A cross-sectional study of retired Great British Olympians (Berlin 1936 - Sochi 2014):Olympic career injuries, joint health in later life, and reasons for retirement from Olympic sport

The relationship between Olympic career sport injury and the long-term musculoskeletal health of the elite athlete remains unclear. This study describes the lifetime prevalence of medical attention injuries that occurred during training and/or competition as part of the athlete’s Olympic career, reasons for retirement from Olympic sport, and the point prevalence of pain and osteoarthritis (OA) among retired Great Britain’s (GB) Olympians

The UK Paediatric Familial Hypercholesterolaemia Register: Statin-related safety and 1-year growth data

BACKGROUND: For children with familial hypercholesterolemia (FH), UK guidelines recommend consideration of statin therapy by age 10 years and dietary and lifestyle advice to maintain an ideal body weight. OBJECTIVES: The objective of the study is to use the UK Paediatric Familial Hypercholesterolemia Register to determine: (1) the prevalence of plasma markers of liver toxicity and muscle damage in statin-treated FH children; (2) the prevalence of obesity in FH children compared to the UK general population; and (3) to compare growth rates in statin-treated and nontreated children. METHODS: Differences in registration and 1-year characteristics were compared by Mann-Whitney U tests. Age and gender body mass index percentiles were compared to UK children's growth charts. RESULTS: In 300 children (51% boys, 75% Caucasian, untreated mean [standard deviation] low-density lipoprotein cholesterol 5.50 [1.49] mmol/L), the proportion on statins varied significantly (P 15 years = 73.2%). Statin treatment reduced low-density lipoprotein cholesterol by 31% (1.84 [1.43] mmol/L), and no child showed elevated levels of markers of liver toxicity or muscle damage. At registration, 16.9% of the FH children were overweight (>85th percentile) and 11.1% were obese (>95th percentile) vs reported in 21.2% in UK non-FH children. There was no difference in annual growth rate in statin vs no-statin groups (age-adjusted weight increases 3.58 vs 3.53 kg; P = .91, height 4.45 vs 4.60 cm P = .73). CONCLUSIONS: We show no evidence for statin-related safety or growth issues, but many FH children over the age of 10 years are not on statin treatment. Fewer UK children with FH are obese compared to UK non-FH children

Evidence for a correlation between the sizes of quiescent galaxies and local environment to z ~ 2

We present evidence for a strong relationship between galaxy size and environment for the quiescent population in the redshift range 1 < z < 2. Environments were measured using projected galaxy overdensities on a scale of 400 kpc, as determined from ~ 96,000 K-band selected galaxies from the UKIDSS Ultra Deep Survey (UDS). Sizes were determined from ground-based K-band imaging, calibrated using space-based CANDELS HST observations in the centre of the UDS field, with photometric redshifts and stellar masses derived from 11-band photometric fitting. From the resulting size-mass relation, we confirm that quiescent galaxies at a given stellar mass were typically ~ 50 % smaller at z ~ 1.4 compared to the present day. At a given epoch, however, we find that passive galaxies in denser environments are on average significantly larger at a given stellar mass. The most massive quiescent galaxies (M_stellar > 2 x 10^11 M_sun) at z > 1 are typically 50 % larger in the highest density environments compared to those in the lowest density environments. Using Monte Carlo simulations, we reject the null hypothesis that the size-mass relation is independent of environment at a significance > 4.8 sigma for the redshift range 1 < z < 2. In contrast, the evidence for a relationship between size and environment is much weaker for star-forming galaxies.Comment: Accepted for publication in MNRAS. 16 pages, 11 figures, 6 table

Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins

RNA binding proteins of the conserved CUGBP1, Elav-like factor (CELF) family contribute to heart and skeletal muscle development and are implicated in myotonic dystrophy (DM). To understand their genome-wide functions, we analyzed the transcriptome dynamics following induction of CELF1 or CELF2 in adult mouse heart and of CELF1 in muscle by RNA-seq, complemented by crosslinking/immunoprecipitation-sequencing (CLIP-seq) analysis of mouse cells and tissues to distinguish direct from indirect regulatory targets. We identified hundreds of mRNAs bound in their 3′ UTRs by both CELF1 and the developmentally induced MBNL1 protein, a threefold greater overlap in target messages than expected, including messages involved in development and cell differentiation. The extent of 3′ UTR binding by CELF1 and MBNL1 predicted the degree of mRNA repression or stabilization, respectively, following CELF1 induction. However, CELF1's RNA binding specificity in vitro was not detectably altered by coincubation with recombinant MBNL1. These findings support a model in which CELF and MBNL proteins bind independently to mRNAs but functionally compete to specify down-regulation or localization/stabilization, respectively, of hundreds of mRNA targets. Expression of many alternative 3′ UTR isoforms was altered following CELF1 induction, with 3′ UTR binding associated with down-regulation of isoforms and genes. The splicing of hundreds of alternative exons was oppositely regulated by these proteins, confirming an additional layer of regulatory antagonism previously observed in a handful of cases. The regulatory relationships between CELFs and MBNLs in control of both mRNA abundance and splicing appear to have evolved to enhance developmental transitions in major classes of heart and muscle genes.Myotonic Dystrophy FoundationNational Institutes of Health (U.S.) (Grant OD017865-02)National Science Foundation (U.S.) (Award 0821391)National Institutes of Health (U.S.) (Grant R01GM085319)National Institutes of Health (U.S.) (Grant RC2HG005624

Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors

The generation of the post-cranial embryonic body relies on the coordinated production of spinal cord neurectoderm and presomitic mesoderm cells from neuromesodermal progenitors (NMPs). This process is orchestrated by pro-neural and pro-mesodermal transcription factors that are co-expressed in NMPs together with Hox genes, which are critical for axial allocation of NMP derivatives. NMPs reside in a posterior growth region, which is marked by the expression of Wnt, FGF and Notch signalling components. While the importance of Wnt and FGF in influencing the induction and differentiation of NMPs is well established, the precise role of Notch remains unclear. Here, we show that the Wnt/FGF-driven induction of NMPs from human embryonic stem cells (hESCs) relies on Notch signalling. Using hESC-derived NMPs and chick embryo grafting, we demonstrate that Notch directs a pro-mesodermal character at the expense of neural fate. We show that Notch also contributes to activation of HOX gene expression in human NMPs, partly in a non-cell-autonomous manner. Finally, we provide evidence that Notch exerts its effects via the establishment of a negative feedback loop with FGF signalling.</p

Emergency department clinical leads’ experiences of implementing primary care services where GPs work in or alongside emergency departments in the UK: a qualitative study

Background To manage increasing demand for emergency and unscheduled care NHS England policy has promoted services in which patients presenting to Emergency Departments (EDs) with non-urgent problems are directed to general practitioners (GPs) and other primary care clinicians working within or alongside emergency departments. However, the ways that hospitals have implemented primary care services in EDs are varied. The aim of this study was to describe ED clinical leads’ experiences of implementing and delivering ‘primary care services’ and ‘emergency medicine services’ where GPs were integrated into the ED team. Methods We conducted interviews with ED clinical leads in England (n = 19) and Wales (n = 2). We used framework analysis to analyse interview transcripts and explore differences across ‘primary care services’, ‘emergency medicine services’ and emergency departments without primary care services. Results In EDs with separate primary care services, success was reported when having a distinct workforce of primary care clinicians, who improved waiting times and flow by seeing primary care-type patients in a timely way, using fewer investigations, and enabling ED doctors to focus on more acutely unwell patients. Some challenges were: trying to align their service with the policy guidance, inconsistent demand for primary care, accessible community primary care services, difficulties in recruiting GPs, lack of funding, difficulties in agreeing governance protocols and establishing effective streaming pathways. Where GPs were integrated into an ED workforce success was reported as managing the demand for both emergency and primary care and reducing admissions. Conclusions Introducing a policy advocating a preferred model of service to address primary care demand was not useful for all emergency departments. To support successful and sustainable primary care services in or alongside EDs, policy makers and commissioners should consider varied ways that GPs can be employed to manage variation in local demand and also local contextual factors such as the ability to recruit and retain GPs, sustainable funding, clear governance frameworks, training, support and guidance for all staff. Whether or not streaming to a separate primary care service is useful also depended on the level of primary care demand

Measurement of the Induced Proton Polarization P_n in the 12C(e,e'\vec{p}) Reaction

The first measurements of the induced proton polarization, P_n, for the 12C (e,e'\vec{p}) reaction are reported. The experiment was performed at quasifree kinematics for energy and momentum transfer (\omega,q) \approx (294 MeV, 756 MeV/c) and sampled a recoil momentum range of 0-250 MeV/c. The induced polarization arises from final-state interactions and for these kinematics is dominated by the real part of the spin-orbit optical potential. The distorted-wave impulse approximation provides good agreement with data for the 1p_{3/2} shell. The data for the continuum suggest that both the 1s_{1/2} shell and underlying l > 1 configurations contribute.Comment: 5 pages LaTeX, 2 postscript figures, accepted by Physical Reveiw Letter

Oxford SWIFT IFS and multi-wavelength observations of the Eagle galaxy at z=0.77

The `Eagle' galaxy at a redshift of 0.77 is studied with the Oxford Short Wavelength Integral Field Spectrograph (SWIFT) and multi-wavelength data from the All-wavelength Extended Groth strip International Survey (AEGIS). It was chosen from AEGIS because of the bright and extended emission in its slit spectrum. Three dimensional kinematic maps of the Eagle reveal a gradient in velocity dispersion which spans 35-75 +/- 10 km/s and a rotation velocity of 25 +/- 5 km/s uncorrected for inclination. Hubble Space Telescope images suggest it is close to face-on. In comparison with galaxies from AEGIS at similar redshifts, the Eagle is extremely bright and blue in the rest-frame optical, highly star-forming, dominated by unobscured star-formation, and has a low metallicity for its size. This is consistent with its selection. The Eagle is likely undergoing a major merger and is caught in the early stage of a star-burst when it has not yet experienced metal enrichment or formed the mass of dust typically found in star-forming galaxies.Comment: accepted for publication in MNRA