparation of Hydrogels from Di-Functional PEG 3400 Benzamide-m-succimidyl Carbonate [0091] In a test tube, 55 mg of di-functional PEG 3400 benzamide-m-succimidyl carbonate was dissolved in 0.36 ml of cold de-ionized water (4° C.). Then 0.36 ml of 8-arm-PEG amine 10,000 (Shearwater Polymers, Inc, AL, USA) solution (110 mg/ml, in pH 7 phosphate buffer) was added. After rapid mixing, the solution was allowed to stand at room temperature. A clear gel formed in a few minutes. Example 11 Degradation of the Hydrogels Prepared from Di-Functional PEG Benzamide-m-succimidyl Carbonate [0092] An approximately 0.2 cm 3 piece of gel prepared from Example 8 was put into about 1 ml of PBS buffer, while the other was put into the same amount of human serum. Both samples were incubated at 37° C. Gel degradation was monitored visually to evaluate the degradation life times. The gel was observed to degrade to yield a clear solution in approximately 4 hours. [0093] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims.

Summary: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

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Summarize: FEDERALLY SPONSORED RESEARCH [0001] Not Applicable SEQUENCE LISTING OR PRINCIPLE [0002] Not Applicable BACKGROUND—FIELD OF INVENTION [0003] This invention relates to pocket billiards learning aids specifically used to teach pocket billiard players how to properly aim a cue ball at an object ball and pocket the object ball while accurately estimating the range of cue ball direction after impact. BACKGROUND DESCRIPTION OF PRIOR ART [0004] There are all sorts of teaching aids used to teach people how to aim pocket billiard shots for different angles. U.S. Pat. No. 6,827,651 by Davis shows a device using lasers to locate the position of the cue ball at impact and 1 fixed direction for the cue ball after impact. The device must sit on the table while the shot is practiced and does not indicate a range of cue ball direction after impact. U.S. Pat. No. 6,053,817 by Flegel shows a device made from cloth temporarily positioned on a pocket billiard table surface. A cue ball is then used to roll onto the surface of the device and make contact with other pocket billiard balls set upon the surface of the device. The problem is you must set the balls on the surface of the device to execute each shot and the device does not give feed back about the range of cue ball direction after impact. U.S. Pat. No. 6,045,450 by Cyr shows a targeting disc that is placed in intimate contact with the object ball on the table. Once positioned the student has indication where to aim. The targeting disc is hard to position and must be left on the table while shooting the shot. Another U.S. Pat. No. 5,401,215 uses an object ball coated with an array of colored dots. This device is difficult to understand and does not give information about the cue ball direction after impact. U.S. Pat. No. 4,178,694 by Bonney shows still another device which acts as a point of aim indicator. This device cannot be used with the actual shot and the object ball must be placed on a pedestal to use it properly and there is no indication of cue ball direction after impact. One of the prior art references U.S. Pat. No. 3,843,120 by Ricci shows an apparatus used for marking an aiming point. The apparatus is shaped like a cue ball and designed to be placed in intimate contact with an object ball and then using a stick of chalk or other marking means to mark the aiming point. The apparatus must be used to set up each and every shot practiced restricting the students ability to concentrate on shooting the same shot a multiplicity of times. Ricci&#39;s apparatus is very difficult to align and accuracy decreases as you move more than 18″ or so away from the target pocket. The apparatus is expensive to manufacture and is very limited in application because the apparatus can only reference an aiming point. This process is time consuming and a shot can not be exactly repeated. All of the above mentioned prior art fail to provide a repeatable condition for shooting exactly the same shot over and over again indicating the exact aiming point, object ball position and cue ball directions for any one of a range of angles for the shot once the training aids are removed from the table surface. OBJECTS AND ADVANTAGES [0005] Accordingly, several objects and advantages of the present invention are: (a) To provide a pocket Billiard Aim Instruction Kit showing the accurate aiming location and range of direction for the cue ball direction after impact. (b) To provide a pocket Billiard Aim Instruction Kit that can be used to set up multiplicity of practice locations on a billiard table surface, while revealing each location&#39;s aiming point reference mark, 5 object ball position marks, 5 different aiming angle reference marks and a center hit cue ball direction reference mark once the Billiard Aim Instruction Kit is removed from the billiard table surface. (c) To provide a Billiard Aim Instruction Kit used to set up a plurality of practice shots in different locations on a pocket billiard table and then once the Position reference tool is removed from the pocket billiard table retain the ability to practice those shots set up with the Billiard Aim Instruction Kit a plurality of times and additionally use said Position Reference tool as a feedback reference for any of the shots executed at any time during the practice session. [0009] Still further objects and advantages will become apparent from a consideration of the ensuing description and drawings. SUMMARY [0010] In accordance with the present invention a Billiard Aim Instruction Kit comprises a position reference tool, 10 rail indicators, 1 center tip indicator and a position marker used on a billiard table surface to help students indicate the precise locations for a billiard object ball and cue ball at the moment of impact while providing detailed information about cue ball direction after impact between the object ball and cue ball occurs. DRAWINGS Drawing Figures [0011] FIG. 1 is a top view of the Billiard Aim Instruction kit showing a position reference tool, 10 rail indicators, 1 center tip indicator and a position marker. [0012] FIG. 2 is a top view showing the precise locations and dimensional relationships of the 12 apertures located on the position reference tool. [0013] FIG. 3 is a top view showing a standard pocket billiard table with the position reference tool positioned on the table surface and the 11 rail indicators positioned on the rails of the pocket billiard table. [0014] FIG. 4 is a close up view of the pocket billiard table showing the talcum powder marks left at the 12 aperture positions on the position reference tool. [0015] FIG. 5 is a side view of a billiard object ball with dimensional references to object ball aiming points for 5 different angles of aim. [0016] FIG. 6 is a dimensional drawing showing the relationships between angle apertures and range graphics. [0017] FIG. 7 is a close up view showing how to set up a pocket billiard practice shot. [0018] FIG. 8 is a side view illustrating the 3 common locations a cue tip makes contact with a cue ball. [0019] FIG. 9 shows a side view of the tip of a common pocket billiard cue stick. DETAILED DESCRIPTION [0020] Referring to FIG. 1, a position reference tool 1 comprises a flat rectangular sheet of plastic with 12 small diameter apertures, angle aperture 6 4, angle aperture 3 6, angle aperture 1. 7 8, angle aperture 1 10, angle aperture. 66 12, left ball aperture 25, universal point aperture 26, top ball aperture 27, center ball aperture 28, bottom ball aperture 29, right ball aperture 30 and center tip aperture 37 centered upon the surface of the position reference tool 1 and positioned as dimensioned in FIG. 2. The position reference tool 1 is made of flexible thin plastic sheet material. The Line to pocket 3 is a bold black line printed on the surface of the position reference tool 1 and extends from one short side of the rectangle through the centers of the universal point aperture 26, bottom ball aperture 29, center ball aperture 28, and top ball aperture 27 to the opposite short edge of the rectangle. Angle line 6 65 is a bold black line printed on the surface of the position reference tool 1 extending from the center of the universal point aperture 26 to the center of angle aperture 6 4. Angle line 3 66 is a bold black line printed on the surface of the position reference tool 1 line extending from the center of the universal point aperture 26 to the center of angle aperture 3 6. Angle line 1. 7 67 is a bold black line printed on the surface of the position reference tool 1 extending from the center of the universal point aperture 26 to the center of angle aperture 1. 7 8. Angle line 1 68 is a bold black line printed on the surface of the position reference tool 1 extending from the center of the universal point aperture 26 to the center of angle aperture 1 10. Angle line. 66 69 is a bold black line printed on the surface of the position reference tool 1 extending from the center of the universal point aperture 26 to the center of angle aperture. 66 12. The angle reference 6 5, angle reference 3 7, angle reference 1. 7 9, angle reference 1 11 and angle reference. 66 13 are printed on the surface of the position reference tool 1 in close proximity to the angle aperture 6 4, angle aperture 3 6, angle aperture 1. 7 8, angle aperture 1 10, angle aperture. 66 12 respectively. The object ball graphic 20 is a graphic image of a pocket billiard ball printed on the surface of position reference tool 1. The position marker 42 is a standard small cloth bag of white talcum powder similar to those sold in billiard rooms and bowling alleys as a product useful for keeping hands dry during play. The object ball aim point. 66 24, object ball aim point 1 23, object ball aim point 1. 7 22, object ball aim point 3 21 and object ball aim point 6 19 are bold black circular dots printed on the surface of the position reference tool 1 having scale dimensional relationships to the object ball 20 as shown in FIG. 5. The aiming reference. 66 14, The aiming reference 1 15, The aiming reference 1. 7 16, The aiming reference 3 17 and The aiming reference 6 18 are printed on the surface of the position reference tool 1 in close proximity to the object ball aim point. 66 24, object ball aim point 1 23, object ball aim point 1. 7 22, object ball aim point 3 21, and object ball aim point 6 19 respectively. Referring to FIGS. 1 and 2 angle aperture 6 4, angle aperture 3 6, angle aperture 1. 7 8, angle aperture 1 10, angle aperture. 66 12 left ball aperture 25, universal point aperture 26, top ball aperture 27, center ball aperture 28, bottom ball aperture 29, right ball aperture 30 and center cue tip aperture 37 are small diameter apertures large enough to allow talcum powder from the position marker 42 to be transferred through the position reference tool 1 on to the surface of a standard billiard table 70 shown in FIG. 3. FIG. 1 shows a range graphic. 66 36, range graphic 1 38, range graphic, range 1. 7 39, graphic 3 40 and range graphic 6 41 are pictorial graphics printed in the shape of various size circle sectors on the surface of position reference tool 1 and positioned as dimensioned in FIG. 6. Cue ball path reference 6 31, cue ball path reference 3 32, cue ball path reference 1. 7 33, cue ball path reference 1 34, and cue ball path reference. 66 35, are printed in close proximity to range graphic 6 41, range graphic 3 40, range graphic 1. 7 39, range graphic 1 38 and range graphic. 66 36 respectively. In FIG. 1 rail indicator 6 H 44, rail indicator 6 L 46, rail indicator 3 H 48, rail indicator 3 L 50, rail indicator 1. 7 H 52, rail indicator 1. 7 L 54, rail indicator 1 H 56, rail indicator 1 L 58, rail indicator. 66 H 60, rail indicator. 66 L 62 and rail indicator CT 64 are small plastic discs small enough to sit upon the rails of a standard pocket billiard table 70 of FIG. 3. The direction reference 6 H 43, direction reference 6 L 45, direction reference 3 H 47, direction reference 3 L 49, direction reference 1. 7 H 51, direction reference 1. 7 L 53, direction reference 1 H 55, direction reference 1 L 57, direction reference. 66 H 59, direction reference. 66 L 61, and direction reference CT 63 are text graphics printed on the surface of rail indicator 6 H 44, rail indicator 6 L 46, rail indicator 3 H 48, rail indicator 3 L 50, rail indicator 1. 7 H 52, rail indicator 1. 7 L 54, rail indicator 1 H 56, rail indicator 1 L 58, rail indicator. 66 H 60, rail indicator. 66 L 62 and rail indicator CT 64 respectively. In FIG. 3, FIG. 4, FIG. 7 and FIG. 8 the cue ball. 73 is a standard cue ball used in the game of pocket billiards. In FIG. 7 the object ball 72 is a standard pocket billiard ball marked with a number from 1 to 15 used in the game of pocket billiards. In FIG. 9 the tip of the cue 89 is a standard cue tip found on the end of all standard billiard cue sticks used in the game of pocket billiards. In FIG. 1 the center ball line 2 is a bold black line with an arrowhead graphic extending from the center of universal point aperture 26 at an angle perpendicular to the line to pocket 3. As stated earlier, other embodiments are possible such as using color coding instead of reference numbers to describe the relationships between angles and cue ball direction. Another embodiment can use pocket billiard chalk instead of talcum powder to mark the position of the position reference tool 1. [0021] Operation [0022] FIG. 3 shows how the position reference tool 1 is set up to practice pocket billiard shots on a standard pocket billiard table 70. The position reference tool 1 is positioned on the surface of pocket billiard table 70 by aligning the line to pocket 3 touching and parallel with an imaginary line extending through the center of the billiard pocket 71 as shown in FIG. 3. Once the position reference tool 1 is properly aligned, the student uses the position marker 42 to apply a light coat of talcum powder on to the billiard table 70 surface using the position reference tool 1 as a mask or stencil, moving the position marker 42 back and forth with a daubing patting and wiping motion over the angle aperture 6 4, angle aperture 3 6, angle aperture 1. 7 8, angle aperture 1 10, angle aperture. 66 12, left ball aperture 25, universal point aperture 26, top ball aperture 27, center ball aperture 28, bottom ball aperture 29, right ball aperture 30 and center tip aperture 37. The student then finds the 2 straight sides for each circle sector shaped range graphic. 66 36, range graphic 1 38, range graphic, range 1. 7 39, graphic 3 40 and range graphic 6 41. The student places rail indicator. 6 H 44, rail indicator 6 L 46, rail indicator 3 H 48, rail indicator 3 L 50, rail indicator 1. 7 H 52, rail indicator 1. 7 L 54, rail indicator 1 H 56, rail indicator 1 L 58, rail indicator. 66 H 60 and rail indicator. 66 L 62 on the rails of the pocket billiard table 70 making sure to position each indicator is aligned and centered along imaginary lines extending from the center of the universal point aperture 26 touching and parallel to both straight sides of each range graphic. 66 36, range graphic 1 38, range graphic, range 1. 7 39, graphic 3 40 and range graphic 6 41 as shown by the dotted lines in FIG. 3. The student places the center tip indicator 64 on the rail of the pocket billiard table 70 making sure to position the center tip indicator 64 aligned and centered on an imaginary line from the center of the universal point aperture 26 touching and parallel to the center ball line 2 as shown by the dotted line in FIG. 3. After the student has marked the pocket billiard table 70 using the position reference tool 1 with the position marker 42 and placed the center tip indicator 64 and rail indicators 44, 48, 52, 56, 60, 62, 58, 54, 50 and 46 on the rails of the pocket billiard table 70 at their defined locations, the position reference tool 1 is removed to reveal a residue of talcum powder forming the pattern on the pocket billiard table 70 as shown in FIG. 4. The pattern in FIG. 4 consists of angle mark 6 74, angle mark 3 75, angle mark 1. 7 76, angle mark 1 77, angle mark. 66 78, universal point mark 79, left ball mark 80, top ball mark 81, center ball mark 82, right ball mark 83, bottom ball mark 84 and center tip mark 85. Before going further the relationships between the angle marks, direction references, angle references, rail indicators, aiming references and object ball aiming points must be understood. Each angle mark has 2 relative direction references. As an example, direction reference 1 H 56 and direction reference 1 L 58 are relative to angle mark 1 77 as shown in FIG. 7. Angle reference 6 5, angle reference 3 7, angle reference 1. 7 9, angle reference 1 11, angle reference. 66 13 is relative to the direction reference CT 63. Angle mark 6 74, angle mark 3 75, angle mark 1. 7 76, angle mark 1 77 and angle mark. 66 78 is relative to the rail indicator CT 64. Aiming reference. 66, 14, aiming reference 1, 15, aiming reference 1. 7, 16, aiming reference 3, 17 and aiming reference 6 18 is relative to angle reference. 66 13, angle reference 1 11, angle reference 1. 7 9, angle reference 3 7 and angle reference 6 5 respectively. Angle mark 6 74, angle mark 3 75, angle mark 1. 7 76, angle mark 1 77, and angle mark. 66 78, is relative to object ball aim point 6 19, object ball aim point 3 21, object ball aim point 1. 7 22, object ball aim point 1 23 and object ball aim point. 66 24 respectively. In FIG. 4 the cue ball 73 is placed centered anywhere along the length of imaginary line “A” starting from the center of the universal point mark 79 extending through the center of angle mark 1 77. In FIG. 7 the object ball 72 is placed centered on the center ball mark 82. The left ball mark 80, top ball mark 81, right ball mark 83 and bottom ball mark 84 are used to double check the alignment of the circumference of the object ball 72 and further insure the exact centered position. The student now observes the rail indicator 1 H 56, rail indicator CT 64 and rail indicator 1 L 58 relative to the angle mark 77 also shown in FIG. 7. The student is now ready to aim the shot to pocket the object ball 72 in the billiard pocket 71 and study different cue ball 73 positions after applying high cue impact point 86, center impact point 87 or low impact point 88 to the cue ball 73 with the tip of the cue 89. To shoot the angle mark 1 77 shot with high cue impact point 86 the student aims the tip of the cue 89 at the universal point mark 79, taking mental note of the object ball aim point 1 23 on the position reference tool 1, while applying the high cue impact point 86 strokes through the cue ball attempting to pocket the object ball 72 in the billiard pocket 71 and position the cue ball near the rail indicator 1 H 56. If the student wishes to practice the same angle mark 1 77 using low cue impact point 88 the objective will be to pocket the object ball 72 in the billiard pocket 71 and position the ball near rail indicator 1 L 58. If the student wishes to practice the same angle mark 1 77 using center cue impact point 87 the objective will be to pocket the object ball 72 in the billiard pocket 71 and position the ball near rail indicator CT 64. The same procedure is used for the other 4 angle marks. The Billiard Aim Instruction Kit is susceptible to various embodiments and forms. For instance, color coding could be used to illustrate the relationships between angles, aiming points and cue ball directions. Paper or metal can be used instead of plastic for the material of construction of the position reference tool. Colored beads can be used instead of lettered and numbered plastic discs for the rail indicators. Angle apertures 4, 6, 8, 10, 12, and center tip aperture 37 can be repeated at mirror image positions on the opposite side of the line to pocket 3 Relative range graphics 36, 38, 39, 40 and 41 can be printed as mirror images on the opposite side of the line to pocket 3. Accordingly, there is described in the drawings and specification a preferred embodiment to be considered as one exemplification of the invention and is not intended to limit the broad scope of the invention to the embodiment. CONCLUSIONS AND RAMIFICATIONS [0023] Accordingly, While my above description contains many specificities these should not be construed as limitations on the scope of the invention, but rather as an exemplification of one preferred embodiment thereof. Many other variations are possible. Some examples are changes to the shape of the Position Reference Tool, using metal instead of plastic for the Position reference tool, using color coding for the rail indicators and angle range graphics, using beads or other shapes for the rail indicators using angle references other than those shown on the graphics as long as they are precisely measured and empirically tested to modify the range graphics and applying the billiard games other than pocket billiards as long as the size of the billiard balls are tested and associated to the graphics by empirical testing. Accordingly, the scope of the invention should be determined not by the embodiment but by the appended claims and their legal equivalent.

Summary: A billiard aim instruction kit for pocket billiards. A position reference tool is placed at locations on a pocket billiard table surface and aligned aiming toward a pocket. A marking powder packet is used to mark each location. The position reference tool is then removed to reveal each location&#39;s aiming point reference mark, 5 object ball position marks, 5 aiming angle reference marks and a center hit cue ball direction reference mark. An object ball is centered on the 5 object ball position marks of each location marked and rail indicators mark the rail for cue ball direction. The student shoots the cue ball from one of 5 different aiming angle reference points a multiplicity of times without further marking procedures. After each shot the student receives feed back as he compares results with the rail indicator and graphics on the position reference tool.

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Write a title and summarize: The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region. The hippocampus plays a crucial role in spatial orientation, learning and memory, and many pathological conditions (e. g., epilepsy and Alzheimer’s disease) are closely associated with synaptic alterations in the hippocampus (Amaral and Lavenex, 2007). As has been previously discussed, one of the first steps towards understanding the way in which neuronal circuits contribute to the functional organization of the brain involves defining the brain’s detailed structural design and mapping its connection matrix (Swanson and Bota, 2010). The connectivity of the brain can be examined at three major levels of resolution (DeFelipe, 2010): (i) macroscopically, focusing on major tract connectivity; (ii) at an intermediate resolution, using light microscopy techniques that allow putative synaptic contacts to be mapped; and (iii) at the ultrastructural level, using electron microscopy (EM) to map true synaptic contacts. Numerous studies have described the ultrastructural characteristics and organization of hippocampal synapses in experimental animals (Bourne and Harris, 2012). However, there is very little information about the synaptic organization of the human hippocampus and the brain in general, which is a major problem since the question remains as to how much of the animal model information can be reliably extrapolated to humans. The majority of these studies are performed in specimens removed during the course of neurosurgery in patients with tumors or intractable epilepsy (Alonso-Nanclares et al., 2008; Alonso-Nanclares et al., 2011; Androuin et al., 2018; Witcher et al., 2010; Yakoubi et al., 2019a; Yakoubi et al., 2019b). Since it is inevitable that surgical excisions pass through cortical regions that are normal, this represents an excellent opportunity to study human brain material. The problem is that although this material is thought to be close to what would be expected in the normal brain, the results cannot be unequivocally considered as representative of the normal condition of the human brain. Thus, a major goal in neuroscience is to directly study human brain with no recorded neurological or psychiatric alterations. In the present study, we started to address the issue of the hippocampal synaptic organization by focusing on the CA1 field. This hippocampal field receives and integrates a massive amount of information in a laminar-specific manner, and sends projections mainly to the subiculum and to extrahippocampal subcortical nuclei and polymodal association cortices (Amaral and Lavenex, 2007). Studying the human brain via EM techniques presents certain problems and the scarcity of human brain tissue that is suitable for the study of synaptic circuitry is one of the most important issues to overcome. Recently, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results (Domínguez-Álvaro et al., 2018; Domínguez-Álvaro et al., 2019). For these reasons, we used FIB/SEM technology to perform a 3D analysis of the synaptic organization in the neuropil in all layers of the CA1 region from five human brain autopsies with a short postmortem delay. Specifically, we studied a variety of synaptic structural parameters including the synaptic density and spatial distribution, type of synapses, postsynaptic targets and the shape and size of the synaptic junctions. The data reported in the present work constitutes the first extensive description of the synaptic organization in the human hippocampal CA1 field, which is a necessary step for better understanding its functional organization in health and disease. First, we estimated the total thickness of the CA1 field ―including the alveus― in the radial axis. The average thickness was 2. 70 ± 0. 62 mm. Following a deep-superficial axis, the average length of each layer was: 0. 34 ± 0. 12 in the alveus; 0. 06 ± 0. 03 mm in SO; 1. 13 ± 0. 33 mm in SP; 0. 55 ± 0. 31 mm in SR; and 0. 62 ± 0. 16 mm in SLM. Thus, in relative terms, SP contributed the most to the total CA1 thickness (42%) followed by SLM (23%) then SR (20%), the alveus (13%) and SO (2%) (Figure 1b, Supplementary file 1A). We then assessed the cellular composition of every CA1 layer, including the volume fraction (Vv) occupied by different cortical elements (i. e., blood vessels, glial and neuronal somata and neuropil), estimated by applying the Cavalieri principle (Gundersen et al., 1988). The neuropil constituted undoubtedly the main element in all layers (more than 90%; Figure 1—figure supplement 2b, f, Supplementary file 1A) followed by blood vessels (range from 4. 79% in SR to 7. 58% in SO; Figure 1—figure supplement 2b, c, Supplementary file 1A). The volume fraction occupied by glial cell and neuronal bodies was less than 2% (Figure 1—figure supplement 2b, d, e, Supplementary file 1A), except for SP, where neuronal cell bodies occupied a volume of 4. 23 ± 1. 07% (Figure 1—figure supplement 2b, e, Supplementary file 1A). As expected, the volume occupied by neurons was significantly higher in SP than in any other layer (ANOVA, p<0. 001). The neuropil was significantly more abundant in SR (94. 19 ± 1. 17%) than in SP (90. 11 ± 1. 32%, ANOVA, p=0. 015) and SO (90. 01 ± 3. 07%; ANOVA, p=0. 012). No further significant differences regarding cortical elements were found between any other layers. Each single reconstructed synapse was sorted according to different qualitative and quantitative parameters (see Material and Methods). Specifically, regarding qualitative characteristics, we distinguished four different parameters: i) the type of synapses: asymmetric synapses (AS) or symmetric synapses (SS); ii) the postsynaptic targets: axospinous (on the head or neck of the dendritic spine) or axodendritic (on spiny or aspiny dendritic shafts); and iii) the synaptic shape: macular, horseshoe-shaped, perforated or fragmented synapses. Additionally, three quantitative parameters were used for classification: i) the synaptic apposition surface (SAS) area, ii) SAS perimeter and iii) SAS curvature. Differences between cases were observed regarding several of the parameters examined in several layers (Supplementary files 1O-AD). All significant differences are reported under the corresponding tables for each individual case. Importantly, differences between individual cases were not necessarily found with respect to the same parameter, or in the same layer or in the same direction (increase or decrease). For instance, case AB1 presented a larger volume fraction of blood vessels in SO than the rest of the cases (ANOVA, p<0. 05; Supplementary file 1O), except for case AB2. In case AB2, the volume fraction occupied by neuronal bodies in SR was higher than in the rest of the subjects, except for AB3 (ANOVA, p<0. 01; Supplementary file 1O). Additionally, the volume occupied by glia in the SLM of case AB1 was higher than in the rest of the cases, except for AB3 (ANOVA, p<0. 05; Supplementary file 1O). Furthermore, compared to the rest of the cases, AB2 and AB3 presented higher synaptic densities in SR (ANOVA, p<0. 05; Supplementary file 1S). Also, compared to the rest of the subjects, AB2 exhibited a higher synaptic density in SO (ANOVA, p<0. 01; Supplementary file 1P). In addition, the proportion of SS was higher in SLM in M17 than in AB1, AB2 and AB3 (χ2, p<0. 001; Supplementary file 1T). When focusing on postsynaptic targets, SLM was one of the layers with the greatest differences among cases (χ2, p=1. 000×10−17; Supplementary file 1Y). In this layer, out of all the cases, case AB1 exhibited the highest proportion of axospinous AS and the lowest percentage of both axodendritic AS and SS (χ2, p<0. 0001; Supplementary file 1Y). Additionally, a larger proportion of axospinous AS was also observed in subject AB3 when compared to cases AB2 and M17 (χ2, p<0. 0001; Supplementary file 1Y). Macular synaptic junctions were clearly the most abundant type in all cases and layers. However, perforated AS were especially abundant in subject AB4 compared to the rest of the cases in all layers (χ2, p<0. 001; Supplementary files 1Z-AD) with the exception of AB1 in sSP. Additionally, in case AB4, the AS in sSP were larger than in the rest of the individuals (ANOVA, p<0. 0001; Supplementary file 1R), apart from in the case of M17. The neuropil represents the main structural component of CA1 (more than 90% of all layers). The contribution of SP to the total CA1 radial extension accounted for almost a half of the total thickness (SP thickness: 1. 13 mm; total CA1 thickness: 2. 70 mm). This great extent of SP represents a major difference with the rodent brain and other species. Indeed, important variances can be observed in the hippocampal neuroanatomy of humans compared to rodents (Amaral and Lavenex, 2007; Benavides-Piccione et al., 2020; Duvernoy, 2005; Slomianka et al., 2011; Tapia-González et al., 2020). In the rat hippocampus, SP is around five cell bodies thick and neuronal somata are densely packed, being SR the layer that contributes the most to the total CA1 thickness. In humans, SP can be up to 30 cell somata thick, with a wider separation of neurons compared to other species. As previously discussed in Benavides-Piccione et al., 2020, this sometimes refers to a ‘corticalization’ of the human CA1 pyramidal cell layer because it resembles a neocortical cytoarchitecture, which most probably has fundamental functional and hodological consequences: the basal and apical dendrites of human pyramidal cells are intermixed in the pyramidal cell layer (Figure 7), whereas in rodents, the basal and apical dendritic arbors are basically separated (basal dendrites in SO; apical dendrites in SR). Synapses were found in all layers except the alveus where they were virtually nonexistent. The mean synaptic density was 0. 67 synapses/µm3. However, synaptic density was not homogenous among layers. Consistently in all individuals, the highest value was found in sSP (0. 99 synapses/µm3), followed by dSP (0. 69 synapses/µm3), while the lowest was observed in SO (0. 45 synapses/µm3). Since no quantitative 3D analysis of the synaptic organization in the human hippocampus has been performed before, our data could not be compared to previous reports. However, in recent studies from our group using FIB/SEM to analyze the synaptic density in the rodent CA1 field, the following values were obtained: 2. 53 synapses/µm3 in SO, 2. 36 synapses/µm3 in SR and 1. 72 synapses/µm3 in SLM in the mouse (Santuy et al., 2020), and 2. 52 synapses/µm3 in SR in the rat (Blazquez-Llorca et al., 2020). These values are much higher than the ones found in the present work for the human CA1 (Table 1). Such huge differences in synaptic density between humans and rodents —together with the above-mentioned divergences in the morphology and distribution of pyramidal cells in the SP of CA1 (Benavides-Piccione et al., 2020), as well as differences in other anatomical, genetic, molecular and physiological features (Benavides-Piccione et al., 2020; Blazquez-Llorca et al., 2020; Ding, 2013; Hawrylycz et al., 2012; Santuy et al., 2020; Tapia-González et al., 2020; van Dijk et al., 2016) — further support the notion that there are remarkable differences between the human and rodent CA1. These differences clearly need to be taken into consideration when making interpretations in translational studies comparing one species to another. While synaptic density differed across layers, the spatial organization of synapses was consistently random in all layers. Randomly distributed synapses have also been described in the somatosensory cortex of rats and the frontal and transentorhinal cortices of the human brain (Blazquez-Llorca et al., 2013; Domínguez-Álvaro et al., 2018; Merchán-Pérez et al., 2014; Santuy et al., 2018a), suggesting that this synaptic characteristic is a widespread ‘rule’ of the cerebral cortex of different species. It has also been consistently reported that the neuropil is characterized by a much higher number of excitatory contacts compared to inhibitory synapses in different brain regions and species (Beaulieu and Colonnier, 1985; Bourne and Harris, 2012; DeFelipe, 2011; Domínguez-Álvaro et al., 2018; Megı́as et al., 2001; Santuy et al., 2018a). In the present study, the density of inhibitory synapses was particularly low in most CA1 layers (AS: SS ratio in all layers was around 95: 5 except for in SLM, where the ratio was close to 90: 10). This data is in line with our study using FIB/SEM to analyze the synaptic density in the mouse (where the proportion of synapses that were inhibitory was 8% in the SLM, and approximately 2% in the case of the SR and SO) (Santuy et al., 2020) and in the rat CA1 field (where 4% of the synapses in SR were inhibitory) (Blazquez-Llorca et al., 2020). Regarding postsynaptic preferences, we observed a clear preference of excitatory axons and inhibitory axons for dendritic spines and dendritic shafts, respectively, which is also characteristic in other cortical regions and species, although variations in their percentages have been reported (Beaulieu and Colonnier, 1985; Beaulieu et al., 1992; Bourne and Harris, 2012; Domínguez-Álvaro et al., 2019; Megı́as et al., 2001; Micheva and Beaulieu, 1996; Santuy et al., 2018a). For example, axospinous AS are especially abundant in sSP (87. 61%) when compared to other brain regions in both humans and other species such as layer II of the human transentorhinal cortex, where axospinous AS account for only 55% of the total synaptic population (Domínguez-Álvaro et al., 2019). Most synapses presented a simple, macular shape (accounting for 86% of the synapses in all layers of CA1), in agreement with previous reports in different brain areas and species (Domínguez-Álvaro et al., 2019; Geinisman et al., 1986; Jones and Calverley, 1991; Neuman et al., 2015; Santuy et al., 2018b). The shape and size of the synaptic junctions are strongly correlated with release probability, synaptic strength, efficacy and plasticity (Biederer et al., 2017; Ganeshina et al., 2004a; Ganeshina et al., 2004b; Holderith et al., 2012). In this regard, all three types of non-macular synapses (with more complex shapes) were larger than macular ones. Although the functional significance of perforations is still unclear, perforated synapses are known to have more AMPA and NMDA receptors than macular synapses and are thought to constitute a relatively powerful population of synapses with more long-lasting memory-related functionality than their smaller, macular counterparts (Ganeshina et al., 2004a; Ganeshina et al., 2004b; Vincent-Lamarre et al., 2018). The size of both types of synaptic junctions (AS and SS) can be fitted to log-normal or log-logistic probability density functions (see Figure 6—figure supplement 2). These distributions show a characteristic skewed shape, with a long tail to the right (Kumar and Kundu, 2009). This is consistent with the fact that small macular synapses predominate, while larger horseshoe or perforated synapses are less common. Indeed, previous studies from our laboratory found that AS and SS followed a log-normal distribution in all layers of the rat somatosensory cortex (Merchán-Pérez et al., 2014; Santuy et al., 2018b). Interestingly, some other synaptic parameters —such as synaptic strength and spike transmission probability— follow log-normal distributions (for review, see Buzsáki and Mizuseki, 2014). For example, the distribution of the size of unitary excitatory postsynaptic potentials (EPSP) is very similar to the distribution of the size of SAS reported here (Lefort et al., 2009; Song et al., 2005). When analyzing the synaptic size distribution of pairs of synapses formed by the same axon, a quantized distribution of synaptic strengths yielding a similar skewed curve was observed in the rat hippocampus (Bartol et al., 2015; Bromer et al., 2018); since we did not trace the parental axon of each segmented synapse in our samples, it remains unclear whether a similar quantitation process occurs in the human hippocampus. Although the extraordinary diversity of excitatory synapse sizes is commonly attributed to activity-dependent processes that drive synaptic growth and diminution, recent studies also point to activity-independent size fluctuations, possibly driven by innate synaptic molecule dynamics, as important generators of size diversity. Specifically, activity-dependent processes seem to primarily dictate the scale rather than the shape of synaptic size distributions (Hazan and Ziv, 2020). Considering all synapses, excitatory contacts were larger than inhibitory ones, as has also been observed in layer II of the human transentorhinal cortex (Domínguez-Álvaro et al., 2018); however, this contrasted with the findings in the somatosensory cortex (Santuy et al., 2018b) and SR of CA1 in the rat (Blazquez-Llorca et al., 2020). A tendency towards axodendritic synapses being bigger than axospinous synapses was also observed; however, this difference was only significant in the case of SLM synapses. Complex-shaped AS were also found more frequently associated with axodendritic AS than with axospinous AS in SLM, while the opposite was the case for the rest of the layers. These findings agree with reports in the rat hippocampus, where excitatory synapses on SLM dendrites were observed to be: (i) larger than synapses in other layers; (ii) more frequently perforated (approximately 40%); and (iii) located to a greater extent on dendritic shafts (Megı́as et al., 2001). The wide range of differences in the synaptic organization of the human CA1 layers found in the present study, especially between SLM and the rest of layers, may be related to the variety of inputs arriving to these layers (Figure 7). Unfortunately, detailed hippocampal human connectivity is far to be known: data directly obtained from human brains are very scarce and most data are inferred from rodents and primates (Insausti and Amaral, 2012; Spruston and McBain, 2007). In the primate brain, the CA1 field receives a wide variety of inputs from multiple subcortical and cortical brain regions (Insausti and Amaral, 2012; Spruston and McBain, 2007), being the major input to CA1 originated in the EC. Specifically, neurons located in layer III (and layer V) of the EC project directly to SLM, whereas neurons in layer II project to the rest of CA1 layers indirectly via the DG and CA3 field (Insausti and Amaral, 2012; Kondo et al., 2009). Considering both the synaptic data obtained in the present study and the connectivity knowledge in monkeys, it may seem that the synaptic organization in the layers receiving CA3 Schaffer collateral inputs (i. e. SO, SP and SR) differs with the synaptic organization found in the layer receiving direct inputs from the EC (i. e. SLM). Additionally, SLM receives a higher number of glutamatergic inputs from the amygdala and from the parietal and medial temporal cortex and higher numbers of serotonergic and Substance-P immunoreactive fibers, with a possible extrinsic origin in the Raphe nuclei and the laterodorsal tegmental nucleus (Figure 7). It has been proposed that the CA3-CA1 synaptic connection plays a key role in the learning-induced synaptic potentiation of the hippocampus (Whitlock et al., 2006), while the direct projection from EC to SLM of CA1 seems to modulate information flow through the hippocampus (Dvorak-Carbone and Schuman, 1999). It has been reported that a high-frequency stimulation in SLM evokes an inhibition sufficiently strong to prevent CA1 pyramidal cells from spiking in response to Schaffer collaterals input (Dvorak-Carbone and Schuman, 1999). This finding could be supported by our present data showing an elevated inhibitory synapse ratio in comparison to other CA1 layers. It has also been described that afferents from the EC contact not only the apical tuft of CA1 pyramidal cells, but also interneurons of the SLM (Lacaille and Schwartzkroin, 1988). One of these interneurons are the neurogliaform cells, which receive monosynaptic inputs from the EC and are also synaptically coupled with each other and with CA1 pyramidal cells (Capogna, 2011). Whether the higher proportion of axodendritic synapses —particularly in aspiny shafts, which are likely to be originated from interneurons —, found in the present study in SLM compared to other CA1 layers is related to a particular synaptic circuit organization involving certain types of interneurons located in this layer remains to be elucidated. Human brain tissue was obtained from autopsies (with short post-mortem delays of less than 4. 5 hours) from 5 subjects with no recorded neurological or psychiatric alterations (supplied by Unidad Asociada Neuromax, Laboratorio de Neuroanatomía Humana, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete and the Laboratorio Cajal de Circuitos Corticales UPM-CSIC, Madrid, Spain) (Supplementary file 1AE). The consent of the individuals was obtained and the sampling procedure was approved by the Institutional Ethical Committee of the Albacete University Hospital. The tissue was obtained following national laws and international ethical and technical guidelines on the use of human samples for biomedical research purposes. Brain tissue was analyzed for Braak stage (Braak and Braak, 1991) and CERAD neuropathological diagnosis (Mirra et al., 1991) and assigned a zero score. Nevertheless, case AB1 showed sparse tau-immunoreactive cells in the hippocampal formation and case AB4 showed a relatively high number of amyloid plaques mainly located in the subicular and the parahippocampal regions. Tissue from some of these human brains has been used in previous unrelated studies (Benavides-Piccione et al., 2020; Tapia-González et al., 2020). After extraction, brain tissue was fixed in cold 4% paraformaldehyde (Sigma-Aldrich, St Louis, MO, USA) in 0. 1 M sodium phosphate buffer (PB; Panreac, 131965, Spain), pH 7. 4, for 24 h. Subsequently, the block of tissue containing the hippocampus was washed in PB and coronal 150 μm-sections were obtained with a vibratome (Vibratome Sectioning System, VT1200S Vibratome, Leica Biosystems, Germany). Coronal sections from the hippocampal body (Duvernoy, 2005) containing the CA1 region were selected and postfixed for 48 h in a solution of 2% paraformaldehyde, 2. 5% glutaraldehyde (TAAB, G002, UK) and 0. 003% CaCl2 (Sigma, C-2661-500G, Germany) in 0. 1 M sodium cacodylate buffer (Sigma, C0250-500G, Germany). The sections were treated with 1% OsO4 (Sigma, O5500, Germany), 0. 1% ferrocyanide potassium (Probus, 23345, Spain) and 0. 003% CaCl2 in sodium cacodylate buffer (0. 1 M) for 1h at room temperature. Sections were then stained with 1% uranyl acetate (EMS, 8473, USA), dehydrated, and flat embedded in Araldite (TAAB, E021, UK) for 48 h at 60°C. Embedded sections were glued onto a blank Araldite block and trimmed. Semithin sections (1 μm) were obtained from the surface of the block and stained with 1% toluidine blue (Merck, 115930, Germany) in 1% sodium borate (Panreac, 141644, Spain). The blocks containing the embedded tissue were then glued onto a sample stub using conductive adhesive tabs (EMS 77825-09, Hatfield, PA, USA). All the surfaces of the block —except for the one to be studied (the top surface) — were covered with silver paint (EMS 12630, Hatfield, PA, USA) to prevent charging artifacts. The stubs with the mounted blocks were then placed into a sputter coater (Emitech K575X, Quorum Emitech, Ashford, Kent, UK) and the top surface was coated with a 10–20 nm thick layer of gold/palladium to facilitate charge dissipation. The exact location of all CA1 layers was determined by examining 1% toluidine blue-stained semithin sections under a light microscope (Figure 1). More specifically, the medial portion of the CA1 region was analyzed. From its deepest level to the surface (i. e., from the ventricular cavity towards the vestigial hippocampal sulcus), the cornu ammonis may be divided into five layers: the alveus, stratum oriens (SO), stratum pyramidale (SP), stratum radiatum (SR) and stratum lacunosum-moleculare (SLM) (Duvernoy, 2005). Within the SP, two sublayers were defined by dividing the layer into a deeper part (dSP; close to the ventricular cavity) and a more superficial part (sSP; close to the vestigial hippocampal sulcus; Figures 1a-b and 7; Andrioli et al., 2007; Braak, 1974). To calculate the thickness of the layers, they were delimited using toluidine blue-stained semithin section adjacent to the block surface (Figure 1). Three measures per case were taken at different medio-lateral levels of CA1. This analysis was performed using ImageJ (ImageJ 1. 51; NIH, USA; http: //imagej. nih. gov/ij/). From each case, three semithin sections (1 μm thick; stained with 1% toluidine blue) were used to estimate the volume fraction occupied by blood vessels, cell bodies, and neuropil in each layer. This estimation was performed applying the Cavalieri principle (Gundersen et al., 1988) by point counting using the integrated Stereo Investigator stereological package (Version 8. 0, MicroBrightField Inc, VT, USA) attached to an Olympus light microscope (Olympus, Bellerup, Denmark) at 40x magnification (Figure 1—figure supplement 2a). A grid whose points had an associated area of 400 µm2 was overlaid over each semithin section to determine the Vv occupied by different elements: blood vessels, glia, neurons and neuropil. Vv occupied by the neuropil was estimated with the following formula: Vv neuropil = 100 - (Vv blood vessels + Vv glia + Vv neurons). A 3D EM study of the samples was conducted using combined FIB/SEM technology (Crossbeam 540 electron microscope, Carl Zeiss NTS GmbH, Oberkochen, Germany), as described in Merchán-Pérez et al., 2009; with some modifications. We used a 7-nA ion beam current with a 30-kV acceleration potential and a first coarse cross-section was milled as a viewing channel for SEM observation. The exposed surface of this cross-section was fine polished by lowering the ion beam current to 700 pA. Subsequently, layers from the fine polished cross-section were serially milled by scanning the ion beam parallel to the surface of the cutting plane using the same ion beam current. To mill each layer, the ion beam was automatically moved closer to the surface of the cross-section by preset increments of 20 nm, which corresponded to the thickness of the layers. After the removal of each slice, the milling process was paused and the freshly exposed surface was imaged using a 1. 8-nA probe current with a 1. 7-kV acceleration potential using the in-column energy-selective backscattered electron detector (EsB). The dwell time was 50 ns. The milling and imaging processes were continuously repeated and long series of images were acquired via a fully automated procedure. The quality and resolution of the images is similar to those achieved with TEM (Merchán-Pérez et al., 2009; Figure 1c-d). This study was conducted in the neuropil —that is, avoiding the neuronal and glial somata, blood vessels, large dendrites and myelinated axons— where most synaptic contacts take place (DeFelipe et al., 1999). Image resolution in the xy plane was 5 nm/pixel. Resolution in the z-axis (section thickness) was 20 nm, and image size was 2,048 x 1,536 pixels. These parameters were optimized to make it possible to obtain a large enough field of view where the different types of synapses can be clearly identified in a reasonable amount of time (12 h per stack of images). The volume per stack ranged from 356 μm3 to 727 μm3 (225 and 459 images, respectively). All measurements were corrected for the tissue shrinkage that occurs during osmication and plastic-embedding of the vibratome sections containing the area of interest, as described by Merchán-Pérez et al., 2009. We measured the surface area and thickness of the vibratome sections with Stereo Investigator (MBF Bioscience, Williston, VT, USA), both before and after they were processed for EM (Oorschot et al., 1991). The surface area after processing was divided by the value before processing to obtain an area shrinkage factor (p2) of 0. 933. The linear shrinkage factor for measurements in the plane of the section (p) was therefore 0. 966. The shrinkage factor in the z-axis was 0. 901. In addition, the total volume was corrected for the presence of fixation artifacts, which did not affect the accurate identification and quantitation of synapses (i. e., swollen neuronal or glial processes). The volume occupied by these artifacts was calculated applying the Cavalieri principle (Gundersen et al., 1988) and was discounted from the volume of the stacks of images to avoid underestimation of the number of synapses per volume. Specifically, a stereological grid with an associated area per point of 400,000 nm2 was superimposed onto each FIB/SEM stack with the Image J Stereology Toolset (Mironov, 2017). Estimations were made every 20th section of each stack. Volume fraction estimation was performed by point counting using the Cavalieri principle (Gundersen et al., 1988), in a similar fashion to the volume fraction estimation of cortical elements in 1% toluidine blue-stained semithin sections outlined above (see' Volume fraction estimation of cortical elements' ). A fixation artifact factor was calculated for each FIB/SEM stack (ranging from 0 to 20% of the stack volume) and was applied to each individual FIB/SEM stack. All parameters measured were corrected to obtain an estimate of the pre-processing values. The shrinkage factor was used to correct the synaptic apposition surface (SAS) area and perimeter data, while both the shrinkage and the fixation artifact factors were used to correct synaptic density values. Corrected and uncorrected data for each parameter are shown in Table 1. A total of 75 stacks of images from all layers of the CA1 field were obtained (3 stacks per case and region in the 5 cases, with a total volume studied of 29,322 μm3) (Figure 1b). The 3D segmentation of synaptic junctions includes both the presynaptic density (active zone; AZ) and the PSD. Since the AZ and the PSD are located face to face, their surface areas are very similar (correlation coefficients over 0. 97; Schikorski and Stevens, 1997; Schikorski and Stevens, 1999). Thus, as previously described in Morales et al., 2013), they can be simplified to a single surface and represented as the surface of apposition between the AZ and the PSD. This surface can be extracted from the 3D segmented synaptic junction (Morales et al., 2013). For the sake of clarity, we have referred to this surface as the synaptic apposition surface (SAS). We consider SAS morphological measurements to be a better approach to the assessment of synaptic size than measurements obtained from the 3D segmented synaptic junctions (see Morales et al., 2013 for more detailed information about SAS extraction and its relation to presynaptic density and PSD). We observed in our samples that the SAS area is highly correlated to the surface (R2 = 0. 96 for AS; R2 = 0. 97 for SS) and the volume (R2 = 0. 91 for AS; R2 = 0. 90 for SS) of the 3D segmented synaptic junctions. The SAS area and perimeter of each synaptic junction was extracted with EspINA software to study morphological parameters regarding synapses. EspINA software also permits the quantitation of the curvature of the synapses as it adapts to the curvature of the synaptic junction. Specifically, curvature measurements are calculated as 1 minus the ratio between the projected area of the SAS and the area of the SAS (Morales et al., 2011). This measurement would be 0 in a flat SAS and would increase its value to a maximum of 1 as the SAS curvature increases. The spatial distribution of synapses was determined by performing a Spatial Point Pattern analysis (Anton-Sanchez et al., 2014; Merchán-Pérez et al., 2014). The position of centroids of the synapses was compared to the Complete Spatial Randomness (CSR) model, which defines a situation where a point is equally probable to occur at any location within a given volume. For each stack of images, functions F, G and K were calculated (Blazquez-Llorca et al., 2015). In addition, the distance of every synapse to its nearest synapse was measured. This study was carried out using Spatstat package and R Project software (Baddeley et al., 2015). Statistical analysis of the data was carried out using GraphPad Prism statistical package (Prism 7. 00 for Windows, GraphPad Software Inc, USA), SPSS software (IBM SPSS Statistics for Windows, Version 24. 0. Armonk, NY: IBM Corp), Easyfit Proffessional 5. 5 (MathWave Technologies) and R Project software (R 3. 5. 1; Bell Laboratories, NJ, USA; http: //www. R-project. org). Differences in the Vv occupied by cortical elements; synaptic density; and morphological and spatial parameters were analyzed performing either a two-sided, one-way analysis of variance (ANOVA), with Tukey post hoc corrections, or Mann-Whitney U (MW) nonparametric test, as appropriate. Frequency distributions were analyzed using Kolmogorov-Smirnov (KS) nonparametric tests. Chi-squared (χ2) tests were used for contingency tables. In general, for any contingency table, the expected frequency for a cell in the ith row and the jth column is Eij = TiTj/T, where Ti is the marginal total for the ith row, Tj is the marginal total for the jth column, and T is the total number of observations. χ² tests of association were applied to these tables (Sharpe, 2015). The criterion for statistical significance was considered to be met for p<0. 05 when the sample size was equal to the number of subjects (i. e., ANOVA and MW tests), and for p<0. 001 when the sample size was equal to the number of synapses (i. e., KS and χ2 tests), in order to avoid overestimation of the differences due to a very big sample size.

Title: Three-dimensional synaptic organization of the human hippocampal CA1 field Summary: There are billions of nerve cells or neurons in the human brain, and each one can form thousands of connections, also called synapses, with other neurons. That means there are trillions of synapses in the brain that keep information flowing. Studying the arrangement of individual neurons in the human brain, and the connections between them, is incredibly difficult because of its complexity. Scientists have tools that can image the whole brain and can measure the activity in different regions, but these tools only visualize brain structures that are large enough to be seen with human eyes. Synapses are much smaller (in the range of nanometers), and can only be seen using thin slices of preserved brain tissue through a technique called electron microscopy. The hippocampus is a part of the human brain that is critical for memory, learning and spatial orientation, and is affected in epilepsy and Alzheimer's disease. Although numerous studies of the hippocampus have been performed in laboratory animals, such as mice, the question remains as to how much of the information gained from these studies applies to humans. Thus, studying the human brain directly is a major goal in neuroscience. However, the scarcity of human brain tissue suitable for the study of synapses is one of the most important issues to overcome. Fortunately, healthy human brain tissue that can be studied using electron microscopy is sometimes donated after death. Using these donations could improve the understanding of the synapses in normal brains and possible changes associated with disease. Now, Montero-Crespo et al. have mapped synapses in the normal human hippocampus in three dimensions - providing the first detailed description of synaptic structure in this part of the brain. Using high-powered electron microscopes and donated brain tissue samples collected after death, Montero-Crespo et al. imaged almost 25,000 connections between neurons. The analysis showed that synapses were more densely packed in some layers of the hippocampus than in others. Most synapses were found to be connected to tiny dendritic'spines' that sprout from dendritic branches of the neuron, and they activated (not suppressed) the next neuron. Beyond its implications for better understanding of brain health and disease, this work could also advance computer modelling attempts to mimic the structure of the brain and its activity.

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Summarize: Mike Stefan regularly sees small aircraft soaring over his hay farm in North Collins, so he wasn’t surprised to see a group of planes flying far overhead on Sunday, a clear, bright morning. But then he saw two of the planes, flying side by side, appear to come together, one on top of the other. What happened next horrified him. “And then the bottom one came up into the top one, and his wing hit, maybe, the tail of the other plane,” Stefan said. “The top plane literally disintegrated.” Three people died in the midair collision and crash, which are under investigation by the National Transportation Safety Board and the Federal Aviation Administration. The crash left a debris field over a one-quarter to one-half-mile section of School Street, between Larkin and Eden roads in North Collins, officials said. One of the victims, Paul A. Rosiek, 60, of Hamburg, was flying a Cessna 120, and the other two victims, Richard J. and Kathleen M. Walker, both 69, of Eden, were flying in a Piper PA-28-140, according to an administrator at Hamburg Airport and aircraft registration records. Rosiek and the Walkers were among a group of six aircraft flying from the Hamburg Airport to a small airport in Pennsylvania to get a meal on Sunday morning, officials said. [Related: News of fatal North Collins crash reached fellow pilot over the radio] The cause of the crash remains under investigation, with the NTSB investigator likely to issue his preliminary report within two weeks. But veteran pilots said collisions can happen even in ideal flying conditions, and the crash has rattled the close-knit community of flyers at Hamburg Airport. “We’re all shaking in our boots now,” Larry Walsh, the airport’s vice president, told The Buffalo News. The group of six aircraft took off into blue skies at about 9 a.m. Sunday from the airport in Lake View, Walsh said, on their way to St. Marys Municipal Airport in St. Marys, Pa. Rosiek and Rich Walker were experienced amateur pilots, each with at least 15 years of flying, Walsh said. Both planes, the Cessna and the Piper, are single-engine, fixed-wing planes. Walsh said he didn’t know the cause of the crash but even on a clear day, with good visibility, one pilot can lose sight of another; for example, if one flies underneath or above the other. “There are a number of blind spots,” Walsh said. The first 911 call came in from a cellphone at 9:24 a.m., sheriff’s officials said. “We have several eyewitnesses who saw the planes approaching before there was contact,” said Scott Joslyn, chief of patrol services. Stefan was one of them. He said he made the 911 call after watching the two planes collide. He said the planes took more than 20 seconds to fall to the ground. A third plane remained overhead, circling the crash site for a time, Stefan said, while the fourth plane traveled on, appearing to not have realized what had happened. Stefan never saw the fifth and sixth planes that took off from Hamburg. Stefan and his 12-year-old son, Ryan, raced over to the crash site. “My immediate thought was, how are we going to find it? The corn is 10 feet high out here,” Mike Stefan said. Karen Ricotta, a North Collins town justice who lives on School Street, said she heard a noise at about 9:30 a.m. “And when I looked outside, you could see something next door on a mowed farm field. I couldn’t identify what it was,” Ricotta told The News. “But when I went outside, another man driving by pulled in my yard and told me it was a plane in the field. I called 911, but they already had been called.” The crash sites for the two aircraft are about 400 yards apart, Joslyn said, one on the south side of School Street and one on the north side. North Collins Supervisor John M. Tobia said the devastation from the crash could have been worse. “It missed a house by 100 feet,” Tobia said. One aircraft landed in a field and the other landed between a metal storage building and a wooded area, the supervisor said. “It’s like a pancake; it’s crushed,” Tobia said. “You can’t tell it’s an aircraft.” Brian Schmitt lives at School Street and Jennings Road near the two crash sites. “I’m upset. I’m shocked that you could be in the air one minute and dead the next,” said Schmitt, a member of Langford Volunteer Fire Company, which responded to the crash. Erie County sheriff’s personnel preserved the scene until federal investigators could get to the area. They were assisted by the North Collins and Langford fire companies, Eden police and North Collins rescue. The Erie County medical examiner also was called. Roads in the immediate area were closed for several hours Sunday. “Locating any piece of those crafts all tell a tale,” Joslyn said. “It’s going to be real important to have a good search of the area.” The FAA sent a team from Rochester and the NTSB investigator was driving in Sunday from New York City, said Peter Knudson, a spokesman for the safety board. The safety board investigator would begin work either Sunday evening, if he arrived while it was still daylight, or first thing Monday morning, Knudson said. The investigator will collect perishable evidence, including any relevant radar images of the flights, recorded conversations with the pilots, witness interviews, flight plans, data from GPS or other electronic devices in the planes or that the passengers were carrying, Knudson said. “They want to get that stuff documented,” he said. A preliminary report should be available within two weeks, but the entire accident investigation likely will take 12 months, Knudson said. Not much was immediately known about the two pilots. However, Kathleen Walker was identified as a retired kindergarten teacher at North Collins Elementary School by Schmitt and by Stefan, who is on the North Collins School Board. Sheriff Chief of Patrol explains what they know abt fatal collision involving two planes in #NorthCollins @TheBuffaloNews @BNphotographers pic.twitter.com/iRzew31zsT — Robert Kirkham (@RobertKirkhamBN) September 25, 2016 Sunday's tragedy isn't the first time that two planes have collided in Western New York skies with deadly consequences. Almost exactly two years ago – on Sept. 27, 2014 – two people died in a crash in Lancaster when one single-engine aircraft clipped another. “It was a perfect clear day,” Sheriff’s Detective Capt. Greg Savage said at a media briefing Sunday, “just like it was in the Lancaster crash.” The two small planes were preparing to land at Buffalo-Lancaster Regional Airport, one in front of the other on the same flight path, just like countless planes on other landing paths at airports every day. Coming up from behind, the bigger, faster Cessna descended and struck a smaller experimental aircraft, called a Searey, before spiraling out of control to the ground. Anthony Mercurio, 78, was flying in a small plane with James Metz, 14. Both were killed. The pilot of the other plane and that plane's passenger, a 9-year-old girl, survived. The two youngsters and volunteer pilots were taking part in an event at the Buffalo-Lancaster Regional Airport designed to introduce young people to the thrill of flying. email: swatson@buffnews.com and krobinson@buffnews.com

Summary: Two private planes collided Sunday in Western New York, reports the Buffalo News, killing all three aboard. The two aircraft-a Cessna 120 and a Piper Cherokee-were apparently part of a larger group of six flying out of the airport in Hamburg, NY, en route to get breakfast in St. Mary's, Pa., and return later Sunday. "We're all shaking in our boots now," says Hamburg Airport's vice president, Larry Walsh. Both pilots, one a 60-year-old and the other a 69-year-old accompanied by his 69-year-old wife, had at least 15 years' experience flying. But "there are a number of blind spots," when planes fly in groups together, says Walsh. There's no official cause of the crash as yet, notes the AP, and the FAA and NTSB will investigate. Says a resident of North Collins, where the planes went down: "I just heard planes flying and a really loud smash."

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Summarize: Background Section 103(a) of the Patent Act provides one of the statutory bars for patentability of inventions: a patent claim will be considered invalid if "the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains." In other words, for the subject matter of an alleged invention or discovery to be patentable, it must be "nonobvious" at the time of its creation. The nonobviousness requirement is met if the subject matter claimed in a patent application is beyond the ordinary abilities of a person of ordinary skill in the art in the appropriate field. In the landmark 1966 case Graham v. John Deere Co. of Kansas City, the Supreme Court established an analytic framework for courts to determine "nonobviousness." The so-called Graham test describes several factors that must be assessed: While the ultimate question of patent validity is one of law... the § 103 condition, which is but one of three conditions, each of which must be satisfied, lends itself to several basic factual inquiries. Under § 103, the scope and content of the prior art are to be determined; differences between the prior art and the claims at issue are to be ascertained; and the level of ordinary skill in the pertinent art resolved. Against this background, the obviousness or nonobviousness of the subject matter is determined. Such secondary considerations as commercial success, long felt but unsolved needs, failure of others, etc., might be utilized to give light to the circumstances surrounding the origin of the subject matter sought to be patented. As indicia of obviousness or nonobviousness, these inquiries may have relevancy. While a single prior art reference could form the basis of a finding of nonobviousness, multiple prior art references are often involved in the analysis. In such a situation, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) had developed an approach in which an invention would be considered obvious only if there was an explicit or implicit "teaching, suggestion, or motivation" that would lead a person of ordinary skill to combine multiple prior art references to produce an invention. Such a "teaching, suggestion, or motivation" (TSM) could have come from either (1) the references themselves, (2) knowledge of those skilled in the art, or (3) the nature of a problem to be solved, leading inventors to look to references relating to possible solutions to that problem. Because § 103 of the Patent Act requires that an invention's obviousness be determined from the standpoint of a person having ordinary skill in the art "at the time the invention was made," the TSM test was designed, in part, to defend against "the subtle but powerful attraction of a hindsight-based obviousness analysis." KSR International v. Teleflex The patents at issue in KSR International v. Teleflex pertain to an adjustable pedal system (APS) for use with automobiles having electronic throttle-controlled engines. Teleflex Inc. holds an exclusive license for the patent on this device that allows a driver to adjust the location of a car's gas and break pedal so that it may reach the driver's foot. KSR International Co. also manufactures an adjustable pedal assembly. Initially, KSR supplied APS for cars with engines that use cable-actuated throttle controls; thus, the APS that KSR manufactured included cable-attachment arms. In mid-2000, KSR designed its APS to incorporate an electronic pedal position sensor in order for it to work with electronically controlled engines, which are being increasingly used in automobiles. In 2002, Teleflex filed a patent infringement lawsuit against KSR after KSR had refused to enter into a royalty arrangement, asserting that this new design came within the scope of its patent claims. In defense, KSR argued that Teleflex's patents were invalid because they were obvious under § 103(a) of the Patent Act—that someone with ordinary skill in the art of designing pedal systems would have found it obvious to combine an adjustable pedal system with an electronic pedal position sensor for it to work with electronically controlled engines. The District Court's Opinion The U.S. District Court for the Eastern District of Michigan agreed with KSR that the patent was invalid for obviousness, granting summary judgment in favor of KSR. The court determined that there was "little difference between the teachings of the prior art and claims of the patent-in-suit." Furthermore, the court opined that "it was inevitable" that APS would be combined with an electronic device to work with electronically controlled engines. The Federal Circuit's Opinion Teleflex appealed the decision to the Federal Circuit. The appellate court vacated the district court's ruling, after finding that the district court had made errors in its obviousness determination. Specifically, the Federal Circuit noted that the district court had improperly applied the TSM test by not adhering to it more strictly—the district court had reached its obviousness ruling "without making findings as to the specific understanding or principle within the knowledge of a skilled artisan that would have motivated one with no knowledge of [the] invention to make the combination in the manner claimed." The Federal Circuit explained that district courts are "required" to make such specific findings pursuant to Federal Circuit case law establishing the TSM standard. In regard to the patent in the case, the appellate court found that the prior art in adjustable pedal design had been focused on solving the "constant ratio problem" (described as when "the force required to depress the pedal remains constant irrespective of the position of the pedal on the assembly"); whereas the motivation behind the patented invention licensed to Teleflex was "to design a smaller, less complex, and less expensive electronic pedal assembly." In the Federal Circuit's view, unless the "prior art references address the precise problem that the patentee was trying to solve," the problem would not motivate a person of ordinary skill in the art to combine the prior art teachings—here, the placement of an electronic sensor on an adjustable pedal. The Supreme Court's Opinion The Supreme Court granted certiorari on June 26, 2006, to review the KSR case, in which the central question before the Court was whether the Federal Circuit had erred in crafting TSM as the sole test for obviousness under § 103(a) of the Patent Act. On April 30, 2007, the Court unanimously reversed the Federal Circuit's judgment, holding that the TSM test for obviousness was incompatible with § 103 and Supreme Court precedents. Associate Justice Anthony Kennedy, delivering the opinion of the Court, explained that the proper framework for a court or patent examiner to employ when determining an invention's obviousness is that set forth in the Court's 1966 opinion Graham v. John Deere Co. of Kansas City. That analytical framework provides "an expansive and flexible approach" to the question of obviousness that the "rigid" and "mandatory" TSM formula does not offer. Justice Kennedy observed that the Graham approach, as further developed in three subsequent Supreme Court cases decided within ten years of that case, is based on several instructive principles for determining the validity of a patent based on the combination of elements found in the prior art: When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, it is likely obvious under § 103 and unpatentable. If a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill. Justice Kennedy then provided additional guidance for courts in following these principles. To determine whether there was an apparent reason to combine the known elements in the manner claimed by the patent at issue, courts should explicitly engage in an analysis that considers the following elements: the interrelated teachings of multiple patents, the effects of demands known to the design community or present in the marketplace, and the background knowledge possessed by a person having ordinary skill in the art. He further explained that a court should not solely take into account the "precise teachings" of the prior art, but rather can consider the "inferences and creative steps" that a person of ordinary skill in the art would likely use. The Federal Circuit's TSM test, and its mandatory application, is contrary to Graham and its progeny because it limits the obviousness analysis and is too formalistic, Justice Kennedy argued. In addition, he believed that the TSM test hindered the ability of courts and patent examiners to rely upon "common sense." In dicta, the Court's opinion appears to imply that the TSM test could have contributed to issued patents or unsuccessful challenges to the validity of certain patents that do not reflect true innovation: "Granting patent protection to advances that would occur in the ordinary course without real innovation retards progress and may, for patents combining previously known elements, deprive prior inventions of their value or utility." Finally, Justice Kennedy criticized the Federal Circuit for "overemphasizing the importance of published articles and the explicit content of issued patents." However, Justice Kennedy allowed that TSM provides "a helpful insight"—that a patent comprised of several elements is not obvious just because each of those elements was, independently, known in the prior art. This "essence" of the TSM test is not necessarily inconsistent with the Graham analysis, and thus he predicted that the Federal Circuit has likely applied the TSM test on many occasions in ways that accord with the Graham principles. It is the Federal Circuit's rigid application of its TSM rule, however, that the Court deemed was problematic in this case. Justice Kennedy identified four specific legal errors committed by the Federal Circuit. First, the appellate court had held that courts and patent examiners should look only to the problem the patentee was trying to solve, rather than other problems addressed by the patent's subject matter. Second, the appellate court had assumed that a person of ordinary skill trying to solve a particular problem will be led only to those elements of prior art designed to solve the same problem; however, "common sense teaches... that familiar items may have obvious uses beyond their primary purposes, and in many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." The third error of the lower court was its erroneous conclusion that a patent claim cannot be proved obvious by showing that the combination of elements was "obvious to try"; instead, Justice Kennedy noted, "the fact that a combination was obvious to try might show that it was obvious under § 103." The final error was the Federal Circuit's adherence to "rigid preventative rules" to avoid the risk of hindsight bias on the part of courts and patent examiners, because such rules "deny factfinders recourse to common sense." As to the specific patent claim at issue in this case, the Court adopted the obviousness analysis of the district court and expressly held that the claim "must be found obvious" in light of the prior art. Concluding Observations The KSR decision potentially may generate litigation over the validity of some patents issued and upheld under the Federal Circuit's TSM standard; the uncertainty over the enforceability of certain patents thus has ramifications for lawsuits between alleged patent infringers and patent holders, as well as between patentees and their licensees (for example, a patent licensee may want to challenge the validity of the patent to avoid paying royalties or even the imposition of an injunction). While the KSR Court rejected TSM as the sole test for obviousness, the Court did not expressly invalidate it either. Instead, the Supreme Court explained that courts and patent examiners, in evaluating a patent's claimed subject matter for obviousness under § 103, must use common sense, ordinary skill, and ordinary creativity in applying the Graham factors and principles to the specific facts of the case.

Summary: The Patent Act provides protection for processes, machines, manufactures, and compositions of matter that are useful, novel, and nonobvious. Of these three statutory requirements, the nonobviousness of an invention is often the most difficult to establish. To help courts and patent examiners make the determination, the U.S. Court of Appeals for the Federal Circuit developed a test called "teaching, suggestion, or motivation" (TSM). This test provided that a patent claim is only proved obvious if the prior art, the nature of the problem to be solved, or the knowledge of those skilled in the art, reveals some motivation or suggestion to combine the prior art teachings. In KSR International Co. v. Teleflex Inc. (550 U.S. ___, No. 04-1350, decided April 30, 2007), the U.S. Supreme Court held that the TSM test, if it is applied by district courts and patent examiners as the sole means to determine the obviousness of an invention, is contrary to Section 103 of the Patent Act and to Supreme Court precedents that call for an expansive and flexible inquiry, including Graham v. John Deere Co. of Kansas City, 383 U.S. 1 (1966).

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Summarize: Introduction Early in the 110 th Congress, the Chairmen of the House and Senate Judiciary Committees introduced essentially identical versions of the Court Security Improvement Act of 2007, as H.R. 660 and S. 378, that mirrored legislation that passed the Senate at the close of the 109 th Congress. Each House reported and passed somewhat different variations, although the basic structure of the legislation remained unchanged in both instances. The Senate subsequently accepted and passed H.R. 660 with slight amendments, which the House in turn accepted under suspension of the rules. The President the bill on January 7, 2008. The bill as passed, Public Law 110-177 ( P.L. 110-177 ), consists of four components: adjustments to applicable provisions of criminal law, reenforcement of the authority and oversight features of the law that governs federal judicial security, grant programs to facilitate increased security for the judiciary of the states, and miscellaneous provisions whose relation to judicial security might initially appear remote. Existing Criminal Law Existing federal criminal law seeks to ensure the safety and integrity of federal judicial and other official proceedings by proscribing threats and violence (1) against federal personnel, (2) against witnesses in official proceedings, and (3) against federal proceedings and facilities. Federal Judges, Officers and Employees It is a federal crime to: assault, kidnap or kill a federal judge during or on account of the performance of his or her duties; or assault, kidnap, or murder an immediate member of a federal judge's family with the intent to obstruct (or retaliate for) the judge's performance of his or her duties; or assault, kidnap, or murder a former federal judge or member of his or her family on account of the performance of judge's duties; or threaten, attempt, or conspire to do so. Moreover, the proscriptions are not limited to federal judges. They protect federal law enforcement officers as well as prosecutors and in fact protect any federal officer or employee or anyone assisting them, as long as the threat, assault, kidnaping or killing has the necessary connection (during or on account of) to the performances of federal duties. The penalties for the offenses are calibrated according to the seriousness of the obstructing offense. P.L. 110-177 Section 1114 (killing federal officers and employees, etc.) adopts by cross reference the penalties of 18 U.S.C. 1112 (manslaughter in the special maritime and territorial jurisdiction) when the offense involves manslaughter committed against federal judges, officials or employees. Section 207 of P.L. 110-177 increases the maximum penalty for manslaughter committed in violation of Section 1114 by increasing the penalties under 18 U.S.C. 1112. In the case of voluntary manslaughter, the term of imprisonment goes from not more than 10 years to not more than 15 years, and in the case of involuntary manslaughter from not more than 6 years to not more than 8 years. Several other federal statutes also adopt the penalty structure of Section 1112 by cross-reference. Consequently, when P.L. 110-177 enhances sanctions of Section 1112 the increases the penalties for manslaughter in violation of both Sections 1112 and 1114, but also manslaughter committed: against a Member of Congress, a senior executive branch official, or, a Supreme Court Justice; in connection with a federal offense that involves the use or possession of armor piercing ammunition during and furtherance of the offense; in connection with the possession of a firearm or dangerous weapon in a federal facility; against protected diplomatic officials; against an American by an American overseas; in the course of an obstruction of justice in violation of 18 U.S.C. 1503, 1512, or 1513; against the President, Vice-President, or senior executive branch officials. Section 208 of P.L. 110-177 leaves the penalties for assaulting federal judges, officers or employees unchanged, but increases those for assaulting members of their families or former judges, officers or employees to: imprisonment for not more than 30 years for assault with a dangerous weapon; not more than 15 years for assault resulting in serious bodily injury; and not more than 10 years for assault resulting in serious injury, 18 U.S.C. 115(b)(1). Section 209 directs the United States Sentencing Commission to review the sentencing guidelines applicable to threats committed in violation of 18 U.S.C. 115 and communicated over the Internet. Federal Witnesses Federal obstruction of justice statutes protect witnesses and potential witnesses in federal judicial, Congressional and administrative proceedings by outlawing murder, assault and threats intended to prevent or influence a witness' testimony or to retaliate for past testimony, 18 U.S.C. 1512 and 1513. The penalties for murder, manslaughter and attempted murder of federal witnesses under Sections 1512 and 1513 are the same as when those crimes are committed against federal officials, but the penalties for assault and conspiracy are a bit more severe. P.L. 110-177 In addition to the penalty increases occurring when the bills change the Section 1112 manslaughter penalties that apply to manslaughter committed in violation of Sections 1512 and 1513 (from imprisonment for not more than10 years to imprisonment for not more than 15 years for voluntary manslaughter; and from not more than 6 years to not more than 8 years for involuntary manslaughter), Sections 205 and 206 boost the maximum penalties for witness tampering or retaliation in violation of 18 U.S.C. 1512 or 1513 when the offense involves the use of physical force from 20 years to 30 years; when it involves the threat of the use of physical force from 10 years to 20 years; and for harassment from 1 year to 3 years. Section 204 adds a venue provision to the witness retaliation offenses in 18 U.S.C. 1513 purporting to permit prosecution of offenses under the section either in the place where the violation occurs or in place where the proceeding occurs. Section 1512 already contains a similar provision. The Constitution may confine Section 204's reach and that of the comparable provision in Section 1512. The Constitution provides that the "trial of all crimes... shall be held in the state where the said crimes shall have been committed," and in "all criminal prosecutions, the accused shall enjoy the right to a speedy and public trial, by an impartial jury of the state and district wherein the crime shall have been committed." The Supreme Court has indicated that the prosecution of offenses, other than where one of its "conduct elements" occurs, poses serious constitutional problems. Federal Proceedings Federal obstruction of justice law also prohibits the use of force or threats to obstruct or to endeavor to obstruct the "due administration of justice" in federal courts or to obstruct Congressional or administrative proceedings. Obstruction of Congressional and administrative proceedings carries a flat sanction of imprisonment for not more than 5 years (not more than 8 years if the proceedings involve international or domestic terrorism). Penalties for the obstruction of federal judicial proceedings are more structured, particularly if a killing occurs. Other than the change attributable to the manslaughter amendments in Section 1112 mentioned earlier, the bill leaves sentencing under Section 1503 as it finds it. Means of Obstruction Beyond the proscriptions addressed to the use of violence against federal officials, witnesses and proceedings, there are federal criminal prohibitions directed at the misuse of firearms, explosives and other dangerous instrumentalities that may be implicated by a breach of court security. For example, the use of explosives as the means of obstruction may trigger a federal proscription that outlaws damaging federal property with explosives, one that exposes offenders to imprisonment for not less than 7 nor more than 40 years if the offense involves a substantial risk of injury; to imprisonment for not less than 20 years or for life (and possible to the death penalty) if the offense results in death; and to imprisonment for not less than 5 nor more than 20 years in all other instances. When firearms are the violent obstructive means employed, a second statute calls for imposition of a progression of mandatory minimum terms of imprisonment based on the type and manner of firearm use. Under its provisions when a firearm is used or carried during and in furtherance of a federal crime of violence, a mandatory minimum term of imprisonment of 5 years is imposed; and the mandatory minimum is 7 years, if the firearm is brandished; 10 years, if it is discharged; 10 years, if it is a short-barreled shotgun or short-barreled rifle; 30 years, if it is a machine gun or fitted with a silencer; 25 years, if the offender has a prior conviction under the section; and life imprisonment, if the offender has such a prior conviction and the firearm is a machine gun or fitted with a silencer. A third federal provision, 18 U.S.C. 930, outlaws the use of a firearm or other dangerous weapon in a fatal attack in a federal facility. It adopts by cross reference the penalties assigned elsewhere for murder, manslaughter, attempted murder or manslaughter, and conspiracy to murder or manslaughter. The same statute punishes possession or attempted possession of a firearm or dangerous weapon within a federal facility with intent to use it there with imprisonment for not more than 5 years, simple possession of a firearm or dangerous weapon within a federal facility other than a federal courthouse with imprisonment for not more than 1 year, and simple possession or attempted possession of a firearm within a federal courthouse with imprisonment for not more than 2 years. P.L. 110-177 Dangerous Weapons Section 203 amends the proscription for simple courthouse firearm possession found in Section 930(e) to include possession of other dangerous weapons as well. The possession with intent proscription already includes coverage of both firearms and dangerous weapons. The existing statute has a definition that excludes small pocket knives from the term "dangerous weapon." Yet, it describes dangerous weapons as any item capable of inflicting serious injury. When used to describe the objects that may be impermissibly used in an assault, its breadth is understandable. In such circumstances, it has been understood to include shoes, belts, rings, chairs, desks, teeth, screwdrivers, and a host of other ordinarily innocent objects that could be misused to inflict serious injury. When the definition makes it a crime to possess such items in a federal courthouse regardless of how innocently they are used, practical problems may arise. If the courts read the definition out of the statute for purposes of simple courthouse possession prosecutions, they may take the small knife exception with it and be left to their own devices to define what constitutes a dangerous weapon. The same incongruity, however, appears to have escaped notice in the case of simple possession of a dangerous weapon in a federal facility other than a federal courthouse under 18 U.S.C. 930(a). Harassing Federal Officials with False Liens Retaliation against federal officials in the past has sometimes taken the form of filing false liens and other legal nuisance actions against their property. Such obstructions have been prosecuted under federal statutes that prohibit obstruction of the due administration of justice (18 U.S.C. 1503) or that prohibit conspiracy to retaliate against federal officials by inflicting economic damage (18 U.S.C. 372). These statutes are not without limitation, however, since most courts insist that a prosecution under Section 1503 requires that the misconduct occur during the pendency of a judicial proceeding and that a prosecution under Section 372 requires a conspiracy, that is, a scheme of two or more defendants. Section 201 of P.L. 110-177 makes it a separate federal crime, punishable by imprisonment for not more than 10 years, to knowingly file a false lien or similar encumbrance against the property of a federal officer or employee on account of the performance of his or her federal duties or to conspire or attempt to do so, 18 U.S.C. 1521. Aiding the Intimidation of Federal Officials It is a federal crime to threaten to kill, kidnap or assault a federal officer or employee, a retired federal officer or employee, or a member of their immediate family to impede or on account of the performance of their federal duties. It is likewise a federal offense to threaten a witness or potential witness in a federal proceeding in order to impede or retaliate for their performance as a witness. And it is a federal crime to threaten federal grand or petit jurors in order to impede or influence their service. Moreover, anyone who aids or abets the commission of these or of any other federal crime is criminally liable to the same extent as the individual who actually commits them. Liability for aiding or abetting, however, can only be incurred upon the commission of the underlying offense. Section 202 of P.L. 110-177 makes it a federal crime to make publicly available certain identifying information such as home addresses, telephone numbers, and social security numbers of federal officials, employees, witnesses, and jurors (grand and petite) either (1) with the intent to threaten, intimidate, or incite a crime of violence against such individuals or members of their immediate families, or (2) with the intent and knowledge that the information will be used for such purpose, 18 U.S.C. 119. Offenders are subject to a term of imprisonment for not more than 5 years, id. There is no requirement that the victims be targeted on account of their federal or family status, that any incited violence be imminent, or that the information be publicly unavailable otherwise. The new section also covers federal, territorial, state and local public safety officers whose agencies receive federal funding, witnesses and informants in federal criminal investigations and prosecutions, and witnesses and informants in state investigations and prosecutions of crimes that have an impact on interstate or foreign commerce, 18 U.S.C. 119(b)(2)(c),(d). First Amendment considerations may color the section's application. The First Amendment has been held to prohibit the punishment of a newspaper for publishing the name of rape victim when her identity was otherwise available as a matter of public record. And it has been held to preclude punishing a newspaper for publishing the name of a juvenile subject to delinquency proceedings when it obtained the information lawfully. On the other hand, neither true threats nor incitement to immediate criminal action are entitled to First Amendment protection. Moreover, in a somewhat analogous case, the Ninth Circuit found a want of First Amendment protection for "true threats" in the form of "wanted" bulletins, posted on the Internet, that listed the pictures, names and address of various doctors after other doctors similarly identified in previous bulletins had been murdered. The statute prohibits disclosure of identifying information only where publication is intended to threaten or incite violence or is intended to be used for such purposes. Proof of such an intent is likely to require evidence that demonstrates the existence of a true threat or the incitement of an immediate crime of violence and therefore satisfies First Amendment concerns. Implementation of Judicial Security Responsibilities of the Marshals Service The United States Marshals Service is located in the Department of Justice. The Director of the Marshals Service and the Marshals for each of the 94 judicial districts and for the Superior Court of the District of Columbia are appointed by the President, with the advice and consent of the Senate. Marshals serve four year terms at the pleasure of the President. Marshals are responsible for the security of the U.S. District Courts, U.S. Courts of Appeal and Court of International Trade sitting in their districts, and for the execution of warrants, subpoenas and other process of those courts. The Marshals are also responsible for the protection of witnesses, the asset forfeiture program, and the arrest of fugitives from federal law. P.L. 110-177 Additional Authorizations Section 105 calls for $20 million in additional authorization of appropriations for each fiscal year through 2011 in order to hire additional marshals to provide security for federal judges and assistant United States attorneys and to augment the resources of the Marshals Service's Office of Protective Intelligence. In a related matter, the President's budget for FY2008 indicates that the Administration will request additional appropriations for the Marshals Service of $25.7 million "for investigating threats against the Judiciary, high-threat trial security, judicial security in the Southwest Border district offices, and enforcement of the Adam Walsh Child Protection and Safety Act." Security for Tax Court Activities The Marshals Service is authorized to provide security and service of process for the federal District Courts, Courts of Appeal and the Court of International Trade. Section 102 expands those responsibilities to the Tax Court, 28 U.S.C. 566(a). They also bolster the authority to serve the Tax Court. Section 7456 of the Internal Revenue Code (26 U.S.C. 7456) ends with the instruction that, "The United States marshal for any district in which the Tax Court is sitting shall, when requested by the chief judge of the Tax Court, attend any session of the Tax Court in such district." P.L. 110-177 amends the section to include an explicit instruction to provide security for the Court, its judges, personnel, witnesses, and other participants in its proceedings, when requested by the Chief Justice of the Tax Court. Coordination with the Judicial Conference The Judicial Conference of the United States oversees the rules and conditions under which the federal courts operate. Section 101 amends the organic statutes for the Marshals Service and the Judicial Conference to ensure regular consultation between the two concerning the judicial security, assessment of threats against members of the judiciary and protection of judicial personnel. Safety of Federal Prosecutors Like federal judges, federal prosecutors have been the subject of both threats and plots to kill them. Neither have express authority to carry firearms in the performance of their duties. Marshals and deputy marshals, on the other hand, do have such express authority. And prosecutors, at least, can be deputized as deputy marshals, a process that carries with it the authority of the office, e.g., the authority to carry a firearm. Section 401 directs the Attorney General to report to the House and Senate Judiciary Committees within 90 days on the security of federal prosecutors. The report must include: the extent and a description of the threats made against federal prosecutors, the steps taken for their security, the number of prosecutors deputized in response to such threats, the policies governing the practices of Department attorneys with state firearm licenses, the security consequences of the considerations under which threatened prosecutors must perform such as after hours work and parking priorities, a discussion of related training available to prosecutors, the identity of the officials responsible for the development of Department policies to deal with such matters, and the role of the Marshals Service and other Department security components in such matters. Redacted Financial Disclosure Statements The Ethics in Government Act requires federal judges, Members of Congress, and senior officials in the legislative, executive and judicial branches to file publicly available financial disclosure reports. Concerned that information contained in the financial disclosure statements of federal judges might be misused in efforts to threaten or intimidate them, Congress temporarily authorized the redaction of certain information from the financial disclosure statements of certain federal judges. Section 104 temporarily extends the provision until December 31, 2011. Grants to the States Witness Protection Part H of the Violent Crime Control and Law Enforcement Act of 1994, 42 U.S.C. 13861-13868, authorizes community-based grants for state, territorial, and tribal prosecutors. Appropriations were last authorized for FY2000, 42 U.S.C. 13867. Section 301 of P.L. 110-177 amends Part H to include state witness protection programs and authorizes appropriations for Part H of $20 million for each fiscal year through 2012. State and Tribal Court Security Sections 515 and 516 of Title I of the Omnibus Crime and Safe Streets Act of 1968 authorizes discretionary Bureau of Justice Assistance Correctional Options grants, 42 U.S.C. 3762a, 3762b. Section 2501 of Title I authorizes a matching grant program to purchase armored vests for state, territorial and tribal law enforcement officers, 42 U.S.C. 3796ll to 3796ll-2. Section 302 of P.L. 110-177 amends Sections 515 and 516 to permit 10 per cent of the funds appropriated for grants under those sections to be available for grants to improve security for state, territorial, or tribal court systems with priority to be given to those demonstrating the greatest need, 42 U.S.C. 3762a, 3762b. To accommodate the new allotment, the percent of appropriations available for corrections alternatives would be reduced from 80 percent to 70 percent of the funds appropriated, 42 U.S.C. 3762b. Section 302 also amends Section 2501 of the Omnibus Crime Control and Safe Streets Act to include matching grants for the purchase of armored vests for state and territorial court officers, 42 U.S.C. 3796ll. Section 302 further permits the Attorney General to require when appropriate that state, territorial or tribal applicants for grants under programs administered by the Department of Justice show that they have considered the security needs of their judicial branch following consultation with judicial and law enforcement authorities. Section 303 authorizes the Attorney General to award grants to permit the highest courts in each state to establish and maintain threat assessment databases in a manner to allow access by other states and the Justice Department. The section authorizes the necessary appropriations for fiscal years 2008 through 2011 as well. Miscellaneous Provisions U.S. Sentencing Commission Procurement Authority The United States Sentencing Commission was established in 1984 as an independent entity located within the judicial branch. Its purpose is to promulgate sentencing guidelines for use by federal courts in criminal cases. Those guidelines, once binding upon the courts, are now simply advisory, although the courts must continue to consider them and the guidelines continue to carry considerable persuasive force. The Commission may enter into contracts in fulfillment of its responsibilities. As a general rule, appropriated funds are available for obligation under contract or otherwise only during the fiscal year for which they were appropriated. There are several exceptions to the general rule. For example, the heads of executive agencies may contract for services that begin in one fiscal year and end in the next. They may also enter into multi-year contracts. And with sufficient security, they may make advance payments on contract obligations to be fulfilled at a later date. In the judicial branch, the Administrative Office of the United States Courts enjoys similar authority. Section 501 temporarily grants the Sentencing Commission comparable authority, 28 U.S.C. 995(f)(expiring on September, 30, 2010). Life Insurance Costs Judges of the United States Courts of Appeal and United States District Courts serve during good behavior, which ordinarily means for life. When they reach 65 years of age with at least 15 years of service or at such later date as their age and years of service equal 80 years, they may remain in active service, they may retire at an annuity equal to their salary on the date of retirement, or they may retire to senior status. Judges in senior status continue to serve but are considered to have left office for vacancy purposes so that replacements may be appointed. Senior judges receive full salary, including any pay increases or adjustments given judges on active service, as long as they essentially carry at least the equivalent of 25% of the workload of a full time member of the court. When the Office of Personnel Management announced life insurance premium increases for District and Appeals Court judges in 1999, the judges and the Administrative Office objected that the increase would operate as a disincentive to serve on senior status. The appropriations legislation for that year included a provision now found in 28 U.S.C. 604(a)(5): The Director... shall... pay on behalf of Justices and judges of the United States appointed to hold office during good behavior, aged 65 or over, any increases in the cost of Federal Employees' Group Life Insurance imposed after April 24, 1999, including any expenses generated by such payments, as authorized by the Judicial Conference of the United States. Similar provisions have been made for judges of the Tax Court and the Court of Federal Claims, judges who serve 15 year terms. They may be recalled to perform judicial duties for periods up to 90 days a year. Section 502 makes this provision applicable to magistrate judges. Assignment of Senior Judges The chief judges of the various United States Courts of Appeal or the various circuit judicial councils may designate and assign senior judges to perform judicial duties within the circuit. As a general matter, senior judges who are designated and assigned enjoy all of the powers of the court, circuit or district to which they are assigned, except for the power to permanently designate a publisher for legal notices or depository of funds or "to appoint any person to a statutory position." Federal statutes describe the appointment authority for several positions in the judicial branch. Bankruptcy judges are appointed by the circuit Court of Appeals, who also appoint their clerks and librarians; circuit judges appoint their own law clerks and secretaries; and circuit chief justices appoint senior staff attorneys. Magistrate judges are appointed by the district court judges, who also appoint their clerks and court reporters; individual judges appoint their own bailiffs, law clerks and secretaries. Beyond the explicit exceptions and the general rule notwithstanding, there are several powers that only a judge in "regular active service" and no senior judge may exercise. Thus, only a judge in regular active service may serve as a chief judge of a federal district or circuit. The decision to present an appeal to all of the judges of a particular circuit (to grant a hearing or rehearing en banc) is made by a majority vote of the judges of that circuit who are in regular active service. A senior judge may participate in an en banc appeal only if he or she was a member of the panel that initially decided the case being heard en banc. Senior judges may serve on the United States Sentencing Commission and on the Board of the Federal Judicial Center. They may serve as well as members of the Judicial Conference of the United States, the rule propounding body for the federal courts. They may also sit on the judicial councils for their circuits, the local rule making authority for the circuit, but the number of members of such councils and their terms of service are determined by a majority vote of the judges in regular active service in the circuit. Section 503 amends 28 U.S.C. 296 to declare that senior judges "when designated and assigned to the court to which such judge was appointed, having performed in the preceding calendar year an amount of work equal to or greater than the amount of work an average judge in active service on that court would perform in 6 months, and having elected to exercise such powers, shall have all the powers of a judge of that court, including participation in appointment of court officers and magistrates, rulemaking, governance, and administrative matters," 28 U.S.C. 296. Although the amendment might under other circumstances be thought to extend merely to those judicial powers and tasks for which there is no contrary instruction by statute or rule, the specific mention of the appointment of magistrate seems to preclude such a construction. It would presumably override the circuit court en banc limitations as well. Appointment of Magistrates Magistrate judges are appointed pursuant to a statute that declares that, "the judges of each United States district court and the district courts of the Virgin Islands, Guam, and the Northern Mariana Islands shall appoint United States magistrate judges..." 28 U.S.C. 631(a). Section 504 amends this language to add, after "the Northern Mariana Islands", the parenthetical "(including any judge in regular active service and any judge who has retired from regular active service under Section 371(b) of this title, when designed and assigned to the court to which such judge was appointed)". The amendment may present an interpretative challenge. The problem is that only United States district court judges retire under Section 371(b); the judges in the Virgin Islands, Guam and the Northern Mariana Islands retire under Section 373. So does the amendment intend to add only senior United States district court judges to the core of judges who may participate in the decision to appoint magistrate judges for their districts? Probably, but that intent would have been more clearly demonstrated if the parenthetical had been added immediately after the phrase "United States district court." Such a reading might be thought to render the amendment redundant since the prior section vests senior judges with share in the appointment of magistrate judges for their districts, but it can also be read as simply confirming the operation of the previous section. Or does the amendment intend to permit both United States district court senior judges who retired under Section 371(b) and territorial judges who retired under Section 373 to participate in the appointment magistrate judges of their courts? Possibly, but read literally it would mean that territorial judges could participate as long as they had elected eligibility for senior status upon retirement regardless of whether they had been actually recalled. Or does the amendment intend only to permit appointment by a senior judge in the district court of the Northern Mariana Islands who retired under Section 373? Very unlikely, for while it is perhaps the most grammatically faithful reading, it would mean affording a senior judge of the Northern Mariana Islands authority that is denied the other territorial district courts. Moreover, senior judges of the Northern Mariana Islands retire under Section 373 rather than 371 as stated in the amendment. Payment of Fines by Former Prisoners Federal courts that sentence an offender to prison may also include a term of supervised release to be served upon completion of the defendant's term of imprisonment, 18 U.S.C. 3583. They may at the same time impose a fine upon the defendant of up to $250,000 for most felonies and lesser amounts for misdemeanors, 18 U.S.C. 3571. Prior law stated that a defendant was not to be released on supervised release unless he agreed to follow an installment schedule for any remaining fine obligations, 18 U.S.C. 3624(e)(2000 ed.). Since the defendant must be released upon service of his sentence, the language suggested he might avoid supervised release simply by refusing to accept an installment schedule. Section 505 amends the prior language to compel the Bureau of Prisons to notify prisoners upon their release of their obligation to follow an installment payment schedule in order to satisfy any outstanding fine obligations, 18 U.S.C. 3624(e). Study of State Open Record Laws Section 506 instructs the Attorney General to study whether public access to state and local public records imperils the safety of federal judges. Authorization of Fugitive Apprehension Task Forces The Presidential Threat Protection Act authorized the Marshals Service to direct and coordinate permanent Fugitive Apprehension Task Forces composed of federal, state and local law enforcement officers in order to capture fugitives from justice. The act authorized appropriations of $30 million for the purpose for FY2001 and $5 million per year for each of the two fiscal years thereafter. Section 507 authorizes appropriations of $10 million for each of the fiscal years from 2008 through 2012 for the Fugitive Apprehension Task Forces. Judicial Exemption from the REAL ID Act The REAL ID Act establishes certain minimum requirements for state drivers' licenses and other state identification documents if they are to be received for federal identification purposes – including the individual's home address. In the case of federal judges, Section 508 allows the states to substitute the address of the court where the federal judge has his or her chambers. Judgeships in the Ninth Circuit Section 509 increases the number of judgeships on the Ninth Circuit Court of Appeals from 28 to 29 and reduces the number on the District of Columbia Circuit Court of Appeals from 12 to 11. The statement in the report of the section's sponsor, Senator Feinstein, indicates the amendment is intended to reflect the relative workloads of the two Circuits and the need to address the growing backlog of cases in the Ninth Circuit, id. at 10 (additional views of Senator Feinstein). Collateral Consequences of Conviction Offenders of federal and state criminal law face the prospect of probation, imprisonment, parole, supervised release, assessments, fines, forfeiture, and/or restitution orders. They may also suffer obligations, disabilities, disqualifications, and ineligibility as a consequence of their convictions, quite apart from the sanctions imposed at the time of sentencing. The law of a particular jurisdiction may authorize authorities to lift the burden of some of these under some circumstances. Section 510 directs the National Institute of Justice to study and report on the collateral consequences of conviction under federal law and the laws of the various states. Although the section provides explicit descriptions of the "collateral sanctions" and "disqualifications" it anticipates the report will describe, the diversity of P.L. 110-177 in the area may make the task challenging. Appendix. 18 U.S.C. 1114 Whoever kills or attempts to kill any officer or employee of the United States or of any agency in any branch of the United States Government (including any member of the uniformed services) while such officer or employee is engaged in or on account of the performance of official duties, or any person assisting such an officer or employee in the performance of such duties or on account of that assistance, shall be punished – (1) in the case of murder, as provided under section 1111; (2) in the case of manslaughter, as provided under section 1112; or (3) in the case of attempted murder or manslaughter, as provided in section 1113. 18 U.S.C. 111 (a) In general.– Whoever– (1) forcibly assaults, resists, opposes, impedes, intimidates, or interferes with any person designated in section 1114 of this title while engaged in or on account of the performance of official duties; or (2) forcibly assaults or intimidates any person who formerly served as a person designated in section 1114 on account of the performance of official duties during such person's term of service, shall, where the acts in violation of this section constitute only simple assault, be fined under this title or imprisoned not more than one year, or both, and in all other cases, be fined under this title or imprisoned not more than 8 years, or both. (b) Enhanced penalty.– Whoever, in the commission of any acts described in subsection (a), uses a deadly or dangerous weapon (including a weapon intended to cause death or danger but that fails to do so by reason of a defective component) or inflicts bodily injury, shall be fined under this title or imprisoned not more than 20 years, or both. 18 U.S.C. 1201 (a) Whoever unlawfully seizes, confines, inveigles, decoys, kidnaps, abducts, or carries away and holds for ransom or reward or otherwise any person, except in the case of a minor by the parent thereof, when... (5) the person is among those officers and employees described in section 1114 of this title and any such act against the person is done while the person is engaged in, or on account of, the performance of official duties; shall be punished by imprisonment for any term of years or for life and, if the death of any person results, shall be punished by death or life imprisonment. * * * (c) If two or more persons conspire to violate this section and one or more of such persons do any overt act to effect the object of the conspiracy, each shall be punished by imprisonment for any term of years or for life. (d) Whoever attempts to violate subsection (a) shall be punished by imprisonment for not more than twenty years. * * * 18 U.S.C. 115 (a)(1) Whoever – (A) assaults, kidnaps, or murders, or attempts or conspires to kidnap or murder, or threatens to assault, kidnap or murder a member of the immediate family of a United States official, a United States judge, a Federal law enforcement officer, or an official whose killing would be a crime under section 1114 of this title; or (B) threatens to assault, kidnap, or murder, a United States official, a United States judge, a Federal law enforcement officer, or an official whose killing would be a crime under such section, with intent to impede, intimidate, or interfere with such official, judge, or law enforcement officer while engaged in the performance of official duties, or with intent to retaliate against such official, judge, or law enforcement officer on account of the performance of official duties, shall be punished as provided in subsection (b). (2) Whoever assaults, kidnaps, or murders, or attempts or conspires to kidnap or murder, or threatens to assault, kidnap, or murder, any person who formerly served as a person designated in paragraph (1), or a member of the immediate family of any person who formerly served as a person designated in paragraph (1), with intent to retaliate against such person on account of the performance of official duties during the term of service of such person, shall be punished as provided in subsection (b). (b)(1) An assault in violation of this section shall be punished as provided in section 111 of this title. (2) A kidnaping, or attempted kidnaping of, or a conspiracy to kidnap, a person in violation of this section shall be punished as provided in Section 1201 of this title for the kidnaping, attempted kidnaping, or conspiracy to kidnap of a person described in section 1201(a)(5) of this title. (3) A murder, attempted murder, or conspiracy to murder in violation of this section shall be punished as provided in sections 1111, 1113, and 1117 of this title. (4) A threat made in violation of this section shall be punished by a fine under this title or imprisonment for a term of not more than 10 years, or both, except that imprisonment for a threatened assault shall not exceed 6 years. (c) As used in this section, the term – (1) "Federal law enforcement officer" means any officer, agent, or employee of the United States authorized by law or by a Government agency to engage in or supervise the prevention, detection, investigation, or prosecution of any violation of Federal criminal law; (2) "immediate family member" of an individual means— (A) his spouse, parent, brother or sister, child or person to whom he stands in loco parentis; or (B) any other person living in his household and related to him by blood or marriage; (3) "United States judge" means any judicial officer of the United States, and includes a justice of the Supreme Court and a United States magistrate judge; and (4) "United States official" means the President, President-elect, Vice President, Vice President-elect, a Member of Congress, a member-elect of Congress, a member of the executive branch who is the head of a department listed in 5 U.S.C. 101, or the Director of the Central Intelligence Agency. (d) This section shall not interfere with the investigative authority of the United States Secret Service, as provided under sections 3056, 871, and 879 of this title 18 U.S.C. 1512 (a)(1) Whoever kills or attempts to kill another person, with intent to – (A) prevent the attendance or testimony of any person in an official proceeding; (B) prevent the production of a record, document, or other object, in an official proceeding; or (C) prevent the communication by any person to a law enforcement officer or judge of the United States of information relating to the commission or possible commission of a Federal offense or a violation of conditions of probation, parole, or release pending judicial proceedings; shall be punished as provided in paragraph (3). (2) Whoever uses physical force or the threat of physical force against any person, or attempts to do so, with intent to – (A) influence, delay, or prevent the testimony of any person in an official proceeding; (B) cause or induce any person to – (i) withhold testimony, or withhold a record, document, or other object, from an official proceeding; (ii) alter, destroy, mutilate, or conceal an object with intent to impair the integrity or availability of the object for use in an official proceeding; (iii) evade legal process summoning that person to appear as a witness, or to produce a record, document, or other object, in an official proceeding; or (iv) be absent from an official proceeding to which that person has been summoned by legal process; or (C) hinder, delay, or prevent the communication to a law enforcement officer or judge of the United States of information relating to the commission or possible commission of a Federal offense or a violation of conditions of probation, supervised release, parole, or release pending judicial proceedings; shall be punished as provided in paragraph (3). (3) The punishment for an offense under this subsection is – (A) in the case of murder (as defined in section 1111), the death penalty or imprisonment for life, and in the case of any other killing, the punishment provided in section 1112; (B) in the case of – (i) an attempt to murder; or (ii) the use or attempted use of physical force against any person; imprisonment for not more than 20 years; and (C) in the case of the threat of use of physical force against any person, imprisonment for not more than 10 years. (b) Whoever knowingly uses intimidation, threatens, or corruptly persuades another person, or attempts to do so, or engages in misleading conduct toward another person, with intent to – (1) influence, delay, or prevent the testimony of any person in an official proceeding; (2) cause or induce any person to – (A) withhold testimony, or withhold a record, document, or other object, from an official proceeding; (B) alter, destroy, mutilate, or conceal an object with intent to impair the object's integrity or availability for use in an official proceeding; (C) evade legal process summoning that person to appear as a witness, or to produce a record, document, or other object, in an official proceeding; or (D) be absent from an official proceeding to which such person has been summoned by legal process; or (3) hinder, delay, or prevent the communication to a law enforcement officer or judge of the United States of information relating to the commission or possible commission of a Federal offense or a violation of conditions of probation supervised release,, parole, or release pending judicial proceedings; shall be fined under this title or imprisoned not more than ten years, or both. (c) Whoever corruptly – (1) alters, destroys, mutilates, or conceals a record, document, or other object, or attempts to do so, with the intent to impair the object's integrity or availability for use in an official proceeding; or (2) otherwise obstructs, influences, or impedes any official proceeding, or attempts to do so, shall be fined under this title or imprisoned not more than 20 years, or both. (d) Whoever intentionally harasses another person and thereby hinders, delays, prevents, or dissuades any person from – (1) attending or testifying in an official proceeding; (2) reporting to a law enforcement officer or judge of the United States the commission or possible commission of a Federal offense or a violation of conditions of probation supervised release, parole, or release pending judicial proceedings; (3) arresting or seeking the arrest of another person in connection with a Federal offense; or (4) causing a criminal prosecution, or a parole or probation revocation proceeding, to be sought or instituted, or assisting in such prosecution or proceeding; or attempts to do so, shall be fined under this title or imprisoned not more than one year, or both. (e) In a prosecution for an offense under this section, it is an affirmative defense, as to which the defendant has the burden of proof by a preponderance of the evidence, that the conduct consisted solely of lawful conduct and that the defendant's sole intention was to encourage, induce, or cause the other person to testify truthfully. (f) For the purposes of this section – (1) an official proceeding need not be pending or about to be instituted at the time of the offense; and (2) the testimony, or the record, document, or other object need not be admissible in evidence or free of a claim of privilege. (g) In a prosecution for an offense under this section, no state of mind need be proved with respect to the circumstance – (1) that the official proceeding before a judge, court, magistrate judge, grand jury, or government agency is before a judge or court of the United States, a United States magistrate judge, a bankruptcy judge, a Federal grand jury, or a Federal Government agency; or (2) that the judge is a judge of the United States or that the law enforcement officer is an officer or employee of the Federal Government or a person authorized to act for or on behalf of the Federal Government or serving the Federal Government as an adviser or consultant. (h) There is extraterritorial Federal jurisdiction over an offense under this section. (i) A prosecution under this section or section 1503 may be brought in the district in which the official proceeding (whether or not pending or about to be instituted) was intended to be affected or in the district in which the conduct constituting the alleged offense occurred. (j) If the offense under this section occurs in connection with a trial of a criminal case, the maximum term of imprisonment which may be imposed for the offense shall be the higher of that otherwise provided by law or the maximum term that could have been imposed for any offense charged in such case. (k) Whoever conspires to commit any offense under this section shall be subject to the same penalties as those prescribed for the offense the commission of which was the object of the conspiracy. 18 U.S.C. 1513 (a)(1) Whoever kills or attempts to kill another person with intent to retaliate against any person for – (A) the attendance of a witness or party at an official proceeding, or any testimony given or any record, document, or other object produced by a witness in an official proceeding; or (B) providing to a law enforcement officer any information relating to the commission or possible commission of a Federal offense or a violation of conditions of probation supervised release, parole, or release pending judicial proceedings, shall be punished as provided in paragraph (2). (2) The punishment for an offense under this subsection is – (A) in the case of a killing, the punishment provided in sections 1111 and 1112; and (B) in the case of an attempt, imprisonment for not more than 20 years. (b) Whoever knowingly engages in any conduct and thereby causes bodily injury to another person or damages the tangible property of another person, or threatens to do so, with intent to retaliate against any person for – (1) the attendance of a witness or party at an official proceeding, or any testimony given or any record, document, or other object produced by a witness in an official proceeding; or (2) any information relating to the commission or possible commission of a Federal offense or a violation of conditions of probation supervised release, parole, or release pending judicial proceedings given by a person to a law enforcement officer; or attempts to do so, shall be fined under this title or imprisoned not more than ten years, or both. (c) If the retaliation occurred because of attendance at or testimony in a criminal case, the maximum term of imprisonment which may be imposed for the offense under this section shall be the higher of that otherwise provided by law or the maximum term that could have been imposed for any offense charged in such case. (d) There is extraterritorial Federal jurisdiction over an offense under this section. (e) Whoever knowingly, with the intent to retaliate, takes any action harmful to any person, including interference with the lawful employment or livelihood of any person, for providing to a law enforcement officer any truthful information relating to the commission or possible commission of any Federal offense, shall be fined under this title or imprisoned not more than 10 years, or both. (e) Whoever conspires to commit any offense under this section shall be subject to the same penalties as those prescribed for the offense the commission of which was the object of the conspiracy. 18 U.S.C. 1503 (emphasis added) (a) Whoever corruptly, or by threats or force, or by any threatening letter or communication, endeavors to influence, intimidate, or impede any grand or petit juror, or officer in or of any court of the United States, or officer who may be serving at any examination or other proceeding before any United States magistrate judge or other committing magistrate, in the discharge of his duty, or injures any such grand or petit juror in his person or property on account of any verdict or indictment assented to by him, or on account of his being or having been such juror, or injures any such officer, magistrate judge, or other committing magistrate in his person or property on account of the performance of his official duties, or corruptly or by threats or force, or by any threatening letter or communication, influences, obstructs, or impedes, or endeavors to influence, obstruct, or impede, the due administration of justice, shall be punished as provided in subsection (b). If the offense under this section occurs in connection with a trial of a criminal case, and the act in violation of this section involves the threat of physical force or physical force, the maximum term of imprisonment which may be imposed for the offense shall be the higher of that otherwise provided by law or the maximum term that could have been imposed for any offense charged in such case. (b) The punishment for an offense under this section is – (1) in the case of a killing, the punishment provided in sections 1111 and 1112; (2) in the case of an attempted killing, or a case in which the offense was committed against a petit juror and in which a class A or B felony was charged, imprisonment for not more than 20 years, a fine under this title, or both; and (3) in any other case, imprisonment for not more than 10 years, a fine under this title, or both. 18 U.S.C. 1505 Whoever, with intent to avoid, evade, prevent, or obstruct compliance, in whole or in part, with any civil investigative demand duly and properly made under the Antitrust Civil Process Act, willfully withholds, misrepresents, removes from any place, conceals, covers up, destroys, mutilates, alters, or by other means falsifies any documentary material, answers to written interrogatories, or oral testimony, which is the subject of such demand; or attempts to do so or solicits another to do so; or Whoever corruptly, or by threats or force, or by any threatening letter or communication influences, obstructs, or impedes or endeavors to influence, obstruct, or impede the due and proper administration of the law under which any pending proceeding is being had before any department or agency of the United States, or the due and proper exercise of the power of inquiry under which any inquiry or investigation is being had by either House, or any committee of either House or any joint committee of the Congress – Shall be fined under this title, imprisoned not more than 5 years or, if the offense involves international or domestic terrorism (as defined in section 2331), imprisoned not more than 8 years, or both. 18 U.S.C. 930 (a) Except as provided in subsection (d), whoever knowingly possesses or causes to be present a firearm or other dangerous weapon in a Federal facility (other than a Federal court facility), or attempts to do so, shall be fined under this title or imprisoned not more than 1 year, or both. (b) Whoever, with intent that a firearm or other dangerous weapon be used in the commission of a crime, knowingly possesses or causes to be present such firearm or dangerous weapon in a Federal facility, or attempts to do so, shall be fined under this title or imprisoned not more than 5 years, or both. (c) A person who kills any person in the course of a violation of subsection (a) or (b), or in the course of an attack on a Federal facility involving the use of a firearm or other dangerous weapon, or attempts or conspires to do such an act, shall be punished as provided in sections 1111, 1112, 1113, and 1117. (d) Subsection (a) shall not apply to – (1) the lawful performance of official duties by an officer, agent, or employee of the United States, a State, or a political subdivision thereof, who is authorized by law to engage in or supervise the prevention, detection, investigation, or prosecution of any violation of law; (2) the possession of a firearm or other dangerous weapon by a Federal official or a member of the Armed Forces if such possession is authorized by law; or (3) the lawful carrying of firearms or other dangerous weapons in a Federal facility incident to hunting or other lawful purposes. (e)(1) Except as provided in paragraph (2), whoever knowingly possesses or causes to be present a firearm in a Federal court facility, or attempts to do so, shall be fined under this title, imprisoned not more than 2 years, or both. (2) Paragraph (1) shall not apply to conduct which is described in paragraph (1) or (2) of subsection (d). (f) Nothing in this section limits the power of a court of the United States to punish for contempt or to promulgate rules or orders regulating, restricting, or prohibiting the possession of weapons within any building housing such court or any of its proceedings, or upon any grounds appurtenant to such building. (g) As used in this section: (1) The term "Federal facility" means a building or part thereof owned or leased by the Federal Government, where Federal employees are regularly present for the purpose of performing their official duties. (2) The term "dangerous weapon" means a weapon, device, instrument, material, or substance, animate or inanimate, that is used for, or is readily capable of, causing death or serious bodily injury, except that such term does not include a pocket knife with a blade of less than 2 ½ inches in length. (3) The term "Federal court facility" means the courtroom, judges' chambers, witness rooms, jury deliberation rooms, attorney conference rooms, prisoner holding cells, offices of the court clerks, the United States attorney, and the United States marshal, probation and parole offices, and adjoining corridors of any court of the United States. (h) Notice of the provisions of subsections (a) and (b) shall be posted conspicuously at each public entrance to each Federal facility, and notice of subsection (e) shall be posted conspicuously at each public entrance to each Federal court facility, and no person shall be convicted of an offense under subsection (a) or (e) with respect to a Federal facility if such notice is not so posted at such facility, unless such person had actual notice of subsection (a) or (e), as the case may be.

Summary: The proposals of the Court Security Improvement Act of 2007 ( P.L. 110-177, H.R. 660 and S. 378 ), fall within one of four categories. One consists of amendments to existing federal criminal law. The bill increases the penalties for manslaughter committed during the course of an obstruction of justice and for witness intimidation and retaliation. It creates new federal crimes proscribing (1) the use of nuisance liens and encumbrances to harass federal officials; (2) the public disclosure of personal, identifying information concerning federal officials in order to intimidate them or incite crimes of violence against them; and (3) the possession of dangerous weapons in federal courthouses. A second category seeks to improve implementation of judicial security measures through increased appropriations, enhanced security for the Tax Court, explicit provisions for consultation between the Department of Justice and the Judicial Conference relating to court security, a report on concerns for the safety of federal prosecutors, and a revival of authority to redact information from certain publicly available judicial financial disclosure statements. A third authorizes grants for state witness protection programs; for increased security of state, territorial and tribal courts; and for acquisition of armored vests for state court officials. The fourth category consists of proposals whose relation to security may appear more tangential: procurement authority for the United States Sentencing Commission; life insurance costs for bankruptcy, magistrate, and territorial judges; the appointment and en banc participation for senior judges; and judgeships in the Ninth Circuit and District of Columbia Courts of Appeal. This report is available in an abridged version – stripped of its footnotes, and most of its citations to authority – as CRS Report RS22607, Court Security Improvement Act of 2007: Public Law 110-177 (H.R. 660 and S. 378) in Brief, by [author name scrubbed].

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Summarize: In questa settimana torna la Champions League. E si parte alla grande con due super sfide mercoledì 15 settembre. A San Siro l'Inter campione d'Italia ospiterà il Real Madrid, mentre il Milan volerà a Liverpool e sfiderà la squadra di Klopp. Martedì 14 invece la Juventus, a secco di vittorie finora in stagione, scenderà in campo a Malmo, mentre l'Atalanta giocherà in casa del Villarreal. Saranno la Juventus e l'Atalanta le prime squadre italiane a scendere in campo nella Champions 2021-2022. I bianconeri, martedì 14, giocheranno in Svezia con il Malmo, mentre l'Atalanta volerà in Spagna per sfidare il Villarreal. Partite di lusso mercoledì 15: Inter-Real Madrid e Liverpool-Milan. Martedì 14 settembre Mercoledì 15 settembre Non sarà semplice seguire la Champions League per gli appassionati di calcio. Perché i diritti TV sono divisi tra tre broadcaster: Sky, Mediaset e Amazon. L'emittente satellitare trasmetterà 121 delle 137 partite in programma. Mediaset invece ha la possibilità di mandare in onda in chiaro un incontro a settimana, e lo farà su Canale 5. Mentre Amazon Prime Video trasmetterà nella prima fase in esclusiva l'incontro più interessante delle squadre italiane che giocheranno al mercoledì.

Summary: Martedì 14 settembre in Svezia scenderà in campo la Juventus che affronterà il Malmo, in un incontro del Gruppo H della Champions League 2021-2022. Il 14 settembre giocherà anche l'Atalanta, che disputerà la Champions per il terzo anno consecutivo. I nerazzurri sfideranno il Villarreal, in un match valido per il Gruppo F. Mercoledì 15 settembre sono in programma due incontri che fanno sognare. A San Siro è in programma Inter-Real Madrid (Gruppo D), mentre ad Anfield Road il Liverpool ospita il Milan (partita del Gruppo B).

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Summarize: Ellen DeGeneres Struts Her Stuff for Richie Rich Email This Fans expecting to see Fans expecting to see Pamela Anderson strut her stuff during Richie Rich's runway show at New York Fashion Week got an even bigger surprise when a spiky-haired Ellen DeGeneres walked the runway during the show's finale. Rich, who is known for his notoriously energetic and outrageous shows, outfitted the comedian in a silver suit, tiny hat and lace-up ankle sneakers. DeGeneres' wife, actress Portia de Rossi, cheered her on from the front row. There was some seating confusion at Lincoln Center, the new home for Mercedes-Benz Fashion Week, which delayed the show.Rich then opened the show with a ballet display followed by Tinsley Mortimer, who kicked off the clothing portion of the evening in a pink party frock. And then, the sex slaves arrived.According to NY Magazine, "For about ten minutes, men and women in skimpy clothes accessorized with chains and leather -- including 'RuPaul's Drag Race' standout Jujubee -- trotted down the runway." Check Out Our Partner Ellen's Video of the Day and Much More Add a location to your Tweets When you tweet with a location, Twitter stores that location. You can switch location on/off before each Tweet and always have the option to delete your location history. Learn more Portia de Rossi Is Now Portia DeGeneres Email This Portia de Rossi has officially taken wife The couple was married in August 2008. The 37-year-old Australian-born actress asked for the name change last month. Portia de Rossi has officially taken wife Ellen DeGeneres'last name. A Los Angeles Superior Court commissioner granted De Rossi's request to take the last name of her partner during a closed hearing Thursday. The television star will now legally be known as Portia Lee James DeGeneres.The couple was married in August 2008. The 37-year-old Australian-born actress asked for the name change last month. http://xml.channel.aol.com/xmlpublisher/fetch.v2.xml?option=expand_relative_urls&dataUrlNodes=uiConfig,feedConfig,entry&id=691977&pid=691976&uts=1273167996 http://www.popeater.com/mm_track/popeater/music/?s_channel=us.musicpop&s_account=aolpopeater,aolsvc&omni=1&ke=1 http://cdn.channel.aol.com/cs_feed_v1_6/csfeedwrapper.swf PopScene: Week's Hottest Pics Gabourey Sidibe attends The American Cancer Society's Choose You luncheon on May 5th in New York City. Amy Sussman, Getty Images Amy Sussman, Getty Images PopScene: Weeks Hottest Pics Neither woman attended the hearing. They married during the five-month window in which gay marriage was legal in California.Portia DeGeneres is well-known for her roles on several television series, including 'Ally McBeal,' 'Arrested Development' and 'Better Off Ted.'

Summary: Portia de Rossi is no more. The actress and wife of Ellen DeGeneres has officially changed her name to Portia Lee James DeGeneres, PopEater reports. "I just got some amazing news. The court has granted Portia's name change. She's now officially Portia Winfrey," DeGeneres joked via Twitter yesterday. Speaking of Ellen, if you missed her Fashion Week appearance, click here to see what she wore.

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Summarize: (The same scene. All the doors are standing open. The lamp is still burning on the table. It is dark outside, except for a faint glimmer of light seen through the windows at the back. MRS. ALVING, with a shawl over her head, is standing in the conservatory, looking out. REGINA, also wrapped in a shawl, is standing a little behind her.) Mrs. Alving. Everything bured--down to the ground. Regina. It is burning still in the basement. Mrs. Alving. I can't think why Oswald doesn't come back. There is no chance of saving anything. Regina. Shall I go and take his hat to him? Mrs. Alving. Hasn't he even got his hat? Regina (pointing to the hall). No, there it is, hanging up. Mrs. Alving. Never mind. He is sure to come back soon. I will go and see what he is doing. (Goes out by the garden door. MANDERS comes in from the hall.) Manders. Isn't Mrs. Alving here? Regina. She has just this moment gone down into the garden. Manders. I have never spent such a terrible night in my life. Regina. Isn't it a shocking misfortune, sir! Manders. Oh, don't speak about it. I scarcely dare to think about it. Regina. But how can it have happened? Manders. Don't ask me, Miss Engstrand! How should I know? Are you going to suggest too--? Isn't it enough that your father--? Regina. What has he done? Manders. He has nearly driven me crazy. Engstrand (coming in from the hall). Mr. Manders--! Manders (turning round with a start). Have you ever followed me here! Engstrand. Yes, God help us all--! Great heavens! What a dreadful thing, your reverence! Manders (walking up and down). Oh dear, oh dear! Regina. What do you mean? Engstrand. Our little prayer-meeting was the cause of it all, don't you see? (Aside, to REGINA.) Now we've got the old fool, my girl. (Aloud.) And to think it is my fault that Mr. Manders should be the cause of such a thing! Manders. I assure you, Engstrand-- Engstrand. But there was no one else carrying a light there except you, sir. Manders (standing still). Yes, so you say. But I have no clear recollection of having had a light in my hand. Engstrand. But I saw quite distinctly your reverence take a candle and snuff it with your fingers and throw away the burning bit of wick among the shavings. Manders. Did you see that? Engstrand. Yes, distinctly. Manders. I can't understand it at all. It is never my habit to snuff a candle with my fingers. Engstrand. Yes, it wasn't like you to do that, sir. But, who would have thought it could be such a dangerous thing to do? Manders (walking restlessly backwards and forwards) Oh, don't ask me! Engstrand (following him about). And you hadn't insured it either, had you, sir? Manders. No, no, no; you heard me say so. Engstrand. You hadn't insured it--and then went and set light to the whole place! Good Lord, what bad luck! Manders (wiping the perspiration from his forehead). You may well say so, Engstrand. Engstrand. And that it should happen to a charitable institution that would have been of service both to the town and the country, so to speak! The newspapers won't be very kind to your reverence, I expect. Manders. No, that is just what I am thinking of. It is almost the worst part of the whole thing. The spiteful attacks and accusations--it is horrible to think of! Mrs. Alving (coming in from the garden). I can't get him away from the fire. Manders. Oh, there you are, Mrs. Alving. Mrs. Alving. You will escape having to make your inaugural address now, at all events, Mr. Manders. Manders. Oh, I would so gladly have-- Mrs. Alving (in a dull voice). It is just as well it has happened. This Orphanage would never have come to any good. Manders. Don't you think so? Mrs. Alving. Do you? Manders. But it is none the less an extraordinary piece of ill luck. Mrs. Alving. We will discuss it simply as a business matter. Are you waiting for Mr. Manders, Engstrand? Engstrand (at the hall door). Yes, I am. Mrs. Alving. Sit down then, while you are waiting. Engstrand. Thank you, I would rather stand. Mrs. Alving (to MANDERS). I suppose you are going by the boat? Manders. Yes: It goes in about an hour-- Mrs. Alving. Please take all the documents back with you. I don't want to hear another word about the matter. I have something else to think about now. Manders. Mrs. Alving-- Mrs. Alving. Later on I will send you a power of attorney to deal with it exactly as you please. Manders. I shall be most happy to undertake that; I am afraid the original intention of the bequest will have to be entirely altered now. Mrs. Alving. Of course. Meanders. Provisionally, I should suggest this way of disposing of it: Make over the Solvik property to the parish. The land is undoubtedly not without a certain value; it will always be useful for some purpose or another. And as for the interest on the remaining capital that is on deposit in the bank, possibly I might make suitable use of that in support of some undertaking that promises to be of use to the town. Mrs. Alving. Do exactly as you please. The whole thing is a matter of indifference to me now. Engstrand. You will think of my Sailors' Home, Mr. Manders? Manders. Yes, certainly, that is a suggestion. But we must consider the matter carefully. Engstrand (aside). Consider!--devil take it! Oh Lord. Manders (sighing). And unfortunately I can't tell how much longer I may have anything to do with the matter--whether public opinion may not force me to retire from it altogether. That depends entirely upon the result of the inquiry into the cause of the fire. Mrs. Alving. What do you say? Manders. And one cannot in any way reckon upon the result beforehand. Engstrand (going nearer to him). Yes, indeed one can; because here stand I, Jacob Engstrand. Manders. Quite so, but-- Engstrand (lowering his voice). And Jacob Engstrand isn't the man to desert a worthy benefactor in the hour of need, as the saying is. Manders. Yes, but, my dear fellow-how--? Engstrand. You might say Jacob Engstrand is an angel of salvation, so to speak, your reverence. Manders. No, no, I couldn't possibly accept that. Engstrand. That's how it will be, all the same. I know someone who has taken the blame for someone else on his shoulders before now, I do. Manders. Jacob! (Grasps his hand.) You are one in a thousand! You shall have assistance in the matter of your Sailors' Home, you may rely upon that. (ENGSTRAND tries to thank him, but is prevented by emotion.) Manders (hanging his wallet over his shoulder). Now we must be off. We will travel together. Engstrand (by the dining-room door, says aside to REGINA). Come with me, you hussy! You shall be as cosy as the yolk in an egg! Regina (tossing her head). Merci! (She goes out into the hall and brings back MANDERS' luggage.) Manders. Good-bye, Mrs. Alving! And may the spirit of order and of what is lawful speedily enter into this house. Mrs. Alving. Goodbye, Mr. Manders. (She goes into the conservatory, as she sees OSWALD coming in by the garden door.) Engstrand (as he and REGINA are helping MANDERS on with his coat). Goodbye, my child. And if anything should happen to you, you know where Jacob Engstrand is to be found. (Lowering his voice.) Little Harbour Street, ahem--! (To MRS. ALVING and OSWALD.) And my house for poor seafaring men shall be called the "Alving Home," it shall. And, if I can carry out my own ideas about it, I shall make bold to hope that it may be worthy of bearing the late Mr. Alving's name. Manders (at the door). Ahem--ahem! Come along, my dear Engstrand. Goodbye--goodbye! (He and ENGSTRAND go out by the hall door.) Oswald (going to the table). What house was he speaking about? Mrs. Alving. I believe it is some sort of a Home that he and Mr. Manders want to start. Oswald. It will be burned up just like this one. Mrs. Alving. What makes you think that? Oswald. Everything will be burned up; nothing will be left that is in memory of my father. Here am I being burned up, too. (REGINA looks at him in alarm.) Mrs. Alving. Oswald! You should not have stayed so long over there, my poor boy. Oswald (sitting down at the table). I almost believe you are right. Mrs. Alving. Let me dry your face, Oswald; you are all wet. (Wipes his face with her handkerchief.) Oswald (looking straight before him, with no expression in his eyes). Thank you, mother. Mrs. Alving. And aren't you tired, Oswald? Don't you want to go to sleep? Oswald (uneasily). No, no--not to sleep! I never sleep; I only pretend to. (Gloomily.) That will come soon enough. Mrs. Alving (looking at him anxiously). Anyhow you are really ill, my darling boy. Regina (intently). Is Mr. Alving ill? Oswald (impatiently). And do shut all the doors! This deadly fear-- Mrs. Alving. Shut the doors, Regina. (REGINA shuts the doors and remains standing by the hall door. MRS. ALVING takes off her shawl; REGINA does the same. MRS. ALVING draws up a chair near to OSWALD'S and sits down beside him.) That's it! Now I will sit beside you-- Oswald. Yes, do. And Regina must stay in here too; Regina must always be near me. You must give me a helping hand, you know, Regina. Won't you do that? Regina. I don't understand-- Mrs. Alving. A helping hand? Oswald. Yes--when there is need for it. Mrs. Alving. Oswald, have you not your mother to give you a helping hand? Oswald. You? (Smiles.) No, mother, you will never give me the kind of helping hand I mean. (Laughs grimly.) You! Ha, ha! (Looks gravely at her.) After all, you have the best right. (Impetuously.) Why don't you call me by my Christian name, Regina? Why don't you say Oswald? Regina (in a low voice). I did not think Mrs. Alving would like it. Mrs. Alving. It will not be long before you have the right to do it. Sit down here now beside us, too. (REGINA sits down quietly and hesitatingly at the other side of the table.) And now, my poor tortured boy, I am going to take the burden off your mind-- Oswald. You, mother? Mrs. Alving. --all that you call remorse and regret and self-reproach. Oswald. And you think you can do that? Mrs. Alving. Yes, now I can, Oswald. A little while ago you were talking about the joy of life, and what you said seemed to shed a new light upon everything in my whole life. Oswald (shaking his head). I don't in the least understand what you mean. Mrs. Alving. You should have known your father in his young days in the army. He was full of the joy of life, I can tell you. Oswald. Yes, I know. Mrs. Alving. It gave me a holiday feeling only to look at him, full of irrepressible energy and exuberant spirits. Oswald. What then? Mrs. Alving, Well, then this boy, full of the joy of life--for he was just like a boy, then--had to make his home in a second-rate town which had none of the joy of life to offer him, but only dissipations. He had to come out here and live an aimless life; he had only an official post. He had no work worth devoting his whole mind to; he had nothing more than official routine to attend to. He had not a single companion capable of appreciating what the joy of life meant; nothing but idlers and tipplers... Oswald. Mother--! Mrs. Alving. And so the inevitable happened! Oswald. What was the inevitable? Mrs. Alving. You said yourself this evening what would happen in your case if you stayed at home. Oswald. Do you mean by that, that father--? Mrs. Alving. Your poor father never found any outlet for the overmastering joy of life that was in him. And I brought no holiday spirit into his home, either. Oswald. You didn't, either? Mrs. Alving. I had been taught about duty, and the sort of thing that I believed in so long here. Everything seemed to turn upon duty--my duty, or his duty--and I am afraid I made your poor father's home unbearable to him, Oswald. Oswald. Why didn't you ever say anything about it to me in your letters? Mrs. Alving. I never looked at it as a thing I could speak of to you, who were his son. Oswald. What way did you look at it, then? Mrs. Alving. I only saw the one fact, that your father was a lost man before ever you were born. Oswald (in a choking voice). Ah--! (He gets up and goes to the window.) Mrs. Alving. And then I had the one thought in my mind, day and night, that Regina in fact had as good a right in this house--as my own boy had. Oswald (turns round suddenly), Regina--? Regina (gets up and asks in choking tones). I--? Mrs. Alving. Yes, now you both know it. Oswald. Regina! Regina (to herself). So mother was one of that sort too. Mrs. Alving. Your mother had many good qualities, Regina. Regina. Yes, but she was one of that sort too, all the same. I have even thought so myself, sometimes, but--. Then, if you please, Mrs. Alving, may I have permission to leave at once? Mrs. Alving. Do you really wish to, Regina? Regina. Yes, indeed, I certainly wish to. Mrs. Alving. Of course you shall do as you like, but-- Oswald (going up to REGINA). Leave now? This is your home. Regina. Merci, Mr. Alving--oh, of course I may say Oswald now, but that is not the way I thought it would become allowable. Mrs. Alving. Regina, I have not been open with you-- Regina. No, I can't say you have! If I had known Oswald was ill-- And now that there can never be anything serious between us--. No, I really can't stay here in the country and wear myself out looking after invalids. Oswald. Not even for the sake of one who has so near a claim on you? Regina. No, indeed I can't. A poor girl must make some use of her youth, otherwise she may easily land herself out in the cold before she knows where she is. And I have got the joy of life in me too, Mrs. Alving! Mrs. Alving. Yes, unfortunately; but don't throw yourself away, Regina. Regina. Oh, what's going to happen will happen. If Oswald takes after his father, it is just as likely I take after my mother, I expect.--May I ask, Mrs. Alving, whether Mr. Manders knows this about me? Mrs. Alving. Mr. Manders knows everything. Regina (putting on her shawl). Oh, well then, the best thing I can do is to get away by the boat as soon as I can. Mr. Manders is such a nice gentleman to deal with; and it certainly seems to me that I have just as much right to some of that money as he--as that horrid carpenter. Mrs. Alving. You are quite welcome to it, Regina. Regina (looking at her fixedly). You might as well have brought me up like a gentleman's daughter; it would have been more suitable. (Tosses her head.) Oh, well--never mind! (With a bitter glance at the unopened bottle.) I daresay someday I shall be drinking champagne with gentlefolk, after all. Mrs. Alving. If ever you need a home, Regina, come to me. Regina. No, thank you, Mrs. Alving. Mr. Manders takes an interest in me, I know. And if things should go very badly with me, I know one house at any rate where I shall feel at home. Mrs. Alving. Where is that? Regina. In the "Alving Home." Mrs. Alving. Regina--I can see quite well--you are going to your ruin! Regina. Pooh!--goodbye. (She bows to them and goes out through the hall.) Oswald (standing by the window and looking out). Has she gone? Mrs. Alving. Yes. Oswald (muttering to himself). I think it's all wrong. Mrs. Alving (going up to him from behind and putting her hands on his shoulders). Oswald, my dear boy--has it been a great shock to you? Oswald (turning his face towards her). All this about father, do you mean? Mrs. Alving. Yes, about your unhappy father. I am so afraid it may have been too much for you. Oswald. What makes you think that? Naturally it has taken me entirely by surprise; but, after all, I don't know that it matters much to me. Mrs. Alving (drawing back her hands). Doesn't matter!--that your father's life was such a terrible failure! Oswald. Of course I can feel sympathy for him, just as I would for anyone else, but-- Mrs. Alving. No more than that! For your own father! Oswald (impatiently). Father--father! I never knew anything of my father. I don't remember anything else about him except that he once made me sick. Mrs. Alving. It is dreadful to think of!--But surely a child should feel some affection for his father, whatever happens? Oswald. When the child has nothing to thank his father for? When he has never known him? Do you really cling to that antiquated superstition--you, who are so broad-minded in other things? Mrs. Alving. You call it nothing but a superstition! Oswald. Yes, and you can see that for yourself quite well, mother. It is one of those beliefs that are put into circulation in the world, and-- Mrs. Alving. Ghosts of beliefs! Oswald (walking across the room). Yes, you might call them ghosts. Mrs. Alving (with an outburst of feeling). Oswald! then you don't love me either! Oswald. You I know, at any rate-- Mrs. Alving. You know me, yes; but is that all? Oswald. And I know how fond you are of me, and I ought to be grateful to you for that. Besides, you can be so tremendously useful to me, now that I am ill. Mrs. Alving. Yes, can't I, Oswald! I could almost bless your illness, as it has driven you home to me. For I see quite well that you are not my very own yet; you must be won. Oswald (impatiently). Yes, yes, yes; all that is just a way of talking. You must remember I am a sick man, mother. I can't concern myself much with anyone else; I have enough to do, thinking about myself. Mrs. Alving (gently). I will be very good and patient. Oswald. And cheerful too, mother! Mrs. Alving. Yes, my dear boy, you are quite right. (Goes up to him.) Now have I taken away all your remorse and self-reproach? Oswald. Yes, you have done that. But who will take away the fear? Mrs. Alving. The fear? Oswald (crossing the room). Regina would have done it for one kind word. Mrs. Alving. I don't understand you. What fear do you mean--and what has Regina to do with it? Oswald. Is it very late, mother? Mrs. Alving. It is early morning. (Looks out through the conservatory windows.) The dawn is breaking already on the heights. And the sky is clear, Oswald. In a little while you will see the sun. Oswald. I am glad of that. After all, there may be many things yet for me to be glad of and to live for-- Mrs. Alving. I should hope so! Oswald. Even if I am not able to work-- Mrs. Alving. You will soon find you are able to work again now, my dear boy. You have no longer all those painful depressing thoughts to brood over. Oswald. No, it is a good thing that you have been able to rid me of those fancies; if only, now, I could overcome this one thing-- (Sits down on the couch.) Let us have a little chat, mother. Mrs. Alving. Yes, let us. (Pushes an armchair near to the couch and sits down beside him.) Oswald. The sun is rising--and you know all about it; so I don't feel the fear any longer. Mrs. Alving. I know all about what? Oswald (without listening to her). Mother, isn't it the case that you said this evening there was nothing in the world you would not do for me if I asked you? Mrs. Alving. Yes, certainly I said so. Oswald. And will you be as good as your word, mother? Mrs. Alving. You may rely upon that, my own dear boy. I have nothing else to live for, but you. Oswald. Yes, yes; well, listen to me, mother, You are very strong-minded, I know. I want you to sit quite quiet when you hear what I am going to tell you. Mrs. Alving. But what is this dreadful thing--? Oswald. You mustn't scream. Do you hear? Will you promise me that? We are going to sit and talk it over quite quietly. Will you promise me that, mother? Mrs. Alving. Yes, yes, I promise--only tell me what it is. Oswald. Well, then, you must know that this fatigue of mine--and my mot being able to think about my work--all that is not really the illness itself-- Mrs. Alving. What is the illness itself? Oswald. What I am suffering from is hereditary; it--(touches his forehead, and speaks very quietly)--it lies here. Mrs. Alving (almost speechless). Oswald! No--no! Oswald. Don't scream; I can't stand it. Yes, I tell you, it lies here, waiting. And any time, any moment, it may break out. Mrs. Alving. How horrible--! Oswald. Do keep quiet. That is the state I am in-- Mrs. Alving (springing up). It isn't true, Oswald! It is impossible! It can't be that! Oswald. I had one attack while I was abroad. It passed off quickly. But when I learned the condition I had been in, then this dreadful haunting fear took possession of me. Mrs. Alving. That was the fear, then-- Oswald. Yes, it is so indescribably horrible, you know If only it had been an ordinary mortal disease--. I am not so much afraid of dying; though, of course, I should like to live as long as I can. Mrs. Alving. Yes, yes, Oswald, you must! Oswald. But this is so appallingly horrible. To become like a helpless child again--to have to be fed, to have to be--. Oh, it's unspeakable! Mrs. Alving. My child has his mother to tend him. Oswald (jumping up). No, never; that is just what I won't endure! I dare not think what it would mean to linger on like that for years--to get old and grey like that. And you might die before I did. (Sits down in MRS. ALVING'S chair.) Because it doesn't necessarily have a fatal end quickly, the doctor said; he called it a kind of softening of the brain--or something of that sort. (Smiles mournfully.) I think that expression sounds so nice. It always makes me think of cherry-coloured velvet curtains--something that is soft to stroke. Mrs. Alving (with a scream). Oswald! Oswald (jumps up and walks about the room). And now you have taken Regina from me! If I had only had her, she would have given me a helping hand, I know. Mrs. Alving (going up to him). What do you mean, my darling boy? Is there any help in the world I would not be willing to give you? Oswald. When I had recovered from the attack I had abroad, the doctor told me that when it recurred--and it will recur--there would be no more hope. Mrs. Alving. And he was heartless enough to-- Oswald. I insisted on knowing. I told him I had arrangements to make--. (Smiles cunningly.) And so I had. (Takes a small box from his inner breast-pocket.) Mother, do you see this? Mrs. Alving. What is it? Oswald. Morphia powders. Mrs. Alving (looking at him in terror). Oswald--my boy! Oswald. I have twelve of them saved up-- Mrs. Alving (snatching at it). Give me the box, Oswald! Oswald. Not yet, mother. (Puts it lack in his pocket.) Mrs. Alving. I shall never get over this! Oswald, You must. If I had had Regina here now, I would have told her quietly how things stand with me--and asked her to give me this last helping hand. She would have helped me, I am certain. Mrs. Alving. Never! Oswald. If this horrible thing had come upon me and she had seen me lying helpless, like a baby, past help, past saving, past hope--with no chance of recovering-- Mrs. Alving. Never in the world would Regina have done it. Oswald. Regina would have done it. Regina was so splendidly light-hearted. And she would very soon have tired of looking after an invalid like me. Mrs. Alving. Then thank heaven Regina is not here! Oswald. Well, now you have got to give me that helping hand, mother. Mrs. Alving (with a loud scream). I! Oswald. Who has a better right than you? Mrs. Alving. I! Your mother! Oswald. Just for that reason. Mrs. Alving. I, who gave you your life! Oswald, I never asked you for life. And what kind of a life was it that you gave me? I don't want it! You shall take it back! Mrs. Alving. Help! Help! (Runs into the hall.) Oswald (following her). Don't leave me! Where are you going? Mrs. Alving (in the hall). To fetch the doctor to you, Oswald! Let me out! Oswald (going into the hall). You shan't go out. And no one shall come in. (Turns the key in the lock.) Mrs. Alving (coming in again). Oswald! Oswald!--my child! Oswald (following her). Have you a mother's heart--and can bear to see me suffering this unspeakable terror? Mrs. Alving (controlling herself, after a moment's silence). There is my hand on it. Oswald. Will you--? Mrs. Alving. If it becomes necessary. But it shan't become necessary: No, no--it is impossible it should! Oswald. Let us hope so. And let us live together as long as we can. Thank you, mother. (He sits down in the armchair, which MRS. ALVING had moved beside the couch. Day is breaking; the lamp is still burning on the table.) Mrs. Alving (coming cautiously nearer). Do you feel calmer now? Oswald. Yes. Mrs. Alving (bending over him). It has only been a dreadful fancy of yours, Oswald. Nothing but fancy. All this upset has been bad for you. But now you will get some rest, at home with your own mother, my darling boy. You shall have everything you want, just as you did when you were a little child.--There, now. The attack is over. You see how easily it passed off! I knew it would.--And look, Oswald, what a lovely day we are going to have? Brilliant sunshine. Now you will be able to see your home properly. (She goes to the table and puts out the lamp. It is sunrise. The glaciers and peaks in the distance are seen bathed in bright morning fight.) Oswald (who has been sitting motionless in the armchair, with his back to the scene outside, suddenly says:) Mother, give me the sun. Mrs. Alving (standing at the table, and looking at him in amazement). What do you say? Oswald (repeats in a dull, toneless voice). The sun--the sun. Mrs. Alving (going up to him). Oswald, what is the matter with you? (OSWALD seems to shrink up in the chair; all his muscles relax; his face loses its expression, and his eyes stare stupidly. MRS. ALVING is trembling with terror.) What is it! (Screams.) Oswald! What is the matter with you! (Throws herself on her knees beside him and shakes him.) Oswald! Oswald! Look at me! Don't you know me! Oswald (in an expressionless voice, as before). The sun--the sun. Mrs. Alving (jumps up despairingly, beats her head with her hands, and screams). I can't bear it! (Whispers as though paralysed with fear.) I can't bear it... I Never! (Suddenly.) Where has he got it? (Passes her hand quickly over his coat.) Here! (Draws back a little spay and cries:) No, no, no!--Yes!--no, no! (She stands a few steps from him, her hands thrust into her hair, and stares at him in speechless terror.) Oswald (sitting motionless, as before). The sun--the sun.

Summary: We're back in the garden room. All the doors stand open and the lamp is still on the table. There's a faint, fiery glow coming through the windows. Mrs. Alving and Regina are looking at the remains of the Orphanage. Mrs. Alving goes out to look for Oswald, and just then Pastor Manders comes in, in a paranoid tizzy. Engstrand comes in hot on Manders' heels, implying that the prayer service is what caused the fire - and therefore Manders is responsible. In fact, Manders is the person who basically lit a match to the whole place. The Pastor is sweating. Engstrand kindly reminds him that the papers won't handle him too gently. Mrs. Alving comes in without Oswald - he's still at the fire. She seems relieved that the orphanage burned down. It wouldn't have done anyone any good. Mrs. Alving asks if the Pastor will take all the papers with him? She doesn't want to hear anymore about it. He can decide what to do with the money that would have kept up the orphanage. Engstrand pipes up: think of the Sailor's Home. Pastor Manders worries that he won't be in charge of anything much longer, if it gets out that he had a hand in the fire. But Engstrand has a solution for that. He will take the blame on himself, just as he did with Johanna. Pastor Manders, after a moment of hesitation, accepts the offer. They will travel together. Engstrand tries to get Regina to come, too, but she haughtily refuses. It's no matter. Engstrand will name his brothel "Chamberlain Alving's Home" - and will guarantee that it's a fitting memorial to Oswald's late father. Oswald has come in. He's disheveled and feverish. Mrs. Alving recognizes that he is seriously ill. This is news to Regina. Mrs. Alving has some news, too. She sits both youngsters down to talk to them. Once she's finished, she thinks Oswald's mind will be relieved. Inspired by Oswald's explanation of the joy of life, Mrs. Alving sees her husband in a different light. She describes him as an innocent, high-spirited man who was destroyed by living in a backward town. She acknowledges her own role in contributing to his ruin, wedded to the idea of duty as she was. Then she comes out with two big wallops: Oswald's father was sick too. And he was also the father of Regina. Regina doesn't waste any time. She wants out. She's not going to stay here and take care of sick people. She's got to get on that steamer as fast as she can, whether it means pursuing something with Pastor Manders, or working at the Sailors' Home. So Mrs. Alving is left alone with her son. She checks in: is he terribly shocked to learn that his father was so miserable? Oswald doesn't care. He doesn't feel any filial obligation - to his father or to her. But Oswald does need her to relieve him of the dread. Now it's his turn to sit her down. He has a request. Oswald explains that he will suffer an attack that softens his brain for good, making him a vegetable. It's the one thing he can't stand. He takes a little box from his pocket: morphine. This is why he wanted Regina here. She would have gotten sick of looking after an invalid, and would have used the morphine to put him to rest. But now she's gone, so he turns this request over to this mother. Mrs. Alving totally flips her lid. She gave him life; she can't think of taking it back. She tries to run away but he locks her in. He begs her. She agrees. But thinks it will never be necessary. All he needed was that promise. He can relax now. Day is breaking. Mrs. Alving gives her boy a speech of comfort, and puts out the lamp. Suddenly Oswald says, "Mother, give me the sun". Mrs. Alving is confused. He repeats, over and over, "The sun." His muscles have relaxed, his eyes are glassy. It's happened. Will she do it? Ibsen leaves us hanging.

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Summarize: Introduction Programs under the Agricultural Trade Development and Assistance Act of 1954, referred to as P.L. 480, historically have been the main vehicles of U.S. international food aid. Title II of P.L. 480, administered by the U.S. Agency for International Development (USAID), is the largest U.S. international food aid program. Title II provides humanitarian donations of U.S. agricultural commodities to respond to emergency food needs or to be used in development projects. Funds available to Title II of P.L. 480 from both regular and supplemental appropriations have averaged $2 billion annually since enactment of the 2002 farm bill (2002-2007). Over time, however, other, smaller food aid programs, administered by the U.S. Department of Agriculture (USDA), have been authorized by Congress—Food for Progress in 1985, the Bill Emerson Humanitarian Trust in 1998, and the McGovern-Dole International School Feeding and Child Nutrition Program in 2003. For USDA-administered programs, the annual average funding over the 2002 farm bill period has been $356 million. Most of the farm bill food aid debate focused on P.L. 480 Title II commodity donations. P.L. 480 Food for Peace The 2008 farm bill changes the name of the underlying P.L. 480 legislation from Agricultural Trade Development and Assistance Act to Food for Peace Act and deletes export market development as one of the objectives of the programs. This modification of objectives is intended to reflect the approach—de-emphasis of export market development for U.S. agricultural commodities and more emphasis on promoting food security—taken in operating the program in recent years. Issues addressed included policy objectives, funding levels, availability of food aid resources for non-emergency (development) projects, and using local/regional commodity purchases to respond more efficiently and effectively to food crises, among others. P.L. 480 Title II The 2008 farm bill amends the purposes of the Title II program to clarify that food deficits to be addressed include those resulting from manmade and natural disasters. Recognition that food deficits can be manmade brings the U.S. definition of disaster more in line with the definition used by United Nations agencies such as the World Food Program. The new farm bill adds promotion of food security and support of sound environmental practices to the objectives of Title II commodity donations, and requests that the administrator of USAID brief relevant congressional committees before responding to disasters that result mostly from poorly devised or discriminatory governmental policies. The new farm law also includes a Sense of Congress declaration that in international negotiations the President shall seek commitments of higher levels of food aid from other donors; ensure that food aid implementing organizations be eligible to receive food aid resources based on their own needs assessments; and ensure that options for providing food aid shall not be subject to limitation, on condition that the provision of the food aid is based on needs assessments, avoids disincentive effects to local production and marketing, and is provided in a manner that avoids disincentives to local production and marketing and with minimal potential to disrupt commercial markets. This declaration reflects a concern in Congress with the issue of how Doha Round multilateral trade negotiations on food aid could affect U.S. food aid policy and programs. Title II Funding The 2008 farm bill extends authorization of P.L. 480 programs through FY2012 and sets the annual authorization level for Title II at $2.5 billion. This level of funding would be $500 million more annually than has been provided for Title II under the 2002 farm bill each fiscal year through a combination of regular and supplemental appropriations. But as this authorization is discretionary, it will be up to appropriations bills to set the amount of annual Title II funding. With a view to providing more cash assistance to organizations—private voluntary organizations (PVOs), cooperatives, intergovernmental organizations—that implement Title II food aid programs, the farm bill increases the range of funds available for administrative and distributional expenses to between 7.5% and 13% of funds available each year to the program (appropriations, carry-over, and reimbursements). (The range of available Title II funds for these purposes under the 2002 farm bill was 5% to 10%). Additionally, the 2008 farm bill provides $4.5 million for FY2009-FY2011 to study and improve food aid quality (e.g., eliminate spoilage). Minimum Volume of Commodities The new farm bill extends the requirement that the Administrator of USAID make a minimum level of 2.5 million metric tons (MMT) of commodities available each fiscal year through 2012 for distribution via Title II. Of that minimum, not less than 1.875 MMT is to be made available for non-emergency (development) projects. This mandated volume of commodities for development food aid has rarely been met. The requirement can be waived, and frequently has been, if the Administrator of USAID determines that such quantities of commodities cannot be used effectively or in order to meet an emergency food security crisis. "Safe Box" for Non-Emergency (Development) Food Aid In recent years, more Title II funds have been allocated to emergency relief than to non-emergency (development) projects. In FY2007, for example, USAID allocated $866.3 million to emergency food aid and $348.4 million to development food aid. The Administration has expressed concerns about the adequacy of food aid resources to respond to emergencies, while food aid organizations indicate concerns about the availability of food aid for use in development projects. The 2008 farm bill provides for a "safe box" for funding of non-emergency, development assistance projects under Title II. The argument in favor of the safe box is that it would provide assurances to the implementing organizations (PVOs, coops, intergovernmental organizations) of a given level of funds with which to carry out development projects. The Administration's principal objection to the safe box is that it will deprive the USAID Administrator of the flexibility needed to respond to emergency food needs. The new farm bill provides a safe box funding level beginning at $375 million in FY2009, ending in FY2012 at $450 million. The mandated funding level can be waived if three criteria are satisfied: (1) the President determines that an extraordinary food emergency exists; (2) resources from the Bill Emerson Humanitarian Trust (see below) have been exhausted, and (3) the President has submitted a request for additional appropriations to Congress equal to the reduction in safe box and Emerson Trust levels. Pilot Program for Local/Regional Cash Purchase The 2008 farm bill includes a scaled-down version of the Administration's only international food aid proposal for legislative authority to use up to $300 million of appropriated P.L. 480 Title II funds for local or regional purchase and distribution of food to assist people threatened by a food security crisis. The farm bill provides that the pilot project be conducted by the Secretary of Agriculture with a total of $60 million in mandatory funding (not P.L. 480 appropriations) during FY2009 and FY2012. The pilot project would entail a study of experiences with local/regional purchase followed by field-based projects that would purchase food commodities locally or regionally. The field-based projects would be funded with grants to PVOs, cooperatives, and intergovernmental organizations, such as the World Food Program. All of the field-based projects would be evaluated by an independent third party beginning in 2011; the Secretary of Agriculture would submit a report to Congress on the pilot project four years after the enactment of the bill. Food Aid Consultative Group The new farm bill extends to 2012 the authority for the Food Aid Consultative Group (FACG), which advises the USAID Administrator on food aid policy and regulations. It requires that a representative of the maritime transportation sector be included in the Group. Micronutrient Fortification Programs The 2008 farm bill reauthorizes the Micronutrient Fortification Program in which grains and other food aid commodities may be fortified with such micronutrients as vitamin A, iodine, iron, and folic acid. It adds new legislative authority to assess and apply technologies and systems to improve food aid. The farm bill also eliminates limitations on the number of countries in which this program can be implemented. Monitoring Non-Emergency (Development) Projects The farm bill authorizes the use of up to $22 million annually to be used for the monitoring and assessment of non-emergency (development) food aid programs. No more than $8 million of these funds may be used for the Famine Early Warning System Network (FEWS-NET), but only if at least $8 million is provided for FEWS-NET from accounts appropriated under the Foreign Assistance Act of 1961. Up to $2.5 million of the funds can be used to upgrade the information technology systems used to monitor and assess the effectiveness of food aid programs. This provision is a response to criticism that monitoring of such programs by USAID has been inadequate due to such factors as limited staff, competitive priorities, and legal restrictions. The USAID Administrator can use these funds to employ contractors as non-emergency food aid monitors. Shelf-Stable Foods and Prepositioning The farm bill increases funding available annually (from Title II funds) from $3 million to $8 million for stockpiling and rapid transportation, delivery, and distribution of shelf-stable, prepackaged foods. Shelf-stable foods are developed under a cost-sharing arrangement that gives preference to organizations that provide additional funds for developing these products. The new bill also reauthorizes prepositioning of commodities overseas and increases the funding for prepositioning to $10 million annually from $2 million annually. USAID maintains that prepositioning (currently at two sites, New Orleans and Dubai, United Arab Emirates) enables it to respond more rapidly to emergency food needs. Critics say, however, that the cost effectiveness of prepositioning has not been evaluated. Farmer-to-Farmer Program The 2008 farm bill reauthorizes the Farmer-to-Farmer program of voluntary technical assistance in agriculture funded with a portion of P.L. 480 funds. The bill provides an annual floor level of funding for the program of $10 million and extends it through 2012. It also increases the authorization of annual appropriations for specific regions (sub-Saharan Africa and the Caribbean Basin) from $10 million to $15 million. P.L. 480 Title I This title of P.L. 480 authorizes provision of long-term, low interest loans to developing countries for the purchase of U.S. agricultural commodities. The new farm bill makes some changes in the program, which has not received an appropriation since 2006 to reflect a food security rather than a market development emphasis of U.S. food aid. Thus the bill strikes references in Title I to recipient countries becoming commercial markets for U.S. agricultural products and the requirement that organizations seeking funding under this title prepare and submit agricultural market development plans. The bill gives Title I of P.L. 480, previously referred to as Trade and Development Assistance, a new name, Economic Assistance and Food Security. Food for Progress The Food for Progress Program (FFP) provides commodities to developing countries that have made commitments to expand free enterprise in their agricultural economies. The 2002 farm bill required that a minimum of 400,000 MT be provided under the FFP program. However, not more than $40 million of Commodity Credit Corporation (CCC) funds may be used to finance transportation of the commodities. This amount effectively caps the volume of commodities that can be shipped under the program. (In FY2007, for example, 342,000 MT were shipped under FFP.) The 2008 farm bill conference agreement extends the program without change through 2012, with the requirement that the Secretary of Agriculture establish a project in Malawi under the FFP. McGovern-Dole Food for Education and International Child Nutrition The McGovern-Dole food aid program provides commodities and financial and technical assistance to carry out preschool and school food for education programs in developing countries. The program is widely viewed as a model food aid program because of the flexibility with which it provides program components. By executive order of the President, the McGovern-Dole program is administered by the Secretary of Agriculture. The main issues in congressional debate about the future of the program were the manner and level of funding. Some argued for changing the funding from discretionary (as in current law) to mandatory and for ramping up funding to $300 million by 2012. Others proposed maintaining discretionary funding for the program with a substantial increase. The 2008 farm bill reauthorizes the program through 2012 and establishes the U.S. Department of Agriculture as the permanent home for the program. The new law maintains funding for McGovern-Dole on a discretionary basis without an increase, but does authorize $84 million in mandatory money for the program in FY2009, to be available until expended. Bill Emerson Humanitarian Trust The Bill Emerson Humanitarian Trust (BEHT) is a reserve of commodities and cash that is used to meet unanticipated food aid needs or to meet food aid commitments when U.S. domestic supplies are short. The BEHT can hold up to 4 MMT of grains (wheat, rice, corn, sorghum) in any combination, but the only commodity ever held has been wheat. USDA has recently sold the remaining wheat in the trust (about 915,000 MT) so that currently the BEHT holds only cash—about $294 million. The cash would be used, according to USDA, when USAID determines it is needed for emergency food aid. The 2008 farm bill reauthorizes the BEHT through FY2012. It removes the 4 million ton cap on commodities that can be held in the trust, and allows the Secretary to invest the funds from the trust in low-risk, short-term securities or instruments so as to maximize its value. The new law replaces the word "replenish" with the word "reimburse" throughout the language to reinforce the notion that resources of the BEHT may be held in cash as well as commodities.

Summary: Provision of U.S. agricultural commodities for emergency relief and economic development is the United States' major response to food security problems in developing countries. Title III in the omnibus farm bill enacted in June 2008, the Food, Conservation, and Energy Act of 2008 (P.L. 110-246, H.R. 6124), reauthorizes and makes a number of changes in U.S. international food aid programs. Farm bill debate over U.S. food aid programs focused generally on how to make delivery of food aid more efficient and more effective. While most of the debate focused on P.L. 480 Title II, the largest food aid program, the farm bill trade title also reauthorizes and modifies other, smaller U.S. food aid programs. One of the most contentious issues was that of using appropriated P.L. 480 funds to purchase commodities overseas, rather than U.S. commodities, to respond to emergency food needs. The Bush Administration had asked for this authority in its farm bill proposals, but many, though not all, of the private voluntary organizations and cooperatives that use U.S. commodities for development projects instead argued for a pilot project for local or regional purchases of commodities.

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Summarize: Nikki Westgarth, pictured with her son Jake Grimes, died from flu four days after giving birth to her second child Eva Rose. A 21-year-old mother-of-two died of flu four days after her baby daughter was delivered via emergency C-section. Nikki Westgarth never got to meet Eva Rose Westgarth-Burrell, who was born on February 4. Lying in a critical condition in hospital, doctors made the decision to deliver her unborn child via C-section. But four days later Miss Westgarth lost her life to the common illness. Her mother Kim Hannant is now bringing up Eva and her older brother Jake Grimes, four. The 57-year-old is now calling for all women in at-risk groups to ensure they have a yearly flu jab - an injection that could have saved her daughter. It was shortly after Christmas last year that Miss Westgarth began to feel tired and run down. But Mrs Hannant said the family just attributed it to her being pregnant. 'Then just after New Year, the whole family came down with the flu,' she said. 'I have asthma and I've had my jab for the last 10 years, so didn't suffer as much as everybody else. 'Nikki lived next door to us, and she came in and complained that she felt like she was dying. 'I thought she was joking, but she was so concerned that she went to hospital, but wasn't admitted. 'The next day she was still very concerned so went to hospital, who admitted her to maternity. 'Once the family were given the all clear from flu, we were able to visit her. She was in good spirits, but said she was in a bit of pain. However whilst I was there, she said she'd started to cough up blood. 'After helping her out of bed to go to the toilet I went to help one of the nurses with some paperwork, and when I came back I couldn't find Nikki. The 21-year-old's mother Kim Hannant, pictured with Eva Rose and Jake, is today urging all pregnant women to ensure they have the seasonal flu jab, which is available free of charge to all expectant mothers, as well as others in at risk groups including anyone over the age of 65 and people with existing health problems. The flu jab is available every year on the NHS to protect adults and some children, at risk. Flu can be an unpleasant illness. But for those who are otherwise healthy, it usually clears up on its own within a week. However, for some people the illness can be much more severe, even life-threatening. Those at risk include:. Anyone in a risk group is likely to develop serious complications, such as pneumonia. The flu vaccine is given free of charge to:. The best time to have a flu vaccine is in the autumn, from the beginning of October to early November. For those not deemed at risk, it is possible to pay to have a flu jab. Boots Pharmacies are offering the vaccination in store. Deepa Songara, Boots flu pharmacist said: 'We spend less time outside and much longer closer together at home or in indoor places. 'This 'togetherness' makes it easier to pass germs from one person to another so it is important to think ahead and try to protect yourself before the cold and flu season really kicks in. 'Busy communal places are ideal breeding environments for winter bugs and simple things like washing your hands or using alcohol based hand gel can help keep you well.' 'I went to the bathroom and found her slumped behind the door. The nurses worked quickly to get her back on to the bed and monitored her very closely.' Miss Westgarth, of Newton Aycliffe, County Durham, came round but her condition took a turn for the worse. She was treated in critical care at Darlington Memorial Hospital for two weeks. Mrs Hannant said: 'She was very agitated and kept saying to me "please mam, don't let me die". 'She was sitting up and talking and about four in the morning they said I would be fine to go home and get some sleep. 'But very quickly after arriving home I got a call that I needed to go back to the hospital as Nikki had taken a turn for the worse and was in critical care. The doctor told us that the baby was fine, but at this stage we were more concerned about Nikki.' As her condition deteriorated doctors arranged to have her transferred to a hospital in Leicester to give birth to Eva Rose with specialist support. It was while she was in critical care that Miss Westgarth turned 21. Her mother said: 'She briefly came round from life-support and was given a Caesarean section to deliver Eva Rose as she was suffering pre-eclampsia. 'She never got to see Eva Rose before she died. 'Four days later, whilst I was away from the hospital resting, I was called back. When I got there, the nurses told me that Nikki's heart had stopped, we'd lost our little girl.' Her relatives are now backing this year's national NHS campaign urging people, including pregnant women, to make sure they have a flu vaccination. Mrs Hannant added: 'If it saves even one person, and saves one family from going through what we went through then her death wasn't for nothing.'

Summary: Nikki Westgarth died four days after giving birth to baby Eva Rose. 21-year-old never got to meet her daughter after emergency C-section. The mother-of-two fell ill with flu shortly after Christmas last year. After two weeks in critical care doctors decided to deliver her unborn child. Eva Rose Westgarth-Burrell was born on February 4. Kim Hannant, her grandmother, is now urging all pregnant women to ensure they have the flu jab this year. She said: 'If it saves one person her death wasn't for nothing' NHS offers the flu vaccine free of charge to adults and children at risk. Includes anyone over the age of 65 and all expectant mothers.

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Summarize: By. Lucy Waterlow. PUBLISHED:. 08:01 EST, 17 March 2014. |. UPDATED:. 10:08 EST, 17 March 2014. A former Miss England who was once taunted for her looks has returned to the beauty pageant scene to help budding models beat the bullies. Jackie Turner, from Bournemouth, was tormented at school by her jealous peers who she said threatened to "slash my face and cut my hair off". Now age 30, Jackie recalls the abuse was so bad she was frightened to go to school and almost gave up on her dream of becoming a model. Triumphed: Jackie Turner is proud she didn't let bullies stop her modelling. Beauty pageant success: Jackie took the Miss Dorset and then Miss England crowns after her mother applied for her to take part by sending in pictures. She explained: 'I used to be really camera shy, I remember when I was eight I would hide my face if I saw a camera. My mum used to enter me into local modelling competitions without me knowing and one day I saw my picture in the paper and I had won. I realised then modelling was something I wanted to do. 'The bullying began when I started high school, girls from the years above would call me names and threaten to slash my face and cut my hair off. Tormented: Jackie was bullied at school because of her looks. Taking to the catwalk: She didn't want the bullies to hold her back so took part in beauty pageants. 'I didn’t feel like I was different from any other girl, yet they treated me so horrendously. I used to be so frightened to go to school. They used to spread rumours about me that I was dating all the older boys and stealing them away. I even had drinks thrown over me.' Jackie said she was too scared to tell the teachers and didn't confide in her family as she didn't want to worry them. As the bullying got worse, she started to turn down modelling jobs and became less sociable. Her twin sister, Shelly, knew something was wrong and eventually the truth came out. Global stage: Jackie, second from left, with some of her fellow Miss World contestants in 2003. Be confident: Older and wiser, right, Jackie wishes her younger self could have known the good things in store thanks to modelling like becoming Miss England, left. Jackie said: 'I was so lonely and sometimes I didn't feel like there was any other way out. Eventually my family and teachers intervened but I still didn't feel safe. I don't know what I would've done without the love and support of my sister and friends.' After school Jackie went on to qualify as a beauty therapist and became a personal trainer whilst taking part in some commercial modelling. In 2003 her mother, Terri, entered her into a beauty pageant, Miss Dorset, without Jackie knowing. Jackie was terrified to enter such a well-known pageant after the years of heartache she had endured at school. But she plucked up the courage to take part and won. Jackie said: 'I loved modelling and I thought it was time to follow my dreams properly again. I didn't want to let the bullies beat me.' Follow in her footsteps: Jackie is organising the Miss Dorset beauty pageant this year. She then went on to take the Miss England crown meaning she could take part in Miss World. 'I was then entered into Miss World and was sent to China to take part. I came 17th out of 108 women which was such an achievement,' she said. 'People imagine pageants to be incredibly lonely but I've never met so many nice women. I was welcomed by strangers and made so many friends.' After her positive experience, Jackie now wants to encourage other young women pursue their dreams and not let bullies stand in their way. She's running this year's Miss Dorset competition so she can support girls keen to follow in her footsteps. Moved on: Jackie said, 'I can't help but laugh now at the girls who used to bully me' She said: 'I can't help but laugh now at the girls who used to bully me. But I wish I could tell the young, vulnerable girl I was back then that we would be okay. Look what we've gone on to achieve. 'I'm running this year's Miss Dorset as I want to help other young girls who have been subjected to bullying because they're doing something they love. 'I want them to know that they shouldn't give up on their dreams like I nearly did. Don't let them beat you.' As well as giving support to the aspiring beauty queens, Jackie also wants to change the reputation of pageants. 'Pageants have such negative press. I want to change that, young girls should be able to be successful and excel in their own right doing something they love,' she said

Summary: Jackie Turner, from Bournemouth, started modelling in her teens. She was tormented at school by her jealous peers. They threatened her with violence and verbal abuse. Almost gave up modelling as result. But her mother entered her in Miss Dorset beauty pageant. She won and was then crowned Miss England. Then came 17th in Miss World. Now age 30, she's organising this year's Miss Dorset pageant. Wants to encourage other young women to follow their dreams.

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Summarize: A 95-year-old man's arm was elevated using a carrier bag and later a pillowcase after nurses struggled to find a specialised medical sling. After waiting for 12 hours on a trolley at New Cross Hospital in Wolverhampton, Joseph Ward's family were told staff would have to use a carrier bag to secure his arm. When he was transferred to another ward, an orthopaedic doctor replaced the bag with a pillowcase, to help drain Mr Ward's arm of excess fluid. Mr Ward's daughter, Jane Crutchley, who said she was forced to go and buy a sling herself, has branded her father's treatment an 'outrage'. Joseph Ward, 95, had his arm elevated using a pillowcase, left, and plastic carrier bag, right, at New Cross Hospital in Wolverhampton, after medics told his family there were no specialised slings available. Ms Crutchley said: 'It is outrageous that staff are so stretched they couldn't even get a sling for a 95-year-old man. 'In the end I was so frustrated that I went and bought one myself for £39.99.' But the hospital said the temporary slings were used to ensure the 95-year-old's medical needs were met and that he was not left in pain. Mr Ward fell at his home in Wednesfield in the West Midlands on February 11. He was found on the floor by a district nurse, who had visited the diabetic 95-year-old to give him his insulin. The nurse took him straight to A&E at New Cross Hospital. There, medics told his family he needed a sling after they diagnosed compartment syndrome - a painful, and potentially serious condition caused by swelling and bleeding in a bundle of muscles. The condition is thought to have been caused by the pressure of Mr Ward lying on his arm all night. Medics said he needed his arm elevating to reduce the swelling and help drain the built-up fluid away. But his daughter claims staff 'couldn't find one (a sling) so they used a triangular bandage combined with a green carrier bag'. She said: 'Later when he was moved to a different ward - diabetic ward C16 - they tried using a pillow case.' His daughter Jane Crutchley, claims she was forced to buy a traditional sling, pictured, branding her father's treatment an 'outrage' Ms Crutchley claims her father still hadn't been given a specialised sling a week later, prompting her to take matters into her own hands. She went to buy a sling herself, at a cost of £39.99. 'His arm needed to be fixed at a specific angle to his shoulder and so a normal sling wasn't enough,' she said. 'So to find out that they were still using a plastic bag and a pillow case a week later was awful. 'It wasn't comfortable and he appeared to be in so much pain. 'Dad is fiercely independent and he lives in his own home. And at the moment it's been taken away from him. 'He's normally very with it but at the time he was so disorientated that I don't think he could protest. 'It's fortunate that my sister and I are there to look after him but so many other people are completely alone and don't have someone who can go and buy them the equipment they need. 'I'm no medic but he is still in pain and his arm doesn't appear to have improved at all. 'I feel that the delay in this could have slowed down the recovery to his arm.' A spokesman for the Royal Wolverhampton NHS Trust, which runs New Cross Hospital, said the trust's head of nursing Rose Baker has personally apologised to Mr Ward. 'With no Bradford sling in stock and to keep the patient comfortable while elevating his arm, staff on both wards used improvised slings and pillows,' he said. 'On ward C21 a temporary sling was made using a bag because it was cleanable and met hospital infection control standards. 'It was then replaced with a pillow case sling by an orthopaedic doctor on ward C16. 'This is a widely used and accepted practice to provide elevation. An alternative sling was then sourced from the fracture clinic which the patient is now using. 'At no time was the patient uncomfortable and his medical needs were met at all times. An incident report has been filed and any lessons learned will be shared with colleagues. 'The trust has agreed to reimburse the family the cost of the two Bradford slings which they purchased.'

Summary: Joseph Ward was taken to hospital in Wolverhampton after a fall. He was diagnosed with compartment syndrome - causing his arm to swell. Medics told his family his arm needed to be elevated to drain the fluid. Used a plastic bag, and then a pillowcase, in the absence of a medical sling. Daughter claims he was left like that for a week, prompting her to buy one. Hospital said pillowcase is 'accepted practice to provide elevation' Temporary sling was used to ensure Mr Ward's medical needs were met.

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Summarize: Background The overall goal of U.S. public diplomacy is to understand, inform, engage, and influence the attitudes and behavior of foreign audiences in ways that support U.S. strategic interests. The State Department leads these efforts, which are guided by the Under Secretary for Public Diplomacy and Public Affairs and include academic and professional exchanges, English language teaching, information programs, and news management. The department’s regional and functional bureaus also contain public diplomacy offices, which report to the relevant assistant secretary. The Under Secretary has direct authority over the three public diplomacy bureaus but does not have line authority over public diplomacy operations in other regional or functional bureaus. In overseas missions, Foreign Service public diplomacy officers (including Public Affairs, Cultural Affairs, Information, Information Resources, and Regional English Language officers) operate under the authority of the chief of mission and report to their regional bureau managers in Washington, D.C. In fiscal year 2005, State dedicated $597 million to public diplomacy and public affairs. According to the department’s performance plan, its investment in public diplomacy continues to increase, particularly for efforts targeting audiences in the Middle East. Exchange programs received $356 million, the majority of fiscal year 2005 funding and a 12.4 percent increase over fiscal year 2004. State’s information programs received roughly $68 million in fiscal year 2005 to fund programs such as the U.S. speakers program, mission Web sites, and American Corners, which are centers that provide information about the United States, hosted in local institutions and staffed by local employees. The remaining public diplomacy funds went to State’s regional bureaus to pay the salaries of locally engaged staff overseas, among other purposes. Public Diplomacy Resources Have Shifted to the Muslim World, but Staffing Numbers Have Leveled Off Since the terrorist attacks of September 11, 2001, State has expanded its public diplomacy efforts globally, focusing particularly on countries in the Muslim world considered to be of strategic importance in the war on terrorism. Between 2004 and 2006, total spending on overseas public diplomacy will increase 21 percent, from $519 million to an estimated $629 million. Much of this increase has gone to regions with significant Muslim populations, including South Asia (39 percent), East Asia and the Pacific (28 percent), and the Near East (25 percent). These increases continue the trend we reported in 2003, when we found that the largest relative increases in overseas public diplomacy resources went to regions with large Muslim populations. However, the Bureau of European and Eurasian Affairs continues to receive the largest overall share of overseas public diplomacy resources—roughly 36 percent of the total for all six regional bureaus. In 2003, we noted that authorized officer positions overseas had significantly expanded, with the most notable increases occurring in State’s Near East (27-percent increase) and South Asia (15-percent increase) bureaus. However, current data show that staff numbers have stayed largely the same over the past 3 years, with increases of 3 percent or less. In January 2006, Secretary Rice announced plans to reposition officers as part of her transformational diplomacy initiative. State officials said that the department will initially reposition approximately 75 Foreign Service officers this year from posts in Europe and Washington, D.C., to India, China, and Latin America, as well as to the Muslim world. According to these officials, 28 of the positions to be relocated are public diplomacy positions. Strategy, Planning, and Coordination Efforts Are Inadequate Since 2003, we have reported on the lack of strategic elements to guide U.S. public diplomacy efforts. Despite several attempts, the United States still lacks an interagency public diplomacy strategy. While State has recently developed a strategic framework for its public diplomacy efforts, it has not issued guidance on how this framework is to be implemented in the field. In addition, posts generally lack a strategic approach to public diplomacy. Government Lacks an Interagency Public Diplomacy Strategy In 2003, we reported that the United States lacked a governmentwide, interagency public diplomacy strategy, defining the messages and means for communication efforts abroad. We reported that the administration had made a number of aborted attempts to develop a strategy, but to date no public diplomacy strategy has been developed. The lack of such a strategy complicates the task of conveying consistent messages, which increases the risk of making damaging communication mistakes. State officials said that the lack of such a strategy diminishes the efficiency and effectiveness of governmentwide public diplomacy efforts, while several reports concluded that a strategy is needed to synchronize agencies’ target audience assessments, messages, and capabilities. On April 8, 2006, the President established a new Policy Coordination Committee on Public Diplomacy and Strategic Communications. This committee, to be led by the Under Secretary for Public Diplomacy and Public Affairs, is intended to coordinate interagency activities to ensure that: all agencies work together to disseminate the President’s themes and all public diplomacy and strategic communications resources, programs, and activities are effectively coordinated to support those messages; and every agency gives public diplomacy and strategic communications the same level of priority that the President does. According to department officials, one of the committee’s tasks will be to issue a formal interagency public diplomacy strategy. It is not clear when this strategy will be developed. State Has Established Public Diplomacy Strategic Framework but Lacks Implementing Guidance In 2005, the Under Secretary established a strategic framework for U.S. public diplomacy efforts, which includes three priority goals: (1) support the President’s Freedom Agenda with a positive image of hope; (2) isolate and marginalize extremists; and (3) promote understanding regarding shared values and common interests between Americans and peoples of different countries, cultures, and faiths. The Under Secretary noted that she intends to achieve these goals using five tactics—engagement, exchanges, education, empowerment, and evaluation—and by using various public diplomacy programs and other means. This framework partially responds to our 2003 recommendation that the department develop and disseminate a strategy to integrate all State’s public diplomacy efforts and direct them toward achieving common objectives. However, the department has not yet developed written guidance that provides details on how the Under Secretary’s new strategic framework should be implemented in the field. In 2005, we noted that State’s efforts to engage the private sector in pursuit of common public diplomacy objectives had met with mixed success and recommended that the Secretary develop a strategy to guide these efforts. State is currently establishing an office of private sector outreach and is partnering with individuals and the private sector on various projects. The Under Secretary plans to institutionalize this function within the department surrounding key public diplomacy objectives, but it is unclear when this office will be established and whether it will develop a comprehensive strategy to engage the private sector. Posts Lack a Strategic Approach to Public Diplomacy GAO and others have suggested that State adopt a strategic approach to public diplomacy by modeling and adapting private sector communication practices to suit its purposes (see fig. 1). However, based on our review of mission performance plans and on fieldwork in Nigeria, Pakistan, and Egypt, we found that the posts’ public diplomacy programming generally lacked these important elements of strategic communications planning. In particular, posts lacked a clear theme or message and did not identify specific target audiences. According to a senior embassy official in Pakistan, the United States has too many competing messages, and the post needs to do a better job of defining and clarifying its message. Posts also failed to develop detailed strategies and tactics to direct available public diplomacy programs and tools toward clear, measurable objectives in the most efficient manner possible. Finally, posts lack detailed, country- level communication plans to coordinate their various activities. Recently, State has begun to help posts improve their strategic communications planning. For example, the department has issued guidance on preparing fiscal year 2008 mission performance plans that calls for more strategic thinking and planning than was required in the past, including identification of specific target audiences, key themes and messages, detailed strategies and tactics, and measurable performance outcomes that can clearly demonstrate the ultimate impact of U.S. public diplomacy efforts. If fully implemented, this guidance should begin to address the shortcomings we found in mission performance plans; however, it will not be implemented for another 2 years, raising significant concerns about what the department intends to do now to address strategic planning shortfalls. Moreover, it is unclear whether this guidance will include all the strategic elements from private sector communication practices. In addition to this guidance, the department is currently developing a sample country-level communication plan and has asked 15 pilot posts to develop specific plans for their host countries. These plans are intended to better focus U.S. efforts to counter ideological support for terrorism, according to State. Part of this process will include the development of a key influencers analysis to help identify target audiences in each country. State officials said that they expect to have plans for these countries by fall or winter 2006. Staffing Challenges and Security Concerns Limit U.S. Public Diplomacy Activities Public diplomacy efforts in the field face several other challenges, many of which are heightened in the Muslim world. Officials at posts we visited said they lacked sufficient staff and time to conduct public diplomacy tasks, and we found that many public diplomacy positions are filled by officers without the requisite language skills. Furthermore, public diplomacy officers struggle to balance security with public access and outreach to local populations. Insufficient Staff and Lack of Staff Time Hinders Public Diplomacy Activities While several recent reports on public diplomacy have recommended an increase in spending on U.S. public diplomacy programs, several embassy officials stated that, with current staffing levels, they do not have the capacity to effectively utilize increased funds. According to State data, the department had established 834 public diplomacy positions overseas in 2005, but 124, or roughly 15 percent, were vacant. Compounding this challenge is the loss of public diplomacy officers to temporary duty in Iraq, which, according to one State official, has drawn down field officers even further. Staffing shortages may also limit the amount of training public diplomacy officers receive. According to the U.S. Advisory Commission on Public Diplomacy, “the need to fill a post quickly often prevents public diplomacy officers from receiving their full training.” In addition, public diplomacy officers at post are burdened with administrative tasks and thus have less time to conduct public diplomacy outreach activities than previously. One senior State official said that administrative duties, such as budget, personnel, and internal reporting, compete with officers’ public diplomacy responsibilities. Another official in Egypt told us that there was rarely enough time to strategize, plan, or evaluate her programs. These statements echo comments we heard during overseas fieldwork and in a survey for our 2003 report. Surveyed officers told us that, while they manage to attend functions within their host country capitals, it was particularly difficult to find time to travel outside the capitals to interact with other communities. This challenge is compounded at posts with short tours of duty, which include many in the Muslim world. According to data provided by State, the average tour length at posts in the Muslim world is about 22 percent shorter than tour lengths elsewhere. Noting the prevalence of one-year tours in the Muslim world, a senior official at State told us that Public Affairs officers who have shorter tours tend to produce less effective work than officers with longer tours. To address these challenges, we recommended in 2003 that the Secretary of State designate more administrative positions to overseas public affairs sections to reduce the administrative burden. Officials at State said that the Management bureau is currently considering options for reducing the administrative burden on posts, including the development of centralized administrative capabilities offshore. State is also repositioning several public diplomacy officers as part of its transformational diplomacy initiative; however, this represents a shift of existing public diplomacy officers and does not increase the overall number of officers in the department. Language Deficiencies Pronounced, Especially in the Muslim World In 2005, 24 percent of language-designated public diplomacy positions were filled by officers without the requisite language proficiency, similar to our findings in 2003. At posts in the Muslim world, this shortfall is even greater, with 30 percent of public diplomacy positions filled by officers without sufficient language skills. This figure is primarily composed of languages that are considered difficult to master, such as Arabic and Persian, but also includes languages considered easier to learn, such as French. Embassies Must Balance Security and Public Outreach Security concerns have limited embassy outreach efforts and public access, forcing public diplomacy officers to strike a balance between safety and mission. Shortly after the terrorist attacks of September 11, 2001, then-Secretary of State Colin Powell stated, “Safety is one of our top priorities… but it can’t be at the expense of the mission.” While posts around the world have faced increased threats, security concerns are particularly acute in countries with significant Muslim populations, where the threat level for terrorism is rated as “critical” or “high” in 80 percent of posts (see fig. 2). Security and budgetary concerns have led to the closure of publicly accessible facilities around the world, such as American Centers and Libraries. In Pakistan, for example, all of the American Centers have closed for security reasons; the last facility, in Islamabad, closed in February 2005. These same concerns have prevented the establishment of a U.S. presence elsewhere. As a result, embassies have had to find other venues for public diplomacy programs, and some activities have been moved onto embassy compounds, where precautions designed to improve security have had the ancillary effect of sending the message that the United States is unapproachable and distrustful, according to State officials. Concrete barriers and armed escorts contribute to this perception, as do requirements restricting visitors’ use of cell phones and pagers within the embassy. According to one official in Pakistan, visitors to the embassy’s reference library have fallen to as few as one per day because many visitors feel humiliated by the embassy’s rigorous security procedures. Other public diplomacy programs have had to limit their publicity to reduce the risk of becoming a target. A recent joint USAID-State report concluded that “security concerns often require a ‘low profile’ approach during events, programs or other situations, which, in happier times, would have been able to generate considerable good will for the United States.” This constraint is particularly acute in Pakistan, where the embassy has had to reduce certain speaker and exchange programs. State has responded to security concerns and the loss of publicly accessible facilities through a variety of initiatives, including American Corners, which are centers that provide information about the United States, hosted in local institutions and staffed by local employees. According to State data, there are currently approximately 300 American Corners throughout the world, including more than 90 in the Muslim world, with another 75 planned (more than 40 of which will be in the Muslim world). However, two of the posts we visited in October 2005 were having difficulty finding hosts for American Corners, as local institutions fear becoming terrorist targets. Mr. Chairman, this concludes my prepared statement. I would be happy to respond to any questions you or other members of the subcommittee may have at this time. Contact and Staff Acknowledgments For questions regarding this testimony, please contact Jess T. Ford at (202) 512-4128 or fordj@gao.gov. Individuals making key contributions to this statement include Diana Glod, Assistant Director; Michael ten Kate; Robert Ball; and Joe Carney. This is a work of the U.S. government and is not subject to copyright protection in the United States. It may be reproduced and distributed in its entirety without further permission from GAO. However, because this work may contain copyrighted images or other material, permission from the copyright holder may be necessary if you wish to reproduce this material separately.

Summary: Public opinion polls have shown continued negative sentiments toward the United States in the Muslim world. Public diplomacy activities--led by the State Department (State)--are designed to counter such sentiments by explaining U.S. foreign policy actions, countering misinformation, and advancing mutual understanding between nations. Since 2003, we have issued three reports on U.S. public diplomacy efforts that examined (1) changes in public diplomacy resources since September 11, 2001; (2) strategic planning and coordination of public diplomacy efforts; and (3) the challenges facing these efforts. We have made several recommendations in the last 3 years to the Secretary of State to address strategic planning issues, private sector engagement, and staffing challenges related to public diplomacy. For example, today's report recommends that the Secretary develop written guidance detailing how the department intends to implement its public diplomacy goals as they apply to the Muslim world. State has consistently concurred with our findings and recommendations for improving public diplomacy, and the department, in several cases, is taking appropriate actions. However, the department has not established a timetable for many of these actions. Since the terrorist attacks of September 11, 2001, State has expanded its public diplomacy efforts globally, focusing particularly on countries in the Muslim world considered to be of strategic importance in the war on terrorism. Since 2001, State has increased its public diplomacy resources, particularly in regions with significant Muslim populations. That funding trend has continued more recently, with increases of 25 percent for the Near East and 39 percent for South Asia from 2004 to 2006, though public diplomacy staffing levels have remained largely the same during that period. The Secretary of State recently announced plans to reposition some staff to better reflect the department's strategic priorities, including plans to shift 28 public diplomacy officers from posts in Europe and Washington, D.C., to China, India, and Latin America, as well as to the Muslim world. In 2003 and again in 2005, we reported that the government lacked an interagency communication strategy to guide governmentwide public diplomacy activities, and it continues to lack this strategy. We also noted that State did not have a strategy to integrate its diverse public diplomacy activities and that efforts to effectively engage the private sector had met with mixed success. Today, although State has developed a strategic framework to focus its public diplomacy efforts and related tactics to achieve these goals, the department has not issued guidance on how to implement these strategies and tactics. In addition, posts' public diplomacy efforts generally lack important strategic communication elements found in the private sector, which GAO and others have suggested adopting as a means to better communicate with target audiences. These elements include having core messages, segmented target audiences, in-depth research and analysis to monitor and evaluate results, and an integrated communication plan to bring all these elements together. State officials indicate that the department has begun to develop communication plans for 15 pilot posts, but it remains to be seen whether these communication plans will contain all of these strategic elements. Posts throughout the world, and particularly in the Muslim world, face several challenges in implementing their public diplomacy programs, including concerns related to staff numbers and language capabilities and the need to balance security with public outreach. For example, we found that 24 percent of language-designated public diplomacy positions worldwide were filled by officers without the requisite language skills. Furthermore, security concerns have limited embassy outreach efforts and public access. State has begun to address many of these challenges, but it is too early to evaluate the effectiveness of many of these efforts.

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Summarize: A man that had been accused of committing numerous sex crimes against his nine-year-old son allegedly killed himself this week. Defense attorney Adam Bollaert told Al.com that on Monday evening his client Carl Herold was found hanged inside a cell at Clay County jail. At the time of his death, Herold had been in the middle of an extradition for federal child pornography charges in New York state, the website reported. Last year, authorities arrested Herold and his partner Charles Dunnavant in November and December, respectively, and in 2014 indicted them with 30 counts, according to Al.com. Dead: Carl Herold, pictured, was found hanged inside a cell at Clay County jail, his attorney has said. Partner: The indictment counts for Charles Dunnavant, Herold's partner, are for conspiracy to commit child sex abuse, sodomy and sexual abuse of a child under 12, aggravated child abuse, and conspiracy to commit sodomy. Herold faced 18 counts for several alleged crimes: conspiracy to commit sodomy, conspiracy to commit sexual abuse, complicity, sodomy, sexual abuse of a child under 12, as well as aggravated child abuse, the outlet reported. It noted that both his child pornography production as well as distribution charges had been dropped. WHNT reported last December that a motion to increase bond said 'The victim in this was kept in Defendant’s home, without schooling or interaction with others outside the supervision on Defendant or his co-defendants, for eight months.' The federal New York indictment from December 2013 'alleges that from August 2011 to about March 2013, Herold compelled a male child to "engage in sexually explicit conduct" to produce images and videos that were produced and transmitted via computer and other means,' AL.com reported. Herold offered 'Computer Science for Everyone' tutorials and had reddit and YouTube pages also meant for teaching, the media outlet earlier found. Dunnavant's counts were for conspiracy to commit child sex abuse, sodomy and sexual abuse of a child under 12, aggravated child abuse, and conspiracy to commit sodomy, the news outlet reported. Multiple investigations: At the time of his death Herold was in the middle of an extradition to New York state for federal child pornography charges. 'Prisoner': Herold's son was allegedly held under extremely close supervision for eight months in this Huntsville, Alabama residence. This past June, Al.com reported Dunnavant did not want the alleged victim's testimony heard -- and that defense attorney Brian White cited the boy's mental health and possible sway from authorities he spoke with. An excerpt of a court filing about the boy - who is a psychiatric hospital patient - from the defense that was published by the website said 'There is a real likelihood that (the child) suffers from a mental condition severe enough to interfere with his ability to have observed events and to now remember and be able to relate those events and to appreciate the grave importance of telling the complete truth.' Bollaert told the news outlet of his client's alleged suicide 'It's really shocking to me, when I met with Mr. Herold last week, in Cullman County, he had great spirits, he seemed up and was ready to continue fighting this case. So, we don't understand what happened.' Speaking to AL.com on Tuesday, Madison County Assistant District Attorney Jason Scully-Clemons said 'My reaction to it, ultimately, is I wish that Carl Herold had been brave enough to face justice in Madison County rather than doing what he did. 'Today above all else, I'm sad for the victim in this case, as I have been all along.' Update November 6, 2014. A previous version of this article mistakenly stated in the fourth paragraph that Defense Attorney Adam Bollaert had been arrested and indicted in connection with this case. In fact Mr Bollaert has not been arrested or indicted. It is his client Carl Herold who was arrested and indicted, together with his partner Charles Dunnavant. We apologise to Mr Bollaert

Summary: Carl Herold was found hanged inside a cell at Clay County jail on Monday evening, his attorney said. He and his partner Charles Dunnavant have been accused and charged with numerous sex crimes against Herold's nine-year-old son. At the time of his death, Herold had been in the middle of an extradition for federal child pornography charges in New York state. Herold faced 18 counts for several alleged crimes, which included sodomy and sexual abuse of a child under 12. His son is now reportedly a patient at a psychiatric hospital.

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Summarize: This undated photo shows Osama bin Laden, center, Ayman Al-Zawahiri, left, a physician and the founder of the Egyptian Islamic Jihad, and Muhammad Atef, right, who has been indicted in the U.S. for his alleged involvement in the 1998 bombings of U.S. embassies in Tanzania and Kenya. (AFP/Getty Images) FILE - In this 1998 file photo, Ayman al-Zawahri, left, poses for a photograph with Osama bin Laden, right, taken in Khost, Afghanistan and made available Friday March 19, 2004. A person familiar with... (Associated Press) The most intense manhunt in history finally caught up with Osama bin Laden, but his life's story will be told many different ways by different people. Reviled in the West as the personification of evil, bin Laden was admired and even revered by some fellow Muslims who embraced his vision of unending jihad against the United States and Arab governments he deemed as infidels. Bin Laden's money and preaching inspired the Sept. 11, 2001, terrorist attacks that killed just under 3,000 people in New York, Washington and Pennsylvania, and forever ripped a hole in America's feeling of security in the world. His actions set off a chain of events that led the United States into wars in Afghanistan, and then Iraq, and a clandestine war against extreme Islamic adherents that touched scores of countries on every continent but Antarctica. America's entire intelligence apparatus was overhauled to counter the threat of more terror attacks at home. Bin Laden was killed in an operation led by the United States, President Barack Obama said Sunday. A small team of Americans carried out the attack and took custody of bin Laden's remains, Obama said. Bin Laden's al-Qaida organization has also been blamed for the 1998 bombings of two U.S. embassies in Africa that killed 231 people and the 2000 attack on the USS Cole that killed 17 American sailors in Yemen, as well as countless other plots, some successful and some foiled Perhaps as significant was his ability _ even from hiding _ to inspire a new generation of terrorists to murder in his name. Most of al-Qaida's top lieutenants have been killed or captured in the years since Sept. 11, 2001, and intelligence officials in Europe and Asia say they now see a greater threat from homegrown radical groups energized by bin Laden's cause. Al-Qaida is not thought to have provided logistical or financial support to the group of North African Muslims who pulled off the March 11, 2004, bombings in Madrid, Spain _ which killed 191 people _ but they were certainly inspired by its dream of worldwide jihad. Likewise, no link has been established between al-Qaida and the four British Muslim suicide bombers who killed 52 people in London on July 7, 2005, but few believe the attack would have taken place had bin Laden not aroused the passions of young Muslim radicals the world over. The war in Iraq _ justified in part by erroneous intelligence that suggested Saddam Hussein had both weapons of mass destruction and a link to al-Qaida _ has become the cauldron in which the world's next generation of terrorists are honing their skills. While scant evidence has emerged of a link between Saddam and bin Laden's inner circle, there is no doubt that al-Qaida took advantage of the chaos of post-Saddam Iraq _ helping to drag the United States into a quagmire that led to the death of some 5,000 American troops, and many scores of thousands of Iraqis. Indeed, bin Laden's legacy is a world still very much on edge. Frightening terms like dirty bomb, anthrax and weapons of mass destruction have become staples of the global vocabulary; and others like Guantanamo, Abu Ghraib and extraordinary rendition have fueled a burning anger in the Muslim world. But long before bin Laden became the world's most hunted man, few believed fate would move him in that direction. Bin Laden was born in Saudi Arabia in 1954. He became known as the most pious of the sons among his wealthy father's 54 children. Bin Laden's path to militant Islam began as a teenager in the 1970s when he got caught up in the fundamentalist movement then sweeping Saudi Arabia. He was a voracious reader of Islamic literature and listened to weekly sermons in the holy city of Mecca. Thin, bearded and over 6 feet tall, bin Laden joined the Afghans' war against invading Soviet troops in the 1980s and gained a reputation as a courageous and resourceful commander. Access to his family's considerable construction fortune certainly helped raise his profile among the mujahedeen fighters. At the time, bin Laden's interests converged with those of the United States, which backed the "holy war" against Soviet occupation with money and arms. When bin Laden returned home to Saudi Arabia, he was showered with praise and donations and was in demand as a speaker in mosques and homes. It did not take long for his aims to diverge from those of his former Western supporters. "When we buy American goods, we are accomplices in the murder of Palestinians," he said in one of the cassettes made of his speeches from those days. A seminal moment in bin Laden's life came in 1990, when U.S. troops landed on Saudi soil to drive Iraq out of Kuwait. Bin Laden tried to dissuade the government from allowing non-Muslim armies into the land where the Prophet Muhammad gave birth to Islam, but the Saudi leadership turned to the United States to protect its vast oil reserves. When bin Laden continued criticizing Riyadh's close alliance with Washington, he was stripped of Saudi citizenship. "I saw radical changes in his personality as he changed from a calm, peaceful and gentle man interested in helping Muslims into a person who believed that he would be able to amass and command an army to liberate Kuwait. It revealed his arrogance and his haughtiness," Prince Turki, the former Saudi intelligence chief, said in an interview with Arab News and MBC television in late 2001. "His behavior at that time left no impression that he would become what he has become," the prince added. The prince, who said he met bin Laden several times years ago in Pakistan and Saudi Arabia, described him as "a gentle, enthusiastic young man of few words who didn't raise his voice while talking." Abdel-Bari Atwan, editor of Al-Quds al-Arabi, London-based newspaper, spent 10 days with bin Laden in an Afghan cave in 1996. He said bin Laden "touched the root of the grievances of millions in the Arab world" when he presented himself as the alternative to Arab regimes that have been incapable of liberating Arab land from Israeli occupation and restoring pride to their people. He said bin Laden and his followers never feared death. "Those guys spoke about death the way young men talk about going to the disco," Atwan said. "They envied those who fell in battle because they died as martyrs in God's cause." Still, bin Laden had a knack for staying alive. After being kicked out of Saudi Arabia, bin Laden sought refuge in Sudan. The African country acceded to a U.S. request and offered to turn bin Laden over to Saudi Arabia in 1996, but his native country declined, afraid a trial would destabilize the country. Back on familiar terrain in Afghanistan _ allowed in by the government of Burhanuddin Rabbani _ bin Laden and his al-Qaida network prepared for the holy war that turned him into Washington's No. 1 enemy. When the Taliban _ who would eventually give him refuge _ first took control of Kabul in September 1996, bin Laden and his Arab followers kept a low profile, uncertain of their welcome under the new regime. The Taliban leader Mullah Mohammed Omar called bin Laden to southern Kandahar from his headquarters in Tora Bora and eventually through large and continual financial contributions to the isolated Taliban, bin Laden became dependent on the religious militia for his survival. In Afghanistan, he would wake before dawn for prayers, then eat a simple breakfast of cheese and bread. He closely monitored world affairs. Almost daily, he and his men _ Egyptians, Yemenis, Saudis, among others _ practiced attacks, hurling explosives at targets and shooting at imaginary enemies. He also went horseback riding, his favorite hobby, and enjoyed playing traditional healer, often prescribing honey, his favorite food, and herbs to treat colds and other illnesses. In Afghanistan, bin Laden was often accompanied by his four wives _ the maximum Islam allows. Estimates on the number of his children range up to 23. Al-Qaida's first major strike after bin Laden returned to Afghanistan was on Aug. 7, 1998, when twin explosions rocked U.S. embassies in Kenya and Tanzania. Most of the victims were African passers-by, but the bombings also killed 12 Americans. Days later, bin Laden escaped a cruise missile strike on one of his training camps in Afghanistan launched by the United States in retaliation. Bin Laden is believed to have been at the Zhawar Kili Al-Badr camp for a meeting with several of his top men, but left shortly before some 70 Tomahawk cruise missiles slammed into the dusty complex. Since Sept. 11, bin Laden stayed a step ahead of the dragnet _ perhaps the largest in history for a single individual. As the Taliban quickly fell under pressure of the U.S. bombardment, bin Laden fled into the inhospitable mountains in the seam that separates Pakistan and Afghanistan, keeping up a spotty stream of chatter _ first in video tapes and then in scratchy audio recordings _ to warn his Western pursuers of more bloodshed. Just hours after the U.S. assault on Afghanistan began on Oct. 7, 2001, bin Laden appeared in a video delivered to Al-Jazeera, an Arab satellite television station, to issue a threat to America. "I swear by God... neither America nor the people who live in it will dream of security before we live it in Palestine, and not before all the infidel armies leave the land of Muhammad, peace be upon him," said bin Laden, dressed in fatigues. He reappeared in a video appearance broadcast by Al-Jazeera on Dec. 27, 2001, shortly after U.S. forces apparently had him cornered in Tora Bora, a giant cave complex in eastern Afghanistan. Hundreds of al-Qaida suspects are believed to have escaped the massive U.S. bombing campaign there, and bin Laden is believed to have been among them. During the past decade, bin Laden and al-Zawahri have appeared regularly in audio and video tapes to issue threats, and comment on a wide range of current events, although the appearances trailed off in recent years. In November 2002, bin Laden threatened Britain, France, Italy, Canada, Germany and Australia for their support for the United States, saying: "It is time we get even. You will be killed just as you kill, and will be bombed just as you bomb." Later, he called on Muslims to rise up against leaders in Saudi Arabia and Kuwait he saw as Washington's stooges. In 2004, he tried a new tack, offering a "truce" to European countries that don't attack Muslims, then later saying that the United States could avoid another Sept. 11 attack if it stopped threatening the security of Muslims. After a long silence, bin Laden stepped up his messages in 2006, and the subjects he addressed became more political. In January 2006, he addressed his comments to the American people rather than U.S. President George W. Bush because, he said, polls showed "an overwhelming majority" of Americans wanted a withdrawal from Iraq. He even recommended Americans pick up a copy of the book "The Rogue State," which he said offered a path to peace. At several points in the years since the Sept. 11 attacks, bin Laden's capture or death had appeared imminent. After the March 2003 arrest of Khalid Shaikh Mohammed, the alleged mastermind of the Sept. 11 attacks, officials in Islamabad and Washington were paraded out to deny a consistent stream of rumors that bin Laden had been captured. U.S. forces poured into the border region looking for him and former Taliban and Taliban in hiding said bin Laden had constantly been on the move, traveling through the mountains with a small entourage of security. Through it all, bin Laden vowed repeatedly that he was willing to die in his fight to drive the Israelis from Jerusalem and Americans from Saudi Arabia and Iraq. "America can't get me alive," bin Laden was quoted as saying in an interview with a Pakistani journalist conducted shortly after the U.S. invasion of Afghanistan. "I can be eliminated, but not my mission."

Summary: Long before Osama bin Laden was America's most reviled terrorist, he was the quiet boy of a rich Saudi family, "a gentle, enthusiastic young man of few words who didn't raise his voice while talking," according to a former Saudi intelligence chief. Born in 1954, bin Laden was one of 54 children and grew up in mansions littered with crystal chandeliers, gold statues, and Italian tapestries, reports the LA Times. As a 10-year-old, he reportedly inherited $300 million after his father died in a plane crash. Bin Laden was a tireless reader of Islamic literature whose path to militant Islam began as a teen in the 1970s, when he got caught up in the fundamentalist movement then sweeping Saudi Arabia, reports the AP. He began to grow more radical in the next decade, after joining the Afghan war against the Soviets, where he was able to use his family's money to help the mujahedeen fighters. But what AP calls the "seminal moment" happened in 1990, when US troops landed in Saudi Arabia to drive Iraqi forces out of the tiny, oil-rich country of Kuwait. When bin Laden criticized Riyadh's close alliance with Washington-bin Laden had offered to pull together an army of Afghan war vets to protect Saudi Arabia, an offer that was refused by the royal family-he was stripped of his Saudi citizenship in 1994. The intelligence chief then describes "radical changes in his personality," from a "gentle man interested in helping Muslims into a person who believed that he would be able to amass and command an army to liberate Kuwait." Things escalated from there; click for more.

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Write a title and summarize: SECTION 1. SHORT TITLE. This Act may be cited as the ``Agricultural Extended Retirement Credit Act of 2002''. SEC. 2. PURPOSES. The purposes of this Act are-- (1) to extend creditable service, for purposes of the Civil Service Retirement System, for periods of service in certain qualified Federal-State cooperative programs which had agricultural or related purposes; (2) to expedite the retirement of certain Federal Government employees by providing them improved retirement opportunities at typical retirement ages, thereby mitigating potentially adverse effects of deficit control measures on the welfare of those and other employees of the United States Department of Agriculture; and (3) to effect savings in budget authority and outlays in the Department of Agriculture in such a manner that the potential for adverse effects on program effectiveness is minimized. SEC. 3. EXTENSION OF CREDITABLE SERVICE. (a) Extended Credit Defined.--Section 8331 of title 5, United States Code, is amended-- (1) by striking ``and'' after the semicolon at the end of paragraph (27); (2) by striking the period at the end of paragraph (28) and inserting ``; and''; and (3) by adding after such paragraph (28) the following: ``(29) `extended credit' means creditable service for periods of service in Federal-State cooperative programs under section 8332(b)(18).''. (b) Creditable Service.--Section 8332(b) of title 5, United States Code, is amended-- (1) by striking ``and'' after the semicolon at the end of paragraph (16); (2) by striking the period at the end of paragraph (17) and inserting ``; and''; and (3) by adding after such paragraph (17) the following: ``(18) subject to sections 8334(c) and 8339(i), service performed before January 1, 1984, by an individual in the employ of a State or an instrumentality of a State, if-- ``(A) such service involved duties related to the carrying out of a Federal-State cooperative program described in subsection (o)(1); ``(B) such individual was later employed in a position which was then subject to this subchapter; and ``(C) such individual (or a survivor thereof) makes application for certification of credit for such service on or before the 180th day following the date of enactment of the Agricultural Extended Retirement Credit Act of 2002.''. (c) Certification.--Section 8332(b) of title 5, United States Code, is further amended by adding at the end the following: ``The Office of Personnel Management shall accept, for purposes of this subchapter, the certification of the Secretary of Agriculture, or his designee, concerning service of the type described in paragraph (18).''. (d) Cooperative Programs Described.--Section 8332 of title 5, United States Code, is amended by adding at the end the following: ``(o)(1) The Federal-State cooperative programs described in this subsection for which creditable service is allowable under subsection (b)(18) are-- ``(A) the Federal-State cooperative program of agricultural research of the State agricultural experiment stations as defined in section 1 of the Act entitled `An Act to consolidate the Hatch Act of 1887 and laws supplementary thereto relating to the appropriation of Federal funds for support of agricultural experiment stations in the States, Alaska, Hawaii, and Puerto Rico', approved August 11, 1955 (69 Stat. 671); ``(B) the Federal-State cooperative program of forestry research at eligible institutions of the State as defined in section 2 of the Act entitled `An Act to authorize the Secretary of Agriculture to encourage and assist the several States in carrying on a program of forestry research, and for other purposes', approved October 10, 1962 (76 Stat. 806), and popularly referred to as the McIntire-Stennis Act; ``(C) the Federal-State cooperative program of agricultural research for the fiscal year ending June 30, 1967 and later fiscal years at the 1890 land-grant colleges, including Tuskegee Institute, as defined in subsection 1445(a) of the `National Agricultural Research, Extension, and Teaching Policy Act of 1977', approved September 29, 1977 (91 Stat. 1009); ``(D) the Federal-State cooperative program of agricultural extension work authorized by the Act entitled `An Act to provide for cooperative agricultural extension work between the agricultural colleges in the several States receiving the benefits of an Act of Congress approved July second, eighteen hundred and sixty-two, and of Acts supplementary thereto, and the United States Department of Agriculture', approved May 8, 1914 (38 Stat. 372), and acts supplementary thereto; ``(E) the Federal-State cooperative program of vocational education, including State programs of instruction in vocational agriculture and home economics authorized by the Act entitled `An Act to provide for the promotion of vocational education; to provide for cooperation with the States in the promotion of such education in agriculture and the trades and industries; to provide for cooperation with the States in the preparation of teachers of vocational subjects; and to appropriate money and regulate its expenditure', approved February 23, 1917 (39 Stat. 929), and acts supplementary thereto; ``(F) the Federal-State cooperative program in marketing service and research authorized by the Agricultural Marketing Act of 1946, approved August 14, 1946 (60 Stat. 1087), and predecessor programs, including programs to inspect, certify, and identify the class, quality, quantity, and condition of agricultural products shipped or received in interstate commerce; ``(G) the Federal-State cooperative program for the control of plant pests and animal diseases authorized by the subheading entitled `Federal Horticulture Board' under the heading entitled `Department of Agriculture' of the Act entitled `An Act making appropriations to supply urgent deficiencies in appropriations for the fiscal year ending June thirtieth, nineteen hundred and eighteen, and prior fiscal years, on account of war expenses, and for other purposes', approved October 6, 1917 (40 Stat. 374); by section 102 of the Department of Agriculture Organic Act of 1944, approved September 21, 1944 (58 Stat. 734); by the joint resolution entitled `Joint resolution making funds available for the control of incipient or emergency outbreaks of insect pests or plant diseases, including grasshoppers, mormon crickets, and chinch bugs', approved April 6, 1937 (50 Stat. 57); by the Act entitled `An Act to provide for regulating, inspecting, cleaning, and, when necessary, disinfecting railway cars, other vehicles, and other materials entering the United States from Mexico', approved January 31, 1942 (56 Stat. 40); by the Act entitled `An Act to regulate the importation of nursery stock and other plants and plant products; to enable the Secretary of Agriculture to establish and maintain quarantine districts for plant diseases and insect pests; to permit and regulate the movement of fruits, plants, and vegetables therefrom, and for other purposes', approved August 20, 1912 (37 Stat. 315); by the first paragraph under the subheading entitled `Enforcement of the Plant-Quarantine Act' under the heading entitled `Miscellaneous' of the Act entitled `An Act making appropriations for the Department of Agriculture for the fiscal year ending June thirtieth, nineteen hundred and fourteen', approved March 4, 1913 (37 Stat. 853), insofar as such paragraph relates to the importation of certain plants for scientific purposes; by the second, third, and fourth paragraphs under the subheading entitled `Enforcement of the Plant-Quarantine Act' under the heading entitled `Miscellaneous' of the Act entitled `An Act making appropriations for the Department of Agriculture for the fiscal year ending June thirtieth, nineteen hundred and sixteen', approved March 4, 1915 (38 Stat. 1113); and by section 11 of the Act entitled `An Act for the establishment of a Bureau of Animal Industry, to prevent the exportation of diseased cattle, and to provide for the suppression and extirpation of pleuropneumonia and other contagious diseases among domestic animals', approved May 29, 1884 (23 Stat. 31); ``(H) the Federal-State cooperative programs of forest protection, management, and improvement performed under authority of the Act entitled `An Act to provide for the protection of forest lands, for the reforestation of denuded areas, for the extension of national forests, and for other purposes, in order to promote the continuous production of timber on the lands chiefly suitable therefore', approved June 7, 1924 (43 Stat. 653); of the Cooperative Forest Management Act, approved August 25, 1950 (64 Stat. 473); and of the Forest Pest Control Act, approved June 25, 1947 (61 Stat. 177); and the predecessor programs of any Act referred to in this paragraph; ``(I) the Federal-State cooperative programs of emergency relief, including State rural rehabilitation corporation programs established for the purposes of the Federal Emergency Relief Act of 1933, approved May 12, 1933 (48 Stat. 55); the Act entitled `An Act making an additional appropriation to carry out the purposes of the Federal Emergency Relief Act of 1933, for continuation of the civil works program, and for other purposes', approved February 15, 1934 (48 Stat. 351); and title II of the Act entitled `An Act making appropriations to supply deficiencies in certain appropriations for the fiscal year ending June 30, 1934, and prior fiscal years, to provide supplemental general and emergency appropriations for the fiscal years ending June 30, 1934, and June 30, 1935, and for other purposes', approved June 19, 1934 (48 Stat. 1021); ``(J) the Federal-State Cooperative Veterans' educational programs, including part-time instruction in on-the-farm training programs, as provided for in title II, chapter IV, `Education of Veterans', of the Serviceman's Readjustment Act of 1944, approved June 22, 1944 (58 Stat. 287), and subsequent amendments and Acts pertaining thereto; ``(K) the Federal-State cooperative programs in wildlife restoration and in fish restoration and management authorized respectively by the Acts entitled `An Act to provide that the United States shall aid these States in wildlife restoration projects, and for other purposes', approved September 2, 1937 (50 Stat. 917), and popularly referred to as the Pittman- Robertson Act, and `An Act to provide that the United States shall aid the States in fish restoration and management projects, and for other purposes', approved August 9, 1950, and popularly referred to as the Dingell-Johnson Act (64 Stat. 431) and the program of animal damage control authorized by the Act entitled `An Act to authorize the Secretary of Agriculture to carry out his ten-year cooperative program for the eradication, suppression, or bringing under control of predatory and other wild animals injurious to agriculture, horticulture, forestry, animal husbandry, wild game, and other interests, and for the suppression of rabies and tularemia in predatory or other wild animals, and for other purposes', approved March 2, 1931 (46 Stat. 1468). ``(2) Within 60 days following the date of enactment of the Agricultural Extended Retirement Credit Act of 2002, the Office of Personnel Management shall promulgate specific extended credit application and certification instructions to be followed by the Secretary of Agriculture in determining eligibility for extended credit for periods of service in the Federal-State cooperative programs enumerated in subsection (b)(18), and by individuals in making application for such extended credit.''. (e) Annuity Adjustments.--Section 8345 of title 5, United States Code, is amended by adding at the end the following: ``(m) If the Secretary of Agriculture certifies to the Office of Personnel Management creditable service for purposes of this subchapter of the type described in section 8332(b)(17), in response to application by an annuitant or survivor annuitant, then the annuity of the annuitant or survivor annuitant shall be adjusted on the first day of the month following the date of enactment of the Agricultural Extended Retirement Credit Act of 2002 so that the amount of the annuity shall be the same as if the total creditable service of the employee or Member, on whose creditable service the annuity was computed, had included, on the original date on which the annuity was computed, the amount of service certified.''. SEC. 4. EXPEDITED RETIREMENT SAVINGS. (a) In General.--Notwithstanding any other provisions of law, the Secretary of Agriculture shall at the end of each pay period for which both the first and last days occur in the expedited retirement period transfer to the expedited retirement trust fund, out of any monies appropriated to the Department of Agriculture, an amount equal to expedited retirement savings for that pay period. (b) Definitions.--For the purpose of this section-- (1) the term ``pay period'' means the biweekly Federal pay period; (2) the term ``expedited retirement period'' means the period beginning on the 60th day after the date of enactment of this Act and ending at the end of the fourth fiscal year which begins on or after the first day of such period; (3) the term ``expedited retiree'' means an individual who retires from a position in the Department of Agriculture on any day of the expedited retirement period and who receives extended credit under the amendments made by this Act; (4) the term ``expedited retiree pay rate'' means the biweekly regular pay rate of an expedited retiree on his or her last day of employment before retirement; (5) the term ``expedited retirement savings'' means, for any given pay period for which both the first and last days occurred within the expedited retirement period, the aggregate of 160 percent of the expedited retiree pay rates for all expedited retirees whose last day of employment prior to retirement occurred on or before the first day of the given pay period; and (6) the term ``expedited retirement trust fund'' means a trust fund of the Department of Agriculture which serves as depository for budget authority and outlay saved in any fiscal year of the expedited retirement period resulting from implementation of this Act and amendments made by this Act. SEC. 5. LIMITATION ON USE OF SAVINGS. (a) In General.--(1) None of the budget authority and outlays saved in any fiscal year by reason of the transfer of expedited retirement savings to the expedited retirement trust fund resulting from the implementation of this Act and the amendments made by this Act may be obligated or expended for any purpose. (2) The total amount of budget authority and outlays saved in any fiscal year (as described in paragraph (1)) shall, at the end of that fiscal year be carried to the surplus fund of the Department of Agriculture and deposited by the Secretary of Agriculture in the Treasury of the United States to the credit of the Civil Service Retirement and Disability Fund, as a contribution of the United States Government to such Fund, under such procedures as the Comptroller General may prescribe. (3) The total amount of budget authority and outlays saved in any fiscal year (as described in paragraph (1)) shall be credited against any amount of pay and other personnel and direct support costs required to be sequestered in such fiscal year under the Balanced Budget and Emergency Deficit Control Act of 1985 (Public Law 99-177). (b) Audits.--The Comptroller General shall notify Congress, in writing, of each noncompliance with the requirements of subsection (a). SEC. 6. PROGRAM REPORT. (a) In General.--Not later than 1 year after the first day of the expedited retirement period, the Director of the Office of Personnel Management shall transmit to Congress a report containing an evaluation of the expedited retirement savings program. (b) Contents of Report.--The report under subsection (a) shall include the following: (1) The number of employees who retired under the expedited retirement program, stated by age group of the retirees, and by grade or other position classification of the retirees. (2) The amount of expedited retirement savings that have resulted, before the date of the report, from the implementation of this Act and the amendments made by this Act. (c) Administrative Provision.--The Director of the Office of Personnel Management may obtain from any agency of the Federal Government such information as the Director determines necessary to prepare the report required by subsection (a).

Title: To amend title 5, United States Code, to allow periods of certain service performed as an employee under certain Cooperative Federal-State programs to be creditable for purposes of civil service retirement Summary: Agricultural Extended Retirement Credit Act of 2002 - Extends creditable service under the Civil Service Retirement System for periods of service in certain Federal-State cooperative programs which had agricultural or related purposes.Requires the Office of Personnel Management (OPM) to promulgate specific extended credit application and certification instructions to be followed by the Secretary of Agriculture in determining eligibility for extended credit for such periods of service, and by individuals in making application for such extended credit. Provides for appropriate annuity adjustments upon certification by the Secretary to the Office of Personnel Management (OPM) in response to annuitant applications.Directs the Secretary to transfer to the expedited retirement trust fund an amount equal to the expedited retirement savings realized by individuals receiving extended retirement credit under this Act.Prohibits the obligation or expenditure of any budget authority or outlays saved in any fiscal year by reason of implementation of this Act. Requires transfer to the Department's surplus fund of the savings resulting from the expedited retirement of those employees of the Department who have been extended such credit. Requires the surplus budget authority and outlays so transferred to be: (1) deposited by the Secretary in the Treasury to the credit of the Civil Service Retirement and Disability Fund, as a Government contribution; and (2) credited against pay and other personnel costs required to be sequestered under the Balanced Budget and Emergency Deficit Control Act of 1985 (Gramm-Rudman-Hollings Act).Requires the Comptroller General to notify the Congress of each instance of noncompliance with such requirements.Directs the OPM Director to report to the Congress an evaluation of the expedited retirement savings program.

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Summarize: BEIJING — The missiles were being prepared even before the two men finished dinner, disrupting the carefully choreographed proceedings. The American attack on Syria on Thursday unraveled China’s well laid plans for a summit meeting that would present President Xi Jinping as a global leader on par with President Trump, at once stealing the spotlight from Mr. Xi and putting him in a difficult position: choosing between condoning the kind of unilateral military action that China has long opposed, or rebuking his host. Mr. Xi’s dilemma was also acute because China has generally sided with Russia in defending Syria’s president, Bashar al-Assad, and because it worries that Mr. Trump might be prepared to order a similar strike on North Korea, Chinese and Western analysts said. “Xi can’t fail to be impressed by Trump’s resolve,” said Alan Dupont, an Australian military analyst who worked for that country’s Defense Department. “Xi will have to reassess what the Trump presidency means for Chinese interests in East Asia, particularly North Korea and the South China Sea.” Image copyright Reuters Image caption Trump and Xi faced each other for Friday talks "Tremendous progress" has been made in talks with Chinese President Xi Jinping, Donald Trump said on the summit's second and final day. "I think truly progress has been made," the US president said, declaring the relationship as "outstanding". The two men and their staff sat face to face for talks at Mr Trump's Mar-a-Lago retreat in Florida. Last year Mr Trump said China had "raped the US" and vowed to brand the superpower a currency manipulator. But at a welcome banquet it was all smiles and the good spirits appeared to continue on Friday as Mr Xi's visit concluded with a working lunch. On the night of the Chinese president's arrival, a US airstrike on an airbase in Syria was launched in response to a suspected chemical weapons attack. The attack was made public on Thursday evening just moments after Mr Xi and his wife left the resort following dinner. Beijing has avoided publicly taking sides on the issue. Xi likely to be angry - Carrie Gracie, BBC China editor China's position on Syria is much closer to Russia's than to the US. And the Chinese government will guess that the timing of the American missile strike was a blunt message that without more robust Chinese help on dismantling Kim Jong-un's nuclear programme, the next target for pre-emptive American military action might be North Korea. In Chinese protocol, sudden moves disrupting setpiece occasions are avoided wherever possible, and in private, President Xi is likely to be angry that President Trump chose to strike on the very night of his visit. But in public Mr Xi stuck to his script about the virtues of co-operation while Mr Trump insisted they'd formed an outstanding relationship and made great progress. As the two presidents went into their final lunch there were no specifics though, and in the aftermath of the US missile strike on Syria, all the big questions which bedevil the US China relationship have been kicked down the road for President Trump's visit to China later this year. Image copyright Reuters Image caption Thy dined on pan-seared Dover sole and New York strip steak "We have made tremendous progress in our relationship with China," Mr Trump said on Friday, without going into detail. Mr Xi urged co-operation on trade and invited his host to visit China. According to a statement on China's foreign ministry website, Mr Xi told Mr Trump: "We have a thousand reasons to get China-US relations right, and not one reason to spoil the China-US relationship." An A-Z of hot topics for Trump and Xi What can Trump do about trade with China? The cost of Trump's 'Winter White House' Media playback is unsupported on your device Media caption What American and Chinese people want On Thursday evening, they dined on pan-seared Dover sole and New York strip steak in an ornate candle-lit private dining room decked with red and yellow flowers. Mr Trump's daughter, Ivanka, and her husband, Jared Kushner, who both work at the White House, were also among guests. The leaders of the world's two most powerful economies are a study in contrasts - one a softly spoken Communist Party apparatchik and the other a brash Manhattan property tycoon. During the election campaign, Mr Trump said massive trade deficits and job losses could no longer be tolerated. Image copyright Reuters Image caption Mr Trump gestures during a discussion with his guests But he has so far not followed through on his threat to formally brand China a "currency manipulator", nor to hit Chinese imports with punitive tariffs. The Republican president's blue-collar supporters hope he can translate his China-bashing election rhetoric into concrete gains for American manufacturing workers. One of the most urgent issues for the US is nuclear-armed North Korea, which is trying to develop an intercontinental ballistic missile capable of hitting the west coast of the US. Media playback is unsupported on your device Media caption Maureen and Isabella don't see eye-to-eye on Trump Beijing has so far been chary of isolating its neighbour, fearing its collapse could spawn a refugee crisis and bring the US military to its doorstep. Some protesters lined the streets on Thursday to voice their opposition to China's policy in the South China Sea. PALM BEACH, Fla. (Reuters) - President Donald Trump pressed Chinese President Xi Jinping to do more to curb North Korea’s nuclear program and help reduce the gaping U.S. trade deficit with Beijing in talks on Friday, even as he toned down the strident anti-China rhetoric of his election campaign. Trump spoke publicly of progress on a range of issues in his first U.S.-China summit – as did several of his top aides – but they provided few concrete specifics other than China’s agreement to work together to narrow disagreements and find common ground for cooperation. As the two leaders wrapped up a Florida summit overshadowed by U.S. missile strikes in Syria overnight, Xi joined Trump in stressing the positive mood of the meetings while papering over deep differences that have caused friction between the world’s two biggest economies. Trump’s aides insisted he had made good on his pledge to raise concerns about China’s trade practices and said there was some headway, with Xi agreeing to a 100-day plan for trade talks aimed at boosting U.S. exports and reducing China’s trade surplus with the United States. Speaking after the two-day summit at Trump’s Mar-a-Lago resort in Florida, U.S. Secretary of State Rex Tillerson also said that Xi had agreed to increased cooperation in reining in North Korea’s missile and nuclear programs – though he did not offer any new formula for cracking Pyongyang’s defiant attitude. Trump had promised during the campaign to stop what he called the theft of American jobs by China. Many blue-collar workers helped propel him to his unexpected election victory on Nov. 8 and Trump is under pressure to deliver for them. The Republican president tweeted last week that the United States could no longer tolerate massive trade deficits and job losses and that his meeting with Xi “will be a very difficult one.” On Friday, the unpredictable Trump not only set a different tone but also avoided any public lapses in protocol that Chinese officials had feared could embarrass their leader. “We have made tremendous progress in our relationship with China,” Trump told reporters as the two delegations met around tables flanked by large U.S. and Chinese flags. “We will be making additional progress. The relationship developed by President Xi and myself I think is outstanding. “And I believe lots of very potentially bad problems will be going away,” he added, without providing details. “AGREE WITH YOU 100 PERCENT” Xi also spoke in mostly positive terms. “We have engaged in deeper understanding, and have built a trust,” he said. “I believe we will keep developing in a stable way to form friendly relations... For the peace and stability of the world, we will also fulfill our historical responsibility.” U.S. President Donald Trump (L) and China's President Xi Jinping walk along the front patio of the Mar-a-Lago estate after a bilateral meeting in Palm Beach, Florida, U.S., April 7, 2017. REUTERS/Carlos Barria “Well, I agree with you 100 percent,” Trump replied. China’s official Xinhua news agency said Xi had encouraged the United States to take part in the “One Belt, One Road” plan, Xi’s signature foreign policy imitative aimed at infrastructure development across Asia, Africa and Europe, seen in some policy circles as a partial answer to the pivot to Asia strategy of Trump’s predecessor Barack Obama. Xi also hailed military to military exchanges and said China and the United States should “make good use of the dialogue mechanism to be established between the two countries’ joint staffs of the armed forces”, although Xinhua did not give further details. Chinese state media on Saturday cheered the meeting as one that showed the world that confrontation between the two powers was not inevitable and established the tone for the development of U.S.-China relations. But in a sign that rough spots remained, Tillerson afterwards described the discussions as “very frank and candid.” “President Trump and President Xi agreed to work in concert to expand areas of cooperation while managing differences based on mutual respect,” he said. After the meeting, Trump took Xi on a walk around the manicured grounds of his lavish Spanish-style complex. Trump could be seen chatting and gesturing to Xi, who did the same. Tillerson said Trump had accepted Xi’s invitation to visit China and that they also agreed to upgrade a U.S.-China dialogue by putting the two presidents at the head of the forum. U.S. Commerce Secretary Wilbur Ross said the Chinese had expressed an interest in reducing China’s trade surplus as a way of controlling their own inflation. “That’s the first time I’ve heard them say that in a bilateral context,” he said. Ross declined to say whether the United States was ready to designate China a currency manipulator, however, referring to an upcoming report in which that issue would be addressed. Although Trump during the presidential election campaign had pledged to label China a currency manipulator on the first day of his administration, he has refrained from doing so. The highly anticipated U.S.-China summit was upstaged by U.S. missile strikes overnight against a Syrian air base from which Trump said a deadly chemical weapon attack had been launched earlier in the week. It was the first direct U.S. assault on the Russian-backed government of Syrian President Bashar al-Assad in six years of civil war. The swift action in Syria could be interpreted as a signal especially to defiant nuclear-armed North Korea – and by extension, its ally China – as well as other countries like Iran and Russia of Trump’s willingness to use military force. North Korea is developing missiles capable of hitting the United States. Slideshow (9 Images) Tillerson said Xi agreed with Trump that North Korea’s nuclear advances had reached a “very serious stage.” He said Trump also raised U.S.concerns about China’s activities in the South China Sea. Beijing is building and fortifying islands in pursuit of expansive territorial claims in the strategic waterway.

Summary: Last week, President Trump tweeted that his meeting with the Chinese president "will be a very difficult one"-not a surprising prediction given Trump once accused China of having "raped the US," but apparently an incorrect one. The BBC reports Trump ended his two-day summit with Xi Jinping by crowing about the "tremendous progress" made by the two. He says they now have an "outstanding" relationship and that "lots of very potentially bad problems will be going away," according to Reuters. Xi echoed Trump's positive generalities and invited the US president to visit China soon, an offer Trump accepted. Chinese state media reported positively on the summit, noting that Trump's granddaughter sang and recited poetry in Chinese, the New York Times reports. Despite the rosy words, there was one dark cloud hanging over the meeting. Xi is likely to be privately angry about the timing of the US airstrike on Syria, which occurred in the middle of the summit. Not only did it break with Chinese protocol, but it upstaged Xi, who had hoped to use the meeting to be seen by the world as Trump's equal. China typically sides with Russia in support of Assad and opposes unilateral military action. Experts believe Xi and China are more likely to take Trump's threats against North Korea seriously following the airstrike, which may result in China doing more to pressure the regime of Kim Jong Un.

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Summarize: WASHINGTON ― Ohio Gov. John Kasich, a top Republican leader and former candidate for the party’s presidential nomination, on Sunday said the GOP may be on a trajectory to lose supporters like him. “If the party can’t be fixed, Jake, then I’m not going to be able to support the party, period,” he told Jake Tapper on CNN’s “State of the Union,” a few minutes after he noted that Americans seem more eager to hear from independent candidates than ever before. The governor’s comment came in response to a question about how Republicans should react to Alabama politician Roy Moore securing their party’s nomination for that state’s open Senate seat. Moore is a former judge who was twice removed from Alabama’s Supreme Court for violating legal standards, and Tapper noted that he has said homosexual conduct should be illegal, questioned the birthplace of former President Barack Obama and suggested Rep. Keith Ellison (D-Minn.) should not be allowed a position in Congress because he is a practicing Muslim. “Well, look, I don’t run the party. I can tell you for me, I don’t support that. I couldn’t vote for that. I don’t know what the heck I would have to do, but I don’t live in that state. I mean, those claims are ― I mean, they’re ludicrous and they’re divisive,” Kasich said, adding that the party needs to be “fixed” to limit the influence of far-right elements and he sees his job as trying to get that done. The governor said he hopes figures like Moore do not represent the GOP’s future. Tapper explicitly asked if Kasich might split from the GOP if it continues being associated with figures like Moore. “No, not at this...” the governor responded, trailing off as if to hint that a time may come when he would consider parting ways with GOP. “What I’m saying to you is, we need to fix it. If our party, if the Republican Party is going to be anti-immigration, if it’s not going to be worried about debt, if it’s going to be anti-trade, this is not where our party can be. So I’m going to fight like everything I have... it’s why I’m on these shows, because I want this party to be straightened out. But I not only want the party to be straightened out, I want the country to be straightened out. And so it’s really a battle again inside of both parties, but people are beginning to say, I don’t like either of them. And that says something big. So hopefully our party leaders will pay attention to this.” Despite his criticisms of President Donald Trump, Kasich retains influence in the party because of his popularity in Ohio and is seen as a standard-bearer for GOP centrists distressed by Trump’s rise. He’s also cultivated an image as a uniter, in contrast to Trump’s divisiveness, reaching out to Democrats on issues like health care reform. The governor recently ruled out rumors of his running in 2020 on a joint ticket with Democratic Gov. John Hickenlooper of Colorado. Ohio Gov. John Kasich (R) pushed back Sunday on President Trump's tweets attacking San Juan Mayor Carmen Yulín Cruz, dubbing them inappropriate. ADVERTISEMENT "It's not appropriate. I mean when people are in the middle of a disaster, you don't start trying to criticize them," Kasich told CNN's Jake Tapper on "State of the Union," adding, "It's just not the way I think it ought to be handled. It's not the way we handle disasters here." "Everything has to be directed that way. These people, their lives are in danger," he said. Kasich's comments come after Trump attacked Cruz in a series of tweets on Saturday, accusing her of showing poor leadership during the island's recovery efforts. The Mayor of San Juan, who was very complimentary only a few days ago, has now been told by the Democrats that you must be nasty to Trump. — Donald J. Trump (@realDonaldTrump) September 30, 2017...Such poor leadership ability by the Mayor of San Juan, and others in Puerto Rico, who are not able to get their workers to help. They.... — Donald J. Trump (@realDonaldTrump) September 30, 2017...want everything to be done for them when it should be a community effort. 10,000 Federal workers now on Island doing a fantastic job. — Donald J. Trump (@realDonaldTrump) September 30, 2017 Cruz had issued an emotional plea for help on Friday, in which she condemned the federal government's response to the disaster. "I will do what I never thought I was going to do. I am begging, begging anyone who can hear us to save us from dying. If anybody out there is listening to us, we are dying, and you are killing us with the inefficiency," Cruz said. The Trump administration is under fire for the slow movement of aid, including food, water and medicine, to Hurricane Maria's victims on Puerto Rico, which was left without power after the storm. Trump has cited the distance to the island from the mainland U.S. as one difficulty in the federal response, which he called "incredible" overall. Story highlights Kasich said he does not support former Judge Roy Moore "I want this party to be straightened out" Washington (CNN) Ohio Republican Gov. John Kasich said on CNN's "State of the Union" Sunday that a time could come when he no longer supports the Republican Party. "If the party can't be fixed, Jake, then I'm not going to be able to support the party. Period. That's the end of it." Kasich said in an interview with anchor Jake Tapper. Asked what that meant for his future in the GOP, Kasich said he was committed to the party and intended to win it over from the surging nationalist wing. "I want this party to be straightened out," Kasich said. Kasich repeatedly pointed to public dissatisfaction with the Republican and Democratic parties, and referenced the strength of independent political identities. He said both parties needed to grapple with ideological currents pulling them away from the center, adding that he had "no idea what the Democrats are for." Read More

Summary: John Kasich revealed over the weekend he's been doing some soul-searching, but it's not his own soul he's scrutinizing. The Ohio governor chatted with Jake Tapper Sunday morning on CNN's State of the Union, and he had harsh words for both major political parties. He admitted he had "no idea what the Democrats are for," but he was even more blunt about his own party. "I want [the GOP] to be straightened out," he said, adding that "what I'm trying to do is struggle for the soul of the Republican Party the way that I see it." And the way he sees it as it stands now is infiltrated by "divisive" far-right forces that are "anti-immigration" and "anti-trade" and not terribly concerned about debt. The conversation arose after Tapper asked Kasich if he supported Judge Roy Moore, who recently won the Alabama GOP primary for Jeff Sessions' former Senate seat. Tapper pointed out Moore has railed against homosexuality, helped perpetuate birtherism lies about Barack Obama, and voiced anti-Muslim sentiments, per HuffPost. ""I don't support that. I couldn't vote for that, "Kasich replied, calling Moore's claims"ludicrous. ""If the party can't be fixed, Jake, then I'm not going to be able to support the party, period, "he said."I'm worried about the country and my kids' future. "He waffled, though, when Tapper asked him if he'd actually ditch the GOP."No, not at this... what I'm saying to you is, we need to fix it, "he said."I want this party to be straightened out. But I not only want the party to be straightened out, I want the country to be straightened out. "Kasich also touched on Trump's Puerto Rico tweets, noting, per the Hill:"It's not appropriate.... When people are in the middle of a disaster, you don't start trying to criticize them.... Their lives are in danger. "

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