Differences in Time to Disease Progression Do Not Predict for Cancer-specific Survival in Patients Receiving Immediate or Deferred Androgen-deprivation Therapy for Prostate Cancer: Final Results of EORTC Randomized Trial 30891 with 12 Years of Follow-up

BACKGROUND Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization. OBJECTIVE Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences. DESIGN, SETTING, AND PARTICIPANTS EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival. RESULTS AND LIMITATIONS After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085). CONCLUSIONS This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.

Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.

Finite element analysis predicts experimental failure patterns in vertebral bodies loaded via intervertebral discs up to large deformation

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R2 improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae.

Results of a Finite-Element Sea-Ice Ocean Model (FESOM) set-up to study the interannual to decadal variability in the deep-water formation rates

The characteristics of a global set-up of the Finite-Element Sea-Ice Ocean Model under forcing of the period 1958-2004 are presented. The model set-up is designed to study the variability in the deep-water mass formation areas and was therefore regionally better resolved in the deep-water formation areas in the Labrador Sea, Greenland Sea, Weddell Sea and Ross Sea. The sea-ice model reproduces realistic sea-ice distributions and variabilities in the sea-ice extent of both hemispheres as well as sea-ice transport that compares well with observational data. Based on a comparison between model and ocean weather ship data in the North Atlantic, we observe that the vertical structure is well captured in areas with a high resolution. In our model set-up, we are able to simulate decadal ocean variability including several salinity anomaly events and corresponding fingerprint in the vertical hydrography. The ocean state of the model set-up features pronounced variability in the Atlantic Meridional Overturning Circulation as well as the associated mixed layer depth pattern in the North Atlantic deep-water formation areas.

DATED-1: compilation of dates and time-slice reconstruction of the build-up and retreat of the last Eurasian (British-Irish, Scandinavian, Svalbard-Barents-Kara Seas) Ice Sheets 40-10 ka

DATED-1 comprises a compilation of dates related to the build-up and retreat of the Eurasian (British-Irish, Scandinavian, Svalbard-Barents-Kara Seas) Ice Sheets, and time-slice maps of the Eurasian Ice sheet margins. Dates are sourced from the published literature. Ice margins are based on published geological and chronological data and include uncertainty bounds (maximum, minimum) as well as what we consider to be the most-credible (mc) based on the available evidence. DATED-1 has a census date of 1 January 2013. Full description and caveats for use are given in: Hughes, A.L.C., Gyllencreutz, R., Lohne, Ø.S., Mangerud, J., Svendsen, J.I. (2015) The last Eurasian Ice Sheets - a chronological database and time-slice reconstruction, DATED-1.

A second order in time modified Lagrange-Galerkin finite element method for the incompressible Navier-Stokes equations

We introduce a second order in time modified Lagrange--Galerkin (MLG) method for the time dependent incompressible Navier--Stokes equations. The main ingredient of the new method is the scheme proposed to calculate in a more efficient manner the Galerkin projection of the functions transported along the characteristic curves of the transport operator. We present error estimates for velocity and pressure in the framework of mixed finite elements when either the mini-element or the $P2/P1$ Taylor--Hood element are used.

A methodology to calibrate structural finite element models for reinforced concrete structures subject to blast loads

Civil buildings are not specifically designed to support blast loads, but it is important to take into account these potential scenarios because of their catastrophic effects, on persons and structures. A practical way to consider explosions on reinforced concrete structures is necessary. With this objective we propose a methodology to evaluate blast loads on large concrete buildings, using LS-DYNA code for calculation, with Lagrangian finite elements and explicit time integration. The methodology has three steps. First, individual structural elements of the building like columns and slabs are studied, using continuum 3D elements models subjected to blast loads. In these models reinforced concrete is represented with high precision, using advanced material models such as CSCM_CONCRETE model, and segregated rebars constrained within the continuum mesh. Regrettably this approach cannot be used for large structures because of its excessive computational cost. Second, models based on structural elements are developed, using shells and beam elements. In these models concrete is represented using CONCRETE_EC2 model and segregated rebars with offset formulation, being calibrated with continuum elements models from step one to obtain the same structural response: displacement, velocity, acceleration, damage and erosion. Third, models basedon structural elements are used to develop large models of complete buildings. They are used to study the global response of buildings subjected to blast loads and progressive collapse. This article carries out different techniques needed to calibrate properly the models based on structural elements, using shells and beam elements, in order to provide results of sufficient accuracy that can be used with moderate computational cost.

A time-domain finite element method for seakeeping and wave resistance problems

El objetivo de la tesis es la investigación de algoritmos numéricos para el desarrollo de herramientas numéricas para la simulación de problemas tanto de comportamiento en la mar como de resistencia al avance de buques y estructuras flotantes. La primera herramienta desarrollada resuelve el problema de difracción y radiación de olas. Se basan en el método de los elementos finitos (MEF) para la resolución de la ecuación de Laplace, así como en esquemas basados en MEF, integración a lo largo de líneas de corriente, y en diferencias finitas desarrollados para la condición de superficie libre. Se han desarrollado herramientas numéricas para la resolución de la dinámica de sólido rígido en sistemas multicuerpos con ligaduras. Estas herramientas han sido integradas junto con la herramienta de resolución de olas difractadas y radiadas para la resolución de problemas de interacción de cuerpos con olas. También se han diseñado algoritmos de acoplamientos con otras herramientas numéricas para la resolución de problemas multifísica. En particular, se han realizado acoplamientos con una herramienta numérica basada de cálculo de estructuras con MEF para problemas de interacción fluido-estructura, otra de cálculo de líneas de fondeo, y con una herramienta numérica de cálculo de flujos en tanques internos para problemas acoplados de comportamiento en la mar con “sloshing”. Se han realizado simulaciones numéricas para la validación y verificación de los algoritmos desarrollados, así como para el análisis de diferentes casos de estudio con aplicaciones diversas en los campos de la ingeniería naval, oceánica, y energías renovables marinas. ABSTRACT The objective of this thesis is the research on numerical algorithms to develop numerical tools to simulate seakeeping problems as well as wave resistance problems of ships and floating structures. The first tool developed is a wave diffraction-radiation solver. It is based on the finite element method (FEM) in order to solve the Laplace equation, as well as numerical schemes based on FEM, streamline integration, and finite difference method tailored for solving the free surface boundary condition. It has been developed numerical tools to solve solid body dynamics of multibody systems with body links across them. This tool has been integrated with the wave diffraction-radiation solver to solve wave-body interaction problems. Also it has been tailored coupling algorithms with other numerical tools in order to solve multi-physics problems. In particular, it has been performed coupling with a MEF structural solver to solve fluid-structure interaction problems, with a mooring solver, and with a solver capable of simulating internal flows in tanks to solve couple seakeeping-sloshing problems. Numerical simulations have been carried out to validate and verify the developed algorithms, as well as to analyze case studies in the areas of marine engineering, offshore engineering, and offshore renewable energy.

Finite temperature dynamics of vortices in the two dimensional anisotropic Heisenberg model

We study the effects of finite temperature on the dynamics of non-planar vortices in the classical, two-dimensional anisotropic Heisenberg model with XY- or easy-plane symmetry. To this end, we analyze a generalized Landau-Lifshitz equation including additive white noise and Gilbert damping. Using a collective variable theory with no adjustable parameters we derive an equation of motion for the vortices with stochastic forces which are shown to represent white noise with an effective diffusion constant linearly dependent on temperature. We solve these stochastic equations of motion by means of a Green's function formalism and obtain the mean vortex trajectory and its variance. We find a non-standard time dependence for the variance of the components perpendicular to the driving force. We compare the analytical results with Langevin dynamics simulations and find a good agreement up to temperatures of the order of 25% of the Kosterlitz-Thouless transition temperature. Finally, we discuss the reasons why our approach is not appropriate for higher temperatures as well as the discreteness effects observed in the numerical simulations.

Got A Minute: Instruction Tune-Up for Time Pressed Librarians

This book contains 19 essays that have been written by current LIS Students who were enrolled in the LIS4330: Library Instruction class at the University of Denver, 2016. Designed to provide a short and pithy overview of a topic that is related to instruction, education, or information literacy, each essays aims to be accessible and approachable for time-pressed librarians who may not have time to catch up.