Playing with the Rules: Influences on the Development of Regulation in Sport

Sport today is a rule-governed practice: constitutive rules, both prescriptive and proscriptive, define required equipment and facilities as well as setting the formal rules of play; auxiliary rules specify and control eligibility: and regulatory rules place restraints on behaviour independent of the sport itself. This article offers a broad sweep examination of the historical process of rule development in sport including an assessment of the influence over time of gambling, fair play ideology, economic pressures, technological developments and legal intervention. En route a seven-stage scheme of constitutive rule development is postulated which it is hoped will set a research agenda for sports historians to test with case studies of particular sports

The QUIET Instrument

The Q/U Imaging ExperimenT (QUIET) is designed to measure polarization in the Cosmic Microwave Background, targeting the imprint of inflationary gravitational waves at large angular scales (~ 1 degree). Between 2008 October and 2010 December, two independent receiver arrays were deployed sequentially on a 1.4 m side-fed Dragonian telescope. The polarimeters which form the focal planes use a highly compact design based on High Electron Mobility Transistors (HEMTs) that provides simultaneous measurements of the Stokes parameters Q, U, and I in a single module. The 17-element Q-band polarimeter array, with a central frequency of 43.1 GHz, has the best sensitivity (69 uK sqrt(s)) and the lowest instrumental systematic errors ever achieved in this band, contributing to the tensor-to-scalar ratio at r < 0.1. The 84-element W-band polarimeter array has a sensitivity of 87 uK sqrt(s) at a central frequency of 94.5 GHz. It has the lowest systematic errors to date, contributing at r < 0.01. The two arrays together cover multipoles in the range l= 25-975. These are the largest HEMT-based arrays deployed to date. This article describes the design, calibration, performance of, and sources of systematic error for the instrument

Towards a model of talent development in physical education

Traditional conceptions of talent generally emphasise the construction of threshold values and the development of relatively unitary abilities, and this approach still dominates talent development programmes for elite sport. Most researchers on high ability, however, now favour domain-specific, multidimensional conceptions of ability that stress the development of behavioural potential and its interaction with personal and environmental characteristics. This paper presents a model of talent in physical education, drawing together findings from a wide range of literature on the realisation and inhibition of abilities, international studies of effective school-based identification and provision strategies, and a conception of the subject as an integration and realisation of different forms of ability. In presenting this model, the authors aim to redress the imbalance within the current debate from an almost total concern with out-of-school clubs and the preparation for adult elite sport, in favour of a more equitable and inclusive approach, premised upon the unique importance of mainstream, curricular physical education within any talent development scheme

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Islet cell transplantation in Australia: screening, remote transplantation, and incretin hormone secretion in insulin independent patients

Published online: October 28, 2014Islet cell transplantation has emerged as a treatment modality for type 1 diabetes in the last 15 years due to the Edmonton protocol leading to consistent and sustained exogenous insulin independence post-transplantation. In recent years, consortia that involve both local and remote islet cell centers have been established, with local centers responsible for processing and shipping of islet cells, and remote centers only transplanting them. There are, however, few data on patient outcomes at remote centers. A tendency for high fasting glucose despite insulin independence was noted by us and others with an unknown mechanism. This review provides a brief history of islet cell transplantation, and focuses on the South Australian remote center experience: the challenges, screening criteria, and the impact on incretin hormone secretion of insulin independent transplant patients.C. S. Marathe, C. J. Drogemuller, J. A. Marathe, T. Loudavaris, W. J. Hawthorne, P. J. O, Connell, T. Radford, T. W. H. Kay, M. Horowitz, P. T. Coates, D. J. Torp