One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Increased particle emissions from early fuel injection timing Diesel low temperature combustion

A clean premixed Diesel combustion strategy, called low temperature combustion (LTC), was able to achieve very low nitrogen oxide emissions (<35 ppm) through use of exhaust gas recirculation (12.1% inlet oxygen), and reduced particulate matter (PM) emissions (<0.05 FSN) through advanced fuel injection timing (-24°aTDC). When varying the injection timing by relatively small increments, large changes in PM mass and number emissions were measured within the premixed LTC regime. A discrepancy is investigated between expected reductions in PM emissions by simple fuel-air premixing and combustion temperature metrics, and actual PM emissions measurements when advancing the fuel injection timing earlier than -24°aTDC. For these earlier injection timings, particle numbers were seen to increase in two distinct particle size modes, whereas only one particle size mode existed at the minimum PM emissions -24°aTDC injection timing. Additional parameters from a 1D free fuel spray model were used to suggest new information that could explain the cause of these unexpected increases in PM. Using 0D and 1D calculations, the engine-out particle size and number emissions are analyzed to better understand their sensitivity to changes in the fuel injection timing within the early injection timing LTC regime. © 2011 Elsevier Ltd. All rights reserved.The authors sincerely thank Gabriel Alcantarilla, Rogerio Jorge Amorim, Simon Arthozoul, and Sara Goska for their great assistance in experimental data collection and post-analysis. The authors wish to acknowledge the Generalitat Valenciana for the financial support through the project GVA PROMETEO CMT 2010 (reference code: GR001/2009/00167539). Financial support of Christopher Kolodziej's research was provided by the Spanish Ministry of Education. This publication comes from a portion of the doctoral thesis work of Christopher Kolodziej.Benajes Calvo, JV.; García Oliver, JM.; Novella Rosa, R.; Kolodziej, CP. (2012). Increased particle emissions from early fuel injection timing Diesel low temperature combustion. Fuel. 94(1):184-190. https://doi.org/10.1016/j.fuel.2011.09.014S18419094

Scientific Opportunities with an X-ray Free-Electron Laser Oscillator

An X-ray free-electron laser oscillator (XFELO) is a new type of hard X-ray source that would produce fully coherent pulses with meV bandwidth and stable intensity. The XFELO complements existing sources based on self-amplified spontaneous emission (SASE) from high-gain X-ray free-electron lasers (XFEL) that produce ultra-short pulses with broad-band chaotic spectra. This report is based on discussions of scientific opportunities enabled by an XFELO during a workshop held at SLAC on June 29 - July 1, 2016Comment: 21 pages, 12 figure

Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury

This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI). MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B (MMP-9), in the acutely injured cord contributes to disruption of the blood-spinal cord barrier, and the influx of leukocytes into the injured cord, as well as apoptosis. MMP-9 and MMP-2 regulate inflammation and neuropathic pain after peripheral nerve injury and may contribute to SCI-induced pain. Early pharmacologic inhibition of MMPs or the gelatinases (MMP-2 and MMP-9) results in an improvement in long-term neurological recovery and is associated with reduced glial scarring and neuropathic pain. During wound healing, gelatinase A (MMP-2) plays a critical role in limiting the formation of an inhibitory glial scar, and mice that are genetically deficient in this protease showed impaired recovery. Together, these findings illustrate complex, temporally distinct roles of MMPs in SCIs. As early gelatinase activity is detrimental, there is an emerging interest in developing gelatinase-targeted therapeutics that would be specifically tailored to the acute injured spinal cord. Thus, we focus this review on the development of selective gelatinase inhibitors

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Shape-Shifting Micro- and Nanopatterns Controlled by Temperature

Herein, features that alter their shape to form a different pattern upon an external trigger are described. Electron-beam lithography was used to fabricate micrometer- and nanometer-sized surface immobilized poly­(triethylene glycol methacrylate) (pTEGMA) that exhibits significant thermal responsivity; the resulting hydrogels collapsed by up to 95% of their height upon addition of heat. Multicomponent features composed of both the thermoresponsive polymer and nonresponsive poly­(ethylene glycol) (PEG) were then prepared. Upon increase in temperature, only the thermally responsive component of the pattern collapsed, causing a significant and predictable alteration in the overall pattern. Reversible micrometer- and nanometer-sized square-to-triangles, squares-to-checkerboards, smiles-to-neutral face, and zeros-to-ones shapes were shown

Tobacco Addiction and Psychological Co-morbidities

Nicotine dependence is a psychiatric disorder characterized by a recurrent, periodic compulsion to use tobacco due to neurophysiological, psychological, and social factors. This disorder has behavioral and physiological characteristics that are similar to those of other addictions, but also unique aspects that require special attention because of its ubiquity on a global scale, its staggering effects on rates of morbidity and mortality, and its high prevalence of psychological comorbidities, including psychiatric disorders. Our chapter focuses on the epidemiology of comorbid nicotine dependence and psychiatric disorders, the underlying biobehavioral mechanisms of comorbidity, cultural factors, psychiatric disorders most often associated with nicotine dependence, and treatment approaches. While there is a need for ongoing studies to more clearly delineate the best treatment interventions for persons with comorbid psychiatric disorders and nicotine dependence, the evidence to date suggests use of all of the medication, behavioral, and peer-support approaches available. Culture changes are needed in mental health and addiction treatment settings to continue to improve access to effective interventions for persons with nicotine dependence and psychological comorbidities

Detection and Quantification of Metastable Photoproducts of Trenbolone and Altrenogest Using Liquid Chromatography–tandem Mass Spectrometry

Here, we developed a novel and sensitive method for the detection and quantification of metastable trenbolone and altrenogest photoproducts in agricultural receiving waters based on solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC–MS/MS). Primary method analytes were seven cycloaddition or photohydration transformation products of 17α-trenbolone (17α-TBOH), 17β-trenbolone (17β-TBOH), trendione (TBO), and altrenogest (ALT), which are key contributors to the fate and environmental risks of these steroidal pharmaceuticals. Because commercial analytical standards are not available, reference standards for photoproducts were generated from trenbolone or ALT with a solar simulator (˜6 h, \u3e10 half-lives). Efficient detection of metastable photoproducts required cold and pH neutral conditions, rapid sample processing, minimal sample storage, and consideration of cationic artifacts. Method detection limits (MDLs) were 0.034-0.40 ng L−1 for parent compounds and 0.16–2.1 ng L−1 for photoproducts, sufficient for their detection in agroecosystems. Matrix suppression was observed and corrected by internal standards, and relative recovery rates were near 100% for all analytes except for 12-OH-17α-TBOH (˜75% recovery). Intra-day variation was \u3c20% and inter-day variation \u3c25% for all the analytes. The developed method is capable of the analysis of trenbolone, altrenogest, and their key bioactive photoproducts in agricultural receiving waters