Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Neodymium doped lanthanide fluoride nanoparticles as contrast agents for luminescent bioimaging and X-ray computed tomography

The synthesis of uniform neodymium-doped lanthanum trifluoride nanoparticles with lenticular shape and a mean diameter around 45nm by using a homogeneous precipitation method is reported. The luminescent properties of the synthesized samples in terms of their emission spectra and emission lifetime are analyzed as a function of the Nd content to find the optimum phosphor and its suitability for luminescent imaging in the second biological window. The X-ray attenuation properties of the optimum phosphor are evaluated to investigate their additional ability as contrast agent for X-ray computed tomography. Finally, the colloidal stability of the obtained nanoparticles in physiological medium and their cytotoxicity are also analyzed to assess their aptness for in vivo bioimaging applications.En este trabajo se ha desarrollado un método de síntesis de nanopartículas uniformes de trifluoruro de lantano dopadas con neodimio, con forma lenticular y un diámetro medio en torno a 45nm, basado en un proceso de precipitación homogénea en medio acuoso. Las propiedades luminiscentes de las muestras sintetizadas en términos de sus espectros de emisión y tiempo de vida de las emisiones se han analizado en función del contenido de neodimio (Nd) para determinar el nanofósforo óptimo y su idoneidad para la obtención de imágenes luminiscentes en la segunda ventana biológica. Asimismo, se han evaluado las propiedades de atenuación de rayos X del nanofósforo óptimo para valorar su capacidad adicional como agente de contraste para tomografía computarizada de rayos X. Por último, también se han analizado la estabilidad coloidal de las nanopartículas obtenidas en medio fisiológico y su citotoxicidad para determinar su aplicabilidad para la obtención de imágenes biológicas in vivo.Peer reviewe

Enhancing Luminescence and X‑ray Absorption Capacity of Eu3+:LaF3 Nanoparticles by Bi3+ Codoping

Bi3+ codoping has been proposed in this work with a twofold objective, namely, enhancing the luminescence emission of Eu3+:LaF3 nanoparticles (NPs) and increasing their X-ray attenuation capacity, with the purpose of obtaining a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography. The synthesis method, reported here for the first time for LaF3 particles, allowed obtaining uniform, nonaggregated NPs using a homogeneous precipitation in polyol medium at room temperature in just 2 h. The simplicity of the synthesis method allows the large-scale production of NPs. LaF3 NPs with different Eu3+ contents were first synthesized to find the critical Eu3+ concentration, producing the highest emission intensity. This concentration was subsequently used to fabricate Bi3+–Eu3+-codoped LaF3 NPs using the same method. The emission intensity of the codoped NPs increased in more than one order of magnitude, thanks to the possibility of excitation through the Bi3+ → Eu3+ energy-transfer band. The luminescence properties of the codoped NPs were analyzed in detail to find the mechanism responsible for the emission enhancement. Finally, it was demonstrated that the high atomic number of Bi3+, higher than that of lanthanides, was an added value of the material because it increased its X-ray attenuation capacity. In summary, the LaF3 NPs codoped with Eu3+ and Bi3+ presented in this work are promising candidates as a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography.We gratefully acknowledge T.C. Rojas for help with TEM. This work was supported by CSIC projects (PIC2016FR1 and PIE201460E005), Fondo Social Europeo-Gobierno de Aragoń and by Siemens Healthcare S.L.U. We acknowledge the use of the CNA’s ICTS NanoCT facilities.Peer reviewe

Application of High-Power Ultrasound for Dehydration of Vegetables: Processes and Devices

9 páginas, 12 figuras.High-intensity ultrasound is a tool with a great potential for vegetable dehydration. Airborne ultrasonic waves have been used for drying materials in combination with hot air systems to obtain adequate drying rates at lower temperatures. Nevertheless, the extension of this technique has been limited because of practical difficulties in the efficient generation of high-intensity ultrasound in air. The implementation of a new technology of plate-transducer power ultrasonic generators has opened up new possibilities in this area. This article reviews the development and testing of an ultrasonic technology for vegetable dehydration based on the application of the new power ultrasound generators. Two experimental procedures have been carried out by airborne ultrasound and ultrasonic vibration in direct contact with the vegetable.Peer reviewe

Design of a nanoprobe for high field magnetic resonance imaging, dual energy X-ray computed tomography and luminescent imaging

The combination of different bioimaging techniques, mainly in the field of oncology, allows circumventing the defects associated with the individual imaging modalities, thus providing a more reliable diagnosis. The development of multimodal endogenous probes that are simultaneously suitable for various imaging modalities, such as magnetic resonance imaging (MRI), X-ray computed tomography (CT) and luminescent imaging (LI) is, therefore, highly recommended. Such probes should operate in the conditions imposed by the newest imaging equipment, such as MRI operating at high magnetic fields and dual-energy CT. They should show, as well, high photoluminescence emission intensity for their use in optical imaging and present good biocompatibility. In this context, we have designed a single nanoprobe, based on a core-shell architecture, composed of a luminescent Eu:BaLuF core surrounded by an external HoF shell that confers the probe with very high magnetic transverse relaxivity at high field. An intermediate, optically inert BaLuF layer was interposed between the core and the shell to hinder Eu–Ho cross-relaxation and avoid luminescence quenching. The presence of Ba and Lu, with different K-edges, allows for good X-ray attenuation at high and low voltages. The core-shell nanoparticles synthesized are good potential candidates as trimodal bioprobes for MRI at high field, dual-energy CT and luminescent imaging.This research was funded by the Spanish Ministry of Science, Innovation, and Universities (RTI2018-094426-B-I00). Siemens Healthcare S.L.U. also supported part of the research. We also acknowledge the use of the CNA’s ICTS NanoCT facilities and support from DGA and Fondos Feder for funding Bionanosurf (E15_17R) research group. S. Garcia-Embid acknowledges the Ministerio de Educación, Cultura y Deportes of Spanish Government for a FPU grant (FPU15/04482)

Synthesis, functionalization and properties of uniform europium-doped sodium lanthanum tungstate and molybdate (NaLa(XO4)2, X = Mo,W) probes for luminescent and X-ray computed tomography bioimaging

A one-pot simple procedure for the synthesis of uniform, ellipsoidal Eu3+-doped sodium lanthanum tungstate and molybdate (NaLa(XO4)2, X  = W, Mo) nanophosphors, functionalized with carboxylate groups, is described. The method is based on a homogeneous precipitation process at 120 °C from appropriate Na+, Ln3+ and tungstate or molybdate precursors dissolved in ethylene glycol/water mixtures containing polyacrylic acid. A comparative study of the luminescent properties of both luminescent materials as a function of the Eu3+ doping level has been performed to find the optimum nanophosphor, whose efficiency as X-ray computed tomography contrast agent is also evaluated and compared with that of a commercial probe. Finally, the cell viability and colloidal stability in physiological pH medium of the optimum samples have also been studied to assess their suitability for biomedical applications.This work has been supported by the Spanish Ministry of Science, Innovation and Universities, Spain (RTI2018-094426-B-I00), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (NANOPHOM, grant agreement no. 715832), DGA and Fondos Feder, Aragón, Spain (Bionanosurf E15_17R) and CSIC, Spain (PIC2016FR1). This work was also supported in part by Siemens Healthcare S.L.U., Spain MM thanks MINECO, Spain for Juan de la Cierva Fellowship.Peer reviewe

Plan de atención personalizada

El proyecto consiste en mejorar la inserción y adaptación de aquellos alumnos que se encuentran en una situación académica y personal con dificultades para mantenerse en el nivel educativo de su grupo. Los objetivos son implicar al alumno y su familia en el proceso educativo; detectar y paliar las deficiencias de aprendizaje de cada uno de los alumnos; fomentar el sentido de disciplina y los hábitos de estudio; facilitar la integración del alumnoo, especialmente de los alumnos inmigrantes para mejorar el conocimiento de la Lengua Española; mejorar la autoestima de alumnos cuya situación de partida presenta mayores desigualdades respecto a los compañeros de su medio. La metodología consiste en agrupar a los alumnos según el nivel educativo y el problema que presentan, para formar grupos homogéneos y orientar mejor el tipo de atención que precisan. Las actividades son de comprensión lectora, de expresión personal y de análisis de dificultades, en Lengua Española; lenguaje matemático, tratamiento de discalculia y de lectura de problemas, en matemáticas y, por último, se trabaja la expresión verbal, escritura de textos, gramática elemental, habilidades sociales e inmersión sociocultural en el caso del español para extranjeros. Otras actividades son visitas de interés y actividades culturales. La evaluación valora la aceptación de los propios alumnos, rentabilidad académica, inmersión social, eficacia de los materiales y grado de satisfacción de profesores.Madrid (Comunidad Autónoma). Consejería de EducaciónMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Proyecto piloto para el establecimiento de una red temática Interuniversitaria sobre adecuación de los estudios universitarios de Informática de las universidades públicas de Castilla y León al Espacio Europeo de Educación Superior

Resumen tomado de la publicaciónSe realiza un proyecto piloto para el establecimiento de una Red Interuniversitaria para la adecuación al Espacio Europeo de Educación Superior de la Titulación de Informática de las diferentes Universidades Públicas de Castilla y León. Se configura, se pone en marcha y se difunde de una Red Temática Interuniversitaria. Se elabora en red desde las distintas universidades participantes, una propuesta de recomendación consensuada sobre la forma de ordenar el proceso de adecuación de los estudios de Informática al esquema ECTS, especialmente en lo referente a los procesos de seguimiento y control de calidad. Se revisa, se debate y se realiza una reflexión sobre los contenidos curriculares de Informática.Castilla y LeónConsejería de Educación. Dirección General de Universidades e Investigación; Monasterio de Nuestra Señora de Prado, Autovía Puente Colgante s. n.; 47071 Valladolid; +34983411881; +34983411939;ES