Boundary Element Analysis of Three-Dimensional Exponentially Graded Isotropic Elastic Solids

A numerical implementation of the Somigliana identity in displacements for the solution of 3D elastic problems in exponentially graded isotropic solids is presented. An expression for the fundamental solution in displacements, Uj , was deduced by Martin et al. (Proc. R. Soc. Lond. A, 458, pp. 1931–1947, 2002). This expression was recently corrected and implemented in a Galerkin indirect 3D BEM code by Criado et al. (Int. J. Numer. Meth. Engng., 2008). Starting from this expression of Uj , a new expression for the fundamental solution in tractions Tj has been deduced in the present work. These quite complex expressions of the integral kernels Uj and Tj have been implemented in a collocational direct 3D BEM code. The numerical results obtained for 3D problems with known analytic solutions verify that the new expression for Tj is correct. Excellent accuracy is obtained with very coarse boundary element meshes, even for a relativelyMinisterio de Educación Cultura y Deporte SAB2003-0088Ministerio de Ciencia y Tecnología MAT2003-0331

Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients.

BACKGROUND: Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF. Therefore, a method to quantify these dynamics and a characterization of differences across disease states is needed. METHODS: Complete intrathecal 3D CSF geometry and CSF flow velocities at six axial locations in the spinal canal were collected by T2-weighted and phase-contrast MRI, respectively. Scans were completed for eight people with ALS and ten healthy controls. Manual segmentation of the spinal subarachnoid space was performed and coupled with an interpolated model of CSF flow within the spinal canal. Geometric and hydrodynamic parameters were then generated at 1 mm slice intervals along the entire spine. Temporal analysis of the waveform spectral content and feature points was also completed. RESULTS: Comparison of ALS and control groups revealed a reduction in CSF flow magnitude and increased flow propagation velocities in the ALS cohort. Other differences in spectral harmonic content and geometric comparisons may support an overall decrease in intrathecal compliance in the ALS group. Notably, there was a high degree of variability between cases, with one ALS patient displaying nearly zero CSF flow along the entire spinal canal. CONCLUSION: While our sample size limits statistical confidence about the differences observed in this study, it was possible to measure and quantify inter-individual and cohort variability in a non-invasive manner. Our study also shows the potential for MRI based measurements of CSF geometry and flow to provide information about the hydrodynamic environment of the spinal subarachnoid space. These dynamics may be studied further to understand the behavior of CSF solute transport in healthy and diseased states

EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting

[EN] Introduction: Durvalumab is the new standard of care for unresectable locally advanced NSCLC, with PD-L1 _1% and who did not have progression after CRT treatment in the European Union. Our study compares the effectiveness and the frequency of radiation pneumonitis in patients treated with concurrent CRT with or without durvalumab consolidation during the same period in real clinical practice. Methods: A single-center retrospective study. 71 treated patients with unresectable stage III NSCLC were included between March 2018 and December 2021, 37 with CRT followed by durvalumab and 34 with CRT alone. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated since the date of the end CRT. Propensity score matching (PSM) 1:1 was used to account for differences in baseline characteristics. Results: Median age was 67 years (range 46-82). 25.4% of the patients were _75 years old. 78.9% were men and 53.5% former smokers. 54.9% had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel (43.7%), receiving induction chemotherapy in up to 54.9% of patients. 73.2% received between 60-66 Gy doses of radiotherapy. Median time from end of CRT to onset durvalumab was 44 days (range 13-120) with a median of 14 infusions (range 6-27). Of the 34 patients without durvalumab treatment, the expression PD-L1 <1% (58.8%) was the most frequent cause for rejecting consolidation therapy. After PSM analysis, patients distributions were well balanced. With a median follow-up of 19.7 months (range 1.4-36.6); median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013). Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab and 29.9 months (95% CI, 23.3-36.6) with durvalumab (p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and 49% vs 100%, 86% and 74%, respectively. The rate of radiation pneumonitis was more frequent with durvalumab consolidation (56.8% against 44.1%), (p¼0.346), especially within 3 months after CRT. G3 pneumonitis was only observed in the consolidation therapy. Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation after CRT in real-world patients with unresectable stage III NSCLC. Further sample and longer follow-up are required to obtain more accurate results. Active surveillance and appropriate management for radiation pneumonitis are needed, in especially in candidates for consolidation treatmentS

EP05.02-002 Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?

[EN] Introduction: Durvalumab received EMA approval as consolidation therapy (CT) for unresectable stage III NSCLC with PD-L1 _1% and who did not have progression after CRT. Our objective was to analyze in real clinical practice the effectiveness of durvalumab and explore the clinical factors that may be associated with the benefit from CT. Methods: Retrospective study was made at Hospital of Leon (Spain), including 37 patients with locally advanced NSCLC treated with durvalumab after CRT treatment between March 2018 and october 2021 (40.5% patients were included in the durvalumab early access program). The neutrophil-to-lymphocyte ratio (NLR) could identified after CRT as a factor that may be benefit from durvalumab. Results: Median age was 67 years (range 46-82 years). 40.5% of patients were _70 years old. 78.4% were male and 51.4% smokers. 54% had non-squamous histology. PD-L1 expression was <1% in 5% and not available in 8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were 24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to onset durvalumab was 44 days (range 13-120 days). Overall median CT duration was 214.8 days (range 69-399 days) with a median of 14 infusions (range 6-27 infusions). With a median follow up of 19.7 months (range 1.4-34.9 months); 67.6% had stopped CT: 37.8% due to completing treatment, 16.2% disease progression, 10.8% adverse event and 2.7% due to COVID19 infection. Median real-world progressionfree survival (rwPFS) was 17 months (95% CI, 11-23). Median realworld overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). % rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively. For patients with post-CRT NLR not exceeding the cohort median value of 6, receipt of durvalumab was associated with an improvement in rwOS (median not reached vs 25.7 months; p¼0.025). 56.8% patients had any grade of radiation pneumonitis (median time from CRT start: 119 days [range 36-241 days]). Of these, 19% patients developed worsening of radiation pneumonitis with durvalumab. 54,1% developed immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation in this patients population in a real-life setting. We identified low NLR after CRT as a potentially predictive factor for the benefit of CT in locally advanced NSCLC.S

Interface crack model using finite fracture mechanics applied to the double pull-push shear test

An analytical procedure predicting a debond (interface crack) onset and growth in an adhesive joint between two beams or plates is developed and applied to a specific configuration often used in reinforcement tests in civil engineering. The procedure is based on Timoshenko beam theory and Linear Elastic-(Perfectly) Brittle Interface Model (LEBIM) combined with the Coupled Criterion of the Finite Fracture Mechanics (CC-FFM) for mixed-mode fracture. First, a sixth order differential equation in the shear stresses along the adhesive layer is deduced and solved, leading to closed form expressions for both shear and normal stresses in the adhesive. Then, the critical value of the applied load necessary to produce debonding is predicted by coupling a stress and an energy condition based on: (i) the stress distribution produced in the interface before the debond onset and (ii) the energy released during the debonding process along the interface. Although the developed procedure can be applied to several types of joints with different geometries, materials and loads (e.g., double lap joint tests including adherents made of steel or composites), herein it is applied to the double pull-push shear test where the debond onset and growth between a Carbon Fibre Reinforced Polymer (CFRP) laminate and a concrete block occurs. For such a case, the debond is produced under predominant fracture mode II; nevertheless, it is shown that relevant normal (peeling) stresses associated to mode I may appear as well. A comparison of the present solution with a previous one by the shear-lag model is provided as well

A numerical implementation of the Coupled Criterion of Finite Fracture Mechanics for elastic interfaces

A new numerical procedure for predicting interface failures between solids is developed. The procedure is based on the Linear Elastic-(Perfectly) Brittle Interface Model (LEBIM) combined with the Coupled Criterion of the Finite Fracture Mechanics (CCFFM). Although in the present investigation this procedure is implemented in a 2D BEM code, a general pseudocode is devised allowing its implementation in any BEM or FEM code. The pull-push shear test is used as a benchmark problem, where the fracture mode II is dominant. Nevertheless, the present procedure can tackle a debond growth occurring under any fracture mode mixity. The pull-push problem is chosen since it allows us to check the obtained numerical results against an available analytical solution based on a beam model. Additionally, the numerical results are compared with some experimental data from literature. Furthermore, an inverse analysis is applied to obtain the interface strength and fracture parameters that the model needs

Emergency contraception under attack in Latin America: Response of the medical establishment and civil society

The concept that it is possible to prevent a pregnancy after coitus is not new, but has gained prominence over the lost 10-15 years. It provides a second chance to women who do not want to get pregnant and who, voluntarily or not, have had unprotected intercourse. Emergency contraception has been under strong attack by the Catholic church and anti-choice orgonisations in Latin America, who claim that the interference with implantation of the fertilised ovum is equivalent to an early abortion. The accumulation of evidence, however, is that the mechanism of action of emergency contraception is to prevent ovulation and that it does not interfere with implantation. This has been ignored by the anti-choice movement The pattern of opposition to emergency contraception has been the some all over the Latin America region. The medical establishment and civil society including the International Consortium for Emergency Contraception, have played a key role in defending access to emergency contraception throughout the region. A positive consequence of the public opposition of the Catholic church is that the concept and the method have become better known, and emergency contraception has become widely Used. The cases of Peru, Brazil and Chile are described as examples. (c) 2007 Reproductive Health Matters. All rights reserved.152913013

SGBEM for cohesive cracks in homogeneous media

5nonenoneTavara L.; Mantic V.; Salvadori A.; Gray L.J.; Parıs F.Tavara, L.; Mantic, V.; Salvadori, Alberto; Gray, L. J.; Parıs, F