University of Rennes

We investigate the H- and E-polarized natural modes of infinite flat grating of graphene strips lying on dielectric-slab substrate. The conductivity of graphene is modelled using the quantum-theory Kubo formulas, while the substrate material is assumed to have gain that offsets the radiation and ohmic losses and allows the modes to reach the lasing threshold. We look for the frequency and the gain index threshold value, specific to each mode, as eigenvalues. To find them, we reduce each field problem to a dual series equation for the complex amplitudes of the Floquet spatial harmonics that we analytically regularize based on the inversion of its static part. This results in a Fredholm second-kind infinite determinantal equation for eigenvalues. Increasing the matrix truncation number guarantees the convergence of these quantities to their exact values. Our findings reveal that the lowest thresholds are associated with the lattice modes and that those of the H-polarized plasmon modes can be controlled by graphene’s chemical potential within the factor of three.

Treatment options for Type 1 Gaucher Disease (GD1) include enzyme replacement therapy and oral substrate reduction therapy. The criteria for treatment initiation vary across regions. Recent retrospective studies have highlighted the natural progression of never‐treated GD1, suggesting that some patients remain asymptomatic or stable for extended periods. However, there is no data on long‐term prospective follow‐up. We conducted a prospective study following a cross‐sectional analysis of 36 never‐treated, non‐splenectomised GD1 patients from the French Gaucher Disease Registry (FGDR). The objective was to describe the natural disease progression, tracking clinical, radiological, and biological characteristics over time. Thirty‐six non‐splenectomised and never‐treated patients (19 women and 17 men) diagnosed with Gaucher Disease were prospectively followed for an additional median duration of 6.5 (5–8.3) years. Of the cohort, 17 remained untreated, 10 initiated treatment, and 7 were lost to follow‐up. Although never‐treated patients tended to be older at the time of first symptoms, diagnosis, and last follow‐up compared to those who received treatment, the difference was not significant in this small cohort. At last follow‐up, never‐treated patients had no worsening of most of their symptoms. No significant changes were observed in platelets, chitotriosidase, and lyso‐Gb1. In this prospective cohort, we highlight that patients with mild GD can remain untreated with no disease progression, offering insights into cost‐effective management strategies. Identifying such patients is still challenging.

Objective Only few data regarding epidemiology and management of ECMO cannula-related infections (ECMO-CRIs) exist. The aim of our study was to describe their epidemiology and prognosis, and to evaluate factors associated with outcome. Methods We performed a multicenter retrospective study in 12 European ICUs, including patients with ECMO-CRI, defined as a clinical suspicion plus a positive bacterial sample of ECMO-cannulation site. Primary objective was to describe ECMO-CRI characteristics and outcomes. Secondary objectives were to evaluate the rates of infection recurrence, their risk factors, and to evaluate the impact of antimicrobial treatment duration on outcome. Results During the study period, 109 patients with ECMO-CRI (78 having concomitant positive blood culture with the same pathogen) were included. Pathogens responsible for infections were predominantly Enterobacteriaceae, coagulase-negative Staphylococcus and Enterococcus spp., and 42% of episodes were polymicrobial. Rates of infection recurrence was 13% and ICU-mortality rate was 51%. Risk factors for death were concomitant bloodstream infection with same pathogen and septic shock Patients with antibiotic course ≤ 8 days had similar infection recurrence rate and outcomes (including mortality) than patients with prolonged (> 8 days) antibiotic course. Conclusion ECMO-CRIs are frequently associated with BSI and frequently polymicrobial. Duration of antimicrobial treatment for ECMO-CRI ≤ 8 days does not seem to be associated with an increased risk of recurrence or death, as compared to longer treatment.

Urban Heat Islands (UHI) pose a significant challenge for tropical cities, especially as global temperatures continue to rise. Despite the prevalence of this problem, medium-sized cities in tropical regions remain underrepresented in UHI studies compared to large cities in temperate climates. This study aimed to characterize the UHI effect in a rapidly growing medium-sized city in a tropical region, which has experienced unplanned urban sprawl. Temperature data were collected using data loggers in ten distinct areas of the city. The results revealed a pronounced UHI effect, with higher intensities in the city center and lower intensities in areas with native vegetation. During the dry season, extreme UHI effects (> 6 °C) were observed 10% of the time, with strong UHI effects (4 °C-6°C) present 50% of the month. In contrast, during the wet season, moderate UHI effects (2 °C-4°C) were recorded only 15% of the time. A strong correlation was identified between land use, particularly vegetation cover, and UHI intensity. This study not only sheds light on the dynamics of UHI in this specific tropical city, but also offers relevant insights for other mid-sized cities in similar tropical contexts around the world. The findings provide valuable knowledge for the development of adaptation and mitigation strategies in urban planning, which can be applied globally to cities facing rapid urbanization in hot climates. Furthermore, this research contributes to the advancement of UHI analysis methodologies that can be replicated in tropical and temperate cities, building on previous studies conducted in Brazil and other regions of the world.

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after >3 years median follow-up. As of July 23, 2022, median follow-up in all patients (N = 78) was 41.6 months. Median OS (95% CI) was 25.6 months (1.2-47.0; N = 78) and was 38.9 months (25.4–not estimable) for responders (n = 58), with 9 patients in ongoing remission without subsequent therapies. Five deaths (none deemed brexu-cel–related) occurred since prior data cut. Benefits from brexu-cel were maintained regardless of age, prior therapies, and subsequent allogeneic stem cell transplantation (alloSCT). Subsequent alloSCT was not associated with survival benefit among responders versus responders without subsequent alloSCT. No secondary T-cell malignancies were reported in ZUMA-3 with long-term follow-up.

Demonstrating cardiovascular (CV) benefits with lipid-lowering therapy (LLT) requires long-term randomized clinical trials (RCTs) with thousands of patients. Innovative approaches such as in silico trials applying a disease computational model to virtual patients receiving multiple treatments offer a complementary approach to rapidly generate comparative effectiveness data. A mechanistic computational model of atherosclerotic cardiovascular disease (ASCVD) was built from knowledge, describing lipoprotein homeostasis, LLT effects, and the progression of atherosclerotic plaques leading to myocardial infarction, ischemic stroke, major acute limb event and CV death. The ASCVD model was successfully calibrated and validated, and reproduced LLT effects observed in selected RCTs (ORION-10 and FOURIER for calibration; ORION-11, ODYSSEY-OUTCOMES and FOURIER-OLE for validation) on lipoproteins and ASCVD event incidence at both population and subgroup levels. This enables the future use of the model to conduct the SIRIUS programme, which intends to predict CV event reduction with inclisiran, an siRNA targeting hepatic PCSK9 mRNA.

Up to now, there were only few reports on Earth‐abundant transition metal catalyzed reductions of thioamides, one of the explanation of this scarcity being the possible metallic catalyst poisoning due to the adsorption of species containing sulfur. In this contribution, we report the first general iron‐catalyzed hydrogenative desulfurization of tertiary thioamides under hydrosilylation conditions at ambient temperature, the reaction being driven by blue light irradiation. To perform selectively the reduction of thioamides leading to amines (30 examples, 29–97 % yields), highlighting the sole cleavage of the C=S bond, Fe(IMes)(CO)4 catalyst was used in the presence of phenylsilane under ambient conditions.

Background Retrospective studies did not show strong evidence of higher risk of adverse neonatal or pregnancy outcomes in women with multiple sclerosis (MS) compared to general population, but there are contradictory data on prematurity, cesarean section, and small birthweight for gestational age (SGA). Methods We compared pregnancy and birth outcomes in MS women included in RESPONSE, a French prospective cohort, with a recent survey (Enquête Nationale Périnatale (ENP)) describing leading indicators in perinatal epidemiology in France. Results On 7 April 2023, 476 pregnancies (461 MS women, 482 expected newborns) from RESPONSE were available. The ENP study reported 12,723 women and 12,939 expected newborns in March 2021. MS patients were older (mean age 32.6 ± 4.4 vs. 30.9 ± 5.3 years, p < 0.001), with similar rate of cesarean (23.8% vs. 21.4%, p = 0.115) and use of locoregional analgesia (86.6% vs. 85.1%, p = 0.51). Preterm birth was less frequent (4.0% vs. 7.0%, p = 0.001). Birthweight of children from MS mothers was similar to general population (3240 ± 477.2 vs. 3264.5 ± 552.9 g, p = 0.22), with slightly more children with SGA (13.4% vs. 9.8%, p = 0.04). Conclusion This prospective and contemporary comparison of pregnancy in MS women and the French population provides reassuring results. In the future, we need to assess the impact of disease-modifying treatment exposure during conception.

Anticoagulant use in patients with hematological malignancies treated on intensive chemotherapy represents a management challenge because of concomitant thrombocytopenia. This prospective multi-center cohort included 100 patients with hematological malignancies on anticoagulation. The aims of the study were to assess the incidence of WHO grade ≥ 2 bleeding, describe physician management strategies during thrombocytopenia (platelet count < 50 × 10⁹//L), and examine short-term outcomes and risk factors for bleeding and thrombosis. Median patients age was 60 years and median duration of severe thrombocytopenia was 16 days. The 30-day cumulative incidence of WHO grade ≥ 2 bleeding was 29.3% (95% CI 19.4–39.8), grade 4 bleeding was 7.2% (95% CI 2.8–14.2) and incidence of thrombus recurrence/progression was 6.2% (95% CI 2.2–13.3). No deaths occurred. The majority of patients received full-dose anticoagulation with a high platelet transfusion threshold. Half of the bleeding episodes grade ≥ 2 occurred with platelets counts between 20 and 50 × 10⁹/L. Longer period of full-dose anticoagulation during thrombocytopenia was associated with increased bleeding risk (16 days [IQR: 6–29] for participants who presented ≥ grade 2 bleeding versus 7 days for those who did not [IQR: 2–14], p < 0.001). So was a HAS-BLED score ≥ 3 (HR = 9 [4.1–20], p < 0.001). Multiple myeloma diagnosis was associated with lower bleeding risk versus other hematological malignancies (HR = 0.2 [0.0–0.9], p = 0.05). Our study underscores the complex trade-off between preventing thrombotic events’ progression or recurrence and avoidance of bleeding. We highlight specific clinical scenarios and consider different risk factors. Future randomized controlled trials are required for these complex situations to achieve a rationalization of their management. Graphical abstract

Concentrating solar power plants convert solar energy into electricity by using mirrors to concentrate sunlight, but dust, particularly in arid and semi-arid regions, reduces their efficiency. This study proposes an innovative AI-based approach for monitoring and predicting soiling. For real-time analysis of CSP mirror images, a ResNet-50 convolutional neural network (CNN) is used, while a recurrent neural network (RNN) with a long, short term memory (LSTM) architecture predicts future soiling rates using the temporary variation in this parameter. By integrating mirror imagery and meteorological data, our hybrid AI model effectively combines CNN for image analysis and RNN temporal predictions, with high accuracy ranging from 89.5% to 95.2%, depending on the application. The application of advanced AI techniques can significantly improve the management of concentrated solar power plants and lead to significant breakthroughs in the solar energy industry.

Objective To explore the impact of online food shopping in France on the selection of products purchased and its potential impact on shoppers' dietary balance. Design A qualitative study involving in-depth semi-structured individual interviews. The interviews were recorded, transcribed verbatim, and analysed through a reflexive thematic analysis approach. Setting France Participants Thirty-four male and female respondents aged between 21 and 61 years old, residing in various regions of France, including urban, suburban, and rural areas, with diverse profiles in terms of gender, age, location, and number of children under 18. Results Five key themes were identified as influencing decision-making with regard to the products purchased, namely ‘less choice, especially for fresh produce’, ‘sense of security in buying the same products’, ‘convenience of online shopping through time-saving and product recommendation lists’, ‘avoiding unplanned purchases’, and ‘less fresh produce purchased, sometimes replaced by more processed items’. In turn, all of these factors potentially have an impact on the diet of online shoppers. Conclusions With grocery e-commerce penetration expected to double in the next five years, the study underscores the consequences of online shopping on consumers' dietary balance. The findings have practical implications for online food retailers, inciting them to develop solutions that would encourage e-grocery shoppers to buy more fresh produce and to sample a more varied diet. Additionally, they highlight the importance of monitoring the influence of technology on the consumer buying process, particularly with regard to food.

Converting planar six‐membered aza‐arenes into C(sp3)‐rich three‐dimensional (3D) scaffolds is a promising way to obtain isosteric mimetics of numerous functional products, but it remains to date a formidable challenge due to the high thermodynamic stability and dynamic inertness as well as the selectivity control. Here, by applying a novel non‐noble bimetallic Mn/Fe catalyst system, we report, for the first time, an approach for direct construction of functional 3D 2‐azabicyclo[2.1.1]hexanes via a hydrodearomatization (HDA) of the aza‐arenes and [2π + 2σ] cycloaddition cascade. Mechanistic investigations reveal that the triplet state of Fe(II) facilitates the activation of both aza‐arenes and bicyclo[1.1.0]butanes (BCBs). The mild reduction nature of manganese catalysis and the steric effects of Fe(II) coordination result in an 1,4‐hydrodearomatization, and the imine species derived from the isomerization of 1,4‐hydrogenated aza‐arenes are then effectively trapped by the polarized BCBs, thus suppressing the thermodynamically favorable over‐hydrogenation of aza‐arenes into cyclic amine by‐products. Given the features of good substrate and functionality compatibility, high step and atom efficiency, and diversified product post‐transformations, the developed chemistry offers a practical platform to access various functional molecules.

Introduction (Pre‐)clinical studies have not ruled out a potential risk of second primary cancer (SCP) under the effect of some new androgen receptor pathway inhibitors (ARPIs), especially enzalutamide (ENZ). Methods Using the French health reimbursement claims database (Système National des Données de Santé), we designed a case–control study nested in a 2013–2020 cohort of new users of androgen‐deprivation therapy. The cases were patients with a first diagnosis of SPC, identified beyond 12 months following cohort entry and up to December 31st , 2021; up to 10 controls were matched per case, based on age and cohort entry date. The main analysis focused on patients who had not switched to a different ARPI. Applying a one‐year lag time, we determined the most frequent and longest cumulative exposure patterns to abiraterone (ABI) or ENZ and estimated the odds ratios. Results The cohort comprised 147 092 patients, including 7928 cases and 78 554 controls eligible for analysis. The SPCs mainly involve the digestive organs, the urinary tract, or the lungs. Recent and short exposure to ENZ was associated with SPC: OR 1.7, 95% CI [1.2–2.4]. Recent one full year of exposure to ABI, as well as full‐year plus part of the second year, was associated with SPC: OR 1.8 [1.2–2.7] and 2.3 [1.3–4.0], respectively. Discussion/Conclusion SPC cases were mainly observed among recently exposed patients, which could be linked to a detection bias. The insufficient number of patients exposed over many years means that no definitive conclusions can be drawn.

The [2+2]‐cycloaddition of olefins and alkynes stands out as a versatile and atom‐economical strategy for synthesizing cyclobutane and cyclobutene building blocks, which are challenging to access through other synthetic methods. While photochemical approaches have traditionally dominated this field, thermally‐driven methods employing transition metals offer distinct advantages, including decreased reliance on pre‐functionalized substrates and improved scalability. This review explores the underlying principles of metal‐catalyzed [2+2]‐cycloadditions and highlights recent advances in thermally‐driven approaches for the efficient synthesis of cyclobutane and cyclobutene frameworks. Particular attention is given to electronically unbiased substrates, which remain a significant challenge for photochemical approaches.

Automated program repair techniques aim to aid software developers with the challenging task of fixing bugs. In heuristic-based program repair, a search space of mutated program variants is explored to find potential patches for bugs. Most commonly, every selection of a mutation operator during search is performed uniformly at random, which can generate many buggy, even uncompilable programs. Our goal is to reduce the generation of variants that do not compile or break intended functionality which waste considerable resources. In this paper, we investigate the feasibility of a reinforcement learning-based approach for the selection of mutation operators in heuristic-based program repair. Our proposed approach is programming language, granularity-level, and search strategy agnostic and allows for easy augmentation into existing heuristic-based repair tools. We conducted an extensive empirical evaluation of four operator selection techniques, two reward types, two credit assignment strategies, two integration methods, and three sets of mutation operators using 30,080 independent repair attempts. We evaluated our approach on 353 real-world bugs from the Defects4J benchmark. The reinforcement learning-based mutation operator selection results in a higher number of test-passing variants, but does not exhibit a noticeable improvement in the number of bugs patched in comparison with the baseline, uniform random selection. While reinforcement learning has been previously shown to be successful in improving the search of evolutionary algorithms, often used in heuristic-based program repair, it has yet to demonstrate such improvements when applied to this area of research.