Toxicité croisée des immunothérapies dans la prise en charge du mélanome métastatique

Introduction: Les immunothérapies, représentées par les anti-CTLA4 (Ipilimumab) et anti-PD1 (Nivolumab et Pembrolizumab) constituent une révolution thérapeutique chez les patients présentant un mélanome métastatique. Leur bénéfice majeur en termes de survie peut s’obtenir au prix d’effets secondaires d’un nouvel ordre : les effets indésirables immunologiques (EII). Objectif: Évaluer la toxicité immunologique croisée de l’Ipilimumab et des anti-PD1, c'est-à dire le risque de récidive d’un EII sévère (grade ≥ 3) à la reprise d’une seconde ligne d’immunothérapie. Patients et méthodes : Étude observationnelle rétrospective multicentrique (CHU de Rouen, Amiens et Caen) ayant inclus les patients de stade III ou IV (AJCC) traités entre le 01/01/2011 et le 01/05/2017 de façon séquentielle par anti-CTLA4 et anti-PD1. Résultats: 76 patients (39 hommes, 37 femmes) ont été inclus. L’âge médian au diagnostic était de 62.2 ans et le suivi minimum de 8 mois. Soixante-trois patients (82.9%) ont présenté au moins un EII dont 34 (44.7%) ≥ 1 EII sévère. Cinquante-huit patients ont reçu la séquence thérapeutique Ipilimumab/anti-PD1 : 14 (soit 24% de ce groupe) ont présenté un EII sévère sous Ipilimumab et 13 patients (22%) sous anti-PD1. Parmi eux, 2 patients ont présenté une toxicité sévère croisée affectant des organes différents : hypophysite de grade 3 puis néphropathie de grade 4/ hépatite de grade 4 puis colite de grade 4. Aucun des patients ayant présenté un EII sévère résolutif sous Ipilimumab n’a donc présenté de récidive de sa toxicité immunologique initiale sous anti-PD1. Dix-huit patients ont reçu la séquence anti- PD1/Ipilimumab : 2 patients (11%) ont présenté un EII sévère sous anti-PD1 et 7 patients (39%) sous Ipilimumab. Deux patients ont présenté une récidive de leur toxicité digestive dans une forme secondairement sévère (colites) mais aucun ayant présenté un EII sévère sous anti- PD1 n’a ensuite récidivé sous Ipilimumab. Il n’y a pas eu de recours à un traitement immunosuppresseur autre que la corticothérapie systémique pour la prise en charge de ces EII. Conclusion: Cette étude fournit donc des résultats rassurants concernant le risque de récidive d’un EII sévère dans un schéma thérapeutique séquentiel d’immunothérapies

Well-Balanced conservative central upwind scheme for solving the dam-break flow problem over erodible bed

This work deals with the numerical solution of dam-break flow over an erodible bed. The mathematical model is a combination of the shallow water, the transport diffusion and the bed morphology change equations. The system is solved by a well-Balanced central upwind scheme with conservative property. Several tests are illustrated in order to validate the accuracy and the performance of the model. A comparison of central upwind scheme and Roe scheme is presented

Numerical modeling of underground flow through porous media using volumes scheme

The Richards equation attracts the attention of several researchers due to its importance in the hydrogeology field especially the flow through porous soil. It is a non linear partial differential equation that has no general analytic solution. Thus, the need to use numerical methods to solve it. In this work, a finite volumes scheme is used to simulate the pressure form and the mixed form of Richards equation in one dimension. Euler explicit and implicit schemes are used for the time discretization and a condition of scheme’s stability is given. Different test cases are done to validate the accuracy and the efficiency of the proposed numerical mode

Motion capture and myoelectric multimodal measurements during static and dynamic bending tasks using a back-assisting exoskeleton: a preliminary study

International audienceWork-related musculoskeletal disorders are causing occupational diseases. While allowing them to control the execution of their picking task, one solution to physically relieve workers performing trunk flexions is to assist them with an exoskeleton. This preliminary study focuses on the determination of the appropriate measurements systems (motion capture and electromyography) to characterize dedicated trajectories of movements responsible of lower back pathologies. Three tests have been realized with and without a back-assisting exoskeleton for loaded box picking. The results of the study help us to understand which body strategies were used to perform the same task from one individual to another under different conditions. This preliminary study validates this multimodal approach to show the use of a back-assisting exoskeleton for posture harness in dynamic conditions

Energy and Environmental National Assessment of Alternative Fuel Buses in Morocco

The heavy reliance on petroleum-based fuels in the road transport industry, especially public transportation, results in substantial emissions of greenhouse gases. A significant obstacle on the path to a more sustainable public transportation sector is the employment of alternative fuels with lower environmental implications. Although there are several in-depth well-to-wheel studies for developed countries, extrapolating those results to gasoline markets in developing countries presents challenges because of significant differences in local fuel conditions and vehicle engine technologies. Notably, this study provides a national-level environmental life cycle assessment of alternative buses in Morocco and compares current diesel buses to potential hybrid diesel-electric buses, battery-electric buses, and fuel-cell buses from a well-to-wheel perspective. The model and approach used in this study applies to other countries with developing economies. Total energy consumption broken out by fuel type, greenhouse gas emissions, and criterion air pollutants is the primary outcome of this investigation. Findings highlight an energy cut of 44.7% from battery-electric buses, 36.3% from fuel-cell buses, and 31.7% from hybrid buses with regard to the current diesel buses. Additionally, alternative fuel buses proved to be less polluting in terms of greenhouse gas emissions with 50.8% less from battery-electric buses, 46.7% less from fuel-cell buses, and 26.8% less from hybrid buses; consequently, this would lead to reduced climate change, air pollution, acidification, and eutrophication, given the Egalitarian Environmental Impact Assessment. Ultimately, Morocco will have to tackle technological, financial, and institutional barriers to fully implement the change by 2030

Energy and environmental evaluation of alternative fuel vehicles in Maghreb countries

This study conducts a well-to-wheel assessment of alternative fuel vehicles in the Maghreb region, aiming to reduce greenhouse gas emissions from the transport sector. The research employs international standards, ISO 14040–14043, to assess diesel, hybrid-electric, battery-electric, and fuel-cell vehicles and highlights the potential benefits of transitioning to electric and fuel-cell vehicles in the Maghreb, offering energy efficiency and reduced environmental impact.The sensitivity analysis suggests that fuel-cell vehicles are the best alternative for Morocco and Algeria, while battery-electric vehicles are preferable in Tunisia. By 2030, fuel-cell vehicles in Morocco and Algeria would consume 128 ​MJ and 125 ​MJ and emit 7.9 CO2eq and 7.1 CO2eq emissions per 100 ​km, respectively, while in Tunisia, battery-electric vehicles are expected to consume 114 ​MJ and emit 6.55 CO2eq emissions per 100 ​km driven. Ultimately, the right adoption of alternative fuel vehicles in the Maghreb region implies half energy need cut off and 60% less GHG emissions from light-duty vehicles leading to improved environmental conditions, health outcomes, and economic growth

Renewable Power Generation: A Supply Chain Perspective

In recent years, the transition to a more sustainable and clean system has focused on the accelerated development of renewable energy technologies. This transition can be perceived as a major priority, especially with the current environmental concerns, threatening various aspects of human life. The objective of this article is, therefore, to highlight the role of the supply chain in the renewable power generation sector. In this context, a detailed assessment of the supply chain contribution to the renewable energy sector is presented. Next, the performance of the renewable energy supply chain is qualitatively evaluated by illustrating the various barriers against continuing development, and the key measures are recommended to overcome these barriers. Then, the main factors influencing the performance of the supply chain are identified and key performance indicators related to the renewable energy supply chain are established to achieve high efficiency and sustainability performances in the power sector