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Sökning: WFRF:(Davidson Michael) > (2015-2019)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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3.
  • Pennells, Lisa, et al. (författare)
  • Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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4.
  • Campbell, Brittany B., et al. (författare)
  • Comprehensive Analysis of Hypermutation in Human Cancer
  • 2017
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:5
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017 Elsevier Inc. We present an extensive assessment of mutation burden through sequencing analysis of > 81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design. A large-scale analysis of hypermutation in human cancers provides insights into tumor evolution dynamics and identifies clinically actionable mutation signatures.
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5.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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6.
  • Wood, Angela M., et al. (författare)
  • Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 391:10129, s. 1513-1523
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies.Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1.14, 95% CI, 1.10-1.17), coronary disease excluding myocardial infarction (1.06, 1.00-1.11), heart failure (1.09, 1.03-1.15), fatal hypertensive disease (1.24, 1.15-1.33); and fatal aortic aneurysm (1.15, 1.03-1.28). By contrast, increased alcohol consumption was loglinearly associated with a lower risk of myocardial infarction (HR 0.94, 0.91-0.97). In comparison to those who reported drinking >0-<= 100 g per week, those who reported drinking >100-<= 200 g per week, >200-<= 350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
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7.
  • Bachelet, Delphine, et al. (författare)
  • Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis : A Collaborative Cohort Analysis
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFN beta)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFN beta-1a subcutaneous and IFN beta-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFN beta-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFN beta therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFN beta in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFN beta. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.
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8.
  • Blasiak, Robert, et al. (författare)
  • Towards greater transparency and coherence in funding for sustainable marine fisheries and healthy oceans
  • 2019
  • Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X .- 1872-9460. ; 107
  • Tidskriftsartikel (refereegranskat)abstract
    • This final manuscript in the special issue on Funding for ocean conservation and sustainable fisheries is the result of a dialogue aimed at connecting lead authors of the special issue manuscripts with relevant policymakers and practitioners. The dialogue took place over the course of a two-day workshop in December 2018, and this coda manuscript seeks to distil thinking around a series of key recurring topics raised throughout the workshop. These topics are collected into three broad categories, or needs: 1) a need for transparency, 2) a need for coherence, and 3) a need for improved monitoring of project impacts. While the special issue sought to collect new research into the latest trends and developments in the rapidly evolving world of funding for ocean conservation and sustainable fisheries, the insights collected during the workshop have helped to highlight remaining knowledge gaps. Therefore, each of the three needs identified within this manuscript is followed by a series of questions that the workshop participants identified as warranting further attention as part of a future research agenda. The crosscutting nature of many of the issues raised as well as the rapid pace of change that characterizes this funding landscape both pointed to a broader need for continued dialogue and study that reaches across the communities of research, policy and practice.
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9.
  • Davidson, Iain F., et al. (författare)
  • Rapid movement and transcriptional re-localization of human cohesin on DNA
  • 2016
  • Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 35:24, s. 2671-2685
  • Tidskriftsartikel (refereegranskat)abstract
    • The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA. It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown. Here, we used single-molecule imaging to show that cohesin can diffuse rapidly on DNA in a manner consistent with topological entrapment and can pass over some DNA-bound proteins and nucleosomes but is constrained in its movement by transcription and DNA-bound CCCTC-binding factor (CTCF). These results indicate that cohesin can be positioned in the genome by moving along DNA, that transcription can provide directionality to these movements, that CTCF functions as a boundary element for moving cohesin, and they are consistent with the hypothesis that cohesin spatially organizes the genome via loop extrusion.
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10.
  • Hamer, Davidson H., et al. (författare)
  • Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016 A GeoSentinel Analysis
  • 2017
  • Ingår i: Annals of Internal Medicine. - Philadelphia : American College of Physicians. - 0003-4819 .- 1539-3704. ; 166:2, s. 99-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barre syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission.
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