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This work is motivated by personalized digital twins based on observations and physical models for treatment and prevention of Hypertension. The models commonly used are simplification of the real process and the aim is to make inference about physically interpretable parameters. To account for model discrepancy we propose to set up the estimation problem in a Bayesian calibration framework. This naturally solves the inverse problem accounting for and quantifying the uncertainty in the model formulation, in the parameter estimates and predictions. We focus on the inverse problem, i.e. to estimate the physical parameters given observations. The models we consider are the two and three parameters Windkessel models (WK2 and WK3). These models simulate the blood pressure waveform given the blood inflow and a set of physically interpretable calibration parameters. The third parameter in WK3 function as a tuning parameter. The WK2 model offers physical interpretable parameters and therefore we adopt it as a computer model choice in a Bayesian calibration formulation. In a synthetic simulation study, we simulate noisy data from the WK3 model. We estimate the model parameters using conventional methods, i.e. least squares optimization and through the Bayesian calibration framework. It is demonstrated that our formulation can reconstruct the blood pressure waveform of the complex model, but most importantly can learn the parameters according to known mathematical connections between the two models. We also successfully apply this formulation to a real case study, where data was obtained from a pilot randomized controlled trial study. Our approach is successful for both the simulation study and the real cases.

Simulation studies are commonly used to evaluate the performance of newly developed meta-analysis methods. For methodology that is developed for an aggregated data meta-analysis, researchers often resort to simulation of the aggregated data directly, instead of simulating individual participant data from which the aggregated data would be calculated in reality. Clearly, distributional characteristics of the aggregated data statistics may be derived from distributional assumptions of the underlying individual data, but they are often not made explicit in publications. This paper provides the distribution of the aggregated data statistics that were derived from a heteroscedastic mixed effects model for continuous individual data. As a result, we provide a procedure for directly simulating the aggregated data statistics. We also compare our distributional findings with other simulation approaches of aggregated data used in literature by describing their theoretical differences and by conducting a simulation study for three meta-analysis methods: DerSimonian and Laird's pooled estimate and the Trim & Fill and PET-PEESE method for adjustment of publication bias. We demonstrate that the choices of simulation model for aggregated data may have a relevant impact on (the conclusions of) the performance of the meta-analysis method. We recommend the use of multiple aggregated data simulation models for investigation of new methodology to determine sensitivity or otherwise make the individual participant data model explicit that would lead to the distributional choices of the aggregated data statistics used in the simulation.

Understanding treatment effect heterogeneity in observational studies is of great practical importance to many scientific fields. Quantile regression provides a natural framework for modeling such heterogeneity. In this paper, we propose a new method for inference on heterogeneous quantile treatment effects in the presence of high-dimensional covariates. Our estimator combines a $\ell_1$-penalized regression adjustment with a quantile-specific bias correction scheme based on quantile regression rank scores. We present a comprehensive study of the theoretical properties of this estimator, including weak convergence of the heterogeneous quantile treatment effect process to a Gaussian process. We illustrate the finite-sample performance of our approach through Monte Carlo experiments and an empirical example, dealing with the differential effect of statin usage for lowering low-density lipoprotein cholesterol levels for the Alzheimer's disease patients who participated in the UK Biobank study.

The selection of essential variables in logistic regression is vital because of its extensive use in medical studies, finance, economics and related fields. In this paper, we explore four main typologies (test-based, penalty-based, screening-based, and tree-based) of frequentist variable selection methods in logistic regression setup. Primary objective of this work is to give a comprehensive overview of the existing literature for practitioners. Underlying assumptions and theory, along with the specifics of their implementations, are detailed as well. Next, we conduct a thorough simulation study to explore the performances of fifteen different methods in terms of variable selection, estimation of coefficients, prediction accuracy as well as time complexity under various settings. We take low, moderate and high dimensional setups and consider different correlation structures for the covariates. A real-life application, using a high-dimensional gene expression data, is also included in this study to further understand the efficacy and consistency of the methods. Finally, based on our findings in the simulated data and in the real data, we provide recommendations for practitioners on the choice of variable selection methods under various contexts.

Clustering time series into similar groups can improve models by combining information across like time series. While there is a well developed body of literature for clustering of time series, these approaches tend to generate clusters independently of model training which can lead to poor model fit. We propose a novel distributed approach that simultaneously clusters and fits autoregression models for groups of similar individuals. We apply a Wishart mixture model so as to cluster individuals while modeling the corresponding autocovariance matrices at the same time. The fitted Wishart scale matrices map to cluster-level autoregressive coefficients through the Yule-Walker equations, fitting robust parsimonious autoregressive mixture models. This approach is able to discern differences in underlying autocorrelation variation of time series in settings with large heterogeneous datasets. We prove consistency of our cluster membership estimator, asymptotic distributions of coefficients and compare our approach against competing methods through simulation as well as by fitting a COVID-19 forecast model.

Dyadic data is often encountered when quantities of interest are associated with the edges of a network. As such it plays an important role in statistics, econometrics and many other data science disciplines. We consider the problem of uniformly estimating a dyadic Lebesgue density function, focusing on nonparametric kernel-based estimators which take the form of U-process-like dyadic empirical processes. We provide uniform point estimation and distributional results for the dyadic kernel density estimator, giving valid and feasible procedures for robust uniform inference. Our main contributions include the minimax-optimal uniform convergence rate of the dyadic kernel density estimator, along with strong approximation results for the associated standardized $t$-process. A consistent variance estimator is introduced in order to obtain analogous results for the Studentized $t$-process, enabling the construction of provably valid and feasible uniform confidence bands for the unknown density function. A crucial feature of U-process-like dyadic empirical processes is that they may be "degenerate" at some or possibly all points in the support of the data, a property making our uniform analysis somewhat delicate. Nonetheless we show formally that our proposed methods for uniform inference remain robust to the potential presence of such unknown degenerate points. For the purpose of implementation, we discuss uniform inference procedures based on positive semi-definite covariance estimators, mean squared error optimal bandwidth selectors and robust bias-correction methods. We illustrate the empirical finite-sample performance of our robust inference methods in a simulation study. Our technical results concerning strong approximations and maximal inequalities are of potential independent interest.

Predictive coding offers a potentially unifying account of cortical function -- postulating that the core function of the brain is to minimize prediction errors with respect to a generative model of the world. The theory is closely related to the Bayesian brain framework and, over the last two decades, has gained substantial influence in the fields of theoretical and cognitive neuroscience. A large body of research has arisen based on both empirically testing improved and extended theoretical and mathematical models of predictive coding, as well as in evaluating their potential biological plausibility for implementation in the brain and the concrete neurophysiological and psychological predictions made by the theory. Despite this enduring popularity, however, no comprehensive review of predictive coding theory, and especially of recent developments in this field, exists. Here, we provide a comprehensive review both of the core mathematical structure and logic of predictive coding, thus complementing recent tutorials in the literature. We also review a wide range of classic and recent work within the framework, ranging from the neurobiologically realistic microcircuits that could implement predictive coding, to the close relationship between predictive coding and the widely-used backpropagation of error algorithm, as well as surveying the close relationships between predictive coding and modern machine learning techniques.

Mixed-effects meta-regression models provide a powerful tool for evidence synthesis. In fact, modelling the study effect in terms of random effects and moderators not only allows to examine the impact of the moderators, but often leads to more accurate estimates of the involved parameters. Nevertheless, due to the often small number of studies on a specific research topic, interactions are often neglected in meta-regression. This was also the case in a recent meta-analysis in acute heart failure where a significant decline in death rate over calendar time was reported. However, we believe that an important interaction has been neglected. We therefore reanalyzed the data with a meta-regression model, including an interaction term of the median recruitment year and the average age of the patients. The model with interaction suggests different conclusions. This led to the new research questions (i) how moderator interactions influence inference in mixed-effects meta-regression models and (ii) whether some inference methods are more reliable than others. Focusing on confidence intervals for main and interaction parameters, we address these questions in an extensive simulation study. We thereby investigate coverage and length of seven different confidence intervals under varying conditions. We conclude with some practical recommendations.

This paper deals with robust inference for parametric copula models. Estimation using Canonical Maximum Likelihood might be unstable, especially in the presence of outliers. We propose to use a procedure based on the Maximum Mean Discrepancy (MMD) principle. We derive non-asymptotic oracle inequalities, consistency and asymptotic normality of this new estimator. In particular, the oracle inequality holds without any assumption on the copula family, and can be applied in the presence of outliers or under misspecification. Moreover, in our MMD framework, the statistical inference of copula models for which there exists no density with respect to the Lebesgue measure on $[0,1]^d$, as the Marshall-Olkin copula, becomes feasible. A simulation study shows the robustness of our new procedures, especially compared to pseudo-maximum likelihood estimation. An R package implementing the MMD estimator for copula models is available.

Heatmap-based methods dominate in the field of human pose estimation by modelling the output distribution through likelihood heatmaps. In contrast, regression-based methods are more efficient but suffer from inferior performance. In this work, we explore maximum likelihood estimation (MLE) to develop an efficient and effective regression-based methods. From the perspective of MLE, adopting different regression losses is making different assumptions about the output density function. A density function closer to the true distribution leads to a better regression performance. In light of this, we propose a novel regression paradigm with Residual Log-likelihood Estimation (RLE) to capture the underlying output distribution. Concretely, RLE learns the change of the distribution instead of the unreferenced underlying distribution to facilitate the training process. With the proposed reparameterization design, our method is compatible with off-the-shelf flow models. The proposed method is effective, efficient and flexible. We show its potential in various human pose estimation tasks with comprehensive experiments. Compared to the conventional regression paradigm, regression with RLE bring 12.4 mAP improvement on MSCOCO without any test-time overhead. Moreover, for the first time, especially on multi-person pose estimation, our regression method is superior to the heatmap-based methods. Our code is available at //github.com/Jeff-sjtu/res-loglikelihood-regression