The shortest period M-dwarf eclipsing system BW3 V38, II: determination of absolute elements

The spectroscopic data for the short-period (0.1984 d)eclipsing binary V38, discovered by the OGLE micro-lensing team in Baade's Window field BW3, are analyzed. Radial velocity curves are derived from mid-resolution spectra obtained with EMMI-NTT at ESO - La Silla, and a simultaneous solution of the existing light curve by OGLE and of the new radial velocity curves is obtained. The system is formed by almost twin M3e dwarf components that are very close, but not yet in contact. The spectra of both dwarfs show signatures of the presence of strong chromospheres. Spectroscopy definitely confirms, therefore, what was suggested on the basis of photometry: BW3 V38 is indeed a unique system, as no other similar binary with M components and in such a tight orbit is known. Within the limits posed by the relatively large errors, due to the combined effect of system faintness and of the constraints on exposure time, the derived physical parameters seem to agree with the relations obtained from the other few known eclipsing binaries with late type components (which indicate a discrepancy between the available evolutionary models and the data at ~ 10% level). A possible explanation is the presence of strong magnetic fields and fast rotation (that applies to the BW3 V38 case as well). A simple computation of the system secular evolution by angular momentum loss and spin orbit synchronization shows that the evolution of a system with M dwarfs components is rather slow, and indicates as well a possible reason why systems similar to BW3 V38 are so rare.Comment: 9 pages, 7 figures, 3 tables, accepted for publication in A&

A-type stars: evolution, rotation and binarity

We discuss the internal structure of stars in the mass range 1.5 to 4 M_sun from the PMS to the subgiant phase with a particular emphasis on the convective core and the convective superficial layers. Different physical aspects are considered such as overshooting, treatment of convection, microscopic diffusion and rotation. Their influence on the internal structure and on the photospheric chemical abundances is briefly described. The role of binarity in determining the observed properties and as a tool to constrain the internal structure is also introduced and the current limits of theories of orbital evolution and of available binary data--sets are discussed. keywords{stars: evolution, stars: binaries: general, stars: rotation}Comment: 11 pages, 7 figures, conference: The A-star Puzzle, IAU Simp. 224, 200

Precision Masses of the low-mass binary system GJ 623

We have used Aperture Masking Interferometry and Adaptive Optics (AO) at the Palomar 200'' to obtain precise mass measurements of the binary M dwarf GJ 623. AO observations spread over 3 years combined with a decade of radial velocity measurements constrain all orbital parameters of the GJ 623 binary system accurately enough to critically challenge the models. The dynamical masses measured are m_{1}=0.371\pm0.015 M_{\sun} (4%) and m_{2}=0.115\pm0.0023 M_{\sun} (2%) for the primary and the secondary respectively. Models are not consistent with color and mass, requiring very low metallicities.Comment: 7 pages, 5 figures. Accepted for Ap

Progressive MS trials: Lessons learned.

Up to very recently, no treatments had proved effective in progressive multiple sclerosis (MS). In 2016, four drugs, two tested in phase 3 and two in phase 2 trials, showed a beneficial effect in primary or secondary progressive MS. Although this could indicate a turning point in progressive MS treatment, most of these successes have been modest and mainly restricted to patients with active inflammation, in the context of trials with powerful anti-inflammatory agents. This paper summarises these reasons, particularly focusing on the main lessons learned for the design of future trials. First, a drug’s mechanism of action should tackle the specific pathogenic mechanisms that characterise progressive MS. Second, trial populations where new drugs are to be tested should be carefully chosen, possibly including younger patients with shorter disease durations, which have greater chances of showing active deterioration during the trial, therefore increasing the power to detect treatment effects. Third, outcome measures used in future phase 2 and phase 3 trials should be highly sensitive and be accompanied by smart trial designs

Non-radial oscillations in the red giant HR7349 measured by CoRoT

Convection in red giant stars excites resonant acoustic waves whose frequencies depend on the sound speed inside the star, which in turn depends on the properties of the stellar interior. Therefore, asteroseismology is the most robust available method for probing the internal structure of red giant stars. Solar-like oscillations in the red giant HR7349 are investigated. Our study is based on a time series of 380760 photometric measurements spread over 5 months obtained with the CoRoT satellite. Mode parameters were estimated using maximum likelihood estimation of the power spectrum. The power spectrum of the high-precision time series clearly exhibits several identifiable peaks between 19 and 40 uHz showing regularity with a mean large and small spacing of Dnu = 3.47+-0.12 uHz and dnu_02 = 0.65+-0.10 uHz. Nineteen individual modes are identified with amplitudes in the range from 35 to 115 ppm. The mode damping time is estimated to be 14.7+4.7-2.9 days.Comment: 8 pages, A&A accepte

T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis

Objectives: Prediction of long term clinical outcome in patients with primary progressive multiple sclerosis (PPMS) using imaging has important clinical implications, but remains challenging. We aimed to determine whether spatial location of T2 and T1 brain lesions predicts clinical progression during a 10-year follow-up in PPMS. Methods: Lesion probability maps of the T2 and T1 brain lesions were generated using the baseline scans of 80 patients with PPMS who were clinically assessed at baseline and then after 1, 2, 5 and 10 years. For each patient, the time (in years) taken before bilateral support was required to walk (time to event (TTE)) was used as a measure of progression rate. The probability of each voxel being ‘lesional’ was correlated with TTE, adjusting for age, gender, disease duration, centre and spinal cord cross sectional area, using a multiple linear regression model. To identify the best, independent predictor of progression, a Cox regression model was used. Results: A significant correlation between a shorter TTE and a higher probability of a voxel being lesional on T2 scans was found in the bilateral corticospinal tract and superior longitudinal fasciculus, and in the right inferior fronto-occipital fasciculus (p<0.05). The best predictor of progression rate was the T2 lesion load measured along the right inferior fronto-occipital fasciculus (p=0.016, hazard ratio 1.00652, 95% CI 1.00121 to 1.01186). Conclusion: Our results suggest that the location of T2 brain lesions in the motor and associative tracts is an important contributor to the progression of disability in PPMS, and is independent of spinal cord involvement

Implications of a Sub-Threshold Resonance for Stellar Beryllium Depletion

Abundance measurements of the light elements lithium, beryllium, and boron are playing an increasingly important role in the study of stellar physics. Because these elements are easily destroyed in stars at temperatures 2--4 million K, the abundances in the surface convective zone are diagnostics of the star's internal workings. Standard stellar models cannot explain depletion patterns observed in low mass stars, and so are not accounting for all the relevant physical processes. These processes have important implications for stellar evolution and primordial lithium production in big bang nucleosynthesis. Because beryllium is destroyed at slightly higher temperatures than lithium, observations of both light elements can differentiate between the various proposed depletion mechanisms. Unfortunately, the reaction rate for the main destruction channel, 9Be(p,alpha)6Li, is uncertain. A level in the compound nucleus 10B is only 25.7 keV below the reaction's energetic threshold. The angular momentum and parity of this level are not well known; current estimates indicate that the resonance entrance channel is either s- or d-wave. We show that an s-wave resonance can easily increase the reaction rate by an order of magnitude at temperatures of approximately 4 million K. Observations of sub-solar mass stars can constrain the strength of the resonance, as can experimental measurements at lab energies lower than 30 keV.Comment: 9 pages, 1 ps figure, uses AASTeX macros and epsfig.sty. Reference added, typos corrected. To appear in ApJ, 10 March 199

A plain language summary of what clinical studies can tell us about the safety of evobrutinib – a potential treatment for multiple sclerosis

Immunology; Rheumatology; Systemic lupus erythematosusInmunología; Reumatología; Lupus eritematoso sistémicoImmunologia; Reumatologia; Lupus eritematós sistèmicWhat is this summary about?: This summary explains the findings from a recent investigation that combined the results of over 1000 people from three clinical studies to understand the safety of evobrutinib. Evobrutinib is an oral medication (taken by mouth), being researched as a potential treatment for multiple sclerosis (MS). This medication was also investigated in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Over 1000 people have taken evobrutinib as part of three separate phase 2 clinical studies. These studies looked at how much of the drug should be taken, how safe the drug is, and how well it might work for treating a certain medical condition. What were the results?: Evobrutinib was well-tolerated by participants in all three studies. The number of side effects reported by participants taking the medication was very similar to those reported by participants taking the placebo (a 'dummy' treatment without a real drug). The most common side effects in clinical studies were urinary tract infections, headache, swelling of the nose and throat, diarrhoea and blood markers of potential liver damage (these returned to normal once the treatment was stopped). What do the results mean?: The safety data from all three clinical studies are encouraging and can be used to inform further research into using evobrutinib in MS.X Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS. D Wallace has received consultant fees from Amgen, Celgene, Eli Lilly, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA (an affiliate of Merck KGaA), Janssen and Merck. MC Genovese is an employee of and has financial interests in Gilead. D Tomic is an employee of Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA, and received stock or an ownership interest from Novartis. D Parsons-Rich was an employee of EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, at the time of the study, and is currently an employee of and has received stock from Pfizer. C Le Bolay and H Guehring are employees of Merck Healthcare KGaA, Darmstadt, Germany. A Kao is an employee of and received stock or an ownership interest from EMD Serono Inc., Billerica, MA, USA, a healthcare business of Merck KGaA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by Merck (CrossRef Funder ID: 10.13039/100009945). This summary was prepared by Lumanity on behalf of, and funded by, Merck KGaA, Darmstadt, Germany

Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study

Alemtuzumab; Disease-modifying therapy; Multiple sclerosisAlemtuzumab; Teràpia modificadora de la malaltia; Esclerosi múltipleAlemtuzumab; Terapia modificadora de la enfermedad; Esclerosis múltipleBackground and objectives: Alemtuzumab demonstrated superior efficacy versus subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2-year CARE-MS I and II trials. Efficacy was maintained in the 4-year CARE-MS extension, during which alemtuzumab-treated participants (‘alemtuzumab-only’) could receive additional courses upon disease activity, and IFN-treated participants switched to alemtuzumab (‘IFN-alemtuzumab’). Participants who completed the CARE-MS extension could enroll in the open-label TOPAZ study which assessed safety and efficacy for 5–7 years (11–13 years after alemtuzumab/IFN initiation). Methods: Participants received additional alemtuzumab courses as needed. Assessments included adverse events (AEs; primary outcome), annualized relapse rate (ARR), 6-month confirmed disability worsening [CDW; ⩾1.0-point Expanded Disability Status Scale (EDSS) score increase or ⩾1.5 if baseline EDSS = 0], and 6-month confirmed disease improvement [CDI; >1.0-point EDSS decrease (baseline score ⩾2.0)]. Results: 43.5% of alemtuzumab-only participants from CARE-MS II and 54.2% from CARE-MS I received no additional alemtuzumab courses; 30.0% and 20.9%, respectively, received one additional course (the median). Incidences of AEs, including thyroid AEs and infections, declined over time. The safety profile of alemtuzumab was similar for participants who received zero, one, or two additional courses. For CARE-MS II participants, who had inadequate response to previous treatment, ARR remained low during Years 3–13 for the alemtuzumab-only [0.17; 95% confidence interval (CI) 0.15–0.20] and IFN-alemtuzumab (0.14; 0.11–0.17) groups. At Year 11, the proportions of participants who were either free from CDW or who had CDI were higher in the alemtuzumab-only group (58% and 49%, respectively) than in the IFN-alemtuzumab group (51% and 37%). For CARE-MS I participants, who were previously treatment-naïve, clinical outcomes remained improved, and no between-group differences were apparent. Conclusion: Safety risks associated with alemtuzumab treatment declined over time. Clinical benefits were maintained up to 11–13 years, and most participants did not require more than one additional course.The TOPAZ study as well as writing and editorial support for this article were funded by Sanofi