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

Greenhouse gas abatement on southern Australian grains farms: B iophysical potential and financial impacts

The agricultural sector generates a substantial proportion of global greenhouse gas (GHG) emissions through emissions of carbon dioxide (CO2) and nitrous oxide (N2O). Changes to agricultural practices can provide GHG abatement by maintaining or increasing soil organic carbon (SOC) stored in soils or vegetation, or by decreasing N2O emissions. However, it can be difficult to identify practices that achieve net abatement because practices that increase SOC stocks may also increase N2O emissions from the soil. This study simulated the net on-farm GHG abatement and gross margins for a range of management scenarios on two grain farms from the western and southern grain growing regions of Australia using the Agricultural Production Systems sIMulator (APSIM) model. The soils and practices selected for the study were typical of these regions. Increased cropping intensity consistently provided emissions reductions for all site-soil combinations. The practice of replacing uncropped or unmanaged pasture fallows with a winter legume crop was the only one of nine scenarios to decrease GHG emissions and increase gross margins relative to baseline practice at both locations over the 100-year simulation period. The greatest abatement was obtained by combining this practice with an additional summer legume crop grown for a short period as green manure. However, adding the summer legume decreased farm gross margins because the summer crop used soil moisture otherwise available to the following cash crop, thus reducing yield and revenue. Annual N2O emissions from the soil were an order of magnitude lower from sandy-well-drained soils at the Western Australian location (Dalwallinu) than at the other location (Wimmera) with clay soil, highlighting the importance of interactions between climate and soil properties in determining appropriate GHG abatement practices. Thus, greatest abatement at Dalwallinu was obtained from maintaining or increasing SOC, but managing both N2O emissions and SOC storage were important for providing abatement at Wimmera

Ninety-day complication rate based on 532 Latarjet procedures in Dutch hospitals with different operation volumes

Background: In this study, we aimed to provide insight into the 90-day complication rates following the Latarjet procedure. Data from 2015 were collected from multiple hospitals in the Netherlands, with different volumes of Latarjet procedures. Our second aim was to examine which patient and surgical factors were associated with complications.Methods: We conducted a retrospective chart review of 13 hospitals between 2015 and 2022. Data regarding complications within 90 days of Latarjet procedures were extracted. The effect of sex, age, body mass index (BMI), smoking, previous shoulder operations, fixation material, hospital volume, screw size, and operation time on the complication rate was assessed by multivariable logistic regression analysis.Results: Of the 532 included patients, 58 (10.9%) had complications. The most common complications were material failure (n = 19, 3.6%) and nerve injury (n = 13, 2.4%). The risk of complications was lower for male patients than for female patients (odds ratio, 0.40; 95% confidence interval, 0.21-0.77; P = .006). Age, BMI, smoking, previous shoulder operations, type of fixation material, hospital volume, screw size, and operation time were not associated with complications.Conclusion: The 90-day complication rate after the Latarjet procedure was 10.9% and was higher in female patients than in male patients. Age, BMI, smoking, previous shoulder operations, type of fixation material, hospital volume, screw size, and operation time did not affect complication rates. We advise setting up a national registry to prevent under-reporting of complications.</p

Ultrafast carrier relaxation and vertical-transport phenomena in semiconductor superlattices: A Monte Carlo analysis

The ultrafast dynamics of photoexcited carriers in semiconductor superlattices is studied theoretically on the basis of a Monte Carlo solution of the coupled Boltzmann transport equations for electrons and holes. The approach allows a kinetic description of the relevant interaction mechanisms such as intra- miniband and interminiband carrier-phonon scattering processes. The energy relaxation of photoexcited carriers, as well as their vertical transport, is investigated in detail. The effects of the multiminiband nature of the superlattice spectrum on the energy relaxation process are discussed with particular emphasis on the presence of Bloch oscillations induced by an external electric field. The analysis is performed for different superlattice structures and excitation conditions. It shows the dominant role of carrier-polar-optical-phonon interaction in determining the nature of the carrier dynamics in the low-density limit. In particular, the miniband width, compared to the phonon energy, turns out to be a relevant quantity in predicting the existence of Bloch oscillations

Multi-layered Ruthenium-modified Bond Coats for Thermal Barrier Coatings

Diffusional approaches for fabrication of multi-layered Ru-modified bond coats for thermal barrier coatings have been developed via low activity chemical vapor deposition and high activity pack aluminization. Both processes yield bond coats comprising two distinct B2 layers, based on NiAl and RuAl, however, the position of these layers relative to the bond coat surface is reversed when switching processes. The structural evolution of each coating at various stages of the fabrication process has been and subsequent cyclic oxidation is presented, and the relevant interdiffusion and phase equilibria issues in are discussed. Evaluation of the oxidation behavior of these Ru-modified bond coat structures reveals that each B2 interlayer arrangement leads to the formation of α-Al 2 O 3 TGO at 1100°C, but the durability of the TGO is somewhat different and in need of further improvement in both cases

Baryon polarization in low-energy unpolarized meson-baryon scattering

We compute the polarization of the final-state baryon, in its rest frame, in low-energy meson--baryon scattering with unpolarized initial state, in Unitarized BChPT. Free parameters are determined by fitting total and differential cross-section data (and spin-asymmetry or polarization data if available) for $pK^-$, $pK^+$ and $p\pi^+$ scattering. We also compare our results with those of leading-order BChPT

Nanocrystal and surface alloy properties of bimetallic Gold-Platinum nanoparticles

We report on the correlation between the nanocrystal and surface alloy properties with the bimetallic composition of gold-platinum(AuPt) nanoparticles. The fundamental understanding of whether the AuPt nanocrystal core is alloyed or phase-segregated and how the surface binding properties are correlated with the nanoscale bimetallic properties is important not only for the exploitation of catalytic activity of the nanoscale bimetallic catalysts, but also to the general exploration of the surface or interfacial reactivities of bimetallic or multimetallic nanoparticles. The AuPt nanoparticles are shown to exhibit not only single-phase alloy character in the nanocrystal, but also bimetallic alloy property on the surface. The nanocrystal and surface alloy properties are directly correlated with the bimetallic composition. The FTIR probing of CO adsorption on the bimetallic nanoparticles supported on silica reveals that the surface binding sites are dependent on the bimetallic composition. The analysis of this dependence further led to the conclusion that the relative Au-atop and Pt-atop sites for the linear CO adsorption on the nanoparticle surface are not only correlated with the bimetallic composition, but also with the electronic effect as a result of the d-band shift of Pt in the bimetallic nanocrystals, which is the first demonstration of the nanoscale core-surface property correlation for the bimetallic nanoparticles over a wide range of bimetallic composition

Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial.

Prostate cancer (PCa) has been under investigation as a target for antigen-specific immunotherapies in metastatic disease settings for the last two decades leading to a licensure of the first therapeutic cancer vaccine, Sipuleucel-T, in 2010. However, neither Sipuleucel-T nor other experimental PCa vaccines that emerged later induce strong T-cell immunity. In this first-in-man study, VANCE, we evaluated a novel vaccination platform based on two replication-deficient viruses, chimpanzee adenovirus (ChAd) and MVA (Modified Vaccinia Ankara), targeting the oncofetal self-antigen 5T4 in early stage PCa. Forty patients, either newly diagnosed with early-stage PCa and scheduled for radical prostatectomy or patients with stable disease on an active surveillance protocol, were recruited to the study to assess the vaccine safety and T-cell immunogenicity. Secondary and exploratory endpoints included immune infiltration into the prostate, prostate-specific antigen (PSA) change, and assessment of phenotype and functionality of antigen-specific T cells. The vaccine had an excellent safety profile. Vaccination-induced 5T4-specific T-cell responses were measured in blood by ex vivo IFN-γ ELISpot and were detected in the majority of patients with a mean level in responders of 198 spot-forming cells per million peripheral blood mononuclear cells. Flow cytometry analysis demonstrated the presence of both CD8+ and CD4+ polyfunctional 5T4-specific T cells in the circulation. 5T4-reactive tumor-infiltrating lymphocytes were isolated from post-treatment prostate tissue. Some of the patients had a transient PSA rise 2-8 weeks following vaccination, possibly indicating an inflammatory response in the target organ. An excellent safety profile and T-cell responses elicited in the circulation and also detected in the prostate gland support the evaluation of the ChAdOx1-MVA 5T4 vaccine in efficacy trials. It remains to be seen if this vaccination strategy generates immune responses of sufficient magnitude to mediate clinical efficacy and whether it can be effective in late-stage PCa settings, as a monotherapy in advanced disease or as part of multi-modality PCa therapy. To address these questions, the phase I/II trial, ADVANCE, is currently recruiting patients with intermediate-risk PCa, and patients with advanced metastatic castration-resistant PCa, to receive this vaccine in combination with nivolumab. The trial was registered with the U.S. National Institutes of Health (NIH) Clinical Trials Registry (ClinicalTrials.gov identifier NCT02390063)

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure