Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk

Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D. Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded. Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. Results: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 – 0.90). Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk. ---------------------------7dc3521430776 Content-Disposition: form-data; name="c14_creators_1_name_family" Halke

Spatially resolved XMM-Newton analysis and a model of the nonthermal emission of MSH 15-52

We present an X-ray analysis and a model of the nonthermal emission of the pulsar wind nebula (PWN) MSH15-52. We analyzed XMM-Newton data to obtain the spatially resolved spectral parameters around the pulsar PSRB1509-58. A steepening of the fitted power-law spectra and decrease in the surface brightness is observed with increasing distance from the pulsar. In the second part of this paper, we introduce a model for the nonthermal emission, based on assuming the ideal magnetohydrodynamic limit. This model is used to constrain the parameters of the termination shock and the bulk velocity of the leptons in the PWN. Our model is able to reproduce the spatial variation of the X-ray spectra. The parameter ranges that we found agree well with the parameter estimates found by other authors with different approaches. In the last part of this paper, we calculate the inverse Compton emission from our model and compare it to the emission detected with the H.E.S.S. telescope system. Our model is able to reproduce the flux level observed with H.E.S.S., but not the spectral shape of the observed TeV {\gamma}-ray emission.Comment: Accepted for publication in A&A, 9 pages, 15 figure

Six Years of Chandra Observations of Supernova Remnants

We present a review of the first six years of Chandra X-ray Observatory observations of supernova remnants. From the official "first-light" observation of Cassiopeia A that revealed for the first time the compact remnant of the explosion, to the recent million-second spectrally-resolved observation that revealed new details of the stellar composition and dynamics of the original explosion, Chandra observations have provided new insights into the supernova phenomenon. We present an admittedly biased overview of six years of these observations, highlighting new discoveries made possible by Chandra's unique capabilities.Comment: 82 pages, 28 figures, for the book Astrophysics Update

Detection of the energetic pulsar PSR B1509-58 and its pulsar wind nebula in MSH 15-52 using the Fermi-Large Area Telescope

We report the detection of high energy gamma-ray emission from the young and energetic pulsar PSR B1509$-$58 and its pulsar wind nebula (PWN) in the composite supernova remnant SNR G320.4-1.2 (aka MSH 15-52). Using 1 year of survey data with the Fermi-Large Area Telescope (LAT), we detected pulsations from PSR B1509-58 up to 1 GeV and extended gamma-ray emission above 1 GeV spatially coincident with the PWN. The pulsar light curve presents two peaks offset from the radio peak by phases 0.96 $\pm$ 0.01 and 0.33 $\pm$ 0.02. New constraining upper limits on the pulsar emission are derived below 1 GeV and confirm a severe spectral break at a few tens of MeV. The nebular spectrum in the 1 - 100 GeV energy range is well described by a power-law with a spectral index of (1.57 $\pm$ 0.17 $\pm$ 0.13) and a flux above 1 GeV of (2.91 $\pm$ 0.79 $\pm$ 1.35) 10^{-9} cm^{-2} s^{-1}. The first errors represent the statistical errors on the fit parameters, while the second ones are the systematic uncertainties. The LAT spectrum of the nebula connects nicely with Cherenkov observations, and indicates a spectral break between GeV and TeV energies.Comment: 14 pages, 6 figures, accepted for publication by Ap

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Limits to scale invariance in alluvial rivers

Assumptions about fluvial processes and process–form relations are made in general models and in many site‐specific applications. Many standard assumptions about reach‐scale flow resistance, bed‐material entrainment thresholds and transport rates, and downstream hydraulic geometry involve one or other of two types of scale invariance: a parameter (e.g. critical Shields number) has the same value in all rivers, or doubling one variable causes a fixed proportional change in another variable in all circumstances (e.g. power‐law hydraulic geometry). However, rivers vary greatly in size, gradient, and bed material, and many geomorphologists regard particular types of river as distinctive. This review examines the tension between universal scaling assumptions and perceived distinctions between different types of river. It identifies limits to scale invariance and departures from simple scaling, and illustrates them using large data sets spanning a wide range of conditions. Scaling considerations and data analysis support the commonly made distinction between coarse‐bed and fine‐bed reaches, whose different transport regimes can be traced to the different settling‐velocity scalings for coarse and fine grains. They also help identify two end‐member sub‐types: steep shallow coarse‐bed ‘torrents’ with distinctive flow‐resistance scaling and increased entrainment threshold, and very large, low‐gradient ‘mega rivers’ with predominantly suspended load, subdued secondary circulation, and extensive backwater conditions

The 2009 multiwavelength campaign on Mrk 421: Variability and correlation studies

We performed a 4.5-month multi-instrument campaign (from radio to VHE gamma rays) on Mrk421 between January 2009 and June 2009, which included VLBA, F-GAMMA, GASP-WEBT, Swift, RXTE, Fermi-LAT, MAGIC, and Whipple, among other instruments and collaborations. Mrk421 was found in its typical (non-flaring) activity state, with a VHE flux of about half that of the Crab Nebula, yet the light curves show significant variability at all wavelengths, the highest variability being in the X-rays. We determined the power spectral densities (PSD) at most wavelengths and found that all PSDs can be described by power-laws without a break, and with indices consistent with pink/red-noise behavior. We observed a harder-when-brighter behavior in the X-ray spectra and measured a positive correlation between VHE and X-ray fluxes with zero time lag. Such characteristics have been reported many times during flaring activity, but here they are reported for the first time in the non-flaring state. We also observed an overall anti-correlation between optical/UV and X-rays extending over the duration of the campaign. The harder-when-brighter behavior in the X-ray spectra and the measured positive X-ray/VHE correlation during the 2009 multi-wavelength campaign suggests that the physical processes dominating the emission during non-flaring states have similarities with those occurring during flaring activity. In particular, this observation supports leptonic scenarios as being responsible for the emission of Mrk421 during non-flaring activity. Such a temporally extended X-ray/VHE correlation is not driven by any single flaring event, and hence is difficult to explain within the standard hadronic scenarios. The highest variability is observed in the X-ray band, which, within the one-zone synchrotron self-Compton scenario, indicates that the electron energy distribution is most variable at the highest energies.Comment: Accepted for publication in A&A, 18 pages, 14 figures (v2 has a small modification in the acknowledgments, and also corrects a typo in the field "author" in the metadata

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July