Role of ivabradine in management of stable angina in patients with different clinical profiles

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD

Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study.

Small vessel disease (mainly hypertensive arteriopathy and cerebral amyloid angiopathy (CAA)) is an important cause of spontaneous intracerebral haemorrhage (ICH), a devastating and still poorly understood stroke type. Enlarged perivascular spaces (EPVS) are a promising neuroimaging marker of small vessel disease. Based on the underlying arteriopathy distributions, we hypothesised that severe centrum semiovale EPVS are more common in lobar ICH attributed to CAA than other ICH. We evaluated EPVS prevalence, severity and distribution, and their clinical-radiological associations

Conceptualizing cultures of violence and cultural change

The historiography of violence has undergone a distinct cultural turn as attention has shifted from examining violence as a clearly defined (and countable) social problem to analysing its historically defined 'social meaning'. Nevertheless, the precise nature of the relationship between 'violence' and 'culture' is still being established. How are 'cultures of violence' formed? What impact do they have on violent behaviour? How do they change? This essay examines some of the conceptual aspects of the relationship between culture and violence. It brings together empirical research into nineteenth-century England with recent research results from other European contexts to examine three aspects of the relationship between culture and violence. These are organised under the labels 'seeing violence', 'identifying the violent' and 'changing violence'. Within a particular society, narratives regarding particular kinds of behaviour shape cultural attitudes. The notion 'violence' is thus defined in relation to physically aggressive acts as well as by being connected to other kinds of attitudes and contexts. As a result, the boundaries between physical aggression which is legitimate and that which is illegitimate (and thus 'violence') are set. Once 'violence' is defined, particular cultures form ideas about who is responsible for it: reactions to violence become associated with social arrangements such as class and gender as well as to attitudes toward the self. Finally, cultures of violence make efforts to tame or eradicate illegitimate forms of physical aggression. This process is not only connected to the development of new forms of power (e.g., new policing or punishment strategies) but also to less tangible cultural influences which aim at changing the behaviour defined as violence (in particular among the social groups identified as violent). Even if successful, this three-tiered process of seeing violence, identifying the violent and changing violence continues anew, emphasising the ways that cultures of violence develop through a continuous process of reevaluation and reinvention

ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations

A Schwarz lemma for K\"ahler affine metrics and the canonical potential of a proper convex cone

This is an account of some aspects of the geometry of K\"ahler affine metrics based on considering them as smooth metric measure spaces and applying the comparison geometry of Bakry-Emery Ricci tensors. Such techniques yield a version for K\"ahler affine metrics of Yau's Schwarz lemma for volume forms. By a theorem of Cheng and Yau there is a canonical K\"ahler affine Einstein metric on a proper convex domain, and the Schwarz lemma gives a direct proof of its uniqueness up to homothety. The potential for this metric is a function canonically associated to the cone, characterized by the property that its level sets are hyperbolic affine spheres foliating the cone. It is shown that for an $n$-dimensional cone a rescaling of the canonical potential is an $n$-normal barrier function in the sense of interior point methods for conic programming. It is explained also how to construct from the canonical potential Monge-Amp\`ere metrics of both Riemannian and Lorentzian signatures, and a mean curvature zero conical Lagrangian submanifold of the flat para-K\"ahler space.Comment: Minor corrections. References adde

Heart Rate and Use of Beta-Blockers in Stable Outpatients with Coronary Artery Disease

<p><b>Background:</b> Heart rate (HR) is an emerging risk factor in coronary artery disease (CAD). However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR.</p> <p><b>Methods and Findings:</b> CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%). Mean (SD) age was 64.2 (10.5) years, HR by pulse was 68.3 (10.6) bpm, and by electrocardiogram was 67.2 (11.4) bpm. Overall, 44.0% had HR≥70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR≥70 bpm. HR≥70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents.</p> <p><b>Conclusions:</b> Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR≥70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.</p&gt

Interacting Supernovae: Types IIn and Ibn

Supernovae (SNe) that show evidence of strong shock interaction between their ejecta and pre-existing, slower circumstellar material (CSM) constitute an interesting, diverse, and still poorly understood category of explosive transients. The chief reason that they are extremely interesting is because they tell us that in a subset of stellar deaths, the progenitor star may become wildly unstable in the years, decades, or centuries before explosion. This is something that has not been included in standard stellar evolution models, but may significantly change the end product and yield of that evolution, and complicates our attempts to map SNe to their progenitors. Another reason they are interesting is because CSM interaction is an efficient engine for making bright transients, allowing super-luminous transients to arise from normal SN explosion energies, and allowing transients of normal SN luminosities to arise from sub-energetic explosions or low radioactivity yield. CSM interaction shrouds the fast ejecta in bright shock emission, obscuring our normal view of the underlying explosion, and the radiation hydrodynamics of the interaction is challenging to model. The CSM interaction may also be highly non-spherical, perhaps linked to binary interaction in the progenitor system. In some cases, these complications make it difficult to definitively tell the difference between a core-collapse or thermonuclear explosion, or to discern between a non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical parameters of individual events and connections to possible progenitor stars make this a rapidly evolving topic that continues to challenge paradigms of stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3 fig