Exact S-matrices for supersymmetric sigma models and the Potts model

We study the algebraic formulation of exact factorizable S-matrices for integrable two-dimensional field theories. We show that different formulations of the S-matrices for the Potts field theory are essentially equivalent, in the sense that they can be expressed in the same way as elements of the Temperley-Lieb algebra, in various representations. This enables us to construct the S-matrices for certain nonlinear sigma models that are invariant under the Lie ``supersymmetry'' algebras sl(m+n|n) (m=1,2; n>0), both for the bulk and for the boundary, simply by using another representation of the same algebra. These S-matrices represent the perturbation of the conformal theory at theta=pi by a small change in the topological angle theta. The m=1, n=1 theory has applications to the spin quantum Hall transition in disordered fermion systems. We also find S-matrices describing the flow from weak to strong coupling, both for theta=0 and theta=pi, in certain other supersymmetric sigma models.Comment: 32 pages, 8 figure

A Randomised Controlled Trial of a Facilitated Home-Based Rehabilitation Intervention in Patients with Heart Failure with Preserved Ejection Fraction and their Caregivers:The REACH-HFpEF Pilot Study

Abstract Introduction Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. Methods and results Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers. We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference −11.5, 95% CI −22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. Conclusions Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness

Adverse prognosis associated with asymmetric myocardial thickening in aortic stenosis

Aims: Asymmetric wall thickening has been described in patients with aortic stenosis. However, it remains poorly characterized and its prognostic implications are unclear. We hypothesized this pattern of adaptation is associated with advanced remodelling, left ventricular decompenzation, and a poor prognosis. Methods and results: In a prospective observational cohort study, 166 patients with aortic stenosis (age 69, 69% males, mean aortic valve area 1.0 ± 0.4 cm2) and 37 age and sex-matched healthy volunteers underwent phenotypic characterization with comprehensive clinical, imaging, and biomarker evaluation. Asymmetric wall thickening on both echocardiography and cardiovascular magnetic resonance was defined as regional wall thickening ≥ 13 mm and > 1.5-fold the thickness of the opposing myocardial segment. Although no control subject had asymmetric wall thickening, it was observed in 26% (n = 43) of patients with aortic stenosis using magnetic resonance and 17% (n = 29) using echocardiography. Despite similar demographics, co-morbidities, valve narrowing, myocardial hypertrophy, and fibrosis, patients with asymmetric wall thickening had increased cardiac troponin I and brain natriuretic peptide concentrations (both P < 0.001). Over 28 [22, 33] months of follow-up, asymmetric wall thickening was an independent predictor of aortic valve replacement (AVR) or death whether detected by magnetic resonance [hazard ratio (HR) = 2.15; 95% confidence interval (CI) 1.29-3.59; P = 0.003] or echocardiography (HR = 1.79; 95% CI 1.08-3.69; P = 0.021). Conclusion: Asymmetric wall thickening is common in aortic stenosis and is associated with increased myocardial injury, left ventricular decompenzation, and adverse events. Its presence may help identify patients likely to proceed quickly towards AVR. Clinical Trial Registration: https://clinicaltrials.gov/show/NCT01755936: NCT01755936

Effect of hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes:A prospective, randomised, open-label, blinded endpoint, cross-over study

Abstract Aims This study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes. Methods In a prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration. Results During hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status (p = .23) or between euglycaemia and hypoglycaemia (p = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period (p = .86). Conclusions A small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem

Self-harm, in-person bullying and cyberbullying in secondary school-aged children: a data linkage study in Wales

Introduction Although the evidence base on bullying victimization and self-harm in young people has been growing, most studies were cross-sectional, relied on self-reported non-validated measures of self-harm, and did not separate effects of in-person and cyberbullying. This study aimed to assess associations of self-harm following in-person bullying at school and cyberbullying victimization controlling for covariates. Methods School survey data from 11 to 16 years pupils collected in 2017 from 39 Welsh secondary schools were linked to routinely collected data. Inverse probability weighting was performed to circumvent selection bias. Survival analyses for recurrent events were conducted to evaluate relative risks (adjusted hazard ratios [AHR]) of self-harm among bullying groups within 2 years following survey completion. Results A total of 35.0% (weighted N = 6813) of pupils reported being bullied, with 18.1%, 6.4% and 10.5% being victims of in-person bullying at school only, cyberbullying only and both in-person bullying at school and cyberbullying respectively. Adjusting for covariates, effect sizes for self-harm were significant after being in-person bullied at school only (AHR = 2.2 [1.1–4.3]) and being both in-person bullied at school and cyberbullied (AHR = 2.2 [1.0–4.7]) but not being cyberbullied only (AHR = 1.2 [0.4–3.3]). Feeling lonely during recent summer holidays was also a robust predictor (AHR = 2.2 [1.2–4.0]). Conclusions We reaffirm the role of in-person bullying victimization on self-harm. Pupils were twice as likely to self-harm following in-person bullying as their nonvictimised peers. Interventions for young people that minimize the potential impacts of bullying on self-harm should also include strategies to prevent loneliness

Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo:Comparison With Myocardial Infarction and General Population

BACKGROUND: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.OBJECTIVES: To investigate cardiovascular mortality and medication use after takotsubo syndrome.METHODS: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010-2017 (n=620) were age, sex and geographically matched to individuals in the general population (1:4, n=2,480) and contemporaneous patients with acute myocardial infarction (1:1, n=620). Electronic health record data linkage of mortality outcomes and drug prescribing were analysed using Cox proportional hazard regression models.RESULTS: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow up. This exceeded mortality rates in the general population [374 (15%)]; hazard ratio [HR] 1.78 [95% confidence interval 1.48-2.15], P&lt;0.0001), especially for cardiovascular (HR 2.47, [1.81-3.39], P&lt;0.001) but also non-cardiovascular (HR 1.48 [1.16-1.87], P=0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR 0.76 [0.62-0.94], P=0.012), which was attributable to lower rates of cardiovascular (HR 0.61 [0.44-0.84], P=0.002) but not non-cardiovascular (HR 0.92 [0.69-1.23], P=0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P=0.01), anti-inflammatory (P=0.002) and psychotropic (P&lt;0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.CONCLUSIONS: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use

Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo:Comparison With Myocardial Infarction and General Population

BACKGROUND: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.OBJECTIVES: To investigate cardiovascular mortality and medication use after takotsubo syndrome.METHODS: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010-2017 (n=620) were age, sex and geographically matched to individuals in the general population (1:4, n=2,480) and contemporaneous patients with acute myocardial infarction (1:1, n=620). Electronic health record data linkage of mortality outcomes and drug prescribing were analysed using Cox proportional hazard regression models.RESULTS: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow up. This exceeded mortality rates in the general population [374 (15%)]; hazard ratio [HR] 1.78 [95% confidence interval 1.48-2.15], P&lt;0.0001), especially for cardiovascular (HR 2.47, [1.81-3.39], P&lt;0.001) but also non-cardiovascular (HR 1.48 [1.16-1.87], P=0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR 0.76 [0.62-0.94], P=0.012), which was attributable to lower rates of cardiovascular (HR 0.61 [0.44-0.84], P=0.002) but not non-cardiovascular (HR 0.92 [0.69-1.23], P=0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P=0.01), anti-inflammatory (P=0.002) and psychotropic (P&lt;0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.CONCLUSIONS: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD) : a randomised controlled trial. (BICS)

Acknowledgments We are grateful for the secretarial and data co-ordination support from Janice Cruden. We would like to acknowledge the principal investigators and staff based in trial recruitment sites across the country, the Clinical Research Networks and staff in the Clinical Trials Pharmacy, and the support of the Trial Steering and Data Monitoring Committees. In particular, we have been grateful for the input to the Trial Steering Committee from two lay representatives, Mr Alister Laird and Mr Dave Bertin. Funding {4b} This project was funded by the National Institute for Health Research, Health Technology Assessment Programme (project number 15/130/20). The cardiac sub-study is funded by British Heart Foundation (BHF) Project Grant no. PG/17/64/33205. This report presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the Health Technology Assessment programme or the Department of Health.Peer reviewe

Biochemical, Structural and Molecular Dynamics Analyses of the Potential Virulence Factor RipA from Yersinia pestis

Human diseases are attributed in part to the ability of pathogens to evade the eukaryotic immune systems. A subset of these pathogens has developed mechanisms to survive in human macrophages. Yersinia pestis, the causative agent of the bubonic plague, is a predominately extracellular pathogen with the ability to survive and replicate intracellularly. A previous study has shown that a novel rip (required for intracellular proliferation) operon (ripA, ripB and ripC) is essential for replication and survival of Y. pestis in postactivated macrophages, by playing a role in lowering macrophage-produced nitric oxide (NO) levels. A bioinformatics analysis indicates that the rip operon is conserved among a distally related subset of macrophage-residing pathogens, including Burkholderia and Salmonella species, and suggests that this previously uncharacterized pathway is also required for intracellular survival of these pathogens. The focus of this study is ripA, which encodes for a protein highly homologous to 4-hydroxybutyrate-CoA transferase; however, biochemical analysis suggests that RipA functions as a butyryl-CoA transferase. The 1.9 Å X-ray crystal structure reveals that RipA belongs to the class of Family I CoA transferases and exhibits a unique tetrameric state. Molecular dynamics simulations are consistent with RipA tetramer formation and suggest a possible gating mechanism for CoA binding mediated by Val227. Together, our structural characterization and molecular dynamic simulations offer insights into acyl-CoA specificity within the active site binding pocket, and support biochemical results that RipA is a butyryl-CoA transferase. We hypothesize that the end product of the rip operon is butyrate, a known anti-inflammatory, which has been shown to lower NO levels in macrophages. Thus, the results of this molecular study of Y. pestis RipA provide a structural platform for rational inhibitor design, which may lead to a greater understanding of the role of RipA in this unique virulence pathway

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.</p