Descriptive profile of scapulothoracic position, strength and flexibility variables in adolescent elite tennis players

Study design Descriptive study, cross-sectional design. Background Tennis requires repetitive overhead movement patterns that can lead to upper extremity injury. The scapula plays a vital role in injury-free playing. Scapular dysfunction has been associated with shoulder injury in the overhead athlete. Objectives The purpose of this study was to describe variables regarding scapular position, muscle strength and flexibility in young elite tennis players. Methods Thirty-five adolescent Swedish elite tennis players (19 boys, aged 13.6 (+/-1.4) years, 16 girls, aged 12.6 (+/-1.3) years), selected on the basis of their national ranking, underwent a clinical screening protocol consisting of: scapular upward rotation at several angles of arm elevation; isometric scapular muscle strength; and anthropometric measurement of pectoralis minor (PM) length. Results The players showed significantly more scapular upward rotation on their dominant side (p<0.001). For both genders, upper trapezius (p=0.003) and serratus anterior (p=0.01) strength was significantly greater on the dominant side, whereas middle and lower trapezius strength showed no side differences. PM was shorter on the dominant side (p<0.001), and in the female players (p=0.006) compared with the boys. Conclusion These results indicate some sports-related adaptations of young tennis players on their dominant side at the scapulothoracic level to exposure to their sport. These data may assist the clinician in the prevention and rehabilitation of sport-specific injuries in adolescent tennis players

Efficiency of subset simulation in the design of lined rock caverns for storage of hydrogen gas

Efforts to substitute the use of fossil fuels in industry by hydrogen gas requires the storage of large volumes of gas with a reliable pressure vessel design. The Hydrogen Breakthrough Ironmaking Technology (HYBRIT) initiative aims to make the whole steel making process in Sweden fossil-free with the storage of industrial scale quantities of hydrogen in underground Lined Rock Cavers (LRCs). The LRC concept is a relatively new design methodology that can be further developed with respect to safety and economic efficiency and reliability-based design methods provide one option to comply with codes and regulations. High reliability is required for the storage of hydrogen gas and the computational time becomes unpractical for the evaluation of a complex system such as the LRC. In this paper, the efficiency of Subset Simulation (SuS) regarding accuracy, precision and required number of samples is studied for the calculation of probability of failure against fatigue of the steel lining. It can be observed that by increasing the number of samples per level and increasing the conditional probability of failure the precision increases as well as the total number of samples. The accuracy of the SuS is checked with respect to Monte Carlo simulation (MCS) showing good agreement and with greater precision for fewer number of samples. A case study is performed for the geologic conditions of Sweden showing that the considered failure mode is unlikely for high stresses and good rock mass quality.This work has been conducted as part of the HYBRIT research project RP-1. The authors gratefully acknowledge the financial support from the Swedish Energy Agency

Characterization of Overlap in Observational Studies

Overlap between treatment groups is required for non-parametric estimation of causal effects. If a subgroup of subjects always receives the same intervention, we cannot estimate the effect of intervention changes on that subgroup without further assumptions. When overlap does not hold globally, characterizing local regions of overlap can inform the relevance of causal conclusions for new subjects, and can help guide additional data collection. To have impact, these descriptions must be interpretable for downstream users who are not machine learning experts, such as policy makers. We formalize overlap estimation as a problem of finding minimum volume sets subject to coverage constraints and reduce this problem to binary classification with Boolean rule classifiers. We then generalize this method to estimate overlap in off-policy policy evaluation. In several real-world applications, we demonstrate that these rules have comparable accuracy to black-box estimators and provide intuitive and informative explanations that can inform policy making.Comment: To appear at AISTATS 202

Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib

This work was supported by five grants to Sonia Laín: Vetenskapsrådet (VR) 521-2014-3341, Cancerfonden (Swedish Cancer Society) 150393, CAN 2014/702, Association for International Cancer Research (AICR) 130086, Barncancerfonden (Swedish Childhood Cancer Foundation) TJ-2014-0038, Barncancerfonden (Swedish Childhood Cancer Foundation) PR-2014-0038; two grants to Ravi Bhatia: Leukemia and Lymphoma Society (LLS) 6137-14 and NIH R01 CA95684; one grant to David P Lane: Vetenskapsrådet (VR) 538-2013-8807; one grant to Marcus J G W Ladds: Karolinska Institute KID Doctoral Student Funding; one grant to Gergana Popova: Karolinska Institutet KID Doctoral Student Funding; two grants to Nicholas J Westwood: Cancer Research UK C21383 and Cancer Research UK A6950; two grants to Gerald McInerney: Vetenskapsrådet (VR) 621-2014-4718 and Cancerfonden (Swedish Cancer Society) 150393, CAN 2015/751; and four grants to Emmet McCormack: Kreftforeningen 182735, Kreftforeningen 732200, Halse Vest 911884, Halse Vest 911789.Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.Publisher PDFPeer reviewe

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions.

Gene fusions have been discussed in the scientific literature since they were first detected in cancer cells in the early 1980s. There is currently no standardized way to denote the genes involved in fusions, but in the majority of publications the gene symbols in question are listed either separated by a hyphen (-) or by a forward slash (/). Both types of designation suffer from important shortcomings. HGNC has worked with the scientific community to determine a new, instantly recognizable and unique separator-a double colon (::)-to be used in the description of fusion genes, and advocates its usage in all databases and articles describing gene fusions