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ABSTRACT We introduce a novel meta-analysis framework to combine dependent tests under a general setting, and utilize it to synthesize various microbiome association tests that are calculated from the same dataset. Our development builds upon the classical meta-analysis methods of aggregating P-values and also a more recent general method of combining confidence distributions, but makes generalizations to handle dependent tests. The proposed framework ensures rigorous statistical guarantees, and we provide a comprehensive study and compare it with various existing dependent combination methods. Notably, we demonstrate that the widely used Cauchy combination method for dependent tests, referred to as the vanilla Cauchy combination in this article, can be viewed as a special case within our framework. Moreover, the proposed framework provides a way to address the problem when the distributional assumptions underlying the vanilla Cauchy combination are violated. Our numerical results demonstrate that ignoring the dependence among the to-be-combined components may lead to a severe size distortion phenomenon. Compared to the existing P-value combination methods, including the vanilla Cauchy combination method and other methods, the proposed combination framework is flexible and can be adapted to handle the dependence accurately and utilizes the information efficiently to construct tests with accurate size and enhanced power. The development is applied to the microbiome association studies, where we aggregate information from multiple existing tests using the same dataset. The combined tests harness the strengths of each individual test across a wide range of alternative spaces, enabling more efficient and meaningful discoveries of vital microbiome associations. 

Abstract Stemming from the high-profile publication of Nissen and Wolski (N Engl J Med 356:2457–2471, 2007) and subsequent discussions with divergent views on how to handle observed zero-total-event studies, defined to be studies that observe zero number of event in both treatment and control arms, the research topic concerning the common odds ratio model with zero-total-event studies remains to be an unresolved problem in meta-analysis. In this article, we address this problem by proposing a novel repro samples method to handle zero-total-event studies and make inference for the common odds ratio. The development explicitly accounts for the sampling scheme that generates the observed data and does not rely on any large sample approximations. It is theoretically justified with a guaranteed finite-sample performance. Simulation studies are designed to demonstrate the empirical performance of the proposed method. It shows that the proposed confidence set, although a little conservative, achieves the desired empirical coverage rate in all situations. The development also shows that the zero-total-event studies contain meaningful information and impact the inference for the common odds ratio. The proposed method is used to perform a meta-analysis of the 48 trials reported in Nissen and Wolski (N Engl J Med 356:2457–2471, 2007) as well 

Abstract Well-known debates among statistical inferential paradigms emerge from conflicting views on the notion of probability. One dominant view understands probability as a representation of sampling variability; another prominent view understands probability as a measure of belief. The former generally describes model parameters as fixed values, in contrast to the latter. We propose that there are actually two versions of a parameter within both paradigms: a fixed unknown value that generated the data and a random version to describe the uncertainty in estimating the unknown value. An inferential approach based on CDs deciphers seemingly conflicting perspectives on parameters and probabilities. 

Abstract The increasing prevalence of wearable devices enables low-cost, long-term collection of health relevant data such as heart rate, exercise, and sleep signals. Currently these data are used to monitor short term changes with limited interpretation of their relevance to health. These data provide an untapped resource to monitor daily and long-term activity patterns. Changes and trends identified from such data can provide insights and guidance to the management of many chronic conditions that change over time. In this study we conducted a machine learning based analysis of longitudinal heart rate data collected over multiple years from Fitbit devices. We built a multi-resolutional pipeline for time series analysis, using model-free clustering methods inspired by statistical conformal prediction framework. With this method, we were able to detect health relevant events, their interesting patterns (e.g., daily routines, seasonal differences, and anomalies), and correlations to acute and chronic changes in health conditions. We present the results, lessons, and insights learned, and how to address the challenge of lack of labels. The study confirms the value of long-term heart rate data for health monitoring and surveillance, as complementary to extensive yet intermittent examinations by health care providers. 

Background: Outcome measures that are count variables with excessive zeros are common in health behaviors research. Examples include the number of standard drinks consumed or alcohol‐related problems experienced over time. There is a lack of empirical data about the relative performance of prevailing statistical models for assessing the efficacy of interventions when outcomes are zero‐inflated, particularly compared with recently developed marginalized count regression approaches for such data.Methods: The current simulation study examined five commonly used approaches for analyzing count outcomes, including two linear models (with outcomes on raw and log‐transformed scales, respectively) and three prevailing count distribution‐based models (ie, Poisson, negative binomial, and zero‐inflated Poisson (ZIP) models). We also considered the marginalized zero‐inflated Poisson (MZIP) model, a novel alternative that estimates the overall effects on the population mean while adjusting for zero‐inflation. Motivated by alcohol misuse prevention trials, extensive simulations were conducted to evaluate and compare the statistical power and Type I error rate of the statistical models and approaches across data conditions that varied in sample size ( to 500), zero rate (0.2 to 0.8), and intervention effect sizes.Results: Under zero‐inflation, the Poisson model failed to control the Type I error rate, resulting in higher than expected false positive results. When the intervention effects on the zero (vs. non‐zero) and count parts were in the same direction, the MZIP model had the highest statistical power, followed by the linear model with outcomes on the raw scale, negative binomial model, and ZIP model. The performance of the linear model with a log‐transformed outcome variable was unsatisfactory.Conclusions: The MZIP model demonstrated better statistical properties in detecting true intervention effects and controlling false positive results for zero‐inflated count outcomes. This MZIP model may serve as an appealing analytical approach to evaluating overall intervention effects in studies with count outcomes marked by excessive zeros. 

Active learning (AL) aims to improve model performance within a fixed labeling budget by choosing the most informative data points to label. Existing AL focuses on the single-domain setting, where all data come from the same domain (e.g., the same dataset). However, many real-world tasks often involve multiple domains. For example, in visual recognition, it is often desirable to train an image classifier that works across different environments (e.g., different backgrounds), where images from each environment constitute one domain. Such a multi-domain AL setting is challenging for prior methods because they (1) ignore the similarity among different domains when assigning labeling budget and (2) fail to handle distribution shift of data across different domains. In this paper, we propose the first general method, dubbed composite active learning (CAL), for multi-domain AL. Our approach explicitly considers the domain-level and instance-level information in the problem; CAL first assigns domain-level budgets according to domain-level importance, which is estimated by optimizing an upper error bound that we develop; with the domain-level budgets, CAL then leverages a certain instance-level query strategy to select samples to label from each domain. Our theoretical analysis shows that our method achieves a better error bound compared to current AL methods. Our empirical results demonstrate that our approach significantly outperforms the state-of-the-art AL methods on both synthetic and real-world multi-domain datasets. Code is available at https://github.com/Wang-ML-Lab/multi-domain-active-learning.