José Bergamín, une voix républicaine et dissidente dans l'Espagne de la Transition

Doctorado Europeo - Cotutela Internacional de Tesis: Universidad de Cádiz (Departamento de Historia Moderna, Contemporánea, de América y del Arte, Grupo de Estudios de Historia Actual HUM 315, Doctorado en Historia, arte y literatura en el mundo hispánico siglos XVI-XX) y Universidad Paris Ouest Nanterre La Défense (École doctorale Lettres, langues et spectacles 138, Centre de recherche Études romanes EA 369, Doctorat de Langues et littératures romanes : Espagnol).Partiendo de una apertura multidisciplinar y privilegiando la relación de los estudios históricos y literarios, se presenta el conjunto de este trabajo en tres partes que corresponden a acercamientos diferentes del tema, centrado en el discurso disidente del escritor José Bergamín en la Transición. La primera parte plantea un acercamiento al tema a partir de cuestiones relacionadas con el movimiento por la memoria en la España actual y con las relecturas de la Transición que se vienen haciendo, contexto en el que la voz disidente de Bergamín adquiere un nuevo significado que cuestiona la marginación que sigue caracterizando a esta destacada figura de la intelectualidad española del siglo XX. La segunda parte ofrece una presentación y una caracterización temática de la fuente principal consultada, que corresponde a la colaboración periodística que mantuvo con la revista Sábado Gráfico, gracias a la cual pudo expresar libremente su opinión, hasta que los problemas con la censura causaron su cese. La tercera y última parte ofrece una lectura política y cronológica del discurso ofrecido por Bergamín en dichos artículos, como una manifestación de la disidencia en la España de la Transición, basada en el rechazo de la monarquía y en la reivindicación de la república como alternativa. Esta investigación confirma la validez de la hipótesis principal planteada, según la cual Bergamín desempeñó el rol de portavoz de una «España peregrina», en base a una fe republicana alimentada por la memoria y la experiencia histórica, confrontada al espíritu de reconciliación y concordia que guió la Transición y que da sentido a la Monarquía parlamentaria vigente, cuya legitimidad de origen no dejó de cuestionar.Volumen 1, 812 páginas

Evaluación de un laboratorio web como complemento de un curso de Electrónica Básica

Ponencia presentada en el Congreso de Tecnologías Aplicadas a la Enseñanza de la Electrónica (TAEE 2004), celebrado en Valencia durante los días 14-17 de julio de 2004.Se presentan los resultados obtenidos de la experiencia docente realizada en la asignatura Electrónica de segundo curso de Ingeniería Informática en la Universidad Autónoma de Madrid. Se ha incorporado un laboratorio accesible desde Web como complemento práctico de un curso de electrónica básica. El laboratorio Web dispone de una colección básica de ejercicios prácticos de análisis de circuitos. Se proponen experimentos complementarios a la teoría que permitan a los estudiantes familiarizarse con la caracterización de dispositivos, y en los cuales, el alumno realiza medidas reales de los dispositivos electrónicos. Los resultados muestran que el interfaz desarrollado para simplificar la utilización del equipo de medida ha sido bien acogido, y en general los alumnos valoran positivamente este tipo de práctica no presencial.Este trabajo ha sido parcialmente financiado por el proyecto europeo número: 100671-CP-1- 2002-1-FR-MINERVA-M y por el proyecto 07T/0052/2003 3 de la Consejería de Educación de la Comunidad de Madri

Emerge: una red educativa europea para la integración de laboratorios accesibles via web

Ponencia presentada en el Congreso de Tecnologías Aplicadas a la Enseñanza de la Electrónica (TAEE 2004), celebrado en Valencia durante los días 14-17 de julio de 2004.El proyecto europeo Emerge propone crear una red educativa que pretende la integración de experimentos de laboratorio accesibles en remoto desde Web. El objetivo final consiste en extender la utilización de los laboratorios fuera de las instituciones individuales que forman parte del proyecto. Mediante tecnologías Web e instrumentación controlada por ordenador los estudiantes europeos tendrán a su disposición un conjunto de prácticas relacionadas con el área de la ingeniería electrónica. Para lograrlo se están desarrollando nuevas soluciones que integran los experimentos de los laboratorios de cada unos de los socios así como los servicios comunes. Se plantea cómo resolver los aspectos de seguridad, el control de acceso y el desarrollo de interfaces de usuario escalables. Las soluciones aportadas están basadas en tecnologías Web estándar como Applets, SOAP o PHP. En este trabajo se presenta el estado actual del proyecto, el material de soporte desarrollado y las prácticas que ya están accesibles desde el portal Web.Este proyecto ha sido llevado a cabo con la ayuda de la Comunidad Europea en el marco del programa Sócrates, EU Programa No: 100671-CP-1-2002-1-FR-MINERVA-

Uso de equipos didácticos de refrigeración en asignaturas de grado y máster

La importancia de enseñar al alumno conceptos teóricos unidos a conceptos prácticos y aplicaciones reales, ha sido, es y seguirá siendo, una de las piezas fundamentales en la formación de cualquier ingeniero. El uso de equipos docentes con los que el alumno pueda interaccionar y desarrollar sus aptitudes, es una de las claves en la rápida asimilación de conceptos y desarrollo de nuevas inquietudes. En este trabajo se presentan una serie de equipos didácticos de refrigeración desarrollados para asignaturas de Grado y Máster, así como las experiencias propuestas al alumno para que éste trabaje de forma autónoma con el equipo. Los equipos desarrollados, corresponden a un ciclo simple de compresión de vapor simple y un sistema de enfriamiento empleando aire como fluido de trabajo.El grupo de investigación GIT (www.git.uji.es), agradece el apoyo económico prestado por la Universidad Jaume I y a la ayuda de los alumnos David Conesa, Hugo Negre, Carlos Rodríguez y Josep San Mateo, miembros de la asociación engiOn, en el desarrollo de este proyecto

Mitochondrial Na+ controls oxidative phosphorylation and hypoxic redox signalling

All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1–4, and both phenomena occur in hypoxia4–8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism

Autoantibodies against the immunodominant sCha epitope discriminate the risk of sudden death in chronic Chagas cardiomyopathy

In Chagas disease (ChD) caused by Trypanosoma cruzi, new biomarkers to predict chronic cardiac pathology are urgently needed. Previous studies in chagasic patients with mild symptomatology showed that antibodies against the immunodominant R3 epitope of sCha, a fragment of the human basic helix-loop-helix transcription factor like 5, correlated with cardiac pathology. To validate sCha as a biomarker and to understand the origin of anti-sCha antibodies, we conducted a multicenter study with several cohorts of chagasic patients with severe cardiac symptomatology. We found that levels of antibodies against sCha discriminated the high risk of sudden death, indicating they could be useful for ChD prognosis. We investigated the origin of the antibodies and performed an alanine scan of the R3 epitope. We identified a minimal epitope MRQLD, and a BLAST search retrieved several T. cruzi antigens. Five of the hits had known or putative functions, of which phosphonopyruvate decarboxylase showed the highest cross-reactivity with sCha, confirming the role of molecular mimicry in the development of anti-sCha antibodies. Altogether, we demonstrate that the development of antibodies against sCha, which originated by molecular mimicry with T. cruzi antigens, could discriminate electrocardiographic alterations associated with a high risk of sudden death.Ministerio de Economía y competitividad and Fondo Europeo de Desarrollo Regional (SAF2015-63868-R (MINECO/FEDER) to N.G., and SAF2016-75988-R (MINECO/FEDER) to M.F.); Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (PGC2018-096132-BI00 (MICINN/FEDER) to N.G.); Universidad Autónoma de Madrid-Banco de Santander Inter-University Cooperation Grant with Latin América (CEAL-AL/2015-12 to N.G.); Red de Investigación de Centros de Enfermedades Tropicales (RICET RD12/0018/0004 to M.F.); and Comunidad de Madrid (S-2010/BMD-2332 to M.F.). CBMSO institutional grants from Fundación Ramón Areces and Banco de Santande

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio