B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease

BACKGROUND: Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main CAD. METHODS: The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized patients with left main CAD and low or intermediate SYNTAX scores (Synergy Between PCI With TAXUS and Cardiac Surgery) to PCI with everolimus-eluting stents versus CABG. The primary end point was the composite of all-cause death, myocardial infarction, or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. RESULTS: BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower left ventricular ejection fraction than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary end point (18.6% versus 11.7%; adjusted hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.16-2.28; P=0.005) and higher mortality (11.5% versus 3.9%; adjusted HR, 2.49; 95% CI, 1.48-4.19; P=0.0006), both from cardiovascular and noncardiovascular causes. In contrast, there were no significant differences in the risks of myocardial infarction, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction ( Pinteraction=0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite end point at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG, 1.54; 95% CI, 0.96-2.47) versus normal BNP (adjusted HR, 0.74; 95% CI, 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable ( Pinteraction=0.002). CONCLUSIONS: In the EXCEL trial, elevated baseline BNP levels in patients with left main CAD undergoing revascularization were independently associated with long-term mortality but not nonfatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI versus CABG for revascularization of left main CAD may be conditioned by the baseline BNP level. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01205776

A robust lentiviral pseudotype neutralisation assay for rabies and lyssavirus serology

The inflexibility of existing serological techniques for rabies can make it difficult to monitor the impact of current control strategies. We have developed a neutralisation assay that uses lentiviral pseudotypes (comprising the outer envelope of rabies virus, human immunodeficiency virus core and a packageable reporter gene) as antigen vectors. The assay can be used for vaccine evaluation, serosurveillance and antiviral screening in low-containment laboratories within developed and resource-limited countries. Post-vaccination serum antibody titres determined using the fluorescent antibody virus neutralisation assay and pseudotype assay show a specificity of 100%, sensitivity of 96.4% and strong correlation (r=0.85; p<0.001). To increase the assay’s utility we incorporated the envelope glycoprotein of lyssavirus isolates from genotypes 1-7 and a range of different reporter genes. Genotype 1 (CVS-11) pseudotypes were highly stable during freeze-thaw cycles and storage at room temperature suggesting the pseudotype assay is a suitable option for undertaking lyssavirus serosurveillance in areas most affected by these infections

Patterns of foot-and-mouth disease virus distribution in Africa

Foot-and-mouth disease (FMD) is one of the most highly contagious diseases of animals. The disease is distributed on three continents (Asia, Africa and South America) where it disrupts the food security of people who depend on livestock and animal products. Substantial economic losses are associated with controlling FMD outbreaks in many countries. For example, during the epidemic in the UK in 2001, losses to agriculture were estimated to be £3.1 billion, with similar losses arising from negative impacts on tourism. Over 4 million animals were slaughtered as part of FMD control measures and a further 2 million were slaughtered due to welfare issues associated with animal movement bans. FMD also has a devastating impact on rural livelihoods and livestock trade opportunities in developing countries where it is endemic. In Africa, historic patterns of FMD virus (FMDV) emergence are likely to have been shaped by the introduction and subsequent eradication of rinderpest. However, important questions remain about contemporary drivers of disease distribution. In particular, the relative contribution of wildlife as sources of infection for livestock and factors affecting the potential for cross-species transmission, and mechanisms of viral maintenance in endemic regions are poorly understood. These issues encompass a complex suite of interacting social, ecological and economic factors that act as drivers of change in patterns of land-use, livestock movements, international trade, and conservation of wildlife-protected areas. Understanding patterns of FMDV infection at the livestock-wildlife interface is of particular importance for designing and developing appropriate disease control strategies in sub-Saharan Africa, and of increasing interest as momentum grows for global control of FMD within the framework of the Progressive Control Pathway (PCP-FMD). This chapter reviews the historical distribution and emergence of FMDV in Africa, and factors that govern the current circulation and maintenance of FMDV in sub-Saharan Africa

Euclid. I. Overview of the Euclid mission

The current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients, dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015-2025 programme of the European Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy, over about 14,000 deg^2 of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structure formation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range of science. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processing steps, and data products. We also highlight the main science objectives and expected performance