Robust Bayesian nonlinear mixed‐effects modeling of time to positivity in tuberculosis trials

Early phase 2 tuberculosis (TB) trials are conducted to characterize the early bactericidal activity (EBA) of anti‐TB drugs. The EBA of anti‐TB drugs has conventionally been calculated as the rate of decline in colony forming unit (CFU) count during the first 14 days of treatment. The measurement of CFU count, however, is expensive and prone to contamination. Alternatively to CFU count, time to positivity (TTP), which is a potential biomarker for long‐term efficacy of anti‐TB drugs, can be used to characterize EBA. The current Bayesian nonlinear mixed‐effects (NLME) regression model for TTP data, however, lacks robustness to gross outliers that often are present in the data. The conventional way of handling such outliers involves their identification by visual inspection and subsequent exclusion from the analysis. However, this process can be questioned because of its subjective nature. For this reason, we fitted robust versions of the Bayesian nonlinear mixed‐effects regression model to a wide range of TTP datasets. The performance of the explored models was assessed through model comparison statistics and a simulation study. We conclude that fitting a robust model to TTP data obviates the need for explicit identification and subsequent “deletion” of outliers but ensures that gross outliers exert no undue influence on model fits. We recommend that the current practice of fitting conventional normal theory models be abandoned in favor of fitting robust models to TTP data.     

Self-exciting threshold models for time series of counts with a finite range

In this article, an integer-valued self-exciting threshold model with a finite range based on the binomial INARCH(1) model is proposed. Important stochastic properties are derived, and approaches for parameter estimation are discussed. A real-data example about the regional spread of public drunkenness in Pittsburgh demonstrates the applicability of the new model in comparison to existing models. Feasible modifications of the model are presented, which are designed to handle special features such as zero-inflation.     

Completing the Circuit: Routine,Reflection, and Ethical Consumption

Efforts to explain why some people incorporate ethical concerns into everyday shopping for food and household goods, while many do not, have so far left significant variation in “ethical consumption” unexplained. Seeking to move beyond explanations that rely mainly on differences in consumers' social class, gender, and political engagement, I draw on concepts associated with “practice theory” to argue that ethical consumption is closely tied to people's willingness and ability to spend time, while shopping, on distinct activities associated with breaking old routines and establishing new ones. The central insight of practice theory is that most consumption is the product of unconscious routine. And it is precisely because consciously departing from routine is, according to my study, a fundamentally time‐consuming process, that lack of time emerges as a crucial obstacle to translating abstract ethical concerns into concrete action as a consumer.     

Dynamic Forecasting Conditional Probability of Bombing Attacks Based on Time‐Series and Intervention Analysis

In recent years, various types of terrorist attacks occurred, causing worldwide catastrophes. According to the Global Terrorism Database (GTD), among all attack tactics, bombing attacks happened most frequently, followed by armed assaults. In this article, a model for analyzing and forecasting the conditional probability of bombing attacks (CPBAs) based on time‐series methods is developed. In addition, intervention analysis is used to analyze the sudden increase in the time‐series process. The results show that the CPBA increased dramatically at the end of 2011. During that time, the CPBA increased by 16.0% in a two‐month period to reach the peak value, but still stays 9.0% greater than the predicted level after the temporary effect gradually decays. By contrast, no significant fluctuation can be found in the conditional probability process of armed assault. It can be inferred that some social unrest, such as America's troop withdrawal from Afghanistan and Iraq, could have led to the increase of the CPBA in Afghanistan, Iraq, and Pakistan. The integrated time‐series and intervention model is used to forecast the monthly CPBA in 2014 and through 2064. The average relative error compared with the real data in 2014 is 3.5%. The model is also applied to the total number of attacks recorded by the GTD between 2004 and 2014.     

Optimal quantization applied to sliced inverse regression

In this paper we consider a semiparametric regression model involving a d-dimensional quantitative explanatory variable X and including a dimension reduction of X via an index β′X. In this model, the main goal is to estimate the Euclidean parameter β and to predict the real response variable Y conditionally to X. Our approach is based on sliced inverse regression (SIR) method and optimal quantization in L^p-norm. We obtain the convergence of the proposed estimators of β and of the conditional distribution. Simulation studies show the good numerical behavior of the proposed estimators for finite sample size.     

真实性学习理念下的教学方法及实践应用

本文分享了作者在美国研修期间亲身经历的体现真实性学习理念的三种教学方法与活动:同伴教学、跨时空对话、视频制作。通过真实再现纽约州立大学奥斯威戈分校研修课堂精彩片段,分析教学方法与原理,并探讨在国内高校尤其是教师教育课堂的应用途径。     

Bayesian optimal sequential design for nonparametric regression via inhomogeneous evolutionary MCMC

We develop a novel computational methodology for Bayesian optimal sequential design for nonparametric regression. This computational methodology, that we call inhomogeneous evolutionary Markov chain Monte Carlo, combines ideas of simulated annealing, genetic or evolutionary algorithms, and Markov chain Monte Carlo. Our framework allows optimality criteria with general utility functions and general classes of priors for the underlying regression function. We illustrate the usefulness of our novel methodology with applications to experimental design for nonparametric function estimation using Gaussian process priors and free-knot cubic splines priors.     

On Modeling Wood Formation Using Parametric and Semiparametric Regressions for Count Data

Understanding how wood develops has become an important problematic of plant sciences. However, studying wood formation requires the acquisition of count data difficult to interpret. Here, the annual wood formation dynamics of a conifer tree species were modeled using generalized linear and additive models (GLM and GAM); GAM for location, scale, and shape (GAMLSS); a discrete semiparametric kernel regression for count data. The performance of models is evaluated using bootstrap methods. GLM was useful to describe the wood formation general pattern but had a lack of fitting, while GAM, GAMLSS, and kernel regression had a higher sensibility to short-term variations.     

Quantile Regression for Location‐Scale Time Series Models with Conditional Heteroscedasticity

This paper considers quantile regression for a wide class of time series models including autoregressive and moving average (ARMA) models with asymmetric generalized autoregressive conditional heteroscedasticity errors. The classical mean‐variance models are reinterpreted as conditional location‐scale models so that the quantile regression method can be naturally geared into the considered models. The consistency and asymptotic normality of the quantile regression estimator is established in location‐scale time series models under mild conditions. In the application of this result to ARMA‐generalized autoregressive conditional heteroscedasticity models, more primitive conditions are deduced to obtain the asymptotic properties. For illustration, a simulation study and a real data analysis are provided.     

Bayesian adaptive dose‐escalation designs for simultaneously estimating the optimal and maximum safe dose based on safety and efficacy

The main purpose of dose‐escalation trials is to identify the dose(s) that is/are safe and efficacious for further investigations in later studies. In this paper, we introduce dose‐escalation designs that incorporate both the dose‐limiting events and dose‐limiting toxicities (DLTs) and indicative responses of efficacy into the procedure. A flexible nonparametric model is used for modelling the continuous efficacy responses while a logistic model is used for the binary DLTs. Escalation decisions are based on the combination of the probabilities of DLTs and expected efficacy through a gain function. On the basis of this setup, we then introduce 2 types of Bayesian adaptive dose‐escalation strategies. The first type of procedures, called “single objective,” aims to identify and recommend a single dose, either the maximum tolerated dose, the highest dose that is considered as safe, or the optimal dose, a safe dose that gives optimum benefit risk. The second type, called “dual objective,” aims to jointly estimate both the maximum tolerated dose and the optimal dose accurately. The recommended doses obtained under these dose‐escalation procedures provide information about the safety and efficacy profile of the novel drug to facilitate later studies. We evaluate different strategies via simulations based on an example constructed from a real trial on patients with type 2 diabetes, and the use of stopping rules is assessed. We find that the nonparametric model estimates the efficacy responses well for different underlying true shapes. The dual‐objective designs give better results in terms of identifying the 2 real target doses compared to the single‐objective designs.