Scaling analysis of deformation field within granular materials: application to strain localization

Discrete element method (DEM) simulations using periodic boundary conditions and molecular dynamics are conducted on a frictional granular media. Two dimensional strain controlled biaxial tests are carried out on an assembly of circular particles interacting via elastic contacts and Coulomb friction. The spatial correlations that take place within the deformation field along the loading path are tracked by a scaling analysis of the continuous strain rate field. This method allows us to discuss the degree of strain localization occurring throughout the test. The analysis of the correlation length in the early stages of macroscopic deformation leads to the identification of two distinct behaviors. First, a divergence of the correlation length on the first deformation invariant, i.e. the divergence, is reported at the onset of macroscopic dilation. This suggests an interpretation of the contraction peak as a critical point. Secondly, an increase of the correlation length on the second deformation invariant, i.e. the shear, is also observed before the peak load. However, saturation remains on the scaling law. We argue that this second behavior is associated to macroscopic shear banding: our analysis accurately gives its outbreak on the stress versus strain curve. Finally, a dependence of the correlation length as a function of the deformation window considered is reported. This shows that scaling properties within the deformation field emerge from long range interactions within an assembly of rigid frictional particles

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Particle Shape Effect on Macroscopic Behaviour of Underground Structures: Numerical and Experimental Study

The mechanical performance of underground flexible structures such as buried pipes or culverts made of plastics depend not only on the properties of the structure, but also on the material surrounding it. Flexible drains can deflect by 30% with the joints staying tight, or even invert. Large deformations of the structure are difficult to model in the framework of Finite Element Method, but straightforward in Discrete Element Methods. Moreover, Discrete Element approach is able to provide information about the grain-grain and grain-structure interactions at the microscale. This paper presents numerical and experimental investigations of flexible buried pipe behaviour with focus placed on load transfer above the buried structure. Numerical modeling was able to reproduce the experimental results. Load repartition was observed, being affected by a number of factors such as particle shape, pipe friction and pipe stiffness

FEMxDEM: a new efficient multi-scale approach for geotechnical problems with strain localization

peer reviewedThe paper presents a multi-scale modeling of Boundary Value Problem (BVP) approach involving cohesive-frictional granular materials in the FEM × DEM multi-scale framework. On the DEM side, a 3D model is defined based on the interactions of spherical particles. This DEM model is built through a numerical homogenization process applied to a Volume Element (VE). It is then paired with a Finite Element code. Using this numerical tool that combines two scales within the same framework, we conducted simulations of biaxial and pressuremeter tests on a cohesive-frictional granular medium. In these cases, it is known that strain localization does occur at the macroscopic level, but since FEMs suffer from severe mesh dependency as soon as shear band starts to develop, the second gradient regularization technique has been used. As a consequence, the objectivity of the computation with respect to mesh dependency is restored

Impact of Body Mass Index on the Agreement Between Ultrasound- and Clinical Assessments of Disease Activity in Rheumatoid Arthritis : Multicenter and Cross-sectional Study

International audienc

Impact of Body Mass Index on the Agreement Between Ultrasound- and Clinical Assessments of Disease Activity in Rheumatoid Arthritis : Multicenter and Cross-sectional Study

International audienc

Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece

International audienceBackground: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.Methods: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were &gt;65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.Results: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).Conclusions: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.)

Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece

International audienceBackground: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.Methods: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were &gt;65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.Results: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).Conclusions: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.)

Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: a joint analysis of the multicenter, observational, real-world French PEMI-BIL and Italian PEMI-REAL cohort studies

Background Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting. Material and Methods A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included. Results Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs. Conclusions These results confirm the effectiveness and safety of pemigatinib in a real-world settin