Bayesian variable selection using partially observed categorical prior information in fine-mapping association studies

Several methods have been proposed to allow functional genomic information to inform prior distributions in Bayesian fine‐mapping case–control association studies. None of these methods allow the inclusion of partially observed functional genomic information. We use functional significance (FS) scores that combine information across multiple bioinformatics sources to inform our effect size prior distributions. These scores are not available for all single‐nucleotide polymorphisms (SNPs) but by partitioning SNPs into naturally occurring FS score groups, we show how missing FS scores can easily be accommodated via finite mixtures of elicited priors. Most current approaches adopt a formal Bayesian variable selection approach and either limit the number of causal SNPs allowed or use approximations to avoid the need to explore the vast parameter space. We focus instead on achieving differential shrinkage of the effect sizes through prior scale mixtures of normals and use marginal posterior probability intervals to select candidate causal SNPs. We show via a simulation study how this approach can improve localisation of the causal SNPs compared to existing mutli‐SNP fine‐mapping methods. We also apply our approach to fine‐mapping a region around the CASP8 gene using the iCOGS consortium breast cancer SNP data

Directional recoil rates for WIMP direct detection

New techniques for the laboratory direct detection of dark matter weakly interacting massive particles (WIMPs) are sensitive to the recoil direction of the struck nuclei. We compute and compare the directional recoil rates ${dR}/{d\cos\theta}$ (where $\theta$ is the angle measured from a reference direction in the sky) for several WIMP velocity distributions including the standard dark halo and anisotropic models such as Sikivie's late-infall halo model and logarithmic-ellipsoidal models. Since some detectors may be unable to distinguish the beginning of the recoil track from its end (lack of head-tail discrimination), we introduce a ``folded'' directional recoil rate ${dR}/{d|\cos\theta|}$, where $|\cos\theta|$ does not distinguish the head from the tail of the track. We compute the CS$_2$ and CF$_4$ exposures required to distinguish a signal from an isotropic background noise, and find that ${dR}/{d|\cos\theta|}$ is effective for the standard dark halo and some but not all anisotropic models.Comment: 39 pages, 15 figure

Using GWAS top hits to inform priors in Bayesian fine-mapping association studies

The default causal single‐nucleotide polymorphism (SNP) effect size prior in Bayesian fine‐mapping studies is usually the Normal distribution. This choice is often based on computational convenience, rather than evidence that it is the most suitable prior distribution. The choice of prior is important because previous studies have shown considerable sensitivity of causal SNP Bayes factors to the form of the prior. In some well‐studied diseases there are now considerable numbers of genome‐wide association study (GWAS) top hits along with estimates of the number of yet‐to‐be‐discovered causal SNPs. We show how the effect sizes of the top hits and estimates of the number of yet‐to‐be‐discovered causal SNPs can be used to choose between the Laplace and Normal priors, to estimate the prior parameters and to quantify the uncertainty in this estimation. The methodology can readily be applied to other priors. We show that the top hits available from breast cancer GWAS provide overwhelming support for the Laplace over the Normal prior, which has important consequences for variant prioritisation. This work in this paper enables practitioners to derive more objective priors than are currently being used and could lead to prioritisation of different variants

Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels

Spectral Properties of PMMA Films Doped by Perylene Dyestuffs for Photoselective Greenhouse Cladding Applications

Luminescent polymethylmethacrylate (PMMA) films were prepared by the solvent-casting technique from polymer solution doped with different concentrations of red perylene dyestuffs (KREMER 94720 and KREMER 94739). The effect of the dye concentration on the structure and spectroscopic properties was studied using X-ray diffraction (XRD), transmission electron microscope (TEM) optical absorption, and fluorescence spectroscopy. The optimum dye concentration of photoselective PMMA films was determined by the fluorescence spectroscopy measurements and showed the best emission properties for the doping concentration 10−3 wt % of the investigated dyes. The accelerated photostability tests showed promising stability of the prepared films towards terrestrial solar ultraviolet radiation (UVA). The results endorsed a promising application of the investigated films in photoselective greenhouse cladding applications as the optimized film fluoresces at the action spectra of special chlorophyll a

Post refractory CPR due to STEMI with three vessels disease complicated cardiac arrest, is it possible to recover the heart after revascularization by PCI post extracorporeal cardio pulmonary resuscitation (ECPR)?

High-risk percutaneous coronary intervention (PCI) remains a viable revascularization strategy for complex coronary arteries diseases. Selective PCI supported by extracorporeal membrane oxygenation (ECMO) is also a viable alternative for patients those are at very high risk for coronary artery bypass grafting (CABG). Extracorporeal membrane oxygenation (ECMO) can direct blood flow from the body to membrane oxygenator then return it back to the body. Thus completely/partially replacing the function of the heart and lungs to increasing the likelihood of functional recovery. We will present a case of refractory CPR post STMI rescued by ECPR with revascularization of three coronary vessels after percutaneous coronary intervention (PCI) under mechanical support of extracorporeal membrane oxygenation (ECMO) after exclusion of surgical choice due to patient risk condition. We think that in selected group of highly critical cases PCI with MCS could replace the need of major surgical intervention like CABG. Keywords: High risk PCI, ECMO, ECPR, Multi vessels disease

Immunogenicity of High-Dose MVA-Based MERS Vaccine Candidate in Mice and Camels

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime–boost vaccinations in mice and camels. Methods: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Results: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). Conclusions: MVA-MERS vaccine, administered in a homologous prime–boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans