We investigate saddlepoint approximations applied to the score test statistic in genome-wide association studies with binary phenotypes. The inaccuracy in the normal approximation of the score test statistic increases with increasing sample imbalance and with decreasing minor allele count. Applying saddlepoint approximations to the score test statistic distribution greatly improve the accuracy, even far out in the tail of the distribution. By using exact results for an intercept model and binary covariate model, as well as simulations for models with nuisance parameters, we emphasize the need for continuity corrections in order to achieve valid $p$-values. The performance of the saddlepoint approximations is evaluated by overall and conditional type I error rate on simulated data. We investigate the methods further by using data from UK Biobank with skin and soft tissue infections as phenotype, using both common and rare variants. The analysis confirms that continuity correction is important particularly for rare variants, and that the normal approximation gives a highly inflated type I error rate for case imbalance.
Many reinforcement learning (RL) environments consist of independent entities that interact sparsely. In such environments, RL agents have only limited influence over other entities in any particular situation. Our idea in this work is that learning can be efficiently guided by knowing when and what the agent can influence with its actions. To achieve this, we introduce a measure of \emph{situation-dependent causal influence} based on conditional mutual information and show that it can reliably detect states of influence. We then propose several ways to integrate this measure into RL algorithms to improve exploration and off-policy learning. All modified algorithms show strong increases in data efficiency on robotic manipulation tasks.
Item response theory (IRT) is the statistical paradigm underlying a dominant family of generative probabilistic models for test responses, used to quantify traits in individuals relative to target populations. The graded response model (GRM) is a particular IRT model that is used for ordered polytomous test responses. Both the development and the application of the GRM and other IRT models require statistical decisions. For formulating these models (calibration), one needs to decide on methodologies for item selection, inference, and regularization. For applying these models (test scoring), one needs to make similar decisions, often prioritizing computational tractability and/or interpretability. In many applications, such as in the Work Disability Functional Assessment Battery (WD-FAB), tractability implies approximating an individual's score distribution using estimates of mean and variance, and obtaining that score conditional on only point estimates of the calibrated model. In this manuscript, we evaluate the calibration and scoring of models under this common use-case using Bayesian cross-validation. Applied to the WD-FAB responses collected for the National Institutes of Health, we assess the predictive power of implementations of the GRM based on their ability to yield, on validation sets of respondents, ability estimates that are most predictive of patterns of item responses. Our main finding indicates that regularized Bayesian calibration of the GRM outperforms the regularization-free empirical Bayesian procedure of marginal maximum likelihood. We also motivate the use of compactly supported priors in test scoring.
Lightning is a destructive and highly visible product of severe storms, yet there is still much to be learned about the conditions under which lightning is most likely to occur. The GOES-16 and GOES-17 satellites, launched in 2016 and 2018 by NOAA and NASA, collect a wealth of data regarding individual lightning strike occurrence and potentially related atmospheric variables. The acute nature and inherent spatial correlation in lightning data renders standard regression analyses inappropriate. Further, computational considerations are foregrounded by the desire to analyze the immense and rapidly increasing volume of lightning data. We present a new computationally feasible method that combines spectral and Laplace approximations in an EM algorithm, denoted SLEM, to fit the widely popular log-Gaussian Cox process model to large spatial point pattern datasets. In simulations, we find SLEM is competitive with contemporary techniques in terms of speed and accuracy. When applied to two lightning datasets, SLEM provides better out-of-sample prediction scores and quicker runtimes, suggesting its particular usefulness for analyzing lightning data, which tend to have sparse signals.
Defeaturing consists in simplifying geometrical models by removing the geometrical features that are considered not relevant for a given simulation. Feature removal and simplification of computer-aided design models enables faster simulations for engineering analysis problems, and simplifies the meshing problem that is otherwise often unfeasible. The effects of defeaturing on the analysis are then neglected and, as of today, there are basically very few strategies to quantitatively evaluate such an impact. Understanding well the effects of this process is an important step for automatic integration of design and analysis. We formalize the process of defeaturing by understanding its effect on the solution of Poisson equation defined on the geometrical model of interest containing a single feature, with Neumann boundary conditions on the feature itself. We derive an a posteriori estimator of the energy error between the solutions of the exact and the defeatured geometries in $\mathbb{R}^n$, $n\in\{2,3\}$, that is simple, reliable and efficient up to oscillations. The dependence of the estimator upon the size of the features is explicit.
Data from both a randomized trial and an observational study are sometimes simultaneously available for evaluating the effect of an intervention. The randomized data typically allows for reliable estimation of average treatment effects but may be limited in sample size and patient heterogeneity for estimating conditional average treatment effects for a broad range of patients. Estimates from the observational study can potentially compensate for these limitations, but there may be concerns about whether confounding and treatment effect heterogeneity have been adequately addressed. We propose an approach for combining conditional treatment effect estimators from each source such that it aggressively weights toward the randomized estimator when bias in the observational estimator is detected. This allows the combination to be consistent for a conditional causal effect, regardless of whether assumptions required for consistent estimation in the observational study are satisfied. When the bias is negligible, the estimators from each source are combined for optimal efficiency. We show the problem can be formulated as a penalized least squares problem and consider its asymptotic properties. Simulations demonstrate the robustness and efficiency of the method in finite samples, in scenarios with bias or no bias in the observational estimator. We illustrate the method by estimating the effects of hormone replacement therapy on the risk of developing coronary heart disease in data from the Women's Health Initiative.
Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces the covariate balance between the RCT and OS, therefore improving the trial-based estimator's generalizability. Exploiting semiparametric efficiency theory, we propose a doubly robust augmented calibration weighting estimator that achieves the efficiency bound derived under the identification assumptions. A nonparametric sieve method is provided as an alternative to the parametric approach, which enables the robust approximation of the nuisance functions and data-adaptive selection of outcome predictors for calibration. We establish asymptotic results and confirm the finite sample performances of the proposed estimators by simulation experiments and an application on the estimation of the treatment effect of adjuvant chemotherapy for early-stage non-small cell lung patients after surgery.
We aim to make inferences about a smooth, finite-dimensional parameter by fusing data from multiple sources together. Previous works have studied the estimation of a variety of parameters in similar data fusion settings, including in the estimation of the average treatment effect, optimal treatment rule, and average reward, with the majority of them merging one historical data source with covariates, actions, and rewards and one data source of the same covariates. In this work, we consider the general case where one or more data sources align with each part of the distribution of the target population, for example, the conditional distribution of the reward given actions and covariates. We describe potential gains in efficiency that can arise from fusing these data sources together in a single analysis, which we characterize by a reduction in the semiparametric efficiency bound. We also provide a general means to construct estimators that achieve these bounds. In numerical experiments, we show marked improvements in efficiency from using our proposed estimators rather than their natural alternatives. Finally, we illustrate the magnitude of efficiency gains that can be realized in vaccine immunogenicity studies by fusing data from two HIV vaccine trials.
Implicit probabilistic models are models defined naturally in terms of a sampling procedure and often induces a likelihood function that cannot be expressed explicitly. We develop a simple method for estimating parameters in implicit models that does not require knowledge of the form of the likelihood function or any derived quantities, but can be shown to be equivalent to maximizing likelihood under some conditions. Our result holds in the non-asymptotic parametric setting, where both the capacity of the model and the number of data examples are finite. We also demonstrate encouraging experimental results.
We demonstrate that many detection methods are designed to identify only a sufficently accurate bounding box, rather than the best available one. To address this issue we propose a simple and fast modification to the existing methods called Fitness NMS. This method is tested with the DeNet model and obtains a significantly improved MAP at greater localization accuracies without a loss in evaluation rate, and can be used in conjunction with Soft NMS for additional improvements. Next we derive a novel bounding box regression loss based on a set of IoU upper bounds that better matches the goal of IoU maximization while still providing good convergence properties. Following these novelties we investigate RoI clustering schemes for improving evaluation rates for the DeNet wide model variants and provide an analysis of localization performance at various input image dimensions. We obtain a MAP of 33.6%@79Hz and 41.8%@5Hz for MSCOCO and a Titan X (Maxwell). Source code available from: //github.com/lachlants/denet
Image segmentation is still an open problem especially when intensities of the interested objects are overlapped due to the presence of intensity inhomogeneity (also known as bias field). To segment images with intensity inhomogeneities, a bias correction embedded level set model is proposed where Inhomogeneities are Estimated by Orthogonal Primary Functions (IEOPF). In the proposed model, the smoothly varying bias is estimated by a linear combination of a given set of orthogonal primary functions. An inhomogeneous intensity clustering energy is then defined and membership functions of the clusters described by the level set function are introduced to rewrite the energy as a data term of the proposed model. Similar to popular level set methods, a regularization term and an arc length term are also included to regularize and smooth the level set function, respectively. The proposed model is then extended to multichannel and multiphase patterns to segment colourful images and images with multiple objects, respectively. It has been extensively tested on both synthetic and real images that are widely used in the literature and public BrainWeb and IBSR datasets. Experimental results and comparison with state-of-the-art methods demonstrate that advantages of the proposed model in terms of bias correction and segmentation accuracy.