Asparaginyl endopeptidase (Legumain) supports human Th1 induction via cathepsin L-mediated intracellular C3 activation

Autocrine activation of the complement receptors C3aR and CD46 by complement activation components C3a and C3b produced through C3 cleavage by the protease cathepsin L (CTSL) during T cell stimulation is a requirement for IFN-γ production and Th1 induction in human CD4+ T cells. Thus, lack of autocrine CD46 activation, such as in CD46-deficient patients, is associated with defective Th1 responses and recurrent infections. We have identified LGMN [the gene coding for legumain, also known as asparaginyl endopeptidase (AEP)] as one of the key genes induced by CD46 co-stimulation during human CD4+ T cell activation. AEP processes and activates a range of proteins, among those α1-thymosin and CTSL, which both drive intrinsically Th1 activity—but has so far not been described to be functionally active in human T cells. Here we found that pharmacological inhibition of AEP during activation of human CD4+ T cells reduced CTSL activation and the CTSL-mediated generation of intracellular C3a. This translated into a specific reduction of IFN-γ production without affecting cell proliferation or survival. In line with these findings, CD4+ T cells isolated from Lgmn−/− mice also displayed a specific defect in IFN-γ secretion and Th1 induction. Furthermore, we did not observe a role for AEP-driven autocrine α1-thymosin activation in T cell-derived IFN-γ production. These data suggest that AEP is an “upstream” activator of the CTSL-C3-IFN-γ axis in human CD4+ T cells and hence an important supporter of human Th1 induction

Methodology for the Accurate Measurement of the Power Dissipated by Braking Rheostats

The energy efficiency of transportation is a crucial point for the rail and metro system today. The optimized recovery of the energy provided by the electrical braking can lead to savings of about 10% to 30%. Such figures can be reached by infrastructure measures which allow the recovery of the breaking energy that is not directly consumed by the rail system and dissipated in rheostat resistors. A methodology for the accurate estimate of such energy is valuable for a reliable evaluation of the cost-benefit ratio associated with the infrastructural investment. The energy can be estimated by measuring a braking current flowing in the rheostats. The varying duty-cycle associated with the high dynamic variation, from zero to thousands of amperes, makes the current measurement very challenging. Moreover, the digitization of such waveforms introduces systematic errors that affect the energy estimation. To overcome these issues, this paper proposes a technique to measure the power and energy dissipated by the rheostat of a DC operated train with high accuracy. By means of an accurate model of the electrical braking circuit (chopper and rheostat) and the frequency characterization of the current transducer, a correction coefficient as a function of the duty-cycle is estimated. The method is then applied to data recorded during a measurement campaign performed on-board a 1.5 kV train of Metro de Madrid during normal operation. Using the proposed technique, the estimation of the dissipated braking energy is improved by 20%

Estudio de propiedades físicas y cristalográficas de materiales secados por microondas en comparativa de secados por estufa

Este TFG se ha centrado en el proceso de secado de áridos comparando ambos métodos, el método de secado por microondas y el método de secado por estufa. Para ello se realiza un estudio con muestras gemelas recogidas de distintas plantas de áridos de la provincia de Aragón, los áridos empleados en los ensayos son silíceos, calizos y dolomíticos. Estas muestras se someten a distintos porcentajes de humedad según su tamaño o según el tipo de árido.En este TFG se van a comparar los resultados de ambos métodos y valorar si el secado por microondas puede ser una alternativa al secado por estufa, con la finalidad de elaborar un borrador de normativa UNE que regule la utilización del horno microondas como método de secado alternativo.<br /

Prehospital emergency care of patients with acute heart failure in Spain: the SEMICA study (Emergency Medical Response Systems for Patients with Acute Heart Failure)

Objectives. To study the means of emergency transport used to bring patients with acute heart failure (AHF) to hospital emergency departments (EDs) and explore associations between factors, type of transport, and prehospital care received. Methods. We gathered the following information on patients treated for AHF at 34 Spanish hospital EDs: means of transport used (medicalized ambulance [MA], nonmedicalized ambulance [NMA], or private vehicle) and treatments administered before arrival at the hospital. Twenty-seven independent variables potentially related to type of transport used were also studied. Indicators of AHF severity were triage level assigned in the ED, need for admission, need for intensive care, in-hospital mortality, and 30-day mortality. Results. A total of 6106 patients with a mean (SD) age of 80 years were included; 56.5% were women, 47.2% arrived in PVs, 37.8% in NMAs, and 15.0% in MAs. Use of an ambulance was associated with female sex, age over 80 years, chronic obstructive pulmonary disease, a history of AHF, functional dependency, New York Heart Association class III-IV, sphincteral incontinence, labored breathing, orthopnea, cold skin, and sensory depression or restlessness. Assignment of a MA was directly associated with living alone, a history of ischemic heart disease, cold skin, sensory depression or restlessness, and high temperature; it was inversely associated with a history of falls. The rates of receipt of prehospital treatments and AHF severity level increased with use of MAs vs. NMAs vs. PV. Seventy-three percent of patients transported in MAs received oxygen, 29% received a diuretic, 13.5% a vasodilator, and 4.7% noninvasive ventilation. Conclusions. Characteristics of the patient with AHF are associated with the assignment of type of transport to a hospital ED. Assignment appears to be related to severity. Treatment given during MA transport could be increased

IMPROV-ED study : outcomes after discharge for an episode of acute-decompensated heart failure and comparison between patients discharged from the emergency department and hospital wards

Objective To define the short-and mid-term outcomes of patients discharged after an episode of acute-decompensated heart failure (ADHF) and evaluate the differences between patients discharged directly from the emergency department (ED) and those discharged after hospitalization. Methods We performed a prospective, multicenter, cohort-designed study, including consecutive patients diagnosed with ADHF in 27 Spanish EDs. Thirty-four variables on epidemiology, comorbidity, baseline status, vital signs, signs of congestion, laboratory tests, and treatment were collected in every patient. The primary outcome was a combined endpoint of ED revisit (without hospitalization) or hospitalization due to ADHF, or all-cause death. Secondary outcomes were each of these three events individually. Outcomes were obtained by survival analysis at different timepoints in the entire cohort, and crude and adjusted comparisons were carried out between patients discharged directly from the ED and after hospitalization. Results Of the 3233 patients diagnosed with ADHF during a 2-month period, we analyzed 2986 patients discharged alive: 787 (26.4%) discharged from the ED and 2199 (73.6%) after hospitalization. The cumulative percentages of events for the whole cohort (at 7/30/180 days) for the combined endpoint were 7.8/24.7/57.8; for ED revisit 2.5/9.4/25.5; for hospitalization 4.6/15.3/40.7; and for death 0.9/4.3/16.8. After adjustment for patient profile and center, significant increases were found in the hazard ratios for ED-compared to hospital-discharged patients in the combined endpoint, ED revisit and hospitalization, being higher at short-term [at 7 days, 2.373 (1.678-3.355), 2.069 (1.188-3.602), and 3.071 (1.915-4.922), respectively] than at mid-term [at 180 days, 1.368 (1.160-1.614), 1.642 (1.265-2.132), and 1.302 (1.044-1.623), respectively]. No significant differences were found in death. Conclusions Patients with ADHF discharged from the ED have worse outcomes, especially at short term, than those discharged after hospitalization. The definition and implementation of effective strategies to improve patient selection for direct ED discharge are needed.Peer reviewe

Rapid response to the M_w 4.9 earthquake of November 11, 2019 in Le Teil, Lower Rhône Valley, France

On November 11, 2019, a Mw 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE-SW La Rouviere normal fault in reverse faulting in agreement with the present-day E-W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them