bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of high-risk HPV DNA in semen and its association with the quality of semen
Authors: Rintala M A M , Greénman S E , Pöllänen P P , Suominen J J O , Syrjänen S M
Published: May 2006

The effects of seminal high-risk human papillomavirus (HPV) DNA were assessed on the quality of semen. Semen samples of 65 men participating in the ongoing Finnish HPV Family Study were collected. Semen analyses were done by the guidelines of the Nordic Association for Andrology. HPV DNA was detected by nested polymerase chain reaction and confirmed by Southern blot hybridization for high-risk types.

Altogether, 10/65 men (15.4%) had high-risk HPV DNA positive semen sample. Seminal high-risk HPV DNA did not affect semen volume, sperm concentration, motility and vitality of spermatozoa. However, semen pH was borderline lower in HPV DNA positive than negative samples (7.4 vs 7.5). Neither oligo- nor asthenozoospermia was associated with seminal HPV DNA.

In conclusion, seminal high-risk HPV DNA was detected in 15% of men. It did not affect the semen analysis, except semen pH by borderline significance. Sperm donors have not been tested for HPV infections, sperm washing does not seem to eliminate the risk of HPV transmission and the consequences of HPV in the semen are at present unknown.
Getting to the bottom of anal itch — a cautionary tale
Authors: Chan D J , Hillman R J , Medley G
Published: May 2006

Peri-anal rash is common and may appear macroscopically benign. In HIV-positive men, however, more serious pathology may be revealed by a biopsy. The high prevalence of human papillomavirus infection in these men predisposes them to pre-cancerous lesions of the peri-anal and anal skin. We report an unusual case of dual pathology in the anal region, which highlights the need to thoroughly investigate peri-anal symptoms in HIV-positive men.
Pigmented penile macules
Authors: Mahto Mrinalini , Woolley Paul David , Ashworth John
Published: May 2006

There are two opposing schools of thought regarding the management of pigmented penile macules. Allan and Spitz, as well as Pack and Davis, are of the opinion that almost all pigmented naevi present on the palms, soles and genitalia are junctional naevi and have a higher incidence of malignant change and, therefore, should be removed. On the other hand, because most cases of penile and urethral melanomas arise de novo with only a few arising from previous long-standing naevi and as precursor lesions are not identified in most cases, Scott et al. and Stegmaire et al. consider prophylactic excision unnecessary. A more practical approach has been taken up by Barnhill et al. and their view is that management should be individualized with multiple biopsies to establish the diagnosis. The purpose of this paper is to review the literature regarding the natural history, risk of melanoma development on the penis and the management of cases presenting with pigmented penile macules.
Critical appraisal of commonly used treatment for genital warts
Authors: Maw Raymond
Published: May 2006

Genital warts are one of the most commonly reported sexually transmitted diseases worldwide. A variety of treatment options are available but few have been assessed in large-scale, randomized, placebo-controlled trials. Provider-applied surgical and non-surgical treatments have traditionally been the therapies of choice. Surgical therapies, including cryotherapy, electrotherapy, laser surgery and surgical excision, are generally equivalent in terms of wart clearance rates, but are associated with high rates of wart recurrence. Trichloroacetic acid is a widely used non-surgical therapy, but little is known about its efficacy, and it is associated with unpleasant side-effects. The patient-applied treatments imiquimod and podophyllotoxin are newer therapy choices which are more acceptable to both patients and practitioners. The wart clearance rates for these two treatments are similar, although imiquimod is associated with lower recurrence rates. In the face of increasing pressures on genitourinary clinic services, patient-applied home therapy represents an attractive option for the treatment of genital warts.
Marginal validity of syndromic management for reproductive tract infections among pregnant women in Jamaica
Authors: Hylton-Kong T , Brathwaite A R , Del Rosario G R , Kristensen S , Kamara P , Jolly P E , Hook E W , Figueroa J P , Vermund S H
Published: May 2006

We assessed the validity of a syndromic case management approach for reproductive tract infections (RTIs) among 371 pregnant women attending antenatal care facilities in Kingston, Jamaica, using an algorithm previously validated in high-risk Jamaican women. For our antenatal attenders, the algorithm had low sensitivities for all RTIs (66.7% for cervicitis, 35.4% for trichomoniasis, 11.1% for bacterial vaginosis (BV) and 24% for candidiasis). Specificities for BV (88.9%) and candidiasis (81.1%) were higher than for cervicitis (62.8%) and trichomoniasis (68.5%). The positive predictive values were lower than 36% for all diagnoses, especially BV (6.9%). Syndromic management of RTIs in pregnant women was problematic using a clinical algorithm that had worked well for high-risk women. Syndromic management for RTIs in Jamaican antenatal clinics is only a temporary solution until more simple and affordable diagnostic tests for RTIs are developed and/or until laboratory support and clinical care can be upgraded at antenatal clinics.
Client perspectives on sexual health service provision
Authors: Melville Catriona R S , Bigrigg Alison , Nandwani Rak
Published: May 2006

Development of integrated genitourinary medicine (GUM) and family planning (FP) services must take into account the views and requirements of service users. As we strive to modernize sexual health services, various changes are being introduced, such as a policy of no microscopy for selected patients attending GUM clinics. In order to determine the views of our clients prior to implementation of change, we performed a qualitative study in our UK centre, which houses both FP and GUM. One hundred women presenting to FP and 100 to GUM were interviewed. In addition, we collected details of their characteristics to identify any significant differences in users attending each clinic. A summary of their views and characteristics is presented. Although near-patient testing results in a longer time spent in clinic, 99% of participants expressed a preference for immediate microscopy results and treatment. GUM and FP clients exhibited many similar characteristics.
Condom use in multi-partnered females
Authors: Tawk H M , Simpson J M , Mindel A
Published: May 2006

Many women attending sexual health clinics have multiple partners, and determining factors associated with condom use may provide useful information for health promotion strategies. Demographic and sexual data were obtained from computerized records at the Sydney Sexual Health Centre from 1991 to 1999. Females with >2 partners were categorized according to their condom use in the last three months and compared using chi-squared (χ2) tests and logistic regression. Of the 2198 women identified, 22% did not use condoms, 28% reported consistent condom use and 50% inconsistent use. Variables independently associated with failure to use condoms included older age and being in a regular relationship. Women with more partners were more likely to use condoms. Students [odds ratio (OR)=0.7 (95% confidence interval (CI) 0.5-0.9)] and those in employment [OR=0.7 (95% CI 0.5-0.9)] were more likely to use condoms than the unemployed. Focusing health promotion on multi-partnered women who fail to use condoms consistently may help in reducing sexually transmitted infections.
Impact of information leaflets on HIV test uptake amongst GUM clinic attendees: an update
Authors: Das Satyajit , Huengsberg Mia , Radcliffe Keith
Published: May 2006

In the Sexual Health Strategy, the targets of HIV testing uptake in genitourinary medicine clinics (GUM) are set at 40% by year 2004 and 60% by 2007. We assessed the uptake of HIV test amongst GUM clinic attendees, more than six months after introducing an information leaflet in place of verbal pre-test counselling (PTC). The uptake rate was significantly higher than in a previous audit conducted in the same year, two weeks after introduction of the leaflets (62% vs 50%, P =0.001).
Increasing response rates to postal questionnaires: a randomised trial of variations in design
Authors: Puffer Suezann , Porthouse Jill , Birks Yvonne , Morton Veronica , Torgerson David
Published: May 2006

Objectives: Low response rates to postal questionnaires can threaten the validity of studies by reducing the effective sample size and introducing bias. The identification of methods with which to optimise response rates could, therefore, improve the quality of studies. In an attempt to identify such methods, we undertook a randomised trial of two simple variations in questionnaire design.

Methods: Using a 2 × 2 factorial design, we conducted a randomised trial to test two variations in questionnaire design; the questionnaires were printed on either single-sided or double-sided paper and had either a single- or multiple-booklet layout. Using equal random allocation, 3836 women were randomised to receive one of these questionnaires as part of a study investigating risk factors for osteoporotic fractures.

Results: One thousand eight hundred and seventy questionnaires were returned, giving an overall response rate of 48.7%. There were no significant differences in the overall response to each of the four questionnaire designs. When the number of responders who completed at least 50% of each of the three sections was identified, it was found that single-booklet questionnaires had a better response than the multiple-booklet questionnaires and that single-sided questionnaires had a better response than double-sided questionnaires. However, these results were not significant at the 5% level. There were no significant differences in the response to questions on the odd (left-hand side) pages for the single- compared with the double-sided questionnaires.

Conclusion: As the most cost-effective use of resources, we would advocate the use of double- rather than single-sided questionnaires, and use of a single- rather than multiple-booklet design.
Health care resource allocation: is the threshold rule good enough?
Authors: Lord Joanne , Laking George , Fischer Alastair
Published: May 2006

We review the foundations of resource allocation rules based on cost-effectiveness information. Comprehensive approaches, where a total budget is allocated in one go, require estimation of the costs and effects of all available health care programmes, which is unlikely to be practical. A common alternative is to assess individual programmes against a cost-effectiveness threshold. This has been shown to be efficient if the threshold is well calibrated and all programmes can be wholly or partially implemented with constant returns to scale. We discuss the feasibility of these assumptions, and the effects of relaxing them, concluding that programme indivisibility is unlikely to be a serious problem at a national level, but that miscalibration of the threshold and non-constant returns to scale might be. A rule that avoids these difficulties has been proposed previously: a new programme should only be implemented if it can be funded by cancelling another less effective programme. This could never reduce efficiency, unlike the threshold rule, though we show that it might sometimes fail to recommend an efficiency-improving change. We suggest a refinement of this reallocation rule based on explicit estimation of the costs and effects of partial implementation of the programmes under review. Research is required to assess the practicality of this option.
Estimation of numbers of British medical graduates working in the National Health Service: comparison of capture–recapture analysis and exhaustive tracing
Authors: Lambert Trevor , Goldacre Michael , Davidson Jean , Parkhouse James
Published: May 2006

Objective: To compare the results of capture–recapture estimates and exhaustive follow-up in identifying the percentage of UK medical graduates who subsequently worked in the British National Health Service (NHS).

Methods: Postal questionnaire survey of all UK-trained doctors who graduated in 1974, with up to three reminders sent to non-respondents. Further exhaustive tracing of non-respondents to obtain whole population estimates of numbers in the NHS. Capture–recapture estimation of numbers working in the NHS, using survey data and Department of Health employment records, for comparison with results from exhaustive tracing.

Results: A total of 85.3% (1460/1712) of respondents were working in the NHS, but further exhaustive tracing of non-respondents revealed that only 75.9% (1758/2317) to 79.2% (1835/2317) of the whole cohort were in the NHS. By comparison, capture–recapture analysis estimated that 76.9% (1781/2317) of the cohort were in the NHS (95% CI: 75.9% to 78.0%).

Conclusions: Survey data alone overestimated the percentage of the whole cohort in the NHS. Capture–recapture estimates were very similar to those obtained by exhaustive tracing but were obtained more quickly and for much less clerical effort.
SRES, IPCC and the Treatment of Economic Issues: What Has Emerged?
Authors: Henderson David
Published: May 2006

This article reviews and extends the continuing debate on the treatment of economic issues by the Intergovernmental Panel on Climate Change (IPCC). Following an introduction, it has four main parts. Section 2, with its accompanying Annex 1, deals with one of the leading technical issues in the debate. It argues that, contrary to IPCC-related sources and some other analysts, exchange rates should not enter into measures or projections of output (real GDP). Section 3, in conjunction with Annexes 2 and 3, reviews again the projections of GDP and emissions that emerge from the IPCC's Special Report on Emissions Scenarios (SRES). It brings out in particular some confusions that have entered into the IPCC process and the arguments deployed in its defence. Section 4 lists the main weaknesses of the SRES, which are not a matter of the specific projections that it makes. These weaknesses cast doubt on the Panel's decision to use the SRES as a point of departure for its Fourth Assessment Report which is now in course of preparation. Section 5 considers the IPCC process as a whole. Attention is drawn again to the mishandling of economic evidence in IPCC documents and by the United Nations Environment Programme which is one of the IPCC's two parent agencies. New evidence of the professionally unrepresentative status of the IPCC milieu is cited from two sources: The Expert Meeting on Emissions Scenarios convened by the IPCC in January 2005; and the proceedings of the House of Lords Select Committee on Economic Affairs which has just reviewed ‘economic aspects of climate change’. The IPCC's dismissive response to independent critics, as illustrated in Annex 3, means that its handling of economic issues can be improved only if its member governments take action. Effective action will require in particular the involvement of the central economic departments of state: these will have to show greater awareness of what is at stake than Her Majesty's Treasury in its evidence to the Select Committee. More broadly, and going beyond economic aspects, it is high time to put in question the IPCC's status as a monopoly provider of information to governments on issues relating to climate change.
Australia's Environment Undergoing Renewal, Not Collapse
Authors: Marohasy Jennifer
Published: May 2006

In his new book Collapse Jared Diamond contends that the Australian environment is generally unproductive and has been irreversibly damaged by European farming, forestry and fisheries practices. Diamond reflects a popular view that is continually reinforced by environmental campaigning in Australia. The reality is more complex. Many Australian farms are amongst the most productive and sustainable in the world and in some situations have successfully broken natural cycles of low fertility. There are many examples where in the past there has been over-exploitation resulting in environmental damage. However government policies now tend to favor conservation over industry. Many once productive forests and fisheries are now closed to harvesting. These areas have become part of Australia's increasing reserve systems. By ignoring the evidence of ecological renewal and suggesting there is everywhere an environmental crisis, Diamond spreads misinformation and makes it difficult to identify the remaining real environmental issues that do need to be addressed.
Restless Bandit Marginal Productivity Indices, Diminishing Returns, and Optimal Control of Make-to-Order/Make-to-StockM/G/1Queues
Authors: Niño-Mora José
Published: May 2006

This paper presents a framework grounded on convex optimization and economics ideas to solve by index policies problems of optimal dynamic allocation of effort to a discrete-state (finite or countable) binary-action (work/rest) semi-Markov restless bandit project, elucidating issues raised by previous work. Its contributions include: (i) the concept of a restless bandit’s marginal productivity index (MPI), characterizing optimal policies relative to general cost and work measures; (ii) the characterization of indexable restless bandits as those satisfying diminishing marginal returns to work, consistently with a nested family of threshold policies; (iii) sufficient indexability conditions via partial conservation laws (PCLs); (iv) the characterization of the MPI as an optimal marginal productivity rate relative to feasible active-state sets; (v) application to semi-Markov bandits under several criteria, including a new mixed average-bias criterion; and (vi) PCL-indexability analyses and MPIs for optimal service control of make-to-order/make-to-stock queues with convex holding costs, under discounted and average-bias criteria.
Monotonic Assignment Rules and Common Pricing
Authors: Bergin James , Zhou Lin
Published: May 2006

In this paper we study the production and pricing of a good by a single supplier (such as a monopolist or government) under some given optimality criterion—for example, profit maximization or social benefit maximization. In general, this may require discriminatory pricing. The primary focus here is on the pricing policy and whether it is possible to achieve the same objective value with common pricing—where each individual acquiring the good pays the same price. We consider the case of declining (marginal) cost and show that for a large class of problems, optimality is achievable with common pricing. Because the environment is one of incomplete information, incentive and participation constraints are important restrictions on the problem. We frame the discussion in terms of interim expected utility. When ex post restrictions are considered, the problem is altered substantially, and the value of the objective may be lower under common pricing.
Measure-Valued Differentiation for Stationary Markov Chains
Authors: Heidergott Bernd , Hordijk Arie , Weisshaupt Heinz
Published: May 2006

We study general state-space Markov chains that depend on a parameter, say, θ. Sufficient conditions are established for the stationary performance of such a Markov chain to be differentiable with respect to θ. Specifically, we study the case of unbounded performance functions and thereby extend the result on weak differentiability of stationary distributions of Markov chains to unbounded mappings. First, a closed-form formula for the derivative of the stationary performance of a general state-space Markov chain is given using an operator-theoretic approach. In a second step, we translate the derivative formula into unbiased gradient estimators. Specifically, we establish phantom-type estimators and score function estimators. We illustrate our results with examples from queueing theory.
Second-Order Necessary Optimality Conditions for Problems Without A Priori Normality Assumptions
Authors: Arutyunov Aram , Pereira Fernando Lobo
Published: May 2006

In this article, we derive second-order necessary conditions of optimality for an abstract optimization problem with equality and inequality constraints and constraints in the form of an inclusion into a given closed set. An important feature is that our optimality conditions dispense with any a priori normality assumptions, such as Robinson’s constraint qualification, and remain informative even for abnormal points. Moreover, our optimality conditions take into account the second-order effect of the curvature of the set in the inclusion constraints.
Empirical Distributions of Beliefs Under Imperfect Observation
Authors: Gossner Olivier , Tomala Tristan
Published: May 2006

Let (xn)nbe a process with values in a finite set X and law P, and let yn= f(xn) be a function of the process. At stage n, the conditional distribution pn= P(xn∣ x1,…,xn−1), element of Π = Δ(X), is the belief that a perfect observer, who observes the process online, holds on its realization at stage n. A statistician observing the signals y1,…,ynholds a belief en= P(pn∣ x1,…,xn) ∈ Δ(Π) on the possible predictions of the perfect observer. Given X and f, we characterize the set of limits of expected empirical distributions of the process (en) when P ranges over all possible laws of (xn)n.
Automorphism Invariance ofP- andGUS-Properties of Linear Transformations on Euclidean Jordan Algebras
Authors: Gowda M. Seetharama , Sznajder Roman
Published: May 2006

Generalizing the P-property of a matrix, Gowda et al. [Gowda, M. S., R. Sznajder, J. Tao. 2004. Some P-properties for linear transformations on Euclidean Jordan algebras. Linear Algebra Appl. 393 203–232] recently introduced and studied P- and globally uniquely solvable (GUS)-properties for linear transformations defined on Euclidean Jordan algebras. In this paper, we study the invariance of these properties under automorphisms of the algebra and of the symmetric cone. By means of these automorphisms and the concept of a principal subtransformation, we introduce and study ultra and super P-(GUS)-properties for a linear transformation on a Euclidean Jordan algebra.
Association of Antisocial Personality Disorder with Psychiatric Morbidity among Patients with Substance Use Disorder
Authors: Westermeyer Joseph , Thuras Paul , Carlson Gregory
Published: May 2006

Objectives

The aims were to determine among patients with Substance Use Disorder (SUD) whether patients with Antisocial Personality Disorder (ASPD) manifest less, the same, or more of the following: (1) psychiatric symptoms, (2) family history of psychiatric disorder, (3) psychiatric disorders and morbidity, and (4) psychiatric treatment, as compared to patients without ASPD.

Design & Definition

Scheduled interview using DSM-III-R criteria for ASPD, with blinded interviewers making the ASPD classification vs. other assessments.

Settings

Alcohol-drug treatment programs located in two university medical centers.

Subjects

Six hundred and six voluntary patients aged 18 and older meeting diagnostic criteria for SUD.

Results

SUD patients with ASPD reported more family history of non-SUD psychiatric diagnoses and endorsed more hostility symptoms. Demographic characteristics, psychiatric disorder, and past psychiatric treatment did not differ in association with ASPD.
Violent Criminal Behavior and Perspectives on Treatment of Criminality in Opiate Treatment
Authors: Mays Darren M. , Gordon Adam J. , Kelley Mary E. , Forman Steven D.
Published: May 2006

Purpose

This study describes and compares the characteristics of patients within a VA Opiate Substitution Therapy Program (OSTP) who report arrests for non-violent and violent crimes and describes patients’ attitudes and preferences of criminal treatment within an OSTP.

Methods

An anonymous survey was distributed to all veterans at one VA-OSTP. Analyses were conducted to describe the sample characteristics and their associations with prior violent and non-violent criminal behavior.

Results

A majority of participants were Caucasian, male, middle-aged, unemployed, and had a history of injection drug use. Participants reported arrests for violent (44%), non-violent (47%), and unspecified crimes (16%). There were few significant differences on demographic and drug use characteristics between participants who reported arrests for any violent and only non-violent crimes, and no arrests. Slightly fewer than half the subjects were satisfied with their ability to access treatment for past criminal behavior within or outside of the VA treatment settings. More veterans reporting violent arrests were satisfied with services addressing criminal behavior within the VA-OSTP than were veterans reporting only nonviolent arrests. Nearly equal proportions of veterans reporting violent (45%) and non-violent (44%) arrests reported dissatisfaction with such services received outside of the VA-OSTP.

Conclusions

Prior violent criminal behavior is common among participants of a VA-OSTP. Many individuals with criminal histories seek treatment for criminality within VA-OSTP.
The Role of Vitamin D in Multiple Sclerosis
Authors: Brown Sherrill J
Published: May 2006

Objective:

To evaluate the literature about the role of vitamin D in the prevention and treatment of multiple sclerosis (MS).

Data Sources:

MEDLINE (1966–April 2006) and International Pharmaceutical Abstracts (1970–April 2006) searches were performed. In addition, pertinent references from identified articles were obtained. Key search terms included vitamin D, 25-hydroxyvitamin D, vitamin D deficiency, and multiple sclerosis.

Data Synthesis:

Vitamin D supplementation prevented the development and progression of experimental autoimmune encephalitis, an animal model of MS, in mice. A large, prospective, cohort study found that vitamin D supplementation was associated with a 40% reduction in the risk of developing MS. Four small, noncontrolled studies suggested that vitamin D supplementation may decrease exacerbation of MS symptoms.

Conclusions:

Vitamin D supplementation may help prevent the development of MS and may be a useful addition to therapy. However, current studies are in small populations and are confounded by other variables, such as additional vitamin and mineral supplementation.
Prevalence of Diarrhea at a University Hospital and Association with Modifiable Risk Factors
Authors: Garey Kevin W , Graham Gail , Gerard Laura , Dao Thanh , Jiang Zhi Dong , Price Margaret , DuPont Herbert L
Published: May 2006

Objective:

To assess the prevalence of diarrhea at a university-affiliated medical center and the presence of modifiable risk factors methods: A point prevalence survey was conducted. All patients hospitalized for more than 24 hours were asked if they were experiencing diarrhea. Stools of patients not previously tested were assessed for Clostridium difficile (CD) toxins A and B. Univariate analysis and multivariate logistic regression analyses were used to identify modifiable variables associated with diarrhea (significance defined as p < 0.05).

Results:

Four hundred eighty-five hospitalized patients were interviewed, of whom 60 (12.4%) reported 2 or more loose, unformed stools in the last 24 hours. Six of 81 (7.4%) patients tested positive for CD toxin. Three (50%) of the CD toxin–positive patients had not previously been tested during the current admission. Patients with diarrhea were more likely to have tested CD toxin–positive (OR 10.6; p = 0.01), received antibiotics (OR 1.79; p = 0.04), or been hospitalized for a longer period of time (p = 0.04).

Conclusions:

Diarrhea was prevalent in 12.4% of hospitalized patients at a large university hospital at one point in time. Patients with diarrhea were more likely to have CD infection, receive antibiotics, or experience a longer hospitalization. Half of the CD diarrhea cases occurring in the hospital had been previously unidentified. Hospitalized patients should be evaluated for diarrhea on an ongoing basis with appropriate interventions instituted.
Law and Order Blues
Authors: Weatherburn Don
Published: May 2006

This paper discusses law and order politics and policy in Australia. It challenges the conventional criminological wisdom that Australia does not have a serious crime problem. It argues that, while political responses to crime are all too frequently irrational, this is not because Australian state and territory governments so often rely on punitive law and order policies. Australian law and order policy is irrational because it usually lacks any clear rationale, is rarely subjected to any effectiveness or cost-effectiveness evaluation, frequently ignores the possibility of unintended side-effects and is occasionally founded on a misdiagnosis of the crime problem that prompts it. The paper concludes by discussing various explanations for this state of affairs and what can be done about it.
Depolarizing GABAergic Conductances Regulate the Balance of Excitation to Inhibition in the Developing Retinotectal CircuitIn Vivo
Authors: Akerman Colin J. , Cline Hollis T.
Published: May 2006

Neurotransmission during development regulates synaptic maturation in neural circuits, but the contribution of different neurotransmitter systems is unclear. We investigated the role of GABAAreceptor-mediated Cl−conductances in the development of synaptic responses in theXenopusvisual system. Intracellular Cl−concentration ([Cl−]i) was found to be high in immature tectal neurons and then falls over a period of several weeks. GABAergic synapses are present at early stages of tectal development and, when activated by optic nerve stimulation or visual stimuli, induce sustained depolarizing Cl−conductances that facilitate retinotectal transmission by NMDA receptors. To test whether depolarizing GABAergic inputs cooperate with NMDA receptors during activity-dependent maturation of glutamatergic synapses, we prematurely reduced [Cl−]iin tectal neuronsin vivoby expressing the Cl−transporter KCC2. This blocked the normal developmental increase in AMPA receptor-mediated retinotectal transmission and increased GABAergic synaptic input to tectal neurons. Therefore, depolarizing GABAergic transmission plays a pivotal role in the maturation of excitatory transmission and controls the balance of excitation and inhibition in the developing retinotectal circuit.
Dynamics of Spontaneous Activity in the Fetal Macaque Retina during Development of Retinogeniculate Pathways
Authors: Warland David K. , Huberman Andrew D. , Chalupa Leo M.
Published: May 2006

Correlated spontaneous activity in the form of retinal “waves” has been observed in a wide variety of developing animals, but whether retinal waves occur in the primate has not been determined previously. To address this issue, we recorded from isolated retinas using multielectrode arrays at six fetal ages: embryonic day 51 (E51), E55, E60, E67, E71, and E76. These recordings revealed that the fetal monkey retina is essentially silent at E51 and E55, with only few cells firing on rare occasions and without any obvious spatial or temporal order. Because previous work has shown that the magnocellular and parvocellular subdivisions of the dorsal lateral geniculate are selectively innervated during this early period, our results suggest that this process is unlikely to be regulated by retinal activity. Highly structured retinal waves were first observed at E60, >1 week before the segregation of eye-specific retinal dorsal lateral geniculate nucleus projections commences. The incidence of such waves decreased rapidly and progressively during the developmental period (E67–E76) when segregated eye-specific projections become established. Our findings indicate that retinal waves first occur in the fetal monkey at a remarkably early stage of development, >100 d before birth, and that this activity undergoes rapid changes in salient properties when eye-specific retinogeniculate projections are being formed.
Enhanced Ryanodine Receptor Recruitment Contributes to Ca2+Disruptions in Young, Adult, and Aged Alzheimer's Disease Mice
Authors: Stutzmann Grace E. , Smith Ian , Caccamo Antonella , Oddo Salvatore , LaFerla Frank M. , Parker Ian
Published: May 2006

Neuronal Ca2+signaling through inositol triphosphate receptors (IP3R) and ryanodine receptors (RyRs) must be tightly regulated to maintain cell viability, both acutely and over a lifetime. Exaggerated intracellular Ca2+levels have been associated with expression of Alzheimer's disease (AD) mutations in young mice, but little is known of Ca2+dysregulations during normal and pathological aging processes. Here, we used electrophysiological recordings with two-photon imaging to study Ca2+signaling in nontransgenic (NonTg) and several AD mouse models (PS1KI, 3xTg-AD, and APPSweTauP301L) at young (6 week), adult (6 months), and old (18 months) ages. At all ages, the PS1KIand 3xTg-AD mice displayed exaggerated endoplasmic reticulum (ER) Ca2+signals relative to NonTg mice. The PS1 mutation was the predominant “calciopathic” factor, because responses in 3xTg-AD mice were similar to PS1KImice,and APPSweTauP301Lmice were not different from controls. In addition, we uncovered powerful signaling interactions and differences between IP3R- and RyR-mediated Ca2+components in NonTg and AD mice. In NonTg mice, RyR contributed modestly to IP3-evoked Ca2+, whereas the exaggerated signals in 3xTg-AD and PS1KImice resulted primarily from enhanced RyR-Ca2+release and were associated with increased RyR expression across all ages. Moreover, IP3-evoked membrane hyperpolarizations in AD mice were even greater than expected from exaggerated Ca2+signals, suggesting increased coupling efficiency between cytosolic [Ca2+] and K+channel regulation. We conclude that lifelong ER Ca2+disruptions in AD are related to a modulation of RyR signaling associated with PS1 mutations and represent a discrete “calciumopathy,” not merely an acceleration of normal aging.
Parkinson's Disease Brain Mitochondrial Complex I Has Oxidatively Damaged Subunits and Is Functionally Impaired and Misassembled
Authors: Keeney Paula M. , Xie Jing , Capaldi Roderick A. , Bennett James P.
Published: May 2006

Loss of mitochondrial complex I catalytic activity in the electron transport chain (ETC) is found in multiple tissues from individuals with sporadic Parkinson's disease (PD) and is a property of some PD model neurotoxins. Using special ETC subunit-specific and complex I immunocapture antibodies directed against the entire complex I macroassembly, we quantified ETC proteins and protein oxidation of complex I subunits in brain mitochondria from 10 PD and 12 age-matched control (CTL) samples. We measured nicotinamide adenine dinucleotide (NADH)-driven electron transfer rates through complex I and correlated these with complex I subunit oxidation levels and reductions of its 8 kDa subunit. PD brain complex I shows 11% increase in ND6, 34% decrease in its 8 kDa subunit and contains 47% more protein carbonyls localized to catalytic subunits coded for by mitochondrial and nuclear genomes We found no changes in levels of ETC proteins from complexes II–V. Oxidative damage patterns to PD complex I are reproduced by incubation of CTL brain mitochondria with NADH in the presence of rotenone but not by exogenous oxidant. NADH-driven electron transfer rates through complex I inversely correlate with complex I protein oxidation status and positively correlate with reduction in PD 8 kDa subunit. Reduced complex I function in PD brain mitochondria appears to arise from oxidation of its catalytic subunits from internal processes, not from external oxidative stress, and correlates with complex I misassembly. This complex I auto-oxidation may derive from abnormalities in mitochondrial or nuclear encoded subunits, complex I assembly factors, rotenone-like complex I toxins, or some combination.
Synaptic Plasticity inCNGA3−/−Mice: Cone Bipolar Cells React on the Missing Cone Input and Form Ectopic Synapses with Rods
Authors: Haverkamp Silke , Michalakis Stylianos , Claes Ellen , Seeliger Mathias W. , Humphries Peter , Biel Martin , Feigenspan Andreas
Published: May 2006

In the mammalian retina, rods and cones connect to distinct sets of bipolar cells. Rods are presynaptic to a single type of rod bipolar cell, whereas cones connect to different types of cone bipolar cells. Synaptic rewiring between cone photoreceptor terminals and rod bipolar cell dendrites has been described as a general result of photoreceptor degeneration. To investigate whether cone bipolar cells also show synaptic plasticity in the absence of cone input, we studied the connectivity of cone bipolar cell dendrites inCNGA3−/−mice, a model with specific loss of cone photoreceptor function. Dendritic connections of ON and OFF cone bipolar cells were visualized using specific cell markers or by intracellular injection with fluorescent dyes. The results show that cone bipolar cells inCNGA3−/−mice form ectopic synapses with rods. In contrast, cone bipolar cells do not form ectopic synapses with rods inCNGA3−/−Rho−/−mice, in which both types of photoreceptors are nonfunctional. In analogy with these results, we found that input-deprived rod bipolar cells form ectopic synapses with functional cones inRho−/−mice but not with inoperable cones in theCNGA3−/−Rho−/−mouse. Our data indicate that the formation of ectopic bipolar cell synapses in the outer plexiform layer requires a functional presynaptic photoreceptor.
Sustained Activity in Topographic Areas of Human Posterior Parietal Cortex during Memory-Guided Saccades
Authors: Schluppeck Denis , Curtis Clayton E. , Glimcher Paul W. , Heeger David J.
Published: May 2006

In a previous study, we identified three cortical areas in human posterior parietal cortex that exhibited topographic responses during memory-guided saccades [visual area 7 (V7), intraparietal sulcus 1 (IPS1), and IPS2], which are candidate homologs of macaque parietal areas such as the lateral intraparietal area and parietal reach region. Here, we show that these areas exhibit sustained delay-period activity, a critical physiological signature of areas in macaque parietal cortex. By varying delay duration, we disambiguated delay-period activity from sensory and motor responses. Mean time courses in the parietal areas were well fit by a linear model comprising three components representing responses to (1) the visual target, (2) the delay period, and (3) the eye movement interval. We estimated the contributions of each component: the response amplitude during the delay period was substantially smaller (<30%) than that elicited by the transient visual target. All three parietal regions showed comparable delay-period response amplitudes, with a trend toward larger responses from V7 to IPS1 and IPS2. Responses to the cue and during the delay period showed clear lateralization with larger responses to trials in which the target was placed in the contralateral visual field, suggesting that both of these components contributed to the topography we measured.
Why the Reserve Price Should Not Be Kept Secret
Authors: Brisset Karine , Naegelen Florence
Published: May 2006

This paper considers the optimality of setting a secret reserve price in ascending auctions. Contrary to intuition, an ascending auction is no longer equivalent to a second price auction when the reserve price is secret. We determine the seller's optimal reserve price policy when the bidders' values are private and independently distributed and when the bidders are risk averse. We show that an optimal secret reserve price policy can dominate an optimal public reserve price policy when the bidders' degree of constant relative risk aversion is sufficiently high and when the seller can commit to a reserve price policy before learning her type. In contrast, a secret reserve price policy can never be part of a Bayesian equilibrium when the seller is informed.
Estimating Behavioral Response to the AIDS Epidemic
Authors: Auld M. Christopher
Published: May 2006

The elasticity of risky sexual behavior to changes in local HIV infection prevalence is estimated using a longitudinal survey of the sexual behavior and health of gay men in San Francisco during the 1980s. An average respondent decreases risky behavior by about 5% in response to a 10% increase in disease prevalence. The average response obscures substantial variation across respondents: High-risk people reduce risky behavior less than low-risk people as prevalence increases. This result is consistent with the predictions of theoretical economic epidemiology and has implications for epidemic dynamics.
Contextual Learning: A Reflective Learning Intervention for Nursing Education
Authors: Forneris Susan G , Peden-McAlpine Cynthia J.
Published: May 2006

Nursing educators need to continue to explore ways that new pedagogies such as narrative pedagogy and reflective practice inform and extend students' thinking in classroom and clinical situations. The goal of instruction becomes creating an opportunity for learning that integrates content knowledge with knowledge of the context. Educational methodologies that incorporate the use of context in a reflective, dialogical approach over time hold much promise in developing a dynamic process of thinking in practice. Contextual learning is a reflective learning intervention that offers new possibilities for nurse educators to prepare nurses to think critically in practice. In this expository paper the design and instructional methodology of contextual learning is discussed, beginning with a brief overview of the nature of critical thinking and the use of narrative as major underpinnings in the development of this intervention. Examples of how the intervention was implemented with novice nurses in practice is provided. Finally, reflections on how the intervention could be refined for nursing students is offered.
China's New Exchange Rate Policy: Will China Follow Japan into a Liquidity Trap?
Authors: McKinnon Ronald I
Published: May 2006

On July 21, 2005, China gave in to concerted foreign pressuresome of it no doubt well meantto give up the fixed exchange rate it had held and grown into over the course of a decade. American pressure on China today to appreciate the renminbi is eerily similar to the American pressure on Japan that began almost 30 years ago to appreciate the yen against the dollar. There are some differences, but downward pressure on interest rates from foreign exchange risk could lead China into a zero-interest liquidity trap much like the one Japan has suffered since the mid-1990s.
Froth in the Silicon Valley Housing Market?
Authors: Quigley John M.
Published: May 2006

Santa Clara County in California was the world capital of the dot-com economy before the bubble burst. Yet since the dot-com bubble burst housing prices have continued to rise. John Quigley asks: What's going on?
Grading the President's Tax Reform Panel's Plan
Authors: Kotlikoff Laurence J
Published: May 2006

Laurence Kotlikoff gives the current tax system a D, the Presidents Tax Reform Panel proposal a B+ and explains what his A+ tax system would look like.
Reply to Donohue and Wolfers on the Death Penalty and Deterrence
Authors: Rubin Paul H.
Published: May 2006

Donohue and Wolfers comment on an article where I was a coauthor. There are some errors and misstatements in their article that should be corrected.
Letter: A Reply to Rubin on the Death Penalty
Authors: Donohue John , Wolfers Justin J
Published: May 2006

Contrary to Paul Rubin's recent testimony to the Senate Judiciary Committee, we believe the fragility of their estimates and the invalidity of their instrumental variables undermine Dezhbakhsh, Rubin, and Shepherd's work as evidence that the death penalty deters murder.
Reply: The Death Penalty Once More
Authors: Rubin Paul H.
Published: May 2006

According to Paul Rubin, John Donohue and Justin Wolfers mischaracterize his analysis of the death penalty.
Tree Balance
Authors: Shao Kwang-Tsao , Sokal Robert R.
Published: May 2006

Hierarchic classifications can differ with respect to tree balance—the degree to which branches divide the subtended taxa into subsets of equal size. Several indices, sensitive to different aspects of tree balance, are compared. Extensions of these indices to multifurcating trees and to trees with varying numbers of OTUs are proposed, and suggestions for employing these indices are furnished. Different tree-forming algorithms may result in trees with differing degrees of balance no matter which index is computed. Tree balance is an important consideration for phylogenetic systematics, because balance of the true phylogeny will affect the accuracy of its estimates.
Hepatocyte Nuclear Factor-4α P2 Promoter Haplotypes Are Associated With Type 2 Diabetes in the Japanese Population
Authors: Hara Kazuo , Horikoshi Momoko , Kitazato Hiroji , Ito Chikako , Noda Mitsuhiko , Ohashi Jun , Froguel Philippe , Tokunaga Katsushi , Tobe Kazuyuki , Nagai Ryozo , Kadowaki Takashi
Published: May 2006

Hepatocyte nuclear factor (HNF)-4α is a transcription factor known as a key molecule in the development and functions of the β-cells. In a previously performed genome-wide scan of Japanese type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene is located. Recent studies have reported associations between type 2 diabetes and polymorphisms in the P2 promoter region specific to β-cells. In this study, we attempted to assess whether the HNF4A gene plays a role in the genetic susceptibility to type 2 diabetes in the Japanese population by analyzing polymorphisms and haplotypes of the HNF4A gene. Linkage disequilibrium across the P2 promoter region was preserved in the Japanese population, consistent with previous reports. Although none of the individual polymorphisms examined showed any significant association with type 2 diabetes, we found very strong evidence of the association between type 2 diabetes and the haplotype consisting of two polymorphisms in the P2 promoter region of the HNF4A gene (P = 3.82 × 10−4). In contrast, there was no association between type 2 diabetes and haplotypes consisting of polymorphisms not located in the P2 promoter region, suggesting that the type 2 diabetes susceptibility loci are localized in the P2 promoter region of the HNF4A gene. The association was replicated using two additional cohorts (P = 1.51 × 10−4 and 0.019, respectively). The results of the present analysis revealed that the HNF4A gene might be a type 2 diabetes susceptibility gene common to different ethnic groups. The study also suggested the possible existence of an as-yet-unidentified but functional polymorphism in the P2 promoter region of the HNF4A gene that directly influences susceptibility to type 2 diabetes.