Collaboration gets the most out of software

By centralizing many of the tasks associated with the upkeep of scientific software, SBGrid allows researchers to spend more of their time on research

cGMP Recombinant FIX for IV and Oral Hemophilia B Therapy

Three specific aims are proposed: Specific Aim # 1. Process engineer and scale-up the recovery and purification of transgenic recombinant human Factor IX. The University of Nebraska-Lincoln Biological Process Development Facility will complete process development and scale-up, and produce clinical grade materials for preclinical studies. The endpoint is a proposed final product specification to help facilitate transfer to current Good Manufacturing Practices compliant production of clinical grade material to support an Investigational New Drug filing with the United States Food and Drug Administration (FDA) leading to clinical trials. Specific Aim #2. Characterize and formulate transgenic recombinant human Factor IX for intravenous dosage, and evaluate in a hemophilia B dog model. These activities are directed toward characterization of the product important to assure the provision of safe and reproducibly effective hemostasis. The results of these investigations will help support an IND filing with the FDA. Specific Aim # 3. Develop an oral dosage form of transgenic recombinant human Factor IX, and evaluate in hemophilia B mice and dog models. Oral administration of coagulation therapy will obviate the invasiveness, discomfort, potential for opportunistic infection, and complications of storage and supplies that accompany intravenous administration. Oral dosage forms of Factor IX will thus greatly increase the proportion of the patient population that can be treated. There is also published evidence suggesting that oral administration may reduce the potential for complicating immune responses to replacement therapy, especially in patients with severe hemophilia

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Tinned fruit consumption and mortality in three prospective cohorts.

Dietary recommendations to promote health include fresh, frozen and tinned fruit, but few studies have examined the health benefits of tinned fruit. We therefore studied the association between tinned fruit consumption and mortality. We followed up participants from three prospective cohorts in the United Kingdom: 22,421 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort (1993-2012), 52,625 participants from the EPIC-Oxford cohort (1993-2012), and 7440 participants from the Whitehall II cohort (1991-2012), all reporting no history of heart attack, stroke, or cancer when entering these studies. We estimated the association between frequency of tinned fruit consumption and all cause mortality (primary outcome measure) using Cox regression models within each cohort, and pooled hazard ratios across cohorts using random-effects meta-analysis. Tinned fruit consumption was assessed with validated food frequency questionnaires including specific questions about tinned fruit. During 1,305,330 person years of follow-up, 8857 deaths occurred. After adjustment for lifestyle factors and risk markers the pooled hazard ratios (95% confidence interval) of all cause mortality compared with the reference group of tinned fruit consumption less often than one serving per month were: 1.05 (0.99, 1.12) for one to three servings per month, 1.10 (1.03, 1.18) for one serving per week, and 1.13 (1.04, 1.23) for two or more servings per week. Analysis of cause-specific mortality showed that tinned fruit consumption was associated with mortality from cardiovascular causes and from non-cardiovascular, non-cancer causes. In a pooled analysis of three prospective cohorts from the United Kingdom self-reported tinned fruit consumption in the 1990s was weakly but positively associated with mortality during long-term follow-up. These findings raise questions about the evidence underlying dietary recommendations to promote tinned fruit consumption as part of a healthy diet.EPIC-Norfolk is supported by the Medical Research Council (grant numbers G1000143, G0401527, G9502233, G0300128) and Cancer Research UK (grant numbers C864/A14136, C865/A2883). EPIC-Oxford is supported by Cancer Research UK (C570/A11691). Whitehall II has been supported by grants from the Medical Research Council; the British Heart Foundation; the British Health and Safety Executive; the British Department of Health; the National Heart, Lung, and Blood Institute (R01HL036310); and the National Institute on Aging at the US National Institutes of Health (NIH). ETA is supported by an academic clinical fellowship awarded by the United Kingdom National Institute for Health Research. EB is funded by the British Heart Foundation. MAHL received grants from Cancer Research UK, and Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared in PLoS ONE 10(2): e0117796. doi: 10.1371/journal.pone.0117796

How Do Different Sources of Partisanship Influence Government Accountability in Europe?

The possibility of holding representatives to account through regular elections is one of the cornerstones of representative democracy. The precise role of partisanship in doing this has not been extensively examined. Using survey data from Europe (2002–2012), we show that partisanship can weaken or strengthen accountability, depending on its sources. If it is an affective-psychological attitude, as the Michigan school suggests, then it weakens accountability because it acts as a perceptual screen. If, however, it is a calculation of party performance which is constantly updated by citizens, then it strengthens accountability. The findings suggest that partisanship in Europe has been quite responsive to performance over the ten-year period. Instead of acting as a screen that inhibits accountability, partisanship appears rooted in calculations of party performance and so enhances accountability. However, the effects are asymmetric with left-leaning partisans more sensitive to the performance of their governments than right-leaning partisans

Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P-=-0.0012) and the net reclassification index with 0.21 (P-=-8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction

Health benefits of a vegetarian diet

Compared with non-vegetarians, Western vegetarians have a lower mean BMI (by about 1 kg/m2), a lower mean plasma total cholesterol concentration (by about 0.5 mmol/l), and a lower mortality from IHD (by about 25 %). They may also have a lower risk for some other diseases such as constipation, diverticular disease, gallstones and appendicitis. No differences in mortality from common cancers have been established. There is no evidence of adverse effects on mortality. Much more information is needed, particularly on other causes of death, other morbidity including osteoporosis, and long-term health in vegans. The evidence available suggests that widespread adoption of a vegetarian diet could prevent approximately 40 000 deaths from IHD in Britain each year.</jats:p