Influence of 100% and 40% oxygen on penumbral blood flow, oxygen level, and T2*-weighted MRI in a rat stroke model

Accurate imaging of the ischemic penumbra is a prerequisite for acute clinical stroke research. T2* magnetic resonance imaging (MRI) combined with an oxygen challenge (OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. However, inducing OC with 100% O2 induces sinus artefacts on human scans and influences cerebral blood flow (CBF), which can affect T2* signal. Therefore, we investigated replacing 100% O2 OC with 40% O2 OC (5 minutes 40% O2 versus 100% O2) and determined the effects on blood pressure (BP), CBF, tissue pO2, and T2* signal change in presumed penumbra in a rat stroke model. Probes implanted into penumbra and contralateral cortex simultaneously recorded pO2 and CBF during 40% O2 (n=6) or 100% O2 (n=8) OC. In a separate MRI study, T2* signal change to 40% O2 (n=6) and 100% O2 (n=5) OC was compared. Oxygen challenge (40% and 100% O2) increased BP by 8.2% and 18.1%, penumbra CBF by 5% and 15%, and penumbra pO2 levels by 80% and 144%, respectively. T2* signal significantly increased by 4.56%±1.61% and 8.65%±3.66% in penumbra compared with 2.98%±1.56% and 2.79%±0.66% in contralateral cortex and 1.09%±0.82% and −0.32%±0.67% in ischemic core, respectively. For diagnostic imaging, 40% O2 OC could provide sufficient T2* signal change to detect penumbra with limited influence in BP and CBF

Household and area determinants of emergency department attendance and hospitalisation in people with multimorbidity:a systematic review

OBJECTIVES: Multimorbidity is one of the greatest challenges facing healthcare internationally. Emergency department (ED) attendance and hospitalisation rates are higher in people with multimorbidity, but most research focuses on associations with individual characteristics, ignoring household or area mediators of service use. DESIGN: Systematic review reported using the synthesis without meta-analysis framework. DATA SOURCES: Twelve electronic databases (1 January 2000–21 September 2021): MEDLINE/OVID, Embase, Global Health, PsycINFO, ASSIA, CAB Abstracts, Science Citation Index Expanded/ISI Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, Sociological Abstracts, the Cochrane Library, and OpenGrey. ELIGIBILITY CRITERIA: Adults aged ≥16 years, with multimorbidity. Exposure(s) were household and/or area determinants of health. Outcomes were ED attendance and/or hospitalisation. The literature search was limited to publications in English. DATA EXTRACTION AND SYNTHESIS: Independent double screening of titles and abstracts to select relevant full-text studies. Methodological quality was assessed using an adaptation of the Newcastle-Ottawa Quality Assessment Scale tool. Given high study heterogeneity, narrative synthesis was performed. RESULTS: After deduplication, 10 721 titles and abstracts were screened, and 142 full-text articles were reviewed, of which 10 were eligible for inclusion. In people with multimorbidity, household food insecurity was associated with hospitalisation (OR 1.58 (95% CI 1.06 to 2.36) in concordant multimorbidity). People with multimorbidity living in the most versus least deprived areas attended ED more frequently (8.9% (95% CI 8.6 to 9.1) in most versus 6.3% (95% CI 6.1 to 6.6) in least), had higher rates of hospitalisation (26% in most versus 22% in least), and higher probability of hospitalisation (6.4% (95% CI 5.8 to 7.2) in most versus 4.2% (95% CI 3.8 to 4.7) in least). There was non-conclusive evidence that household income is associated with ED attendance and hospitalisation. No statistically significant relationships were found between marital status, living with others with multimorbidity, or rurality with ED attendance or hospitalisation. CONCLUSIONS: There is some evidence that household and area contexts mediate associations of multimorbidity with ED attendance and hospitalisation, but firm conclusions are constrained by the small number of studies published and study design heterogeneity. Further research is required on large population samples using robust analytical methods. PROSPERO REGISTRATION NUMBER: CRD42021283515

Age, sex, and socioeconomic differences in multimorbidity measured in four ways:UK primary care cross-sectional analysis

Background: Multimorbidity poses major challenges to healthcare systems worldwide. Definitions with cut-offs in excess of ≥2 long-term conditions (LTCs) might better capture populations with complexity but are not standardised. Aim: To examine variation in prevalence using different definitions of multimorbidity. Design and setting: Cross-sectional study of 1 168 620 people in England. Method: Comparison of multimorbidity (MM) prevalence using four definitions: MM2+ (≥2 LTCs), MM3+ (≥3 LTCs), MM3+ from 3+ (≥3 LTCs from ≥3 International Classification of Diseases, 10th revision chapters), and mental–physical MM (≥2 LTCs where ≥1 mental health LTC and ≥1 physical health LTC are recorded). Logistic regression was used to examine patient characteristics associated with multimorbidity under all four definitions. Results: MM2+ was most common (40.4%) followed by MM3+ (27.5%), MM3+ from 3+ (22.6%), and mental–physical MM (18.9%). MM2+, MM3+, and MM3+ from 3+ were strongly associated with oldest age (adjusted odds ratio [aOR] 58.09, 95% confidence interval [CI] = 56.13 to 60.14; aOR 77.69, 95% CI = 75.33 to 80.12; and aOR 102.06, 95% CI = 98.61 to 105.65; respectively), but mental–physical MM was much less strongly associated (aOR 4.32, 95% CI = 4.21 to 4.43). People in the most deprived decile had equivalent rates of multimorbidity at a younger age than those in the least deprived decile. This was most marked in mental–physical MM at 40–45 years younger, followed by MM2+ at 15–20 years younger, and MM3+ and MM3+ from 3+ at 10–15 years younger. Females had higher prevalence of multimorbidity under all definitions, which was most marked for mental–physical MM. Conclusion: Estimated prevalence of multimorbidity depends on the definition used, and associations with age, sex, and socioeconomic position vary between definitions. Applicable multimorbidity research requires consistency of definitions across studies

The impact of varying the number and selection of conditions on estimated multimorbidity prevalence::a cross-sectional study using a large, primary care population dataset

Background: Multimorbidity prevalence rates vary considerably depending on the conditions considered in the morbidity count, but there is no standardised approach to the number or selection of conditions to include. Methods and findings: We conducted a cross-sectional study using English primary care data for 1,168,260 participants who were all people alive and permanently registered with 149 included general practices. Outcome measures of the study were prevalence estimates of multimorbidity (defined as ≥2 conditions) when varying the number and selection of conditions considered for 80 conditions. Included conditions featured in ≥1 of the 9 published lists of conditions examined in the study and/or phenotyping algorithms in the Health Data Research UK (HDR-UK) Phenotype Library. First, multimorbidity prevalence was calculated when considering the individually most common 2 conditions, 3 conditions, etc., up to 80 conditions. Second, prevalence was calculated using 9 condition-lists from published studies. Analyses were stratified by dependent variables age, socioeconomic position, and sex. Prevalence when only the 2 commonest conditions were considered was 4.6% (95% CI [4.6, 4.6] p < 0.001), rising to 29.5% (95% CI [29.5, 29.6] p < 0.001) considering the 10 commonest, 35.2% (95% CI [35.1, 35.3] p < 0.001) considering the 20 commonest, and 40.5% (95% CI [40.4, 40.6] p < 0.001) when considering all 80 conditions. The threshold number of conditions at which multimorbidity prevalence was >99% of that measured when considering all 80 conditions was 52 for the whole population but was lower in older people (29 in >80 years) and higher in younger people (71 in 0- to 9-year-olds). Nine published condition-lists were examined; these were either recommended for measuring multimorbidity, used in previous highly cited studies of multimorbidity prevalence, or widely applied measures of “comorbidity.” Multimorbidity prevalence using these lists varied from 11.1% to 36.4%. A limitation of the study is that conditions were not always replicated using the same ascertainment rules as previous studies to improve comparability across condition-lists, but this highlights further variability in prevalence estimates across studies. Conclusions: In this study, we observed that varying the number and selection of conditions results in very large differences in multimorbidity prevalence, and different numbers of conditions are needed to reach ceiling rates of multimorbidity prevalence in certain groups of people. These findings imply that there is a need for a standardised approach to defining multimorbidity, and to facilitate this, researchers can use existing condition-lists associated with highest multimorbidity prevalence

Validity of the iPhone M7 Motion Coprocessor to Estimate Physical Activity During Structured and Free-Living Activities in Healthy Adults

Modern smartphones such as the iPhone contain an integrated accelerometer, which can be used to measure body movement and estimate the volume and intensity of physical activity. Objectives: The primary objective was to assess the validity of the iPhone to measure step count and energy expenditure during laboratory-based physical activities. A further objective was to compare free-living estimates of physical activity between the iPhone and the ActiGraph GT3X+ accelerometer. Methods: Twenty healthy adults wore the iPhone 5S and GT3X+ in a waist-mounted pouch during bouts of treadmill walking, jogging, and other physical activities in the laboratory. Step counts were manually counted, and energy expenditure was measured using indirect calorimetry. During two weeks of free-living, participants (n = 17) continuously wore a GT3X+ attached to their waist and were provided with an iPhone 5S to use as they would their own phone. Results: During treadmill walking, iPhone (703 ± 97 steps) and GT3X+ (675 ± 133 steps) provided accurate measurements of step count compared with the criterion method (700 ± 98 steps). Compared with indirect calorimetry (8 ± 3 kcal·min−1), the iPhone (5 ± 1 kcal·min−1) underestimated energy expenditure with poor agreement. During free-living, the iPhone (7,990 ± 4,673 steps·day−1) recorded a significantly lower (p

Multicentre open label randomised controlled trial of immediate enhanced ambulatory ECG monitoring versus standard monitoring in acute unexplained syncope patients:the ASPIRED study

Introduction Diagnosing underlying arrhythmia in emergency department (ED) syncope patients is difficult. There is a evidence that diagnostic yield for detecting underlying arrhythmia is highest when cardiac monitoring devices are applied early, ideally at the index visit. This strategy has the potential to change current syncope management from low diagnostic yield Holter to higher yield ambulatory monitoring, reduce episodes of syncope, reduce risk of recurrence and its potential serious consequences, reduce hospital admissions, reduce overall health costs and increase quality of life by allowing earlier diagnosis, treatment and exclusion of clinically important arrhythmias. Methods and analyses This is a UK open prospective parallel group multicentre randomised controlled trial of an immediate 14-day ambulatory patch heart monitor vs standard care in 2234 patients presenting acutely with unexplained syncope. Our patient focused primary endpoint will be number of episodes of syncope at 1 year. Health economic evaluation will estimate the incremental cost per syncope episode avoided and quality-adjusted life year gained. Ethics and dissemination Informed consent for participation will be sought. The ASPIRED trial received a favourable ethical opinion from South East Scotland Research Ethics Committee 01 (21/SS/0073). Results will be disseminated via scientific publication, lay summary and visual abstract

Heroes and villains of world history across cultures

© 2015 Hanke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedEmergent properties of global political culture were examined using data from the World History Survey (WHS) involving 6,902 university students in 37 countries evaluating 40 figures from world history. Multidimensional scaling and factor analysis techniques found only limited forms of universality in evaluations across Western, Catholic/Orthodox, Muslim, and Asian country clusters. The highest consensus across cultures involved scientific innovators, with Einstein having the most positive evaluation overall. Peaceful humanitarians like Mother Theresa and Gandhi followed. There was much less cross-cultural consistency in the evaluation of negative figures, led by Hitler, Osama bin Laden, and Saddam Hussein. After more traditional empirical methods (e.g., factor analysis) failed to identify meaningful cross-cultural patterns, Latent Profile Analysis (LPA) was used to identify four global representational profiles: Secular and Religious Idealists were overwhelmingly prevalent in Christian countries, and Political Realists were common in Muslim and Asian countries. We discuss possible consequences and interpretations of these different representational profiles.This research was supported by grant RG016-P-10 from the Chiang Ching-Kuo Foundation for International Scholarly Exchange (http://www.cckf.org.tw/). Religion Culture Entropy China Democracy Economic histor

Trajectories in chronic disease accrual and mortality across the lifespan in Wales, UK (2005-2019), by area deprivation profile : linked electronic health records cohort study on 965,905 individuals

Funding: This work was supported by Health Data Research UK (HDRUK) Measuring and Understanding Multimorbidity using Routine Data in the UK (MUrMuRUK, HDR-9006; CFC0110). Health Data Research UK (HDR-9006) is funded by: UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, the National Institute for Health Research (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. This work also was co-funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) through grant number MR/S027750/1. The work was supported by the ADR Wales programme of work, part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1).Background  Understanding and quantifying the differences in disease development in different socioeconomic groups of people across the lifespan is important for planning healthcare and preventive services. The study aimed to measure chronic disease accrual, and examine the differences in time to individual morbidities, multimorbidity, and mortality between socioeconomic groups in Wales, UK. Methods  Population-wide electronic linked cohort study, following Welsh residents for up to 20 years (2000-2019). Chronic disease diagnoses were obtained from general practice and hospitalisation records using the CALIBER disease phenotype register. Multi-state models were used to examine trajectories of accrual of 132 diseases and mortality, adjusted for sex, age and area-level deprivation. Restricted mean survival time was calculated to measure time spent free of chronic disease(s) or mortality between socioeconomic groups. Findings  In total, 965,905 individuals aged 5-104 were included, from a possible 2·9m individuals following a 5-year clearance period, with an average follow-up of 13·2 years (12·7 million person-years). Some 673,189 (69·7 %) individuals developed at least one chronic disease or died within the study period. From ages 10 years upwards, the individuals living in the most deprived areas consistently experienced reduced time between health states, demonstrating accelerated transitions to first and subsequent morbidities and death compared to their demographic equivalent living in the least deprived areas. The largest difference were observed in 10 and 20 year old males developing multimorbidity (-0·45 years (99%CI:-0·45,-0·44)) and in 70 year old males dying after developing multimorbidity (-1·98 years (99%CI:-2·01,-1·95)). Interpretation  This study adds to the existing literature on health inequalities by demonstrating that individuals living in more deprived areas consistently experience accelerated time to diagnosis of chronic disease and death across all ages, accounting for competing risks.Publisher PDFPeer reviewe

Women, resettlement and desistance

With the numbers of women imprisoned increasing across Western jurisdictions over the last 15 or so years, so too have the numbers of women returning to the community following a period in custody. Despite increasing policy attention in the UK and elsewhere to prisoner resettlement, women’s experiences on release from prison have received limited empirical and policy attention. Drawing upon interviews with women leaving prison in Victoria, Australia, this article discusses the resettlement challenges faced by the women and highlights their similarity to the experiences of women leaving prison in other jurisdictions. Women had mixed (and predominantly negative) experiences and views of accessing services and supports following release, though experiences of parole supervision by community corrections officers were often positive, especially if women felt valued and supported by workers who demonstrated genuine concern. Analysis of factors associated with further offending and with desistance, points to the critical role of flexible, tailored and women-centred post-release support building, and, where possible, upon relationships established with women while they are still in prison

Gene silencing in the marine diatom Phaeodactylum tricornutum

Diatoms are a major but poorly understood phytoplankton group. The recent completion of two whole genome sequences has revealed that they contain unique combinations of genes, likely recruited during their history as secondary endosymbionts, as well as by horizontal gene transfer from bacteria. A major limitation for the study of diatom biology and gene function is the lack of tools to generate targeted gene knockout or knockdown mutants. In this work, we have assessed the possibility of triggering gene silencing in Phaeodactylum tricornutum using constructs containing either anti-sense or inverted repeat sequences of selected target genes. We report the successful silencing of a GUS reporter gene expressed in transgenic lines, as well as the knockdown of endogenous phytochrome (DPH1) and cryptochrome (CPF1) genes. To highlight the utility of the approach we also report the first phenotypic characterization of a diatom mutant (cpf1). Our data open the way for reverse genetics in diatoms and represent a major advance for understanding their biology and ecology. Initial molecular analyses reveal that targeted downregulation likely occurs through transcriptional and post-transcriptional gene silencing mechanisms. Interestingly, molecular players involved in RNA silencing in other eukaryotes are only poorly conserved in diatoms