Epoxy-diamine based composite materials are widely used in aeronautical structures operating under high-temperature environments due to their favourable specific mechanical properties and the thermal stability of the epoxy matrix. To anticipate their long-term performance, robust numerical tools are required to simulate aging processes. This work presents a comprehensive finite element framework for modelling the thermo-oxidative aging of epoxy networks and its consequences on stress and strain gradients across the through-thickness direction. The diffusion-reaction model was first implemented in a custom Python code and successfully transferred to a commercial finite element software (Abaqus (c)), enabling the prediction of the thickness of the oxidized layer (TOL) under any pre-defined aging condition. The TOL predictions were validated against experimental data in 1D, 2D, and 3D configurations, demonstrating strong agreement. In a second stage, a hybrid methodology was employed to compute strain and stress fields: oxidation-induced shrinkage was deduced from experiments using high-resolution microscopy techniques, while stress distributions were derived from the degraded material's constitutive behaviour. This approach allows the estimation of mechanical gradients directly from oxidation profiles, forming the basis for defining aging criteria related to the material's mechanical response.

This article outlines a numerical calculation code developed under finite elements to simulate as accurately as possible the thermal aging of epoxy-diamine (EPO-DA) matrices below and above their glass transition temperature (Tg). The code is based on a kinetic model that couples, in a single balance equation, the diffusion of oxygen (O2) and its consumption by the chemical reaction with the epoxy network. The reliability of the oxidation rate expression was carefully checked for six EPO-DA matrices over wide ranges of temperature and O2 partial pressure in previous publications. The code gives access to the oxidation gradients within the sample thickness whose validity is successfully checked through a literature compilation (completed by our own recent results) of more than 40 thicknesses of oxidized layer (TOL), measured with different physico-chemical techniques on various EPO-DA matrices thermally aged in air below and above their Tg. In the glassy state, where the coefficient of O2 diffusion (DO2) obeys a well-established Arrhenius’ law depending on the chemical structure of the diamine hardener (either aliphatic or aromatic), the estimates of TOL are in nice agreement with the experimental data. In the rubbery state, in contrast, the calculations largely underestimate the experimental data for the stiffest EPO-DA matrices if a sharp increase in DO2 is not also considered when passing above Tg. This positive jump in DO2 places all EPO-DA matrices at the same level of molecular mobility in the rubbery state, thus completely erasing the stiffening effect of aromatic rings observed in the glassy state.

Ethylene Propylene Diene Monomer (EPDM) was sulfur-crosslinked and aged in air at 130 degrees C to study the impact of thermo-oxidative aging on the polymer structure and water sorption properties. The oxidized functions formed during aging were identified and titrated by infrared spectroscopy. Density and swelling measurements performed on aged samples showed an increase in polymer density due to oxygen grafting, and a decrease in swelling assigned to a cross-linking phenomenon. This last phenomenon was confirmed by an increase in the glass transition temperature. Concerning water transport properties, it was evidenced that, with the creation of oxidized functions and the decrease in molecular mobility, the water diffusion slowed down, while the amount of sorbed water increased. Finally, the sorption isotherms obtained for EPDM before and after aging were modelled with a good accuracy by the Park's and the GAB's models. Both models led to the conclusion that aging mainly affects the polymer affinity with water, without modifying the mean size of the water clusters evidenced at high water activity.

Phenolic antioxidants are widely used to prevent oxidation, which is the main degradation process for many polymers, in particular polyolefins among which polyethylene is the most employed one. Although it is generally understood that one of the main mechanisms by which phenolic antioxidants prevent or slow down oxidation is by deactivating radicals and preventing the formation of alkyl radicals, detailed understanding at the atomic scale of the hierarchy of radical reactions is still lacking. Here, we investigate the interaction of a prototypical phenolic antioxidant, butylated hydroxytoluene (BHT), with radicals in a polyethylene model by means of static and dynamic simulations based on density functional theory. We focus on the H-transfer reactions between BHT and radical species by evaluating the associated energy barriers and analyses the conditions in which these relevant reactions occur by first principles molecular dynamics simulation. Our polyethylene model includes a realistic surface of a crystalline lamella, thus describing the local atomic environment in which the reactions mainly take place. Our results suggest that the H-transfer reaction of the BHT molecule with an alkoxy radical is spontaneous and the energy barrier is small (~0.1 eV) with a peroxy radical. Conversely, direct scavenging of alkyl radicals by BHT seems excluded. Our molecular dynamics simulations highlight the influence of steric hindrance and antioxidant diffusion within amorphous regions on antioxidant efficiency.

The thermal oxidation of low-density polyethylene and poly(ethylene-co-vinyl acetate) both cross-linked with triallyl isocyanurate (respectively denoted XLPE and EVA) was studied at 165 °C in air by Fourier transform infrared (FTIR) spectroscopy, dielectric spectroscopy and uniaxial tension. Monitoring the carbonyl index throughout the exposure allowed showing that these two polymers have similar oxidation reactions, taking place on their ethylene monomers, and therefore similar oxidation kinetics. In addition, in EVA, the acetate side groups thermally decompose into several degradation products during the exposure, such as: trans-vinylene double bond, acetic acid, saturated and unsaturated γ-lactone, and methane, but without interacting with the oxidation reaction. As oxidation is diffusion controlled, it leads to the development of oxidation profiles across the sheets of about 1 mm thick of these two polymers. In addition, as the oxygen transport properties (both solubility and diffusivity) are higher in EVA than in XLPE, oxidation affects the center of the EVA sheets from the early periods of exposure, whereas it is necessary to wait for high conversion ratios of the oxidation reaction to observe the same types of chain-shaped profiles in XLPE sheets. Oxidation results in dramatic changes in functional properties (both electrical and mechanical properties) for both polymers. Before thermal aging, EVA is already a poor insulating material compared to XLPE, due to the presence of polar side groups (i.e. acetates). In contrast, EVA exhibits a higher ductility, which justifies its use as nanofillers in PE-based insulating materials in order to improve their mechanical properties. The establishment of correlations between the changes in functional properties and the progress of oxidation allows the proposal of structural, electrical and mechanical end-of-life criteria for both polymers, corresponding to critical values of carbonyl index, dielectric constant, and elongation at break, respectively.

This paper presents a comprehensive study on the impact of antioxidants (AOs) on the aging process of insulating polymeric materials, specifically complex permittivity, conductivity, and AC breakdown voltage. Accelerated aging was achieved through high temperatures (up to 130°C) in air on crosslinked polyethylene (XLPE) both with and without AOs. In addition to electrical tests, chemical analyses were performed to better understand the role of AOs during thermal aging. The results indicate that AOs effectively inhibit oxidation, preventing the formation of degradation species. As long as AOs are present, minimal changes in the electrical properties are observed. However, once the AOs are almost completely depleted, oxidation products significantly alter the electrical properties, resulting in a worsening of the material electrical performance.

Knowing the diffusion coefficients of antioxidants in packaging materials is essential to assess their effectiveness in protecting materials against oxidation, but also to prevent their eventual migration to food. In this work, the diffusion of a commercial phenolic antioxidant (Irganox 1035) was measured experimentally in pristine high-density polyethylene (HDPE) and in HDPE nanocomposite filled with 3 wt% of nanoclays (Cloisite (R) 15A). Diffusion experiments were performed using the Roe's method between 60 and 100 degrees C. The local concentration of Irganox1035 in each film was measured by UV-Vis spectroscopy from the UV absorbance at 282 nm. The adjustment of the experimental data by Fick's second law allowed us to deduce the values of the diffusion coefficient of Irganox1035 at each temperature and to show that the temperature dependence of this coefficient obeys an Arrhenius' law. It is shown that the incorporation of 3 wt% of Cloisite (R) 15A into HDPE significantly hinders the diffusion of Irganox 1035 and increases its activation energy. Several mechanistic assumptions could explain this result, first the increase in the tortuosity of diffusion paths, but also the possible establishment of strong intermolecular interactions between the antioxidant and some chemical groups on the nanofiller surface, or even the formation of an interphase with reduced molecular mobility around the nanofillers.

Objectives: The aim of this noninterventional, retrospective ALFA study was to describe belantamab mafodotin effectiveness and safety in patients with relapsed/refractory multiple myeloma in a real-world setting in France. Methods: Response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. Results: Among the 184 patients initiating belantamab mafodotin treatment, the overall response rate was 32.7% (>= very good partial response [VGPR] 20.4%, partial response [PR] 12.3%). The median PFS (mPFS) was 2.4 months (95% confidence interval [CI]: 1.9, 3.3), and median OS (mOS) was 8.8 months (95% CI: 6.3, 11.6). According to best response, mPFS was 20.6 months (95% CI: 12.1, not reached [NR]) in patients with >= VGPR and 7.1 months (95% CI: 4.6, 9.4) in patients with PR; mOS was NR in patients with >= VGPR and 17.5 months (95% CI: 7.7, NR) in patients with PR. For both OS and PFS, no differences were found in subgroups of interest. The adverse events (AEs) reported in 159 patients (86.4%) were mostly ocular AEs. Conclusions: ALFA, the largest real-world cohort conducted so far, confirms the results of belantamab mafodotin as reported in the DREAMM-2 clinical trial. The clinical benefit is significant as long as the patient is a responder.

The effect of cyclic fast charging on the mechanical and physicochemical properties of the lithium-ion battery separator is investigated. For that purpose, six battery pouch cells were cycled at 4C charge and 0.5C discharge rates for up to 400, 800, and 1600 cycles. Once the fast charging cycles were completed, the battery pouch cells were fully discharged and carefully disassembled. The physical and chemical microstructural properties of pristine and cycled separators were investigated using scanning electron micrographs (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). Additionally, the mechanical behavior of the pristine and cycled separators was also investigated through uniaxial tensile and biaxial punch tests. While the XPS and FTIR analyses of the cycled separator surfaces did not reveal the presence of chemical degradation, the mechanical properties presented a decrease in toughness and ductility with an increased number of charging cycles. A thorough discussion of the possible degradation mechanisms of the cycled separator is provided by combining the results of our analysis and of those reported in the literature.

Objective Evaluate the overall survival (OS) of patients with multiple myeloma (MM) at different treatment stages in France.Methods This retrospective observational cohort study used data from the French National Health Insurance database to study patients with MM (diagnosis 2013-2019). Patient outcomes included OS (all-cause mortality), time-to-next treatment (TTNT), and duration of therapy (DoT) from initial diagnosis, the start of different lines of therapy (LOTs), triple-class exposure (TCE), and subsequent treatment following TCE. The Kaplan-Meier method analyzed "time-to-event" data.Results From diagnosis, death rates increased from 1% at 1 month to 24% at 2 years; median OS was 63.8 months (N = 14 309). Median OS from the start of LOTs declined from 61.0 months (LOT1) to 14.8 months (LOT4). Median OS from TCE start was 14.7 months. There was a large variation in TTNT within LOTs (e.g., LOT1: bortezomib + lenalidomide: TTNT = 26.4 months, OS = 61.7 months; lenalidomide: TTNT = 20.0 months, OS = 39.6 months); DoT was similar for LOT1 and LOT2, then progressively declined at LOT4. Patients with stem cell transplant, younger age, and less comorbidity had better survival outcomes.Conclusions Patients with MM face a poor prognosis after relapse to multiple LOTs and TCE, demonstrating a worsening of survival outcomes. Access to novel therapies may improve outcomes.

IntroductionLes options de traitement du myélome multiple (MM) ont évolué ces dernières années avec l'introduction de nouvelles thérapies. Bien qu'une rémission à long terme puisse être observée, le MM reste incurable. Ces dernières années, des études en vie réelle réalisées aux Etats-Unis et dans plusieurs pays européens ont montré une augmentation de la survie globale (SG). En France la survie nette à cinq ans a été estimée à 60 % entre 2010 et 2015 mais les données récentes restent limitées.ObjectifsCette étude vise à décrire la survie globale des patients atteints de MM en France à partir du diagnostic, des lignes de traitement et du traitement suivant une première exposition triple classe (TCE) définie par l'exposition durant les lignes antérieures à au moins un inhibiteur du protéasome (IP), un immunomodulateur (IMiD) et un anticorps anti-CD38.Matériel et méthodesLes patients inclus étaient identifiés dans la base exhaustive du Système national des données de santé (SNDS) comme nouvellement diagnostiqués et traités pour le MM entre 2013 et 2017. Les patients étaient suivis jusqu'en 2019 assurant une durée de suivi potentielle de 2 ans minimum. Les lignes de traitement ont été reconstruites à partir d'un algorithme basé sur la date d'administration des traitements, la durée du traitement et le délai entre les cycles. La SG a été décrite à différents points de repère temporels : 1) à la date du premier diagnostic ; 2) au début de chaque ligne de traitement (L1 à L5+) ; 3) à la date de la première TCE ; 4) au début du traitement suivant la première TCE (post TCE) ou du dernier traitement ; 5) au début du traitement post TCE ou du dernier traitement, pour les patients ayant reçu au moins quatre lignes antérieures. La SG des patients a été évaluée par la méthode Kaplan-Meier.RésultatsAu total, 14 309 patients ont été inclus, avec un âge médian de 71 ans au moment du diagnostic, 51 % étaient des hommes. La SG médiane depuis le diagnostic était supérieure à 5 ans (>60 mois). Une légère augmentation de la SG était constatée pour les patients diagnostiqués plus récemment : 63,8 mois pour les patients diagnostiqués avant 2018 contre 60.8 mois pour les patients diagnostiqués avant 2015. De la L1 à la L4, la SG médiane diminuait de 61 à 14,8 mois, soit une baisse comprise entre 30 % et 50 % entre chaque ligne consécutive. A la date de la première TCE, le daratumumab (anti-CD38) en monothérapie était le schéma thérapeutique privilégié. En cas de rechute, la norme de soins post TCE est le retraitement avec les agents thérapeutiques précédemment utilisés. La SG médiane post TCE des patients avec au moins quatre lignes antérieures était de 3,8 mois. Parmi ces patients, 43 % avaient reçu un traitement post TCE avec une SG médiane de 8,2 mois. Pour les patients n'ayant pas bénéficié de nouveau traitement, la SG médiane n'était que de 1 mois, indexée à la date du dernier traitement observé.ConclusionLa survie des patients atteints de MM diminue après le diagnostic au fur et à mesure des lignes de traitement consécutives. Malgré les progrès thérapeutiques et la légère augmentation de la SG pour les patients diagnostiqués plus récemment, le pronostic est particulièrement défavorable pour les patients triple réfractaires notamment pour ceux n'ayant pas bénéficié de nouveau traitement post TCE. Face à ces besoins thérapeutiques non couverts, la nécessité d'un accès facilité aux nouvelles thérapies reste un sujet essentiel.Mots-clésMyélome multiple ; Survie Globale ; Triple réfractaireDéclaration de liens d'intérêtsEtude supervisée et financée par GSK et réalisée par IQVIA France.

This work presents an innovative model for the derivation of permittivity evolution of polyethylene (PE)-based materials with aging. First, the derivation of the microscale contributions to the real permittivity of methylene unit [constitutive repetitive unit (CRU) of PE] and its oxidation products, that is, ketones and hydroperoxides, in the solid state is presented. Then, a chemical kinetic model is recalled predicting the concentration, under proper hypotheses, of the oxidized species created during polymer aging. The proposed model combines the concentrations of methylene unit and its oxidation products with the respective contribution to permittivity, providing the trend of permittivity of polymer with aging. Results depict good agreement with the experimental data, validating the model.

The thermal aging of two electrical cable insulations made of cross‐linked low density polyethylene (XLPE) only differing by their stabilization system was studied in air between 125 and 200°C. The chemical consumption of the two types of antioxidants (phenol and sulfide), the build‐up of oxidation products and the consequences of thermal oxidation on the mechanical properties were respectively determined by measurement of the oxidation induction time (OIT), Fourier transform infrared spectroscopy (FTIR) and uniaxial tensile testing. It was found that the chemical consumption of each antioxidant occurs in turn almost independently, starting with the sulfide antioxidant and involving small but well detectable antagonistic effects. As soon as the antioxidant concentration becomes very low, that is, practically undetectable by OIT measurements, the thermal oxidation of XLPE is detected by FTIR spectroscopy causing a catastrophic decrease in the fracture properties. It was shown that the complete consumption of antioxidants coincides with the end of the oxidation induction period and the onset of the sudden decrease in the elongation at break. Based on all these experimental results, a simplified kinetic model was developed to account as faithfully as possible for the consumption kinetics of antioxidants, evaluate their antagonistic effects and, using a relevant end‐of‐life criterion, predict the lifetime of the two XLPE insulations. It was found a satisfying agreement between theory and experiment.

This article deals with the long-term behaviour of radiation cured polymers. Among the wide variety of possible ageing modes, the attention is focused on two key processes for users of radio-cured polymers: humid ageing of polymer glasses and thermal oxidative ageing of rubbers. These two processes are illustrated by numerous results coming from literature or our own research works. In both cases, the consequences of the structural modifications on the use properties (in particular, on mechanical properties) are described. It is found that the ageings of radiochemically and thermally cured polymers are not so different. It is thus concluded that a great part of the very abundant literature published on the ageing of thermally cured polymers remains exploitable for radio-cured polymers.

Real-world data on health care resource utilisation (HCRU) and costs for French patients with multiple myeloma (MM) are limited due to the quickly evolving MM treatment landscape. This retrospective, national-level study quantified the MM economic burden in France. The study included patients with newly diagnosed MM from the Système National des Données de Santé coverage claims database between 2013 and 2018 who received active treatment within 30 days of diagnosis. HCRU included hospitalisations, drugs, consultations, procedures, tests, devices, transport, and sick leave. Costs were annualized to 2019 prices. Drug treatments, reported by line of therapy (LOT), were algorithmically defined using drug regimen, duration of therapy, and gaps between treatments. Analyses were stratified by stem cell transplantation status and LOT. Among 6413 eligible patients, 6229 (97.1

Polyethylene is a widely used polymer and a prototypical polyolefin. Understanding degradation mechanisms at the atomic scale leading to oxidation under the effect of temperature and/or irradiation is crucial for many long-term applications. Here, we focus on a subset of reactions belonging to the generally assumed radio-oxidation reaction scheme and involving alkoxy radicals. We follow a theoretical approach based on density functional theory, in order to assess the role of these species, which are short lived and thus hard to detect experimentally. For every considered reaction, we calculate the reaction enthalpy and the energy barrier, and we evaluate the influence of the local atomic environment, taking advantage of a model surface of a crystalline lamella which mimics the interface between crystalline and amorphous zones. Our results suggest that in certain conditions, the kinetic pathway can bypass the formation of hydroperoxides. The concentrations of alkoxy and peroxy radicals during radio-oxidation and their ratio are important parameters controlling the predominance of chain scission or crosslinking in the polymer. The data presented here constitute part of a database that can be used to set up kinetic simulations based on homogeneous chemical kinetics or Monte Carlo algorithms.

The radiothermal ageing of silane-crosslinked low-density PE (Si-XLPE) films was studied in the air under three different γ dose rates (8.5, 77.8, and 400 Gy·h−1) at a low temperature close to ambient (47, 47, and 21 °C, respectively). Changes in crystalline morphology were investigated using a multi-technique approach based on differential scanning calorimetry (DSC), wide- (WAXS) and small-angle X-ray scattering (SAXS), and density measurements. In particular, the changes in four structural variables were accurately monitored during radiothermal ageing: crystallinity ratio (XC), crystalline lamellae thickness (LC), long period (Lp), and interlamellar spacing (La). Concerning the changes in XC, a perfect agreement was found between DSC and WAXS experiments. Successive sequences of self-nucleation and annealing (SSA) were also performed on aged Si-XLPE samples in the DSC chamber in order to assess the thickness distribution of crystalline lamellae. This method allowed the thermally splitting of the melting domain of Si-XLPE into a series of elementary melting peaks, with each one characterised by a distinct thickness of crystalline lamellae. DSC (used with the SSA method) showed a slight increase in LC during the oxidation of Si-XLPE, while SAXS confirmed a catastrophic decrease in La. The critical value of the interlamellar spacing characterising the ductile/brittle transition of Si-XLPE was found to be of the same order of magnitude as that for linear polyethylene (LaF≈6 nm). This structural end-of-life criterion can now be used for predicting the lifetime of Si-XLPE in a nuclear environment.

This study focuses on the degradation of a silane cross-linked polyethylene (Si-XLPE) matrix filled with three different aluminum tri-hydrate (ATH) contents: 0, 25, and 50 phr. These materials are subjected to radiochemical ageing in air under three different dose rates (8.5, 77.8, and 400 Gy h(-1)) at two temperatures (47 and 21 degrees C). Changes due to ageing have been investigated by FTIR spectroscopy, DSC analysis, and density measurements in order to more precisely define their chemical composition and microstructure and to evidence the possible influence of ATH fillers on the oxidation kinetics of the Si-XLPE matrix.

Background: While treatment options for multiple myeloma (MM) have expanded with the introduction of novel therapies, it remains unclear how this has translated into better patient outcomes. Although some patients can achieve long-term remission, MM remains incurable. In oncology, overall survival (OS) is the gold standard for measuring the clinical benefit of an agent. Real-world studies in several countries have shown increases in OS in recent years for patients with MM; up-to-date real-world data on MM survival in France are limited. Aims: To assess the OS of patients with MM in France from diagnosis and by line of therapy (LOT) and post triple-class exposure (TCE). Secondary aims were survival outcomes by different subpopulations based on standard of care (SoC) treatment regimens and transplant status. Methods: This longitudinal retrospective cohort study used data from the French National Healthcare database (Système National des Données de Santé – SNDS) from Jan 2013‒Dec 2019, which included records of outpatient claims, hospital discharges and death registry, demographics, and reimbursement data for hospital and outpatient services. Eligible patients (≥18 years) had ≥2 records of an MM diagnosis (ICD-10 codes C90/C90.0), and/or long-term disease during the study period; ≥1 dispensation/administration of MM drug treatment and date of death available. LOT was algorithmically defined based on drug regimen, time since administration, and gap between regimens. OS was analyzed from five time points: 1) from time of diagnosis; 2) from the start of line of LOT1 to LOT4; 3) from the start of first TCE (defined as prior exposure to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody); 4) from the subsequent treatment following TCE, and 5) from the subsequent treatment/no treatment following TCE and LOT5+ (indexed at the date of the last observed treatment). Patient OS was assessed by Kaplan–Meier method and death rates were calculated. Results: A total of 14,309 patients were included in this analysis. Median age was 71 years at diagnosis and 51% of patients were male. Patient survival outcomes deteriorated as their LOT advanced (Figure). Median OS from initial diagnosis was >5 years with a slight increase for patients diagnosed more recently (63.8 months for patients diagnosed in 2017 or later vs 60.8 months in those diagnosed in 2014 or later). From LOT1 to LOT4 OS decreased from 61 to 14.8 months or about 30% to 50% with each additional LOT. At the time of first TCE, daratumumab monotherapy/combination therapy were the most common regimens. Median OS following TCE was 3.8 months. Retreatment with previous agents were the SoC following TCE. Among TCE patients who had 4 prior LOTs, 43% of them received a subsequent LOT with a median OS estimate of 8.2 months. For those who discontinued treatment, median OS was only 1 month, indexing at the date of the last observed treatment. Image:Summary/Conclusion: Patients with MM experience worsening survival outcomes with increasing time from diagnosis and with subsequent LOT. Prognosis was especially poor among TCE patients who received subsequent therapy and worse for those who did not receive additional treatment. Despite therapeutic advances and slight increase in OS for patients diagnosed more recently, an unmet need for improved access to novel therapies remains, especially in those TCE patients.