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Testing cross-sectional independence in panel data models is of fundamental importance in econometric analysis with high-dimensional panels. Recently, econometricians began to turn their attention to the problem in the presence of serial dependence. The existing procedure for testing cross-sectional independence with serial correlation is based on the sum of the sample cross-sectional correlations, which generally performs well when the alternative has dense cross-sectional correlations, but suffers from low power against sparse alternatives. To deal with sparse alternatives, we propose a test based on the maximum of the squared sample cross-sectional correlations. Furthermore, we propose a combined test to combine the p-values of the max based and sum based tests, which performs well under both dense and sparse alternatives. The combined test relies on the asymptotic independence of the max based and sum based test statistics, which we show rigorously. We show that the proposed max based and combined tests have attractive theoretical properties and demonstrate the superior performance via extensive simulation results. We apply the two new tests to analyze the weekly returns on the securities in the S\&P 500 index under the Fama-French three-factor model, and confirm the usefulness of the proposed combined test in detecting cross-sectional independence.

We present a novel computational model for the dynamics of alveolar recruitment/derecruitment (RD), which reproduces the underlying characteristics typically observed in injured lungs. The basic idea is a pressure- and time-dependent variation of the stress-free reference volume in reduced dimensional viscoelastic elements representing the acinar tissue. We choose a variable reference volume triggered by critical opening and closing pressures in a time-dependent manner from a straightforward mechanical point of view. In the case of (partially and progressively) collapsing alveolar structures, the volume available for expansion during breathing reduces and vice versa, eventually enabling consideration of alveolar collapse and reopening in our model. We further introduce a method for patient-specific determination of the underlying critical parameters of the new alveolar RD dynamics when integrated into the tissue elements, referred to as terminal units, of a spatially resolved physics-based lung model that simulates the human respiratory system in an anatomically correct manner. Relevant patient-specific parameters of the terminal units are herein determined based on medical image data and the macromechanical behavior of the lung during artificial ventilation. We test the whole modeling approach for a real-life scenario by applying it to the clinical data of a mechanically ventilated patient. The generated lung model is capable of reproducing clinical measurements such as tidal volume and pleural pressure during various ventilation maneuvers. We conclude that this new model is an important step toward personalized treatment of ARDS patients by considering potentially harmful mechanisms - such as cyclic RD and overdistension - and might help in the development of relevant protective ventilation strategies to reduce ventilator-induced lung injury (VILI).

Magnetic resonance imaging has evolved as a key component for prostate cancer (PCa) detection, substantially increasing the radiologist workload. Artificial intelligence (AI) systems can support radiological assessment by segmenting and classifying lesions in clinically significant (csPCa) and non-clinically significant (ncsPCa). Commonly, AI systems for PCa detection involve an automatic prostate segmentation followed by the lesion detection using the extracted prostate. However, evaluation reports are typically presented in terms of detection under the assumption of the availability of a highly accurate segmentation and an idealistic scenario, omitting the propagation of errors between modules. For that purpose, we evaluate the effect of two different segmentation networks (s1 and s2) with heterogeneous performances in the detection stage and compare it with an idealistic setting (s1:89.90+-2.23 vs 88.97+-3.06 ncsPCa, P<.001, 89.30+-4.07 and 88.12+-2.71 csPCa, P<.001). Our results depict the relevance of a holistic evaluation, accounting for all the sub-modules involved in the system.

Conventional neural network elastoplasticity models are often perceived as lacking interpretability. This paper introduces a two-step machine-learning approach that returns mathematical models interpretable by human experts. In particular, we introduce a surrogate model where yield surfaces are expressed in terms of a set of single-variable feature mappings obtained from supervised learning. A postprocessing step is then used to re-interpret the set of single-variable neural network mapping functions into mathematical form through symbolic regression. This divide-and-conquer approach provides several important advantages. First, it enables us to overcome the scaling issue of symbolic regression algorithms. From a practical perspective, it enhances the portability of learned models for partial differential equation solvers written in different programming languages. Finally, it enables us to have a concrete understanding of the attributes of the materials, such as convexity and symmetries of models, through automated derivations and reasoning. Numerical examples have been provided, along with an open-source code to enable third-party validation.

Accurately labeling biomedical data presents a challenge. Traditional semi-supervised learning methods often under-utilize available unlabeled data. To address this, we propose a novel reliability-based training data cleaning method employing inductive conformal prediction (ICP). This method capitalizes on a small set of accurately labeled training data and leverages ICP-calculated reliability metrics to rectify mislabeled data and outliers within vast quantities of noisy training data. The efficacy of the method is validated across three classification tasks within distinct modalities: filtering drug-induced-liver-injury (DILI) literature with title and abstract, predicting ICU admission of COVID-19 patients through CT radiomics and electronic health records, and subtyping breast cancer using RNA-sequencing data. Varying levels of noise to the training labels were introduced through label permutation. Results show significant enhancements in classification performance: accuracy enhancement in 86 out of 96 DILI experiments (up to 11.4%), AUROC and AUPRC enhancements in all 48 COVID-19 experiments (up to 23.8% and 69.8%), and accuracy and macro-average F1 score improvements in 47 out of 48 RNA-sequencing experiments (up to 74.6% and 89.0%). Our method offers the potential to substantially boost classification performance in multi-modal biomedical machine learning tasks. Importantly, it accomplishes this without necessitating an excessive volume of meticulously curated training data.

Tens of thousands of simultaneous hypothesis tests are routinely performed in genomic studies to identify differentially expressed genes. However, due to unmeasured confounders, many standard statistical approaches may be substantially biased. This paper investigates the large-scale hypothesis testing problem for multivariate generalized linear models in the presence of confounding effects. Under arbitrary confounding mechanisms, we propose a unified statistical estimation and inference framework that harnesses orthogonal structures and integrates linear projections into three key stages. It first leverages multivariate responses to separate marginal and uncorrelated confounding effects, recovering the confounding coefficients' column space. Subsequently, latent factors and primary effects are jointly estimated, utilizing $\ell_1$-regularization for sparsity while imposing orthogonality onto confounding coefficients. Finally, we incorporate projected and weighted bias-correction steps for hypothesis testing. Theoretically, we establish various effects' identification conditions and non-asymptotic error bounds. We show effective Type-I error control of asymptotic $z$-tests as sample and response sizes approach infinity. Numerical experiments demonstrate that the proposed method controls the false discovery rate by the Benjamini-Hochberg procedure and is more powerful than alternative methods. By comparing single-cell RNA-seq counts from two groups of samples, we demonstrate the suitability of adjusting confounding effects when significant covariates are absent from the model.

We propose reinforcement learning to control the dynamical self-assembly of the dodecagonal quasicrystal (DDQC) from patchy particles. The patchy particles have anisotropic interactions with other particles and form DDQC. However, their structures at steady states are significantly influenced by the kinetic pathways of their structural formation. We estimate the best policy of temperature control trained by the Q-learning method and demonstrate that we can generate DDQC with few defects using the estimated policy. The temperature schedule obtained by reinforcement learning can reproduce the desired structure more efficiently than the conventional pre-fixed temperature schedule, such as annealing. To clarify the success of the learning, we also analyse a simple model describing the kinetics of structural changes through the motion in a triple-well potential. We have found that reinforcement learning autonomously discovers the critical temperature at which structural fluctuations enhance the chance of forming a globally stable state. The estimated policy guides the system toward the critical temperature to assist the formation of DDQC.

While several previous studies have devised methods for segmentation of polyps, most of these methods are not rigorously assessed on multi-center datasets. Variability due to appearance of polyps from one center to another, difference in endoscopic instrument grades, and acquisition quality result in methods with good performance on in-distribution test data, and poor performance on out-of-distribution or underrepresented samples. Unfair models have serious implications and pose a critical challenge to clinical applications. We adapt an implicit bias mitigation method which leverages Bayesian epistemic uncertainties during training to encourage the model to focus on underrepresented sample regions. We demonstrate the potential of this approach to improve generalisability without sacrificing state-of-the-art performance on a challenging multi-center polyp segmentation dataset (PolypGen) with different centers and image modalities.

When students and users of statistical methods first learn about regression analysis there is an emphasis on the technical details of models and estimation methods that invariably runs ahead of the purposes for which these models might be used. More broadly, statistics is widely understood to provide a body of techniques for "modelling data", underpinned by what we describe as the "true model myth", according to which the task of the statistician/data analyst is to build a model that closely approximates the true data generating process. By way of our own historical examples and a brief review of mainstream clinical research journals, we describe how this perspective leads to a range of problems in the application of regression methods, including misguided "adjustment" for covariates, misinterpretation of regression coefficients and the widespread fitting of regression models without a clear purpose. We then outline an alternative approach to the teaching and application of regression methods, which begins by focussing on clear definition of the substantive research question within one of three distinct types: descriptive, predictive, or causal. The simple univariable regression model may be introduced as a tool for description, while the development and application of multivariable regression models should proceed differently according to the type of question. Regression methods will no doubt remain central to statistical practice as they provide a powerful tool for representing variation in a response or outcome variable as a function of "input" variables, but their conceptualisation and usage should follow from the purpose at hand.

Recent advances in 3D fully convolutional networks (FCN) have made it feasible to produce dense voxel-wise predictions of volumetric images. In this work, we show that a multi-class 3D FCN trained on manually labeled CT scans of several anatomical structures (ranging from the large organs to thin vessels) can achieve competitive segmentation results, while avoiding the need for handcrafting features or training class-specific models. To this end, we propose a two-stage, coarse-to-fine approach that will first use a 3D FCN to roughly define a candidate region, which will then be used as input to a second 3D FCN. This reduces the number of voxels the second FCN has to classify to ~10% and allows it to focus on more detailed segmentation of the organs and vessels. We utilize training and validation sets consisting of 331 clinical CT images and test our models on a completely unseen data collection acquired at a different hospital that includes 150 CT scans, targeting three anatomical organs (liver, spleen, and pancreas). In challenging organs such as the pancreas, our cascaded approach improves the mean Dice score from 68.5 to 82.2%, achieving the highest reported average score on this dataset. We compare with a 2D FCN method on a separate dataset of 240 CT scans with 18 classes and achieve a significantly higher performance in small organs and vessels. Furthermore, we explore fine-tuning our models to different datasets. Our experiments illustrate the promise and robustness of current 3D FCN based semantic segmentation of medical images, achieving state-of-the-art results. Our code and trained models are available for download: //github.com/holgerroth/3Dunet_abdomen_cascade.