Angina at Low heart rate And Risk of imminent Myocardial infarction (the ALARM study): a prospective, observational proof-of-concept study

BACKGROUND: Myocardial infarction (MI) is often preceded by unstable angina. Helping patients identify the onset of unstable angina rather than MI may result in earlier treatment and improve outcomes. Unstable angina is angina occurring at a lower-than-usual workload. Since heart rate (HR) is correlated with degree of exertion, we hypothesised that angina occurring at low HR is a warning signal for unstable angina and MI. METHODS: In this prospective study, 111 patients with acute coronary syndrome (ACS) or prognostically significant coronary disease were recruited. Each patient’s HR was measured using a portable electrocardiogram (ECG) recorder after regular class III exercise on the Canadian Cardiovascular Society Angina Grading Scale and the cumulative moving average and three-sigma (standard deviation) range were calculated for each new measurement. The HR was subsequently measured at the beginning of angina; a HR lower than the preceding three-sigma ranges for class III or anginal HR was regarded as a ‘warning signal’. The proportion of warning signals associated with ACS occurring in the following 2 weeks was compared with that for non-warning signals. RESULTS: Nine cases of ACS occurred in eight patients. Two cases were preceded by warning signals; a signal marked the onset of ACS in a third patient, and four patients failed to make anginal ECG recordings. There were 591 documented episodes of angina during the study and ECGs were available for 383 (64.8 %) of these of which 55 were warning signals. Of these warning signals, 4 occurred in the 2 weeks preceding ACS, compared with 4 of 328 non-warning signals (odds ratio, 6.4; 95 % confidence interval, 1.5–26.2; p = 0.01; positive predictive value, 7.3 %; negative predictive value, 98.8 %). CONCLUSIONS: Low HR angina may identify unstable angina and serve as an early warning for MI. In addition, angina that does not occur at a low heart rate indicates that ACS is very unlikely

On the Inverse Problem of Binocular 3D Motion Perception

It is shown that existing processing schemes of 3D motion perception such as interocular velocity difference, changing disparity over time, as well as joint encoding of motion and disparity, do not offer a general solution to the inverse optics problem of local binocular 3D motion. Instead we suggest that local velocity constraints in combination with binocular disparity and other depth cues provide a more flexible framework for the solution of the inverse problem. In the context of the aperture problem we derive predictions from two plausible default strategies: (1) the vector normal prefers slow motion in 3D whereas (2) the cyclopean average is based on slow motion in 2D. Predicting perceived motion directions for ambiguous line motion provides an opportunity to distinguish between these strategies of 3D motion processing. Our theoretical results suggest that velocity constraints and disparity from feature tracking are needed to solve the inverse problem of 3D motion perception. It seems plausible that motion and disparity input is processed in parallel and integrated late in the visual processing hierarchy

Trans youth, science and art: creating (trans) gendered space

This article is based on empirical research which was undertaken as part of the Sci:dentity project funded by the Wellcome Trust. Sci:dentity was a year-long participatory arts project which ran between March 2006 and March 2007. The project offered 18 young transgendered and transsexual people, aged between 14 and 22, an opportunity to come together to explore the science of sex and gender through art. This article focuses on four creative workshops which ran over two months, being the ‘creative engagement’ phase of the project. It offers an analysis of the transgendered space created which was constituted through the logics of recognition, creativity and pedagogy. Following this, the article explores the ways in which these transgendered and transsexual young people navigate gendered practices, and the gendered spaces these practices constitute, in their everyday lives shaped by gendered and sexual normativities. It goes on to consider the significance of trans virtual and physical cultural spaces for the development of trans young peoples' ontological security and their navigations and negotiations of a gendered social world

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