Noise-augmented directional clustering of genetic association data identifies distinct mechanisms underlying obesity.

Funder: NIHR Cambridge Biomedical Research CentreClustering genetic variants based on their associations with different traits can provide insight into their underlying biological mechanisms. Existing clustering approaches typically group variants based on the similarity of their association estimates for various traits. We present a new procedure for clustering variants based on their proportional associations with different traits, which is more reflective of the underlying mechanisms to which they relate. The method is based on a mixture model approach for directional clustering and includes a noise cluster that provides robustness to outliers. The procedure performs well across a range of simulation scenarios. In an applied setting, clustering genetic variants associated with body mass index generates groups reflective of distinct biological pathways. Mendelian randomization analyses support that the clusters vary in their effect on coronary heart disease, including one cluster that represents elevated body mass index with a favourable metabolic profile and reduced coronary heart disease risk. Analysis of the biological pathways underlying this cluster identifies inflammation as potentially explaining differences in the effects of increased body mass index on coronary heart disease

Effects of Timber Harvesting and Plantation Development on Cavity-nesting Birds in New Brunswick

We studied the abundance of cavity-nesting birds in forestry-related habitats in a region of Acadian forest in New Brunswick. We examined five reference stands of natural forest, a chronosequence of conifer plantations up to 19 years old (the oldest in the study area), two selectively harvested stands, and a 30-year-old naturally regenerated clear-cut. The species richness and abundance of cavity-nesting birds were higher in reference forest (average 10.0 species per stand; 5.3 territories per 10 ha) than in plantations (2.3/stand; 1.0/10 ha), selectively harvested stands (7.0/stand; 3.8/10 ha), or the naturally regenerated clear-cut (5.0/stand; 2.5/10 ha). A cluster analysis segregated the “community” of cavity-nesting birds of natural forest from those of other treatments. Of the various harvested stands and plantations, five with a relatively large number of residual snags clustered similarly in the cluster analysis, while those with no or very few snags also clustered together. We used arrays of nest boxes (12 per stand) to examine whether the availability of cavities was limiting the use of habitats otherwise suitable for foraging by cavity-dependent species. Nest-box use for nesting and roosting was much higher in the seven plantations examined (average 4.0/10 ha for nesting and 2.9/10 ha for roosting) than in three reference stands (each 0.3/10 ha), suggesting that the plantations were deficient in this critical-habitat element. Our results suggest that certain mitigations, such as leaving residual snags and living cavity-trees, would help maintain populations of some cavity-dependent birds in clear-cuts and plantations. However, some cavity-dependent species might not be accommodated by these mitigations and are potentially at risk in intensively managed areas, unless landscape-scale management plans ensure the survival of sufficient areas of older mixed-wood forest

Evaluating interventions for informed consent for surgery (ICONS) :Protocol for the development of a core outcome set

Abstract Background The concept of informed consent is fundamental to medical practice. Shortcomings in the process can lead to patient complaints, litigation, unmet expectations and poor outcomes. Consent research has focused on developing tools to improve patient recall and understanding. However, the definitions, methods of measurement and timing of measurement vary widely across the studies that have been done. Although a Cochrane review has reported that many of these interventions appear to work, the high level of heterogeneity in outcome reporting prevents the identification of those interventions that work best and why they do so. It is also not clear which outcomes are most important to each party involved in the consent process and why. Methods/design This project will develop a core outcome set for assessing the effects of interventions aimed at improving informed consent for surgery and other invasive procedures for adult patients with the capacity to consent for themselves. We will conduct a systematic review of the qualitative and quantitative literature to identify outcomes used to date in consent research and map these into domains. A series of semi-structured key stakeholder interviews will also be used to identify relevant outcomes. These processes will produce a list of potential outcomes for assessing the effects of interventions to improve consent, which will be refined through an international Delphi survey and consensus webinars involving key stakeholders to produce the core outcome set. Discussion The ICONS study aims to develop a core outcome set for use in trials and reviews of interventions designed to improve the informed consent process for surgery and other invasive procedures. Our aim is that this core outcome set will reduce the level of selection and reporting bias in consent research and help clinicians to compare tools to improve consent

A Complete Scheme of Ionization Cooling for a Muon Collider

A complete scheme for production and cooling a muon beam for three specified muon colliders is presented. Parameters for these muon colliders are given. The scheme starts with the front end of a proposed neutrino factory that yields bunch trains of both muon signs. Emittance exchange cooling in slow helical lattices reduces the longitudinal emittance until it becomes possible to merge the trains into single bunches, one of each sign. Further cooling in all dimensions is applied to the single bunches in further slow helical lattices. Final transverse cooling to the required parameters is achieved in 50 T solenoids using high Tc superconductor at 4 K. Preliminary simulations of each element are presented.Comment: 3 pages, 6 figure

Ovarian responses to undernutrition in pregnant ewes, USA

In most mammals oogonia proliferate by mitosis and begin meiotic development during fetal life. Previous studies indicated that there is a delay in the progression to the first stage of meiotic arrest in germ cells of female fetuses of undernourished ewes. We report that underfeeding (50% NRC requirement beginning on Day 28 of pregnancy) provokes an increase in oxidative base lesions within DNA of mid-gestational (Day 78) fetal oogonia; this condition was associated with up-regulation of the tumor suppressor/cell-cycle arrest modulator p53, antiapoptotic factor Bcl-2, and base-excision repair polymerase β. Fetal ovarian weights and germ cell concentrations were not altered by nutrient deprivation. Ovaries of ewes on control diets (100% NRC) contained more tertiary follicles than their restricted counterparts; however, peripheral venous estradiol-17β was not different between groups. There was no effect of treatment on p53 accumulation in maternal oocytes. Luteal structure-function was not perturbed by undernutrition. No fetal losses were attributed to the dietary restriction. It is proposed that DNA of interphase fetal oogonia is vulnerable to oxidative insults perpetrated by a nutritional stress to the dam, and that multiple/integrated adaptive molecular response mechanisms of cell-cycle inhibition (providing the time required for base repairs) and survival hence sustain the genomic integrity and population stability of the germline

An Integrated Content and Metadata based Retrieval System for Art

In this paper we describe aspects of the Artiste project to develop a distributed content and metadata based analysis, retrieval and navigation system for a number of major European Museums. In particular, after a brief overview of the complete system, we describe the design and evaluation of some of the image analysis algorithms developed to meet the specific requirements of the users from the museums. These include a method for retrievals based on sub images, retrievals based on very low quality images and retrieval using craquelure type

Circulating endothelial microparticles reduce in concentration following an exercise programme in women with polycystic ovary syndrome

Purpose: Endothelial dysfunction is a known comorbidity in women with polycystic ovary syndrome (PCOS). The aim was to assess if supervised, moderate intensity exercise could potentially impact markers of endothelial disruption; endothelial cell derived microparticles (EMP). Methods: The current study investigated the effects of a supervised 8-week moderate intensity exercise programme on EMP in women with PCOS (n=11) and control women free from any known disease (n=10). EMP were enumerated via specific antibody (CD105, CD106) labelling and flow cytometry.Results: CD105+MP significantly reduced in women with PCOS from pre to post exercise programme, with CD105+ MP reducing from 2114 CD105+ MP per µl platelet free plasma (PFP) to 424 CD105+ MP per µl PFP (p = 0.025). Control women showed no significant change in CD105+ MP (p = 0.25) after completing the same exercise programme. CD106+ MP showed no change in either PCOS (p = 0.95) or control groups (p = 0.99). No significant correlations existed with the changes in endothelial microparticles (EMP) compared to body composition changes as a result of exercise. Conclusion: Supervised, moderate intensity exercise independent of substantial weight loss reduced circulating CD105+MP, likely reflecting an improvement in endothelial function in women with PCOS compared to healthy control women. Additionally, EMP may be a useful marker for physical improvement in exercise programmes for clinical populations

Venom Ontogeny in the Mexican Lance-Headed Rattlesnake (Crotalus polystictus)

As trophic adaptations, rattlesnake venoms can vary in composition depending on several intrinsic and extrinsic factors. Ontogenetic changes in venom composition have been documented for numerous species, but little is known of the potential age-related changes in many rattlesnake species found in México. In the current study, venom samples collected from adult and neonate Crotalus polystictus from Estado de México were subjected to enzymatic and electrophoretic analyses, toxicity assays (LD50), and MALDI-TOF mass spectrometry, and a pooled sample of adult venom was analyzed by shotgun proteomics. Electrophoretic profiles of adult males and females were quite similar, and only minor sex-based variation was noted. However, distinct differences were observed between venoms from adult females and their neonate offspring. Several prominent bands, including P-I and P-III snake venom metalloproteinases (SVMPs) and disintegrins (confirmed by MS/MS) were present in adult venoms and absent/greatly reduced in neonate venoms. Age-dependent differences in SVMP, kallikrein-like, phospholipase A2 (PLA2), and L-amino acid oxidase (LAAO) activity levels were confirmed by enzymatic activity assays, and like many other rattlesnake species, venoms from adult snakes have higher SVMP activity than neonate venoms. Conversely, PLA2 activity was approximately 2.5 X greater in venoms from neonates, likely contributing to the increased toxicity (neonate venom LD50 = 4.5 μg/g) towards non-Swiss albino mice when compared to adult venoms (LD50 = 5.5 μg/g). Thrombin-like (TLE) and phosphodiesterase activities did not vary significantly with age. A significant effect of sex (between adult male and adult female venoms) was also observed for SVMP, TLE, and LAAO activities. Analysis of pooled adult venom by LC-MS/MS identified 14 toxin protein families, dominated by bradykinin-inhibitory peptides, SVMPs (P-I, P-II and P-III), disintegrins, PLA2s, C-type-lectins, CRiSPs, serine proteinases, and LAAOs (96% of total venom proteins). Neonate and adult C. polystictus in this population consume almost exclusively mammals, suggesting that age-based differences in composition are related to physical differences in prey (e.g., surface-to-volume ratio differences) rather than taxonomic differences between prey. Venoms from adult C. polystictus fit a Type I pattern (high SVMP activity, lower toxicity), which is characteristic of many larger-bodied rattlesnakes of North America.Funding for this study was provided in part by the Colorado Office for Economic Development and International Trade (to SPM). Additional funds were provided by the UNC Office of Research

The barrier method as a new tool to assist in career selection: covert observational study

Objective To determine if senior doctors’ parking habits and skills are associated with clinical specialty and, if so, whether observation of junior doctors’ parking could provide guidance in choice of specialty