Integrated survival analysis using an event-time approach in a Bayesian framework

Event-time or continuous-time statistical approaches have been applied throughout the bio-statistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. this has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed in integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. this provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest \u3c5 days old and were lower for chicks with larger birth weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data

Statistics of Solar Wind Electron Breakpoint Energies Using Machine Learning Techniques

Solar wind electron velocity distributions at 1 au consist of a thermal "core" population and two suprathermal populations: "halo" and "strahl". The core and halo are quasi-isotropic, whereas the strahl typically travels radially outwards along the parallel and/or anti-parallel direction with respect to the interplanetary magnetic field. With Cluster-PEACE data, we analyse energy and pitch angle distributions and use machine learning techniques to provide robust classifications of these solar wind populations. Initially, we use unsupervised algorithms to classify halo and strahl differential energy flux distributions to allow us to calculate relative number densities, which are of the same order as previous results. Subsequently, we apply unsupervised algorithms to phase space density distributions over ten years to study the variation of halo and strahl breakpoint energies with solar wind parameters. In our statistical study, we find both halo and strahl suprathermal breakpoint energies display a significant increase with core temperature, with the halo exhibiting a more positive correlation than the strahl. We conclude low energy strahl electrons are scattering into the core at perpendicular pitch angles. This increases the number of Coulomb collisions and extends the perpendicular core population to higher energies, resulting in a larger difference between halo and strahl breakpoint energies at higher core temperatures. Statistically, the locations of both suprathermal breakpoint energies decrease with increasing solar wind speed. In the case of halo breakpoint energy, we observe two distinct profiles above and below 500 km/s. We relate this to the difference in origin of fast and slow solar wind.Comment: Published in Astronomy & Astrophysics, 11 pages, 10 figure

Restricted streptomycin use in apple orchards did not adversely alter the soil bacteria communities

Streptomycin has been authorized for restricted use in the prevention of the fire blight disease of pome fruit orchards in the EU and Switzerland. This study addresses the important topic of the influence of the use of streptomycin in agriculture on the total bacteria community within the soil ecosystem. Soil samples were taken from soils under apple trees, prior to streptomycin application and 2 weeks post streptomycin application or water application (untreated control). High throughput 16S rRNA gene amplicon sequencing was used to generate datasets from the soils under apple trees in apple orchards from three different locations in Switzerland. We hypothesized that the use of streptomycin would reduce the bacterial diversity within the soil samples and enhance a reduction in the variety of taxa present. Bacterial species such as Pseudomonas, Burkholderia, and Stenotrophomonas are intrinsically resistant to many antibiotics and as such it is of interest to investigate if the use of streptomycin provided a selective advantage for these bacteria in the soil ecosystem. The application of streptomycin did not influence the abundance and diversities of major bacteria taxa of the soils or the Pseudomonas, Burkholderia, and Stenotrophomonas species. We also discovered that apple orchards under the same management practices, did not harbor the same bacterial communities. The restricted application of streptomycin in the protection of apple orchards from the fire blight pathogen Erwinia amylovora under the guidelines in Switzerland did not alter either the bacterial diversity or abundance within these soil ecosystems

Genetic Variants of Milk Proteins - Relevance to Milk Composition and Cheese Production.

End of Project ReportObjectives: (i) to develop rapid screening procedures for the determination of milk protein polymorphism (genetic variants) (ii) to determine the frequency distribution of milk protein genetic variants in a large population of Irish Holstein-Friesians and to determine if there was an association between κ-casein variant and milk yield and composition in this group of animals, and (iii) to make Cheddar and low-moisture part-skim Mozzarella cheese from different κ-casein genetic variant milks and to assess any effect on cheese yield, composition and functional characteristics. Conclusions:Analysis of 6,007 individual Irish Holstein-Friesian milks showed that the phenotype distribution of the κ-casein BB variant was very low at 1.98% compared to 53.07% for κ-casein AA and 44.95% for κ-casein AB. While no statistically significant associations were observed between κ-casein variant and milk yield and composition, κ-casein BB variant milks had superior rennet coagulation properties to that of the AA or AB variants. Generally, κ-casein variant had little effect on compositional attributes of cheese apart from FDM (fat in dry matter) which was significantly higher in cheeses from κ-casein BB milk than in those from κ-casein AA milk. Generally, κ-casein variant had no significant effects on either primary or secondary proteolysis, or on the sensory and/or textural characteristics of Cheddar or Mozzarella cheese throughout ripening; or on the functional characteristics (e.g. flow and stretch) of baked Mozzarella on storage for 90 days at 4°C. However, κ-casein BB variant milk gave significantly higher actual, and moisture adjusted yields of Cheddar and Mozzarella cheese than either κ-casein AB or AA variant milks. For example, the moisture adjusted Cheddar yield from κ-casein BB milk was 8.2% higher than from κ-casein AA milk. In the case of Mozzarella, the moisture adjusted yield was 12% higher. Based on the results, it is estimated that the actual yield of cheese in a plant producing 20,000 tonnes per year from κ-casein AA milk would increase to approximately 21,180 tonnes of Cheddar, or 21,780 tonnes of Mozzarella if made from κ-casein BB milk. Where κ-casein AB milk is used instead of κ-casein BB milk, the estimated yield of Mozzarella would increase to 21,580 tonnes.Department of Agriculture, Food and the Marin

Vitamin D and subsequent all-age and premature mortality: a systematic review

<br>Background: All-cause mortality in the population < 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.</br> <br>Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.</br> <br>Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).</br> <br>Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.</br&gt

Structural elements of an NRPS cyclization domain and its intermodule docking domain

Epothilones are thiazole-containing natural products with anticancer activity that are biosynthesized by polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA–F. A cyclization domain of EpoB (Cy) assembles the thiazole functionality from an acetyl group and L-cysteine via condensation, cyclization, and dehydration. The PKS carrier protein of EpoA contributes the acetyl moiety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes L-cysteine. To visualize the structure of a cyclization domain with an accompanying docking domain, we solved a 2.03-Å resolution structure of this bidomain EpoB unit, comprising residues M1-Q497 (62 kDa) of the 160-kDa EpoB protein. We find that the N-terminal docking domain is connected to the V-shaped Cy domain by a 20-residue linker but otherwise makes no contacts to Cy. Molecular dynamic simulations and additional crystal structures reveal a high degree of flexibility for this docking domain, emphasizing the modular nature of the components of PKS-NRPS hybrid systems. These structures further reveal two 20-Å-long channels that run from distant sites on the Cy domain to the active site at the core of the enzyme, allowing two carrier proteins to dock with Cy and deliver their substrates simultaneously. Through mutagenesis and activity assays, catalytic residues N335 and D449 have been identified. Surprisingly, these residues do not map to the location of the conserved HHxxxDG motif in the structurally homologous NRPS condensation (C) domain. Thus, although both C and Cy domains have the same basic fold, their active sites appear distinct