51 research outputs found

    Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations

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    Background: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations. Methods: Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals. Results: Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation. Conclusions: Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development

    A nuclear phylogenomic study of the angiosperm order Myrtales, exploring the potential and limitations of the universal Angiosperms353 probe set

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    Premise: To further advance the understanding of the species-rich, economically and ecologically important angiosperm order Myrtales in the rosid clade, comprising nine families, approximately 400 genera and almost 14,000 species occurring on all continents (except Antarctica), we tested the Angiosperms353 probe kit. Methods: We combined high-throughput sequencing and target enrichment with the Angiosperms353 probe kit to evaluate a sample of 485 species across 305 genera (76 of all genera in the order). Results: Results provide the most comprehensive phylogenetic hypothesis for the order to date. Relationships at all ranks, such as the relationship of the early-diverging families, often reflect previous studies, but gene conflict is evident, and relationships previously found to be uncertain often remain so. Technical considerations for processing HTS data are also discussed. Conclusions: High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events

    Changes in meltwater chemistry over a 20-year period following a thermal regime switch from polythermal to cold-based glaciation at Austre Broggerbreen, Svalbard

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    Our long-term study gives a rare insight into meltwater hydrochemistry following the transition of Austre Brøggerbreen from polythermal to cold-based glaciation and its continued retreat. We find that the processes responsible for ion acquisition did not change throughout the period of records but became more productive. Two regimes before and after July/August 2000 were identified from changes in solute concentrations and pH. They resulted from increased chemical weathering occurring in ice-marginal and proglacial environments that have become progressively exposed by glacier retreat. Carbonate carbonation nearly doubled between 2000 and 2010, whilst increases in the weathering of silicate minerals were also marked. In addition, the end of ablation season chemistry was characterized by reactions in long residence time flow paths like those in subglacial environments, in spite of their absence in the watershed. Furthermore, the retreat of the glacier caused the sudden re-routing of meltwaters through its immediate forefield during 2009, which more than doubled crustal ion yields in this particular year and influenced chemical weathering in 2010 regardless of a low water flux. Such a “flush” of crustally derived ions can be meaningful for downstream terrestrial and marine ecosystems. We therefore find that, during glacier retreat, the recently exposed forefield is the most chemically active part of the watershed, making high rates of weathering possible, even when ice losses have caused a switch to cold-based conditions with no delayed subglacial drainage flowpaths. In addition, the drainage system reorganization events result in significant pCO2 depletion in an otherwise high pCO2 system

    The Worden sum rule; stochastic differential equations and lattice chiral models

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    SIGLEAvailable from British Library Document Supply Centre- DSC:D59401 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    The Worden sum rule and perturbative QCD

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    SIGLEAvailable from British Library Document Supply Centre- DSC:9106.16(DAMTP--85/33) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Carbon-14 Project Phase 2 - Formation of a Gas Phase and its Migration.

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    Carbon-14 is a key radionuclide in the assessment of the safety of a geological disposal facility (GDF) for radioactive waste, because of the potential radiological impact of gaseous carbon-14 bearing species. RWM has established a project team, in which the partners work together to develop an holistic approach to carbon-14 management in a geological disposal system. This report is part one a suite of reports produced as part of the project. This report is concerned with work to understand the likely formation of a gas phase, and its subsequent migration through the near and far field. In the absence of (i) a site for geological disposal of radioactive wastes and (ii) detailed information on the GDF design, it is not possible to develop a single conceptual model for how carbon-14 bearing gases might migrate from a GDF to the biosphere. Rather, at this generic stage, it is appropriate to consider a range of behaviours. A set of illustrative, post-closure cases is defined, which can be used to link the generation rates of carbon-14 bearing gases to radiological ris

    Cost analysis of breast cancer diagnostic assessment programs

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    ObjectivesDiagnostic assessment programs (daps) appear to improve the diagnosis of cancer, but evidence of their cost-effectiveness is lacking. Given that no earlier study used secondary financial data to estimate the cost of diagnostic tests in the province of Ontario, we explored how to use secondary financial data to retrieve the cost of key diagnostic test services in daps, and we tested the reliability of that cost-retrieving method with hospital-reported costs in preparation for future cost-effectiveness studies.MethodsWe powered our sample at an alpha of 0.05, a power of 80%, and a margin of error of ±5%, and randomly selected a sample of eligible patients referred to a dap for suspected breast cancer during 1 January-31 December 2012. Confirmatory diagnostic tests received by each patient were identified in medical records. Canadian Classification of Health Intervention procedure codes were used to search the secondary financial data Web portal at the Ontario Case Costing Initiative for an estimate of the direct, indirect, and total costs of each test. The hospital-reported cost of each test received was obtained from the host-hospital's finance department. Descriptive statistics were used to calculate the cost of individual or group confirmatory diagnostic tests, and the Wilcoxon signed-rank test or the paired t-test was used to compare the Ontario Case Costing Initiative and hospital-reported costs.ResultsFor the 191 identified patients with suspected breast cancer, the estimated total cost of 72,195.50wasnotsignificantlydifferentfromthehospitalreportedtotalcostof72,195.50 was not significantly different from the hospital-reported total cost of 72,035.52 (p = 0.24). Costs differed significantly when multiple tests to confirm the diagnosis were completed during one patient visit and when confirmatory tests reported in hospital data and in medical records were discrepant. The additional estimated cost for non-salaried physicians delivering diagnostic services was $28,387.50.ConclusionsIt was feasible to use secondary financial data to retrieve the cost of key diagnostic tests in a breast cancer dap and to compare the reliability of the costs obtained by that estimation method with hospital-reported costs. We identified the strengths and challenges of each approach. Lessons learned from this study have to be taken into consideration in future cost-effectiveness studies
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