Weak signal detection: A discrete window of opportunity for achieving ‘Vision 90:90:90’?

INTRODUCTION: UNAIDS’ Vision 90:90:90 is a call to ‘end AIDS’. Developing predictive foresight of the unpredictable changes that this journey will entail could contribute to the ambition of ‘ending AIDS’. There are few opportunities for managing unpredictable changes. We introduce ‘weak signal detection’ as a potential opportunity to fill this void. METHOD: Combining futures and complexity theory, we reflect on two pilot case studies that involved the Archetype Extraction technique and the SenseMakerw CollectorTM tool. RESULTS: Both the piloted techniques have the potentials to surface weak signals but there is room for improvement. DISCUSSION: A management response to a complex weak signal requires pattern management, rather than an exclusive focus on behaviour management. CONCLUSION: Weak signal detection is a window of opportunity to improve resilience to unpredictable changes in the HIV/AIDS landscape that can both reduce the risk that emerges from the changes and increase the visibility of opportunities to exploit the unpredictable changes that could contribute to ‘ending AIDS’.IS

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

[West Nile viral meningo-encephalitis in Tunisia].

Archives de Medecine Tropicale sur Gallica (https://gallica.bnf.fr/ark:/12148/bpt6k6458624h.texteImage)International audienceIn autumn 1997 an epidemic outbreak of meningoencephalitis was observed in two coastal districts of Tunisia. A total of 173 cases were recorded with 8 deaths. Detection with IgM capture and indirect IgG ELISAs demonstrated West Nile virus infection in 86% of patients from whom specimens were collected. West Nile is endemic in Asia and Sub-Saharan Africa. Epidemics in humans and horses have also been reported in the Mediterranean region and southern European countries. However this is the first report in Tunisia. Special West Nile virus surveillance is necessary especially in countries at high-risk for repeated introduction of this arbovirus.L'automne 1997 a été marqué par l'éclosion d'une épidémie de méningo-encéphalite dans deux governorats côtiers en Tunisie comptant au total 173 cas dont 8 décédés. Une infection par le Virus West Nile a été retrouvé chez 86% des patients prélevés avec des tests ELISA immunocapture et indirect pour la recherche d'IgM et d'IgC respectivement. Le virus West Nile sévit à l'état à l'état endémique en Asie et Afrique Sud-Saharienne, des épidémies humaines ou équines ont été rapportées dans des pays non endémiques particulièrement en région Méditerranéenne et en Europe du sud, mais c'est la première fois qu'une telle épidémie est rapportée en Tunisie. Une surveillance attentive de cette arbovirose migrante s'avère nécessaire particulièrement dans les pays à risque de ré-introductions répétitives du virus

Investigation of the 3D crystalline network impact on the elastic properties of semi-crystalline polymers from a multi-scale modelling approach

International audienceNowadays, computational resources allow carrying out mechanical calculations on complex multi-scale materials. Finite Element (FE) calculations can especially be directly performed on microstructures of materials. This work is a first attempt to analyse the impact of the crystalline architecture at a mesoscopic scale on the macroscopic elastic properties of Semi-Crystalline Polymers (SCP). Such polymers can be considered biphasic materials, which are composed of an amorphous phase embedded in a crystalline network. The material studied here is Polyethylene (PE). Molecular Dynamics (MD) calculations are carried out on a 100% crystallized Polyethylene model to determine the elastic properties of the crystalline regions of the material. 3D mesostructures of the typical layout of the spherulitic crystalline network of Semi-Crystalline Polymers are then constructed from experimental observations. These material data and this geometrical description are then integrated in computations with the Finite Element method on elementary volumes to finally determine the macroscopic elastic properties of the material. In this work, which is a first attempt to test such a multi-scale workflow, no amorphous phase is considered. Different 3D architectures are compared demonstrating the role of the crystalline arrangement on the stiffness of the material. Three main types of mesostructures have been analysed: crystalline lamellae disposed in a complete random arrangement, crystalline lamellae disposed in a spherulite arrangement, crystalline lamellae with branches disposed in a spherulite arrangement. It appears that the 3D configuration of the lamellae, as well as the presence of branches, have an influence on the macroscopic elastic properties of the material. Then, comparisons with experimental data suggest that the macroscopic elastic properties can be represented with a purely cohesive crystalline network for crystalline degree up to about 50%. This result questions the role of the amorphous phase on the elastic properties of such systems

FROGG high-risk prostate cancer workshop: patterns of practice and literature review: part I: intact prostate

Australian and New Zealand radiation oncologists with an interest in uro-oncology were invited to participate in a pattern-of-practice survey dealing with the management of intact high-risk prostate cancer. Responses from 46 practitioners (representing 73% of all potential respondents) revealed that high-dose radiation therapy is the standard of care. However, there is variability in practice with regard to the methods used to achieve dose escalation, the use of whole-pelvic radiation therapy and the optimal duration of androgen deprivation therapy employed. A review of the literature outlining the current body of knowledge and the planned and ongoing studies in intact high-risk prostate cancer is presented

Reversibility of paraneoplastic bilateral diaphragmatic paralysis after nephrectomy for renal cell carcinoma

Bilateral diaphragmatic paralysis is usually caused by anatomic lesions of both phrenic nerves (e.g., after cardiothoracic surgery), generalized neurologic diseases (e.g., primary motor neuron disease, amyotrophic lateral sclerosis) or is without a known cause (idiopathic). We report a case of a patient with renal cell carcinoma complicated by an isolated bilateral diaphragmatic paralysis without clinical or electromyographic signs of other muscle or nerve involvement. There has been progressive, though till now partial, recovery of his vital capacity rising from 44% to 72% of predicted values, and maximal inspiratory pressures during the two years following the curative resection of his renal cell carcinoma. We believe this is the first report of a paraneoplastic bilateral diaphragmatic paralysis with actual recovery after tumour therapy