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11.
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
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Leyi Wang Saraswathi Lanka Debbie Cassout Nohra E. Mateus‐Pinilla Ganwu Li William C. Wilson Dongwan Yoo Paul Shelton Richard L. Fredrickson 《Transboundary and Emerging Diseases》2019,66(5):1809-1820
First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double‐stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year. 相似文献
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Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration. 相似文献
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Kit Galvin Jen Krenz Marcy Harrington Pablo Palmández Richard A. Fenske 《Journal of agromedicine》2016,21(1):113-122
Development of the Practical Solutions for Pesticide Safety guide used participatory research strategies to identify and evaluate solutions that reduce pesticide exposures for workers and their families and to disseminate these solutions. Project principles were (1) workplace chemicals belong in the workplace, and (2) pesticide handlers and farm managers are experts, with direct knowledge of production practices. The project’s participatory methods were grounded in self-determination theory. Practical solutions were identified and evaluated based on five criteria: practicality, adaptability, health and safety, novelty, and regulatory compliance. Research activities that had more personal contact provided better outcomes. The Expert Working Group, composed of farm managers and pesticide handlers, was key to the identification of solutions, as were farm site visits. Audience participation, hands-on testing, and orchard field trials were particularly effective in the evaluation of potential solutions. Small work groups in a Regional Advisory Committee provided the best direction and guidance for a “user-friendly” translational document that provided evidence-based practical solutions. The “farmer to farmer” format of the guide was endorsed by both the Expert Working Group and the Regional Advisory Committee. Managers and pesticide handlers wanted to share their solutions in order to “help others stay safe,” and they appreciated attribution in the guide. The guide is now being used in educational programs across the region. The fundamental concept that farmers and farmworkers are innovators and experts in agricultural production was affirmed by this study. The success of this process demonstrates the value of participatory industrial hygiene in agriculture. 相似文献
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While once considered as incurable systemic disease, treatment options for liver metastases have increased over the last 30 years and safety has improved dramatically, such that for a selected group of patients the hope of cure can now be offered with radical treatment, and low morbidity interventions can be offered which prolong survival, even in patients with more widely disseminated disease. Advances have been made in selection and surgical technique for liver resection and several adjuncts to resection now exist in the form of portal vein embolization, thermal ablation and targeted drug or radiotherapy delivery options. A natural consequence of these developments has been the delivery of services within fewer specialist units, with the result that later complications of therapy may present to local hospitals, rather than directly to the specialist centres. This article will describe the current common liver-directed therapies and outline the presentation and management of their complications. 相似文献
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Phantana-angkool April Voci Amy E. Warren Yancey E. Livasy Chad A. Beasley Lakesha M. Robinson Myra M. Hadzikadic-Gusic Lejla Sarantou Terry Forster Meghan R. Sarma Deba White Richard L. 《Annals of surgical oncology》2019,26(12):3874-3882
Annals of Surgical Oncology - The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. Our aim was to assess... 相似文献