96 research outputs found

    Critiquing the rationales for using comparative judgement: a call for clarity

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    Comparative judgment is gaining popularity as an assessment tool, including for high-stakes testing purposes, despite relatively little research on the use of the technique. Advocates claim two main rationales for its use: that comparative judgment is valid because humans are better at comparative than absolute judgment, and because it distils the aggregate view of expert judges. We explore these contentions. We argue that the psychological underpinnings used to justify the method are superficially treated in the literature. We conceptualise and critique the notion that comparative judgment is ‘intrinsically valid’ due to its use of expert judges. We conclude that the rationales as presented by the comparative judgment literature are incomplete and inconsistent. We recommend that future work should clarify its position regarding the psychological underpinnings of comparative judgment, and if necessary present a more compelling case; for example, by integrating the comparative judgment literature with evidence from other fields

    Asynchronous Execution of Python Code on Task Based Runtime Systems

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    Despite advancements in the areas of parallel and distributed computing, the complexity of programming on High Performance Computing (HPC) resources has deterred many domain experts, especially in the areas of machine learning and artificial intelligence (AI), from utilizing performance benefits of such systems. Researchers and scientists favor high-productivity languages to avoid the inconvenience of programming in low-level languages and costs of acquiring the necessary skills required for programming at this level. In recent years, Python, with the support of linear algebra libraries like NumPy, has gained popularity despite facing limitations which prevent this code from distributed runs. Here we present a solution which maintains both high level programming abstractions as well as parallel and distributed efficiency. Phylanx, is an asynchronous array processing toolkit which transforms Python and NumPy operations into code which can be executed in parallel on HPC resources by mapping Python and NumPy functions and variables into a dependency tree executed by HPX, a general purpose, parallel, task-based runtime system written in C++. Phylanx additionally provides introspection and visualization capabilities for debugging and performance analysis. We have tested the foundations of our approach by comparing our implementation of widely used machine learning algorithms to accepted NumPy standards

    An Independent Review of USGS Circular 1370: An Evaluation of the Science Needs to Inform Decisions on Outer Continental Shelf Energy Development in the Chukchi and Beaufort Seas, Alaska

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    Reviews the U.S. Geological Survey's findings and recommendations on Alaska's Arctic Ocean, including geology, ecology and subsistence, effect of climate change on, and impact of oil spills. Makes recommendations for data management and other issues

    A robust system for RNA interference in the chicken using a modified microRNA operon

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    AbstractRNA interference (RNAi) provides an effective method to silence gene expression and investigate gene function. However, RNAi tools for the chicken embryo have largely been adapted from vectors designed for mammalian cells. Here we present plasmid and retroviral RNAi vectors specifically designed for optimal gene silencing in chicken cells. The vectors use a chicken U6 promoter to express RNAs modelled on microRNA30, which are embedded within chicken microRNA operon sequences to ensure optimal Drosha and Dicer processing of transcripts. The chicken U6 promoter works significantly better than promoters of mammalian origin and in combination with a microRNA operon expression cassette (MOEC), achieves up to 90% silencing of target genes. By using a MOEC, we show that it is also possible to simultaneously silence two genes with a single vector. The vectors express either RFP or GFP markers, allowing simple in vivo tracking of vector delivery. Using these plasmids, we demonstrate effective silencing of Pax3, Pax6, Nkx2.1, Nkx2.2, Notch1 and Shh in discrete regions of the chicken embryonic nervous system. The efficiency and ease of use of this RNAi system paves the way for large-scale genetic screens in the chicken embryo

    DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

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    Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342, 596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formalmediation analysis.DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing b cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-termmetabolic health. The specific mechanism awaits elucidation.</p

    Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23.

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    BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk. RESULTS: Although the function of disease-associated non-coding single nucleotide polymorphisms (SNPs) at 6q23 is unknown, the association is generally assigned to TNFAIP3, the closest gene. However, the DNA fragment containing the associated SNPs interacts through chromatin looping not only with TNFAIP3, but also with IL20RA, located 680 kb upstream. The risk allele of the most likely causal SNP, rs6927172, is correlated with both a higher frequency of interactions and increased expression of IL20RA, along with a stronger binding of both the NFκB transcription factor and chromatin marks characteristic of active enhancers in T-cells. CONCLUSIONS: Our results highlight the importance of gene assignment for translating GWAS findings into biologically meaningful mechanisms of disease and potential therapeutic targets; indeed, monoclonal antibody therapy targeting IL-20 is effective in the treatment of rheumatoid arthritis and psoriasis, both with strong GWAS associations to this region

    Study Protocol – Improving Access to Kidney Transplants (IMPAKT): A detailed account of a qualitative study investigating barriers to transplant for Australian Indigenous people with end-stage kidney disease

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    <p>Abstract</p> <p>Background</p> <p>Indigenous Australians are slightly more than 2% of the total Australian population however, in recent years they have comprised between 6 and 10% of new patients beginning treatment for end-stage kidney disease (ESKD). Although transplant is considered the optimal form of treatment for many ESKD patients there is a pronounced disparity between the rates at which Indigenous ESKD patients receive transplants compared with their non-Indigenous counterparts. The IMPAKT (Improving Access to Kidney Transplants) Interview study investigated reasons for this disparity through a large scale, in-depth interview study involving patients, nephrologists and key decision-making staff at selected Australian transplant and dialysis sites.</p> <p>Methods</p> <p>The design and conduct of the study reflected the multi-disciplinary membership of the core IMPAKT team. Promoting a participatory ethos, IMPAKT established partnerships with a network of hospital transplant units and hospital dialysis treatment centres that provide treatment to the vast majority of Indigenous patients across Australia. Under their auspices, the IMPAKT team conducted in-depth interviews in 26 treatment/service centres located in metropolitan, regional and remote Australia. Peer interviewing supported the engagement of Indigenous patients (146), and nephrologists (19). In total IMPAKT spoke with Indigenous and non-Indigenous patients (241), key renal nursing and other (non-specialist) staff (95) and a small number of relevant others (28). Data analysis was supported by QSR software. At each site, IMPAKT also documented educational programs and resources, mapped an hypothetical ‘patient journey’ to transplant through the local system and observed patient care and treatment routines.</p> <p>Discussion</p> <p>The national scope, inter-disciplinary approach and use of qualitative methods in an investigation of a significant health inequality affecting Indigenous people is, we believe, an Australian first. An exceptionally large cohort of Indigenous participants provided evaluative comment on their health services in relation to dialysis and transplant. Additionally, the data includes extensive parallel commentary from a cohort of specialists, nurses and other staff. The study considers a ‘patient journey’ to transplant within a diverse range of Australian treatment centre/workplace settings. The IMPAKT Interview study protocol may contribute to improvements in multi-disciplinary, flexible design health services research with hard to reach or vulnerable populations in Australia and elsewhere.</p
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