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

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

Influence of root parallelism on the stability of extraction-site closures

Introduction: In premolar extraction cases, root parallelism is recommended to preserve the stability of space closures. The influence of the degree of root parallelism on relapse of tooth extraction spaces has been a controversial topic in the literature. The aim of this study was to compare the angle between the long axes of the canine and the second premolarin patients with and without stability of extraction-space closures. Methods: A sample of 56 patients, treated with 4 premolar extractions, was divided into 2 groups: group 1, consisting of 25 patients with reopening of extraction spaces; and group 2, consisting of 31 patients without reopening of extraction spaces. Panoramic radiographs of each patient were analyzed at the posttreatment and 1-year posttreatment stages. The data were statistically analyzed by using chi-square tests, t tests, analysis of variance (ANOVA), and Pearson correlation coefficients. Results: The results showed that the groups did not differ regarding the angle between the canine and the second premolar, and there was no correlation between angular changes and reopening of extraction spaces, showing that dental angular changes are not determining factors for relapse, and other factors should be investigated. Conclusions: The final angle and the posttreatment changes observed in the angle between the long axes of the canine and the second premolar showed no influence on the relapse of extraction spaces. (Am J Orthod Dentofacial Orthop 2011; 139: e505-e510

Human identification analysis using PCR from the root portion of dental elements under different conditions of temperature and exposure time

Introduction and objective: The main exogenous factors limiting the retrieval of information from human remains are fire and accidents involving high temperatures. Teeth, due to their relatively high degree of chemical and physical resistance, offer the possibility for the recovery of genetic material, becoming important in forensic cases. With the aim to contribute to a standardization of the protocols employed in DNA extraction and analysis, it was evaluated the integrity of DNA recovered from dental roots submitted to high temperatures, simulating what happens to burnt people. Material and methods: Extractions of genomic DNA were made from the dental root after exposure to high temperatures (600ºC, 800ºC and 1000ºC), during 10, 30 and 60 minutes. Results and conclusion: After molecular analysis through PCR technique, it was verified that DNA amplification of the samples was not possible at any of the periods and temperatures analyzed

Cárie dentária em população ribeirinha do Estado de Rondônia, Região Amazônica, Brasil, 2005/2006 Dental caries in a riverine community in Rondônia State, Amazon Region, Brazil, 2005-2006

O objetivo foi analisar experiência de cárie dentária na população ribeirinha residente às margens dos rios Machado e Preto (Rondônia, Brasil), em 2005 e 2006. Foram examinados 469 indivíduos com formulário preconizado pela Organização Mundial da Saúde, sob luz natural e utilização de espátulas de madeira e sonda CPI. Na faixa etária de 4-5 anos de idade, ceod = 4,30 e 19,64% livres de cárie; 6-10 anos, CPOD = 1,04, ceod = 3,52, 17,05% livres de cárie; aos 12 anos, CPOD = 2,65 e 30,76% livres de cárie; aos 18 anos, CPOD = 5,41 e 19,51% livres de cárie; 35-44 anos, CPOD = 17,74 e 2,98% livres de cárie; 65-74 anos, CPOD = 21,56 e 4,34% livres de cárie. Na análise por componentes, constatou-se que o componente cariado tem maior prevalência nas idades de 0-3, 4-5, 6-10, 12 e 18 anos. Em adultos e idosos, o componente que mais contribui é o perdido. Conclui-se que a população apresenta índices de cárie dentária elevados, sendo necessária a atuação em âmbito educativo, preventivo e curativo.<br>This study aimed to analyze dental caries patterns among riverine people from Rondônia State, Brazil (Machado and Preto rivers) in 2005 and 2006. A total of 469 subjects were examined, using the World Health Organization form, under natural light, using a wooden tongue depressor and CPI probe in cases of doubts about the presence of dental caries. The results were: 4-5-year age bracket, dmtf = 4.30 and 19.64% caries-free; 6-10 years, DMTF = 1.04, dmtf = 3.52 and 17.05% caries-free; 12 years, DMTF = 2.65 and 30.76% caries-free; 18 years, DMTF = 5.41 and 19.51% caries-free; 35-44 years, DMTF = 17.74 and 2.98% caries-free; 65-74 years, DMTF = 21.56 and 4.34% caries-free. When each component was analyzed separately in the dmtf and DMTF indices, decay was most prevalent in the 0-3, 4-5, 6-10, 12, and 18-year brackets. However, in young and older adults, the most prevalent component was missing teeth. In conclusion, the study population showed a high dental caries index, thus highlighting the need for educational, preventive, and curative measures

Extraprensa. Cultura e comunicação na América Latina (Edição Especial sep 2019)

A revista Extraprensa é um periódico destinado à publicação da produção científica nas áreas da cultura e da comunicação no Brasil e América Latina, abrangendo temas como a diversidade cultural, cidadania, expressões das culturas populares, artes, mídias alternativas, epistemologia e metodologia em cultura e comunicação

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field