The long term effects of sports concussion on retired Australian football players: a study using Transranial Magnetic Stimulation

This study investigated corticomotor excitability and inhibition, cognitive functioning, and fine motor dexterity in retired elite and amateur Australian football (AF) players who had sustained concussions during their playing careers. Forty male AF players who played at the elite level (n=20; mean age 49.7±5.7 years) or amateur level (n=20; mean age 48.4±6.9 years), and had sustained on average 3.2 concussions 21.9 years previously, were compared with 20 healthy age-matched male controls (mean age 47.56±6.85 years). All participants completed assessments of fine dexterity, visuomotor reaction time, spatial working memory (SWM), and associative learning (AL). Transcranial magnetic stimulation (TMS) was used to measure corticospinal excitability: stimulus-response (SR) curves and motor evoked potential (MEP) 125% of active motor threshold (aMT); and intracortical inhibition: cortical silent period (cSP), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). Healthy participants performed better in dexterity (p=0.003), reaction (p=0.003), and movement time (p=0.037) than did both AF groups. Differences between AF groups were found in AL (p=0.027) and SWM (p=0.024). TMS measures revealed that both AF groups showed reduced cSP duration at 125% aMT (p>0.001) and differences in SR curves (p>0.001) than did healthy controls. Similarly, SICI (p=0.012) and LICI (p=0.009) were reduced in both AF groups compared with controls. Regression analyses revealed a significant contribution to differences in motor outcomes with the three measures of intracortical inhibition. The measures of inhibition differed, however, in terms of which performance measure they had a significant and unique predictive relationship with, reflecting the variety of participant concussion injuries. This study is the first to demonstrate differences in motor control and intracortical inhibition in AF players who had sustained concussions during their playing career two decades previously

Exploration of the equilibrium operating space for NSTX-Upgrade

This paper explores a range of high-performance equilibrium scenarios available in the NSTX-Upgrade device [J.E. Menard, submitted for publication to Nuclear Fusion]. NSTX-Upgrade is a substantial upgrade to the existing NSTX device [M. Ono, et al., Nuclear Fusion 40, 557 (2000)], with significantly higher toroidal field and solenoid capabilities, and three additional neutral beam sources with significantly larger current drive efficiency. Equilibria are computed with freeboundary TRANSP, allowing a self consistent calculation of the non-inductive current drive sources, the plasma equilibrium, and poloidal field coil current, using the realistic device geometry. The thermal profiles are taken from a variety of existing NSTX discharges, and different assumptions for the thermal confinement scalings are utilized. The no-wall and idealwall n=1 stability limits are computed with the DCON code. The central and minimum safety factors are quite sensitive to many parameters: they generally increases with large outer plasmawall gaps and higher density, but can have either trend with the confinement enhancement factor. In scenarios with strong central beam current drive, the inclusion of non-classical fast ion diffusion raises qmin, decreases the pressure peaking, and generally improves the global stability, at the expense of a reduction in the non-inductive current drive fraction; cases with less beam current drive are largely insensitive to additional fast ion diffusion. The non-inductive current level is quite sensitive to the underlying confinement and profile assumptions. For instance, for BT=1.0 T and Pinj=12.6 MW, the non-inductive current level varies from 875 kA with ITER-98y,2 thermal confinement scaling and narrow thermal profiles to 1325 kA for an ST specific scaling expression and broad profiles. This sensitivity should facilitate the determination of the correct scaling of transport with current and field to use for future fully non-inductive ST devices. Scenarios are presented which can be sustained for 8-10 seconds, or (20-30)τCR, at βN=3.8-4.5, facilitating, for instance, the study of disruption avoidance for very long pulse. Scenarios have been documented which can operate with βT~25% and equilibrated qmin>1. The value of qmin can be controlled at either fixed non-inductive fraction of 100% or fixed plasma current, by varying which beam sources are used, opening the possibility for feedback qmin control. In terms of quantities like collisionality, neutron emission, non-inductive fraction, or stored energy, these scenarios represent a significant performance extension compared to NSTX and other present spherical torii

Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at onset of AN and age at menarche. Methods A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed which included 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at onset, early-onset AN (< 13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (SNP-h2) were 0.01-0.04 for age at onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age at onset and early-onset AN estimated from independent GWASs significantly predicted age at onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions Our results provide evidence consistent with a common variant genetic basis for age at onset and implicate biological pathways regulating menarche and reproduction.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

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