CHALLENGE 6: Exposing the roots of mental disorders

Mental disorders have devastating and increasing impact in our societies. CSIC researchers face the challenge of determining the biological and social causes and consequences of these disorders, and of finding efficient therapies. To these aims, the collaborative effort of neuroscientists, neurologists, psychiatrists, psychologists and human and social scientists, the use and development of state-of-the-art technologies and the contact with patient associations and pharma industry are required.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Bordón : revista de pedagogía

El título aparece en español y, a continuación, el título traducido al inglés: ‘Solving arithmetic problems using an innovative technological methodology'Se resumen los aspectos relevantes de una investigación sobre la clasificación de los problemas aritméticos según su estructura semántica. Además se comenta cómo puede abordarse su didáctica desde una metodología innovadora basada en la utilización de las tecnologías de aprendizaje y la comunicación. La investigación se lleva a cabo en siete centros educativos de Castilla y León.Madrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; Calle General Ricardos 179; 28025 Madrid; Tel. +34915250893; Fax +34914660991; [email protected]

La evaluación : Seminario de Educación Física

No publicadoEn este volumen se recogen los trabajos finales de los asistentes al Curso 'La evaluación en Educación Física', celebrado en el CPR de León durante el cuso 1995-1996. Estos trabajos toman la forma de Unidades Didácticas, en las que se pone especial énfasis en la evaluación, sus métodos y técnicas. La apreciación de la evaluación dentro del área de Educación Física puede presentar algunas dificultades añadidas a las presentadas a la hora de hacer cualquier tipo de evaluación. Por ello, los grupos de trabajo han optado por reflexionar acerca del planteamiento de la evaluación en Primaria, realizando una ficha de observación en la que se contengan todos los bloques temáticos para poder obtener unos puntos de referencia en la observación lo más objetivos posibles y adecuados al momento de trabajo. .CEP de LeónCastilla y LeónES

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

Search for flavor-changing neutral current interactions of the top quark mediated by a Higgs boson in proton-proton collisions at 13 TeV

International audienceA search for flavor-changing neutral current interactions of the top quark (t) and the Higgs boson (H) is presented. The search is based on proton-proton collision data collected in 2016-2018 at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, and corresponding to an integrated luminosity of 138 fb$^{-1}$. Events containing a pair of leptons with the same-sign electric charge and at least one jet are considered. The results are used to constrain the branching fraction ($\mathcal{B}$) of the top quark decaying to a Higgs boson and an up (u) or charm (c) quark. No significant excess above the estimated background was found. The observed (expected) upper limits at 95% confidence level are found to be 0.072% (0.059%) for $\mathcal{B}$(t $\to$ Hu) and 0.043% (0.062%) for $\mathcal{B}$(t $\to$ Hc). These results are combined with two other searches performed by the CMS Collaboration for flavor-changing neutral current interactions of top quarks and Higgs bosons in final states with a pair of photons or of bottom quarks. The resulting observed (expected) upper limits at 95% confidence level are 0.019% (0.027%) for $\mathcal{B}$(t $\to$ Hu) and 0.037% (0.035%) for $\mathcal{B}$(t $\to$ Hc). These results constitute the most stringent limits on these branching fractions to date

Search for new resonances decaying to pairs of merged diphotons in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search is presented for an extended Higgs sector with two new particles, X and $\phi$, in the process X $\to$$\phi\phi$$\to$$(\gamma\gamma)(\gamma\gamma)$. Novel neural networks classify events with diphotons that are merged and determine the diphoton masses. The search uses LHC proton-proton collision data at $\sqrt{s}$ = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 138 fb$^{-1}$. No evidence of such resonances is seen. Upper limits are set on the production cross section versus the resonance masses, representing the most sensitive search in this channel

Overview of high-density QCD studies with the CMS experiment at the LHC

International audienceThe heavy ion (HI) physics program has proven to be an essential part of the overall physics program at the Large Hadron Collider at CERN. Its main purpose has been to provide a detailed characterization of the quark-gluon plasma (QGP), a deconfined state of quarks and gluons created in high-energy nucleus-nucleus collisions. From the start of the LHC HI program with lead-lead collisions, the CMS Collaboration has performed measurements using additional data sets in different center-of-mass energies with xenon-xenon, proton-lead, and proton-proton collisions. A broad collection of observables related to high-density quantum chromodynamics (QCD), precision quantum electrodynamics (QED), and even novel searches of phenomena beyond the standard model (BSM) have been studied. Major advances toward understanding the macroscopic and microscopic QGP properties were achieved at the highest temperature reached in the laboratory and for vanishingly small values of the baryon chemical potential. This article summarizes key QCD, QED, as well as BSM physics, results of the CMS HI program for the LHC Runs 1 (2010-2013) and 2 (2015-2018). It reviews findings on the partonic content of nuclei and properties of the QGP and describes the surprising QGP-like effects in collision systems smaller than lead-lead or xenon-xenon. In addition, it outlines the scientific case of using ultrarelativistic HI collisions in the coming decades to characterize the QGP with unparalleled precision and to probe novel fundamental physics phenomena

Measurement of boosted Higgs bosons produced via vector boson fusion or gluon fusion in the H →\tobbˉ\mathrm{b\bar{b}} decay mode using LHC proton-proton collision data at s\sqrt{s} = 13 TeV

International audienceA measurement is performed of Higgs bosons produced with high transverse momentum ($p_\mathrm{T}$) via vector boson or gluon fusion in proton-proton collisions. The result is based on a data set with a center-of-mass energy of 13 TeV collected in 2016-2018 with the CMS detector at the LHC and corresponds to an integrated luminosity of 138 fb$^{-1}$. The decay of a high-$p_\mathrm{T}$ Higgs boson to a boosted bottom quark-antiquark pair is selected using large-radius jets and employing jet substructure and heavy-flavor taggers based on machine learning techniques. Independent regions targeting the vector boson and gluon fusion mechanisms are defined based on the topology of two quark-initiated jets with large pseudorapidity separation. The signal strengths for both processes are extracted simultaneously by performing a maximum likelihood fit to data in the large-radius jet mass distribution. The observed signal strengths relative to the standard model expectation are 4.9$^{+1.9}_{-1.6}$ and 1.6$^{+1.7}_{-1.5}$ for the vector boson and gluon fusion mechanisms, respectively. A differential cross section measurement is also reported in the simplified template cross section framework