Screening of a HUVEC cDNA library with transplant-associated coronary artery disease sera identifies RPL7 as a candidate autoantigen associated with this disease.

A HUVEC cDNA library was screened with sera from two patients who had developed transplant-associated coronary artery disease (TxCAD) following cardiac transplantation. A total of six positive clones were isolated from a primary screen of 40 000 genes. Subsequent DNA sequence analysis identified these to be lysyl tRNA synthetase, ribosomal protein L7, ribosomal protein L9, beta transducin and TANK. Another gene whose product could not be identified showed homology to a human cDNA clone (DKFZp566M063) derived from fetal kidney. Full-length constructs of selected genes were expressed as his-tag recombinant fusion proteins and used to screen a wider patient base by ELISA to determine prevalence and association with TxCAD. Of these ribosomal protein L7 showed the highest prevalence (55.6%) with TxCAD sera compared to 10% non-CAD

Write-rationing garbage collection for hybrid memories

Emerging Non-Volatile Memory (NVM) technologies offer high capacity and energy efficiency compared to DRAM, but suffer from limited write endurance and longer latencies. Prior work seeks the best of both technologies by combining DRAM and NVM in hybrid memories to attain low latency, high capacity, energy efficiency, and durability. Coarse-grained hardware and OS optimizations then spread writes out (wear-leveling) and place highly mutated pages in DRAM to extend NVM lifetimes. Unfortunately even with these coarse-grained methods, popular Java applications exact impractical NVM lifetimes of 4 years or less. This paper shows how to make hybrid memories practical, without changing the programming model, by enhancing garbage collection in managed language runtimes. We find object write behaviors offer two opportunities: (1) 70% of writes occur to newly allocated objects, and (2) 2% of objects capture 81% of writes to mature objects. We introduce writerationing garbage collectors that exploit these fine-grained behaviors. They extend NVM lifetimes by placing highly mutated objects in DRAM and read-mostly objects in NVM. We implement two such systems. (1) Kingsguard-nursery places new allocation in DRAM and survivors in NVM, reducing NVM writes by 5x versus NVM only with wear-leveling. (2) Kingsguard-writers (KG-W) places nursery objects in DRAM and survivors in a DRAM observer space. It monitors all mature object writes and moves unwritten mature objects from DRAM to NVM. Because most mature objects are unwritten, KG-W exploits NVM capacity while increasing NVM lifetimes by 11x. It reduces the energy-delay product by 32% over DRAM-only and 29% over NVM-only. This work opens up new avenues for making hybrid memories practical

Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Background International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population. Findings Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4–7·3) of transmissions occurred within lakeside areas, 89·2% (86·0–91·8) within inland areas, 1·3% (0·6–2·6) from lakeside to inland areas, and 3·7% (2·3–5·8) from inland to lakeside areas. Interpretation Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics. Funding The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention

Critical appraisal in environmental evidence synthesis: challenges and options

Critical appraisal is a crucial step in systematic reviews that, when conducted appropriately, enables threats to the validity of evidence to be identified and accounted for in the data synthesis. However, critical appraisal in published environmental management systematic reviews, and those submitted to the Collaboration for Environmental Evidence, is often conducted inconsistently, does not always focus on threats to validity, and does not always inform the data synthesis. The validity of conclusions from many environmental systematic reviews may therefore be questionable, but there is a lack of reliable tools to guide consistent critical appraisal of environmental research studies. This presentation will discuss a conceptual model-based framework that could improve the consistency and transparency of critical appraisal. It aims to guide review teams on how to identify different threats to validity (e.g. risks of bias) in primary research studies, and has flexibility for application alongside existing critical appraisal tools, where available

Effects of some commonly-used foliar fungicides on springtails (collembola) in winter cereals

Carbendazim (a selective fungicide) and the broad-spectrum compounds propiconazole, pyrazophos and triadimenol were screened in the laboratory to assess their toxicity to Sminthurinus aureus and all caused significant increases in mortality, pyrazophos being the most toxic. White sand and plaster of Paris were unsuitable as substrates for Collembola in toxicological experiments. Suction (D-vac) sampling in winter barley in 1985 showed that pyrazophos applied to replicated plots of area c. 2.7 ha significantly reduced populations of five out of 11 species of surface-dwelling Collembola (Sminthurus viridis, Sminthurinus elegans, S. aureus, Jeannenotia stachi and Isotoma viridis). Reductions in populations were large when compared with the effects of the broad-spectrum insecticide dimethoate. Suction and pitfall trap sampling in winter wheat in 1986 showed that populations of seven out of 13 surface-dwelling Collembola species (S. viridis, S. elegans, Deuterosminthurus spp., J. stachi, Pseudosinella alba, Lepidocyrtus cyaneus and I. viridis) were significantly reduced by applications of carbendazim, propiconazole and triadimenol to replicated 10m x 10m barriered and unbarriered plots. Nearly all the significant effects were in unbarriered plots and few ere detected by pitfall-trapping. Temporal patterns in populations of Collembola in wheat were investigated in summer 1987. All species exhibited a diurnal peak in catches on several dates, in contrast to the results of some other studies. Plant-climbing species were identified by sweep net sampling. The efficiencies of different methods for sampling surface-dwelling Collembola were compared and the number of samples needed for accurate sampling determined. The relevance of a correction for spatial variability in pre-treatment insect counts is discussed. The limitations of this and other recent pesticide studies are considered and recommendations for improvements are proposed.</p

Peer review of health research funding proposals: A systematic map and systematic review of innovations for effectiveness and efficiency

ObjectiveTo investigate methods and processes for timely, efficient and good quality peer review of research funding proposals in health. MethodsA two-stage evidence synthesis: (1) a systematic map to describe the key characteristics of the evidence base, followed by (2) a systematic review of the studies stakeholders prioritised as relevant from the map on the effectiveness and efficiency of peer review ‘innovations’. Standard processes included literature searching, duplicate inclusion criteria screening, study keyword coding, data extraction, critical appraisal and study synthesis. ResultsA total of 83 studies from 15 countries were included in the systematic map. The evidence base is diverse, investigating many aspects of the systems for, and processes of, peer review. The systematic review included eight studies from Australia, Canada, and the USA, evaluating a broad range of peer review innovations. These studies showed that simplifying the process by shortening proposal forms, using smaller reviewer panels, or expediting processes can speed up the review process and reduce costs, but this might come at the expense of peer review quality, a key aspect that has not been assessed. Virtual peer review using videoconferencing or teleconferencing appears promising for reducing costs by avoiding the need for reviewers to travel, but again any consequences for quality have not been adequately assessed. ConclusionsThere is increasing international research activity into the peer review of health research funding. The studies reviewed had methodological limitations and variable generalisability to research funders. Given these limitations it is not currently possible to recommend immediate implementation of these innovations. However, many appear promising based on existing evidence, and could be adapted as necessary by funders and evaluated. Where feasible, experimental evaluation, including randomised controlled trials, should be conducted, evaluating impact on effectiveness, efficiency and quality.<br/