Instability strips of main sequence B stars: a parametric study of iron enhancement

The discovery of beta Cephei stars in low metallicity environments, as well as the difficulty to theoretically explain the excitation of the pulsation modes observed in some beta Cephei and SPB stars, suggest that the iron opacity ``bump'' provided by standard models could be underestimated. We investigate, by means of a parametric study, the effect of a local iron enhancement on the location of the beta Cephei and SPB instability strips.Comment: 2 pages, to appear in the proceedings of "Vienna Workshop on the Future of Asteroseismology", September 20-22, 200

Effects of rotation on the evolution and asteroseismic properties of red giants

The influence of rotation on the properties of red giants is studied in the context of the asteroseismic modelling of these stars. While red giants exhibit low surface rotational velocities, we find that the rotational history of the star has a large impact on its properties during the red giant phase. In particular, for stars massive enough to ignite He burning in non-degenerate conditions, rotational mixing induces a significant increase of the stellar luminosity and shifts the location of the core helium burning phase to a higher luminosity in the HR diagram. This of course results in a change of the seismic properties of red giants at the same evolutionary state. As a consequence the inclusion of rotation significantly changes the fundamental parameters of a red giant star as determined by performing an asteroseismic calibration. In particular rotation decreases the derived stellar mass and increases the age. Depending on the rotation law assumed in the convective envelope and on the initial velocity of the star, non-negligible values of rotational splitting can be reached, which may complicate the observation and identification of non-radial oscillation modes for red giants exhibiting moderate surface rotational velocities. By comparing the effects of rotation and overshooting, we find that the main-sequence widening and the increase of the H-burning lifetime induced by rotation (Vini=150 km/s) are well reproduced by non-rotating models with an overshooting parameter of 0.1, while the increase of luminosity during the post-main sequence evolution is better reproduced by non-rotating models with overshooting parameters twice as large. This is due to the fact that rotation not only increases the size of the convective core but also changes the chemical composition of the radiative zone.Comment: 9 pages, 13 figures, accepted for publication in A&

Synthesis and characterization of a click-assembled 18-atom macrocycle that displays selective AXL kinase inhibitory activity

A novel macrocyclic construct consisting of a pyrazolopyrimidine scaffold concatenated to a benzene ring through two triazoles has been developed to investigate uncharted chemical space with bioactive potential. The 18-atom macrocycle was assembled via a double copper-catalyzed alkyne−azide cycloaddition (CuAAC) reaction between 1,3- bis(azidomethyl)benzene and a bis-propargylated pyrazolo[3,4-d]pyrimidine core. The resulting macrocycle was functionalized further into a multicyclic analog that displays selective inhibitory activity against the receptor tyrosine kinase AXL.O.C.-L. and B.L. thank Spain Ministry of Education, Culture and Sport and the Erasmus + Traineeship programme for funding, respectively. C.T. thanks the CMVM for a Principal’s Scholarship. F.F. acknowledges support from Universidad de Granada. SHM and AU-B are grateful to Scottish Power and CRUK for funding

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

Low abundances of heavy elements in the solar outer layers: comparisons of solar models with helioseismic inversions

Recent solar photospheric abundance analyses have led to a significant reduction of the metal abundances compared to the previous determinations. The solar models computed with standard opacities and diffusion processes using these new abundances give poor agreement with helioseismic inversions for the sound-speed profile, the surface helium abundance, and the convective zone depth. We attempt to obtain a good agreement between helioseismic inversions and solar models which present the "old" mixture in the interior and new chemical composition in the convective zone. To reach this result, we assume an undermetallic accretion at the beginning of the main sequence. We compute solar models with the Toulouse-Geneva Evolution Code, in which we simulate an undermetallic accretion in the early stages of the main sequence, in order to obtain new mixture in the outer convective zone. We compare the sound-speed profile, the convective zone depth, and the surface helium abundance with those deduced from helioseismology. The model with accretion but without any mixing process inside is in better agreement with helioseismology than the solar model with the new abundances throughout. There is, however, a spike under the convective zone which reaches 3.4%. Furthermore, the convective zone depth and the surface helium abundance are too low. Introducing undershooting below the convective zone allows us to recover the good convective zone radius and the addition of rotation-induced mixing and tachocline allows us to reconcile the surface helium abundance. But in any case the agreement of the sound-speed profile with helioseismic inference is worse than obtained with the old abundances.Comment: 5 pages, 2 figure

Probing the properties of convective cores through g modes: high-order g modes in SPB and gamma Doradus stars

In main sequence stars the periods of high-order gravity modes are sensitive probes of stellar cores and, in particular, of the chemical composition gradient that develops near the outer edge of the convective core. We present an analytical approximation of high-order g modes that takes into account the effect of the mu gradient near the core. We show that in main-sequence models, similarly to the case of white dwarfs, the periods of high-order gravity modes are accurately described by a uniform period spacing superposed to an oscillatory component. The periodicity and amplitude of such component are related, respectively, to the location and sharpness of the mu gradient. We investigate the properties of high-order gravity modes for stellar models in a mass domain between 1 and 10 Msun, and the effects of the stellar mass, evolutionary state, and extra-mixing processes on period spacing features. In particular, we show that for models of a typical SPB star, a chemical mixing that could likely be induced by the slow rotation observed in these stars, is able to significantly change the g-mode spectra of the equilibrium model. Prospects and challenges for the asteroseismology of gamma Doradus and SPB stars are also discussed.Comment: 18 pages, 29 figures, accepted for publication in MNRA

Design of a precision compactor for use in guided bone regeneration in the area of oral surgery

During the processes of guided bone regeneration in the maxillary bones, which aim to recover or preserve support tissue for the placement of implants on which dental prostheses are retained, the use of various particulate graft biomaterials from different sources (animal or synthetic) is standardized. At present, the pressure of compaction of this material in the recipient bone is manual, dependent on the clinician, although there is some scientific evidence on the effects of different compressive forces on angiogenesis and prognosis of the regeneration of the grafted areas. The aim of the present study is to design, calibrate and verify in vitro a compaction instrument for clinical use, which allows a controlled and precise compaction pressure of the particulate graft biomaterial and standardize the procedure. The designed instrument is a precision compactor of adequate size for proper intra and extraoral clinical manageability and manufactured in a sterilizable material by autoclaving. The range of compression that allows (0 -1, 82 Newton), is within the forces that are commonly applied in surgery and that have been determined by a specific test on 8 oral surgeons. Instrument calibration has been performed by an independent accredited company. The testing of the instrument was carried out by an in vitro test where the biomaterial was compacted at different forces (0, 80 and 1, 82 Newton) and was observed by a computerized micro-tomography that when increasing the compression force, decreased the space between particles provided for the migration and proliferation of new blood vessels and cells. Durante los procedimientos de regeneración ósea guiada en los huesos maxilares, que tienen como objetivo recuperar o preservar tejido de soporte para la colocación de implantes sobre los que se retienen las prótesis dentales, está estandarizado el uso de diversos biomateriales de injerto particulado de diferente procedencia (animal o sintético). En la actualidad la presión de compactación de dicho material en el hueso receptor es manual, clínico dependiente, pese a que existe cierta evidencia científica sobre los efectos de las diferentes fuerzas de compresión en la angiogénesis y pronóstico de la regeneración de las zonas injertadas. El objetivo del presente estudio es el de diseñar, calibrar y comprobar in vitro un instrumento de compactación para uso clínico, que permita una presión de compactación controlada y precisa del biomaterial de injerto particulado y estandarizar el procedimiento. El instrumento diseñado es un compactador de precisión de tamaño adecuado para una correcta manejabilidad clínica intra y extraoral y fabricado en un material esterilizable por autoclavado. El rango de compresión que permite (0 – 1, 82 Newton), está dentro de las fuerzas que se aplican comúnmente en cirugía y que se han determinado mediante una prueba específica sobre 8 cirujanos orales. La calibración del instrumento se ha realizado por una empresa acreditada independiente. La comprobación del instrumento se ha realizado mediante un ensayo in vitro donde se compactó el biomaterial a diferentes fuerzas (0, 80 y 1, 82 Newton) y se observó mediante micro-tomografía computerizada que al aumentar la fuerza de compresión disminuía el espacio entre partículas provisto para la migración y proliferación de los nuevos vasos sanguíneos y células

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

BACKGROUNG: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. OBJECTIVE: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. METHODS: In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. RESULTS: There was a significant increase in INL volume in eyes with new MSON during the study (N = 61/1562, β = 0.01 mm(3), p < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005, p = .025). INL volume was independent of disease progression (β = 0.002 mm(3), p = .474). CONCLUSION: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod : The Spanish GILENYA registry

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continuedto be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance