Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

The RESOLVE Survey Atomic Gas Census and Environmental Influences on Galaxy Gas Reservoirs

We present the H i mass inventory for the REsolved Spectroscopy Of a Local VolumE (RESOLVE) survey, a volume-limited, multi-wavelength census of >1500 z = 0 galaxies spanning diverse environments and complete in baryonic mass down to dwarfs of ~109 ${M}_{\odot }$. This first 21 cm data release provides robust detections or strong upper limits (1.4M H i 1012 ${M}_{\odot }$) halos, suggesting that gas stripping and/or starvation may be induced by interactions with larger halos or the surrounding cosmic web. We find that the detailed relationship between G/S and environment varies when we examine different subvolumes of RESOLVE independently, which we suggest may be a signature of assembly bias

Application of chemometric analysis to infrared spectroscopy for the identification of wood origin

Chemical characteristics of wood are used in this study for plant taxonomy classification based on the current Angiosperm Phylogeny Group classification (APG III System) for the division, class and subclass of woody plants. Infrared spectra contain information about the molecular structure and intermolecular interactions among the components in wood but the understanding of this information requires multivariate techniques for the analysis of highly dense datasets. This article is written with the purposes of specifying the chemical differences among taxonomic groups, and predicting the taxa of unknown samples with a mathematical model. Principal component analysis, t-test, stepwise discriminant analysis and linear discriminant analysis, were some of the chosen multivariate techniques. A procedure to determine the division, class, subclass and order of unknown samples was built with promising implications for future applications of Fourier Transform Infrared spectroscopy in wood taxonomy classification

Strongly exchange-coupled triplet pairs in an organic semiconductor

From biological complexes to devices based on organic semiconductors, spin interactions play a key role in the function of molecular systems. For instance, triplet-pair reactions impact operation of organic light-emitting diodes as well as photovoltaic devices. Conventional models for triplet pairs assume they interact only weakly. Here, using electron spin resonance, we observe long-lived, strongly-interacting triplet pairs in an organic semiconductor, generated via singlet fission. Using coherent spin-manipulation of these two-triplet states, we identify exchange-coupled (spin-2) quintet complexes co-existing with weakly coupled (spin-1) triplets. We measure strongly coupled pairs with a lifetime approaching 3 µs and a spin coherence time approaching 1 µs, at 10 K. Our results pave the way for the utilization of high-spin systems in organic semiconductors.Gates-Cambridge Trust, Winton Programme for the Physics of Sustainability, Freie Universität Berlin within the Excellence Initiative of the German Research Foundation, Engineering and Physical Sciences Research Council (Grant ID: EP/G060738/1)This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nphys3908

Cost-effectiveness of minimal interventional procedures for chronic mechanical low back pain: design of four randomised controlled trials with an economic evaluation

Background: Minimal interventional procedures are frequently applied in patients with mechanical low back pain which is defined as pain presumably resulting from single sources: facet, disc, sacroiliac joint or a combination of these. Usually, these minimal interventional procedures are an integral part of a multidisciplinary pain programme. A recent systematic review issued by the Dutch Health Insurance Council showed that the effectiveness of these procedures for the total group of patients with chronic low back pain is yet unclear and cost-effectiveness unknown. The aim of the study is to evaluate whether a multidisciplinary pain programme with minimal interventional procedures is cost-effective compared to the multidisciplinary pain programme alone for patients with chronic mechanical low back pain who did not respond to conservative primary care and were referred to a pain clinic. Methods. All patients with chronic low back pain who are referred to one of the 13 participating pain clinics will be asked to participate in an observational study. Patients with a suspected diagnosis of facet, disc or sacroiliac joint problems will receive a diagnostic block to confirm this diagnosis. If confirmed, they will be asked to participate in a Randomized Controlled Trial (RCT). For each single source a separate RCT will be conducted. Patients with a combination of facet, disc or sacroiliac joint problems will be invited for participation in a RCT as well. An economic evaluation from a societal perspective will be performed alongside these four RCTs. Patients will complete questionnaires at baseline, 3 and 6 weeks, 3, 6, 9 and 12 months after start of the treatment

Adolescent Female Text Messaging Preferences to Prevent Pregnancy After an Emergency Department Visit: A Qualitative Analysis

Background: Over 15 million adolescents use the emergency department (ED) each year in the United States. Adolescent females who use the ED for medical care have been found to be at high risk for unintended pregnancy. Given that adolescents represent the largest users of text messaging and are receptive to receiving text messages related to their sexual health, the ED visit represents an opportunity for intervention. Objective: The aim of this qualitative study was to explore interest in and preferences for the content, frequency, and timing of an ED-based text message intervention to prevent pregnancy for adolescent females. Methods: We conducted semistructured, open-ended interviews in one urban ED in the United States with adolescent females aged 14-19 years. Eligible subjects were adolescents who were sexually active in the past 3 months, presented to the ED for a reproductive health complaint, owned a mobile phone, and did not use effective contraception. Using an interview guide, enrollment continued until saturation of key themes. The investigators designed sample text messages using the Health Beliefs Model and participants viewed these on a mobile phone. The team recorded, transcribed, and coded interviews based on thematic analysis using the qualitative analysis software NVivo and Excel. Results: Participants (n=14) were predominantly Hispanic (13/14; 93%), insured (13/14; 93%), ED users in the past year (12/14; 86%), and frequent text users (10/14; 71% had sent or received >30 texts per day). All were interested in receiving text messages from the ED about pregnancy prevention, favoring messages that were “brief,” “professional,” and “nonaccusatory.” Respondents favored texts with links to websites, repeated information regarding places to receive “confidential” care, and focused information on contraception options and misconceptions. Preferences for text message frequency varied from daily to monthly, with random hours of delivery to maintain “surprise.” No participant feared that text messages would violate her privacy. Conclusions: Adolescent female patients at high pregnancy risk are interested in ED-based pregnancy prevention provided by texting. Understanding preferences for the content, frequency, and timing of messages can guide in designing future interventions in the ED

A bootstrap approach for assessing the uncertainty of outcome probabilities when using a scoring system

Background: Scoring systems are a very attractive family of clinical predictive models, because the patient score can be calculated without using any data processing system. Their weakness lies in the difficulty of associating a reliable prognostic probability with each score. In this study a bootstrap approach for estimating confidence intervals of outcome probabilities is described and applied to design and optimize the performance of a scoring system for morbidity in intensive care units after heart surgery. Methods: The bias-corrected and accelerated bootstrap method was used to estimate the 95% confidence intervals of outcome probabilities associated with a scoring system. These confidence intervals were calculated for each score and each step of the scoring-system design by means of one thousand bootstrapped samples. 1090 consecutive adult patients who underwent coronary artery bypass graft were assigned at random to two groups of equal size, so as to define random training and testing sets with equal percentage morbidities. A collection of 78 preoperative, intraoperative and postoperative variables were considered as likely morbidity predictors. Results: Several competing scoring systems were compared on the basis of discrimination, generalization and uncertainty associated with the prognostic probabilities. The results showed that confidence intervals corresponding to different scores often overlapped, making it convenient to unite and thus reduce the score classes. After uniting two adjacent classes, a model with six score groups not only gave a satisfactory trade-off between discrimination and generalization, but also enabled patients to be allocated to classes, most of which were characterized by well separated confidence intervals of prognostic probabilities. Conclusions: Scoring systems are often designed solely on the basis of discrimination and generalization characteristics, to the detriment of prediction of a trustworthy outcome probability. The present example demonstrates that using a bootstrap method for the estimation of outcome-probability confidence intervals provides useful additional information about score-class statistics, guiding physicians towards the most convenient model for predicting morbidity outcomes in their clinical context

Accelerating Community College Graduation Rates: A Benefit–Cost Analysis

This article reports a benefit–cost evaluation of the Accelerated Study in Associate Programs (ASAP) of the City University of New York (CUNY). ASAP was designed to accelerate associate degree completion within 3 years of degree enrollment at CUNY’s community colleges. The program evaluation revealed that the completion rate for the examined cohort increased from 24.1% to 54.9%, and cost per graduate declined considerably (Levin & Garcia, 2012; Linderman & Kolenovic, 2012). The returns on investment to the taxpayer include the benefits from higher tax revenues and lower costs of spending on public health, criminal justice, and public assistance. For each dollar of investment in ASAP by taxpayers, the return was $3 to$4. For each additional graduate, the taxpayer gained an amount equal to a certificate of deposit with a value of $146,000 (net of the costs of the investment). Based on these estimated returns, a cohort of 1,000 students enrolled in ASAP would generate net fiscal benefits for the taxpayer of more than$46 million relative to enrolling in the conventional degree program. ASAP results demonstrate that an effective educational policy can generate returns to the taxpayer that vastly exceed the public investment required