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

Development and application of a novel Peptide Nucleic Acid probe for the specific detection of Cronobacter (Enterobacter sakazakii) in powdered infant formula

Cronobacter spp. are causative agents of meningitis, septicemia and necrotizing enterocolitis in neonates and immunocompromised infants. Recently, contaminated powdered infant formula (PIF) has been reported as a source of these infections. In order to minimize the risk of infection, the development of a rapid, sensitive and specific method for the early detection of this bacterium in infant formula is of the utmost importance. Fluorescence in situ hybridization (FISH), a technique that allows direct visualization of whole cells, has been combined with specific peptide nucleic acid (PNA) probes, a new synthetic molecule with a better hybridization performance than DNA probes. In this work, a new FISH method for the detection of Cronobacter spp. using a novel PNA probe is reported. This PNA-FISH method was then adapted for the detection of this bacterium in PIF. The PNA-FISH procedure using the Cronobacter probe proved to be a reliable method for the detection of this pathogen in PIF samples and an alternative to existing molecular methods. It presented high specificity and sensitivity, detected less than 1 CFU per 10g of Cronobacter in infant formula and provided detection in less than 12 hours. Direct visualization of bacterial cells was possible and the method was simple and easy to use, without any special equipment apart from an epifluorescence microscope. The samples can be also analysed by flow cytometry

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

Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark : prospective, nationwide cohort study

Supported by a grant (11645) from the Novo Nordisk Foundation. The funder had no role in the study design; in the collection, analysis and interpretation of data, in the writing of the paper or in the decision to submit the paper for publication.Peer reviewedPublisher PD

Experimental poisoning by Baccharis megapotamica var. weirii in buffalo

Five male 6-8 month-old Murrah buffalo calves were orally dosed with the fresh aerial parts of Baccharis megapotamica var. weirii at doses of 1, 3, 4, 5 and 10g/kg body weight (bw) (~1-10mg macrocyclic trichothecenes/kg/bw). The B. megapotamica used for the experiment was harvested on a farm where a recent spontaneous outbreak of poisoning caused by such plant had occurred. Clinical signs appeared 4-20 hours and 4 buffaloes died 18-49 hours after the ingestion of the plant. Clinical signs were apathy, anorexia, and watery diarrhea, fever, colic, drooling, muscle tremors, restlessness, laborious breathing and ruminal atony, and dehydration. The most consistent gross findings were restricted to the gastrointestinal (GI) tract consisted of varying degrees of edema and reddening of the mucosa of the forestomach. Histopathological findings consisted of varying degrees of necrosis of the epithelial lining of the forestomach and of lymphocytes within lymphoid organs and aggregates. Fibrin thrombi were consistently found in sub-mucosal vessels of the forestomach and in the lumen of hepatic sinusoids. It is suggested that dehydration, septicemia and disseminated intravascular coagulation participate in the pathogenesis of the intoxication and play a role as a cause of death. A subsample of B. megapotamica var. weirii was frozen-dried and ground and analyzed using UHPLC (Ultra High Performance Liquid Chromatography) with high resolution Time of Flight mass spectrometry and tandem mass spectrometry, it was shown that the plant material contained at least 51 different macrocyclic trichothecenes at a total level of 1.1-1.2mg/g. About 15-20% of the total trichothecenes contents was found to be monosaccharide conjugates, with two thirds of these being glucose conjugates and one third constituted by six aldopentose conjugates (probably xylose), which has never been reported in the literature

Generalized Weierstrass Relations and Frobenius reciprocity

This article investigates local properties of the further generalized Weierstrass relations for a spin manifold $S$ immersed in a higher dimensional spin manifold $M$ from viewpoint of study of submanifold quantum mechanics. We show that kernel of a certain Dirac operator defined over $S$, which we call submanifold Dirac operator, gives the data of the immersion. In the derivation, the simple Frobenius reciprocity of Clifford algebras $S$ and $M$ plays important roles.Comment: 17pages. to be published in Mathematical Physics, Analysis and Geometr

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

The effect of harmonized emissions on aerosol properties in global models – an AeroCom experiment

The effects of unified aerosol sources on global aerosol fields simulated by different models are examined in this paper. We compare results from two AeroCom experiments, one with different (ExpA) and one with unified emissions, injection heights, and particle sizes at the source (ExpB). Surprisingly, harmonization of aerosol sources has only a small impact on the simulated diversity for aerosol burden, and consequently optical properties, as the results are largely controlled by model-specific transport, removal, chemistry (leading to the formation of secondary aerosols) and parameterizations of aerosol microphysics (e.g. the split between deposition pathways) and to a lesser extent on the spatial and temporal distributions of the (precursor) emissions. The burdens of black carbon and especially sea salt become more coherent in ExpB only, because the large ExpA diversity for these two species was caused by few outliers. The experiment also indicated that despite prescribing emission fluxes and size distributions, ambiguities in the implementation in individual models can lead to substantial differences. These results indicate the need for a better understanding of aerosol life cycles at process level (including spatial dispersal and interaction with meteorological parameters) in order to obtain more reliable results from global aerosol simulations. This is particularly important as such model results are used to assess the consequences of specific air pollution abatement strategies