Multi-level hp-finite cell method for embedded interface problems with application in biomechanics

This work presents a numerical discretization technique for solving three-dimensional material interface problems involving complex geometry without conforming mesh generation. The finite cell method (FCM), which is a high-order fictitious domain approach, is used for the numerical approximation of the solution without a boundary-conforming mesh. Weak discontinuities at material interfaces are resolved by using separate FCM meshes for each material sub-domain, and weakly enforcing the interface conditions between the different meshes. Additionally, a recently developed hierarchical hp-refinement scheme is employed to locally refine the FCM meshes in order to resolve singularities and local solution features at the interfaces. Thereby, higher convergence rates are achievable for non-smooth problems. A series of numerical experiments with two- and three-dimensional benchmark problems is presented, showing that the proposed hp-refinement scheme in conjunction with the weak enforcement of the interface conditions leads to a significant improvement of the convergence rates, even in the presence of singularities. Finally, the proposed technique is applied to simulate a vertebra-implant model. The application showcases the method's potential as an accurate simulation tool for biomechanical problems involving complex geometry, and it demonstrates its flexibility in dealing with different types of geometric description

Multi-level hp-adaptivity and explicit error estimation

Recently, a multi-level hp-version of the finite element method (FEM) was proposed to ease the difficulties of treating hanging nodes, while providing full hp-approximation capabilities. In the original paper, the refinement procedure made use of a-priori knowledge of the solution. However, adaptive procedures can produce discretizations which are more effective than an intuitive choice of element sizes h and polynomial degree distributions p. This is particularly prominent when a-priori knowledge of the solution is only vague or unavailable. The present contribution demonstrates that multi-level hp-adaptive schemes can be efficiently driven by an explicit a-posteriori error estimator. To this end, we adopt the classical residual-based error estimator. The main insight here is that its extension to multi-level hp-FEM is possible by considering the refined-most overlay elements as integration domains. We demonstrate on several two- and three-dimensional examples that exponential convergence rates can be obtained.(VLID)270440

Endothelial NOS (NOS3) impairs myocardial function in developing sepsis

Endothelial nitric oxide synthase (NOS)3-derived nitric oxide (NO) modulates inotropic response and diastolic interval for optimal cardiac performance under non-inflammatory conditions. In sepsis, excessive NO production plays a key role in severe hypotension and myocardial dysfunction. We aimed to determine the role of NOS3 on myocardial performance, NO production, and time course of sepsis development. NOS3(−/−) and C57BL/6 wildtype mice were rendered septic by cecum ligation and puncture (CLP). Cardiac function was analyzed by serial echocardiography, in vivo pressure and isolated heart measurements. Cardiac output (CO) increased to 160 % of baseline at 10 h after sepsis induction followed by a decline to 63 % of baseline after 18 h in wildtype mice. CO was unaltered in septic NOS3(−/−) mice. Despite the hyperdynamic state, cardiac function and mean arterial pressure were impaired in septic wildtype as early as 6 h post CLP. At 12 h, cardiac function in septic wildtype was refractory to catecholamines in vivo and respective isolated hearts showed impaired pressure development and limited coronary flow reserve. Hemodynamics remained stable in NOS3(−/−) mice leading to significant survival benefit. Unselective NOS inhibition in septic NOS3(−/−) mice diminished this survival benefit. Plasma NO(x)- and local myocardial NO(x)- and NO levels (via NO spin trapping) demonstrated enhanced NO(x)- and bioactive NO levels in septic wildtype as compared to NOS3(−/−) mice. Significant contribution by inducible NOS (NOS2) during this early phase of sepsis was excluded. Our data suggest that NOS3 relevantly contributes to bioactive NO pool in developing sepsis resulting in impaired cardiac contractility. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-013-0330-8) contains supplementary material, which is available to authorized users

ADRIA LITHOSPHERE INVESTIGATION ALPHA - Cruise No. M86/3, January 20 - February 04, 2012, Brindisi (Italy) - Dubrovnik (Croatia)

The Adriatic Sea and underlying lithosphere remains the least investigated part of the Mediterranean Sea. To shed light on the plate tectonic setting in this central part of southern Europe, R/V METEOR cruise M86/3 set out to acquire deep penetrating seismic data in the Adriatic Sea. M86/3 formed the core of an amphibious investigation crossing Adria from the Italian Peninsula into Montenegro/Albania. A total of 111 OBS/OBH deployments were successfully carried out, in addition to 47 landstations both in Italy and Montenegro/Albania, which recorded the offshore airgun shots. In the scope of this shoreline-crossing study, the aim is to quantify the shallow geometry, deep boundaries and the architecture of the southern Adriatic crust and lithosphere and to provide insights on a possible decoupling zone between the northern and southern Adriatic domains. Investigating the structure of the Adriatic crust and lithospheric mantle and analyzing the tectonic activity are essential for understanding the mountain-building processes that underlie the neotectonics and earthquake hazard of the Periadriatic region, especially in the vicinity of local decoupling zones

Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial

Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Background: Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. Methods: The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results: HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant >= 90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. Conclusions: HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients' outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated