4,610 research outputs found
Bayesian model search and multilevel inference for SNP association studies
Technological advances in genotyping have given rise to hypothesis-based
association studies of increasing scope. As a result, the scientific hypotheses
addressed by these studies have become more complex and more difficult to
address using existing analytic methodologies. Obstacles to analysis include
inference in the face of multiple comparisons, complications arising from
correlations among the SNPs (single nucleotide polymorphisms), choice of their
genetic parametrization and missing data. In this paper we present an efficient
Bayesian model search strategy that searches over the space of genetic markers
and their genetic parametrization. The resulting method for Multilevel
Inference of SNP Associations, MISA, allows computation of multilevel posterior
probabilities and Bayes factors at the global, gene and SNP level, with the
prior distribution on SNP inclusion in the model providing an intrinsic
multiplicity correction. We use simulated data sets to characterize MISA's
statistical power, and show that MISA has higher power to detect association
than standard procedures. Using data from the North Carolina Ovarian Cancer
Study (NCOCS), MISA identifies variants that were not identified by standard
methods and have been externally ``validated'' in independent studies. We
examine sensitivity of the NCOCS results to prior choice and method for
imputing missing data. MISA is available in an R package on CRAN.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS322 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Evidence for a direct band gap in the topological insulator Bi2Se3 from theory and experiment
Using angle-resolved photoelectron spectroscopy and ab-initio GW
calculations, we unambiguously show that the widely investigated
three-dimensional topological insulator Bi2Se3 has a direct band gap at the
Gamma point. Experimentally, this is shown by a three-dimensional band mapping
in large fractions of the Brillouin zone. Theoretically, we demonstrate that
the valence band maximum is located at the Brillouin center only if many-body
effects are included in the calculation. Otherwise, it is found in a
high-symmetry mirror plane away from the zone center.Comment: 8 pages, 4 figure
Exploring positive pathways to care for members of the UK Armed Forces receiving treatment for PTSD: a qualitative study
Objective: To examine the factors which facilitate UK military personnel with post-traumatic stress disorder (PTSD) to engage in help-seeking behaviours. Methods: The study recruited active service personnel who were attending mental health services, employed a qualitative design, used semi-structured interview schedules to collect data, and explored these data using interpretative phenomenological analysis (IPA). Results: Five themes emerged about how participants were able to access help; having to reach a crisis point before accepting the need for help, overcoming feelings of shame, the importance of having an internal locus of control, finding a psychological explanation for their symptoms and having strong social support. Conclusions: This study reported that for military personnel who accessed mental health services, there were a number of factors that supported them to do so. In particular, factors that combated internal stigma, such as being supported to develop an internal locus of control, appeared to be critical in supporting military personnel to engage in help-seeking behaviour
Lifetime cancer risk and combined oral contraceptives : the Royal College of General Practitioners’ Oral Contraception Study
Funding: The study has received funding from the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care Ltd, Wyeth Ayerst International, Ortho Cilag and, Searle. None of these funders have contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.Peer reviewedPostprin
HIV-infected sex workers with beneficial HLA-variants are potential hubs for selection of HIV-1 recombinants that may affect disease progression
Cytotoxic T lymphocyte (CTL) responses against the HIV Gag protein are associated with lowering viremia; however, immune control is undermined by viral escape mutations. The rapid viral mutation rate is a key factor, but recombination may also contribute. We hypothesized that CTL responses drive the outgrowth of unique intra-patient HIV-recombinants (URFs) and examined gag sequences from a Kenyan sex worker cohort. We determined whether patients with HLA variants associated with effective CTL responses (beneficial HLA variants) were more likely to carry URFs and, if so, examined whether they progressed more rapidly than patients with beneficial HLA-variants who did not carry URFs. Women with beneficial HLA-variants (12/52) were more likely to carry URFs than those without beneficial HLA variants (3/61) (p < 0.0055; odds ratio = 5.7). Beneficial HLA variants were primarily found in slow/standard progressors in the URF group, whereas they predominated in long-term non-progressors/survivors in the remaining cohort (p = 0.0377). The URFs may sometimes spread and become circulating recombinant forms (CRFs) of HIV and local CRF fragments were over-represented in the URF sequences (p < 0.0001). Collectively, our results suggest that CTL-responses associated with beneficial HLA variants likely drive the outgrowth of URFs that might reduce the positive effect of these CTL responses on disease progression
Contaminated mouth swabs caused a multi-hospital outbreak of Pseudomonas aeruginosa infection
Report and preliminary results of R/V POSEIDON cruise POS495, Las Palmas (Canary Islands) - Las Palmas (Canary Islands), 18.02.2016 - 02.03.2016
Report and preliminary results of R/V POSEIDON cruise POS481, Las Palmas (Canary Islands) - Las Palmas (Canary Islands), 15.03.2015 - 03.03.2015
Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies
Acknowledgements Access to UK Biobank data was approved and facilitated by UK Biobank (application number: 34374). Access to Primary Care Clinical Informatics Unit (PCCIU) data was approved and facilitated by the PCCIU Research team, University of Aberdeen. Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM. Funding: Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM. Liu P was supported by a joint scholarship from Queen's University Belfast and the Chinese Scholarship Council (201708060458). Data availability: The UK Biobank data (https://www.ukbiobank.ac.uk/) and PCCIU data (https://www.abdn.ac.uk/iahs/research/primary-care/pcciur/) are available, following the access procedures, for researchers to access to conduct health related research in the public interest.Peer reviewedPostprin
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