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Many public health interventions are conducted in settings where individuals are connected to one another and the intervention assigned to randomly selected individuals may spill over to other individuals they are connected to. In these spillover settings, the effects of such interventions can be quantified in several ways. The average individual effect measures the intervention effect among those directly treated, while the spillover effect measures the effect among those connected to those directly treated. In addition, the overall effect measures the average intervention effect across the study population, over those directly treated along with those to whom the intervention spills over but who are not directly treated. Here, we develop methods for study design with the aim of estimating individual, spillover, and overall effects. In particular, we consider an egocentric network-based randomized design in which a set of index participants is recruited from the population and randomly assigned to treatment, while data are also collected from their untreated network members. We use the potential outcomes framework to define two clustered regression modeling approaches and clarify the underlying assumptions required to identify and estimate causal effects. We then develop sample size formulas for detecting individual, spillover, and overall effects. We investigate the roles of the intra-class correlation coefficient and the probability of treatment allocation on the required number of egocentric networks with a fixed number of network members for each egocentric network and vice-versa.

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Saliency maps have become one of the most widely used interpretability techniques for convolutional neural networks (CNN) due to their simplicity and the quality of the insights they provide. However, there are still some doubts about whether these insights are a trustworthy representation of what CNNs use to come up with their predictions. This paper explores how rescuing the sign of the gradients from the saliency map can lead to a deeper understanding of multi-class classification problems. Using both pretrained and trained from scratch CNNs we unveil that considering the sign and the effect not only of the correct class, but also the influence of the other classes, allows to better identify the pixels of the image that the network is really focusing on. Furthermore, how occluding or altering those pixels is expected to affect the outcome also becomes clearer.

The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical trial in type 2 diabetes, targeting the effects of randomised treatment, handling rescue treatment and discontinuation of randomised treatment using the so-called hypothetical strategy. We show how this can be estimated using mixed models for repeated measures, multiple imputation, inverse probability of treatment weighting, G-formula and G-estimation. We describe their assumptions and practical details of their implementation using packages in R. We report the results of these analyses, broadly finding similar estimates and standard errors across the estimators. We discuss various considerations relevant when choosing an estimation approach, including computational time, how to handle missing data, whether to include post intercurrent event data in the analysis, whether and how to adjust for additional time-varying confounders, and whether and how to model different types of ICE separately.

Discovering causal relationships from observational data is a fundamental yet challenging task. In some applications, it may suffice to learn the causal features of a given response variable, instead of learning the entire underlying causal structure. Invariant causal prediction (ICP, Peters et al., 2016) is a method for causal feature selection which requires data from heterogeneous settings. ICP assumes that the mechanism for generating the response from its direct causes is the same in all settings and exploits this invariance to output a subset of the causal features. The framework of ICP has been extended to general additive noise models and to nonparametric settings using conditional independence testing. However, nonparametric conditional independence testing often suffers from low power (or poor type I error control) and the aforementioned parametric models are not suitable for applications in which the response is not measured on a continuous scale, but rather reflects categories or counts. To bridge this gap, we develop ICP in the context of transformation models (TRAMs), allowing for continuous, categorical, count-type, and uninformatively censored responses (we show that, in general, these model classes do not allow for identifiability when there is no exogenous heterogeneity). We propose TRAM-GCM, a test for invariance of a subset of covariates, based on the expected conditional covariance between environments and score residuals which satisfies uniform asymptotic level guarantees. For the special case of linear shift TRAMs, we propose an additional invariance test, TRAM-Wald, based on the Wald statistic. We implement both proposed methods in the open-source R package "tramicp" and show in simulations that under the correct model specification, our approach empirically yields higher power than nonparametric ICP based on conditional independence testing.

Recently established, directed dependence measures for pairs $(X,Y)$ of random variables build upon the natural idea of comparing the conditional distributions of $Y$ given $X=x$ with the marginal distribution of $Y$. They assign pairs $(X,Y)$ values in $[0,1]$, the value is $0$ if and only if $X,Y$ are independent, and it is $1$ exclusively for $Y$ being a function of $X$. Here we show that comparing randomly drawn conditional distributions with each other instead or, equivalently, analyzing how sensitive the conditional distribution of $Y$ given $X=x$ is on $x$, opens the door to constructing novel families of dependence measures $\Lambda_\varphi$ induced by general convex functions $\varphi: \mathbb{R} \rightarrow \mathbb{R}$, containing, e.g., Chatterjee's coefficient of correlation as special case. After establishing additional useful properties of $\Lambda_\varphi$ we focus on continuous $(X,Y)$, translate $\Lambda_\varphi$ to the copula setting, consider the $L^p$-version and establish an estimator which is strongly consistent in full generality. A real data example and a simulation study illustrate the chosen approach and the performance of the estimator. Complementing the afore-mentioned results, we show how a slight modification of the construction underlying $\Lambda_\varphi$ can be used to define new measures of explainability generalizing the fraction of explained variance.

With an increasing focus on precision medicine in medical research, numerous studies have been conducted in recent years to clarify the relationship between treatment effects and patient characteristics. The treatment effects for patients with different characteristics are always heterogeneous, and various heterogeneous treatment effect machine learning estimation methods have been proposed owing to their flexibility and high prediction accuracy. However, most machine learning methods rely on black-box models, preventing direct interpretation of the relationship between patient characteristics and treatment effects. Moreover, most of these studies have focused on continuous or binary outcomes, although survival outcomes are also important in medical research. To address these challenges, we propose a heterogeneous treatment effect estimation method for survival data based on RuleFit, an interpretable machine learning method. Numerical simulation results confirmed that the prediction performance of the proposed method was comparable to that of existing methods. We also applied a dataset from an HIV study, the AIDS Clinical Trials Group Protocol 175 dataset, to illustrate the interpretability of the proposed method using real data. Consequently, the proposed method established an interpretable model with sufficient prediction accuracy.

To improve the statistical power for imaging biomarker detection, we propose a latent variable-based statistical network analysis (LatentSNA) that combines brain functional connectivity with internalizing psychopathology, implementing network science in a generative statistical process to preserve the neurologically meaningful network topology in the adolescents and children population. The developed inference-focused generative Bayesian framework (1) addresses the lack of power and inflated Type II errors in current analytic approaches when detecting imaging biomarkers, (2) allows unbiased estimation of biomarkers' influence on behavior variants, (3) quantifies the uncertainty and evaluates the likelihood of the estimated biomarker effects against chance and (4) ultimately improves brain-behavior prediction in novel samples and the clinical utilities of neuroimaging findings. We collectively model multi-state functional networks with multivariate internalizing profiles for 5,000 to 7,000 children in the Adolescent Brain Cognitive Development (ABCD) study with sufficiently accurate prediction of both children internalizing traits and functional connectivity, and substantially improved our ability to explain the individual internalizing differences compared with current approaches. We successfully uncover large, coherent star-like brain functional architectures associated with children's internalizing psychopathology across multiple functional systems and establish them as unique fingerprints for childhood internalization.

Country comparisons using standardized test scores may in some cases be misleading unless we make sure that the potential sample selection bias created by drop-outs and non-enrollment patterns does not alter the analysis. In this paper, I propose an answer to this issue which consists in comparing the counterfactual distribution of achievement (I mean the distribution of achievement if there was hypothetically no selection) and the observed distribution of achievements. If the difference is statistically significant, international comparison measures like means, quantiles, and inequality measures have to be computed using that counterfactual distribution. I identify the quantiles of that latent distribution by readjusting the percentile levels of the observed quantile function of achievement. Because the data on test scores is by nature truncated, I have to rely on auxiliary data to borrow identification power. I finally applied my method to 6 sub-Saharan countries using 6th-grade test scores.

We examine a stochastic formulation for data-driven optimization wherein the decision-maker is not privy to the true distribution, but has knowledge that it lies in some hypothesis set and possesses a historical data set, from which information about it can be gleaned. We define a prescriptive solution as a decision rule mapping such a data set to decisions. As there does not exist prescriptive solutions that are generalizable over the entire hypothesis set, we define out-of-sample optimality as a local average over a neighbourhood of hypotheses, and averaged over the sampling distribution. We prove sufficient conditions for local out-of-sample optimality, which reduces to functions of the sufficient statistic of the hypothesis family. We present an optimization problem that would solve for such an out-of-sample optimal solution, and does so efficiently by a combination of sampling and bisection search algorithms. Finally, we illustrate our model on the newsvendor model, and find strong performance when compared against alternatives in the literature. There are potential implications of our research on end-to-end learning and Bayesian optimization.

Knowledge graphs (KGs) of real-world facts about entities and their relationships are useful resources for a variety of natural language processing tasks. However, because knowledge graphs are typically incomplete, it is useful to perform knowledge graph completion or link prediction, i.e. predict whether a relationship not in the knowledge graph is likely to be true. This paper serves as a comprehensive survey of embedding models of entities and relationships for knowledge graph completion, summarizing up-to-date experimental results on standard benchmark datasets and pointing out potential future research directions.

Graph representation learning for hypergraphs can be used to extract patterns among higher-order interactions that are critically important in many real world problems. Current approaches designed for hypergraphs, however, are unable to handle different types of hypergraphs and are typically not generic for various learning tasks. Indeed, models that can predict variable-sized heterogeneous hyperedges have not been available. Here we develop a new self-attention based graph neural network called Hyper-SAGNN applicable to homogeneous and heterogeneous hypergraphs with variable hyperedge sizes. We perform extensive evaluations on multiple datasets, including four benchmark network datasets and two single-cell Hi-C datasets in genomics. We demonstrate that Hyper-SAGNN significantly outperforms the state-of-the-art methods on traditional tasks while also achieving great performance on a new task called outsider identification. Hyper-SAGNN will be useful for graph representation learning to uncover complex higher-order interactions in different applications.

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