Embedded solids of any dimension in the X-FEM. Part II - Imposing Dirichlet boundary conditions

peer reviewedThis paper focuses on the design of a stable Lagrange multiplier space dedicated to enforce Dirichlet boundary conditions on embedded boundaries of any dimension. It follows a previous paper in a series of two, on the topic of embedded solids of any dimension within the context of the extended finite element method. While the first paper is devoted to the design of a dedicated P1 function space to solve elliptic equations defined on manifolds of codimension one or two (curves in 2D and surfaces in 3D, or curves in 3D), the general treatment of Dirichlet boundary conditions, in such a setting, remains to be addressed. This is the aim of this second paper. A new algorithm is introduced to build a stable Lagrange multiplier space from the traces of the shape functions defined on the background mesh. It is general enough to cover: (i) boundary value problems investigated in the first paper (with, for instance, Dirichlet boundary conditions defined along a line in a 3D mismatching mesh); but also (ii) those posed on manifolds of codimension zero (a domain embedded in a mesh of the same dimension) and already considered in Béchet et al. 2009. In both cases, the compatibility between the Lagrange multiplier space and that of the bulk approximation (the dedicated P1 function space used in (i), or classical shape functions used in (ii)) — resulting in the inf–sup condition — is investigate through the numerical Chapelle-Bath test. Numerical validations are performed against analytical and finite element solutions on problems involving 1D or 2D boundaries embedded in a 2D or 3D background mesh. Comparisons with Nitsche’s method and the stable Lagrange multiplier space proposed in Hautefeuille et al. 2012, when they are feasible, highlight good performance of the approach

Embedded solids of any dimension in the X-FEM. Part I - Building a dedicated P1 function space

peer reviewedThis paper focuses on the design of a dedicated P1 function space to model elliptic boundary value problem on a manifold embedded in a space of higher dimension. Using the traces of the linear P1 shape functions, it introduces an algorithm to reduce the function space into an equivalent space having the same properties than a P1 Lagrange approximation. Convergence studies involving problems of codimension one or two embedded in 2D or 3D show good accuracy with regard to classical finite element and analytical solutions. The effects of the relative position of the domain with respect to the mesh are studied in a sensitivity analysis; it illustrates how the proposed solution allows to keep the condition number bounded. A comparative study is performed with the method introduced by Olshanskii et al. 2009 on a closed surface to validate our approach. The robustness of the proposed approach is investigated with regard to their method and that of Burman et al. 2016. This paper is the first in a series of two, on the topic of embedded solids of any dimension within the context of the extended finite element method. It investigates problems involving borderless domains or domains with boundary subject to Dirichlet constraint defined only on the boundaries of the bulk mesh, while the forthcoming paper overcomes this limitation by introducing a new stable Lagrange multiplier space for Dirichlet boundary condition (and more generally stiff condition), that is valid for every combination of the background mesh and manifold dimensions. The combination of both algorithms allows to handle any embedding i.e. 1D, 2D and 3D problems embedded in 2D or 3D background meshes

High resolution pQCT micro architectureal parameters to predict bone failure in the case of forward fall

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Analyse du comportement dynamique de mousses de polyuréthane par des tests vibratoires

L’objectif de cet article est de décrire les techniques expérimentales et l’identification des propriétés dynamiques de mousses de polyuréthane. En effet, le niveau de confort d’un siège automobile est établien considérant les propriétés quasi-statiques – densité, portance et résilience – et dynamiques – transmissibilité – de la mousse flexible de polyuréthane. Notre dispositif d’essai est un système à un degré de liberté, composé d’un dispositif expérimental reposant sur le vérin d’une machine d’essai dynamique. Ce dispositif expérimental est composé d’un plateau supérieur avec une masse libre et d’un plateau inférieur solidaire de la machine d’essai, entre lesquels est placé un échantillon de mousse de dimensions100x100x50 mm3. Les vibrations transmises à travers la mousse sont mesurées pour déterminerles caractéristiques dynamiques de l’échantillon et permettent de réaliser le diagramme de Bodede la transmissibilité de l’échantillon. Cinq types de mousses de polyuréthane utilisées dans l’automobile seront comparés dans cet article

Hydro-mechanical simulation and analysis of induced seismicity for a hydraulic stimulation test at the Reykjanes geothermal field, Iceland

The combination of seismic analysis with advanced physics-based simulation provides an opportunity to further understand injection-induced fault reactivation, including the hydro-mechanical interplay between different faults and the rock where they reside. Here, this is investigated based on data from hydraulic stimulation of a well at the Reykjanes geothermal field. Central is the development of an interdisciplinary framework for integration of different data types towards a 3D, hydro-mechanical and faulted geothermal reservoir simulation model. This work shows how seismic interpretations can improve simulation models and, reciprocally, how fully coupled physics-based modeling can add to seismic interpretations in analysis of fault reactivation.publishedVersio

Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC:A Comparison Study

Simple Summary We compared the UltraSEEK (TM) Lung Panel on the MassARRAY (R) System (Agena Bioscience) with the FDA-approved Cobas (R) EGFR Mutation Test v2 for the detection of EGFR mutations in liquid biopsies of NSCLC patients, accompanied with preanalytical sample assessment using the novel Liquid IQ (R) Panel. For the detection of relevant predictive mutations using the UltraSEEK (TM) Lung Panel, an input of over 10 ng showed 100% concordance with Cobas (R) EGFR Mutation Test v2 and detection of all tissue confirmed mutations. In case of lower ccfDNA input, the risk of missing clinically relevant mutations should be considered. The use of a preanalytical ccfDNA quality control assay such as the Liquid IQ (R) Panel is recommended to confidently interpret results, avoiding bias induced by non-specific genomic DNA and low input of specific tumoral ccfDNA fragments. Plasma-based tumor mutational profiling is arising as a reliable approach to detect primary and therapy-induced resistance mutations required for accurate treatment decision making. Here, we compared the FDA-approved Cobas (R) EGFR Mutation Test v2 with the UltraSEEK (TM) Lung Panel on the MassARRAY (R) System on detection of EGFR mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ (R) Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas (R) and UltraSEEK (TM) tests. Liquid IQ (R) analysis was initially validated (n = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ (R) results were applied to harmonize ccfDNA input for the Cobas (R) and UltraSEEK (TM) tests for 63 NSCLC patients. The overall concordance between the Cobas (R) and UltraSEEK (TM) tests was 86%. The Cobas (R) test detected more EGFR exon19 deletions and L858R mutations, while the UltraSEEK (TM) test detected more T790M mutations. A 100% concordance in both the clinical (n = 137) and harmonized (n = 63) cohorts was observed when >10 ng of ccfDNA was used as determined by the Liquid IQ (R) Panel. The Cobas (R) and UltraSEEK (TM) tests showed similar sensitivity in EGFR mutation detection, particularly when ccfDNA input was sufficient. It is recommended to preanalytically determine the ccfDNA concentration accurately to ensure sufficient input for reliable interpretation and treatment decision making

Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.

International audienceBone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout ((-/-)) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP(-/-) mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (>/=12 mo) BSP(-/-) mice. At 4 mo, BSP(-/-) mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP(-/-) versus WT bone marrow stromal cultures. BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP(-/-) mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN(-/-) mice

Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis

Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin

Prediction of Incident Hip Fracture with the Estimated Femoral Strength by Finite Element Analysis of DXA Scans in the Study of Osteoporotic Fractures

A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of DXA scans, with incident hip fracture in comparison to hip BMD, FRAX(®) and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean±SD follow-up of 12.8±5.7 yrs from the Study of Osteoporotic Fractures (n=7860 community-dwelling women ≥67 yr of age). We analyzed the baseline DXA scans (Holgoic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age-BMI-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21, 95% CI 1.95–2.50) was greater than that for TH BMD (1.86, 95% CI 1.67–2.08; p<0.05), FN BMD (2.04, 95% CI 1.79–2.32; p>0.05), FRAX(®) scores (range 1.32–1.68; p<0.0005) and many HSA variables (range 1.13–2.43; p<0.005), and the association was still significant (p<0.05) after further adjustment for hip BMD or FRAX(®) scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759, p<0.05) and FRAX(®) scores (0.711–0.743, p<0.0001) but not FN BMD (0.762, p>0.05) Similar findings were obtained for intra- and extra-capsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women