Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Minimization of phonon-tunneling dissipation in mechanical resonators

Micro- and nanoscale mechanical resonators have recently emerged as ubiquitous devices for use in advanced technological applications, for example in mobile communications and inertial sensors, and as novel tools for fundamental scientific endeavors. Their performance is in many cases limited by the deleterious effects of mechanical damping. Here, we report a significant advancement towards understanding and controlling support-induced losses in generic mechanical resonators. We begin by introducing an efficient numerical solver, based on the "phonon-tunneling" approach, capable of predicting the design-limited damping of high-quality mechanical resonators. Further, through careful device engineering, we isolate support-induced losses and perform the first rigorous experimental test of the strong geometric dependence of this loss mechanism. Our results are in excellent agreement with theory, demonstrating the predictive power of our approach. In combination with recent progress on complementary dissipation mechanisms, our phonon-tunneling solver represents a major step towards accurate prediction of the mechanical quality factor.Comment: 12 pages, 4 figure

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

Effectiveness of eHealth weight management interventions in overweight and obese adults from low socioeconomic groups: a systematic review.

BACKGROUND: Low socioeconomic status (SES) is associated with increased rates of overweight and obesity. Proponents of electronic health (eHealth) hypothesise that its inclusion in weight management interventions can improve efficacy by mitigating typical barriers associated with low SES. OBJECTIVES: To establish the scope of eHealth weight management interventions for people with overweight and obesity from a low SES. Secondary objectives were to determine the efficacy of eHealth interventions in facilitating weight loss, physical activity and fitness improvements. METHODS: Four databases and grey literature were systematically searched to identify eligible studies published in English from inception to May 2021. Studies examining an eHealth intervention with low SES participants were included. Outcomes included temporal change in weight and BMI, anthropometry, physiological measures and physical activity levels. The number and heterogeneity of studies precluded any meta-analyses; thus, a narrative review was undertaken. RESULTS: Four experimental studies with low risk of bias were reviewed. There was variance in how SES was defined. Study aims and eHealth media also varied and included reducing/maintaining weight or increasing physical activity using interactive websites or voice responses, periodic communication and discourse via telephone, social media, text messaging or eNewsletters. Irrespectively, all studies reported short-term weight loss. eHealth interventions also increased short-term physical activity levels where it was assessed, but did not change anthropometry or physiological measures. None reported any effect on physical fitness. CONCLUSIONS: This review revealed short-term effects of eHealth interventions on weight loss and increased physical activity levels for low SES participants. Evidence was limited to a small number of studies, with small to moderate sample sizes. Inter-study comparison is challenging because of considerable variability. Future work should prioritise how to utilise eHealth in the longer term either as a supportive public health measure or by determining its long-term efficacy in engendering volitional health behaviour changes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021243973

Outcomes Following eHealth Weight Management Interventions in Adults With Overweight and Obesity From Low Socioeconomic Groups: Protocol for a Systematic Review.

BACKGROUND: Obesity is a complex health condition with multiple associated comorbidities and increased economic costs. People from low socioeconomic status (SES) backgrounds are more likely to be overweight and obese and are less successful in traditional weight management programs. It is possible that eHealth interventions may be more successful in reaching people from low SES groups than traditional face-to-face models, by overcoming certain barriers associated with traditional interventions. It is not yet known, however, if eHealth weight management interventions are effective in people living with overweight and obesity from a low SES background. OBJECTIVE: The primary aim of this study is to evaluate the efficacy of eHealth weight management interventions for people with overweight and obesity from low SES groups. METHODS: A systematic review on relevant electronic databases (MEDLINE, Embase, Emcare, and CINAHL) will be undertaken to identify eligible studies published in English up until May 2021. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement to guide the systematic review, two reviewers will independently screen, select, and extract data and complete a risk of bias assessment of search results according to predefined criteria. Studies that have investigated an eHealth weight management intervention within a low SES population will be included. Primary outcomes include weight, BMI, and percentage weight change compared at baseline and at least one other time point. Secondary outcomes may include a range of anthropometric and physical fitness and activity measures. If sufficient studies are homogeneous, then we will pool results of individual outcomes using meta-analysis. RESULTS: Searches have been completed, resulting in 2256 studies identified. Once duplicates were removed, 1545 studies remained for title and abstract review. CONCLUSIONS: The use of eHealth in weight management programs has increased significantly in recent years and will continue to do so; however, it is uncertain if eHealth weight management programs are effective in a low SES population. The results of this systematic review will therefore provide a summary of the evidence for interventions using eHealth for people living with overweight and obesity and from a low SES background. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021243973; https://tinyurl.com/2p8fxtnw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34546

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV