Case-cohort analysis of clusters of recurrent events.

The case-cohort sampling, first proposed in Prentice (Biometrika 73:1-11, 1986), is one of the most effective cohort designs for analysis of event occurrence, with the regression model being the typical Cox proportional hazards model. This paper extends to consider the case-cohort design for recurrent events with certain specific clustering feature, which is captured by a properly modified Cox-type self-exciting intensity model. We discuss the advantage of using this model and validate the pseudo-likelihood method. Simulation studies are presented in support of the theory. Application is illustrated with analysis of a bladder cancer data.

NFTracer: Tracing NFT Impact Dynamics in Transaction-flow Substitutive Systems with Visual Analytics.

Impact dynamics are crucial for estimating the growth patterns of NFT projects by tracking the diffusion and decay of their relative appeal among stakeholders. Machine learning methods for impact dynamics analysis are incomprehensible and rigid in terms of their interpretability and transparency, whilst stakeholders require interactive tools for informed decision-making. Nevertheless, developing such a tool is challenging due to the substantial, heterogeneous NFT transaction data and the requirements for flexible, customized interactions. To this end, we integrate intuitive visualizations to unveil the impact dynamics of NFT projects. We first conduct a formative study and summarize analysis criteria, including substitution mechanisms, impact attributes, and design requirements from stakeholders. Next, we propose the Minimal Substitution Model to simulate substitutive systems of NFT projects that can be feasibly represented as node-link graphs. Particularly, we utilize attribute-aware techniques to embed the project status and stakeholder behaviors in the layout design. Accordingly, we develop a multi-view visual analytics system, namely NFTracer, allowing interactive analysis of impact dynamics in NFT transactions. We demonstrate the informativeness, effectiveness, and usability of NFTracer by performing two case studies with domain experts and one user study with stakeholders. The studies suggest that NFT projects featuring a higher degree of similarity are more likely to substitute each other. The impact of NFT projects within substitutive systems is contingent upon the degree of stakeholders' influx and projects' freshness.

ANALYSIS OF MULTIVARIATE FAILURE TIME DATA USING MARGINAL PROPORTIONAL HAZARDS MODEL.

The marginal proportional hazards model is an important tool in the analysis of multivariate failure time data in the presence of censoring. We propose a method of estimation via the linear combinations of martingale residuals. The estimation and inference procedures are easy to implement numerically. The estimation is generally more accurate than the existing pseudo-likelihood approach: the size of efficiency gain can be considerable in some cases, and the maximum relative efficiency in theory is infinite. Consistency and asymptotic normality are established. Empirical evidence in support of the theoretical claims is shown in simulation studies.

Adaptive Learning Recommendation Strategy Based on Deep Q-learning.

Personalized recommendation system has been widely adopted in E-learning field that is adaptive to each learner's own learning pace. With full utilization of learning behavior data, psychometric assessment models keep track of the learner's proficiency on knowledge points, and then, the well-designed recommendation strategy selects a sequence of actions to meet the objective of maximizing learner's learning efficiency. This article proposes a novel adaptive recommendation strategy under the framework of reinforcement learning. The proposed strategy is realized by the deep Q-learning algorithms, which are the techniques that contributed to the success of AlphaGo Zero to achieve the super-human level in playing the game of go. The proposed algorithm incorporates an early stopping to account for the possibility that learners may choose to stop learning. It can properly deal with missing data and can handle more individual-specific features for better recommendations. The recommendation strategy guides individual learners with efficient learning paths that vary from person to person. The authors showcase concrete examples with numeric analysis of substantive learning scenarios to further demonstrate the power of the proposed method.

Curiosity-driven recommendation strategy for adaptive learning via deep reinforcement learning.

The design of recommendation strategies in the adaptive learning systems focuses on utilizing currently available information to provide learners with individual-specific learning instructions. As a critical motivate for human behaviours, curiosity is essentially the drive to explore knowledge and seek information. In a psychologically inspired view, we propose a curiosity-driven recommendation policy within the reinforcement learning framework, allowing for an efficient and enjoyable personalized learning path. Specifically, a curiosity reward from a well-designed predictive model is generated to model one's familiarity with the knowledge space. Given such curiosity rewards, we apply the actor-critic method to approximate the policy directly through neural networks. Numerical analyses with a large continuous knowledge state space and concrete learning scenarios are provided to further demonstrate the efficiency of the proposed method.

In vivo single-cell lineage tracing in zebrafish using high-resolution infrared laser-mediated gene induction microscopy.

Heterogeneity broadly exists in various cell types both during development and at homeostasis. Investigating heterogeneity is crucial for comprehensively understanding the complexity of ontogeny, dynamics, and function of specific cell types. Traditional bulk-labeling techniques are incompetent to dissect heterogeneity within cell population, while the new single-cell lineage tracing methodologies invented in the last decade can hardly achieve high-fidelity single-cell labeling and long-term in-vivo observation simultaneously. In this work, we developed a high-precision infrared laser-evoked gene operator heat-shock system, which uses laser-induced CreERT2 combined with loxP-DsRedx-loxP-GFP reporter to achieve precise single-cell labeling and tracing. In vivo study indicated that this system can precisely label single cell in brain, muscle and hematopoietic system in zebrafish embryo. Using this system, we traced the hematopoietic potential of hemogenic endothelium (HE) in the posterior blood island (PBI) of zebrafish embryo and found that HEs in the PBI are heterogeneous, which contains at least myeloid unipotent and myeloid-lymphoid bipotent subtypes.

Animals begin life as a single cell that then divides to become a complex organism with many different types of cells. Every time a cell divides, each of its two daughter cells can either stay the same type as their parent or adopt a different identity. Once a cell acquires an identity, it usually cannot 'go back' and choose another. Eventually, this process will produce daughter cells with the identity of a specific tissue or organ and that cannot divide further. Multipotent cells are cells that can produce daughter cells with different identities, including other multipotent cells. These cells can usually give rise to different cell types in a specific organ, and generate more cells to replace any cells that die in that organ. Tracking the cells descended from a multipotent cell in a specific tissue can provide information about how the tissue develops. Hemogenic endothelium cells produce the multipotent cells that give rise to two types of white blood cells: myeloid cells and lymphoid cells. Myeloid cells include innate immune cells that protect the body from infection non-specifically; while lymphoid cells include T cells and B cells with receptors that detect specific bacteria or viruses. It remains unclear whether each of these two cell types originate from a single population of hemogenic endothelium cells or from two distinct subpopulations. He et al. have now developed a new optical technique to label a single hemogenic endothelium cell in a zebrafish and track the cell and its descendants. This method revealed that there are at least two distinct populations of hemogenic endothelium cells. One of them can give rise to both lymphoid and myeloid cells, while the other can only give rise to myeloid cells. These findings shed light on the mechanisms of blood formation, and potentially could provide useful tools to study the development of diseases such as leukemia. Additionally, the single-cell labeling technology He et al. have developed could be applied to study the development of other tissues and organs.

Broken adaptive ridge regression and its asymptotic properties.

This paper studies the asymptotic properties of a sparse linear regression estimator, referred to as broken adaptive ridge (BAR) estimator, resulting from an L 0-based iteratively reweighted L 2 penalization algorithm using the ridge estimator as its initial value. We show that the BAR estimator is consistent for variable selection and has an oracle property for parameter estimation. Moreover, we show that the BAR estimator possesses a grouping effect: highly correlated covariates are naturally grouped together, which is a desirable property not known for other oracle variable selection methods. Lastly, we combine BAR with a sparsity-restricted least squares estimator and give conditions under which the resulting two-stage sparse regression method is selection and estimation consistent in addition to having the grouping property in high- or ultrahigh-dimensional settings. Numerical studies are conducted to investigate and illustrate the operating characteristics of the BAR method in comparison with other methods.

Functional and Parametric Estimation in a Semi- and Nonparametric Model with Application to Mass-Spectrometry Data.

Motivated by modeling and analysis of mass-spectrometry data, a semi- and nonparametric model is proposed that consists of linear parametric components for individual location and scale and a nonparametric regression function for the common shape. A multi-step approach is developed that simultaneously estimates the parametric components and the nonparametric function. Under certain regularity conditions, it is shown that the resulting estimators is consistent and asymptotic normal for the parametric part and achieve the optimal rate of convergence for the nonparametric part when the bandwidth is suitably chosen. Simulation results are presented to demonstrate the effectiveness and finite-sample performance of the method. The method is also applied to a SELDI-TOF mass spectrometry data set from a study of liver cancer patients.

Semiparametric transformation models for causal inference in time to event studies with all-or-nothing compliance.

We consider causal inference in randomized survival studies with right censored outcomes and all-or-nothing compliance, using semiparametric transformation models to estimate the distribution of survival times in treatment and control groups, conditional on covariates and latent compliance type. Estimands depending on these distributions, for example, the complier average causal effect (CACE), the complier effect on survival beyond time t, and the complier quantile effect are then considered. Maximum likelihood is used to estimate the parameters of the transformation models, using a specially designed expectation-maximization (EM) algorithm to overcome the computational difficulties created by the mixture structure of the problem and the infinite dimensional parameter in the transformation models. The estimators are shown to be consistent, asymptotically normal, and semiparametrically efficient. Inferential procedures for the causal parameters are developed. A simulation study is conducted to evaluate the finite sample performance of the estimated causal parameters. We also apply our methodology to a randomized study conducted by the Health Insurance Plan of Greater New York to assess the reduction in breast cancer mortality due to screening.

Least Absolute Relative Error Estimation.

Multiplicative regression model or accelerated failure time model, which becomes linear regression model after logarithmic transformation, is useful in analyzing data with positive responses, such as stock prices or life times, that are particularly common in economic/financial or biomedical studies. Least squares or least absolute deviation are among the most widely used criterions in statistical estimation for linear regression model. However, in many practical applications, especially in treating, for example, stock price data, the size of relative error, rather than that of error itself, is the central concern of the practitioners. This paper offers an alternative to the traditional estimation methods by considering minimizing the least absolute relative errors for multiplicative regression models. We prove consistency and asymptotic normality and provide an inference approach via random weighting. We also specify the error distribution, with which the proposed least absolute relative errors estimation is efficient. Supportive evidence is shown in simulation studies. Application is illustrated in an analysis of stock returns in Hong Kong Stock Exchange.

Global Partial Likelihood for Nonparametric Proportional Hazards Models.

As an alternative to the local partial likelihood method of Tibshirani and Hastie and Fan, Gijbels, and King, a global partial likelihood method is proposed to estimate the covariate effect in a nonparametric proportional hazards model, λ(t|x) = exp{ψ(x)}λ(0)(t). The estimator, ψ̂(x), reduces to the Cox partial likelihood estimator if the covariate is discrete. The estimator is shown to be consistent and semiparametrically efficient for linear functionals of ψ(x). Moreover, Breslow-type estimation of the cumulative baseline hazard function, using the proposed estimator ψ̂(x), is proved to be efficient. The asymptotic bias and variance are derived under regularity conditions. Computation of the estimator involves an iterative but simple algorithm. Extensive simulation studies provide evidence supporting the theory. The method is illustrated with the Stanford heart transplant data set. The proposed global approach is also extended to a partially linear proportional hazards model and found to provide efficient estimation of the slope parameter. This article has the supplementary materials online.