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Controlling Cumulative Adverse Risk in Learning Optimal Dynamic Treatment Regimens

学习最优动态治疗方案时控制累积不良风险

Dynamic treatment regimen (DTR) is one of the most important tools to tailor treatment in personalized medicine. For many diseases such as cancer and type 2 diabetes mellitus (T2D), more aggressive treatments can lead to a higher efficacy but may also increase risk. However, few methods for estimating DTRs can take into account both cumulative benefit and risk. In this work, we propose a general statistical learning framework to learn optimal DTRs that maximize the reward…

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A Semiparametric Inverse Reinforcement Learning Approach to Characterize Decision Making for Mental Disorders

刻画精神障碍决策行为的半参数逆强化学习方法

Major depressive disorder (MDD) is one of the leading causes of disability-adjusted life years. Emerging evidence indicates the presence of reward processing abnormalities in MDD. An important scientific question is whether the abnormalities are due to reduced sensitivity to received rewards or reduced learning ability. Motivated by the probabilistic reward task (PRT) experiment in the EMBARC study, we propose a semiparametric inverse reinforcement learning (RL) approach to…

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Mixed-Response State-Space Model for Analyzing Multi-Dimensional Digital Phenotypes

分析多维数字表型的混合响应状态空间模型

Digital technologies (e.g., mobile phones) can be used to obtain objective, frequent, and real-world digital phenotypes from individuals. However, modeling these data poses substantial challenges since observational data are subject to confounding and various sources of variabilities. For example, signals on patients' underlying health status and treatment effects are mixed with variation due to the living environment and measurement noises. The digital phenotype data thus…

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Modelling temporal biomarkers with semiparametric nonlinear dynamical systems

用半参数非线性动力系统建模时变生物标志物

Summary Dynamical systems based on differential equations are useful for modelling the temporal evolution of biomarkers. Such systems can characterize the temporal patterns of biomarkers and inform the detection of interactions between biomarkers. Existing statistical methods for dynamical systems deal mostly with single time-course data based on a linear model or generalized additive model. Hence, they cannot adequately capture the complex interactions between biomarkers;…

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Learning Individualized Treatment Rules for Multiple-Domain Latent Outcomes

针对多领域潜在结局的个体化治疗规则学习

For many mental disorders, latent mental status from multiple-domain psychological or clinical symptoms may perform as a better characterization of the underlying disorder status than a simple summary score of the symptoms, and they may also serve as more reliable and representative features to differentiate treatment responses. Therefore, in order to address the complexity and heterogeneity of treatment responses for mental disorders, we provide a new paradigm for learning…

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Matched Learning for Optimizing Individualized Treatment Strategies Using Electronic Health Records

利用电子健康记录优化个体化治疗策略的匹配学习

Current guidelines for treatment decision making largely rely on data from randomized controlled trials (RCTs) studying average treatment effects. They may be inadequate to make individualized treatment decisions in real-world settings. Large-scale electronic health records (EHR) provide opportunities to fulfill the goals of personalized medicine and learn individualized treatment rules (ITRs) depending on patient-specific characteristics from real-world patient data. In…

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Fused kernel-spline smoothing for repeatedly measured outcomes in a generalized partially linear model with functional single index

重复测量结果的函数单指标广义部分线性模型:核与样条融合平滑

We propose a generalized partially linear functional single index risk score model for repeatedly measured outcomes where the index itself is a function of time. We fuse the nonparametric kernel method and regression spline method, and modify the generalized estimating equation to facilitate estimation and inference. We use local smoothing kernel to estimate the unspecified coefficient functions of time, and use B-splines to estimate the unspecified function of the single…

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Efficient estimation of nonparametric genetic risk function with censored data

删失数据下非参数遗传风险函数的有效估计

With an increasing number of causal genes discovered for complex human disorders, it is crucial to assess the genetic risk of disease onset for individuals who are carriers of these causal mutations and compare the distribution of age-at-onset with that in non-carriers. In many genetic epidemiological studies aiming at estimating causal gene effect on disease, the age-at-onset of disease is subject to censoring. In addition, some individuals' mutation carrier or non-carrier…

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Targeted Local Support Vector Machine for Age-Dependent Classification

用于年龄依赖分类的针对性局部支持向量机

We develop methods to accurately predict whether pre-symptomatic individuals are at risk of a disease based on their various marker profiles, which offers an opportunity for early intervention well before definitive clinical diagnosis. For many diseases, existing clinical literature may suggest the risk of disease varies with some markers of biological and etiological importance, for example age. To identify effective prediction rules using nonparametric decision functions,…

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A Marginal Approach to Reduced-Rank Penalized Spline Smoothing With Application to Multilevel Functional Data

降秩惩罚样条平滑的边际方法及其多层函数数据应用

Multilevel functional data is collected in many biomedical studies. For example, in a study of the effect of Nimodipine on patients with subarachnoid hemorrhage (SAH), patients underwent multiple 4-hour treatment cycles. Within each treatment cycle, subjects' vital signs were reported every 10 minutes. This data has a natural multilevel structure with treatment cycles nested within subjects and measurements nested within cycles. Most literature on nonparametric analysis of…

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Auxiliary Marker-Assisted Classification in the Absence of Class Identifiers

缺少类别标识时的辅助标记分类

Constructing classification rules for accurate diagnosis of a disorder is an important goal in medical practice. In many clinical applications, there is no clinically significant anatomical or physiological deviation exists to identify the gold standard disease status to inform development of classification algorithms. Despite absence of perfect disease class identifiers, there are usually one or more disease-informative auxiliary markers along with feature variables…

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Nonparametric Estimation for Censored Mixture Data With Application to the Cooperative Huntington’s Observational Research Trial

删失混合数据的非参数估计及亨廷顿病观察研究应用

This work presents methods for estimating genotype-specific distributions from genetic epidemiology studies where the event times are subject to right censoring, the genotypes are not directly observed, and the data arise from a mixture of scientifically meaningful subpopulations. Examples of such studies include kin-cohort studies and quantitative trait locus (QTL) studies. Current methods for analyzing censored mixture data include two types of nonparametric maximum…

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