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

Información Investigador: Avila Sosa, Edward Ebner

Resumen Curricular Edward Ávila es químico (ULA) y, actualmente, estudiante del Programa de Doctorado en Química, Mención Estudios de Materiales del PIQA-ULA. Fue instructor en la VI Escuela Venezolana para la Enseñanza de la Química. Además, ha trabajado como ayudante de investigación de las líneas de investigación: Efectos del medio en la estructura cristalina de compuestos zwitteriónicos (CDCHT-ULA) y Síntesis, estudio estructural, comportamiento térmico y magnético de algunos complejos del tipo A3B (C2O4)3.H2O (CDCHT-ULA). Y colaborador en de los Profesores Asiloé Mora y Gerzon Delgado. Actualmente, prepara su línea de investigación en el estudio estructural de compuestos con aplicaciones en Biomimética Inorgánica.Universitario40 - 2005Estudio de estructuras moleculares y cristalinas de pro-ligandos nitro-sulfurados con aplicaciones en Bio-mimética Inorgánica.Noviembre de 2005Licenciado en Química+58 274 2401372Facultad de Ciencias.Personal de [email protected]

VI Escuela Venezolana para la Enseñanza de la Química. - El enlace puente - hidrógeno y sus aplicaciones.

Contenido 1. El enlace de hidrógeno 1.1. Naturaleza y definición. Reseña histórica. 1.2. Definición del enlace de hidrógeno en términos de geometría y energía. 1.2.1. Los parámetros geométricos. 1.2.2. Los parámetros energéticos. 2. El agua y los enlaces de hidrógeno 3. Importancia del agua y sus interacciones en los sistemas biológicos 4. El enlace de hidrógeno en la química supramolecular 4.1. Ingeniería de cristales. 4.2 Reconocimiento molecular. 5. Los aminoácidos y los enlaces de hidrogeno 5.1 Definición y naturaleza. 5.2 El enlace de hidrógeno en los aminoácidos. 5.3. Enlace de hidrógeno bifurcado donador en aminoácidos. 5.4. Efectos cooperativos y patrones de enlaces de hidrógeno en los aminoácidos. 6. [email protected]@ula.veNivel analític

Mechanical properties and X-ray diffraction analyses of clay/sand pellets for CO

In this work, we report the mechanical properties of an alternative material based on a mixture of natural clay and ferruginous sand in pellet form for CO2 capture. These raw materials were collected from Ecuador, and they contain iron and titanium oxides from volcanic origin. To evaluate the effect of the sand content on the mechanical properties of pellets, the samples were manually prepared with 0 (control sample), 15, and 25 wt.% sand contents and analyzed using free-fall drop impact and uniaxial compression tests. The uniaxial compression test was carried out under three conditions: using sieved sand, using sand without sieving, and under wet conditions. The sand contents caused the drop number to decrease in the free-fall drop impact test. From the uniaxial compression test, the compressive strength, elastic modulus, and toughness were calculated. The elastic modulus showed a better performance for samples with lower porosity. The compressive strength demonstrated higher values for samples with 15 wt.% sand contents than for samples with the other sand contents. The toughness values did not significantly change. It was evidenced that the porosity, mineral composition, and humidity exerted an influence during the mechanical tests. The mineral phases were analyzed by X-ray diffraction, and quantitative analysis based on whole-powder-pattern fitting revealed that the iron and titanium oxide contents increased as the concentration of sand in the pellets increased

Porcine Hemagglutinating Encephalomyelitis Virus Infection In Vivo and Ex Vivo.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a betacoronavirus that causes vomiting and wasting disease and/or encephalomyelitis in suckling pigs. This study characterized PHEV infection, pathogenesis, and immune response in cesarean-derived, colostrum-deprived (CDCD) neonatal pigs. Infected animals developed mild respiratory, enteric, and neurological clinical signs between 2 to 13 days postoronasal inoculation (dpi). PHEV did not produce viremia, but virus shedding was detected in nasal secretions (1 to 10 dpi) and feces (2 to 7 dpi) by reverse transcriptase quantitative PCR (RT-qPCR). Viral RNA was detected in all tissues except liver, but the detection rate and RT-qPCR threshold cycle (CT ) values decreased over time. The highest concentration of virus was detected in inoculated piglets necropsied at 5 dpi in turbinate and trachea, followed by tonsils, lungs, tracheobronchial lymph nodes, and stomach. The most representative microscopic lesions were gastritis lymphoplasmacytic, moderate, multifocal, with perivasculitis, and neuritis with ganglia degeneration. A moderate inflammatory response, characterized by increased levels of interferon alpha (IFN-α) in plasma (5 dpi) and infiltration of T lymphocytes and macrophages were also observed. Increased plasma levels of interleukin-8 (IL-8) were detected at 10 and 15 dpi, coinciding with the progressive resolution of the infection. Moreover, a robust antibody response was detected by 10 dpi. An ex vivo air-liquid CDCD-derived porcine respiratory cells culture (ALI-PRECs) system showed virus replication in ALI-PRECs and cytopathic changes and disruption of ciliated columnar epithelia, thereby confirming the tracheal epithelia as a primary site of infection for PHEV.IMPORTANCE Among the ∼46 virus species in the family Coronaviridae, many of which are important pathogens of humans and 6 of which are commonly found in pigs, porcine hemagglutinating encephalomyelitis remains one of the least researched. The present study provided a comprehensive characterization of the PHEV infection process and immune responses using CDCD neonatal pigs. Moreover, we used an ex vivo ALI-PRECs system resembling the epithelial lining of the tracheobronchial region of the porcine respiratory tract to demonstrate that the upper respiratory tract is a primary site of PHEV infection. This study provides a platform for further multidisciplinary studies of coronavirus infections

Catheter Ablation for Atrial Fibrillation in Adult Congenital Heart Disease: An International Multicenter Registry Study

BACKGROUND: Data on atrial fibrillation (AF) ablation and outcomes are limited in patients with congenital heart disease (CHD). We aimed to investigate the characteristics of patients with CHD presenting for AF ablation and their outcomes. METHODS: A multicenter, retrospective analysis was performed of patients with CHD undergoing AF ablation between 2004 and 2020 at 13 participating centers. The severity of CHD was classified using 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society guidelines. Clinical data were collected. One-year complete procedural success was defined as freedom from atrial tachycardia or AF in the absence of antiarrhythmic drugs or including previously failed antiarrhythmic drugs (partial success). RESULTS: Of 240 patients, 127 (53.4%) had persistent AF, 62.5% were male, and mean age was 55.2±13.3 years. CHD complexity categories included 147 (61.3%) simple, 68 (28.3%) intermediate, and 25 (10.4%) severe. The most common CHD type was atrial septal defect (n=78). More complex CHD conditions included transposition of the great arteries (n=14), anomalous pulmonary veins (n=13), tetralogy of Fallot (n=8), cor triatriatum (n=7), single ventricle physiology (n=2), among others. The majority (71.3%) of patients had trialed at least one antiarrhythmic drug. Forty-six patients (22.1%) had reduced systemic ventricular ejection fraction <50%, and mean left atrial diameter was 44.1±8.2 mm. Pulmonary vein isolation was performed in 227 patients (94.6%); additional ablation included left atrial linear ablations (40%), complex fractionated atrial electrogram (19.2%), and cavotricuspid isthmus ablation (40.8%). One-year complete and partial success rates were 45.0% and 20.5%, respectively, with no significant difference in the rate of complete success between complexity groups. Overall, 38 patients (15.8%) required more than one ablation procedure. There were 3 (1.3%) major and 13 (5.4%) minor procedural complications. CONCLUSIONS: AF ablation in CHD was safe and resulted in AF control in a majority of patients, regardless of complexity. Future work should address the most appropriate ablation targets in this challenging population

Ensaio de proficiência em cachaça : relatório final - 2ª rodada

39 f.: il.Com a crescente demanda por parte dos organismos reguladores e clientes que exigem provas regulares e independentes de competência, o ensaio de proficiência torna-se uma ferramenta indispensável para todos os laboratórios que avaliam a qualidade de produtos. Desta forma, a participação de laboratórios em ensaios de proficiência é de fundamental importância para que se verifique a consistência das atividades desenvolvidas. Os resultados obtidos constituem-se evidência da qualidade e competência, assim como uma ferramenta de melhoria de desempenho. Num contexto geral, o ensaio de proficiência traz como benefícios: avaliação do desempenho do laboratório e monitoração contínua; evidência de obtenção de resultados confiáveis, identificação de problemas relacionados com a sistemática de ensaios; possibilidade de tomada de ações corretivas e/ou preventivas; avaliação da eficiência de controles internos; determinação das características de desempenho e validação de métodos e tecnologias; padronização das atividades frente ao mercado, e reconhecimento de resultados de ensaios, em nível nacional e internacional. Este relatório apresenta uma análise estatística dos resultados dos laboratórios participantes da 2a rodada do Ensaio de Proficiência em Cachaça, que teve a coordenação técnica da Divisão de Metrologia Química (Dquim) e coordenação geral do Programas de Ensaios de Proficiência (PEP) da Diretoria de Metrologia Científica e Industrial (Dimci) do Instituto Nacional de Metrologia, Normalização e Qualidade Industrial – Inmetro. Os analitos incluídos nesse Ensaio de Proficiência (cobre, arsênio, chumbo, metanol, 1-butanol e carbamato de etila) foram escolhidos em razão de estarem descritos como contaminantes da cachaça de acordo com a Instrução Normativa no 13, de 29/06/2005 (DOU 30/06/2005), do Ministério da Agricultura, Pecuária e Abastecimento – MAPA. Além disto, esse Ensaio de Proficiência proverá aos laboratórios participantes subsídios para o processo de acreditação de acordo com o Regulamento de Avaliação da Conformidade da Cachaça estabelecido pelo Inmetro, de 24 de junho de 2005 (DOU 28/06/2005), item 10. Trinta e dois (32) laboratórios se inscreveram para a participação do Ensaio de Proficiência em Cachaça – segunda rodada