The on-axis view of GRB 170817A

The peculiar short gamma-ray burst GRB 170817A has been firmly associated to the gravitational wave event GW170817, which has been unaninmously interpreted as due to the coalescence of a double neutron star binary. The unprecedented behaviour of the non-thermal afterglow led to a debate about its nature, which was eventually settled by high-resolution VLBI observations, which strongly support the off-axis structured jet scenario. Using information on the jet structure derived from multi-wavelength fitting of the afterglow emission and of the apparent VLBI image centroid motion, we compute the appearance of a GRB 170817A-like jet as seen by an on-axis observer and we compare it to the previously observed population of SGRB afterglows and prompt emission events. We find that the intrinsic properties of the GRB 170817A jet are representative of a typical event in the SGRB population, hinting at a quasi-universal jet structure. The diversity in the SGRB afterglow population could therefore be ascribed in large part to extrinsic (redshift, density of the surrounding medium, viewing angle) rather than intrinsic properties. Although more uncertain, the comparison can be extended to the prompt emission properties, leading to similar conclusions.Comment: 9 pages, 3 figures, submitted to A&A. Comments and suggestions are welcom

The magnetospheric radius of an inclined rotator in the magnetically threaded disk model

The estimate of the magnetospheric radius in a disk-fed neutron star X-ray binary is a long standing problem in high energy Astrophysics. We review the magnetospheric radius calculations in the so-called magnetically threaded disk model, comparing the simplified approach originally proposed by Ghosh & Lamb (1979) with the revised version proposed by Wang (1987), Wang (1995), and Wang (1997). We show that for a given set of fixed parameters (assuming also a comparable screening factor of the neutron star magnetic field by the currents induced on the disk surface) the revised magnetically threaded disk model predicts a magnetospheric radius that is significantly smaller than that derived from the Ghosh & Lamb (1979) treatment. For a fixed value of the neutron star magnetic field and a wide range of mass accretion rates, the inclusion of a large inclination angle between the neutron star rotation and magnetic field axes ($\chi$$\gtrsim$60 deg) leads to a further decrease of the magnetospheric radius. To illustrate the relevance of these calculations, we consider, as an example, the case of the transitional pulsars. During the so-called "high mode" of their sub-luminous accretion disk state, these sources have shown X-ray pulsations interpreted as due to accretion at an unprecedented low luminosity level compared to other neutron stars in X-ray binaries. In the context of the magnetic threaded disk model, we show that accretion at luminosities of $\sim$10$^{33}$ erg s$^{-1}$ (and thus accretion-driven X-ray pulsations) can be more easily explained when the prescription of the magnetospheric radius provided by Wang (1997) is used. This avoids the need of invoking very strong propeller outflows in the transitional pulsars, as proposed in other literature works.Comment: Accepted for publication in A&

Gamma-ray burst jet propagation, development of angular structure, and the luminosity function

The fate and observable properties of gamma-ray burst jets depend crucially on their interaction with the progenitor material that surrounds the central engine. We present a semi-analytical model of such interaction, which builds upon several previous analytical and numerical works, aimed at predicting the angular distribution of jet and cocoon energy and Lorentz factor after breakout, given the properties of the ambient material and of the jet at launch. Using this model, we construct synthetic populations of structured jets, assuming either a collapsar (for long gamma-ray bursts -- LGRBs) or a binary neutron star merger (for short gamma-ray bursts -- SGRBs) as progenitor. We assume all progenitors to be identical, and we allow little variability in the jet properties at launch: our populations therefore feature a quasi-universal structure. These populations are able to reproduce the main features of the observed LGRB and SGRB luminosity functions, although several uncertainties and caveats remain to be addressed.Comment: 15 pages, 12 figures. Revised version, submitted to A&A (several new figures and expanded discussion. Conclusions unchanged). Comments and suggestions are welcome

Poly(N-isopropylacrylamide-co-N-vinylpyrrolidone) thermoresponsive microspheres: The low drug loading ensures the pulsatile release mechanism

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Structural bases for substrate and inhibitor recognition by matrix metaloproteinases

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases which are involved in the proteolytic processing of several components of the extracellular matrix. As a consequence, MMPs are implicated in several physiological and pathological processes, like skeletal growth and remodelling, wound healing, cancer, arthritis, and multiple sclerosis, raising a very widespread interest toward this class of enzymes as potential therapeutic targets. Here, structure-function relationships are discussed to highlight the role of different MMP domains on substrate/inhibitor recognition and processing and to attempt the formulation of advanced guidelines, based on natural substrates, for the design of inhibitors more efficient in vivo. © 2008 Bentham Science Publishers Ltd

Pathophysiologic risk stratification of chronic heart failure: coexisting left atrial and right ventricular damage and the role of pulmonary circulation

Abstract Funding Acknowledgements Type of funding sources: None. Background in heart failure with reduced ejection fraction (HFrEF) the chronic increase of filling pressures progressively involves left atrium (LA), pulmonary circulation (PC) and right ventricle (RV), leading to worse outcome. Purpose we investigated the prognostic impact of either isolate LA impairment, RV dysfunction combined with pulmonary hypertension, or both, in HFrEF, using basic and advanced echocardiography. Methods 106 outpatients with HFrEF were enrolled. Exclusion criteria were primary lung disease, non-sinus rhythm, previous cardiac surgery, poor acoustic window. Clinical examination and basic echocardiography were performed. Speckle tracking analysis was used to measure peak atrial longitudinal strain (PALS) and a new marker of interaction between RV and PC: absolute free wall RV longitudinal strain(fwRVLS)/systolic pulmonary artery pressure(sPAP). Patients were followed for all-cause or cardiovascular death and heart failure (HF) hospitalization. Results of 84 eligible patients [mean age: 60.1 ± 11.5; 82% male, mean left ventricular ejection fraction (LV EF) 28 ± 5%], 48 reached the combined endpoint. Population was divided into 3 groups: Group 1 [PALS≥15 and fwRVLS/sPAP ≤ 0.5]; Group 2 [PALS ≤ 15 and fwRVLS/sPAP ≤ 0.5 or PALS≥15 and fwRVLS/sPAP≥0.5]; Group 3 [PALS ≤ 15 and fwRVLS/sPAP≥0.5]. Mean follow-up was 3.5 ± 0.3years. The increasing severity groups were associated with higher LA volume index (LAVI), New York Heart Association (NYHA) class, mitral regurgitation (MR) and tricuspid regurgitation (TR) grades, lower LV EF, LV global longitudinal strain (GLS), PALS, tricuspid annular plane systolic excursion (TAPSE), sPAP, fwRVLS and global RVLS(p < 0.0001). Reduced PALS and fwRVLS/sPAP were independent predictors of NYHA > 2 at univariate and multivariate analysis adjusted for age, sex, LV EF, and of any events with adjusted Cox models (Table 1). Kaplan-Meier curves showed a clear divergence between the groups for the prediction of the combined endpoint (Fig.1), cardiovascular death and HF hospitalization. Conclusions the combination of LA and RV damage could represent the transition point to end-stage HF, with considerably worse prognosis. Its assessment with PALS and fwRVLS/sPAP could help risk stratification of HFrEF patients in order to provide early treatment. Table 1 Unadjusted hazard ratio [95% CI] Adjusted for GLS hazard ratio [95% CI] Adjusted for GLS, LAVi, TR, RVFAC hazard ratio [95% CI] Group 3 vs 1 10.61 [4.16-27.06], p < 0.0001 10.24 [3.49-30.02], p < 0.0001 9.54 [2.95-30.92], p = 0.0002 Group 3 vs 2 3.90 [1.92-7.93], p = 0.0002 3.82 [1.74-8.36], p = 0.0008 3.78 [1.66-8.61], p = 0.002 Group 2 vs 1 2.72 [1.03-7.20], p = 0.04 2.69 [0.99-7.25], p = 0.05 2.53 [0.84-7.58], p = 0.1 CI, confidence interval; EF, ejection fraction; GLS, global longitudinal strain;LAVI, left atrial volume index; MR, mitral regurgitation, TR, tricuspid regurgitation Abstract Figure. Fig.

The rise and fall of the high-energy afterglow emission of GRB 180720B

The Gamma Ray Burst (GRB) 180720B is one of the brightest events detected by the Fermi satellite and the first GRB detected by the H.E.S.S. telescope above 100 GeV. We analyse the Fermi (GBM and LAT) and Swift (XRT and BAT) data and describe the evolution of the burst spectral energy distribution in the 0.5 keV - 10 GeV energy range over the first 500 seconds of emission. We reveal a smooth transition from the prompt phase, dominated by synchrotron emission in a moderately fast cooling regime, to the afterglow phase whose emission has been observed from the radio to the GeV energy range. The LAT (0.1 - 100 GeV) light curve initially rises ($F_{\rm LAT}\propto t^{2.4}$), peaks at $\sim$78 s, and falls steeply ($F_{\rm LAT}\propto t^{-2.2}$) afterwards. The peak, which we interpret as the onset of the fireball deceleration, allows us to estimate the bulk Lorentz factor $\Gamma_{0}\sim 150 \ (300)$ under the assumption of a wind-like (homogeneous) circum-burst medium density. We derive a flux upper limit in the LAT energy range at the time of H.E.S.S. detection, but this does not allow us to unveil the nature of the high energy component observed by H.E.S.S. We fit the prompt spectrum with a physical model of synchrotron emission from a non-thermal population of electrons. The 0 - 35 s spectrum after its $E F(E)$ peak (at 1 - 2 MeV) is a steep power law extending to hundreds of MeV. We derive a steep slope of the injected electron energy distribution $N(\gamma)\propto \gamma^{-5}$. Our fit parameters point towards a very low magnetic field ($B'\sim 1$ G) in the emission region.Comment: 10 pages, 6 figures, submitted to A&

Growth and glycemic control in children with type 1 diabetes and asymptomatic celiac disease treated with a gluten -free diet for 1 year

To compare growth and glycemic control in children with type 1 diabetes and silent celiac disease treated with a gluten-free diet for 1 year with those of similar age and gender with type 1 diabetes but without celiac disease, 16 type 1 diabetes patients with silent celiac disease were enrolled and each celiac disease-positive case was matched for age, sex, and duration of diabetes with two type 1 diabetes controls with negative serologic markers of celiac disease. All 16 children with positive celiac disease serology had histologic features consistent with celiac disease despite the absence of symptoms. The mean growth and metabolic control values were similar between children with type 1 diabetes and celiac disease and those with type 1 diabetes but without celiac disease. This study seems to suggest that the early diagnosis of celiac disease and initiation of a gluten-free diet may prevent further deterioration in the nutritional status of children with type 1 diabetes and celiac disease and may reduce the prospect of celiac disease complications without any impact on type 1 diabetes control

Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects

Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies