Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION.

OBJECTIVES: The aim of this study was to assess for a treatment interaction between statin use and exercise training (ET) response. BACKGROUND: Recent data suggest that statins may attenuate ET response, but limited data exist in patients with heart failure (HF). METHODS: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity (peak oxygen consumption and 6-min walk distance) from baseline to 3 months. We also assessed for a treatment interaction among atorvastatin, simvastatin, and pravastatin and change in these endpoints with ET. Multiple linear regression analyses were performed for each endpoint, adjusting for baseline covariates. RESULTS: Of 2,331 patients in the HF-ACTION trial, 1,353 (58%) were prescribed statins at baseline. Patients treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers. There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity, nor was there evidence of differential association between statin type and ET response for these endpoints (all p values \u3e0.05). CONCLUSIONS: In a large chronic HF cohort, there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET. These findings contrast with recent reports of an attenuation in ET response with statins in a different population, highlighting the need for future prospective studies. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437)

Prior Antithrombotic Use Is Associated With Favorable Mortality and Functional Outcomes in Acute Ischemic Stroke

Acknowledgments Drs Myint and Smith conceived the idea and developed the analysis plan with critical input from coauthors. A.S. Hellkamp analyzed the data. Drs Myint and Smith drafted the article with input from all coauthors. All authors contributed in interpretation of results and in making an important intellectual contribution to the article. Sources of Funding The Get With The Guidelines (GWTG)-Stroke program is currently supported, in part, by a charitable contribution from Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. These funding agencies did not participate in design or analysis, article preparation, or approval of this study.Peer reviewedPostprin

Identification of upper thermal thresholds during development in the endangered Nechako white sturgeon with management implications for a regulated river

Climate change-induced warming effects are already evident in river ecosystems, and projected increases in temperature will continue to amplify stress on fish communities. In addition, many rivers globally are impacted by dams, which have many negative effects on fishes by altering flow, blocking fish passage, and changing sediment composition. However, in some systems, dams present an opportunity to manage river temperature through regulated releases of cooler water. For example, there is a government mandate for Kenney dam operators in the Nechako river, British Columbia, Canada, to maintain river temperature <20°C in July and August to protect migrating sockeye salmon (Oncorhynchus nerka). However, there is another endangered fish species inhabiting the same river, Nechako white sturgeon (Acipenser transmontanus), and it is unclear if these current temperature regulations, or timing of the regulations, are suitable for spawning and developing sturgeon. In this study, we aimed to identify upper thermal thresholds in white sturgeon embryos and larvae to investigate if exposure to current river temperatures are playing a role in recruitment failure. We incubated embryos and yolk-sac larvae in three environmentally relevant temperatures (14, 18 and 21°C) throughout development to identify thermal thresholds across different levels of biological organization. Our results demonstrate upper thermal thresholds at 21°C across physiological measurements in embryo and yolk-sac larvae white sturgeon. Before hatch, both embryo survival and metabolic rate were reduced at 21°C. After hatch, sublethal consequences continued at 21°C because larval sturgeon had decreased thermal plasticity and a dampened transcriptional response during development. In recent years, the Nechako river has reached 21°C by the end of June, and at this temperature, a decrease in sturgeon performance is evident in most of the traits measured. As such, the thermal thresholds identified here suggest current temperature regulations may not be suitable for developing white sturgeon and future recruitment

Relationship Between Galectin-3 Levels and Mineralocorticoid Receptor Antagonist Use in Heart Failure: Analysis From HF-ACTION

Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRA) modulate cardiac fibrosis in HF patients, and have been shown to improve long term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in the HF-ACTION study

Healthcare Resource Availability, Quality of Care, and Acute Ischemic Stroke Outcomes

Background: Healthcare resources vary geographically, but associations between hospital‐based resources and acute stroke quality and outcomes remain unclear. Methods and Results: Using Get With The Guidelines‐Stroke and Dartmouth Atlas of Health Care data, we examined associations between healthcare resource availability, stroke care, and outcomes. We categorized hospital referral regions with high‐, medium‐, or low‐resource levels based on the 2006 national per‐capita availability median of 6 relevant acute stroke care resources. Using multivariable logistic regression, we examined healthcare resource level and in‐hospital quality and outcomes. Of 1 480 308 admitted ischemic stroke patients (2006–2013), 28.8% were hospitalized in low‐, 44.4% in medium‐, and 26.9% in high‐resource hospital referral regions. Quality‐of‐care/timeliness metrics, adjusted length of stay, and in‐hospital mortality were similar across all resource levels. Conclusions: Significant variation exists in regional availability of healthcare resources for acute ischemic stroke treatment, yet among Get With the Guidelines‐Stroke hospitals, quality of care and in‐hospital outcomes did not differ by regional resource availability

The pore structure and gating mechanism of K2P channels

K2P potassium channels are important regulators of cellular excitability. This study reveals that in contrast to most other K+ channels the primary gating mechanism in the K2P channel TREK-1 does not involve opening and closure of the cytoplasmic bundle crossing, but takes place close to or within the selectivity filter

GWTC-1: A Gravitational-Wave Transient Catalog of Compact Binary Mergers Observed by LIGO and Virgo during the First and Second Observing Runs

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1 Ma™ during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6-0.7+3.2 Mâ™ and 84.4-11.1+15.8 Mâ™ and range in distance between 320-110+120 and 2840-1360+1400 Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110-3840 Gpc-3 y-1 for binary neutron stars and 9.7-101 Gpc-3 y-1 for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610 Gpc-3 y-1. © 2019 authors. Published by the American Physical Society

A US perspective on closing the carbon cycle to defossilize difficult-to-electrify segments of our economy

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets