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Method Accounts (method + account)
Selected AbstractsDetermining a Maximum-Tolerated Schedule of a Cytotoxic AgentBIOMETRICS, Issue 2 2005Thomas M. Braun Summary Most phase I clinical trials are designed to determine a maximum-tolerated dose (MTD) for one initial administration or treatment course of a cytotoxic experimental agent. Toxicity usually is defined as the indicator of whether one or more particular adverse events occur within a short time period from the start of therapy. However, physicians often administer an agent to the patient repeatedly and monitor long-term toxicity due to cumulative effects. We propose a new method for such settings. It is based on the time to toxicity rather than a binary outcome, and the goal is to determine a maximum-tolerated schedule (MTS) rather than a conventional MTD. The model and method account for a patient's entire sequence of administrations, with the overall hazard of toxicity modeled as the sum of a sequence of hazards, each associated with one administration. Data monitoring and decision making are done continuously throughout the trial. We illustrate the method with an allogeneic bone marrow transplantation (BMT) trial to determine how long a recombinant human growth factor can be administered as prophylaxis for acute graft-versus-host disease (aGVHD), and we present a simulation study in the context of this trial. [source] Numerical studies of shear banding in interface shear tests using a new strain calculation method,INTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 12 2007Jianfeng Wang Abstract Strain localization is closely associated with the stress,strain behaviour of an interphase system subject to quasi-static direct interface shear, especially after peak stress state is reached. This behaviour is important because it is closely related to deformations experienced by geotechnical composite structures. This paper presents a study using two-dimensional discrete element method (DEM) simulations on the strain localization of an idealized interphase system composed of densely packed spherical particles in contact with rough manufactured surfaces. The manufactured surface is made up of regular or irregular triangular asperities with varying slopes. A new simple method of strain calculation is used in this study to generate strain field inside a simulated direct interface shear box. This method accounts for particle rotation and captures strain localization features at high resolution. Results show that strain localization begins with the onset of non-linear stress,strain behaviour. A distinct but discontinuous shear band emerges above the rough surface just before the peak stress state, which becomes more expansive and coherent with post-peak strain softening. It is found that the shear bands developed by surfaces with smaller roughness are much thinner than those developed by surfaces with greater roughness. The maximum thickness of the intense shear zone is observed to be about 8,10 median particle diameters. The shear band orientations, which are mainly dominated by the rough boundary surface, are parallel with the zero extension direction, which are horizontally oriented. Published in 2007 by John Wiley & Sons, Ltd. [source] Contribution to X-ray analysis of carbo-nitrided steel layersJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 5 2001J. M. Sprauel The non-destructive X-ray diffraction method is used to analyse carbo-nitrided steel layers after wear testing. These measurements are carried out on the two major phases of the material, i.e. the martensite and the retained austenite. Such measurements are particularly difficult for three reasons. First, strong gradients exist across the wear track. Second, the diffraction peaks obtained for the martensite are broadened, as a result of the overlap of different reflections of the tetragonal structure. Third, the studied material is multiphase. Its major phases are martensite and austenite, but it also contains carbide and nitride clusters, which lead to incoherent scattering of X-rays. A new quantitative phase analysis method is thus proposed to define the volume fractions of these different constituents of the material. This method accounts for the evolution of the background level during wear. A micro-mechanical model is then developed to process the diffraction peak positions obtained for the martensite and the retained austenite. This model defines the `true' stress and carbon content of both phases. It also allows separation of the reflections of the martensite. The true widths of the diffraction peaks, which characterize the plastic deformation, can thus be quantified. Results for wear-test specimens show a strong plastic deformation of the retained austenite during contact fatigue. This leads to a partial transformation of this phase into martensite. In the martensite, on the contrary, the plastic deformation remains low but the carbon content decreases. This is caused by a stress-induced precipitation of carbides. [source] Game theoretic approach to multiobjective designs: Focus on inherent safetyAICHE JOURNAL, Issue 1 2006Anjana Meel Abstract A method for designing processes that are inherently safer,with the primary focus on disturbances having the potential for unbounded hazardous responses,is introduced. In cases where safety is not threatened (as in isothermal fermentation reactors), but product quality can rapidly degrade, this method provides designs that ensure high product quality (as in pharmaceutical processes). Using game theory, the method accounts for the trade-offs in profitability, controllability, safety and/or product quality, and flexibility. For nonlinear processes that are hard to control; that is, have an unstable and/or nonminimum-phase steady state, over a wide range of operating conditions, extended bifurcation diagrams are introduced. When a steady state is nonminimum phase, the process may exhibit inverse response. The steady states of processes are classified on the basis of instability and nonminimum-phase behavior to segregate the operating regimes into distinct zones. Locally optimal designs, one corresponding to each zone, are obtained first. These are compared with other locally optimal designs at alternate operating conditions, and/or process reconfigurations, to obtain the globally optimal design using game theory. Four indices,profitability, controllability, safety and/or product quality, and flexibility,characterize the optimality of a design. A novel index for safe operation and/or product quality at a steady state is formulated as a function of the eigenvalues of the Jacobian of the process model and the Jacobian of the process zero dynamics, providing a quantitative measure of instability and nonminimum-phase behavior. The application of the proposed method to an isothermal, continuous stirred-tank reactor (CSTR) with van der Vusse reactions, an exothermic CSTR, and an anaerobic fermentor with substrate and product inhibition is presented. © 2005 American Institute of Chemical Engineers AIChE J, 2006 [source] Joint Assessment of Optimal Sales Force Sizes and Sales Call Guidelines: A Management-Oriented ToolCANADIAN JOURNAL OF ADMINISTRATIVE SCIENCES, Issue 3 2005René Y. Darmon Abstract Sales force sizing and sales effort allocation methods vary from simplistic rules of thumb to sophisticated analytical procedures. The former methods are easy to understand and implement, but they are typically inaccurate and probably invalid. The latter procedures may provide more accurate and valid results, but they are more difficult to explain to management and require data collection and analysis that are often quite elaborate. This paper proposes a method of optimal estimation of total sales effort level and time allocation that combines the advantages of both approaches. For each customer segment, this method accounts for the so far neglected, but relevant, optimal call effort allocation between number of calls per account during a planning period and length of sales calls. A case study illustrates this method. Résumé Les méthodes de détermination de la taille et de l'allocation des efforts de vente vont des règles empiriques les plus simples aux procédures analytiques les plus complexes. Les premières sont faciles à comprendre et à appliquer, mais elles sont imprècises et souvent non valides. Les autres méthodes peuvent donner des résultats plus exacts, mais elles sont plus difficiles à expliquer aux managers et nécessitent souvent une collecte et une analyse de données fort laborieuses. Le présent article propose une méthode d'estimation optimale de la taille et de l'allocation des efforts de vente qui combine les avantages des deux approches. Pour chaque segment de la clientèle, la méthode rend compte de l'allocation optimale (souvent négligée, mais pertinente), de l'effort de vente entre le nombre de visites à faire à un client pendant une période de planification et la longueur des visites. Un cas concret illustre la méthode. [source] | ||||||||||