The effects of a graduated aerobic exercise programme on cardiovascular disease risk factors in the NHS workplace: a randomised controlled trial

BACKGROUND: Sufficient levels of physical activity provide cardio-protective benefit. However within developed society sedentary work and inflexible working hours promotes physical inactivity. Consequently to ensure a healthy workforce there is a requirement for exercise strategies adaptable to occupational time constraint. This study examined the effect of a 12 week aerobic exercise training intervention programme implemented during working hours on the cardiovascular profile of a sedentary hospital workforce. METHODS: Twenty healthy, sedentary full-time staff members of the North West London Hospital Trust cytology unit were randomly assigned to an exercise (n = 12; mean +/- SD age 41 +/- 8 years, body mass 69 +/- 12 kg) or control (n = 8; mean +/- SD age 42 +/- 8 years, body mass 69 +/- 12 kg) group. The exercise group was prescribed a progressive aerobic exercise-training programme to be performed 4 times a week for 8 weeks (initial intensity 65% peak oxygen consumption (VO2 peak)) and to be conducted without further advice for another 4 weeks. The control was instructed to maintain their current physical activity level. Oxygen economy at 2 minutes (2minVO2), 4 minutes (4minVO2), VO2 peak, systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, C-reactive protein (CRP), fasting glucose (GLU) and total cholesterol (TC) were determined in both groups pre-intervention and at 4 week intervals. Both groups completed a weekly Leisure Time Questionnaire to quantify additional exercise load. RESULTS: The exercise group demonstrated an increase from baseline for VO2 peak at week 4 (5.8 +/- 6.3 %) and 8 (5.0 +/- 8.7 %) (P < 0.05). 2minVO2 was reduced from baseline at week 4 (-10.2 +/- 10.3 %), 8 (-16.8 +/- 10.6 %) and 12 (-15.1 +/- 8.7 %), and 4minVO2 at week 8 (-10.7 +/- 7.9 %) and 12 (-6.8 +/- 9.2) (P < 0.05). There was also a reduction from baseline in CRP at week 4 (-0.4 +/- 0.6 mg.L-1) and 8 (-0.9 +/- 0.8 mg.L-1) (P < 0.05). The control group showed no such improvements. CONCLUSION: This is the first objectively monitored RCT to show that moderate exercise can be successfully incorporated into working hours, to significantly improve physical capacity and cardiovascular health

Debate:Challenges in sports cardiology; US versus European approaches

For practitioners working with elite athletes, the field of sports cardiology provides clinical, academic, administrative and fiscal challenges. These challenges are exemplified and reinforced by the lack of consistency and consensus both in the literature and academic presentations. Through thepresentation of a series of clinical questions, this debate attempts to ‘cut to the chase’ on cardiovascular issues relevant to the clinician dealing with elite athletes. In so doing, we hope to crystallize some of the most important elements of the complex cardiological management of elite athletes, in a concise, readable format. Frequently over the last 10 years, many of the controversies in this field have been (rightly or wrongly) presented in aEurope versus USA paradigm. We have chosen to test whether there really are polarised views across the Atlantic, by deliberately pitting specialists from the USA against those from the UK. Professors Levine and Thompson are both internationally recognised sports cardiologists, with immense academic and clinical credibility, and who will represent the ‘US approach’. Professor Whyte and Doctor Wilson are cardiac physiologists with a wealth of experience in the testing, evaluation and screening of elite athletes, and who have equally impressive academic credibility and for the purposes of this debate, they will be representing the ‘European approach’. To initiate this process, each team was required to provide a concise answer (circa 200–300 words) to a series of fiveclinical conundrums. Subsequently, each team had the opportunity to provide a rebuttal to the opposing team’s answers, and the following reflects the consolidation of those answers

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

Seriously personal:The reasons that motivate entrepreneurs to address climate change

This is the author accepted manuscript. The final version is freely available from Springer Verlag via the DOI in this record.Scholars increasingly argue that entrepreneurs and their small- and medium-sized enterprises should play a central role in reducing the rate and magnitude of climate change. However, evidence suggests that while some entrepreneurs recognize their crucial role in addressing climate change, most do not. Why some entrepreneurs nevertheless concern themselves with climate change has largely been overlooked. Some initial work in this area tentatively suggests that these entrepreneurs may engage with climate change because of their personal values, which either focus on financial or socio-ecological reasons, or a combination of both. Yet, it is unclear if all for-profit entrepreneurs engage with climate change for the same reasons, or if indeed their motivations vary across business types. Over a period of four years, we examined entrepreneurs’ motivations to engage with climate change through a variety of qualitative research methods. Our findings illustrate how entrepreneurs who address climate change have motivations specific to their business activity/industry and level of maturity. In each instance, we link these motivations to distinct conceptualizations of time and place. We contend that, through a more differentiated understanding of entrepreneurial motivations, policy-makers can draft climate change-related policies tailored to entrepreneurial needs. Policies could both increase the number of entrepreneurs who already engage in climate change mitigation and leverage the impact of those entrepreneurs already mitigating climate change.This study was funded by the European Social Fund (09099NCO5). We acknowledge with thanks the participation of the entrepreneurs and the support of Business Leaders for Low Carbon, Cornwall Council, and Cornwall Sustainable Tourism Project. The authors wish to thank Professor John Amis, Professor Kenneth Amaeshi and the anonymous reviewers who provided useful feedback on earlier versions of the article

Is the pen mightier than the sword? Exploring urban and rural health in Victorian England and Wales using the Registrar General Reports

YesIn AD 1836, the General Register Office (GRO) was established to oversee the national system of civil registration in England and Wales, recording all births, deaths and marriages. Additional data regarding population size, division size and patterns of occupation within each division permit urban and rural areas (and those with both urban and rural characteristics, described here as ‘mixed’) to be directly compared to each other. The annual Reports of the Registrar General summarize the collected data, including cause of and age at death, which is of particular value to historical demographers and bioarcheologists, allowing us to investigate demographic patterns in urban and rural districts in the nineteenth century. Overall, this paper aims to highlight how this documentary evidence can supplement osteological and paleopathological data to investigate how urbanization affected the health of past populations. It examines the data contained within the first Registrar General report (for 1837-8), in order to assess patterns of mortality of diverse rural, urban, and mixed populations within England and Wales at a point in time during a period of rapid urbanization. It shows that urban and mixed districts typically had lower life expectancy and different patterns in cause of death compared to rural areas. The paper briefly compares how the documentary data differs from information regarding health from skeletal populations, focusing on the city of London, highlighting that certain age groups (the very young and very old) are typically underrepresented in archeological assemblages and reminding us that, while the paleopathological record offers much in terms of chronic health, evidence of acute disease and importantly cause of death can rarely be ascertained from skeletal remains.This research was funded by the Royal Society of London (Grant Reference IES\R1\180138) and supported by the University of Bradford and SUNY Plattsburgh

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

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

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

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