Mendelian randomization (MR) is a widely-used method to estimate the causal relationship between a risk factor and disease. A fundamental part of any MR analysis is to choose appropriate genetic variants as instrumental variables. Genome-wide association studies often reveal that hundreds of genetic variants may be robustly associated with a risk factor, but in some situations investigators may believe that only a smaller subset of these variants are valid instruments. Nevertheless, using the full set of instruments could lead to biased but more precise estimates, and therefore in terms of mean squared error it may be unclear which set of instruments is optimal. For this purpose, we consider a method for "focused" instrument selection whereby genetic variants are selected to minimise the estimated asymptotic mean squared error of causal effect estimates. In a setting of many weak and locally invalid instruments, we consider a novel strategy to construct confidence intervals for post-selection focused estimators which guards against the worst case loss in asymptotic coverage. In empirical applications to: (i) validate lipid drug targets; and (ii) investigate vitamin D effects on a wide range of outcomes, our findings suggest that the optimal selection of instruments does not involve only a small number of biologically-justified valid instruments, but also many potentially invalid instruments.
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In several large-scale replication projects, statistically non-significant results in both the original and the replication study have been interpreted as a "replication success". Here we discuss the logical problems with this approach: Non-significance in both studies does not ensure that the studies provide evidence for the absence of an effect and "replication success" can virtually always be achieved if the sample sizes are small enough. In addition, the relevant error rates are not controlled. We show how methods, such as equivalence testing and Bayes factors, can be used to adequately quantify the evidence for the absence of an effect and how they can be applied in the replication setting. Using data from the Reproducibility Project: Cancer Biology we illustrate that many original and replication studies with "null results" are in fact inconclusive, and that their replicability is lower than suggested by the non-significance approach. We conclude that it is important to also replicate studies with statistically non-significant results, but that they should be designed, analyzed, and interpreted appropriately.
The central space of a joint distribution $(\vX,Y)$ is the minimal subspace $\mathcal S$ such that $Y\perp\hspace{-2mm}\perp \vX \mid P_{\mathcal S}\vX$ where $P_{\mathcal S}$ is the projection onto $\mathcal S$. Sliced inverse regression (SIR), one of the most popular methods for estimating the central space, often performs poorly when the structural dimension $d=\operatorname{dim}\left( \mathcal S \right)$ is large (e.g., $\geqs 5$). In this paper, we demonstrate that the generalized signal-noise-ratio (gSNR) tends to be extremely small for a general multiple-index model when $d$ is large. Then we determine the minimax rate for estimating the central space over a large class of high dimensional distributions with a large structural dimension $d$ (i.e., there is no constant upper bound on $d$) in the low gSNR regime. This result not only extends the existing minimax rate results for estimating the central space of distributions with fixed $d$ to that with a large $d$, but also clarifies that the degradation in SIR performance is caused by the decay of signal strength. The technical tools developed here might be of independent interest for studying other central space estimation methods.
Most existing studies on linear bandits focus on the one-dimensional characterization of the overall system. While being representative, this formulation may fail to model applications with high-dimensional but favorable structures, such as the low-rank tensor representation for recommender systems. To address this limitation, this work studies a general tensor bandits model, where actions and system parameters are represented by tensors as opposed to vectors, and we particularly focus on the case that the unknown system tensor is low-rank. A novel bandit algorithm, coined TOFU (Tensor Optimism in the Face of Uncertainty), is developed. TOFU first leverages flexible tensor regression techniques to estimate low-dimensional subspaces associated with the system tensor. These estimates are then utilized to convert the original problem to a new one with norm constraints on its system parameters. Lastly, a norm-constrained bandit subroutine is adopted by TOFU, which utilizes these constraints to avoid exploring the entire high-dimensional parameter space. Theoretical analyses show that TOFU improves the best-known regret upper bound by a multiplicative factor that grows exponentially in the system order. A novel performance lower bound is also established, which further corroborates the efficiency of TOFU.
State-of-the-art research of traditional computer vision is increasingly leveraged in the surgical domain. A particular focus in computer-assisted surgery is to replace marker-based tracking systems for instrument localization with pure image-based 6DoF pose estimation. However, the state of the art has not yet met the accuracy required for surgical navigation. In this context, we propose a high-fidelity marker-less optical tracking system for surgical instrument localization. We developed a multi-view camera setup consisting of static and mobile cameras and collected a large-scale RGB-D video dataset with dedicated synchronization and data fusions methods. Different state-of-the-art pose estimation methods were integrated into a deep learning pipeline and evaluated on multiple camera configurations. Furthermore, the performance impacts of different input modalities and camera positions, as well as training on purely synthetic data, were compared. The best model achieved an average position and orientation error of 1.3 mm and 1.0{\deg} for a surgical drill as well as 3.8 mm and 5.2{\deg} for a screwdriver. These results significantly outperform related methods in the literature and are close to clinical-grade accuracy, demonstrating that marker-less tracking of surgical instruments is becoming a feasible alternative to existing marker-based systems.
Motivated by recent findings that within-subject (WS) visit-to-visit variabilities of longitudinal biomarkers can be strong risk factors for health outcomes, this paper introduces and examines a new joint model of a longitudinal biomarker with heterogeneous WS variability and competing risks time-to-event outcome. Specifically, our joint model consists of a linear mixed-effects multiple location-scale submodel for the individual mean trajectory and WS variability of the longitudinal biomarker and a semiparametric cause-specific Cox proportional hazards submodel for the competing risks survival outcome. The submodels are linked together via shared random effects. We derive an expectation-maximization algorithm for semiparametric maximum likelihood estimation and a profile-likelihood method for standard error estimation. We implement efficient computational algorithms that scales to biobank-scale data with tens of thousands of subjects. Our simulation results demonstrate that, in the presence of heterogeneous WS variability, the proposed method has superior performance for estimation, inference, and prediction, over the classical joint model with homogeneous WS variability. An application of our method to a Multi-Ethnic Study of Atherosclerosis (MESA) data reveals that there is substantial heterogeneity in systolic blood pressure (SBP) WS variability across MESA individuals and that SBP WS variability is an important predictor for heart failure and death, (independent of, or in addition to) the individual SBP mean level. Furthermore, by accounting for both the mean trajectory and WS variability of SBP, our method leads to a more accurate dynamic prediction model for heart failure or death. A user-friendly R package \textbf{JMH} is developed and publicly available at \url{//github.com/shanpengli/JMH}.
When an exposure of interest is confounded by unmeasured factors, an instrumental variable (IV) can be used to identify and estimate certain causal contrasts. Identification of the marginal average treatment effect (ATE) from IVs relies on strong untestable structural assumptions. When one is unwilling to assert such structure, IVs can nonetheless be used to construct bounds on the ATE. Famously, Balke and Pearl (1997) proved tight bounds on the ATE for a binary outcome, in a randomized trial with noncompliance and no covariate information. We demonstrate how these bounds remain useful in observational settings with baseline confounders of the IV, as well as randomized trials with measured baseline covariates. The resulting bounds on the ATE are non-smooth functionals, and thus standard nonparametric efficiency theory is not immediately applicable. To remedy this, we propose (1) under a novel margin condition, influence function-based estimators of the bounds that can attain parametric convergence rates when the nuisance functions are modeled flexibly, and (2) estimators of smooth approximations of these bounds. We propose extensions to continuous outcomes, explore finite sample properties in simulations, and illustrate the proposed estimators in a randomized experiment studying the effects of vaccination encouragement on flu-related hospital visits.
In this paper we discuss potentially practical ways to produce expander graphs with good spectral properties and a compact description. We focus on several classes of uniform and bipartite expander graphs defined as random Schreier graphs of the general linear group over the finite field of size two. We perform numerical experiments and show that such constructions produce spectral expanders that can be useful for practical applications. To find a theoretical explanation of the observed experimental results, we used the method of moments to prove upper bounds for the expected second largest eigenvalue of the random Schreier graphs used in our constructions. We focus on bounds for which it is difficult to study the asymptotic behaviour but it is possible to compute non-trivial conclusions for relatively small graphs with parameters from our numerical experiments (e.g., with less than 2^200 vertices and degree at least logarithmic in the number of vertices).
Blockchain enables peer-to-peer transactions in cyberspace without a trusted third party. The rapid growth of Ethereum and smart contract blockchains generally calls for well-designed Transaction Fee Mechanisms (TFMs) to allocate limited storage and computation resources. However, existing research on TFMs must consider the waiting time for transactions, which is essential for computer security and economic efficiency. Integrating data from the Ethereum blockchain and memory pool (mempool), we explore how two types of events affect transaction latency. First, we apply regression discontinuity design (RDD) to study the causal inference of the Merge, the most recent significant upgrade of Ethereum. Our results show that the Merge significantly reduces the long waiting time, network loads, and market congestion. In addition, we verify our results' robustness by inspecting other compounding factors, such as censorship and unobserved delays of transactions via private changes. Second, examining three major protocol changes during the merge, we identify block interval shortening as the most plausible cause for our empirical results. Furthermore, in a mathematical model, we show block interval as a unique mechanism design choice for EIP1559 TFM to achieve better security and efficiency, generally applicable to the market congestion caused by demand surges. Finally, we apply time series analysis to research the interaction of Non-Fungible token (NFT) drops and market congestion using Facebook Prophet, an open-source algorithm for generating time-series models. Our study identified NFT drops as a unique source of market congestion -- holiday effects -- beyond trend and season effects. Finally, we envision three future research directions of TFM.
Interference is a ubiquitous problem in experiments conducted on two-sided content marketplaces, such as Douyin (China's analog of TikTok). In many cases, creators are the natural unit of experimentation, but creators interfere with each other through competition for viewers' limited time and attention. "Naive" estimators currently used in practice simply ignore the interference, but in doing so incur bias on the order of the treatment effect. We formalize the problem of inference in such experiments as one of policy evaluation. Off-policy estimators, while unbiased, are impractically high variance. We introduce a novel Monte-Carlo estimator, based on "Differences-in-Qs" (DQ) techniques, which achieves bias that is second-order in the treatment effect, while remaining sample-efficient to estimate. On the theoretical side, our contribution is to develop a generalized theory of Taylor expansions for policy evaluation, which extends DQ theory to all major MDP formulations. On the practical side, we implement our estimator on Douyin's experimentation platform, and in the process develop DQ into a truly "plug-and-play" estimator for interference in real-world settings: one which provides robust, low-bias, low-variance treatment effect estimates; admits computationally cheap, asymptotically exact uncertainty quantification; and reduces MSE by 99\% compared to the best existing alternatives in our applications.
With the rapid increase of large-scale, real-world datasets, it becomes critical to address the problem of long-tailed data distribution (i.e., a few classes account for most of the data, while most classes are under-represented). Existing solutions typically adopt class re-balancing strategies such as re-sampling and re-weighting based on the number of observations for each class. In this work, we argue that as the number of samples increases, the additional benefit of a newly added data point will diminish. We introduce a novel theoretical framework to measure data overlap by associating with each sample a small neighboring region rather than a single point. The effective number of samples is defined as the volume of samples and can be calculated by a simple formula $(1-\beta^{n})/(1-\beta)$, where $n$ is the number of samples and $\beta \in [0,1)$ is a hyperparameter. We design a re-weighting scheme that uses the effective number of samples for each class to re-balance the loss, thereby yielding a class-balanced loss. Comprehensive experiments are conducted on artificially induced long-tailed CIFAR datasets and large-scale datasets including ImageNet and iNaturalist. Our results show that when trained with the proposed class-balanced loss, the network is able to achieve significant performance gains on long-tailed datasets.
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