Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine

Background: Calcitonin gene–related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks. Methods: In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential adaptive treatment-assignment design was used to minimize the number of patients exposed. Results: The 2.5-mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain-free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events. Conclusions: The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine

Dynamics and gravitational wave signature of collapsar formation

We perform 3+1 general relativistic simulations of rotating core collapse in the context of the collapsar model for long gamma-ray bursts. We employ a realistic progenitor, rotation based on results of stellar evolution calculations, and a simplified equation of state. Our simulations track self-consistently collapse, bounce, the postbounce phase, black hole formation, and the subsequent early hyperaccretion phase. We extract gravitational waves from the spacetime curvature and identify a unique gravitational wave signature associated with the early phase of collapsar formatio

Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial

<p><b>Background and Purpose:</b> NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke. We conducted analyses on additional end points and sensitivity analyses to confirm our findings.</p> <p><b>Methods:</b> We randomized 1722 patients with acute ischemic stroke to a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours of stroke onset. The primary outcome was disability at 90 days, as measured by the modified Rankin Scale (mRS), a 6-point scale ranging from 0 (no residual symptoms) to 5 (bed-bound, requiring constant care). Additional and exploratory analyses included mRS at 7 and 30 days; subgroup interactions with final mRS; assessments of activities of daily living by Barthel index; and National Institutes of Health Stroke Scale (NIHSS) neurological scores at 7 and 90 days.</p> <p><b>Results:</b> NXY-059 significantly improved the distribution of the mRS disability score compared with placebo at 7, 30, and 90 days (Cochran-Mantel-Haenszel test P=0.002, 0.004, 0.038, respectively; 90-day common odds ratio 1.20; 95% CI, 1.01 to 1.42). The benefit was not attributable to any specific baseline characteristic, stratification variable or subgroup interaction. Neurological scores were improved at 7 days (odds ratio [OR], 1.46; 95% CI, 1.13, 1.89; P=0.003) and the Barthel index was improved at 7 and 30 days (OR, 1.55; 95% CI, 1.22, 1.98; P<0.0001; OR, 1.27; 95% CI, 1.01, 1.59; P=0.02).</p> <p><b>Conclusions:</b> NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. Benefit on neurological scores and activities of daily living was detectable early but not significant at 90 days; however, our trial was underpowered to measure effects on the neurological examination. The benefit on disability is not confounded by interactions and is supported by other outcome measures.</p&gt

Conseil-santé dans la médecine de premier recours, partie 2

Les maladies non transmissibles (MNT, en anglais «non-communicable diseases») ont gagné du terrain dans le monde entier. Les approches de conseil fourni au cabinet médical ont déjà été présentées dans un premier article. Le présent article se consacre aux conditions permettant à ces approches de déployer leur efficacité au niveau de la population. Ceci est illustré sur la base des programmes suisses actuels «Vivre sans tabac», PAPRICA et «Coaching Santé» ainsi que de l’exemple historique «Ça débouche sur quoi?»

A template bank for gravitational waveforms from coalescing binary black holes: non-spinning binaries

Gravitational waveforms from the inspiral and ring-down stages of the binary black hole coalescences can be modelled accurately by approximation/perturbation techniques in general relativity. Recent progress in numerical relativity has enabled us to model also the non-perturbative merger phase of the binary black-hole coalescence problem. This enables us to \emph{coherently} search for all three stages of the coalescence of non-spinning binary black holes using a single template bank. Taking our motivation from these results, we propose a family of template waveforms which can model the inspiral, merger, and ring-down stages of the coalescence of non-spinning binary black holes that follow quasi-circular inspiral. This two-dimensional template family is explicitly parametrized by the physical parameters of the binary. We show that the template family is not only \emph{effectual} in detecting the signals from black hole coalescences, but also \emph{faithful} in estimating the parameters of the binary. We compare the sensitivity of a search (in the context of different ground-based interferometers) using all three stages of the black hole coalescence with other template-based searches which look for individual stages separately. We find that the proposed search is significantly more sensitive than other template-based searches for a substantial mass-range, potentially bringing about remarkable improvement in the event-rate of ground-based interferometers. As part of this work, we also prescribe a general procedure to construct interpolated template banks using non-spinning black hole waveforms produced by numerical relativity.Comment: A typo fixed in Eq.(B11

Spin effects in Bose-Glass phases

We study the mechanism of formation of Bose glass (BG) phases in the spin-1 Bose Hubbard model when diagonal disorder is introduced. To this aim, we analyze first the phase diagram in the zero-hopping limit, there disorder induces superposition between Mott insulator (MI) phases with different filling numbers. Then BG appears as a compressible but still insulating phase. The phase diagram for finite hopping is also calculated with the Gutzwiller approximation. The bosons' spin degree of freedom introduces another scattering channel in the two-body interaction modifying the stability of MI regions with respect to the action of disorder. This leads to some peculiar phenomena such as the creation of BG of singlets, for very strong spin correlation, or the disappearance of BG phase in some particular cases where fluctuations are not able to mix different MI regions