Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Évaluation du métabolisme énergétique de la boxe anglaise de haut niveau de performance

International audienceLa boxe anglaise est un sport technique occasionnant une dépense énergétique importante (Dal Monte et Menchinelli, 1986 ; Victorov et al, 1976). L'entraîneur doit intégrer les deux composantes, technique et énergétique, dans la préparation des boxeurs. L'entraînement technique se fait lors de séances spécifiques de type « frappe au sac » ou combat. L'entraînement physique se fait soit sous forme de course à pied ou de « saut à la corde », soit lors de séances plus spécifiques comme la «frappe au sac». Ces séances d'entraînement font partie de la « culture pugilistique » et ont été peu modifiées ces dernières années. Aussi, pour définir la programmation de l'entraînement, est-il important de connaître la nature des sollicitations du métabolisme énergétique lors de ces séances. Or peu d'études dans le domaine de la boxe anglaise ont été réalisées. Ces études ont utilisé la fréquence cardiaque. Victorov et al (1976) ont utilisé la fréquence cardiaque pour évaluer quantitativement l'intensité des charges d'entraînement. Dal Monte et Menchinelli (1986) ont étudié l'évolution de la fréquence cardiaque au cours de combats amateurs de boxe anglaise. Leur conclusion est que les combats sollicitent alternativement les métabolismes aérobie et anaérobie. Le fait que ces études utilisent uniquement la fréquence cardiaque ne permet pas de déterminer avec précision la filière énergétique dominante pour chaque exercice. C'est pour cette raison que nous avons essayé de mettre en relation dans cette étude la lactatémie et la fréquence cardiaque mesurées sur le terrain et les mêmes paramètres mesurés en laboratoire pour étudier le métabolisme énergétique sollicité lors des séances d'entraînement chez des boxeurs de haut niveau

International Coordination of Large-Scale Human Induced Pluripotent Stem Cell Initiatives: Wellcome Trust and ISSCR Workshops White Paper

There is growing recognition of the potential value of human induced pluripotent stem cells (hiPSC) for understanding disease and identifying drugs targets. This has been reflected in the establishment of multiple large-scale hiPSC initiatives worldwide. Representatives of these met recently at a workshop supported by the Welcome Trust in the UK and in a focus session at the 2014 ISSCR annual meeting in Vancouver. The purpose was to discuss strategies for making thousands of hiPSC lines widely available with as few restrictions as possible while retaining financial viability and donor privacy. The outcome of these discussions is described here