Whatever Happened to Community Music?:AHRC Research Network Project Report

This document reports on an AHRC Research Network (2013) whose aim was to improve understanding of the historic, current, and potential roles that community music can play in promoting community engagement

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

MEDIA STUDIES AND STATISTICS: REAL-WORLD DEMANDS, CLASSROOM QUANDARIES, AND ON-LINE SOLUTIONS

Communication professionals include journalists and advertising/public relations executives, faced with an explosive growth of numerical data have to make sense of an increasingly complex world in an ever-changing media environment. We argue that the classroom training in statistical thinking that we offer our students is not currently responding to the challenges coming at us from the real-world media where we hope to place these students. We also recognize our students ’ interest in hands-on problem-solving and their increasing sophistication with online technologies in building our argument for more discipline-specific training in statistics, and the grounding of this statistical training online, beginning with the integration of online statistical simulations into the curriculum

Ligand-enhanced expression and in-cell assay of human peroxisome proliferator-activated receptor alpha ligand binding domain

A human peroxisome proliferator-activated receptor alpha ligand binding domain (PPAR&alpha;LBD)-maltose binding protein fusion construct was expressed in Escherichia coli. A codon optimized DNA sequence encoding human PPAR&alpha;LBD (aa196&ndash;468) was synthesized and ligated into the pDEST17 E. coli expression vector downstream of a MBP solubility fusion tag and an intermittent TEV protease cleavage site. Following auto-induction at 28 &deg;C, PPAR&alpha;LBD protein was purified to electrophoretic homogeneity by a nickel affinity chromatographic step, on-column TEV protease cleavage followed by Sephacryl S200 size exclusion chromatography. The recombinant protein displayed cross-reactivity with goat anti-(human PPAR&alpha;) polyclonal antibody and was identified as human PPAR&alpha; by trypic peptide mass finger-printing. The addition of a PPAR&alpha; specific ligand (fenofibric acid, GW7647 or GW590735) to the growth media significantly stabilized the PPAR&alpha;LBD structure and enhanced the expression of soluble protein. In-cell ligand binding was examined by monitoring the enhancement of PPAR&alpha;LBD expression as a function of the concentration of ligand in the growth media. The efficient expression and in-cell assay of the reported PPAR&alpha;LBD construct make it amenable to high through-put screening assays in drug discovery programs.<br /

CREATE a new path to a smoke-free Australia

In 1950, two landmark articles were published by researchers in the United States and the United Kingdom demonstrating the relationship between smoking and lung cancer. Yet, today, 70 years later, tobacco smoking remains the leading cause of preventable death globally. Each year, 7.1 million people who smoke will die from diseases caused by smoking, and an additional 1.2 million people will die from exposure to second-hand smoke.In Australia, smoking causes nearly one in seven deaths and 9% of the disease burden. While smoking prevalence is declining in Australia, progress is slow, with an average fall of only 0.4% per year since 2010. Currently, around 2.3 million Australians smoke tobacco daily.Smoking prevalence is declining among Indigenous Australians (from 49% of adults in 2004–05 to 37% in 2018–19), but remains substantially higher than among non-Indigenous Australians. Smoking also reduces the life expectancy of people with severe mental illness, people with alcohol and other drug use disorders, and people who are homeless, among whom smoking prevalence remains much higher than the general population.These statistics, and the sustained harm caused by smoking, have given rise to discussion of how to end the cigarette epidemic. Often described as “the tobacco endgame”, this goal means permanently reducing overall smoking prevalence to a minimal level within a defined timeframe. Once seen as unthinkable, this goal is now part of mainstream public health research, and incorporated into government health policy in some countries