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In cluster-randomized experiments, there is emerging interest in exploring the causal mechanism in which a cluster-level treatment affects the outcome through an intermediate outcome. Despite an extensive development of causal mediation methods in the past decade, only a few exceptions have been considered in assessing causal mediation in cluster-randomized studies, all of which depend on parametric model-based estimators. In this article, we develop the formal semiparametric efficiency theory to motivate several doubly-robust methods for addressing several mediation effect estimands corresponding to both the cluster-average and the individual-level treatment effects in cluster-randomized experiments--the natural indirect effect, natural direct effect, and spillover mediation effect. We derive the efficient influence function for each mediation effect, and carefully parameterize each efficient influence function to motivate practical strategies for operationalizing each estimator. We consider both parametric working models and data-adaptive machine learners to estimate the nuisance functions, and obtain semiparametric efficient causal mediation estimators in the latter case. Our methods are illustrated via extensive simulations and two completed cluster-randomized experiments.

Deep neural networks (DNNs) are increasingly deployed in safety-critical domains, but their vulnerability to adversarial attacks poses serious safety risks. Existing neuron-level methods using limited data lack efficacy in fixing adversaries due to the inherent complexity of adversarial attack mechanisms, while adversarial training, leveraging a large number of adversarial samples to enhance robustness, lacks provability. In this paper, we propose ADVREPAIR, a novel approach for provable repair of adversarial attacks using limited data. By utilizing formal verification, ADVREPAIR constructs patch modules that, when integrated with the original network, deliver provable and specialized repairs within the robustness neighborhood. Additionally, our approach incorporates a heuristic mechanism for assigning patch modules, allowing this defense against adversarial attacks to generalize to other inputs. ADVREPAIR demonstrates superior efficiency, scalability and repair success rate. Different from existing DNN repair methods, our repair can generalize to general inputs, thereby improving the robustness of the neural network globally, which indicates a significant breakthrough in the generalization capability of ADVREPAIR.

The causal inference literature frequently focuses on estimating the mean of the potential outcome, whereas quantiles of the potential outcome may carry important additional information. We propose a unified approach, based on the inverse estimating equations, to generalize a class of causal inference solutions from estimating the mean of the potential outcome to its quantiles. We assume that a moment function is available to identify the mean of the threshold-transformed potential outcome, based on which a convenient construction of the estimating equation of quantiles of potential outcome is proposed. In addition, we give a general construction of the efficient influence functions of the mean and quantiles of potential outcomes, and explicate their connection. We motivate estimators for the quantile estimands with the efficient influence function, and develop their asymptotic properties when either parametric models or data-adaptive machine learners are used to estimate the nuisance functions. A broad implication of our results is that one can rework the existing result for mean causal estimands to facilitate causal inference on quantiles. Our general results are illustrated by several analytical and numerical examples.

We consider an incidence problem in $\mathbb{R}^4$ which asks, for a set of $L$ lines and a set of $S$ planes in general position, what the maximum number of line-plane incidences is. A line-plane incidence is defined as a point where a line and a plane intersect. We prove that, when the lines and planes are in a truly 4-dimensional configuration such that no more than $L^{\frac{1}{2}+\epsilon}$ lines are contained in any 2-dimensional surface of degree at most $D$ and no more than $S^{\frac{1}{2}+\epsilon}$ 2-planes are contained in any 3-dimensional hypersurface of degree at most $D$, and if $L^{1/2} \ll S \ll L$, then for a constant $D>1$ and an $\epsilon>0$ there exists a non-trivial upper bound for incidences between lines and planes: $L^{\frac{3}{4}+\frac{1}{2}\epsilon}S + LS^{\frac{1}{2}+\epsilon}$. We also prove several supporting lemmas.

Robust pedestrian trajectory forecasting is crucial to developing safe autonomous vehicles. Although previous works have studied adversarial robustness in the context of trajectory forecasting, some significant issues remain unaddressed. In this work, we try to tackle these crucial problems. Firstly, the previous definitions of robustness in trajectory prediction are ambiguous. We thus provide formal definitions for two kinds of robustness, namely label robustness and pure robustness. Secondly, as previous works fail to consider robustness about all points in a disturbance interval, we utilise a probably approximately correct (PAC) framework for robustness verification. Additionally, this framework can not only identify potential counterexamples, but also provides interpretable analyses of the original methods. Our approach is applied using a prototype tool named TrajPAC. With TrajPAC, we evaluate the robustness of four state-of-the-art trajectory prediction models -- Trajectron++, MemoNet, AgentFormer, and MID -- on trajectories from five scenes of the ETH/UCY dataset and scenes of the Stanford Drone Dataset. Using our framework, we also experimentally study various factors that could influence robustness performance., Comment: ICCV 2023 version

Comparative effectiveness research frequently addresses a time-to-event outcome and can require unique considerations in the presence of treatment noncompliance. Motivated by the challenges in addressing noncompliance in the ADAPTABLE pragmatic trial, we develop a multiply robust estimator to estimate the principal survival causal effects under the principal ignorability and monotonicity assumption. The multiply robust estimator involves several working models including that for the treatment assignment, the compliance strata, censoring, and time-to-event of interest. The proposed estimator is consistent even if one, and sometimes two, of the working models are misspecified. We apply the multiply robust method in the ADAPTABLE trial to evaluate the effect of low- versus high-dose aspirin assignment on patients' death and hospitalization from cardiovascular diseases. We find that, comparing to low-dose assignment, assignment to the high-dose leads to differential effects among always high-dose takers, compliers, and always low-dose takers. Such treatment effect heterogeneity contributes to the null intention-to-treatment effect, and suggests that policy makers should design personalized strategies based on potential compliance patterns to maximize treatment benefits to the entire study population. We further perform a formal sensitivity analysis for investigating the robustness of our causal conclusions under violation of two identification assumptions specific to noncompliance.

We consider assessing causal mediation in the presence of a post-treatment event (examples include noncompliance, a clinical event, or a terminal event). We identify natural mediation effects for the entire study population and for each principal stratum characterized by the joint potential values of the post-treatment event. We derive efficient influence functions for each mediation estimand, which motivate a set of multiply robust estimators for inference. The multiply robust estimators are consistent under four types of misspecifications and are efficient when all nuisance models are correctly specified. We illustrate our methods via simulations and two real data examples.

Mediation analysis is widely used in health science research to evaluate the extent to which an intermediate variable explains an observed exposure-outcome relationship. However, the validity of analysis can be compromised when the exposure is measured with error. Motivated by the Health Professionals Follow-up Study (HPFS), we investigate the impact of exposure measurement error on assessing mediation with a survival outcome, based on the Cox proportional hazards outcome model. When the outcome is rare and there is no exposure-mediator interaction, we show that the uncorrected estimators of the natural indirect and direct effects can be biased into either direction, but the uncorrected estimator of the mediation proportion is approximately unbiased as long as the measurement error is not large or the mediator-exposure association is not strong. We develop ordinary regression calibration and risk set regression calibration approaches to correct the exposure measurement error-induced bias when estimating mediation effects and allowing for an exposure-mediator interaction in the Cox outcome model. The proposed approaches require a validation study to characterize the measurement error process. We apply the proposed approaches to the HPFS (1986-2016) to evaluate extent to which reduced body mass index mediates the protective effect of vigorous physical activity on the risk of cardiovascular diseases, and compare the finite-sample properties of the proposed estimators via simulations.

T cells monitor the health status of cells by identifying foreign peptides displayed on their surface. T-cell receptors (TCRs), which are protein complexes found on the surface of T cells, are able to bind to these peptides. This process is known as TCR recognition and constitutes a key step for immune response. Optimizing TCR sequences for TCR recognition represents a fundamental step towards the development of personalized treatments to trigger immune responses killing cancerous or virus-infected cells. In this paper, we formulated the search for these optimized TCRs as a reinforcement learning (RL) problem, and presented a framework TCRPPO with a mutation policy using proximal policy optimization. TCRPPO mutates TCRs into effective ones that can recognize given peptides. TCRPPO leverages a reward function that combines the likelihoods of mutated sequences being valid TCRs measured by a new scoring function based on deep autoencoders, with the probabilities of mutated sequences recognizing peptides from a peptide-TCR interaction predictor. We compared TCRPPO with multiple baseline methods and demonstrated that TCRPPO significantly outperforms all the baseline methods to generate positive binding and valid TCRs. These results demonstrate the potential of TCRPPO for both precision immunotherapy and peptide-recognizing TCR motif discovery.

Constraint solving is an elementary way for verification of deep neural networks (DNN). In the domain of AI safety, a DNN might be modified in its structure and parameters for its repair or attack. For such situations, we propose the incremental DNN verification problem, which asks whether a safety property still holds after the DNN is modified. To solve the problem, we present an incremental satisfiability modulo theory (SMT) algorithm based on the Reluplex framework. We simulate the most important features of the configurations that infers the verification result of the searching branches in the old solving procedure (with respect to the original network), and heuristically check whether the proofs are still valid for the modified DNN. We implement our algorithm as an incremental solver called DeepInc, and exerimental results show that DeepInc is more efficient in most cases. For the cases that the property holds both before and after modification, the acceleration can be faster by several orders of magnitude, showing that DeepInc is outstanding in incrementally searching for counterexamples. Moreover, based on the framework, we propose the multi-objective DNN repair problem and give an algorithm based on our incremental SMT solving algorithm. Our repair method preserves more potential safety properties on the repaired DNNs compared with state-of-the-art.