Ethnic differences in and childhood influences on early adult pulse wave velocity: the determinants of adolescent, now young adult, social wellbeing, and health longitudinal study

Early determinants of aortic stiffness as pulse wave velocity are poorly understood. We tested how factors measured twice previously in childhood in a multiethnic cohort study, particularly body mass, blood pressure, and objectively assessed physical activity affected aortic stiffness in young adults. Of 6643 London children, aged 11 to 13 years, from 51 schools in samples stratified by 6 ethnic groups with different cardiovascular risk, 4785 (72%) were seen again at aged 14 to 16 years. In 2013, 666 (97% of invited) took part in a young adult (21–23 years) pilot follow-up. With psychosocial and anthropometric measures, aortic stiffness and blood pressure were recorded via an upper arm calibrated Arteriograph device. In a subsample (n=334), physical activity was measured >5 days via the ActivPal. Unadjusted pulse wave velocities in black Caribbean and white UK young men were similar (mean±SD 7.9±0.3 versus 7.6±0.4 m/s) and lower in other groups at similar systolic pressures (120 mm Hg) and body mass (24.6 kg/m2). In fully adjusted regression models, independent of pressure effects, black Caribbean (higher body mass/waists), black African, and Indian young women had lower stiffness (by 0.5–0.8; 95% confidence interval, 0.1–1.1 m/s) than did white British women (6.9±0.2 m/s). Values were separately increased by age, pressure, powerful impacts from waist/height, time spent sedentary, and a reported racism effect (+0.3 m/s). Time walking at >100 steps/min was associated with reduced stiffness (P<0.01). Effects of childhood waist/hip were detected. By young adulthood, increased waist/height ratios, lower physical activity, blood pressure, and psychosocial variables (eg, perceived racism) independently increase arterial stiffness, effects likely to increase with age

Individual bacteria in structured environments rely on phenotypic resistance to phage

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All relevant data are within the paper and its Supporting Information files.Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria-phage interactions in naturally structured environments.Medical Research Council (MRC)Engineering and Physical Sciences Research Council (EPSRC)Gordon and Betty and Gordon Moore FoundationEuropean Research Council (ERC)Biotechnology and Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC)Marie Skłodowska-Curie ActionsDefence Science and Technology Laboratory (Dstl)Royal Societ

The influence of racism on cigarette smoking: longitudinal study of young people in a British multiethnic cohort

Introduction: Studies, predominantly from the US, suggest that positive parenting, social support, academic achievement, and ethnic identity may buffer the impact of racism on health behaviours, including smoking, but little is known about how such effects might operate for ethnically diverse young people in the United Kingdom. We use the Determinants of young Adult Social well-being and Health (DASH), the largest UK longitudinal study of ethnically diverse young people, to address the following questions: a) Is racism associated with smoking? b) Does the relationship between racism and smoking vary by gender and by ethnicity? (c) Do religious involvement, parenting style and relationship with parents modify any observed relationship? and d) What are the qualitative experiences of racism and how might family or religion buffer the impact? Methods: The cohort was recruited from 51 London schools. 6643 were seen at 11-13y and 4785 seen again at 14-16y. 665 participated in pilot follow-up at 21-23y, 42 in qualitative interviews. Self-report questionnaires included lifestyles, socio-economic and psychosocial factors. Mixed-effect models examined the associations between racism and smoking. Results: Smoking prevalence increased from adolescence to age 21-23y, although ethnic minorities remained less likely to smoke. Racism was an independent longitudinal correlate of ever smoking throughout adolescence (odds ratio 1.77, 95% Confidence Interval 1.45–2.17) and from early adolescence to early 20s (1.90, 95% CI 1.25–2.90). Smoking initiation in late adolescence was associated with cumulative exposure to racism (1.77, 95% CI 1.23–2.54). Parent-child relationships and place of worship attendance were independent longitudinal correlates that were protective of smoking. Qualitative narratives explored how parenting, religion and cultural identity buffered the adverse impact of racism. Conclusions: Racism was associated with smoking behaviour from early adolescence to early adulthood, regardless of gender, ethnicity or socio-economic circumstances adding to evidence of the need to consider racism as an important social determinant of health across the life course

The Determinants of young Adult Social well-being and Health (DASH) study: diversity, psychosocial determinants and health.

Purpose: The Determinants of young Adult Social well-being and Health longitudinal study draws on life-course models to understand ethnic differences in health. A key hypothesis relates to the role of psychosocial factors in nurturing the health and well-being of ethnic minorities growing up in the UK. We report the effects of culturally patterned exposures in childhood. Methods: In 2002/2003, 6643 11–13 year olds in London, ~80 % ethnic minorities, participated in the baseline survey. In 2005/2006, 4782 were followed-up. In 2012–2014, 665 took part in a pilot follow-up aged 21–23 years, including 42 qualitative interviews. Measures of socioeconomic and psychosocial factors and health were collected. Results: Ethnic minority adolescents reported better mental health than White British, despite more adversity (e.g. economic disadvantage, racism). It is unclear what explains this resilience but findings support a role for cultural factors. Racism was an adverse influence on mental health, while family care and connectedness, religious involvement and ethnic diversity of friendships were protective. While mental health resilience was a feature throughout adolescence, a less positive picture emerged for cardio-respiratory health. Both, mental health and cultural factors played a role. These patterns largely endured in early 20s with family support reducing stressful transitions to adulthood. Education levels, however, signal potential for socio-economic parity across ethnic groups

Experimental Aspects of Synthesis

We discuss the problem of experimentally evaluating linear-time temporal logic (LTL) synthesis tools for reactive systems. We first survey previous such work for the currently publicly available synthesis tools, and then draw conclusions by deriving useful schemes for future such evaluations. In particular, we explain why previous tools have incompatible scopes and semantics and provide a framework that reduces the impact of this problem for future experimental comparisons of such tools. Furthermore, we discuss which difficulties the complex workflows that begin to appear in modern synthesis tools induce on experimental evaluations and give answers to the question how convincing such evaluations can still be performed in such a setting.Comment: In Proceedings iWIGP 2011, arXiv:1102.374

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

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