Amorçage de fissures de corrosion sous contrainte du Zircaloy-4 recristallisé en milieu méthanol iodé

En situation d’interaction pastille-gaine (IPG), les gaines de crayons combustible en alliage de zirconium sont susceptibles de rompre lors de transitoires de puissance incidentels dans les réacteurs à eau pressurisée, par un mécanisme de corrosion sous contrainte induite par l’iode (CSC-I). Cette étude traite de l’amorçage intergranulaire des fissures de CSC-I dans le Zircaloy-4 recristallisé, en milieu méthanol iodé à température ambiante, en s’intéressant particulièrement aux paramètres mécaniques critiques et à la concentration en iode. Pour cela, une approche mêlant expériences et simulations numériques a été adoptée. Un modèle de comportement mécanique macroscopique de l’alliage, viscoplastique et anisotrope, a été établi et validé sur une large gamme de sollicitations. Par la réalisation de nombreux essais de traction à vitesse de déformation imposée et de fluage en flexion quatre points, nous avons montré l’existence d’une concentration seuil I0 proche de 10-6 g.g-1 nécessaire à l’apparition du dommage de CSC-I, mais également celle d’une concentration de transition I1 proche de 2 10-4 g.g-1 au-delà de laquelle le mécanisme change, menant à un amorçage anticipé des fissures et une sensibilité réduite de l’endommagement aux paramètres mécaniques. L’importance de la concentration sur des paramètres tels que la densité des fissures, leur longueur moyenne et la vitesse de propagation intergranulaire et transgranulaire a été mise en évidence. Les résultats expérimentaux montrent que la déformation plastique macroscopique n’est pas indispensable à l’amorçage de fissures de CSC-I, pour un temps d’essais suffisamment long en présence de contrainte. Son principal effet est de précipiter l’apparition de fissures par la création de sites d’amorçage, par rupture de la couche d’oxyde et accumulation de contrainte intergranulaire. En dessous de I1 la détermination des déformations critiques à l’amorçage montre un fort effet de vitesse. Dans ce domaine, une contrainte seuil de 100 MPa a été déterminée, bien inférieure à la limite élastique. L’utilisation d’éprouvettes entaillées et de la simulation numérique a permis de mettre en évidence un fort effet protecteur de l’augmentation de la biaxialité des contraintes vis-à-vis de l’amorçage, dans le domaine élastique comme dans le domaine plastique. Des éprouvettes préalablement irradiées aux protons à une dose de 2 dpa ont été testées dans les mêmes conditions que les éprouvettes non irradiées. La sensibilité accrue du matériau irradié à la CSC-I a pu être quantifiée et nous avons constaté qu’un effet de concentration et un effet de vitesse de sollicitation subsistent après irradiation. L’irradiation induit une localisation plus importante de la déformation menant à un amorçage prématuré des fissures, mais une sensibilité chimique plus importante, tendance à la piquration et décalage de I1, apparaît comme le principal responsable de la plus forte sensibilité de l’irradié. ABSTRACT : During the pellet-cladding interaction, Zirconium-alloy fuel claddings might fail when subjected to incidental power transient in nuclear Pressurized Water Reactors, by Iodine-induced Stress Corrosion Cracking (I-SCC). This study deals with the intergranular initiation of I-SCC cracks in fully recrystallized Zircaloy-4, in methyl alcohol solution of iodine at room temperature, with the focus on critical mechanical parameters and iodine concentration. It was carried out with an approach mixing experiments and numerical simulations. An anisotropic and viscoplastic mechanical behavior model was established and validated over a wide range of loadings. With numerous constant elongation rate tensile tests and four points bending creep tests, the existence of a threshold iodine concentration I0 close to 10-6 g.g-1 was highlighted, necessary to the occurrence of I-SCC damage, along with a transition concentration I1 close to 2 10-4 g.g-1. Above I1 the mechanism changes, leading to a sped up crack initiation and a loss of sensitivity towards mechanical parameters. The importance of concentration on parameters such as crack density, crack average length and intergranular and transgranular crack velocities was evidenced. Experimental results show that plastic strain is not required for I-SCC crack initiation, if the test time is long enough in the presence of stress. Its main influence is to rush the occurrence of cracking by creating initiation sites, by way of breaking the oxide layer and building up intergranular stress. Below I1, the critical strains at initiation show a substantial strain rate sensitivity. In this domain, a threshold stress of 100 MPa was found, well below the yield stress. Thanks to the combined use of notched specimens and numerical simulations, a strong protective effect of an increasing stress biaxiality ratio was found, both in the elastic and plastic domains. Proton-irradiated samples, up to a dose of 2 dpa, were tested in the same conditions as fresh specimens. The higher I-SCC sensitivity of the irradiated material was measured and the effects of concentration and strain rate were found to remain. Irradiation leads to a higher strain localization causing early crack initiation, but the main reason for the higher sensitivity of the irradiated material seems to be a chemical one, with higher pitting occurrence and a shift of I1

Mechanical behavior of recrystallized Zircaloy-4 under monotonic loading at room temperature: Tests and simplified anisotropic modeling

Mechanical behavior of recrystallized Zircaloy-4 was studied at room temperature in the rolling-transverse plane of a thin sheet. Uniaxial constant elongation rate tests (CERTs) were performed along with creep tests, over a wide range of strain rates. Based on a simplified formulation, different sets of parameters for an anisotropic viscoplastic model were found to fit the stress–strain curves. Notched specimen tensile tests were carried out with a digital image correlation (DIC) technique in order to determine the strain field evolution. From these measurements and the determination of Lankford coefficients, the most consistent model was selected and simulated data were successfully compared with the experimental observations

Stress corrosion crack initiation of Zircaloy-4 cladding tubes in an iodine vapor environment during creep, relaxation, and constant strain rate tests

During accidental power transient conditions with Pellet Cladding Interaction (PCI), the synergistic effect of the stress and strain imposed on the cladding by thermal expansion of the fuel, and corrosion by iodine released as a fission product, may lead to cladding failure by Stress Corrosion Cracking (SCC). In this study, internal pressure tests were conducted on unirradiated cold-worked stress-relieved Zircaloy-4 cladding tubes in an iodine vapor environment. The goal was to investigate the influence of loading type (constant pressure tests, constant circumferential strain rate tests, or constant circumferential strain tests) and test temperature (320, 350, or 380 °C) on iodine-induced stress corrosion cracking (I-SCC). The experimental results obtained with different loading types were consistent with each other. The apparent threshold hoop stress for I-SCC was found to be independent of the test temperature. SEM micrographs of the tested samples showed many pits distributed over the inner surface, which tended to coalesce into large pits in which a microcrack could initiate. A model for the time-to-failure of a cladding tube was developed using finite element simulations of the viscoplastic mechanical behavior of the material and a modified Kachanov's damage growth model. The times-to-failure predicted by this model are consistent with the experimental data

Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive

Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, pre-viously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan\u2013Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontin-uation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 \ub1 13.8 years and with an ETA duration of 4.1 \ub1 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients

Apremilast retention rate in clinic practice:observations from an Italian multi-center study

Objective There are few real-world setting studies focused on apremilast efectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention ratein real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and thefactors related to treatment persistence. Methods In ffteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan–Meier curve and the Coxanalysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value<0.05 was considered statistically signifcant. Results The 356 enrolled patients (median age 60 [interquartile range IQR 52–67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7–34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefcacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefcacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96–0.99; p=0.048 and 0.54 IQR 0.31–0.95; p=0.03). Conclusion Almost three-ffths of PsA patients receiving apremilast were still in treatment after 3 years. This study confrmed its efectiveness and safety profle. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbiditi

OP0063 QUANTITATIVE COMPUTED TOMOGRAPHY PREDICTS 10-YEAR MORTALITY IN INTERSTITIAL LUNG DISEASE RELATED TO SYSTEMIC SCLEROSI

Background: Interstitial lung disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Chest CT is the gold standard in detecting ILD although it is not easy to understand its prognostic value. ILD qualitative assessment is almost worthless. Goh et al. semi quantitative score of ILD extent is related to mortality risk but it is burdened by relevant inter/intra-readers variability. An operator independent algorithm based on voxel-wise analysis proved to identify SSc patients with an increased risk of mortality according to prediction models. Objectives: To verify if quantitative analysis of chest CT (QCT) predict 10 years-mortality in SSc patients. Methods: SSc patients with availability of a chest CT were enrolled in 13 different centers. The CT voxel-wise analysis with a free software (www.horosproject.com) provided QCT indexes: kurtosis, skewness, mean lung attenuation and standard deviation. Patients

Overall mortality in combined pulmonary fibrosis and emphysema related to systemic sclerosis

OBJECTIVES: This multicentre study aimed to investigate the overall mortality of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) and to compare CPFE-SSc characteristics with those of other SSc subtypes (with interstitial lung disease-ILD, emphysema or neither). METHODS: Chest CTs, anamnestic data, immunological profile and pulmonary function tests of patients with SSc were retrospectively collected. Each chest CT underwent a semiquantitative assessment blindly performed by three radiologists. Patients were clustered in four groups: SSc-CPFE, SSc-ILD, SSc-emphysema and other-SSc (without ILD nor emphysema). The overall mortality of these groups was calculated by Kaplan-Meier method and compared with the stratified log-rank test; Kruskal-Wallis test, t-Student test and χ² test assessed the differences between groups. P<0.05 was considered statistically significant. RESULTS: We enrolled 470 patients (1959 patient-year); 15.5 % (73/470) died during the follow-up. Compared with the SSc-ILD and other-SSc, in SSc-CPFE there was a higher prevalence of males, lower anticentromere antibodies prevalence and a more reduced pulmonary function (p<0.05). The Kaplan-Meier survival analysis demonstrates a significantly worse survival in patients with SSc-CPFE (HR vs SSc-ILD, vs SSc-emphysema and vs other-SSc, respectively 1.6 (CI 0.5 to 5.2), 1.6 (CI 0.7 to 3.8) and 2.8 (CI 1.2 to 6.6). CONCLUSIONS: CPFE increases the mortality risk in SSc along with a highly impaired lung function. These findings strengthen the importance to take into account emphysema in patients with SSc with ILD

Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis

<p>Abstract</p> <p>Background</p> <p>Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later.</p> <p>Objectives</p> <p>The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO).</p> <p>Methods</p> <p>Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of < 35 mm/Hg measured by echocardiography, were enrolled between September 2007 and September 2009. They had a mean age of 51 ± 13 years, body mass index of 25 ± 5 kg/m²). They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO), HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs) derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR) derived from the acceleration time of the pulmonary outflow tract (ACTpo), and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE). Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test.</p> <p>The data are given as mean values ± SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's <it>r </it>coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant.</p> <p>Results</p> <p>Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 ± 8 mmHg), whereas right ventricular function was normal (TAPSE 23 ± 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of < 46 mm/Hg (p > 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.</p> <p>There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01).</p> <p>Conclusions</p> <p>Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.</p

Stress corrosion cracks initiation of recrystallized Zircaloy-4 in iodine-methanol solutions

En situation d’interaction pastille-gaine (IPG), les gaines de crayons combustible en alliage de zirconium sont susceptibles de rompre lors de transitoires de puissance incidentels dans les réacteurs à eau pressurisée, par un mécanisme de corrosion sous contrainte induite par l’iode (CSC-I). Cette étude traite de l’amorçage intergranulaire des fissures de CSC-I dans le Zircaloy-4 recristallisé, en milieu méthanol iodé à température ambiante, en s’intéressant particulièrement aux paramètres mécaniques critiques et à la concentration en iode. Pour cela, une approche mêlant expériences et simulations numériques a été adoptée. Un modèle de comportement mécanique macroscopique de l’alliage, viscoplastique et anisotrope, a été établi et validé sur une large gamme de sollicitations. Par la réalisation de nombreux essais de traction à vitesse de déformation imposée et de fluage en flexion quatre points, nous avons montré l’existence d’une concentration seuil I0 proche de 10-6 g.g-1 nécessaire à l’apparition du dommage de CSC-I, mais également celle d’une concentration de transition I1 proche de 2 10-4 g.g-1 au-delà de laquelle le mécanisme change, menant à un amorçage anticipé des fissures et une sensibilité réduite de l’endommagement aux paramètres mécaniques. L’importance de la concentration sur des paramètres tels que la densité des fissures, leur longueur moyenne et la vitesse de propagation intergranulaire et transgranulaire a été mise en évidence. Les résultats expérimentaux montrent que la déformation plastique macroscopique n’est pas indispensable à l’amorçage de fissures de CSC-I, pour un temps d’essais suffisamment long en présence de contrainte. Son principal effet est de précipiter l’apparition de fissures par la création de sites d’amorçage, par rupture de la couche d’oxyde et accumulation de contrainte intergranulaire. En dessous de I1 la détermination des déformations critiques à l’amorçage montre un fort effet de vitesse. Dans ce domaine, une contrainte seuil de 100 MPa a été déterminée, bien inférieure à la limite élastique. L’utilisation d’éprouvettes entaillées et de la simulation numérique a permis de mettre en évidence un fort effet protecteur de l’augmentation de la biaxialité des contraintes vis-à-vis de l’amorçage, dans le domaine élastique comme dans le domaine plastique. Des éprouvettes préalablement irradiées aux protons à une dose de 2 dpa ont été testées dans les mêmes conditions que les éprouvettes non irradiées. La sensibilité accrue du matériau irradié à la CSC-I a pu être quantifiée et nous avons constaté qu’un effet de concentration et un effet de vitesse de sollicitation subsistent après irradiation. L’irradiation induit une localisation plus importante de la déformation menant à un amorçage prématuré des fissures, mais une sensibilité chimique plus importante, tendance à la piquration et décalage de I1, apparaît comme le principal responsable de la plus forte sensibilité de l’irradié.During the pellet-cladding interaction, Zirconium-alloy fuel claddings might fail when subjected to incidental power transient in nuclear Pressurized Water Reactors, by Iodine-induced Stress Corrosion Cracking (I-SCC). This study deals with the intergranular initiation of I-SCC cracks in fully recrystallized Zircaloy-4, in methyl alcohol solution of iodine at room temperature, with the focus on critical mechanical parameters and iodine concentration. It was carried out with an approach mixing experiments and numerical simulations. An anisotropic and viscoplastic mechanical behavior model was established and validated over a wide range of loadings. With numerous constant elongation rate tensile tests and four points bending creep tests, the existence of a threshold iodine concentration I0 close to 10-6 g.g-1 was highlighted, necessary to the occurrence of I-SCC damage, along with a transition concentration I1 close to 2 10-4 g.g-1. Above I1 the mechanism changes, leading to a sped up crack initiation and a loss of sensitivity towards mechanical parameters. The importance of concentration on parameters such as crack density, crack average length and intergranular and transgranular crack velocities was evidenced. Experimental results show that plastic strain is not required for I-SCC crack initiation, if the test time is long enough in the presence of stress. Its main influence is to rush the occurrence of cracking by creating initiation sites, by way of breaking the oxide layer and building up intergranular stress. Below I1, the critical strains at initiation show a substantial strain rate sensitivity. In this domain, a threshold stress of 100 MPa was found, well below the yield stress. Thanks to the combined use of notched specimens and numerical simulations, a strong protective effect of an increasing stress biaxiality ratio was found, both in the elastic and plastic domains. Proton-irradiated samples, up to a dose of 2 dpa, were tested in the same conditions as fresh specimens. The higher I-SCC sensitivity of the irradiated material was measured and the effects of concentration and strain rate were found to remain. Irradiation leads to a higher strain localization causing early crack initiation, but the main reason for the higher sensitivity of the irradiated material seems to be a chemical one, with higher pitting occurrence and a shift of I1