A three-season comparison of match performances among selected and unselected elite youth rugby league players

This is an author's accepted manuscript of an article published in Journal of Sports Sciences, 28 February 2014, available online: http:www.tandfonline.com/10.1080/02640414.2014.889838This study compared technical actions, movements, heart rates and perceptual responses of selected and unselected youth rugby league players during matches (under-15 to under-17). The players’ movements and heart rates were assessed using 5 Hz Global Positioning Systems (GPS), while their technical actions were analysed using video analysis. The maturity of each player was predicted before each season for statistical control. There were no differences (P > 0.05) between selected and unselected players in the under-15 or the under-17 age groups for any variables. However, in the under-16 group, the selected players (57.1 ± 11.9 min) played for longer than the unselected players (44.1 ± 12.3 min; P = 0.017; ES = 1.08 ± CI = 0.87), and covered more distance (5,181.0 ± 1063.5 m cf. 3942.6 ± 1,108.6m, respectively; P = 0.012; ES = 1.14 ± CI = 0.88) and high intensity distance (1,808.8 ± 369.3 m cf. 1,380.5 ± 367.7 m, respectively; P = 0.011; ES = 1.16 ± CI = 0.88). Although successful carries per minute was higher in the selected under-15 group, there were no other differences (P > 0.05) in match performance relative to playing minutes between groups. Controlling for maturity, the less mature, unselected players from the under-16 group performed more high-intensity running (P < 0.05). Our findings question the use of match- related measurements in differentiating between selected and unselected players, showing that later maturing players were unselected, even when performing greater high-intensity running during matches

Seven-day ischaemic preconditioning improves muscle efficiency during cycling

Ischaemic preconditioning (IPC) has emerged as a potential non-invasive ergogenic aid to enhance exercise performance. Repeated application of IPC has demonstrated clinical efficacy, therefore our aims were to investigate its effect on endurance cycling performance and muscle efficiency. Twenty participants undertook 7-d repeated bilateral lower limb occlusion (4 x 5-min) of IPC (220 mmHg) or sham (20 mmHg). Prior to and 72-h following the intervention, participants performed submaximal cycling at 70, 80 and 90% of ventilatory threshold (VT) followed by an incremental exercise test. IPC had no effect on VO2max (P = 0.110); however, time to exhaustion increased by ~ 9% and Wmax by ~ 5 % (IPC pre 307 ± 45 to post 323 ± 51 W) relative to sham (P = 0.002). There were no changes in gross efficiency (GE) (P > 0.05); however, delta efficiency (DE) increased by 3.1% following IPC (P = 0.011). Deoxyhaemoglobin (HHb) was reduced following IPC ~ 30% (P = 0.017) with no change in total haemoglobin (tHb). Repeated IPC over 7-d enhanced muscle efficiency and extended cycling performance. The physiological effects of repeated IPC on skeletal muscle efficiency explains the notable improvements in endurance performance

Dietary Factors May Be Associated With Measures of Ultrasound-derived Skeletal Muscle Echo Intensity

Skeletal muscle echo intensity (EI) is affected by ageing and physical activity; however, the effects of nutrition are less understood. The aim of this study was to explore whether habitual nutrient intake may be associated with ultrasound-derived EI. Partial least squares regression (PLSR) models were trained on an initial sample (n=100, M=45; F=55; 38±15 years) to predict EI of two quadriceps muscles from 19 variables, using the ‘jack-knife’ function within the ‘pls’ package (RStudio), which was then tested in an additional dataset (n= 30, M=13; F=17; 38±16 years). EI was determined using B-mode ultrasonography of the rectus femoris (RF) and vastus lateralis (VL) and nutritional intake determined via three-day weighed food diaries. Mean daily intake of specific nutrients were included as predictor variables with age, sex and self-reported physical activity. PLSR training model 1 explained ~52% and model 2 ~46% of the variance in RF and VL EI, respectively. Model 1 also explained ~35% and model 2 ~30% of the variance in RF and VL EI in the additional testing dataset. Age and biological sex were associated with EI in both models (P<0.025). Dietary protein (RF: β=-7.617,VL: β=-7.480), and selenium (RF: β=-7.144,VL: β=-4.775) were associated with EI in both muscles (P<0.05), whereas fibre intake (RF: β=-5.215) was associated with RF EI only and omega-3 fatty acids (n-3/ω-3 FAs, RF: β=3.145) with VL EI only (P<0.05). Therefore, absolute protein, selenium, fibre and n-3 FAs may be associated with skeletal muscle EI, although further mechanistic work is required before claiming causal inference

The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain

The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially “druggable” point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340

Anti-prion drug mPPIg5 inhibits PrP(C) conversion to PrP(Sc).

Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future

An Introduction to the Chandra Carina Complex Project

The Great Nebula in Carina provides an exceptional view into the violent massive star formation and feedback that typifies giant HII regions and starburst galaxies. We have mapped the Carina star-forming complex in X-rays, using archival Chandra data and a mosaic of 20 new 60ks pointings using the Chandra X-ray Observatory's Advanced CCD Imaging Spectrometer, as a testbed for understanding recent and ongoing star formation and to probe Carina's regions of bright diffuse X-ray emission. This study has yielded a catalog of properties of >14,000 X-ray point sources; >9800 of them have multiwavelength counterparts. Using Chandra's unsurpassed X-ray spatial resolution, we have separated these point sources from the extensive, spatially-complex diffuse emission that pervades the region; X-ray properties of this diffuse emission suggest that it traces feedback from Carina's massive stars. In this introductory paper, we motivate the survey design, describe the Chandra observations, and present some simple results, providing a foundation for the 15 papers that follow in this Special Issue and that present detailed catalogs, methods, and science results.Comment: Accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html through 2011 at least. 43 pages; 18 figure

Major lower limb amputation audit - introduction and implementation of a multimodal perioperative pain management guideline

[no abstract

Perineural Local Anaesthetic Catheter aftEr Major lowEr limb amputatioN Trial (PLACEMENT):results from a randomised controlled feasibility trial

Objectives To determine the feasibility of undertaking a randomised controlled effectiveness trial evaluating the use of a perineural catheter (PNC) after major lower limb amputation with postoperative pain as the primary outcome. Design Randomised controlled feasibility trial. Setting Two vascular Centres in South Wales, UK. Participants 50 patients scheduled for major lower limb amputation (below or above knee) for complications of peripheral vascular disease. Interventions The treatment arm received a PNC placed adjacent to the sciatic or tibial nerve at the time of surgery, with continuous infusion of levobupivacaine hydrochloride 0.125% for up to 5 days. The control arm received neither local anaesthetic nor PNC. Both arms received usual perioperative anaesthesia and postoperative analgesia. Primary and secondary outcome measures The primary outcomes were the proportion of eligible patients who were randomised and the proportion of recruited patients who provided primary effectiveness outcome data. Secondary outcomes were: the proportion of recruited patients reaching 2 and 6 month follow-up and supplying pain data; identification of key cost drivers; development of an economic analysis framework for a future effectiveness trial; identification of barriers to recruitment and site set-up; and identification of the best way to measure postoperative pain. Results Seventy-six of 103 screened patients were deemed eligible over a 10 month period. Fifty (64.5%) of these patients were randomised, with one excluded in the perioperative period. Forty-five (91.3%) of 49 recruited patients provided enough pain scores on a 4-point verbal rating scale to allow primary effectiveness outcome evaluation. Attrition rates were high; 18 patients supplied data at 6 month follow-up. Costs were dominated by length of hospital stay. Patients and healthcare professionals reported that trial processes were acceptable. Conclusions Recruitment of patients into a trial comparing PNC use to usual care after major lower limb amputation with postoperative pain measured on a 4-point verbal rating scale is feasible. Evaluation of longer-term symptoms is difficult

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Relationships between adverse childhood experiences and adult mental well-being: results from an English national household survey.

BACKGROUND: Individuals' childhood experiences can strongly influence their future health and well-being. Adverse childhood experiences (ACEs) such as abuse and dysfunctional home environments show strong cumulative relationships with physical and mental illness yet less is known about their effects on mental well-being in the general population. METHODS: A nationally representative household survey of English adults (n = 3,885) measuring current mental well-being (Short Edinburgh-Warwick Mental Well-being Scale SWEMWBS) and life satisfaction and retrospective exposure to nine ACEs. RESULTS: Almost half of participants (46.4 %) had suffered at least one ACE and 8.3 % had suffered four or more. Adjusted odds ratios (AORs) for low life satisfaction and low mental well-being increased with the number of ACEs. AORs for low ratings of all individual SWEMWBS components also increased with ACE count, particularly never or rarely feeling close to others. Of individual ACEs, growing up in a household affected by mental illness and suffering sexual abuse had the most relationships with markers of mental well-being. CONCLUSIONS: Childhood adversity has a strong cumulative relationship with adult mental well-being. Comprehensive mental health strategies should incorporate interventions to prevent ACEs and moderate their impacts from the very earliest stages of life