A multi-model comparison of meteorological drivers of surface ozone over Europe

The implementation of European emission abatement strategies has led to a significant reduction in the emissions of ozone precursors during the last decade. Ground-level ozone is also influenced by meteorological factors such as temperature, which exhibit interannual variability and are expected to change in the future. The impacts of climate change on air quality are usually investigated through air-quality models that simulate interactions between emissions, meteorology and chemistry. Within a multi-model assessment, this study aims to better understand how air-quality models represent the relationship between meteorological variables and surface ozone concentrations over Europe. A multiple linear regression (MLR) approach is applied to observed and modelled time series across 10 European regions in springtime and summertime for the period of 2000–2010 for both models and observations. Overall, the air-quality models are in better agreement with observations in summertime than in springtime and particularly in certain regions, such as France, central Europe or eastern Europe, where local meteorological variables show a strong influence on surface ozone concentrations. Larger discrepancies are found for the southern regions, such as the Balkans, the Iberian Peninsula and the Mediterranean basin, especially in springtime. We show that the air-quality models do not properly reproduce the sensitivity of surface ozone to some of the main meteorological drivers, such as maximum temperature, relative humidity and surface solar radiation. Specifically, all air-quality models show more limitations in capturing the strength of the ozone–relative-humidity relationship detected in the observed time series in most of the regions, for both seasons. Here, we speculate that dry-deposition schemes in the air-quality models might play an essential role in capturing this relationship. We further quantify the relationship between ozone and maximum temperature (mo3 − T, climate penalty) in observations and air-quality models. In summertime, most of the air-quality models are able to reproduce the observed climate penalty reasonably well in certain regions such as France, central Europe and northern Italy. However, larger discrepancies are found in springtime, where air-quality models tend to overestimate the magnitude of the observed climate penalty

Diagn?stico y propuesta de plan estrat?gico para el esquema de c?rceles productivas peruanas

La presente tesis tiene como objetivo realizar un diagn?stico y una propuesta de plan estrat?gico para el esquema de C?rceles Productivas en el Per?. En ese sentido, se analiz? la participaci?n de la empresa privada en el Programa de C?rceles Productivas (espec?ficamente en los talleres productivos) los cuales han podido beneficiar hasta el momento a un peque?o porcentaje de la poblaci?n penitenciaria. De esta manera, la investigaci?n abord? la normativa vigente nacional y comparada; as? como tambi?n se realiz? entrevistas a diferentes funcionarios, expertos y empresarios que participan actualmente del programa para mostrar la manera en que se ha ido gestionando. Es as? que, de las entrevistas y la experiencia internacional, se ha desarrollado un plan tipo de implantaci?n que ser?a desarrollado en el marco de una estrategia propuesta cuyo objetivo es incrementar el n?mero de empresas privadas que participan el programa C?rceles Productivas y por ende el n?mero de internos a ser contratados mediante el otorgamiento de beneficios tributarios a los empresarios participantes en el programa y mejoras operativas. Finalmente se han propuesto modificaciones legales y administrativas para el ?xito de la estrategia

Neuroanatomical and psychological considerations in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular `non-epileptic¿ brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients ¿ with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue. Thus, to better determine how `normal¿ the resected tissue is, it is fundamental to know certain clinical, anatomical and psychological characteristics of the patients. Unfortunately, this information is frequently not fully available for the patient from which the resected tissue has been obtained ¿ or is not fully appreciated by the neuroscientists analyzing the brain samples, who are not necessarily experts in epilepsy. In order to present the full picture of TLE in a way that would be accessible to multiple communities (e.g., basic researchers in neuroscience, neurologists, neurosurgeons and psychologists), we have reviewed 34 TLE patients, who were selected due to the availability of detailed clinical, anatomical, and psychological information for each of the patients. Our aim was to convey the full complexity of the disorder, its putative anatomical substrates, and the wide range of individual variability, with a view toward: (1) emphasizing the importance of considering critical patient information when using brain samples for basic research and (2) gaining a better understanding of normal and abnormal brain functioning. In agreement with a large number of previous reports, this study (1) reinforces the notion of substantial individual variability among epileptic patients, and (2) highlights the common but overlooked psychopathological alterations that occur even in patients who become ¿seizure-free¿ after surgery. The first point is based on pre- and post-surgical comparisons of patients with hippocampal sclerosis and patients with normal-looking hippocampus in neuropsychological evaluations. The second emerges from our extensive battery of personality and projective tests, in a two-way comparison of these two types of patients with regard to pre- and post-surgical performance.This work was supported by grants from the following entities: Grant PID2021-127924NB-I00 funded by MCIN/AEI/10.13039/501100011033; Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066); and CSIC Interdisciplinary Thematic Platform (PTI) Cajal Blue Brain (PTI-BLUEBRAIN; Spain). RA was supported by ANDIA grant #0011-3947-2021-000023 from the Gobierno de Navarra

Towards a holistic understanding of pastoralism

Pastoralism is a globally-important livelihood, with large social, environmental and economic importance across much of our planet. Yet, it is also a vulnerable practice with widespread crises, urgently calling for better systemic understanding. The current disciplinary compartmentalization of research not only hampers this but allows perpetuation of unfortunate misconceptions. Furthermore, a long-standing marginalization of the livelihood prevails, with pastoralism being largely overlooked in international environmental and economic forums or sustainability agendas. Here we call for transformative approaches to pastoralism research that can advance an integrated understanding of these social-ecological systems through a comparative lens. We develop a framework that uses: i) timescales from the distant past to the present, ii)social, economic and environmental dimensions, and iii) diverse geographic contexts and scales, to capture emerging properties allowing for cross-cultural comparisons. We provide specific guidelines for formally developing a coherent set of sustainability indicators that are transferable across time and space, and can track sustainability. In an exploratory exercise, we also show that very distinct pastoralist systems have undergone similar transitions across time, approaching critical thresholds and then either collapsing or recovering. An integrated view of the interactions between the environmental, social and economic dimensions of these transitions allows for an improved understanding of potential tipping points, hence supporting more proactive and informed decision-making. We conclude that the need for a paradigm shift in pastoralism science and policy is pressing. Determining when, where and how is pastoralism not only sustainable, but also the most adaptive livelihood, has become a priority. This paper is based on Manzano et al. (2021).Peer reviewe

Toward a holistic understanding of pastoralism

Pastoralism is globally significant in social, environmental and economic terms. However, it experiences crises rooted in misconceptions and poor interdisciplinary understanding, while being largely overlooked in international sustainability forums and agendas. Here we propose a transdisciplinary research approach to understand pastoralist transitions using i) social, economic and environmental dimensions, ii) diverse geographic contexts and scales to capture emerging properties, allowing for cross-system comparisons, and iii) timescales from the distant past to the present. We provide specific guidelines to develop indicators for this approach, within a social-ecological resilience analytical framework to understand change. Distinct systems undergo similar transitions over time, crossing critical thresholds and then either collapsing or recovering. Such an integrated view of multidimensional interactions improves understanding of possible tipping points, thereby supporting better-informed decision-making. The need for a paradigm shift in pastoralism science and policy is pressing. This research approach, including participatory methods, can provide the solutions urgently needed.Peer reviewe

Mutations in epigenetic regulators including SETD2 are gained during relapse in pediatric acute lymphoblastic leukemia

Relapsed pediatric acute lymphoblastic leukemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signaling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance

Reducing inappropriate polypharmacy: the process of deprescribing

Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application

The Pediatric Cell Atlas:Defining the Growth Phase of Human Development at Single-Cell Resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms