Cobbtobin7356

The UK Biobank is an unprecedented resource for human disease research. In March 2019, 49,997 exomes were made publicly available to investigators. Here we note that thousands of variant calls are unexpectedly absent from this dataset, with 641 genes showing zero variation. We show that the reason for this was an erroneous read alignment to the GRCh38 reference. The missing variants can be recovered by modifying read alignment parameters to correctly handle the expanded set of contigs available in the human genome reference. Given the size and complexity of such population scale datasets, we propose a simple heuristic that can uncover systematic errors using summary data accessible to most investigators. © 2020 John Wiley & Sons Ltd/University College London.INTRODUCTION An increasing number of cervical cancer survivors combined with lack of data on the efficacy of long-term surveillance, challenges existing follow-up models. However, before introducing new follow-up models, cervical cancer survivors' own views on follow up are important. We aimed to explore preferences for follow up in long-term cervical cancer survivors and their associations with self-reported late-effects. MATERIAL AND METHODS In 2013, we mailed 974 Norwegian long-term cervical cancer survivors treated during 2000-2007 a questionnaire with items covering preferences for follow up after treatment, clinical variables and validated questionnaires covering anxiety, neuroticism and depression. RESULTS We included 471 cervical cancer survivors (response rate 57%) with a median follow up of 11 years. In all, 77% had FIGO stage I disease, and 35% were attending a follow-up program at the time of survey. Of the patients, 55% preferred more than 5 years of follow up. This was also preferred by 57% of cervical cancer survivors who were treated with conization only. In multivariable analyses, chemo-radiotherapy or surgery with radiation and/or chemotherapy (heavy treatment) and younger age were significantly associated with a preference for more than 5 years' follow up. Late effects were reported by more than 70% of the cervical cancer survivors who had undergone heavy treatment. CONCLUSIONS Our study reveals the need for targeted patient education about the benefits and limitations of follow up. To meet increasing costs of cancer care, individualized follow-up procedures adjusted to risk of recurrence and late-effects in cervical cancer survivors are warranted. © The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).BACKGROUND Deterioration after ICU discharge may lead to readmission or even death. Interventions (eg, critical care transition programs) have been developed to improve the clinical handover between the ICU and the ward. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) according to Cochrane Handbook and Grading of recommendations, assessment, development and evaluations (GRADE) methodology to assess the impact of these interventions on readmission and death (PROSPERO, no CRD42019121746). METHODS We searched PubMed/MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Register for Controlled Trials from inception until January 2019. We included historically controlled studies that evaluated critical care transition programs in adults discharged from the ICU. Readmission and in-hospital mortality were the primary outcomes. Risk of bias, publications bias, and the quality of evidence were assessed with the ROBINS-Itool, funnel plot and GRADE, respectively. RESULTS Fifteen observational studies were included (11 in meta-analysis). All studies had at least serious risk of bias. DW71177 ICU discharge within a critical care transition program modestly reduced the risk of readmission (RR 0.78; 95% CI 0.64-0.96; TSA-adjusted 95% CI 0.59-1.03) but not in-hospital mortality (RR 0.82; 95% CI 0.64-1.06; TSA-adjusted 95% CI 0.49-1.37). There was substantial heterogeneity among studies. TSA indicated lack of firm evidence. The GRADE quality of evidence on outcomes was very low. CONCLUSIONS We found no clear benefit in terms of reducing risk of readmission or death after ICU discharge, however, with overall very low certainty of evidence. © 2020 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.BACKGROUND AND PURPOSE To investigate the vasorelaxant effect of glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 on retinal capillaries under normal and ischemia-reperfusion (I/R) conditions. EXPERIMENTAL APPROACH The regulation of capillary diameters by exendin-4 on whole-mounted retina was directly observed using the infrared differential interference contrast microscopy. A rat model of retinal I/R was established using high perfusion pressure in an anterior chamber. To observe the possible protective role of exendin-4, the peptide drug was administered through subcutaneous injection, intravitreal injection, or eye drops. The underlying mechanism was explored by immunofluorescence, qPCR, and Simple Western. KEY RESULTS Immunofluorescence staining showed that GLP-1R was expressed in the endothelial cells of retinal capillaries. Exendin-4 significantly relaxed the capillaries pre-contracted by noradrenaline, which was abolished by denuding endothelium with CHAPS and inhibited by GLP-1R antagonist exendin-9-39, endothelium nitric oxide synthase (eNOS) inhibitor L-NAME, and the guanylate cyclase blocker ODQ, but not by cyclooxygenase inhibitor indomethacin. Retina capillary was constricted in I/R injury and perfusion of exendin-4 could restored it effectively. The expression level of PI3K and AKT, phosphorylation level of eNOS, and NO production in I/R group was lower than that in the normal control group, and the administration of exendin-4 improved the changes. CONCLUSION AND IMPLICATION Exendin-4 can restore injured microvascular patency in I/R. Exendin-4 may regulate retinal capillaries through the GLP-1R-PI3K/AKT-eNOS/NO-cGMP pathway. Therefore, exendin-4 may be an effective treatment for improving tissue perfusion in I/R-related diseases. This article is protected by copyright. All rights reserved.