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Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group
No full textInternational audienceBackground: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial.Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979.Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively.Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn.Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche
Fingerprinting sources of beach sands by grain-size, using mid-infrared spectroscopy (MIRS) and portable XRF. Implications for coastal recovery along a tsunami-struck delta coastline
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Optimisation topologique en dynamique des structures : vibrations, résistance à la rupture et incertitudes
No full textThe objective of this thesis is to develop density based-topology optimization methods for several challenging dynamic structural problems. First, we propose a normalization strategy for elastodynamics to obtain optimized material distributions of the structures that reduces frequency response and improves the numerical stabilities of the bi-directional evolutionary structural optimization (BESO). Then, to take into account uncertainties in practical engineering problems, a hybrid interval uncertainty model is employed to efficiently model uncertainties in dynamic structural optimization. A perturbation method is developed to implement an uncertainty-insensitive robust dynamic topology optimization in a form that greatly reduces the computational costs. In addition, we introduce a model of interval field uncertainty into dynamic topology optimization. The approach is applied to single material, composites and multi-scale structures topology optimization. Finally, we develop a topology optimization for dynamic brittle fracture structural resistance, by combining topology optimization with dynamic phase field fracture simulations. This framework is extended to design impact-resistant structures. In contrast to stress-based approaches, the whole crack propagation is taken into account into the optimization processL'objectif de cette thèse est de développer des méthodes d'optimisation topologiques basées sur la densité pour plusieurs problèmes difficiles de structure en dynamique. Premièrement, nous proposons une stratégie de normalisation en élasto-dynamique en vue d'obtenir une distribution optimale de matériau dans la structure qui réduit la réponse aux excitations dynamiques en fréquence et améliore la stabilité numérique dans la méthode BESO (bi-directional evolutionary structural optimisation). Ensuite, pour décrire les incertitudes de paramètres pouvant intervenir dans des problèmes réalistes en ingénierie, un modèle d'incertitudes à intervalle hybride est développé pour prendre en compte les incertitudes dans le problème d'optimisation en dynamique. Une méthode de perturbation est développée pour une optimisation topologique robuste vis-à-vis des incertitudes et permettant des gains de temps de calculs importants. De plus, nous introduisons un modèle d'incertitude de champ d'intervalle dans ce cadre. L'approche est appliquée à l'optimisation topologique des structures mono-matériaux, composites et multi-échelles. Enfin, nous développons un cadre d'optimisation topologique pour la résistance des structures à la fissuration quasi-fragile dans un cadre dynamique, par combinaison avec la méthode de champs de phase. Ce cadre est étendu à la conception de structures résistantes à des impacts. Contrairement aux approches basées sur les contraintes, la totalité de la propagation des fissures est prise en compte dans le processus d'optimisatio
Les enjeux énergétiques et climatiques transforment-ils réellement le champ de l’amélioration de l’habitat ?
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The December 2016 extreme weather and particulate matter pollution episode in the Paris region (France)
No full textInternational audienceHighlights• Study of an intense winter episode of particulate pollution in the Paris region.• Exceptional stagnant conditions explain the highest concentrations.• Organic matter of local origin dominates the chemical composition of the particles with also a strong nitrate component from traffic.• Significant values of oxidative potential are observed
Decompositions of inequality measures from the perspective of the Shapley-Owen value
No full textInternational audienceThis article proposes three new decompositions of inequality measures, drawn from the framework of cooperative game theory. It allows the impact of players' interactions, rather than players' contributions to inequality, to be taken into consideration. These innovative approaches are especially suited for the study of income inequality when the income has a hierarchical structure: the income is composed of several primary sources, with the particularity that each of them is also composed of secondary sources. We revisit the Shapley-Owen value that quantifies the importance of each of these secondary sources in the overall income inequality. Our main contribution is to decompose this importance into two parts: the pure marginal contribution of the considered source and a weighted sum of pairwise interactions. We then provide an axiomatic characterization of each additive interaction decomposable (AID) coalitional value considered in this paper. We give an application of these decompositions in the context of inequality theory
Biocidal substances in the Seine River: contribution from urban sources in the Paris megacity
No full textInternational audienceThis work addresses river contamination by biocidal substances up- and downstream a megacity, with the aim of investigating the contribution of the urban discharges, and proposing effective and concerted mitigation solutions. To this end, ten campaigns were conducted in the two main rivers of the Paris conurbation. Eighteen previously prioritized biocides were all quantified at three sampling locations, and several were found at concentrations that may present a risk to the aquatic ecosystem (dichloroisothiazolinone, diuron, benzalkonium C12 and C14, with concentrations up to 42, 75, 1700, and 150 ng/L, respectively). The collected data enabled daily mass loads of biocides to be assessed (from <1 g/day to several tens of kg/day, the highest values being observed for benzalkonium C12 and C14) and put into perspective with previously characterized loads from the major urban sources. A shift in the distribution of biocide loads between up- and downstream the Paris conurbation was observed for several molecules (benzisothiazolinone, terbutryn, thiabendazole, the median load of which increased by a factor of 1.5 to 3), thus suggesting the contribution of urban discharges to the contamination of receiving waters by biocides. Analysing the long-term dynamics of biocides in the Seine River showed that even if the ban of several molecules as pesticides did have a noticeable impact on surface water contamination, a background pollution remained (3<diuron<75 ng/L, 0.1<isoproturon<5.7 ng/L), which may be related to urban inputs. Our results offer prospects for specific mitigation solutions at three scales: emissions, transport in the sewer system and treatment before discharge
Crisisification et la Boussole Strategique: redéfinition l'(auto)représentation du rôle de l'UE sur la scène internationale ?
No full textInternational audienceTo improve its capacity building, cohesion and effectiveness in the international arena, the EU would like to strengthen the capacity for crisis prevention, intervention and management, through the Strategic Compass. A decision-making method oriented, above all, to crisis response and prevention is already present alongside “traditional” EU decision-making method – i.e., based on long consultations with stakeholders, a long process of mediation and balance between positions to achieve solutions based on consensus and long-term policies. This phenomenon – this change in the nature of the processes by which collective decisions are made – is called crisisification by Mark Rhinard: it consists in ‘finding the next urgent event, prioritizing speed in decision-making, ushering in new constellations of concerned actors and emphasizing new narratives of what matters in European governance’ (Rhinard 2019). According to the discourse of the EU institutions (EEAS 2021), past and, above all, future crises play an essential role in the construction of the Strategic Compass and the “next CSDP”: this could mean that crisisificaiton could, potentially, “prevail” on the traditional method of decision-making, reshaping the (self)representation of the EU role as foreign policy actor and the political processes (internal and external, formal and informal) of CSDP. To do this, the CSDP political discourse arising from the last three decades of political debate – e.g., EU as "civilian power" (Telò 2006), "slow power" etc. – must be first "reform" through a reframing operation which has already begun with the publication of the European Union Global Strategy in 2016 (EUGS) but which could “change gear” with the adoption and publication of the Strategic Compass. More in detail, framing consists of ‘promot[ing] a particular problem definition, causal interpretation, moral evaluation and/or treatment recommendation. [...] Frames diagnose, evaluate and prescribe’ (Entman 1993). Through the comparative analysis of the CSDP documents and official speeches (starting from the EUGS up to the Strategic Compass), this communication questions the main reframing elements of the CSDP discourse arising from the Strategic Compass, how these could impact the self-representation of European actors (governments and institutions) in the international arena and how (and how much) these changes could potentially lead to a crisisification of the CSDP – with important consequences on the identity of European foreign policy and the resulting political processes
Algorithms for pixelwise shape deformations preserving digital convexity
No full textInternational audienceIn this article, we propose algorithms for pixelwise deformations of digital convex sets preserving their convexity using the combinatorics on words to identify digital convex sets via their boundary words, namely Lyndon and Christoffel words. The notion of removable and insertable points are used with a geometric strategy for choosing one of those pixels for each deformation step. The worst-case time complexity of each deflation and inflation step, which is the atomic deformation, is also analysed
Lizards from warm and declining populations are born with extremely short telomeres
No full textInternational audienceAging is the price to pay for acquiring and processing energy through cellular activity and life history productivity. Climate warming can exacerbate the inherent pace of aging, as illustrated by a faster erosion of protective telomere DNA sequences. This biomarker integrates individual pace of life and parental effects through the germline, but whether intra- and intergenerational telomere dynamics underlies population trends remains an open question. Here, we investigated the covariation between life history, telomere length (TL), and extinction risk among three age classes in a cold-adapted ectotherm ( Zootoca vivipara ) facing warming-induced extirpations in its distribution limits. TL followed the same threshold relationships with population extinction risk at birth, maturity, and adulthood, suggesting intergenerational accumulation of accelerated aging rate in declining populations. In dwindling populations, most neonates inherited already short telomeres, suggesting they were born physiologically old and unlikely to reach recruitment. At adulthood, TL further explained females’ reproductive performance, switching from an index of individual quality in stable populations to a biomarker of reproductive costs in those close to extirpation. We compiled these results to propose the aging loop hypothesis and conceptualize how climate-driven telomere shortening in ectotherms may accumulate across generations and generate tipping points before local extirpation