Focus on the Future: A Plan for the HOPE Village Initiative Area

http://deepblue.lib.umich.edu/bitstream/2027.42/110953/1/focusonthefuture2010.pd

Associations between change in blood pressure and functional outcome, early events and death: results from the Efficacy of Nitric Oxide in Stroke trial.

OBJECTIVES: High blood pressure (BP) is associated with a poor outcome after acute stroke. Early reduction in BP may be associated with fewer early adverse events and deaths, and improved functional outcome. METHODS: Analyses used data from the Efficacy of Nitric Oxide in Stroke trial, a multicentre randomized single-masked and outcome-masked trial of glyceryl trinitrate vs. no glyceryl trinitrate in 4011 patients recruited within 48 h of an ischaemic or haemorrhagic stroke and with raised SBP (140-220 mmHg). Change in SBP from baseline to day 1 was categorized as: more than 15% decrease, 15-5% decrease, 5% decrease to 5% increase (no change - reference) and more than 5% increase. The primary outcome was functional outcome (modified Rankin scale) score at 90 days. RESULTS: Across all patients, both moderate (5-15%) and large (>15%) decreases in SBP were associated with beneficial shifts in the modified Rankin scale relative to patients with no change in BP: adjusted common odds ratio (OR) 0.81 [95% confidence interval (CI) 0.70-0.90] and OR 0.84 (95% CI 0.71-1.00), respectively. A moderate decrease in SBP was also associated with a lower risk of early adverse events, adjusted OR 0.69 (95% CI 0.52-0.90). CONCLUSION: Modest decreases in SBP in acute stroke appear to be associated with fewer early events and better long-term functional outcome

Effect of glyceryl trinitrate on haemodynamics in acute stroke: data from the Efficacy of Nitric Oxide in Stroke trial

Background and Purpose: Increased blood pressure (BP), heart rate and their derivatives (variability, pulse pressure, rate-pressure product [RPP]) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on haemodynamic parameters, and these on outcome in participants in the Efficacy of Nitric Oxide in Stroke trial.Methods: 4011 patients with acute stroke and raised BP were randomised within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral haemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as standard deviation) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale (mRS) and cognition as telephone mini-mental state examination (t-MMSE) at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference (MD) or odds ratios (OR) with 95% confidence intervals (CI).Results: Increased baseline BP (diastolic, variability), heart rate and RPP were each associated with unfavourable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in mRS (highest quintile adjusted OR 1.65, 95% CI 1.37 to 1.99), worse cognitive scores (t-MMSE: highest quintile adjusted MD -2.03, 95% CI -2.84 to -1.22) and increased odds of death at day 90 (highest quintile adjusted OR 1.57, 95% CI 1.12 to 2.19). GTN lowered BP and RPP, and increased heart rate at day 1; and reduced between-visit systolic BP variability.Conclusions: Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and RPP, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study

OSIRIS-REx Encounters Bennu: Initial Assessment from the Approach Phase

The OSIRIS-REx spacecraft launched on September 8, 2016, on a seven-year journey to return samples from asteroid (101955) Bennu. This presentation summarizes the scientific results from the Approach and Preliminary Survey phases. Bennu observations are set to begin on August 17, 2018,when the asteroid is bright enough for detection by the PolyCam. PolyCam and MapCam collect data to survey the asteroid environment for any hazards and characterize the asteroid point-source photometric properties. Resolved images acquired during final approach, starting in late October 2018, allow the creation of a shape model using stereophotoclinometry (SPC), needed by both the navigation team and science planners. The OVIRS and OTES spectrometers characterize the point- source spectral properties over a full rotation period, providing a first look at any features and thermophysical properties. TAGSAM is released from the launch container and deployed into the sampling configuration then returned to the stow position.Preliminary Survey follows the Approach Phase in early December 2018. This phase consists of a series of hyperbolic trajectories that cross over the North and South poles and the equator of Bennu at a close-approach distance of 7 km. Images from these Preliminary Survey passes provide data to complete the 75-cm resolution SPC global shape model and solve for the rotation state. Once the shape model is complete, the asteroid coordinate system is defined for co-registration of all data products. These higher-resolution images also constrain the photometric properties and allow for an initial assessment of the geology. In Preliminary Survey the team also obtains the first OLA data, providing a measure of the surface topography. OVIRS and OTES collect data as "ride-along" instruments, with the spacecraft pointing driven by imaging constraints. These data provide a first look at the spectral variation across the surface of Bennu. Radio science measurements, combined with altimetry and imagery, determine Bennu's mass, a prerequisite to placing the spacecraft into orbit in late December 2018. Together, data from the Approach and Preliminary Survey phases set the stage for the extensive mapping planned for 2019. These dates are the baseline plan. Any contingency or unexpected discovery may change this mission profile

A MISSING-LINK IN THE SUPERNOVA-GRB CONNECTION: THE CASE OF SN 2012ap

Gamma Ray Bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However supernovae, with heavy ejecta, can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. Yet the ejecta from SN 2009bb was baryon loaded, and in nearly-free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB, but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than a sixth of the fluence from GRB 980425. This shows for the first time that central engines in type Ic supernovae, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.Comment: 8 pages, 5 figures, 1 table, accepted for publication in Ap

Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period

Objectives: People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52\u200aweeks in PWH. Design: This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420\u200amg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24\u200aweeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART. Methods: Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined. Results: Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4\u200ayears, 82.5% male, mean duration with HIV of 17.4\u200ayears). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP. Conclusion: Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events. Trail registration: NCT02833844. Video abstract: http://links.lww.com/QAD/C441

The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans.

Histiocytic sarcoma (HS) is a rare malignant proliferation of histiocytes of uncertain molecular pathogenesis. Here, genetic analysis of coincident loss of Pten and Ink4a/Arf tumor suppressors in the mouse revealed a neoplastic phenotype dominated by a premalignant expansion of biphenotypic myelolymphoid cells followed by the development of HS. Pten protein loss occurred only in the histiocytic portion of tumors, suggesting a stepwise genetic inactivation in the generation of HS. Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS. These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer