Positional match demands of professional rugby league competition

The purpose of this study was to examine the differences in physical performance and game-specific skill demands between 5 positional groups in a professional rugby league team. Positional groups consisted of the backs (n = 8), forwards (n = 8), fullback (n = 7), hooker (n = 8), and service players (n = 8). Time-motion analysis was used to determine physical performance measures (exercise intensity, distance travelled, time, frequency, and speed measures) and game-specific skill measures (ball carries, supports, ball touches, play the balls, and tackling indices) per minute of playing time. The main finding was that the fullback completed more very high-intensity running (VHIR) because of more support runs when compared to all other positional groups (p = 0.017). THe VHIR (p = 0.004) and sprinting indices (p < 0.002) were also greater in the second half of a match for the fullback than in any other positional group. The hooker spent more time jogging than the backs and forwards (p < 0.001) and touched the ball on more occasions than any other positional group (p < 0.001). The backs spent more time walking than the forwards, hooker, and service players (p < 0.001). The forwards, hooker, and service players completed more tackles per minute during a match than the backs and fullback (p < 0.001). The fullback and forwards also ran the ball on more occasions than the backs, hooker, and service players did (p < 0.001). These results show that positional roles play an important part in determining the amount of physical and game-specific skill involvement during match play. © 2011 National Strength and Conditioning Association

Kinetic profiling of therapeutic strategies for inhibiting the formation of amyloid oligomers

Protein self-assembly into amyloid fibrils underlies several neurodegenerative conditions, including Alzheimer's and Parkinson's diseases. It has become apparent that the small oligomers formed during this process constitute neurotoxic molecular species associated with amyloid aggregation. Targeting the formation of oligomers represents therefore a possible therapeutic avenue to combat these diseases. However, it remains challenging to establish which microscopic steps should be targeted to suppress most effectively the generation of oligomeric aggregates. Recently, we have developed a kinetic model of oligomer dynamics during amyloid aggregation. Here, we use this approach to derive explicit scaling relationships that reveal how key features of the time evolution of oligomers, including oligomer peak concentration and life-time, are controlled by the different rate parameters. We discuss the therapeutic implications of our framework by predicting changes in oligomer concentrations when the rates of the individual microscopic events are varied. Our results identify the kinetic parameters that control most effectively the generation of oligomers, thus opening the way for the systematic rational design of therapeutic strategies against amyloid-related diseases

Phase equilibria in the Fe-Mo-Ti ternary system at 1000 °C

An isothermal section of the Fe-Mo-Ti ternary system at 1000 °C has been constructed using data acquired from a series of seven alloys. The limit of solubility of Fe in the continuous A2 phase field between Ti and Mo has been determined, as have the extents to which Mo may be accommodated in the B2 TiFe phase, and Ti in the D8$_5$ Fe$_7$Mo$_6$ phase. The B2, D8$_5$ and C14 Fe$_2$ (Ti, Mo) intermetallics were found to have limited tolerance for non-stoichiometric compositions. The positions of the A2 + B2 + C14 and A2 + C14 + D8$_5$ three-phase fields were determined, along with the extents of the A2 + B2, A2 + D8$_5$, A2 + C14, C14 + B2 and C14 + D8$_5$ two-phase fields. No ternary phases were observed in any of the alloys studied.This work was support by the Rolls-Royce/EPSRC Strategic Partnership under EP/H022309/1, EP/H500375/1 and EP/M005607/1.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ijrmhm.2016.07.00

Devitrite-based optical diffusers.

Devitrite is a novel material produced by heat treatment of commercial soda-lime-silica glass. It consists of fans of needle-like crystals which can extend up to several millimeters and have interspacings of up to a few hundred nanometers. To date, only the material properties of devitrite have been reported, and there has been a distinct lack of research on using it for optical applications. In this study, we demonstrate that randomly oriented fans of devitrite crystals can act as highly efficient diffusers for visible light. Devitrite crystals produce phase modulation of light because of their relatively high anisotropy. The nanoscale spacings between these needles enable light to be diffused to large scattering angles. Experimentally measured results suggest that light diffusion patterns with beam widths of up to 120° are produced. Since devitrite is an inexpensive material to produce, it has the potential to be used in a variety of commercial applications.HB would like to thank The Leverhulme Trust and Cambridge Philosophical Society for research funding.This is the author accepted manuscript. The final version can be found on the publisher's website at: http://pubs.acs.org/doi/abs/10.1021/nn500155e Copyright © 2014 American Chemical Societ

Cr-Mo-V-W: A new refractory and transition metal high-entropy alloy system

Cr-Mo-V-W high-entropy alloy (HEA) is studied, with 2553 K equilibrium solidus and high Cr content to promote protective oxide scale formation, suggesting potential applications in hot, oxidising environments. Alloy Search and Predict (ASAP) and phase diagram calculations found a single phase, body-centred cubic (BCC) solid solution at elevated temperatures, across the range of compositions present within the system - uncommon for a HEA of refractory and transition metals. Density functional theory identified solubility of 22 at.% Cr at solidus temperature, with composition-dependent drive for segregation during cooling. An as-cast, BCC single-phase with the composition 31.3Cr-23.6Mo-26.4 V-18.7 W exhibiting dendritic microsegregation was verified

PREDICT-PD: Identifying risk of Parkinson's disease in the community: methods and baseline results

To present methods and baseline results for an online screening tool to identify increased risk for Parkinson's disease (PD) in the UK population

Maternal ethnicity and the prevalence of British pregnancies affected by neural tube defects

Background: Few data are available on the prevalence of neural tube defects (NTDs) within different ethnic communities of the United Kingdom. This study aimed to calculate prevalence estimates for NTD‐affected pregnancies, classified by maternal ethnicity, and to explore why variations in prevalence might exist. / Methods: A cross‐sectional study was performed with data from regional congenital anomaly registers in England and Wales, for NTD‐affected pregnancies between 2006 and 2011. Using binomial regression models, we examined NTD‐affected pregnancy prevalence estimates and rate ratios (PRRs), by maternal ethnicity. / Results: The prevalence of NTDs was 12.14 per 10,000 births, with no differences between study years. Anencephaly, encephalocele and spina bifida occurred at 4.98, 1.37 and 5.80 per 10,000 births respectively. Mothers of Indian ethnicity were 1.84 times more likely (95% CI: 1.24, 2.73) and Bangladeshi mothers 2.86 times more likely (95% CI: 1.48, 5.53) than White mothers to have an NTD‐affected pregnancy, after adjusting for maternal deprivation and maternal age. The excess prevalence in Indian mothers was specifically for anencephaly (PRR 2.57; 95% CI: 1.52, 4.34), and in Bangladeshi mothers the trend was for increased spina bifida (PRR 3.86; 95% CI: 0.72, 8.69). Anencephaly in Indian mothers was especially associated with other congenital anomalies (non‐isolated NTDs). / Conclusions: Different British ethnic groups vary in NTD prevalence. The excess prevalence of anencephaly as a non‐isolated NTD in pregnancies of Indian mothers could indicate involvement of genetic or other unmeasured behavioral factors. Future work is needed to seek etiological explanations for the ethnicity differences and to develop improved methods for primary prevention

Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P&lt;10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P&lt;10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no&nbsp;SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P&lt;1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples