Sociocultural considerations in aging men's health: implications and recommendations for the clinician

http://dx.doi.org/10.1016/j.jomh.2009.07.00

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

The 2dF-SDSS LRG and QSO Survey: the LRG 2-point correlation function and redshift-space distortions

We present a clustering analysis of luminous red galaxies (LRGs) using nearly 9000 objects from the final, three-year catalogue of the 2dF-SDSS LRG and QSO (2SLAQ) Survey. We measure the redshift-space two-point correlation function, ξ(s) and find that, at the mean LRG redshift of shows the characteristic downturn at small scales (1 h−1 Mpc) expected from line-of-sight velocity dispersion. We fit a double power law to ξ(s) and measure an amplitude and slope of s0 = 17.3+2.5−2.0 h−1 Mpc, γ = 1.03 ± 0.07 at small scales (s 4.5 h−1 Mpc). In the semiprojected correlation function, wp(σ), we find a simple power law with γ = 1.83 ± 0.05 and r0 = 7.30 ± 0.34 h−1 Mpc fits the data in the range 0.4 < σ < 50 h−1 Mpc, although there is evidence of a steeper power law at smaller scales. A single power law also fits the deprojected correlation function ξ(r), with a correlation length of r0 = 7.45 ± 0.35 h−1 Mpc and a power-law slope of γ = 1.72 ± 0.06 in the 0.4 < r < 50 h−1 Mpc range. But it is in the LRG angular correlation function that the strongest evidence for non-power-law features is found where a slope of γ = −2.17 ± 0.07 is seen at 1 < r < 10 h−1 Mpc with a flatter γ = −1.67 ± 0.07 slope apparent at r 1 h−1 Mpc scales. We use the simple power-law fit to the galaxy ξ(r), under the assumption of linear bias, to model the redshift-space distortions in the 2D redshift-space correlation function, ξ(σ, π). We fit for the LRG velocity dispersion, wz, the density parameter, Ωm and β(z), where β(z) = Ω0.6m/b and b is the linear bias parameter. We find values of wz = 330 km s−1, Ωm = 0.10+0.35−0.10 and β = 0.40 ± 0.05. The low values for wz and β reflect the high bias of the LRG sample. These high-redshift results, which incorporate the Alcock–Paczynski effect and the effects of dynamical infall, start to break the degeneracy between Ωm and β found in low-redshift galaxy surveys such as 2dFGRS. This degeneracy is further broken by introducing an additional external constraint, which is the value β(z = 0.1) = 0.45 from 2dFGRS, and then considering the evolution of clustering from z 0 to zLRG 0.55. With these combined methods we find Ωm(z = 0) = 0.30 ± 0.15 and β(z = 0.55) = 0.45 ± 0.05. Assuming these values, we find a value for b(z = 0.55) = 1.66 ± 0.35. We show that this is consistent with a simple ����high-peak’ bias prescription which assumes that LRGs have a constant comoving density and their clustering evolves purely under gravity

Experiments on a high quality grid oscillating in superfluid 4He at very low temperatures.

We have investigated a copper-mesh grid oscillating at its fundamental (0, 1) Bessel mode in superfluid 4He for temperatures 10< T <1500 mK at a pressure of P = 5 bar. The high quality factor (Q ∼ 10 to power 5) of the oscillator allowed us to observe new features of its response to a periodic drive which, at the lowest T, was found to depend on the prehistory of the helium. The experiments have confirmed the existence of two critical velocities, and we discuss whether these critical velocities are associated with quantized vortices

Initiation of continuous renal replacement therapy versus intermittent hemodialysis in critically ill patients with severe acute kidney injury: a secondary analysis of STARRT-AKI trial.

There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days

A Delphi study and International Consensus Recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 164 (2021) 115-12