cssi/SciSciGPT-SciSciNet huggingface dataset:
Cardiovascular Effects of Duloxetine: Preclinical and Clinical Findings

Background We summarize cardiac effects of duloxetine based on in vitro and animal studies, and human trials including higher doses and chronic treatment. Methods The affinity of duloxetine for cardiac ion channels was determined in vitro in a stably expressed human cell line. Cardiovascular parameters were evaluated in single- and repeat-dose studies in rats and dogs. In humans, cardiovascular safety was analyzed in (1) healthy volunteers receiving duloxetine up to 400 mg/d; (2) 8 placebo-controlled MDD trials of duloxetine (40-120 mg/d) for 8-9 weeks, compared with paroxetine or fluoxetine in 6 trials; (3) 52-week, open-label duloxetine study (80-120 mg/d); (4) 12-week MDD study of duloxetine versus venlafaxine. Results Duloxetine, at the maximum unbound plasma concentration observed clinically, had no adverse effect on the human cardiac ion channels tested in vitro. Blood pressure (BP) and heart rate (HR) were not significantly altered in conscious animals following single oral doses of 7 or 20 mg/kg in rats and 10 mg/kg in dogs. Cardiac rhythm, conduction, and HR were unaffected in dogs by up to 1 year of treatment with 3, 10, or 30 mg/kg. In healthy volunteers, duloxetine had a modest effect on BP and HR elevation with no prolongation of QTc interval. In patients with MDD, small increases in HR and BP were observed. Although there were statistically significant differences in HR from baseline to endpoint between duloxetine versus fluoxetine or paroxetine, changes were clinically insignificant. In the study of duloxetine (60-120 mg/day) and venlafaxine (75-225 mg/day) in MDD, no statistically significant differences occurred in elevated HR and BP except for significantly more venlafaxine patients with sustained systolic BP during the first 6 weeks. Discussion Consistent with the lack of effect on human cardiac ion channel binding in vitro, and the lack of effect on conduction parameters in repeat-dose dog studies, no QTc prolongation was seen in humans. Consistent with the HR and BP findings in animals, humans had a few small effects with these measures. In summary, duloxetine has a good cardiovascular safety profile, possibly due to its lack of affinity for crucial cardiac ion channels and/or other unknown factors. Funding provided by Eli Lilly and Company.
CT FINDINGS OF HYPERVASCULAR MALIGNANT PERITONEAL MESOTHELIOMA

A case of peritoneal mesothelioma is presented in which CT demonstrated abnormal regions of increased vascularity in the omentum corresponding to hypervascular omental lesions shown by angiography. This CT appearance has not been described in prior reports of CT in peritoneal mesothelioma.
Solving iTOUGH2 simulation and optimization problems using the PEST protocol

The PEST protocol has been implemented into the iTOUGH2 code, allowing the user to link any simulation program (with ASCII-based inputs and outputs) to iTOUGH2's sensitivity analysis, inverse modeling, and uncertainty quantification capabilities. These application models can be pre- or post-processors of the TOUGH2 non-isothermal multiphase flow and transport simulator, or programs that are unrelated to the TOUGH suite of codes. PEST-style template and instruction files are used, respectively, to pass input parameters updated by the iTOUGH2 optimization routines to the model, and to retrieve the model-calculated values that correspond to observable variables. We summarize the iTOUGH2 capabilities and demonstrate the flexibility added by the PEST protocol for the solution of a variety of simulation-optimization problems. In particular, the combination of loosely coupled and tightly integrated simulation and optimization routines provides both the flexibility and control needed to solve challenging inversion problems for the analysis of multiphase subsurface flow and transport systems.
The acquisitiveness of youth: CEO age and acquisition behavior.

Abstract I demonstrate that acquisitions are accompanied by large, permanent increases in Chief Executive Officer (CEO) compensation, which create strong financial incentives for CEOs to pursue acquisitions earlier in their career. Accordingly, I document that a firm's acquisition propensity is decreasing in the age of its CEO: a firm with a CEO who is 20 years older is ∼ 30 % less likely to announce an acquisition. This negative effect of CEO age on acquisitions is strongest among firms where CEOs likely anticipate or can influence high post-acquisition compensation, and is absent for other investment decisions that are not rewarded with permanent compensation gains. The age effect cannot be explained by the selection of young CEOs by acquisition-prone firms, nor by a story of declining overconfidence with age. This paper underscores the relevance of CEO personal characteristics and CEO-level variation in agency problems for corporate decisions.
A test method to determine rapidly if polymers are biodegradable

Polycaprolactone and polycaprolactone/polyethylene blends were exposed to two consortia, one containing three fungi (Aspergillus niger, Gliocladium virens, andPenicillium funiculosum) and one five fungi (the three aforementioned plusAureobasidium pullulans andChaetomium globosum). Evidence of metabolization of the polymer by the five-fungus consortium was obtained from the greater oxygen consumption in the presence of polycaprolactone than in the absence of the polymer. Minor differences in the composition of the consortium result in major differences in the ability of the consortium to utilize the polymer as a carbon source.
Project Succeed Academy: A Public-Private Partnership to Develop a Holistic Approach for Serving Students With Behavior Problems.

Alarming numbers of students, particularly minority students, are being suspended and expelled from our nations’ schools. The surface issue is discipline; however, the underlying issues are literacy and barriers to academic success. To address these issues, a large urban district opened a new school for students who were not succeeding in traditional settings, had escalating discipline problems, and were failing academically. It was called Project Succeed Academy. This article details the lessons learned in the schools design, implementation, and evolution. An analysis of the political, community, and financial issues that caused reduction of the original design are discussed.
Gender Is an Independent Risk Factor for Mortality After Open or Endovascular Aortoiliac Reconstruction

Objectives: Due to the small numbers of thoracic outlet syndrome (TOS) patients treated with bilateral first rib resection and scalenectomy (FRRS), this patient subset has not been well studied. We examined a large cohort of TOS patients who underwent bilateral FRRS to evaluate patient characteristics and outcomes. Methods: Patients treated with bilateral FRRS at Johns Hopkins Medical Institutions from 2003-2012 were identified by review of a prospectively maintained database. Statistical analysis compared patients with unilateral and bilateral FRRS, and bilateral patients with different TOS indications. Results: 53 patients underwent bilateral FRRS with a mean follow-up of 11.4 months. Average time between operations was 17.0 (range, 5.1-59.8) months. Compared to 408 unilateral FRRS patients, bilateral patients were younger (30 vs 35 years; P < .008) with no significant difference in gender. Among patients with dual-sided FRRS, 25 (47%) had bilateral neurogenic (N) symptoms, two (4%) had bilateral arterial symptoms, and 26 (49%) had venous symptoms with the first side due to intermittent compression (IC) in five (second side 4 IC, 1 N) and effort thrombosis (ET) in 21 (second side 9 ET, 8 IC, 4 N). 12 patients had prophylactic FRRS to prevent contralateral venous or arterial thrombosis, and eight had cervical ribs. Compared to neurogenic patients, venous patients were younger (25 vs 35 years; P < .002) with a trend towards more competitive athletes (7 venous vs 2 N). Symptomatic restenosis requiring dilation occurred after four FRRS for venous symptoms at a mean of 32 months, and rethrombosis occurred after four FRRS at a mean of 4 weeks (1 treated with warfarin, 3 with tPA), all on the primary side. Overall, 89% of FRRS led to resolved symptoms at last follow-up. Conclusions: Bilateral FRRS is an effective method for symptomatic and prophylactic treatment of TOS. Venous bilateral patients are more often younger, competitive athletes, and must be monitored closely postoperatively for recurrent stenosis and thrombosis.
Sequential, randomized trial of a low-fat, high-fiber diet and soy supplementation: Effects on circulating IGF-I and its binding proteins in premenopausal women

Despite evidence supporting the involvement of the IGF system in the development of breast and other cancers, the major determinants of interindividual variability in circulatory IGF-I levels are not well understood. Previous research has pointed to important genetic influences as well as dietary effects through marked calorie or protein restriction. We conducted a randomized trial to determine the effects of 2 dietary patterns on serum IGF-1, IGFBP1 and IGFBP3 in free-living premenopausal women: phase 1, an isocaloric low-fat, high-fiber (LFHF) vs. usual diet, and phase 2, a soy supplement either with or without isoflavones (soy+IF vs. soy-IF). Participants completed 12 menstrual cycles on phase 1 and then were randomly assigned to a soy supplement for 3 cycles while maintaining the phase 1 diet. Before and after each phase, 154 women provided serum. We found no difference in the change in IGF-I, BP1 or BP3 in the LFHF group compared to the usual diet group. In phase 2, there were no differences in any IGF protein between the soy+IF and the soy-IF groups or any evidence of interaction between isoflavone exposure and the background diet. However, there was a small but statistically significant decrease (2.3%) in BP3 and an increase in the IGF-I:BP3 molar ratio among all 153 subjects following either soy supplement. These changes were correlated with changes in intake of calcium, total vegetable protein and soy. The results are compatible with previous data suggesting that increases in dietary calcium, protein and soy, in particular, could increase circulating levels of bioavailable IGF-I.
Power laws in compartmental analysis. part I: a unified stochastic model

Abstract The transport of radioactive tracers and trace pollutants through the body is usually modeled as a multi-compartment linear differential system with constant exchange rates. The specific activity curves must then necessarily be mixtures of exponentials and non-negative integer powers of the time since injection. This is inconsistent with observations on many systems, which exhibit specific-activity curves with either negative powers of time or arbitrary non-integer positive powers of time with an exponential modification (Gamma densities). A physiologically plausible random-walk model is proposed by which a single four-parameter compound Poisson process for the residence time of a molecule of tracer in a compartment can fit all of the observed types of specific activity curves. The parameters have direct interpretations in terms of an age-dependent molecular exchange rate between compartments. Multi-compartment systems can be similarly modeled as a Markov renewal process.
Boys Will Be Boys, or Will They? Literacy and Masculinities

This conversation re-creates a lively e-mail debate between the authors, who bring different theoretical perspectives to consideration of literacy among boys.
Two Reagans? Genre Imperatives, Ghostwriters, and Presidential Personality Profiling

Attempts to gauge presidential personality on the basis of speeches and other public statements are subject to several potential validity threats. This paper presents a test of the genre imperative of the tendency to make the president sound “presidential,” in combination with the fact that most presidential addresses are drafted by ghostwriters. The test involves comparing the “activity” and “positivity” levels of 235 syndicated radio commentaries that Ronald Reagan wrote and delivered during the years immediately before he became president and 299 weekly radio addresses that he delivered while he was president. The two Reagans were by no means fundamentally different, but the differences between them nonetheless sound a note of caution about basing personality assessments on presidents’ public statements.
Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype–phenotype relationships and its relevance to crop improvement

More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties.
Effects of external calcium on zinc modulation of AMPA receptors

Abstract The effects of calcium on zinc modulation of current responses from two similar homomeric glutamate receptors, GluR1 and GluR3, was examined using the Xenopus oocyte expression system. Previous experiments carried out using normal (calcium-containing) physiological solution showed that kainate-evoked current responses from GluR3, but not GluR1, were potentiated by low μM concentrations of zinc. Furthermore this potentiation was observed only over a narrow range of zinc concentrations. In contrast, the present experimens demonstrated that in calcium-free solution (magnesium replacement) zinc can potentiate both GluR3, as expected, but also GluR1. In addition, the potentiation occurs over a large range of zinc concentrations (> log units). Re-supply of calcium to the solution interferes with zinc potentiation in a concentration-dependent manner. When supernormal concentrations of calcium are present, zinc greatly inhibits currents at zinc concentrations that would cause potentiation in the absence of calcium, and that would cause smaller inhibition in normal solution. Because zinc is co-released along with neurotransmitter at many glutamatergic synapses in vertebrate brains, and synaptic calcium levels are subject to variable control, calcium regulation of zinc sensitivity may be physiologicall relevant.
Parasite-induced parthenogenesis in a freshwater snail: stable, persistent patterns of parasitism.

The role of parasites in the evolution of host reproductive modes has gained renewed interest in evolutionary ecology. It was previously argued that obligate parthenogenesis (all-female reproduction) arose in a freshwater snail, Campeloma decisum, as a consequence of severe sperm limitation caused by an unencysted trematode, Leucochloridiomorpha constantiae. In the present study, certain conditions are examined for parasitic castration to account for the maintenance of parthenogenesis: the spatial patterns of the prevalence and intensity of infection on a broad geographical scale and its relationship to host genotype; the recovery from infection after isolation from sources of infection; age-related patterns of infections; and the effects of L. constantiae on snail fecundity.
Defined Contribution Plans Emerging in the Public Sector: The Manifestation of Defined Contributions and the Effects of Workplace Financial Literacy Education

This article discusses the history of the Employee Retirement Income Security Act (ERISA). The implementation of the act developed an environment for employers, public and private, to transition fr...
A NEW APPROACH FOR ESTIMATING IRRIGATION CONVEYANCE LOSSES AND THEIR ECONOMIC EVALUATION

: In this paper a new methodology for estimating conveyance efficiency within irrigation systems is presented. Based on statistical analysis of daily water releases from the source of supply and deliveries to the farmers in an irrigation district in Mexico, a linear model is obtained for estimating conveyance efficiency and two component factors. One of these factors points out the relative importance of the operational losses (i.e., losses due to water management), and the second shows the importance of the fixed losses which can be attributed to the average flow through the canal network without variations. In the last part of this paper, an analysis of the expected benefits and costs accruing from system improvement permits derivation of a decision rule which may be used for analyzing the economic feasibility of lining in-place canals.
Importance of anchor genomes for any plant genome project

Progress in agricultural and environmental technologies is hampered by a slower rate of gene discovery in plants than animals. The vast pool of genes in plants, however, will be an important resource for insertion of genes, via biotechnological procedures, into an array of plants, generating unique germ plasms not achievable by conventional breeding. It just became clear that genomes of grasses have evolved in a manner analogous to Lego blocks. Large chromosome segments have been reshuffled and stuffer pieces added between genes. Although some genomes have become very large, the genome with the fewest stuffer pieces, the rice genome, is the Rosetta Stone of all the bigger grass genomes. This means that sequencing the rice genome as anchor genome of the grasses will provide instantaneous access to the same genes in the same relative physical position in other grasses (e.g., corn and wheat), without the need to sequence each of these genomes independently. (i) The sequencing of the entire genome of rice as anchor genome for the grasses will accelerate plant gene discovery in many important crops (e.g., corn, wheat, and rice) by several orders of magnitudes and reduce research and development costs for government and industry at a faster pace. (ii) Costs for sequencing entire genomes have come down significantly. Because of its size, rice is only 12% of the human or the corn genome, and technology improvements by the human genome project are completely transferable, translating in another 50% reduction of the costs. (iii) The physical mapping of the rice genome by a group of Japanese researchers provides a jump start for sequencing the genome and forming an international consortium. Otherwise, other countries would do it alone and own proprietary positions.
Mechanism of interaction of magnetic fields with biological systems

A review is presented of the known mechanisms by which magnetic fields can interact with biological systems. The basic equations for exerting forces by both AC and DC magnetic fields on charged particles and dipoles are reviewed. Examples are given that allow order-of-magnitude estimates of the induced current densities and forces to be obtained. These estimates are compared with values known to induce measurable changes in the behavior of biological systems. >
The Effects of Forward- Versus Backward-Looking Wage Indexation on Price Stabilization Programs

A standard open-economy model is used to show that price stabilization programs are more likely to succeed if labor contracts specify forward-looking wage indexation. Compared with contracts specifying backward-looking wage indexation or wages based on static expectations, such contracts will result in a greater reduction in inflation with lower output costs, smaller misalignment of real wages, smaller outflows of reserves, smaller disruptions caused by policy announcements, and a reduced impact of some shocks during price stabilization programs. These results are generally true whether or not capital is mobile and whether or not expectations are rational.
How Not to Build Nuclear Reactors

The hype about building new nuclear power plants could backfire if suppliers and labor make big plans today on a future that is far from assured.
P-639 - Privacy, health information technology and psychiatry

Introduction The use of health information technology (HIT) to facilitate record-keeping and communication, and ultimately to improve quality, is increasing worldwide. While providing significant opportunity for improving the care provided to patients with psychiatric illness, this also raises privacy concerns, as it may put sensitive information at greater risk of improper dissemination. This presentation will explore the privacy implications of the increased use of HIT to the field of psychiatry. Objectives 1) To define the concepts of privacy, confidentiality, and security; 2) To outline mechanisms by which electronic information can be compromised; 3) To list categories of clinical information that may be deemed “sensitive”; 4) To present approaches for protecting privacy in an electronic environment; 5) To list consequences to psychiatric care from inadequate privacy protection, and conversely to discuss concerns if the flow of psychiatric documentation is excessively restricted; 6) To provide recommendations for clinicians. Aims 1) To provide an overview of the privacy implications of HIT to psychiatry; 2) to encourage dialog amongst psychiatrists; 3) To prepare psychiatrists to contribute to HIT activities. Methods The information for this presentation is derived from the author's experience with HIT developments in the United States on behalf of the American Psychiatric Association; existing literature; and communications with practicing psychiatrists. Results Not Applicable. Conclusions HIT is revolutionizing how healthcare is delivered and documented, and has significant implications for patient privacy. Psychiatrists need to be conversant in this area to ensure potential benefits to patients with psychiatric illness while minimizing the privacy risks.
Weak Links, Strong Ties

A look at the past few years in the magazine's history, and a farewell message from the editor in chief.
Dynamic force identification based on enhanced least squares and total least-squares schemes in the frequency domain

Identifying dynamic forces from structural responses is necessary when direct measurement of those dynamic forces is impossible using conventional means. A common approach to address this problem is to determine the frequency response function (FRF) matrix, measure the structural responses, and calculate the dynamic forces based on least-squares (LS) scheme. This approach has been proven to be effective in reducing the random errors that occur in structural response signals. Unfortunately, the accuracy of this approach is often hindered by the inversion of an ill-conditioned FRF matrix at frequencies near the structural resonances. To overcome this inversion instability, two regularization filters, namely the truncated singular value decomposition (TSVD) filter and the Tikhonov filter, are used in conjunction with the conventional LS scheme at specific frequencies. Here a criterion for applying these enhanced LS schemes is proposed to aid in determining when the increase in computational effort is better utilized. Furthermore, a new LS form of the Morozov's discrepancy principle is formulated to aid in selecting the optimum regularization parameter for these filters at each frequency. The accuracy in using conventional LS, TSVD-based LS, and Tikhonov filter-based LS schemes are compared analytically and numerically in this paper. It is found that for small-sized FRF matrices, the Tikhonov filter-based LS scheme tends to work better than the TSVD filter-based LS scheme. Since these approaches can only deal with the random errors in the measured structural responses, a total least-squares (TLS) scheme that can also address errors associated with the FRF matrix is proposed in this research. Numerical simulations demonstrate that under certain conditions, the TLS scheme is more effective in reducing the impact of these errors.
An update on economies of scale in credit unions

When employing the Benston-Bell-Murphy cost specification, most studies on economies of scale in financial institutions have consistently found small, yet significant economies. However, when a similar approach on credit unions was used, the results were conflicting. This paper, through the use of a different methodological and statistical approach, provides additional evidence on the existence of economies of scale in credit unions.
The 5' noncoding region sequence of the Choristoneura biennis entomopoxvirus spheroidin gene functions as an efficient late promoter in the mammalian vaccinia expression system.

Abstract About 100 nucleotides of DNA sequence at the 5′ noncoding region of the Choristoneura biennis entomopoxvirus spheroidin gene was chemically synthesized and inserted into a vaccinia expression vector, interrupting the vaccinia thymidine kinase gene. When the bacterial β-galactosidase gene was introduced downstream of this sequence and a recombinant vaccinia virus containing these inserts was obtained by homologous recombination, β-galactosidase was shown to be expressed at a high level late in the vaccinia infection cycle. The level of β-galactosidase expression was four- to fivefold higher with this spheroidin-vaccinia recombinant virus than with a similar recombinant in which the β-galactosidase gene was under the control of the vaccinia 7.5-kDa promoter. Primer extension and S1 mapping of the 5′ terminus of the β-galactosidase transcript located the transcription initiation site within the spheroidin DNA sequence, confirming the promoter nature of this DNA sequence in the vaccinia system. Dot blot analysis indicated that the difference in β-galactosidase expression with these two recombinant viruses can be attributed to the difference in their transcript levels. We also demonstrated that full promoter activity encoded in the spheroidin 5′ noncoding sequence was contained within a 38-nucleotide DNA fragment.
Herbal and homeopathic medicine: understanding the difference

Abstract Homeopathy is frequently confused with holistic medicine and with herbal products. The latter is particularly problematic when homeopathic medicines are made from herbs with which they share the same nomenclature. However, homeopathy differs in both toxicity and therapeutic paradigm with important implications for use and future research. The article illustrates this with cases and a review of the history of homeopathy.
Glioblastoma invasion, cathepsin B, and the potential for both to be inhibited by auranofin, an old anti-rheumatoid arthritis drug.

Cathepsin B activity is absent in normal brain tissue but overexpressed in glioblastomas. Immunohistochemistry localizes cathepsin B to areas of invasion and neovascularization. Several research teams have confirmed the relationship between higher cathepsin B expression, more aggressive glioblastoma course and a shorter overall survival. An old anti-rheumatoid arthritis drug, auranofin, has a documented micromolar range for the inhibition of cathepsin B. Such levels are clinically achievable with the adequately tolerated doses that are used to treat rheumatoid arthritis. The side-effect profile of auranofin, although not entirely problem-free, is benign enough to warrant further trials in good fidelity rodent glioblastoma models followed by a translation to clinical trials if these confirm a potential for benefit. A newly discovered amplification loop between cathepsin B and urokinase-type plasminogen activator outlined in this paper is active in glioblastoma and makes auranofin inhibition particularly attractive for its potential to inhibit the matrix degrading feedback cycle.
Evidence from intron 1 of the nuclear transthyretin (Prealbumin) gene for the phylogeny of African mole-rats (Bathyergidae).

Abstract A 900- to 1100-bp fragment encompassing intron 1 of the nuclear transthyretin (prealbumin) gene was examined in 12 taxa of Old World hystricognath rodents of the families Bathyergidae, Petromuridae, Thryonomyidae, and Hystricidae. Within the Bathyergidae, Heterocephalus glaber (naked mole-rat) was basal, and the other East African species, Heliophobius argenteocinereus (silvery mole-rat), was sister to a southern African clade containing Bathyergus, Cryptomys, and Georychus (dune, common, and cape mole-rats). These results are congruent with studies using mitochondrial 12S rRNA gene sequences. A combined analysis of transthyretin and 12S rRNA data resulted in a well-supported topology with better resolution than either gene analyzed separately. These data support the findings by M. W. Allard and R. L. Honeycutt (1992, Mol. Biol. Evol. 9: 27–40) and R. L. Honeycutt (1992, Am. Sci. 80: 43–53) that complex social systems evolved independently at least twice, in the common and naked mole-rats.
A Parallel Micro Turbulent Flow Chromatography-Tandem Mass Spectrometry Method for the Analysis of a Pharmaceutical Compound in Plasma

Turbulent flow chromatography coupled to tandem mass spectrometry (TFC-MS-MS) has been widely used within bioanalysis, because of the ability to inject directly neat biological samples with no prior pretreatment. TFC-MS-MS removes the need for time consuming sample preparation procedures such as protein precipitation, liquid-liquid extraction or solid-phase extraction. There are two standard configurations that are commonly adopted for the use of TFC, namely fast elute and focus mode. In this paper, a new micro TFC column which has the advantages of reducing solvent consumption and improving mass sensitivity, was used to develop a fast elute method. A wide range of pharmaceutical compounds with various physicochemical properties was used to assess the system performance. Carry-over has often been identified as a potential source of inaccuracy in a fast elute mode. This paper shows how by using a systematic approach, carryover was eliminated. The parameters influencing the robustness of the micro TFC column are also discussed. This method was fully validated for a Pfizer development compound in human plasma using a new TFC parallel platform allowing two systems to be operated in parallel. Multiplexing the sample analysis allowed a 2-fold increase in throughput and provided an efficient use of the mass spectrometer.
Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis

Background During infection, Mycobacterium tuberculosis confronts a generally hostile and nutrient-poor in vivo host environment. Existing models and analyses of M. tuberculosis metabolic networks are able to reproduce experimentally measured cellular growth rates and identify genes required for growth in a range of different in vitro media. However, these models, under in vitro conditions, do not provide an adequate description of the metabolic processes required by the pathogen to infect and persist in a host.
Model building and phenomenology of flux-induced supersymmetry breaking on D3-branes

Abstract We study supersymmetry breaking effects induced on D3-branes at singularities by the presence of NSNS and RR 3-form fluxes. First, we discuss some local constructions of chiral models from D3-branes at singularities, as well as their global embedding in flux compactifications. The low energy spectrum of these constructions contains features of the supersymmetric Standard Model. In these models, both the soft SUSY parameters and the μ-term are generated by turning on the 3-form NSNS and RR fluxes. We then explore some model-independent phenomenological features as, e.g., the fine-tuning problem of electroweak symmetry breaking in flux compactifications. We also comment on other phenomenological features of this scenario.
Perivascular innate immune events modulate early murine vein graft adaptations.

Objective Innate immunity drives numerous cardiovascular pathologies. Vein bypass grafting procedures are frequently accompanied by low-grade wound contamination. We hypothesized that a peri-graft innate immune challenge, via an outside-in route, augments inflammatory responses, which subsequently drive a component of negative vein graft wall adaptations; moreover, adipose tissue mediates this immune response. Methods The inferior vena cava from a donor mouse was implanted into the common carotid artery of a recipient mouse utilizing a validated cuff technique (9-week-old male C57BL/6J mice). Slow-release low-dose (5 μg) lipopolysaccharide (LPS) (n = 9) or vehicle (n = 9) was applied peri-graft; morphologic analysis was completed (day 28). In parallel, vein-grafted mice received peri-graft LPS (n = 12), distant subcutaneous LPS (n = 6), or vehicle (n = 12), then day-1 and -3 harvest of grafts and adipose tissue for cytokines and toll-like receptor (TLR) signaling mRNA expression (qRT-PCR). Results All recipient mice survived, and all vein grafts were patent. Acute low-dose local LPS challenge enhanced vein graft lumen loss ( P = .04) and tended to augment intimal hyperplasia ( P = .06). The surgical trauma of vein grafting universally upregulated key pro- and anti-inflammatory mediators within the day-1 graft wall, but varied on TLR signaling gene expression. Local and distant LPS accentuated these patterns until at least postoperative day 3. LPS challenge enhanced the inflammatory response in adipose tissue (locally > distantly); local LPS upregulated adipose TLR-4 dramatically. Conclusions Perivascular and distant inflammatory challenges potentiate the magnitude and duration of inflammatory responses in the early vein graft wall, negatively modulating wall adaptations, and thus, potentially contribute to vein graft failure. Furthermore, surgery activates innate immunity in adipose tissue, which is augmented (regionally > systemically) by LPS. Modulation of these local and distant inflammatory signaling networks stands as a potential strategy to enhance the durability of vascular interventions such as vein grafts.
Natural history of patients after abdominal-perineal resection implications for radiation therapy

The records of one hundred twenty-three consecutive abdominal perineal resections for rectosigmoid carcinoma were reviewed. One hundred sixteen cases were adenocarcinoma, and seven cases squamous cell carcinoma. Clinical outcome was documented in 111 cases. Overall, 42% survived five years or more. Ultimately 44 of the 123 patients (36%) were proven to have died with tumor and 19 patients (15%) developed clinical manifestations of recurrent pelvic tumor. Five of the 116 patients with adenocarcinoma (4%) died with evidence of pelvic disease only. Second primary tumors were observed in 22 patients (18%). The authors suggest preoperative irradiation to reduce local recurrence and possibly increase disease-free survival. Physicians following these patients should consider them at high risk for cancer in general.
Testicular tumours in children: a single-institutional experience.

Authors from the USA present a retrospective review of children in their institution who were treated for testicular cancer. They found that most of the lesions were benign, the commonest being testicular. They also found several malignant and paratesticular lesions, and make recommendations as to the surgical approach. OBJECTIVE To report our experience of testicular and paratesticular tumours in children, as such tumours are rare, and historically yolk sac tumour has been described as the most common lesion in children, but recent reports suggest that benign testicular lesions might be more common. PATIENTS AND METHODS We reviewed retrospectively the records of children treated for testicular tumours from 1998 to 2005. The patients’ age, clinical presentation, diagnostic procedures, treatment methods, histopathological findings, and outcome were recorded. Patients aged >144 months and those with non-primary metastatic lesions were excluded. RESULTS In all, 11 patients met our criteria, with a mean age of 37 months (range 9 days to 144 months). Pathological analysis revealed teratoma in four patients, yolk sac tumour in two, epidermoid cysts in two, extrarenal nephroblastomatosis in one, and paratesticular rhabdomyosarcomas in two. The most common clinical presentation was a painless testicular mass. Depending on the clinical presentation and pathology, scrotal ultrasonography, tumour markers (α-fetoprotein and β-human chorionic gonadotrophin), and/or staging computed tomography (CT) were obtained in eight patients. All patients had a radical orchidectomy. Three patients had elevated tumour markers that normalized after orchidectomy. CT revealed extensive mediastinal adenopathy in one patient with rhabdomyosarcoma. Chemotherapy was administered to both patients with rhabdomyosarcoma. CONCLUSION Although there were few patients, most of the lesions were benign tumours, with the most common histological subtype being teratoma. As both malignant and paratesticular lesions occurred at a significant frequency, we would continue to advocate an initial radical inguinal approach at which time testis-sparing could be considered if the preoperative evaluation was favourable, and frozen-section analysis at the time of surgery confirms a benign lesion.
Learning Disabilities and Competency-Based Instruction Intertwined or Poles Apart?

In the first of two articles, the reasons for movement toward a competency-based methodology in personnel preparation teacher training programs are discussed. Characteristics ofCBTE schemes are described and evaluated, and it was found that numerous problems exist with this approach, problems which so far have been ignored by special educators. An inquiry into the differences between teaching competencies and teacher competence is analyzed.
In-line supervisory control in a photolithographic workcell

In this paper we describe an in-line supervisory control system that uses statistical criteria in conjunction with feedback and feed-forward control in order to improve the capability of a photolithographic workcell. The three major components of the system namely process monitoring modeling and control were developed together and thus are perfectly compatible. The issue of monitoring is addressed by the development of metrology suitable for the economical in-line measurement of photoresist thickness and reflectance. Statistically designed experiments are used to develop equipment models that relate the process settings to in-line measurable responses. Finally the statistical process control concepts of the regression chart and acceptance chart are used as the basis of the criteria that initiate process control actions. A prototype of this system has been applied on the photolithographic sequence in the Berkeley microfabrication laboratory.
Using and re-using partial plans

Partial (or default) plans are plans that are constructed or applied without insuring that all support for the operators used in the plan is present in the planner's world model. Despite the apparent carelessness in their construction and application, partial plans are responsible for much of the efficiency of human problem solving. The ability to use partial plans relaxes some of the stringent requirements for thoroughness in planning and allows the application of very general, existing plans to typical, but specific situations. A plan's initial degree of partialness (and ultimate success) depends upon the Planner's estimate of the hospitality of the execution environment and its depth of knowledge. Consequently, a quickly produced partial plan may succeed quietly or may fail to achieve the expected results.
Relationship Between Psychiatric Diagnosis and Patient Aggression

Patient aggression is a common problem on psychiatric units. Recent research has focused on the relationship between aggressive behavior and various patient characteristics, including psychopathology. The purpose of this study was to examine the relationship between diagnostic groups and particular types of patient aggression in a state psychiatric hospital. A secondary analysis was performed on existing data. There was no significant difference noted among DSM III diagnoses in total patient aggression. However, there was a significant difference between individuals with organic disorders and individuals with paranoid schizophrenia in the category of physical aggression against other people. Improved ability to identify a particular diagnostic group with the potential for aggression will strengthen efforts to decrease the risk of patient aggression in psychiatric facilities.
The effect of subcutaneously administered low-molecular-weight heparin on microarterial thrombosis in the rat.

Objective To examine the effect of administration of a low-molecular-weight heparin derivative, enoxaparin, on the rate of arterial thrombosis in a rat model. Study Design Prospective, randomized, blinded study. Methods A standard microarterial anastomosis tuck injury was created in both femoral arteries of 25 Long Evans retired breeder rats. Thirteen animals received a subcutaneous injection of 50 IU/kg of enoxaparin 2 hours before the procedure, while 12 control animals received vehicle (isotonic sodium chloride solution) alone. Sites of injury/repair were assessed 2 hours after the procedure for anastomotic patency or thrombosis. Results Six (23%) of 26 vessels in the drug-treated group developed an arterial thrombosis at the site of repair, while 6 (25%) of 24 vessels in the control group developed thrombosis. There was no statistically significant difference at the 95% confidence limit between the 2 groups based on a comparison-of-proportions test. Conclusion The preoperative subcutaneous administration of 50 IU/kg of enoxaparin did not alter the rate of arterial thrombosis following the creation of a thrombogenic tuck injury/repair of the rat femoral artery.
A chloroplast DNA phylogeny of eastern Phlox (Polemoniaceae): implications of congruence and incongruence with the ITS phylogeny

The comparison of independent phylogenies is a valuable approach to the study of evolutionary pattern and process. Available data on eastern North American Phlox, including our recent ITS phylogeny, suggest that relationships are complicated in the group and that hybridization may have been a contributing factor. We used restriction site data from the chloroplast genome to develop a second phylogeny for eastern Phlox. Sampling was the same as that for the ITS study and consisted of 79 samples (including all 22 eastern Phlox species and most eastern subspecies, as well as multiple populations of many taxa). The resulting cpDNA phylogeny agrees with the ITS phylogeny in many respects, strengthening earlier conclusions. Nevertheless, incongruence between the trees is noteworthy: many samples, particularly of members of the P. pilosa and P. glaberrima complexes, are placed in different clades. A variety of tests were carried out to assess congruence in terms of topological patterns, character congruence, and homogeneity of data sets. Significant conflict between the phylogenies is discussed in light of the hypothesis that hybridization has affected relationships in this genus.
Reliving the Past: The Worlds of Social History

Five historians uncover the ties between people's daily routines and the all-encompassing framework of their lives. They trace the processes of social construction in Western Europe, the United States, Latin America, Africa, and China, discussing both the historical similarities and the ways in which individual history has shaped each area's development. They stress the need for a social history that connects individuals to major ideological, political, and economic transformations.
The ARTEMIS Mission

The Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon’s Interaction with the Sun (ARTEMIS) mission is a spin-off from NASA’s Medium-class Explorer (MIDEX) mission THEMIS, a five identical micro-satellite (hereafter termed “probe”) constellation in high altitude Earth-orbit since 17 February 2007. By repositioning two of the five THEMIS probes (P1 and P2) in coordinated, lunar equatorial orbits, at distances of ∼55–65 R E geocentric (∼1.1–12 R L selenocentric), ARTEMIS will perform the first systematic, two-point observations of the distant magnetotail, the solar wind, and the lunar space and planetary environment. The primary heliophysics science objectives of the mission are to study from such unprecedented vantage points and inter-probe separations how particles are accelerated at reconnection sites and shocks, and how turbulence develops and evolves in Earth’s magnetotail and in the solar wind. Additionally, the mission will determine the structure, formation, refilling, and downstream evolution of the lunar wake and explore particle acceleration processes within it. ARTEMIS’s orbits and instrumentation will also address key lunar planetary science objectives: the evolution of lunar exospheric and sputtered ions, the origin of electric fields contributing to dust charging and circulation, the structure of the lunar interior as inferred by electromagnetic sounding, and the lunar surface properties as revealed by studies of crustal magnetism. ARTEMIS is synergistic with concurrent NASA missions LRO and LADEE and the anticipated deployment of the International Lunar Network. It is expected to be a key element in the NASA Heliophysics Great Observatory and to play an important role in international plans for lunar exploration.
Pneumonia and empyema: causal, casual or unknown

Parapneumonic effusions complicating pneumonia are associated with increased morbidity and mortality. Along with increased mortality, complicated parapneumonic effusion and empyema often necessitate prolonged treatment, longer hospital stay and interventions. Parapneumonic effusions arise from inflammation in the lungs and pleural space from direct invasion of bacteria, cascade of inflammatory events and bacteriologic virulence features. Patient factors and comorbidities also contribute to the pathophysiology of parapneumonic effusion development. The evolution of parapneumonic effusion can be divided into three progressive stages: (I) exudative stage; (II) fibrinopurulent stage; and (III) organizing stage with pleural peel formation. These stages can help categorize effusions into groups in order to evaluate the risk of a complicated course requiring intervention. We recommend that clinical data be evaluated and a stepwise approach be taken in management of these patients. This review article discusses current understanding of the development and relationship of parapneumonic effusions with pneumonia.
Tensor products which do not preserve operator algebras

Of late the link between operator algebras and certain tensor products has been reiterated [ 5 ]. We prove here that the projective and Haagerup tensor products of two infinite-dimensional C *-algebras is not even topologically isomorphic to an algebra of operators on a Hilbert space. Estimates are given for the distance of the tensor product from such an algebra. Nonetheless with respect to a natural multiplication the Haagerup tensor product of two algebras of Hilbert space operators is completely isometrically isomorphic to an algebra of operators on some B (ℋ).