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Dynamic treatment regimes (DTRs) formalize medical decision-making as a sequence of rules for different stages, mapping patient-level information to recommended treatments. In practice, estimating an optimal DTR using observational data from electronic medical record (EMR) databases can be complicated by covariates that are missing not at random (MNAR) due to informative monitoring of patients. Since complete case analysis can result in consistent estimation of outcome model parameters under the assumption of outcome-independent missingness \citep{Yang_Wang_Ding_2019}, Q-learning is a natural approach to accommodating MNAR covariates. However, the backward induction algorithm used in Q-learning can introduce complications, as MNAR covariates at later stages can result in MNAR pseudo-outcomes at earlier stages, leading to suboptimal DTRs, even if outcome variables are fully observed. To address this unique missing data problem in DTR settings, we propose two weighted Q-learning approaches where inverse probability weights for missingness of the pseudo-outcomes are obtained through estimating equations with valid nonresponse instrumental variables or sensitivity analysis. Asymptotic properties of the weighted Q-learning estimators are derived and the finite-sample performance of the proposed methods is evaluated and compared with alternative methods through extensive simulation studies. Using EMR data from the Medical Information Mart for Intensive Care database, we apply the proposed methods to investigate the optimal fluid strategy for sepsis patients in intensive care units.

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Adversarial training is a widely used method to improve the robustness of deep neural networks (DNNs) over adversarial perturbations. However, it is empirically observed that adversarial training on over-parameterized networks often suffers from the \textit{robust overfitting}: it can achieve almost zero adversarial training error while the robust generalization performance is not promising. In this paper, we provide a theoretical understanding of the question of whether overfitted DNNs in adversarial training can generalize from an approximation viewpoint. Specifically, our main results are summarized into three folds: i) For classification, we prove by construction the existence of infinitely many adversarial training classifiers on over-parameterized DNNs that obtain arbitrarily small adversarial training error (overfitting), whereas achieving good robust generalization error under certain conditions concerning the data quality, well separated, and perturbation level. ii) Linear over-parameterization (meaning that the number of parameters is only slightly larger than the sample size) is enough to ensure such existence if the target function is smooth enough. iii) For regression, our results demonstrate that there also exist infinitely many overfitted DNNs with linear over-parameterization in adversarial training that can achieve almost optimal rates of convergence for the standard generalization error. Overall, our analysis points out that robust overfitting can be avoided but the required model capacity will depend on the smoothness of the target function, while a robust generalization gap is inevitable. We hope our analysis will give a better understanding of the mathematical foundations of robustness in DNNs from an approximation view.

Network meta-analysis combines aggregate data (AgD) from multiple randomised controlled trials, assuming that any effect modifiers are balanced across populations. Individual patient data (IPD) meta-regression is the "gold standard" method to relax this assumption, however IPD are frequently only available in a subset of studies. Multilevel network meta-regression (ML-NMR) extends IPD meta-regression to incorporate AgD studies whilst avoiding aggregation bias, but currently requires the aggregate-level likelihood to have a known closed form. Notably, this prevents application to time-to-event outcomes. We extend ML-NMR to individual-level likelihoods of any form, by integrating the individual-level likelihood function over the AgD covariate distributions to obtain the respective marginal likelihood contributions. We illustrate with two examples of time-to-event outcomes, showing the performance of ML-NMR in a simulated comparison with little loss of precision from a full IPD analysis, and demonstrating flexible modelling of baseline hazards using cubic M-splines with synthetic data on newly diagnosed multiple myeloma. ML-NMR is a general method for synthesising individual and aggregate level data in networks of all sizes. Extension to general likelihoods, including for survival outcomes, greatly increases the applicability of the method. R and Stan code is provided, and the methods are implemented in the multinma R package.

Deep learning (DL) is gaining popularity as a parameter estimation method for quantitative MRI. A range of competing implementations have been proposed, relying on either supervised or self-supervised learning. Self-supervised approaches, sometimes referred to as unsupervised, have been loosely based on auto-encoders, whereas supervised methods have, to date, been trained on groundtruth labels. These two learning paradigms have been shown to have distinct strengths. Notably, self-supervised approaches have offered lower-bias parameter estimates than their supervised alternatives. This result is counterintuitive - incorporating prior knowledge with supervised labels should, in theory, lead to improved accuracy. In this work, we show that this apparent limitation of supervised approaches stems from the naive choice of groundtruth training labels. By training on labels which are deliberately not groundtruth, we show that the low-bias parameter estimation previously associated with self-supervised methods can be replicated - and improved on - within a supervised learning framework. This approach sets the stage for a single, unifying, deep learning parameter estimation framework, based on supervised learning, where trade-offs between bias and variance are made by careful adjustment of training label.

During the diagnostic process, doctors incorporate multimodal information including imaging and the medical history - and similarly medical AI development has increasingly become multimodal. In this paper we tackle a more subtle challenge: doctors take a targeted medical history to obtain only the most pertinent pieces of information; how do we enable AI to do the same? We develop a wrapper method named MINT (Make your model INTeractive) that automatically determines what pieces of information are most valuable at each step, and ask for only the most useful information. We demonstrate the efficacy of MINT wrapping a skin disease prediction model, where multiple images and a set of optional answers to $25$ standard metadata questions (i.e., structured medical history) are used by a multi-modal deep network to provide a differential diagnosis. We show that MINT can identify whether metadata inputs are needed and if so, which question to ask next. We also demonstrate that when collecting multiple images, MINT can identify if an additional image would be beneficial, and if so, which type of image to capture. We showed that MINT reduces the number of metadata and image inputs needed by 82% and 36.2% respectively, while maintaining predictive performance. Using real-world AI dermatology system data, we show that needing fewer inputs can retain users that may otherwise fail to complete the system submission and drop off without a diagnosis. Qualitative examples show MINT can closely mimic the step-by-step decision making process of a clinical workflow and how this is different for straight forward cases versus more difficult, ambiguous cases. Finally we demonstrate how MINT is robust to different underlying multi-model classifiers and can be easily adapted to user requirements without significant model re-training.

In this work some advances in the theory of curvature of two-dimensional probability manifolds corresponding to families of distributions are proposed. It is proved that location-scale distributions are hyperbolic in the Information Geometry sense even when the generatrix is non-even or non-smooth. A novel formula is obtained for the computation of curvature in the case of exponential families: this formula implies some new flatness criteria in dimension 2. Finally, it is observed that many two parameter distributions, widely used in applications, are locally hyperbolic, which highlights the role of hyperbolic geometry in the study of commonly employed probability manifolds. These results have benefited from the use of explainable computational tools, which can substantially boost scientific productivity.

Methods for estimating heterogeneous treatment effects (HTE) from observational data have largely focused on continuous or binary outcomes, with less attention paid to survival outcomes and almost none to settings with competing risks. In this work, we develop censoring unbiased transformations (CUTs) for survival outcomes both with and without competing risks.After converting time-to-event outcomes using these CUTs, direct application of HTE learners for continuous outcomes yields consistent estimates of heterogeneous cumulative incidence effects, total effects, and separable direct effects. Our CUTs enable application of a much larger set of state of the art HTE learners for censored outcomes than had previously been available, especially in competing risks settings. We provide generic model-free learner-specific oracle inequalities bounding the finite-sample excess risk. The oracle efficiency results depend on the oracle selector and estimated nuisance functions from all steps involved in the transformation. We demonstrate the empirical performance of the proposed methods in simulation studies.

Large-scale language-vision pre-training models, such as CLIP, have achieved remarkable text-guided image morphing results by leveraging several unconditional generative models. However, existing CLIP-guided image morphing methods encounter difficulties when morphing photorealistic images. Specifically, existing guidance fails to provide detailed explanations of the morphing regions within the image, leading to misguidance. In this paper, we observed that such misguidance could be effectively mitigated by simply using a proper regularization loss. Our approach comprises two key components: 1) a geodesic cosine similarity loss that minimizes inter-modality features (i.e., image and text) on a projected subspace of CLIP space, and 2) a latent regularization loss that minimizes intra-modality features (i.e., image and image) on the image manifold. By replacing the na\"ive directional CLIP loss in a drop-in replacement manner, our method achieves superior morphing results on both images and videos for various benchmarks, including CLIP-inversion.

Medical image representations can be learned through medical vision-language contrastive learning (mVLCL) where medical imaging reports are used as weak supervision through image-text alignment. These learned image representations can be transferred to and benefit various downstream medical vision tasks such as disease classification and segmentation. Recent mVLCL methods attempt to align image sub-regions and the report keywords as local-matchings. However, these methods aggregate all local-matchings via simple pooling operations while ignoring the inherent relations between them. These methods therefore fail to reason between local-matchings that are semantically related, e.g., local-matchings that correspond to the disease word and the location word (semantic-relations), and also fail to differentiate such clinically important local-matchings from others that correspond to less meaningful words, e.g., conjunction words (importance-relations). Hence, we propose a mVLCL method that models the inter-matching relations between local-matchings via a relation-enhanced contrastive learning framework (RECLF). In RECLF, we introduce a semantic-relation reasoning module (SRM) and an importance-relation reasoning module (IRM) to enable more fine-grained report supervision for image representation learning. We evaluated our method using four public benchmark datasets on four downstream tasks, including segmentation, zero-shot classification, supervised classification, and cross-modal retrieval. Our results demonstrated the superiority of our RECLF over the state-of-the-art mVLCL methods with consistent improvements across single-modal and cross-modal tasks. These results suggest that our RECLF, by modelling the inter-matching relations, can learn improved medical image representations with better generalization capabilities.

Human cognition operates on a "Global-first" cognitive mechanism, prioritizing information processing based on coarse-grained details. This mechanism inherently possesses an adaptive multi-granularity description capacity, resulting in computational traits such as efficiency, robustness, and interpretability. The analysis pattern reliance on the finest granularity and single-granularity makes most existing computational methods less efficient, robust, and interpretable, which is an important reason for the current lack of interpretability in neural networks. Multi-granularity granular-ball computing employs granular-balls of varying sizes to daptively represent and envelop the sample space, facilitating learning based on these granular-balls. Given that the number of coarse-grained "granular-balls" is fewer than sample points, granular-ball computing proves more efficient. Moreover, the inherent coarse-grained nature of granular-balls reduces susceptibility to fine-grained sample disturbances, enhancing robustness. The multi-granularity construct of granular-balls generates topological structures and coarse-grained descriptions, naturally augmenting interpretability. Granular-ball computing has successfully ventured into diverse AI domains, fostering the development of innovative theoretical methods, including granular-ball classifiers, clustering techniques, neural networks, rough sets, and evolutionary computing. This has notably ameliorated the efficiency, noise robustness, and interpretability of traditional methods. Overall, granular-ball computing is a rare and innovative theoretical approach in AI that can adaptively and simultaneously enhance efficiency, robustness, and interpretability. This article delves into the main application landscapes for granular-ball computing, aiming to equip future researchers with references and insights to refine and expand this promising theory.

Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.

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