BALLET DANCER INJURIES DURING PERFORMANCE AND REHEARSAL ON VARIED DANCE SURFACES

Three dance surfaces regularly used by a professional touring ballet company (n=60) were quantified using standard sports surface testing apparatus. Surface sub-structure construction varied between surfaces and a range of surface force reduction values were reported. Injuries and associated variables occurring within the ballet company were recorded by the company medical staff. An injury was recorded if a dancer experienced an incident that restricted the dancer from performing all activities that were required of them for the period 24hrs after the incident. Injuries were delimited to those occurring in the lower limbs or trunk during reported non-lifting dance activity. Analysis of statistical significance was restricted due to a low injury data sample size. However certain trends in the injury data warrant future research. The surface with the highest variability in intra-surface force reduction was associated with the highest injury rates per week, lower limb injuries per week, mean days lost dancing per injury and likelihood of injury per performance day. Variability in intra-surface force reduction may have a stronger association with injury risk than mean surface force reduction magnitudes

Effects of CYP46A1 inhibition on long-term-depression in hippocampal slices ex vivo and 24S-hydroxycholesterol levels in mice in vivo

The manipulation of cholesterol and its metabolites has been hypothesized to be therapeutically beneficial for mood disorders, neurodegenerative disorders, and epilepsies. A major regulator of cholesterol clearance and turnover in the central nervous system is CYP46A1, a brain enriched enzyme responsible for metabolism of cholesterol into 24S-hydroxycholesterol. Inhibition of this enzyme may negatively modulate NMDARs as 24S-hydroxycholesterol was shown to enhance NMDAR function. In addition, alterations of local cholesterol or other changes mediated by CYP46A1 activity could have important influences on central nervous system function. Here we demonstrate that humans and mice display brain region specific and similar CYP46A1 and 24S-hydroxycholesterol distribution. Treatment with distinct classes of CYP46A1 inhibitors led to central 24S-hydroxycholesterol reductio

Discovery of selective Toxoplasma gondii dihydrofolate reductase inhibitors for the treatment of toxoplasmosis

A safer treatment for toxoplasmosis would be achieved by improving the selectivity and potency of dihydrofolate reductase (DHFR) inhibitors, such as pyrimethamine (1), for Toxoplasma gondii DHFR ( TgDHFR) relative to human DHFR ( hDHFR). We previously reported on the identification of meta-biphenyl analog 2, designed by in silico modeling of key differences in the binding pocket between TgDHFR and hDHFR. Compound 2 improves TgDHFR selectivity 6.6-fold and potency 16-fold relative to 1. Here, we report on the optimization and structure-activity relationships of this arylpiperazine series leading to the discovery of 5-(4-(3-(2-methoxypyrimidin-5-yl)phenyl)piperazin-1-yl)pyrimidine-2,4-diamine 3. Compound 3 has a TgDHFR I

Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees

The authors are grateful to the Royal Zoological Society of Scotland for providing core funding for the Budongo Conservation Field Station. The fieldwork of CH was funded by the Leverhulme Trust, the Lucie Burgers Stichting, and the British Academy. TP was funded by the Canadian Research Chair in Continental Ecosystem Ecology, and received computational support from the Theoretical Ecosystem Ecology group at UQAR. The research leading to these results has received funding from the People Programme (Marie Curie Actions) and from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007–2013) REA grant agreement n°329197 awarded to TG, ERC grant agreement n° 283871 awarded to KZ. WH was funded by a BBSRC grant (BB/I007997/1).Social network analysis methods have made it possible to test whether novel behaviors in animals spread through individual or social learning. To date, however, social network analysis of wild populations has been limited to static models that cannot precisely reflect the dynamics of learning, for instance, the impact of multiple observations across time. Here, we present a novel dynamic version of network analysis that is capable of capturing temporal aspects of acquisition-that is, how successive observations by an individual influence its acquisition of the novel behavior. We apply this model to studying the spread of two novel tool-use variants, "moss-sponging'' and "leaf-sponge re-use,'' in the Sonso chimpanzee community of Budongo Forest, Uganda. Chimpanzees are widely considered the most "cultural'' of all animal species, with 39 behaviors suspected as socially acquired, most of them in the domain of tool-use. The cultural hypothesis is supported by experimental data from captive chimpanzees and a range of observational data. However, for wild groups, there is still no direct experimental evidence for social learning, nor has there been any direct observation of social diffusion of behavioral innovations. Here, we tested both a static and a dynamic network model and found strong evidence that diffusion patterns of moss-sponging, but not leaf-sponge re-use, were significantly better explained by social than individual learning. The most conservative estimate of social transmission accounted for 85% of observed events, with an estimated 15-fold increase in learning rate for each time a novice observed an informed individual moss-sponging. We conclude that group-specific behavioral variants in wild chimpanzees can be socially learned, adding to the evidence that this prerequisite for culture originated in a common ancestor of great apes and humans, long before the advent of modern humans.Publisher PDFPeer reviewe

TeV Gamma-Ray Sources from a Survey of the Galactic Plane with Milagro

A survey of Galactic gamma-ray sources at a median energy of ~20 TeV has been performed using the Milagro Gamma Ray Observatory. Eight candidate sources of TeV emission are detected with pre-trials significance $>4.5\sigma$ in the region of Galactic longitude $l\in[30^\circ,220^\circ]$ and latitude $b\in[-10^\circ,10^\circ]$. Four of these sources, including the Crab nebula and the recently published MGRO J2019+37, are observed with significances $>4\sigma$ after accounting for the trials involved in searching the 3800 square degree region. All four of these sources are also coincident with EGRET sources. Two of the lower significance sources are coincident with EGRET sources and one of these sources is Geminga. The other two candidates are in the Cygnus region of the Galaxy. Several of the sources appear to be spatially extended. The fluxes of the sources at 20 TeV range from ~25% of the Crab flux to nearly as bright as the Crab.Comment: Submitted to Ap

Variability in COVID-19 in-hospital mortality rates between national health service trusts and regions in England: A national observational study for the Getting It Right First Time Programme

Background A key first step in optimising COVID-19 patient outcomes during future case-surges is to learn from the experience within individual hospitals during the early stages of the pandemic. The aim of this study was to investigate the extent of variation in COVID-19 outcomes between National Health Service (NHS) hospital trusts and regions in England using data from March–July 2020. Methods This was a retrospective observational study using the Hospital Episode Statistics administrative dataset. Patients aged ≥ 18 years who had a diagnosis of COVID-19 during a hospital stay in England that was completed between March 1st and July 31st, 2020 were included. In-hospital mortality was the primary outcome of interest. In secondary analysis, critical care admission, length of stay and mortality within 30 days of discharge were also investigated. Multilevel logistic regression was used to adjust for covariates. Findings There were 86,356 patients with a confirmed diagnosis of COVID-19 included in the study, of whom 22,944 (26.6%) died in hospital with COVID-19 as the primary cause of death. After adjusting for covariates, the extent of the variation in-hospital mortality rates between hospital trusts and regions was relatively modest. Trusts with the largest baseline number of beds and a greater proportion of patients admitted to critical care had the lowest in-hospital mortality rates. Interpretation There is little evidence of clustering of deaths within hospital trusts. There may be opportunities to learn from the experience of individual trusts to help prepare hospitals for future case-surges

Viking Afterbody Heating Computations and Comparisons to Flight Data

Computational fluid dynamics predictions of Viking Lander 1 entry vehicle afterbody heating are compared to flight data. The analysis includes a derivation of heat flux from temperature data at two base cover locations, as well as a discussion of available reconstructed entry trajectories. Based on the raw temperature-time history data, convective heat flux is derived to be 0.63-1.10 W/sq cm for the aluminum base cover at the time of thermocouple failure. Peak heat flux at the fiberglass base cover thermocouple is estimated to be 0.54-0.76 W/sq cm, occurring 16 seconds after peak stagnation point heat flux. Navier-Stokes computational solutions are obtained with two separate codes using an 8-species Mars gas model in chemical and thermal non-equilibrium. Flowfield solutions using local time-stepping did not result in converged heating at either thermocouple location. A global time-stepping approach improved the computational stability, but steady state heat flux was not reached for either base cover location. Both thermocouple locations lie within a separated flow region of the base cover that is likely unsteady. Heat flux computations averaged over the solution history are generally below the flight data and do not vary smoothly over time for both base cover locations. Possible reasons for the mismatch between flight data and flowfield solutions include underestimated conduction effects and limitations of the computational methods

A role for XRCC2 gene polymorphisms in breast cancer risk and survival

Background The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer. Methods The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC). Results The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10−4, minor allele frequency (MAF)=0.23). This SNP yielded an ORrec of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-ORrec of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01). Conclusions These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations