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1.
Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases. 相似文献
2.
Haochu Li Xiaoming Li Lai Sze Tso Shan Qiao Eleanor Holroyd Yuejiao Zhou 《Vulnerable children and youth studies》2016,11(2):173-179
In HIV/AIDS research, few studies to date have evaluated ways to improve parental HIV disclosure practices using feedback from HIV-negative children who have recently experienced this event. We conducted semi-structured in-depth interviews with 20 children (aged 6–15) who were partially to fully aware of their parents’ HIV status in rural Guangxi, China. Of the 20 children, eight children who were of older age (11.38 years in average) endorsed parental HIV disclosure, five discouraged it and seven expressed uncertainty. Children’s different experiences and attitudes towards disclosure were seen to be associated with their family dynamics (especially the parent–child relationship), social support and care, experiences of stigma and discrimination, psychosocial suffering, comprehension of the disease and the children’s age. Our study contributes to building a child-centered comprehensive understanding for Chinese parental HIV disclosure. It is imperative that counselors and community advocates assess and help parents achieve optimal readiness preceding disclosure of their illness to their HIV-negative children. 相似文献
3.
Aurora Perez-Cornago Georgina K. Fensom Colm Andrews Eleanor L. Watts Naomi E. Allen Richard M. Martin Mieke Van Hemelrijck Timothy J. Key Ruth C. Travis 《British journal of cancer》2020,123(12):1808
Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.Subject terms: Predictive markers, Prostate cancer, Risk factors 相似文献
4.
ABSTRACT Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases. 相似文献
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7.
Jay Magaziner Eleanor M. Simonsick T. Michael Kashner J. Richard Hebel 《Journal of clinical epidemiology》1988,41(11)
The present study evaluates the response comparability between 361 elderly hip fracture patients admitted from the community to seven Baltimore area hospitals between 1984 and 1986 and interviewer selected proxies on items pertaining to patients' pre-fracture health and functional status. Agreement across items ranges from very poor to good and varies with respect to the health or functional area assessed. Proxies tend to overestimate patient disability relative to the patients themselves, especially with regard to capacity to perform instrumental activities of daily living. Although proxies who report the greatest contact with patients respond most comparably to the patients, when they do disagree, proxies with the greatest patient contact tend to overestimate patient disability. The authors suggest that attention to item construction and phrasing may improve response comparability. 相似文献
8.
A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'v) rather than equivalent dioptric power (Fm) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use. 相似文献
9.
J. M. Johnston P. Grondziowski R. M. Windisch R. A. Eder L. Lytle 《Acta diabetologica》1995,32(4):213-216
A feasibility study was undertaken to evaluate laboratory phlebotomists performing bedside glucose monitoring (BGM) over a
3-month period on a medical and surgical floor. Specific questions included: feasibility of providing testing on a 24-h basis,
accuracy, appropriate utilization, effect on patient care, and an analysis of cost. In all, 1975 tests were performed on 114
patients. BGM results were within 15% of the laboratory's result 97% of the time. Patient and physician satisfaction was high.
Although the cost of BGM is slightly higher than a laboratory glucose test, its use appeared to reduce the length of hospital
stay by 0.47 days. Practical information on initiating a highly successful BGM program is provided. 相似文献
10.
Sixty-three mallards were fed one of ten poly(methyl methacrylate) based synthetic grit formulations containing varying concentrations of a proposed wildlife contraceptive (nicarbazin), plasticizer (acetyl tributylcitrate) and/or cross-linking agent (1,4-butanediol diacrylate). Release characteristics of the contraceptive agent were monitored for the purpose of developing a contraceptive formulation for control of pest waterfowl in urban settings. The addition of plasticizer increased the erosion rate (t(1/2)=0.97-2.85 days), cross-linking the polymer matrix slightly decreased the erosion rate (t(1/2)=4.45-5.05 days) and increasing the concentration of the contraceptive agent increased the erosion rate (t(1/2)=3.3 and 9.9 days at 60% and 7.5% active ingredient, respectively). The larger and smaller grit pieces had longer half lives at 11.0 and 11.6 days, respectively while the mid sized grit had a half life of 4.95 days. Control grit had a half life of 12.7 days based on weight loss. Analysis of blood and feces for monitoring release from the grit and approximate indirect plasma levels of the active ingredient proved feasible. 相似文献