A Bayesian adaptive marker‐stratified design for molecularly targeted agents with customized hierarchical modeling

It is well known that the treatment effect of a molecularly targeted agent (MTA) may vary dramatically, depending on each patient's biomarker profile. Therefore, for a clinical trial evaluating MTA, it is more reasonable to evaluate its treatment effect within different marker subgroups rather than evaluating the average treatment effect for the overall population. The marker‐stratified design (MSD) provides a useful tool to evaluate the subgroup treatment effects of MTAs. Under the Bayesian framework, the beta‐binomial model is conventionally used under the MSD to estimate the response rate and test the hypothesis. However, this conventional model ignores the fact that the biomarker used in the MSD is, in general, predictive only for the MTA. The response rates for the standard treatment can be approximately consistent across different subgroups stratified by the biomarker. In this paper, we proposed a Bayesian hierarchical model incorporating this biomarker information into consideration. The proposed model uses a hierarchical prior to borrow strength across different subgroups of patients receiving the standard treatment and, therefore, improve the efficiency of the design. Prior informativeness is determined by solving a “customized” equation reflecting the physician's professional opinion. We developed a Bayesian adaptive design based on the proposed hierarchical model to guide the treatment allocation and test the subgroup treatment effect as well as the predictive marker effect. Simulation studies and a real trial application demonstrate that the proposed design yields desirable operating characteristics and outperforms the existing designs

Gene-Based Association Tests Using New Polygenic Risk Scores and Incorporating Gene Expression Data

Recently, gene-based association studies have shown that integrating genome-wide association studies (GWAS) with expression quantitative trait locus (eQTL) data can boost statistical power and that the genetic liability of traits can be captured by polygenic risk scores (PRSs). In this paper, we propose a new gene-based statistical method that leverages gene-expression measure-ments and new PRSs to identify genes that are associated with phenotypes of interest. We used a generalized linear model to associate phenotypes with gene expression and PRSs and used a score-test statistic to test the association between phenotypes and genes. Our simulation studies show that the newly developed method has correct type I error rates and can boost statistical power compared with other methods that use either gene expression or PRS in association tests. A real data analysis Figurebased on UK Biobank data for asthma shows that the proposed method is applicable to GWAS

Implementation and benchmarking of the local weight window generation function for OpenMC

OpenMC is a community-driven open-source Monte Carlo neutron and photon transport simulation code. The Weight Window Mesh (WWM) function and an automatic Global Variance Reduction (GVR) method was recently developed and implemented in a developmental branch of OpenMC. This WWM function and GVR method broaden OpenMC\u27s usage in general purposes deep penetration shielding calculations. However, the Local Variance Reduction (LVR) method, which suits the source-detector problem, is still missing in OpenMC. In this work, the Weight Window Generator (WWG) function has been developed and benchmarked for the same branch. This WWG function allows OpenMC to generate the WWM for the source-detector problem on its own. Single-material cases with varying shielding and sources were used to benchmark the WWG function and investigate how to set up the particle histories utilized in WWG-run and WWM-run. Results show that there is a maximum improvement of WWM generated by WWG. Based on the above results, instructions on determining the particle histories utilized in WWG-run and WWM-run for optimal computation efficiency are given and tested with a few multi-material cases. These benchmarks demonstrate the ability of the OpenMC WWG function and the above instructions for the source-detector problem. This developmental branch will be released and merged into the main distribution in the future

An Investigation of the Effect of Chitosan on Isothermal Crystallization, Thermal Decomposition, and Melt Index of Biodegradable Poly(L-lactic acid)

Biodegradable chitosan (CS) was introduced into another biodegradable poly(L-lactic acid) (PLLA) to prepare the PLLA/CS composites, and the effect of CS on thermal behavior and melt index of PLLA was investigated using modern testing technologies including optical depolarizer, thermogravimetric analysis instrument, and melt index instrument. The relevant testing results showed that both crystallization temperature and CS concentration affected the isothermal crystallization behavior of PLLA. Compared to neat PLLA, the t1/2 of PLLA/5% CS decreased from 2991.54 s to the minimum value 208.76 s at 105°C. However, the t1/2 of PLLA/CS composites in high crystallization temperature zone was different from that in low crystallization temperature zone. The increase of CS concentration and heating rate made the thermal decomposition temperature of PLLA/CS composites shift to higher temperature. The melt index results indicated that 3% CS made the fluidity of PLLA become better

Two types of development application

Includes bibliographical references (p. 169-185).Thesis (B.Sc)--University of Hong Kong, 2009.published_or_final_versio