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Clinical drug trials are costly and time-consuming. Bayesian methods alleviate the inefficiencies in the testing process while providing user-friendly probabilistic inference and predictions from the sampled posterior distributions, saving resources, time, and money. We propose a dynamic linear model to estimate the mean response at each dose level, borrowing strength across dose levels. Our model permits nonmonotonicity of the dose-response relationship, facilitating precise modeling of a wider array of dose-response relationships (including the possibility of toxicity). In addition, we incorporate an adaptive approach to the design of the clinical trial, which allows for interim decisions and assignment to doses based on dose-response uncertainty and dose efficacy. The interim decisions we consider are stopping early for success and stopping early for futility, allowing for patient and time savings in the drug development process. These methods complement current clinical trial design research.

No description available.

No description available.

No description available.

No description available.

To propose a methodology for the uncertainty estimation in water quality modeling as related to TMDL development, four Monte Carlo (MC) based techniques—single-phase MC, two-phase MC, Generalized Likelihood Uncertainty Estimation (GLUE), and Markov Chain Monte Carlo (MCMC) —were applied to a Hydrological Simulation Program–FORTRAN (HSPF) model developed for the Mossy Creek bacterial TMDL in Virginia. Predictive uncertainty in percent violations of instantaneous fecal coliform concentration criteria for the prediction period under two TMDL pollutant allocation scenarios was estimated. The average percent violations of the applicable water quality criteria were less than 2% for all the evaluated techniques. Single-phase MC reported greater uncertainty in percent violations than the two-phase MC for one of the allocation scenarios. With the two-phase MC, it is computationally expensive to sample the complete parameter space, and with increased simulations, the estimates of single and two-phase MC may be similar. Two-phase MC reported significantly greater effect of knowledge uncertainty than stochastic variability on uncertainty estimates. Single and two-phase MC require manual model calibration as opposed to GLUE and MCMC that provide a framework to obtain posterior or calibrated parameter distributions based on a comparison between observed and simulated data and prior parameter distributions. Uncertainty estimates using GLUE and MCMC were similar when GLUE was applied following the log-transformation of observed and simulated FC concentrations. GLUE provides flexibility in selecting any model goodness of fit criteria for calculating the likelihood function and does not make any assumption about the distribution of residuals, but this flexibility is also a controversial aspect of GLUE. MCMC has a robust formulation that utilizes a statistical likelihood function, and requires normal distribution of model errors. However, MCMC is computationally expensive to apply in a watershed modeling application compared to GLUE. Overall, GLUE is the preferred approach among all the evaluated uncertainty estimation techniques, for the application of watershed modeling as related to bacterial TMDL development. However, the application of GLUE in watershed-scale water quality modeling requires further research to evaluate the effect of different likelihood functions, and different parameter set acceptance/rejection criteria. / Ph. D.

This paper directs interest on country-specific labour market discrimination Roma may suffer in South East Europe. The study lies in the tradition of statistical Blinder-Oaxaca decomposition analysis. We use microdata from UNDP's 2004 survey of Roma minorities, and apply a Bayesian approach, proposed by Keith and LeSage (2004), for the decomposition analysis of wage differentials. This approach is based on a robust Bayesian heteroscedastic linear regression model in conjunction with Markov Chain Monte Carlo (MCMC) estimation. The results obtained indicate the presence of labour market discrimination in Albania and Kosovo, but point to its absence in Bulgaria, Croatia, and Serbia. (authors' abstract)

Pour réduire le temps d'acquisition ou bien améliorer la résolution spatio-temporelle dans certaines application en IRM, de puissantes techniques parallèles utilisant plusieurs antennes réceptrices sont apparues depuis les années 90. Dans ce contexte, les images d'IRM doivent être reconstruites à partir des données sous-échantillonnées acquises dans le "k-space". Plusieurs approches de reconstruction ont donc été proposées dont la méthode SENSitivity Encoding (SENSE). Cependant, les images reconstruites sont souvent entâchées par des artéfacts dus au bruit affectant les données observées, ou bien à des erreurs d'estimation des profils de sensibilité des antennes. Dans ce travail, nous présentons de nouvelles méthodes de reconstruction basées sur l'algorithme SENSE, qui introduisent une régularisation dans le domaine transformé en ondelettes afin de promouvoir la parcimonie de la solution. Sous des conditions expérimentales dégradées, ces méthodes donnent une bonne qualité de reconstruction contrairement à la méthode SENSE et aux autres techniques de régularisation classique (e.g. Tikhonov). Les méthodes proposées reposent sur des algorithmes parallèles d'optimisation permettant de traiter des critères convexes, mais non nécessairement différentiables contenant des a priori parcimonieux. Contrairement à la plupart des méthodes de reconstruction qui opèrent coupe par coupe, l'une des méthodes proposées permet une reconstruction 4D (3D + temps) en exploitant les corrélations spatiales et temporelles. Le problème d'estimation d'hyperparamètres sous-jacent au processus de régularisation a aussi été traité dans un cadre bayésien en utilisant des techniques MCMC. Une validation sur des données réelles anatomiques et fonctionnelles montre que les méthodes proposées réduisent les artéfacts de reconstruction et améliorent la sensibilité/spécificité statistique en IRM fonctionnelle.