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- Jerusalem, G, et al.
(författare)
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Continuous versus intermittent extended adjuvant letrozole for breast cancer: Final results of randomized phase 3 SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.
- 2021
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1256-1266
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Tidskriftsartikel (refereegranskat)abstract
- Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy. In animal models, resistance was reversed with restoration of circulating estrogen level during interruption of letrozole treatment. This phase 3 randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen sub-study (SOLE-EST) analyzed the level of estrogen during the interruption of treatment.SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant endocrine therapy. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all year 5).Intention-to-treat population included 4851 women in SOLE (n=2425 in intermittent and n=2426 in continuous letrozole groups) and 103 women in SOLE-EST (n=78 in intermittent and n=25 in continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival was 81.4% in intermittent group and 81.5% in continuous group (hazard ratio: 1.03, 95%CI: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.Extended adjuvant endocrine therapy by intermittent administration of letrozole did not improve disease-free survival compared to continuous use despite the recovery of circulating estrogen level. The similar disease-free survival coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
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- Vigueras, G., et al.
(författare)
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An XFEM/CZM implementation for massively parallel simulations of composites fracture
- 2015
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Ingår i: Composite structures. - : Elsevier BV. - 0263-8223 .- 1879-1085. ; 125, s. 542-557
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Tidskriftsartikel (refereegranskat)abstract
- Because of their widely generalized use in many industries, composites are the subject of many research campaigns. More particularly, the development of both accurate and flexible numerical models able to capture their intrinsically multiscale modes of failure is still a challenge. The standard finite element method typically requires intensive remeshing to adequately capture the geometry of the cracks and high accuracy is thus often sacrificed in favor of scalability, and vice versa. In an effort to preserve both properties, we present here an extended finite element method (XFEM) for large scale composite fracture simulations. In this formulation, the standard FEM formulation is partially enriched by use of shifted Heaviside functions with special attention paid to the scalability of the scheme. This enrichment technique offers several benefits since the interpolation property of the standard shape function still holds at the nodes. Those benefits include (i) no extra boundary condition for the enrichment degree of freedom, and (ii) no need for transition/blending regions; both of which contribute to maintaining the scalability of the code.Two different cohesive zone models (CZM) are then adopted to capture the physics of the crack propagation mechanisms. At the intralaminar level, an extrinsic CZM embedded in the XFEM formulation is used. At the interlaminar level, an intrinsic CZM is adopted for predicting the failure. The overall framework is implemented in ALYA, a mechanics code specifically developed for large scale, massively parallel simulations of coupled multi-physics problems. The implementation of both intrinsic and extrinsic CZM models within the code is such that it conserves the extremely efficient scalability of ALYA while providing accurate physical simulations of computationally expensive phenomena. The strong scalability provided by the proposed implementation is demonstrated. The model is ultimately validated against a full experimental campaign of loading tests and X-ray tomography analyzes.
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| 8. |
- Wu, L., et al.
(författare)
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A micro-meso-model of intra-laminar fracture in fiber-reinforced composites based on a discontinuous Galerkin/cohesive zone method
- 2013
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Ingår i: Engineering Fracture Mechanics. - : Elsevier BV. - 0013-7944 .- 1873-7315. ; 104, s. 162-183
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Tidskriftsartikel (refereegranskat)abstract
- The recently developed hybrid discontinuous Galerkin/extrinsic cohesive law framework is extended to the study of intra-laminar fracture of composite materials. Toward this end, micro-volumes of different sizes are studied. The method captures the debonding process, which is herein proposed to be assimilated to a damaging process, before the strain softening onset, and the density of dissipated energy resulting from the damage (debonding) remains the same for the different studied cell sizes. Finally, during the strain softening phase a micro-crack initiates and propagates in agreement with experimental observations. We thus extract a resulting mesoscale cohesive law, which is independent on the cell sizes, using literature methods.
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| 9. |
- Barba, D., et al.
(författare)
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A thermodynamically consistent constitutive model for diffusion-assisted plasticity in Ni-based superalloys
- 2018
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Ingår i: International journal of plasticity. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0749-6419 .- 1879-2154. ; 105, s. 74-98
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Tidskriftsartikel (refereegranskat)abstract
- An elasto-viscoplastic thermodynamically consistent constitutive model for diffusion-assisted phase transformations is presented here. The model accounts for the different deformation mechanisms, their time dependence, the crystal rotations produced by microtwin propagation and the chemistry-plasticity coupling occurring at high temperature. It is applied to the study of the chemically assisted microtwinning observed in Ni-based superalloys in the temperature range of 600-800 degrees C. The model parameters are calibrated against multi-directional mechanical data from tensile creep tests of single crystal superalloy MD2. The constitutive model is then implemented into a crystal plasticity finite element code to study the activation of the different deformation mechanisms within single crystal and polycrystalline aggregates. Doing so, a relation between the rotations of the crystal and the creep life of the different crystal orientations is established. The results eventually reveal the critical role of the strong anisotropy of microtwin formation on the asymmetric behavior of the alloy and its relevant role on the mechanical performance.
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