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

Fundamental changes in the activity of the natrocarbonatite volcano Oldoinyo Lengai, Tanzania, II: eruptive behaviour during the 2007–2008 explosive eruptions

On September 4,2007, after 25 years of effusive natrocarbonatite eruptions, the eruptive activity of Oldoinyo Lengai (OL), N Tanzania, changed abruptly to episodic explosive eruptions. This transition was preceded by a voluminous lava eruption in March 2006, a year of quiescence, resumption of natrocarbonatite eruptions in June 2007, and a volcano-tectonic earthquake swarm in July 2007. Despite the lack of ground-based monitoring, the evolution in OL eruption dynamics is documented based on the available field observations, ASTER and MODIS satellite images, and almost-daily photos provided by local pilots. Satellite data enabled identification of a phase of voluminous lava effusion in the 2 weeks prior to the onset of explosive eruptions. After the onset, the activity varied from 100 m high ash jets to 2-15 km high violent, steady or unsteady, eruption columns dispersing ash to 100 km distance. The explosive eruptions built up a similar to 400 m wide, similar to 75 m high intra-crater pyroclastic cone. Time series data for eruption column height show distinct peaks at the end of September 2007 and February 2008, the latter being associated with the first pyroclastic flows to be documented at OL. Chemical analyses of the erupted products, presented in a companion paper (Keller et al. 2010), show that the 2007-2008 explosive eruptions are associated with an undersaturated carbonated silicate melt. This new phase of explosive eruptions provides constraints on the factors causing the transition from natrocarbonatite effusive eruptions to explosive eruptions of carbonated nephelinite magma, observed repetitively in the last 100 years at OL

Effect of occurrence thinning on geographical sample bias.

<p>The colors on the map represent the regional sampling density, warmer colors indicating higher sample densities. Occurrence thinning substantially reduces the geographic sampling bias, as illustrated by the disappearance of the red blob along the French Riviera and closeby localities (panel A → B). There is less geographic sampling bias in the native range, so occurrence thinning does not have a big influence on the kernel density maps of that region (panel C → D). Note that the slightly elevated density close to the Spanish-French border in the Bay of Biscay (panels A and B) is caused by samples in the Mediterranean of which the kernel extends across land; there are no occurrences of <i>C</i><i>. cylindracea</i> known from that area.</p

Impact of modeling choices on the transferability of SDMs.

<p>The transferability of models is approximated by test AUC (panel A) and the global niche overlap (Schoener’s D, panel B). Columns and rows represent the combinations of the four factors that were varied in our experimental design and are identical in both panels. The values are also plotted as colors along a color gradient to permit rapid visual assessment of the important factors, with warmer colors indicating higher values. Each AUC value in panel A represent the average of the AUC_{native-invaded} and AUC_{invaded-native} for the corresponding condition.</p

Results of the surveying procedure to identify the predictors present in top-scoring models.

<p>Each box contains the results of the survey for occurrence records from the native range, the invaded European range, or both ranges combined. Each column within a box represents a single survey carried out on one set of thinned coordinates. The circle diameter represents how often the variable in question occurred in the top 10 highest-scoring models (test AUC) for that set of thinned occurrences. The representation of each predictor in the top 10 is also summarized across columns (percentage indicates how many of the top 10 models had the predictor), and the consensus predictor set across ranges is indicated in the box on the right.</p

EPOXI at Comet Hartley 2

International audienceUnderstanding how comets work-what drives their activity-is crucial to the use of comets in studying the early solar system. EPOXI (Extrasolar Planet Observation and Deep Impact Extended Investigation) flew past comet 103P/Hartley 2, one with an unusually small but very active nucleus, taking both images and spectra. Unlike large, relatively inactive nuclei, this nucleus is outgassing primarily because of CO2, which drags chunks of ice out of the nucleus. It also shows substantial differences in the relative abundance of volatiles from various parts of the nucleus