Bayesian adaptive designs for drug combinations in early phase clinical trials

Treating patients with combined agents is a growing trend in cancer clinical trials. Evaluating the synergism of multiple drugs is often the primary motivation for such drug-combination studies. Focusing on the drug combination study in the early phase clinical trials, our research is composed of three parts: (1) We conduct a comprehensive comparison of four dose-finding designs in the two-dimensional toxicity probability space and propose using the Bayesian model averaging method to overcome the arbitrariness of the model specification and enhance the robustness of the design; (2) Motivated by a recent drug-combination trial at MD Anderson Cancer Center with a continuous-dose standard of care agent and a discrete-dose investigational agent, we propose a two-stage Bayesian adaptive dose-finding design based on an extended continual reassessment method; (3) By combining phase I and phase II clinical trials, we propose an extension of a single agent dose-finding design. We model the time-to-event toxicity and efficacy to direct dose finding in two-dimensional drug-combination studies. We conduct extensive simulation studies to examine the operating characteristics of the aforementioned designs and demonstrate the designs' good performances in various practical scenarios.^

A Dynamically Adaptable Bus Architecture for Trading-Off Among Performance, Consumption and Dependability in Cyber-Physical Systems

Cyber-Physical Systems need to handle increasingly complex tasks, which additionally, may have variable operating conditions over time. Therefore, dynamic resource management to adapt the system to different needs is required. In this paper, a new bus-based architecture, called ARTICo3, which by means of Dynamic Partial Reconfiguration, allows the replication of hardware tasks to support module redundancy, multi-thread operation or dual-rail solutions for enhanced side-channel attack protection is presented. A configuration-aware data transaction unit permits data dispatching to more than one module in parallel, or provide coalesced data dispatching among different units to maximize the advantages of burst transactions. The selection of a given configuration is application independent but context-aware, which may be achieved by the combination of a multi-thread model similar to the CUDA kernel model specification, combined with a dynamic thread/task/kernel scheduler. A multi-kernel application for face recognition is used as an application example to show one scenario of the ARTICo3 architecture.

Nonstationary brand variables in category management: A cointegration perspective

Category-management models serve to assist in the development of plans for pricing and promotions of individual brands. Techniques to solve the models can have problems of accuracy and interpretability because they are susceptible to spurious regression problems due to nonstationary time-series data. Improperly stated nonstationary systems can reduce the accuracy of the forecasts and undermine the interpretation of the results. This is problematic because recent studies indicate that sales are often a nonstationary time-series. Newly developed correction techniques can account for nonstationarity by incorporating error-correction terms into the model when using a Bayesian Vector Error-Correction Model. The benefit of using such a technique is that shocks to control variates can be separated into permanent and temporary effects and allow cointegration of series for analysis purposes. Analysis of a brand data set indicates that this is important even at the brand level. Thus, additional information is generated that allows a decision maker to examine controllable variables in terms of whether they influence sales over a short or long duration. Only products that are nonstationary in sales volume can be manipulated for long-term profit gain, and promotions must be cointegrated with brand sales volume. The brand data set is used to explore the capabilities and interpretation of cointegration.

Predicting returns in U.S. financial sector indices

This study focuses on: (i) the responsiveness of the U.S. financial sector stock indices to foreign exchange (FX) and interest rate changes; and, (ii) the extent to which good model specification can enhance the forecasts from the associated models. Three models are considered. Only the error-correction model (ECM) generated efficient and consistent coefficient estimates. Furthermore, a simple zero lag model in differences which is clearly mis-specified, generated forecasts that are better than those of the ECM, even if the ECM depicts relationships that are more consistent with economic theory. In brief, FX and interest rate changes do not impact on the return-generating process of the stock indices in any substantial way. Most of the variation in the sector stock indices is associated with past variation in the indices themselves and variation in the market-wide stock index. These results have important implications for financial and economic policies.

Cost economies, efficiency and productivity growth in the Chinese banking industry:evidence from a quarterly panel dataset

This article examines cost economies, productivity growth and cost efficiency of the Chinese banks using a unique panel dataset that identifies banks' four outputs and four input prices over the period of 1995-2001. By assessing the appropriateness of model specification, and making use of alternative methodologies in evaluating the performance of banks, we find that the joint-stock commercial banks outperform state-owned commercial banks in productivity growth and cost efficiency. Under the variable cost assumption, Chinese banks display economies of scale, with state-owned commercial banks enjoying cost advantages over the joint-stock commercial banks. Consequently, our results highlight the ownership advantage of these two types of banks and generally support the ongoing banking reform and transformation that is currently taking place in China.

Wage bargaining, privatisation, ability to pay, and outside options:evidence from Hungary

This paper examines the determinants of short-term wage dynamics, using a sample of large Hungarian companies for the period of 1996-1999. We test the basic implications of an efficient contract model of bargaining between the incumbent employees and the managers, which we are unable to reject. In particular, there are structural differences between the ownership sectors consistent with our prior knowledge on relative bargaining strength and unionisation measures. Stronger bargaining position of workers leads to higher ability to pay elasticity of wages, and lower outside option elasticity. Our results indicate that while bargaining position of workers in domestic privatised firms may be weaker than in the state sector, the more robust difference relate to state sector workers versus the privatised firms with the majority foreign ownership. We examine several extensions. We augment the bargaining specification by controls related to workers' skills and find that the basic findings are robust to that. We take a closer look at the outside options of the workers. We find some interactive effects, where unemployment modify the impact of availability of rents on wages. We interpret our results as an indication that bargaining power of workers may be affected by changes in their outside options. We also experiment with one concise indicator of reservation wage which is closest to the theoretical model specification and combines sectoral wages, unemployment benefits and regional unemployment levels,. We found that measure performing well. Finally, we found that while responsiveness of wages towards ability to pay is higher in the state sector, variation in wage dynamics is lower. This may indicate some wage smoothing in the state sector, consistent with the preferences of employees.

Mitigating the obsolescence of quality specifications models in service-based systems

Requirements-aware systems address the need to reason about uncertainty at runtime to support adaptation decisions, by representing quality of services (QoS) requirements for service-based systems (SBS) with precise values in run-time queryable model specification. However, current approaches do not support updating of the specification to reflect changes in the service market, like newly available services or improved QoS of existing ones. Thus, even if the specification models reflect design-time acceptable requirements they may become obsolete and miss opportunities for system improvement by self-adaptation. This articles proposes to distinguish "abstract" and "concrete" specification models: the former consists of linguistic variables (e.g. "fast") agreed upon at design time, and the latter consists of precise numeric values (e.g. "2ms") that are dynamically calculated at run-time, thus incorporating up-to-date QoS information. If and when freshly calculated concrete specifications are not satisfied anymore by the current service configuration, an adaptation is triggered. The approach was validated using four simulated SBS that use services from a previously published, real-world dataset; in all cases, the system was able to detect unsatisfied requirements at run-time and trigger suitable adaptations. Ongoing work focuses on policies to determine recalculation of specifications. This approach will allow engineers to build SBS that can be protected against market-caused obsolescence of their requirements specifications. © 2012 IEEE.

Keeping Variables within Bounds: Using Information between Observations

This research develops an econometric framework to analyze time series processes with bounds. The framework is general enough that it can incorporate several different kinds of bounding information that constrain continuous-time stochastic processes between discretely-sampled observations. It applies to situations in which the process is known to remain within an interval between observations, by way of either a known constraint or through the observation of extreme realizations of the process. The main statistical technique employs the theory of maximum likelihood estimation. This approach leads to the development of the asymptotic distribution theory for the estimation of the parameters in bounded diffusion models. The results of this analysis present several implications for empirical research. The advantages are realized in the form of efficiency gains, bias reduction and in the flexibility of model specification. A bias arises in the presence of bounding information that is ignored, while it is mitigated within this framework. An efficiency gain arises, in the sense that the statistical methods make use of conditioning information, as revealed by the bounds. Further, the specification of an econometric model can be uncoupled from the restriction to the bounds, leaving the researcher free to model the process near the bound in a way that avoids bias from misspecification. One byproduct of the improvements in model specification is that the more precise model estimation exposes other sources of misspecification. Some processes reveal themselves to be unlikely candidates for a given diffusion model, once the observations are analyzed in combination with the bounding information. A closer inspection of the theoretical foundation behind diffusion models leads to a more general specification of the model. This approach is used to produce a set of algorithms to make the model computationally feasible and more widely applicable. Finally, the modeling framework is applied to a series of interest rates, which, for several years, have been constrained by the lower bound of zero. The estimates from a series of diffusion models suggest a substantial difference in estimation results between models that ignore bounds and the framework that takes bounding information into consideration.

A model of specification-based testing of interactive systems

In this paper we present a model of specification-based testing of interactive systems. This model provides the basis for a framework to guide such testing. Interactive systems are traditionally decomposed into a functionality component and a user interface component; this distinction is termed dialogue separation and is the underlying basis for conceptual and architectural models of such systems. Correctness involves both proper behaviour of the user interface and proper computation by the underlying functionality. Specification-based testing is one method used to increase confidence in correctness, but it has had limited application to interactive system development to date.

Model driven development implementation of a control systems user interfaces specification tool

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Informática

A proposal for a new specification for a conditionally heteroskedastic variance model: the Quadratic Moving-Average Conditional Heteroskedasticity and an application to the D. Mark-U.S. dollar Exchange Rate

Ever since the appearance of the ARCH model [Engle(1982a)], an impressive array of variance specifications belonging to the same class of models has emerged [i.e. Bollerslev's (1986) GARCH; Nelson's (1990) EGARCH]. This recent domain has achieved very successful developments. Nevertheless, several empirical studies seem to show that the performance of such models is not always appropriate [Boulier(1992)]. In this paper we propose a new specification: the Quadratic Moving Average Conditional heteroskedasticity model. Its statistical properties, such as the kurtosis and the symmetry, as well as two estimators (Method of Moments and Maximum Likelihood) are studied. Two statistical tests are presented, the first one tests for homoskedasticity and the second one, discriminates between ARCH and QMACH specification. A Monte Carlo study is presented in order to illustrate some of the theoretical results. An empirical study is undertaken for the DM-US exchange rate.

The Open Provenance Model Core Specification (v1.1)

The Open Provenance Model is a model of provenance that is designed to meet the following requirements: (1) To allow provenance information to be exchanged between systems, by means of a compatibility layer based on a shared provenance model. (2) To allow developers to build and share tools that operate on such a provenance model. (3) To define provenance in a precise, technology-agnostic manner. (4) To support a digital representation of provenance for any 'thing', whether produced by computer systems or not. (5) To allow multiple levels of description to coexist. (6) To define a core set of rules that identify the valid inferences that can be made on provenance representation. This document contains the specification of the Open Provenance Model (v1.1) resulting from a community-effort to achieve inter-operability in the Provenance Challenge series.

Simulation analysis of the EU ELV/RoHS directives based on an applied general equilibrium model with Melitz-type trade specification

This paper explores the potential usefulness of an AGE model with the Melitz-type trade specification to assess economic effects of technical regulations, taking the case of the EU ELV/RoHS directives as an example. Simulation experiments reveal that: (1) raising the fixed exporting cost to make sales in the EU market brings results that exports of the targeted commodities (motor vehicles and parts for ELV and electronic equipment for RoHS) to the EU from outside regions/countries expand while the domestic trade in the EU shrinks when the importer's preference for variety (PfV) is not strong; (2) if the PfV is not strong, policy changes that may bring reduction in the number of firms enable survived producers with high productivity to expand production to be large-scale mass producers fully enjoying the fruit of economies of scale; and (3) When the strength of the importer's PfV is changed from zero to unity, there is the value that totally changes simulation results and their interpretations.

A graphical specification of model transformations with triple graph grammars

Models and model transformations are the core concepts of OMG's MDA (TM) approach. Within this approach, most models are derived from the MOF and have a graph-based nature. In contrast, most of the current model transformations are specified textually. To enable a graphical specification of model transformation rules, this paper proposes to use triple graph grammars as declarative specification formalism. These triple graph grammars can be specified within the FUJABA tool and we argue that these rules can be more easily specified and they become more understandable and maintainable. To show the practicability of our approach, we present how to generate Tefkat rules from triple graph grammar rules, which helps to integrate triple graph grammars with a state of a art model transformation tool and shows the expressiveness of the concept.