Hard thermal loops and the entropy of supersymmetric Yang-Mills theories

We apply the previously proposed scheme of approximately self-consistent hard-thermal-loop resummations in the entropy of high-temperature QCD to N=4 supersymmetric Yang-Mills (SYM) theories and compare with a (uniquely determined) R[4,4] Pad\'e approximant that interpolates accurately between the known perturbative result and the next-to-leading order strong-coupling result obtained from AdS/CFT correspondence. We find good agreement up to couplings where the entropy has dropped to about 85% of the Stefan-Boltzmann value. This is precisely the regime which in purely gluonic QCD corresponds to temperatures above 2.5 times the deconfinement temperature and for which this method of hard-thermal-loop resummation has given similar good agreement with lattice QCD results. This suggests that in this regime the entropy of both QCD and N=4 SYM is dominated by effectively weakly coupled hard-thermal-loop quasiparticle degrees of freedom. In N=4 SYM, strong-coupling contributions to the thermodynamic potential take over when the entropy drops below 85% of the Stefan-Boltzmann value.Comment: 14 pages, 2 figures, JHEP3. v2: revised and expanded, with unchanged HTL results but corrected NLO strong-coupling result from AdS/CFT (which is incorrectly reproduced in almost all previous papers comparing weak and strong coupling results of N=4 SYM) and novel (unique) Pade approximant interpolating between weak and strong coupling result

Determinants of Advanced Bone Age in Childhood Obesity

Background: Childhood obesity is associated with advanced bone age (BA). Previous studies suggest that androgens, oestrogens, sex hormone-binding globulin, and insulin are responsible for this phenomenon, but results are contradictory and might be biased by confounders. We aim to elucidate this matter by applying a multivariate approach. Method: We performed a correlation analysis of BA standard deviation score (SDS) with age- and sex-specific SDS for androgens, oestrogens, and with indicators of insulin secretion derived from oral glucose tolerance testing, in a group of obese children. A multivariate analysis was performed to investigate which parameters were independently predictive of BA SDS. Results: In this cohort (n = 101; mean age 10.9 years; mean BA 11.8 years; mean BMI SDS 3.3), BMI SDS was significantly correlated to BA SDS (r = 0.55, p < 0.001). In a regression analysis in the total cohort (B = 0.27, p < 0.001) as well as in females (B = 0.34, p = 0.042), males (B = 0.31, p = 0.006), and pubertal children (B = 0.32, p = 0.046), dehydroepiandrosterone sulphate (DHEAS) showed a positive, independent association with BA SD

Local influence of boundary conditions on a confined supercooled colloidal liquid

We study confined colloidal suspensions as a model system which approximates the behavior of confined small molecule glass-formers. Dense colloidal suspensions become glassier when confined between parallel glass plates. We use confocal microscopy to study the motion of confined colloidal particles. In particular, we examine the influence particles stuck to the glass plates have on nearby free particles. Confinement appears to be the primary influence slowing free particle motion, and proximity to stuck particles causes a secondary reduction in the mobility of free particles. Overall, particle mobility is fairly constant across the width of the sample chamber, but a strong asymmetry in boundary conditions results in a slight gradient of particle mobility.Comment: For conference proceedings, "Dynamics in Confinement", Grenoble, March 201

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

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