Stable isotope composition of freshwater mollusk shells from Central-Western Argentina

The variability in δ18O and δ13C composition of modern and fossil mollusk shells in central-western Argentina was assessed in order to contribute to a better understanding of their value as paleoclimatic indicators. Living mollusks were collected from 17 sites distributed along a latitudinal/altitudinal gradient in Mendoza Province. Quaternary mollusks were obtained from fi ve alluvial successions outcropping in river margins from the same area. Results indicated that δ18Oshell refl ects the isotope composition of ambient water. For rivers, mollusks refl ect the highly depleted isotopic values recorded in the catchment areas (glaciers). Mollusks inhabiting brackish lakes exhibited the maximum enrichment isotope values in coincidence with high evaporation. Variations in δ13Cshell were consistent with regional variations in productivity. No differences in δ18O and δ13C values were recorded among different species coexisting at the same site, suggesting that mollusks exhibit minor, if any, physiological fractionation effects. The high δ18O values obtained in Late Pleistocene shells suggest an increased evaporation rate for this moment, in coincidence with the development of damp areas characterized by an increase of ice melting in a warmer phase. An 18O enrichment together with a 13C depletion was recorded during the Holocene, suggesting less productive paleoenvironments, probably due to the incidence of more arid conditions than present.Variações de δ18O e δ13C em conchas de moluscos fósseis e atuais do centro-oeste da Argentina foram avaliadas a fim de se contribuir para a melhor compreensão do valor desses elementos como indicadores paleoclimáticos. Moluscos vivos foram coletados en 17 locais distribuídos ao longo de um gradiente latitudinal/altitudinal na Província de Mendoza. Moluscos quaternários foram obtidos em cinco depósitos aluviais afl orantes nas margens do rios desta região. Os resultados indicaram que os valores de δ18Oconcha refl etem a composição isotópica da água do ambiente. Nos rios, os moluscos refl etiram os valores isotópicos altamente empobrecidos, registrados nas áreas de captação (geleiras). Em lagos de água salobra, os moluscos apresentaram os valores máximos de enriquecimento de isótopos, que refl etiram a alta taxa de evaporação. Variações nos valores de δ13Cconcha foram consistentes com variações regionais de produtividade. Diferenças nos valores de δ18O e δ13C não foram registradas entre espécies diferentes convivendo nos mesmos locais, sugerindo que moluscos exibem pouco ou nenhum efeito fi siológico ao fracionamento. Os altos valores de δ18O obtidos em conchas do Pleistoceno Superior sugerem que uma taxa de evaporação mais elevada deve ter ocorrido neste intervalo de tempo, concomitantemente ao desenvolvimento de áreas úmidas e ao aumento no degelo que ocorreram em fase de temperatura mais quente. Um enriquecimento de 18O, acompanhado por uma depleção de 13C, foi registrado durante o Holoceno, sugerindo a existência de paleoambientes menos produtivos, provavelmente devido à incidência de condições mais secas do que no presente.Fil: de Francesco, Claudio German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras; Argentina;Fil: Hassan, Gabriela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras; Argentina

Geoarchaeological and Paleoenvironmental context of the human settlement in the Eastern Tandilia Range, Argentina

The Tandilia range is a discontinuous series of hills and valleys located at the central area of the Pampean region (Argentina). The process of human settlement reached in this zone the highest population densities and reoccupation levels of Southern South America, developing under the strongly changing climatic conditions that characterized the Pleistocene–Holocene transition. This paper analyzes the geoarchaeological and paleoenvironmental record of the Pleistocene–Holocene transition (c. 9400–10,500 14C BP) recovered from cave and rockshelter sedimentary successions of the Tandilia range. The analysis of several lines of evidence (stratigraphic, geoarchaeological, archaeological, zooarchaeological, and paleobotanical), suggests that a cold arid to semi-arid climate characterized the late Pleistocene (c. 10,500 BP), and changed abruptly to warmer conditions towards the beginning of the Post-Glacial Period. As a consequence of this climatic amelioration, the populations inhabiting the Tandilia range would have been benefited by a higher availability of resources, which could explain the higher levels of site density and reoccupation found in the area during this period.Fil: Martinez, Gustavo Adolfo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Geología de Costas y del Cuaternario. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto de Geología de Costas y del Cuaternario; Argentina. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueología Regional Bonaerense; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mazzanti, Diana Leonis. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueología Regional Bonaerense; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Quintana, Carlos. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueología Regional Bonaerense; ArgentinaFil: Zucol, Alejandro Fabian. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Colobig, María de Los Milagros. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Hassan, Gabriela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Brea, Mariana. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Passeggi, Esteban. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentin

Las lagunas pampeanas del sureste bonaerense: Una historia de 12.000 años

Un viaje al origen y a la historia de las lagunas pampeanas reconstruidos a partirde los restos de organismos preservados en sus sedimentos.Fil: de Francesco, Claudio German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Hassan, Gabriela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Stutz, Silvina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Sanchez Vuichard, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Tonello, Marcela Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

Avances en los estudios arqueológicos, geoarqueológicos y paleoambientales en las Sierras Orientales de Tandilia. Resultados preliminares de los sitios Alero el Mirador y Abrigo la Grieta

Este trabajo presenta las características de los registros arqueológicos de dos sitios recientemente retomados, denominados Alero El Mirador y Abrigo La Grieta, analizando los conjuntos líticos, su relación con las unidades estratigráficas, el registro zooarqueológico y paleoambiental (obtenidos a partir de la evidencias de diatomeas, antracología y fitolitos). Esta información proxy permite hipotetizar aspectos del manejo antrópico de recursos naturales locales y de eventos paleoclimáticos ocurridos en el sector serrano de Tandilia oriental durante distintos tramos de la secuencia Pleistoceno-Holoceno. Esta primera contribución abarca las cronologías asignadas al Holoceno medio y comienzos del Holoceno tardío respectivamente, hallándose en curso dataciones por AMS del nivel basal de uno de estos sitios (AEM).This paper presents the characteristics of the archaeological record of two sites recently taken up, called Alero El Mirador and Abrigo La Grieta. The study of different proxy data like lithic assemblages, zooarchaeological and paleoenvironmental record (obtained by diatoms, phytoliths and anthracology inferences) and their relationship to stratigraphic units, allows us to hypothesize anthropic management aspects of local natural resources and paleoclimatic events occurred in the eastern of Tandilia hill during different moments of the Pleistocene-Holocene archaeological sequence.Fil: Mazzanti, Diana Leonis. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueologia Regional Bonaerense; Argentina;Fil: Martinez, Gustavo Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras; Argentina;Fil: Colobig, María de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico y Transferencia de Tecnologia A la Producción; Argentina;Fil: Zucol, Alejandro Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico y Transferencia de Tecnologia A la Producción; Argentina;Fil: Passeggi, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico y Transferencia de Tecnologia A la Producción; Argentina;Fil: Brea, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico y Transferencia de Tecnologia A la Producción; Argentina;Fil: Bonnat, Gustavo Federico. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueologia Regional Bonaerense; Argentina;Fil: Hassan, Gabriela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Mar del Plata. Instituto de Investigaciones Marinas y Costeras; Argentina;Fil: Soria, Juan Carlos. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueologia Regional Bonaerense; Argentina;Fil: Vera, Jorge Andrés. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueologia Regional Bonaerense; Argentina;Fil: Quintana, Carolina. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Laboratorio de Arqueologia Regional Bonaerense; Argentina

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca