Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)

Infrared Eclipses of the Strongly Irradiated Planet WASP-33b, and Oscillations of its Host Star

We observe two secondary eclipses of the strongly irradiated transiting planet WASP-33b in the Ks band, and one secondary eclipse each at 3.6- and 4.5 microns using Warm Spitzer. This planet orbits an A5V delta-Scuti star that is known to exhibit low amplitude non-radial p-mode oscillations at about 0.1-percent semi-amplitude. We detect stellar oscillations in all of our infrared eclipse data, and also in one night of observations at J-band out of eclipse. The oscillation amplitude, in all infrared bands except Ks, is about the same as in the optical. However, the stellar oscillations in Ks band have about twice the amplitude as seen in the optical, possibly because the Brackett-gamma line falls in this bandpass. We use our best-fit values for the eclipse depth, as well as the 0.9 micron eclipse observed by Smith et al., to explore possible states of the exoplanetary atmosphere, based on the method of Madhusudhan and Seager. On this basis we find two possible states for the atmospheric structure of WASP-33b. One possibility is a non-inverted temperature structure in spite of the strong irradiance, but this model requires an enhanced carbon abundance (C/O>1). The alternative model has solar composition, but an inverted temperature structure. Spectroscopy of the planet at secondary eclipse, using a spectral resolution that can resolve the water vapor band structure, should be able to break the degeneracy between these very different possible states of the exoplanetary atmosphere. However, both of those model atmospheres absorb nearly all of the stellar irradiance with minimal longitudinal re-distribution of energy, strengthening the hypothesis of Cowan et al. that the most strongly irradiated planets circulate energy poorly. Our measurement of the central phase of the eclipse yields e*cos(omega)=0.0003 +/-0.00013, which we regard as being consistent with a circular orbit.Comment: 23 pages, 9 figures, 3 tables, accepted for the Astrophysical Journa

Know the Star, Know the Planet. II. Speckle Interferometry of Exoplanet Host Stars

A study of the host stars to exoplanets is important to understanding their environment. To that end, we report new speckle observations of a sample of exoplanet host primaries. The bright exoplanet host HD 8673 (= HIP 6702) is revealed to have a companion, although at this time we cannot definitively establish the companion as physical or optical. The observing lists for planet searches and for these observations have for the most part been pre-screened for known duplicity, so the detected binary fraction is lower than what would otherwise be expected. Therefore, a large number of double stars were observed contemporaneously for verification and quality control purposes, to ensure the lack of detection of companions for exoplanet hosts was valid. In these additional observations, ten pairs are resolved for the first time and sixty pairs are confirmed. These observations were obtained with the USNO speckle camera on the NOAO 4m telescopes at both KPNO and CTIO from 2001 to 2010.Comment: 2 figures, 3 table

An adaptive agent model for analysing co-evolution of management and policies in a complex rangeland system

This paper describes an adaptive agent model of rangelands based on concepts of complex adaptive systems. The behavioural and biological processes of pastoralists, regulators, livestock, grass and shrubs are modelled as well as the interactions between these components. The evolution of the rangeland system is studied under different policy and institutional regimes that affect the behaviour and learning of pastoralists, and hence the state of the ecological system. Adaptive agent models show that effective learning and effective ecosystem management do not necessarily coincide and can suggest potentially useful alternatives to the design of policies and institutions. (C) 2000 Elsevier Science B.V

Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program

The James Webb Space Telescope will revolutionize transiting exoplanet atmospheric science due to its capability for continuous, long-duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful future transiting exoplanet characterization programs. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed "community targets") that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations.(Abridged)Comment: This is a white paper that originated from an open discussion at the Enabling Transiting Exoplanet Science with JWST workshop held November 16 - 18, 2015 at STScI (http://www.stsci.edu/jwst/science/exoplanets). Accepted for publication in PAS

Systematic adjudication of myocardial infarction end-points in an international clinical trial

BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. CONCLUSIONS: End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates