Reliability and validity of the vitiligo signs of activity score (VSAS)

Background The associations between disease activity and several clinical signs in vitiligo have been described, but a widely accepted and validated scoring system is lacking. Objectives To validate the Vitiligo Signs of Activity Score (VSAS) for physicians. Methods Three visible clinical signs were scored on 15 body locations: confetti-like depigmentation (c), Koebner phenomenon (k) and hypochromic areas/borders (h). The inter- and intrarater reliability of the global VSAS and VSAS subscores (c-VSAS, k-VSAS and h-VSAS) were tested by four and three raters (physicians), respectively. Construct validity and feasibility were evaluated. Results The VSAS demonstrated good inter-rater reliability, with an intraclass correlation coefficient (ICC) of 0 center dot 87 in the first round and 0 center dot 90 in the second round. The intrarater reliability ICCs were all >= 0 center dot 86. The inter-rater reliabilities of the subscores were excellent for c-VSAS and fair for k-VSAS and h-VSAS (ICC 0 center dot 83, 0 center dot 51 and 0 center dot 53, respectively, in the first round). Evidence for construct validity was provided. The completion time by the raters (median 2 center dot 18 min per patient) improved during the second round (median 1 center dot 33 min per patient). A limitation of the study is the low number of patients, mainly of skin phototypes II-III, from a single tertiary centre. Conclusions The VSAS appears to be a valid and reliable instrument to score visible clinical signs linked to disease activity in a standardized way. What is already known about this topic? Evidence exists for a possible link between several visible clinical signs in vitiligo and disease activity. A widely accepted and validated scoring system to quantify these clinical signs is lacking. What does this study add? The Vitiligo Signs of Activity Score (VSAS) underwent preliminary validation and may assist quantification of visible clinical signs linked to disease activity in a standardized way in clinical practice and trials

Pedagogía Pandémica. Reproducción Funcional o Educación Antihegemónica

La actual pandemia provocada por el coronavirus es más que una crisis de salud. Es también una crisis política e ideológica generada tras años de negligencia por parte de gobiernos que, a través de políticas preferentemente neoliberales, negaron la importancia del bienestar público (particularmente de la salud y de la educación), al mismo tiempo que desvalorizaron las instituciones que lo hicieron posible. Por esta razón es que la actual situación no puede separarse de las crisis previas producidas por las masivas desigualdades de riqueza, ingresos y poder. Tampoco puede estar ajena de la crisis de valores democráticos, educativos y de destrucción del medio ambiente que ya se arrastran desde hace décadas (Touraine y Rivera-Vargas, 2017)

Non-linear magnetohydrodynamic modeling of plasma response to resonant magnetic perturbations

The interaction of static Resonant Magnetic Perturbations (RMPs) with the plasma flows is modeled in toroidal geometry, using the non-linear resistive MHD code JOREK, which includes the X-point and the scrape-off-layer. Two-fluid diamagnetic effects, the neoclassical poloidal friction and a source of toroidal rotation are introduced in the model to describe realistic plasma flows. RMP penetration is studied taking self-consistently into account the effects of these flows and the radial electric field evolution. JET-like, MAST, and ITER parameters are used in modeling. For JET-like parameters, three regimes of plasma response are found depending on the plasma resistivity and the diamagnetic rotation: at high resistivity and slow rotation, the islands generated by the RMPs at the edge resonant surfaces rotate in the ion diamagnetic direction and their size oscillates. At faster rotation, the generated islands are static and are more screened by the plasma. An intermediate regime with static islands which slightly oscillate is found at lower resistivity. In ITER simulations, the RMPs generate static islands, which forms an ergodic layer at the very edge (ψ ≥0.96) characterized by lobe structures near the X-point and results in a small strike point splitting on the divertor targets. In MAST Double Null Divertor geometry, lobes are also found near the X-point and the 3D-deformation of the density and temperature profiles is observed

Association of combined PD- L1 expression and tumour- infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

BackgroundRecent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death- 1 (PD- 1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD- L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas.ObjectivesWe investigated whether the presence and the features of pretreatment CD8+tumour- infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma.MethodsIn this retrospective study, we evaluated the association of PD- L1 expression - ¥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non- ICIs).ResultsPD- L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (κ = 0.283). No significant association was noted between PD- L1 expression and CD8+TIL profile analysed as single markers and OS or response to immunotherapy. Instead, their combined analysis in primary melanoma samples showed that the PD- L1- /CD8+status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non- ICIs (P = 0.009). Conversely, the PD- L1+/CD8+ status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non- ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8+TIL+/PD- L1- (P = 0.02).ConclusionsThe pretreatment combination of PD- L1 expression with the level of CD8+TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155478/1/jdv16016_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155478/2/jdv16016.pd

Sociología del campo filosófico español entre el Franquismo y la Transición democrática: una validación cuantitativa

La más reciente investigación dedicada al análisis del campo filosófico español entre el tardofranquismo y la Transición, señaló la existencia de dos redes intelectuales: una, denominada «oficial», que aglutinaba a los filósofos de perfil más estrictamente académico (v. g. Sergio Rábade), y otra, designada como «alternativa», que integraba a los pensadores más vanguardistas (v. g. López Aranguren). Los materiales utilizados en La filosofía española. Herederos y pretendientes. Una lectura sociológica (1963-1990) (Vázquez García 2009), fueron objeto en esta obra de una aproximación cualitativa. Nuestro objetivo en este artículo, privilegiando la fiabilidad sobre la validez, es la realización de un análisis de correspondencias múltiples, en el que se han cuantificado más de 15 variables sobre cincuenta filósofos españoles. En las conclusiones se profundiza en las diferencias y similitudes entre los resultados obtenidos con las metodologías cualitativa y cuantitativ

Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment

International audienceBACKGROUND: Epidermolysis bullosa simplex generalized severe is a genetic disorder caused by mutation in KRT5 or KRT14 genes. Usually considered as a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: The aim of this study was to assess the inflammation in the skin of patients with EBS. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 EBS-gen sev patients. A second multicenter prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemistry analysis and quantitative real time PCR. Cytokine expression was analyzed in blister fluid and compared with controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocytes infiltrate in skin biopsies of blister (n=17) as well as in rubbed skin (n=5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases and an increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of Th17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast with a dramatic improvement of skin blistering and good tolerance. CONCLUSION: Our study demonstrates the importance of inflammation in EBS-gen sev patients and underlines the key role for Th17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder. This article is protected by copyright. All rights reserved

A 5D gyrokinetic full-f global semi-lagrangian code for flux-driven ion turbulence simulations

International audienceThis paper addresses non-linear gyrokinetic simulations of ion temperature gradient (ITG) turbulence in tokamak plasmas. The electrostatic Gysela code is one of the few international 5D gyrokinetic codes able to perform global, full-f and flux-driven simulations. Its has also the numerical originality of being based on a semi-Lagrangian (SL) method. This reference paper for the Gysela code presents a complete description of its multi-ion species version including: (i) numerical scheme, (ii) high level of parallelism up to 500k cores and (iii) conservation law properties