SurgiMedia (France)

Management of amyotrophic lateral sclerosis (ALS) is complicated by heterogeneous presentation and unpredictable disease course. This study described disease trajectories before and after initiation of non-invasive ventilation (NIV) therapy in individuals with ALS, examined the relationship between NIV initiation timing and survival and analysed health trajectory clusters. Data were extracted from the French national health insurance reimbursement system database for individuals with ≥1 reimbursement for NIV from January 2015 to December 2019, and ≥1 ALS disease code. Health trajectory clusters were determined using time sequence analysis through K-clustering. We analysed data from 3443 individuals with ALS (58% male, median age 67 years). The median (IQR) time from ALS diagnosis to NIV initiation was 10.8 (4.5-22.2) months and death occurred 21.5 (12.8-33.9) months after diagnosis. Tracheostomy/gastrostomy was performed in 3.9%/33.4% of patients, respectively. Unsupervised machine learning clustering identified four distinct patient groups. NIV initiation was late in two Clusters (A and B); these individuals were younger, had fewer comorbidities and more physiotherapy sessions before/after NIV. Survival after NIV initiation was longer in Clusters B and C; these individuals had lower rates of depression/anxiety, more prescription of mechanical in/exsufflation therapy and fewer home and emergency hospitalisations. Cluster B was unique, showing late NIV initiation and long post-NIV survival. This cluster was more likely to have spinal onset, a higher rate of obstructive sleep apnoea and fewer comorbidities. There was marked heterogeneity between patients with ALS and their care trajectories. Our data do not support a universal benefit for early initiation of NIV therapy.

In the ICARUS project, European partners collaborate to develop and scale innovative technologies for recovering and refining secondary raw materials from silicon photovoltaic (PV) manufacturing. The production of photovoltaic modules generates significant quantities of waste, particularly silicon kerf, graphite, and silica residues from ingot and wafer manufacturing. ICARUS aims to transform these waste streams into high‐value secondary materials suitable for reintegration into the PV value chain and other industrial applications. Four industrial pilot‐scale processes are developed, targeting the purification and reuse of these materials. Results from the pilots demonstrate both the technical feasibility and economic potential of substituting these recovered materials for virgin and critical raw materials. This work provides a viable pathway toward a more resource‐efficient and circular PV manufacturing industry.

<bold>Rationale:</bold> Coexisting COPD and OSA is known as Overlap Syndrome. This condition may represent a distinct clinical phenotype, exhibiting differing characteristic responses to long-term home NIV therapy for hypercapnic chronic respiratory failure. However, current data remain scarce. <bold>Objectives:</bold> This multistate model analysis estimated the impact of home NIV therapy on transitions between three different states (without/recovery from severe exacerbation, severe exacerbation and death) in patients with Overlap Syndrome or COPD without OSA. Measurements and Main Results: Model data came from the French national health insurance reimbursement system database for individuals with COPD aged ≥40 years and ≥1 NIV reimbursement in 2015–2019. Outcomes in the Overlap Syndrome and COPD without OSA groups were compared using a Cox model and inverse probability of treatment weighting analysis, adjusted for baseline characteristics. Data from 54,545 patients were included (median age 70 years, 51.2% male). The probabilities of transitioning from severe exacerbation to death (10% vs. 22%) and from without severe exacerbation to death (5% vs. 18%) were lower in the Overlap Syndrome versus COPD without OSA group. The rate of transition from severe exacerbation to without exacerbation (recovery) was also higher in the Overlap Syndrome group. During NIV, the mortality rate was 33% lower in people with overlap syndrome versus COPD without OSA. <bold>Conclusion:</bold> These data suggest that people with Overlap Syndrome are likely to benefit from long-term home NIV to a greater extent than those with COPD without OSA. this finding higlights the need for OSA screening in people with COPD.

Abstract To meet the needs of modelling small-sized detectors of orthovoltage X-rays, for spatially fractionated radiotherapy, we propose a model to determine responses of the detectors in cases of highly heterogeneous cavity. The model was applied to a detector whose cavity features a sparse high-Z perovskite scintillation layer embedded in an epoxy resin. Irradiations were carried out using the Small Animal Radiation Research Platform. Local photon and electron spectra were computed by the SpekPy toolbox and Penelope Monte Carlo simulations, respectively. The detector model considers that X-ray photons mainly interact with medium surrounding the scintillation layer, and that the output of the detector mainly results from secondary electrons in this layer. Results from model computations are compared with measurement data, showing differences less than 16% for beam energies in the 60 kVp −220 kVp range.

The 5.0 industry promotes collaborative robots (cobots). This research studies the impacts of cobot collaboration using an experimental setup. 120 participants realized a simple and a complex assembly task. 50% collaborated with another human (H/H) and 50% with a cobot (H/C). The workload and the acceptability of the cobotic collaboration were measured. Working with a cobot decreases the effect of the task complexity on the human workload and on the output quality. However, it increases the time completion and the number of gestures (while decreasing their frequency). The H/C couples have a higher chance of success but they take more time and more gestures to realize the task. The results of this research could help developers and stakeholders to understand the impacts of implementing a cobot in production chains.

Abstract Introduction: Anti-PD1 treatment has become a backbone treatment in several cancers such as melanoma and lung carcinoma. Adding new drugs to PD-1 requires careful evaluation of combination treatments in preclinical models to evaluate efficacy and tolerability. Syngeneic tumor model remains one of the best way of preclinical evaluation of combinations, as such evaluation requires fully immune competent animals to correctly assess both the PD-1 contribution and the added value or synergistic effect of new drugs in the combination. Anti mouse PD-1 such as RMP1.14, a rat IgG2a, is widely used in these models as anti-PD-1 mAb surrogate for such studies. Although RMP1.14 demonstrated efficacy in several models such as MC38, and CT26, it may not fully recapitulate the use of blocking mAb in the human as it may be immunogenic in mice and may retain some agonist activity due to its rat isotype. Here, we demonstrate that engineering this antibody with a mice Fc silent backbone increases its activity in MC38 model. Methods: VH/VL from RMP1.14 rat IgG2a (mPD1) were sequenced and engineered with a mouse Fc silent IgG1 backbone (N297Q) and produced in CHO. Both antibodies (mPD-1: rat IgG2a; and MOS2-mPD-1: Fc silent mouse IgG1) were purified on protein A using standard procedures. MC38 (1million cells) were injected subcutaneously in C57BL/6 mice, and randomized when tumor volume reached 100mm3. Dose effect of mPD-1 and MOS2-mPD-1 and their corresponding isotype controls were tested in this MC38 model at doses of 0.5; 1.25; 2.5 and 12.5 mg/kg at day 0, day 3, and day 7 post randomization (8 mice per group). Treatment route effect was tested in the same model by comparing intraperitoneal and intravenous injections in an additional experiment using both antibodies at 1.25 mg/kg and 12.5 mg/kg doses. Results: Both mPD-1 and MOS2-mPD-1 demonstrated efficacy in survival in MC38 model at all tested doses (p&amp;lt;0,05 Mantel-Cox test) compared to their isotype controls. MOS2-mPD-1 demonstrated increased efficacy in terms of complete responses in the above escalated doses (CR of 12.5, 12.5, 12.5 and 37.5 % and 0, 75, 50 and 62.5 % for mPD-1 and MOS2-mPD-1 respectively). Tumor volumes and survival were also always lower in the MOS2-mPD-1 groups compared to dose corresponding mPD-1 groups and were statistically different in two independent experiments at medium doses (P&amp;lt;0,05 Dunn’s test performed at 1.25mg/kg at day 27, and Mantel-Cox test). IP and IV routes were equivalent in efficacy at the tested doses. Conclusion: Mouse Fc engineered surrogate have significantly different behavior in mice models compared to the commonly used surrogates usually from rat origin. These new formatted antibodies should better mimick the efficacy and tolerability of antibodies used in human, and should be preferred when new combinations of treatments are tested. Citation Format: Ester Morgado, Laurent Pouyet, Olivier Deas, François Romagne. Fc silencing of commonly used surrogate anti-PD-1 RMP1.14 increases its therapeutic profile in MC38 syngeneic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2665.

We present adult normalized data for MindPulse (MP), a new tool evaluating attentional and executive functioning (AEF) in decision-making. We recruited 722 neurotypical participants (18–80 years), with 149 retested. The MP test includes three tasks: Simple Reaction Time (SRT), Go/No-go, and complex Go/No-go, involving perceptual components, motor responses, and measurements of reaction time (RT) and correctness. We compare responses, evaluating 14 cognitive indices (including new composite indices to describe AEF: Executive Speed and Reaction to Difficulty). We adjust for age/sex effects, introduce a difficulty scale, and consider standard deviations, aberrant times, and Spearman Correlation for speed-accuracy balance. Wilcoxon unpaired rank test is used to assess sex effects, and linear regression is employed to assess the age linear dependency model on the normalized database. The study demonstrated age and sex effects on RTs, in all three subtests, and the ability to correct it for individual results. The test showed excellent validity (Cronbach Alpha for the three subtasks is 92, 87, 95%) and high internal consistency (p < 0.001 for each subtask significantly faster than the more complex subtask) of the MP across the wide age range. Results showed correlation within the three RT parts of the test (p < .001 for each) and the independence of SRT, RD, and ES indices. The Retest effect was lower than intersubject variance, showing consistency over time. This study highlights the MP test’s strong validity on a homogeneous, large adult sample. It emphasizes assessing AEF and Reaction to Difficulty dynamically with high sensitivity.

De nombreux territoires font face à des risques grandissants et de plus en plus multiples et interconnectés. Sur la base du matériel rassemblé lors d’un atelier de prospective INRAE et d’une analyse bibliographique et bibliométrique, cet article propose un état des lieux transversal des risques environnementaux en 2020 et de la recherche menée à INRAE sur le sujet. Le périmètre de l’analyse inclut les risques de catastrophe, les risques physicochimiques et les risques pour les écosystèmes. Les leçons de cet état des lieux sont mises en perspective au regard des besoins de la recherche nationale et internationale sur le sujet et du contexte d’urgence environnementale actuelle. L’analyse fait ressortir l’intérêt d’une approche holistique et intégrée des risques environnementaux incluant l’ensemble du périmètre considéré et la nécessité d’inscrire l’appréhension des risques environnementaux dans une démarche de sciences de la durabilité pour surmonter les verrous associés.

Atmospheric ammonia (NH3) is a gaseous precursor of secondary inorganic aerosols, which represent a significant part of concentrations of fine particulate matter PM2.5 measured in the French region Auvergne-Rh&amp;#244;ne-Alpes (AuRA). Although French State gives an objective for reducing territorial NH3 emissions, ammonia concentrations in ambient air are not regulated. Very few continuous measurement stations exist in France and cover a time range of a few years at most. Ammonia can also be monitored by satellite remote sensing, which offers a better spatial coverage over more than a decade.&amp;#160; Atmo Auvergne-Rh&amp;#244;ne-Alpes (Atmo AuRA) is a regional observatory of air quality approved by the French State. Atmo AuRA extends its activities to the use of&amp;#160;satellite remote sensing data as an external source of information to test the consistency of its emission cadastres, air quality forecasts and hindcasts and potentially improve them.&amp;#160; Since 2015, Amo AuRA maintains a station in Lyon with an analyzer measuring continuously NH3 mixing ratios. The association also builds regional emission inventories of air pollutants, including NH3, and runs routinely CHIMERE chemistry-transport model to evaluate and forecast regional air quality. The chemistry-transport modeling can be used to simulate NH3 atmospheric content for given emissions from inventories and be compared with actual measurements.&amp;#160; In this study, we compare different datasets describing NH3 atmospheric content in AuRA region. Morning in situ measurements in Lyon are compared with NH3 level 2 data of total columns retrieved from the Infrared Atmospheric Sounding Interferometer (IASI), to evaluate their covariations on the period 2016-2021. The temporal consistency between ground measurements and simulations from CHIMERE is also investigated over the same period. Finally, a comparative analysis on CHIMERE and IASI data is done both in terms of spatial distribution and temporal evolution.&amp;#160;