867 resultados para Bayesian hierarchical model
Resumo:
In geographical epidemiology, maps of disease rates and disease risk provide a spatial perspective for researching disease etiology. For rare diseases or when the population base is small, the rate and risk estimates may be unstable. Empirical Bayesian (EB) methods have been used to spatially smooth the estimates by permitting an area estimate to "borrow strength" from its neighbors. Such EB methods include the use of a Gamma model, of a James-Stein estimator, and of a conditional autoregressive (CAR) process. A fully Bayesian analysis of the CAR process is proposed. One advantage of this fully Bayesian analysis is that it can be implemented simply by using repeated sampling from the posterior densities. Use of a Markov chain Monte Carlo technique such as Gibbs sampler was not necessary. Direct resampling from the posterior densities provides exact small sample inferences instead of the approximate asymptotic analyses of maximum likelihood methods (Clayton & Kaldor, 1987). Further, the proposed CAR model provides for covariates to be included in the model. A simulation demonstrates the effect of sample size on the fully Bayesian analysis of the CAR process. The methods are applied to lip cancer data from Scotland, and the results are compared. ^
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In regression analysis, covariate measurement error occurs in many applications. The error-prone covariates are often referred to as latent variables. In this proposed study, we extended the study of Chan et al. (2008) on recovering latent slope in a simple regression model to that in a multiple regression model. We presented an approach that applied the Monte Carlo method in the Bayesian framework to the parametric regression model with the measurement error in an explanatory variable. The proposed estimator applied the conditional expectation of latent slope given the observed outcome and surrogate variables in the multiple regression models. A simulation study was presented showing that the method produces estimator that is efficient in the multiple regression model, especially when the measurement error variance of surrogate variable is large.^
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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.^
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My dissertation focuses mainly on Bayesian adaptive designs for phase I and phase II clinical trials. It includes three specific topics: (1) proposing a novel two-dimensional dose-finding algorithm for biological agents, (2) developing Bayesian adaptive screening designs to provide more efficient and ethical clinical trials, and (3) incorporating missing late-onset responses to make an early stopping decision. Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which toxicity and efficacy monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a phase I/II trial design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multi-arm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while at the same time allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while at the same time providing higher power to identify the best treatment at the end of the trial. Phase II trial studies usually are single-arm trials which are conducted to test the efficacy of experimental agents and decide whether agents are promising to be sent to phase III trials. Interim monitoring is employed to stop the trial early for futility to avoid assigning unacceptable number of patients to inferior treatments. We propose a Bayesian single-arm phase II design with continuous monitoring for estimating the response rate of the experimental drug. To address the issue of late-onset responses, we use a piece-wise exponential model to estimate the hazard function of time to response data and handle the missing responses using the multiple imputation approach. We evaluate the operating characteristics of the proposed method through extensive simulation studies. We show that the proposed method reduces the total length of the trial duration and yields desirable operating characteristics for different physician-specified lower bounds of response rate with different true response rates.
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There are two practical challenges in the phase I clinical trial conduct: lack of transparency to physicians, and the late onset toxicity. In my dissertation, Bayesian approaches are used to address these two problems in clinical trial designs. The proposed simple optimal designs cast the dose finding problem as a decision making process for dose escalation and deescalation. The proposed designs minimize the incorrect decision error rate to find the maximum tolerated dose (MTD). For the late onset toxicity problem, a Bayesian adaptive dose-finding design for drug combination is proposed. The dose-toxicity relationship is modeled using the Finney model. The unobserved delayed toxicity outcomes are treated as missing data and Bayesian data augment is employed to handle the resulting missing data. Extensive simulation studies have been conducted to examine the operating characteristics of the proposed designs and demonstrated the designs' good performances in various practical scenarios.^
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Early phase clinical trial designs have long been the focus of interest for clinicians and statisticians working in oncology field. There are several standard phse I and phase II designs that have been widely-implemented in medical practice. For phase I design, the most commonly used methods are 3+3 and CRM. A newly-developed Bayesian model-based mTPI design has now been used by an increasing number of hospitals and pharmaceutical companies. The advantages and disadvantages of these three top phase I designs have been discussed in my work here and their performances were compared using simulated data. It was shown that mTPI design exhibited superior performance in most scenarios in comparison with 3+3 and CRM designs. ^ The next major part of my work is proposing an innovative seamless phase I/II design that allows clinicians to conduct phase I and phase II clinical trials simultaneously. Bayesian framework was implemented throughout the whole design. The phase I portion of the design adopts mTPI method, with the addition of futility rule which monitors the efficacy performance of the tested drugs. Dose graduation rules were proposed in this design to allow doses move forward from phase I portion of the study to phase II portion without interrupting the ongoing phase I dose-finding schema. Once a dose graduated to phase II, adaptive randomization was used to randomly allocated patients into different treatment arms, with the intention of more patients being assigned to receive more promising dose(s). Again simulations were performed to compare the performance of this innovative phase I/II design with a recently published phase I/II design, together with the conventional phase I and phase II designs. The simulation results indicated that the seamless phase I/II design outperform the other two competing methods in most scenarios, with superior trial power and the fact that it requires smaller sample size. It also significantly reduces the overall study time. ^ Similar to other early phase clinical trial designs, the proposed seamless phase I/II design requires that the efficacy and safety outcomes being able to be observed in a short time frame. This limitation can be overcome by using validated surrogate marker for the efficacy and safety endpoints.^
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Existing models estimating oil spill costs at sea are based on data from the past, and they usually lack a systematic approach. This make them passive, and limits their ability to forecast the effect of the changes in the oil combating fleet or location of a spill on the oil spill costs. In this paper we make an attempt towards the development of a probabilistic and systematic model estimating the costs of clean-up operations for the Gulf of Finland. For this purpose we utilize expert knowledge along with the available data and information from literature. Then, the obtained information is combined into a framework with the use of a Bayesian Belief Networks. Due to lack of data, we validate the model by comparing its results with existing models, with which we found good agreement. We anticipate that the presented model can contribute to the cost-effective oil-combating fleet optimization for the Gulf of Finland. It can also facilitate the accident consequences estimation in the framework of formal safety assessment (FSA).
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This paper estimates the elasticity of labor productivity with respect to employment density, a widely used measure of the agglomeration effect, in the Yangtze River Delta, China. A spatial Durbin model is presented that makes explicit the influences of spatial dependence and endogeneity bias in a very simple way. Results of Bayesian estimation using the data of the year 2009 indicate that the productivity is influenced by factors correlated with density rather than density itself and that spatial spillovers of these factors of agglomeration play a significant role. They are consistent with the findings of Ke (2010) and Artis, et al. (2011) that suggest the importance of taking into account spatial dependence and hitherto omitted variables.
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Learning the structure of a graphical model from data is a common task in a wide range of practical applications. In this paper, we focus on Gaussian Bayesian networks, i.e., on continuous data and directed acyclic graphs with a joint probability density of all variables given by a Gaussian. We propose to work in an equivalence class search space, specifically using the k-greedy equivalence search algorithm. This, combined with regularization techniques to guide the structure search, can learn sparse networks close to the one that generated the data. We provide results on some synthetic networks and on modeling the gene network of the two biological pathways regulating the biosynthesis of isoprenoids for the Arabidopsis thaliana plant
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Belief propagation (BP) is a technique for distributed inference in wireless networks and is often used even when the underlying graphical model contains cycles. In this paper, we propose a uniformly reweighted BP scheme that reduces the impact of cycles by weighting messages by a constant ?edge appearance probability? rho ? 1. We apply this algorithm to distributed binary hypothesis testing problems (e.g., distributed detection) in wireless networks with Markov random field models. We demonstrate that in the considered setting the proposed method outperforms standard BP, while maintaining similar complexity. We then show that the optimal ? can be approximated as a simple function of the average node degree, and can hence be computed in a distributed fashion through a consensus algorithm.
Resumo:
The authors are from UPM and are relatively grouped, and all have intervened in different academic or real cases on the subject, at different times as being of different age. With precedent from E. Torroja and A. Páez in Madrid Spain Safety Probabilistic models for concrete about 1957, now in ICOSSAR conferences, author J.M. Antón involved since autumn 1967 for euro-steel construction in CECM produced a math model for independent load superposition reductions, and using it a load coefficient pattern for codes in Rome Feb. 1969, practically adopted for European constructions, giving in JCSS Lisbon Feb. 1974 suggestion of union for concrete-steel-al.. That model uses model for loads like Gumbel type I, for 50 years for one type of load, reduced to 1 year to be added to other independent loads, the sum set in Gumbel theories to 50 years return period, there are parallel models. A complete reliability system was produced, including non linear effects as from buckling, phenomena considered somehow in actual Construction Eurocodes produced from Model Codes. The system was considered by author in CEB in presence of Hydraulic effects from rivers, floods, sea, in reference with actual practice. When redacting a Road Drainage Norm in MOPU Spain an optimization model was realized by authors giving a way to determine the figure of Return Period, 10 to 50 years, for the cases of hydraulic flows to be considered in road drainage. Satisfactory examples were a stream in SE of Spain with Gumbel Type I model and a paper of Ven Te Chow with Mississippi in Keokuk using Gumbel type II, and the model can be modernized with more varied extreme laws. In fact in the MOPU drainage norm the redacting commission acted also as expert to set a table of return periods for elements of road drainage, in fact as a multi-criteria complex decision system. These precedent ideas were used e.g. in wide Codes, indicated in symposia or meetings, but not published in journals in English, and a condensate of contributions of authors is presented. The authors are somehow involved in optimization for hydraulic and agro planning, and give modest hints of intended applications in presence of agro and environment planning as a selection of the criteria and utility functions involved in bayesian, multi-criteria or mixed decision systems. Modest consideration is made of changing in climate, and on the production and commercial systems, and on others as social and financial.
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OntoTag - A Linguistic and Ontological Annotation Model Suitable for the Semantic Web
1. INTRODUCTION. LINGUISTIC TOOLS AND ANNOTATIONS: THEIR LIGHTS AND SHADOWS
Computational Linguistics is already a consolidated research area. It builds upon the results of other two major ones, namely Linguistics and Computer Science and Engineering, and it aims at developing computational models of human language (or natural language, as it is termed in this area). Possibly, its most well-known applications are the different tools developed so far for processing human language, such as machine translation systems and speech recognizers or dictation programs.
These tools for processing human language are commonly referred to as linguistic tools. Apart from the examples mentioned above, there are also other types of linguistic tools that perhaps are not so well-known, but on which most of the other applications of Computational Linguistics are built. These other types of linguistic tools comprise POS taggers, natural language parsers and semantic taggers, amongst others. All of them can be termed linguistic annotation tools.
Linguistic annotation tools are important assets. In fact, POS and semantic taggers (and, to a lesser extent, also natural language parsers) have become critical resources for the computer applications that process natural language. Hence, any computer application that has to analyse a text automatically and ‘intelligently’ will include at least a module for POS tagging. The more an application needs to ‘understand’ the meaning of the text it processes, the more linguistic tools and/or modules it will incorporate and integrate.
However, linguistic annotation tools have still some limitations, which can be summarised as follows:
1. Normally, they perform annotations only at a certain linguistic level (that is, Morphology, Syntax, Semantics, etc.).
2. They usually introduce a certain rate of errors and ambiguities when tagging. This error rate ranges from 10 percent up to 50 percent of the units annotated for unrestricted, general texts.
3. Their annotations are most frequently formulated in terms of an annotation schema designed and implemented ad hoc.
A priori, it seems that the interoperation and the integration of several linguistic tools into an appropriate software architecture could most likely solve the limitations stated in (1). Besides, integrating several linguistic annotation tools and making them interoperate could also minimise the limitation stated in (2). Nevertheless, in the latter case, all these tools should produce annotations for a common level, which would have to be combined in order to correct their corresponding errors and inaccuracies. Yet, the limitation stated in (3) prevents both types of integration and interoperation from being easily achieved.
In addition, most high-level annotation tools rely on other lower-level annotation tools and their outputs to generate their own ones. For example, sense-tagging tools (operating at the semantic level) often use POS taggers (operating at a lower level, i.e., the morphosyntactic) to identify the grammatical category of the word or lexical unit they are annotating. Accordingly, if a faulty or inaccurate low-level annotation tool is to be used by other higher-level one in its process, the errors and inaccuracies of the former should be minimised in advance. Otherwise, these errors and inaccuracies would be transferred to (and even magnified in) the annotations of the high-level annotation tool.
Therefore, it would be quite useful to find a way to
(i) correct or, at least, reduce the errors and the inaccuracies of lower-level linguistic tools;
(ii) unify the annotation schemas of different linguistic annotation tools or, more generally speaking, make these tools (as well as their annotations) interoperate.
Clearly, solving (i) and (ii) should ease the automatic annotation of web pages by means of linguistic tools, and their transformation into Semantic Web pages (Berners-Lee, Hendler and Lassila, 2001). Yet, as stated above, (ii) is a type of interoperability problem. There again, ontologies (Gruber, 1993; Borst, 1997) have been successfully applied thus far to solve several interoperability problems. Hence, ontologies should help solve also the problems and limitations of linguistic annotation tools aforementioned.
Thus, to summarise, the main aim of the present work was to combine somehow these separated approaches, mechanisms and tools for annotation from Linguistics and Ontological Engineering (and the Semantic Web) in a sort of hybrid (linguistic and ontological) annotation model, suitable for both areas. This hybrid (semantic) annotation model should (a) benefit from the advances, models, techniques, mechanisms and tools of these two areas; (b) minimise (and even solve, when possible) some of the problems found in each of them; and (c) be suitable for the Semantic Web. The concrete goals that helped attain this aim are presented in the following section.
2. GOALS OF THE PRESENT WORK
As mentioned above, the main goal of this work was to specify a hybrid (that is, linguistically-motivated and ontology-based) model of annotation suitable for the Semantic Web (i.e. it had to produce a semantic annotation of web page contents). This entailed that the tags included in the annotations of the model had to (1) represent linguistic concepts (or linguistic categories, as they are termed in ISO/DCR (2008)), in order for this model to be linguistically-motivated; (2) be ontological terms (i.e., use an ontological vocabulary), in order for the model to be ontology-based; and (3) be structured (linked) as a collection of ontology-based