Evaluation intégrée des mesures agro-environnementales territorialisées à enjeu "qualité des eaux" sur la période 2007 à 2011 : le projet MAEVEAU

The MAEVEAU project has developed an approach for an integrated assessment of effectiveness of regionalized Agro-Environmental Measures (MAET) intended to preserve water quality in relation to pesticides. This approach investigates the concept of efficiency through a triple analysis: the impact (net effects), the environmental cost-effectiveness and the role of organizational factors in the contracting process. The impact is assessed by a quasi-experimental approach by counterfactuals and examines adaptation of the matching method to the regionalized MAET. Cost-effectiveness analysis is based on integrated modeling spatially distributed coupling the agro-hydrological SWAT model, pesticides pressure indicators and a bio-economic model optimizing gross margin. The effectiveness of organizational factors focuses on transaction costs, the role of collective action and preferences for alternative contracts.La recherche conduite dans le projet MAEVEAU a développé une démarche d'évaluation intégrée de l'efficacité des Mesures Agro-Environnementales Territorialisées (MAET) à enjeu préservation de la qualité de l'eau vis-à-vis des pesticides sur la période 2007 à 2011. La question scientifique traite le concept d'efficacité de la politique en s'appuyant sur une triangulation des approches: une évaluation de l'impact (c'est-à-dire des effets propres de la politique), une évaluation coût-efficacité environnementale et une évaluation du rôle des facteurs organisationnels dans le processus d'adhésion. L'impact est évalué par une approche quasi-expérimentale par contrefactuel et questionne l'adaptation de la méthode du matching à la territorialisation des MAET. L'analyse coût-efficacité s'appuie sur une modélisation intégrée spatialisée couplant modèle agro-hydrologique, indicateurs pesticides spatialisés et optimisation économique des marges brutes. L'efficacité des facteurs organisationnels s'est intéressée aux coûts de transaction, au rôle de l'action collective et aux préférences pour des contrats alternatifs

Sickle cell disease: An international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of asuitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. Themedian age at transplantation was 9 years, and themedian follow-up was longer than 5 years. Most patients received amyeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bonemarrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Eventfree survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P<.001) and higher for transplantations performed after 2006 (HR, 0.95; P = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD

Sickle cell disease: An international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of asuitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. Themedian age at transplantation was 9 years, and themedian follow-up was longer than 5 years. Most patients received amyeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bonemarrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Eventfree survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P<.001) and higher for transplantations performed after 2006 (HR, 0.95; P = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD

Assessment of recent process analytical technology (PAT) trends : a multiauthor review

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old