Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

1978-2003 : 25 años del IES Larra, 25 años de Aluche

Este proyecto, dirigido a alumnos de ESO y Bachillerato, se basa en un estudio del instituto y del papel que ha tenido en el barrio donde está ubicado. Se analizan, por un lado, aspectos sociológicos, económicos y familiares de la zona de Aluche; y por otro, la labor académica y formativa del centro. Además, con el proyecto se pretende aplicar las nuevas tecnologías a la recogida y análisis de información sobre el origen y la evolución del barrio, desde los años 70 hasta el momento actual. Los objetivos son que alumnos y profesores conozcan la realidad del barrio; detectar los problemas e intentar aportar soluciones pedagógicas; y que todos los alumnos del centro se impliquen en un proyecto común. Para llevarlo a cabo, los alumnos investigan en la hemeroteca para detectar la evolución del barrio y de sus instituciones; elaboran encuestas, para analizar las características del centro y de otros centros de su entorno; y crean indicadores y métodos de evaluación para estudiar los datos. Entre los contenidos trabajados por los grupos destacan aspectos demográficos y sociales del barrio; racismo en institutos de la zona; el papel de las asociaciones en las mejoras del barrio; carteles de la exposición, maqueta y página web; o guía del ocio de Aluche. En anexos incluye diversos materiales como memoria de los distintos grupos de trabajo, encuestas, modelos de evaluación o fichas de antiguos alumnos.Madrid (Comunidad Autónoma). Consejería de EducaciónMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Fortalecer los compromisos entre familia y escuela : un ejemplo de buena práctica : Instituto de Educación Secundaria Mariano José de Larra

Contiene numerosos anexos con documentos y fichas de trabajoEn este libro se recoge las experiencias del Instituto de Educación Secundaria de la Comunidad de Madrid Mariano José de Larra, para favorecer la convivencia escolar a través de unos compromisos, concretados en el Plan de Mejora, que se establecen entre el centro educativo y las familias.MadridBiblioteca Regional de Madrid Joaquín Leguina; Calle Ramírez de Prado, 3; 28045 Madrid; 917208850; 917208890; [email protected]

Proyecto de mejora del estilo cognitivo

Trata el desarrollo de habilidades que ayuden al alumnado a mejorar su rendimiento a través de ejercicios que potencian la habilidad cognitiva. Pretende fomentar la reflexión e investigación individual y colectiva del profesorado en el aula, modificar en el alumnado el estilo cognitivo impulsivo haciéndoles más reflexivos e influir en la dinámica del aula fomentando las interacciones del alumnado-profesorado. La dinámica de trabajo tiene cuatro fases: identificar el problema y toma de conciencia de lo que exige, centrar la atención en la respuesta que se da a esa pregunta autoformulada, eliminar las alternativas no válidas hasta encontrar la correcta y autoevaluarse y autoesforzarse. Evalua el grado de consecución de los objetivos a partir de la observación y fichas de control.Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12)

Abstract Background The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. Methods/design The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3–8,and 1 mg/month in weeks 9–52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. Discussion The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment. Trial registration This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.</p

The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer

Introduction Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. Methods Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and â\u80\u9cbestâ\u80\u9d stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. Results The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. Conclusions The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts

The tenth data release of the Sloan Digital Sky Survey : first spectroscopic data from the SDSS-III Apachhe Point Observatory galactic evolution experiment

The Sloan Digital Sky Survey (SDSS) has been in operation since 2000 April. This paper presents the Tenth Public Data Release (DR10) from its current incarnation, SDSS-III. This data release includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July. The APOGEE instrument is a near-infrared R ∼ 22,500 300 fiber spectrograph covering 1.514–1.696μm. The APOGEE survey is studying the chemical abundances and radial velocities of roughly 100,000 red giant star candidates in the bulge, bar, disk, and halo of the MilkyWay. DR10 includes 178,397 spectra of 57,454 stars, each typically observed three or more times, from APOGEE. Derived quantities from these spectra (radial velocities, effective temperatures, surface gravities, and metallicities) are also included. DR10 also roughly doubles the number of BOSS spectra over those included in the Ninth Data Release. DR10 includes a total of 1,507,954 BOSS spectra comprising 927,844 galaxy spectra, 182,009 quasar spectra, and 159,327 stellar spectra selected over 6373.2 deg2