Effect of high energy proton irradiation on MAPbI 3 films for space applications observed by micro-Raman spectroscopy

Irradiation of samples with 10 MeV protons is a standard test for simulation of outer space environment in order to qualify devices and materials for space applications. Micro-Raman spectroscopy allows to determine the irradiation effect in methylammonium lead iodide (MAPbI3) thin films under ambient conditions and encapsulated. For the unprotected films, the vibrational modes matched previously reported lead oxide phonon frequencies and the appearance of superficial oxides was confirmed by EDAXS analysis. However, the Raman shifts corresponding to PbO were not observed for the irradiated encapsulated samples, indicating that oxidation occurs after surface exposure to ambient oxygen. Similar effects were observed by photooxidation where the superoxide highly reactive radical is involved in the oxidation mechanism. We propose that irradiation promotes excitation of the electronic cloud that readily reduces the surface adsorbed oxygen and later bonds to the accessible Pb atoms.Fil: Herrera Martinez, Walter Oswaldo. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; ArgentinaFil: Giudici, Paula Inés. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; ArgentinaFil: Correa Guerrero, Natalia Belén. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; ArgentinaFil: Ibarra, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; Argentina. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; ArgentinaFil: Perez, Maria Dolores. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; Argentin

Estudio de la factibilidad de fabricación de celdas solares de perovskitas en Argentina mediante análisis de ciclo de vida e indicadores energéticos.

Las celdas solares de perovskita (PSC por sus siglas en inglés) son objeto de estudio en el campo de las energías renovables gracias a sus elevadas eficiencias de fotoconversión. En este trabajo se presenta el análisis de ciclo de vida (ACV) de la cuna a la puerta de PSC fabricadas en C.A.B.A. para evaluar su impacto adoptando como unidad funcional 1m2 de PSC fabricada considerando la configuración de una celda típica construida en los laboratorios de CNEA mediante spin coating. Se realizó un estudio de indicadores energéticos EPBT y EROI (Energy PayBack Time y Energy Return of Investment) de donde se obtuvo el tiempo de vida requerido para que la fabricación de los dispositivos pueda ser viable energéticamente. Además se estudió cómo varían estos según la localidad donde se implementen los dispositivos y cómo sería la variación de energía en todo el proceso si se aplican técnicas de encapsulado. Las PSC con eficiencias de 15% alcanzaron valores de EPBT de 10 meses en C.A.B.A., y valores de EROI comparables a otras tecnologías fotovoltaicas si se extrapola el tiempo de vida a 5 años como mínimo. Además del ACV se pudo observar que el mayor aporte energético está dado por el tipo de proceso elegido en la fabricación.Perovskite solar cells (PSC) are a relevant subject of study in the field on renewable energies due to their excepcional photoconversion efficiency. Even though the laboratory reports are very promising, it is necessary to perform a scale-up factibility analysis in order to determine if PSCs can become a useful technology. In this report we performed a life cycle assessment (LCA) from-cradle-to-door of PSCs fabricated in the Buenos Aires city area in order to evaluate the impact of each fabrication process. The functional unit consist of cells of 1m2 prepared at the CNEA laboratories via spin coating. The energy payback time (EPBT) and the energy return of investment (EROI) were analysed in order to examine the energy generation of the PSCs. Additionally, we studied those indicators under different conditions like solar irradiation and incorporating an extra encapsulation step in the PSC fabrication device. EPBT values for PSC with 15% photo conversion efficiency (PCE) result in 10 months for Buenos Aires. Moreover, the EROI values were similar to those reported in literature. From the LCA we could determine that the major energy intake is due to the kind of technology of choice for the device fabrication.Fil: Correa Guerrero, Natalia Belén. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; ArgentinaFil: Herrera Martinez, Walter Oswaldo. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Perez, Maria Dolores. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Constituyentes.; Argentin

Electroluminescence transients and correlation with steady-state solar output in solution-prepared CH3NH3PbI3 perovskite solar cells using different contact materials

Electroluminescence (EL) transients of solution-prepared CH3NH3PbI3 perovskite solar cells were recorded under different biasing voltage conditions. The EL transients are reversible and show a sharp increase and a peak in the range of 1 s to 10 s, while after the peak the signal decays in 30 s to 60 s. The possible origins of the different features are discussed, pointing to a shift in the region of dominating recombination during biasing, governing the EL increase, and the creation of ion migration-induced non-radiative recombination centers during the EL decrease. Moreover, when ramping up the polarization voltage, the EL transients shorten, suggesting an acceleration of the microscopic mechanism with increasing electric fields. Cells prepared with compact instead of mesoporous TiO2 electron contact show faster dynamics, highlighting the link between dynamics and interface properties. Furthermore, experiments using cells with different hole contacts show that the observed behavior and the duration of the transient is similar in cells using Spiro-OmeTAD and copper phatlocyanine (CuPc). When considering the steady-state EL, the open circuit voltage under solar operation correlates with EL across samples with different HTL materials. A non-monotonous behavior is also observed in temperature-dependent EL transients, where maxima in EL as well as in time to the peak are observed around 30 °C, which is close to the temperature of crystalline phase change from tetragonal to cubic phase known in CH3NH3PbI3 at 37 °C.Fil: Córdoba, Matías Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas; ArgentinaFil: Herrera Martinez, Walter Oswaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; Argentina. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; ArgentinaFil: Koffman Frischknecht, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas; ArgentinaFil: Correa Guerrero, Natalia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; Argentina. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; ArgentinaFil: Perez, Maria Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes | Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología - Nodo Constituyentes; Argentina. Comision Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones no Nucleares. Gerencia Física (CAC). Grupo Energía Solar; ArgentinaFil: Taretto, Kurt Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas. Universidad Nacional del Comahue. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas; Argentin

Características seminales de ovinos bajo condiciones ambientales del Caribe Colombiano

The aim of this study was to evaluate the seminal characteristics and the physical and functional conditions of native and introduced sheep breeds under the environmental conditions of the Colombian Caribbean. In total, 117 Santa Inés, Dorper, Katahdin and Ovinos de Pelo Colombiano (OPC) rams older than 11 months were evaluated for 14 months. The animals were from 18 farms of the departments of Córdoba, Sucre, Bolívar, Cesar and La Guajira. The physical-functional examinations of the males were carried out, as well as the macroscopic and microscopic characteristics of the semen. There were no differences (p>0.05) between breeds, departments and collection methods for the variables testicular volume, testicular length and width, scrotal circumference and testicular tone. In the humid Caribbean, mass motility was 76.36 ± 6.13% and the sperm concentration was 2707 ± 573x106 sperm/ml as compared to those found in the dry Caribbean (64.41 ± 5.45% and 962 ± 509.72 x106 sperm/ml, respectively). Semen collection method had a significant influence (p<0.05) on ejaculate volume, viability, vigour and sperm concentration. Seminal parameters were higher in the second and third trimester of the year and the relative humidity of the Caribbean had a significant effect on testicular volume (r=-0.23) and sperm abnormalities (r=0.29). It is concluded that the Santa Inés, Dorper, Katahdin and OPC sheep have satisfactory and viable characteristics for their reproduction in the Colombian Caribbean.El objetivo del presente estudio fue evaluar las características seminales y las condiciones físicas y funcionales de ovinos nativos y foráneos bajo las condiciones ambientales del Caribe Colombiano. Se evaluaron durante 14 meses a 117 carneros Santa Inés, Dorper, Katahdin y Ovinos de Pelo Colombiano (OPC) mayores de 11 meses. Los animales eran de 18 fincas de los departamentos de Córdoba, Sucre, Bolívar, Cesar y La Guajira. Se realizaron los exámenes físico-funcionales de los machos, así como las características macroscópicas y microscópicas del semen. No hubo diferencias (p>0.05) entre razas, departamentos o métodos de colecta para las variables volumen testicular, largo y ancho testicular, circunferencia escrotal y tono testicular. En el Caribe húmedo la motilidad masal fue 76.36 ± 6.13% y la concentración espermática de 2707 ± 573x106 espermatozoides/ml en comparación con los encontrados en el Caribe Seco (64.41 ± 5.45% y 962 ± 509.72 x106 espermatozoides/ml, respectivamente). El método de extracción seminal influyó significativamente (p<0.05) sobre el volumen del eyaculado, viabilidad, vigor y concentración espermática. Los parámetros seminales fueron más elevados en el segundo y tercer trimestre del año y la humedad relativa del caribe tuvo efecto significativo en el volumen testicular (r=-0.23) y anormalidades espermáticas (r=0.29). Se concluye que los ovinos Santa Inés, Dorper, Katahdin y OPC presentan características satisfactorias y viables para su reproducción en el Caribe Colombiano

Efecto de la suplementación energético-proteica sobre el desempeño productivo en vacas Romosinuano durante el pre y posparto

The effect of energy and protein densities of diets on homeostasis, metabolic profile and productive performance during pre and postpartum periods of Romosinuano cows was evaluated. Thirty grazing cows were assigned to three nutritional supplementation groups: TC: 0.0, T1: 2.35 and T2: 2.8 kg/animal/day of energy-protein supplement. The experiment ran from 30 days before calving to 60 days postpartum. Body weight (BW), body condition (BCS) and serum concentrations of glucose, cholesterol, total protein, β-hydroxybutyrate, non-esterified fatty acids (NEFAs), urea, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. The prepartum supplementation did not affect BW (p=0.4557) nor BCS (p=0.1893). In the postpartum period, there was a significant effect of supplementation on BW (p=0.0343) and BCS (p=0.029) in T1 and T2 and on glucose at prepartum in T2 (p=0.0019). For cholesterol, there was a significant effect on prepartum in T2 (p=0.0036), as well as on days 5 and 60 postpartum in T1 and T2 (p=0.001). In β-hydroxybutyrate there was a significant effect on postpartum days 5 and 12 in TC (p=0.0365). For NEFAs there were no differences between treatments in the two phases. For total protein, a significant effect was found in the postpartum in T2 (p=0.0163) while for urea it was in the prepartum in TC (p=0.0334). For AST there was a significant effect on postpartum day 5 in T2 (p=0.0202) and for ALT at postpartum day 60 in T2 (p=0.0018). The supply of up to 2.8 kg/animal/day of energy-protein supplement optimizes the metabolic state of Romosinuano cows during the pre and postpartum period, and the productive performance, BW and BCS postpartum.Se evaluó el efecto de densidades energéticas y proteicas de dietas sobre la homeostasis, perfil metabólico y desempeño productivo durante el pre y postparto de vacas Romosinuano. Treinta vacas en pastoreo fueron asignadas a tres grupos de suplementación nutricional: TC: 0.0 T1: 2.35 y T2: 2.8 kg/animal/día de suplemento energético-proteico. El experimento se desarrolló desde 30 días antes del parto hasta 60 días posparto. Se evaluó el peso corporal (Pcorp), condición corporal (CC) y concentraciones séricas de glucosa, colesterol, β-hidroxibutirato, ácidos grasos no esterificados (NEFAs), proteína total, urea, aspartato aminotransferasa (AST) y alanina aminotransferasa (ALT). La suplementación al preparto no afectó el Pcorp (p=0.4557) y CC (p=0.1893). En el posparto hubo efecto significativo de la suplementación sobre PC (p=0.0343) y CC (p=0.029) en T1 y T2 y de glucosa al preparto en T2 (p=0.0019). Para colesterol hubo efecto significativo en el preparto en T2 (p=0.0036), así como al día 5 y 60 del posparto en T1 y en T2 (p=0.001). En β-hidroxibutirato hubo efecto significativo a los días 5 y 12 posparto en TC (p=0.0365). Para NEFAs no hubo diferencias entre tratamientos en las dos fases. Para proteína total se encontró efecto significativo en el posparto en T2 (p=0.0163), en tanto que para urea fue en el preparto en TC (p=0.0334). Para AST hubo efecto significativo al día 5 del posparto en T2 (p=0.0202) y para ALT al día 60 posparto en T2 (p=0.0018). El suministro de hasta 2.8 kg/animal/día de suplemento energético-proteico optimiza el estado metabólico de vacas Romosinuano durante el pre y postparto, y el desempeño productivo, Pcorp y CC al posparto

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

Genome-wide association study of asthma exacerbations despite inhaled corticosteroids use

Rationale Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies. Methods A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 European-descent children treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed. Results Ten independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078, p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found. Conclusions The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years