Towards Foundation Models for Critical Care Time Series

Notable progress has been made in generalist medical large language models across various healthcare areas. However, large-scale modeling of in-hospital time series data - such as vital signs, lab results, and treatments in critical care - remains underexplored. Existing datasets are relatively small, but combining them can enhance patient diversity and improve model robustness. To effectively utilize these combined datasets for large-scale modeling, it is essential to address the distribution shifts caused by varying treatment policies, necessitating the harmonization of treatment variables across the different datasets. This work aims to establish a foundation for training large-scale multi-variate time series models on critical care data and to provide a benchmark for machine learning models in transfer learning across hospitals to study and address distribution shift challenges. We introduce a harmonized dataset for sequence modeling and transfer learning research, representing the first large-scale collection to include core treatment variables. Future plans involve expanding this dataset to support further advancements in transfer learning and the development of scalable, generalizable models for critical healthcare applications.

Generalizable Single-Source Cross-modality Medical Image Segmentation via Invariant Causal Mechanisms

Single-source domain generalization (SDG) aims to learn a model from a single source domain that can generalize well on unseen target domains. This is an important task in computer vision, particularly relevant to medical imaging where domain shifts are common. In this work, we consider a challenging yet practical setting: SDG for cross-modality medical image segmentation. We combine causality-inspired theoretical insights on learning domain-invariant representations with recent advancements in diffusion-based augmentation to improve generalization across diverse imaging modalities. Guided by the ``intervention-augmentation equivariant'' principle, we use controlled diffusion models (DMs) to simulate diverse imaging styles while preserving the content, leveraging rich generative priors in large-scale pretrained DMs to comprehensively perturb the multidimensional style variable. Extensive experiments on challenging cross-modality segmentation tasks demonstrate that our approach consistently outperforms state-of-the-art SDG methods across three distinct anatomies and imaging modalities. The source code is available at \href{https://github.com/ratschlab/ICMSeg}{https://github.com/ratschlab/ICMSeg}.

Uncertainty-Penalized Direct Preference Optimization

Aligning Large Language Models (LLMs) to human preferences in content, style, and presentation is challenging, in part because preferences are varied, context-dependent, and sometimes inherently ambiguous. While successful, Reinforcement Learning from Human Feedback (RLHF) and Direct Preference Optimization (DPO) are prone to the issue of proxy reward overoptimization. Analysis of the DPO loss reveals a critical need for regularization for mislabeled or ambiguous preference pairs to avoid reward hacking. In this work, we develop a pessimistic framework for DPO by introducing preference uncertainty penalization schemes, inspired by offline reinforcement learning. The penalization serves as a correction to the loss which attenuates the loss gradient for uncertain samples. Evaluation of the methods is performed with GPT2 Medium on the Anthropic-HH dataset using a model ensemble to obtain uncertainty estimates, and shows improved overall performance compared to vanilla DPO, as well as better completions on prompts from high-uncertainty chosen/rejected responses.

Towards Dynamic Feature Acquisition on Medical Time Series by Maximizing Conditional Mutual Information

Knowing which features of a multivariate time series to measure and when is a key task in medicine, wearables, and robotics. Better acquisition policies can reduce costs while maintaining or even improving the performance of downstream predictors. Inspired by the maximization of conditional mutual information, we propose an approach to train acquirers end-to-end using only the downstream loss. We show that our method outperforms random acquisition policy, matches a model with an unrestrained budget, but does not yet overtake a static acquisition strategy. We highlight the assumptions and outline avenues for future work.

Preference Elicitation for Offline Reinforcement Learning

Applying reinforcement learning (RL) to real-world problems is often made challenging by the inability to interact with the environment and the difficulty of designing reward functions. Offline RL addresses the first challenge by considering access to an offline dataset of environment interactions labeled by the reward function. In contrast, Preference-based RL does not assume access to the reward function and learns it from preferences, but typically requires an online interaction with the environment. We bridge the gap between these frameworks by exploring efficient methods for acquiring preference feedback in a fully offline setup. We propose Sim-OPRL, an offline preference-based reinforcement learning algorithm, which leverages a learned environment model to elicit preference feedback on simulated rollouts. Drawing on insights from both the offline RL and the preference-based RL literature, our algorithm employs a pessimistic approach for out-of-distribution data, and an optimistic approach for acquiring informative preferences about the optimal policy. We provide theoretical guarantees regarding the sample complexity of our approach, dependent on how well the offline data covers the optimal policy. Finally, we demonstrate the empirical performance of Sim-OPRL in different environments.

Multi-Modal Contrastive Learning for Online Clinical Time-Series Applications

Electronic Health Record (EHR) datasets from Intensive Care Units (ICU) contain a diverse set of data modalities. While prior works have successfully leveraged multiple modalities in supervised settings, we apply advanced self-supervised multi-modal contrastive learning techniques to ICU data, specifically focusing on clinical notes and time-series for clinically relevant online prediction tasks. We introduce a loss function Multi-Modal Neighborhood Contrastive Loss (MM-NCL), a soft neighborhood function, and showcase the excellent linear probe and zero-shot performance of our approach.

Dynamic Survival Analysis for Early Event Prediction

This study advances Early Event Prediction (EEP) in healthcare through Dynamic Survival Analysis (DSA), offering a novel approach by integrating risk localization into alarm policies to enhance clinical event metrics. By adapting and evaluating DSA models against traditional EEP benchmarks, our research demonstrates their ability to match EEP models on a time-step level and significantly improve event-level metrics through a new alarm prioritization scheme (up to 11% AuPRC difference). This approach represents a significant step forward in predictive healthcare, providing a more nuanced and actionable framework for early event prediction and management.

Learning Genomic Sequence Representations using Graph Neural Networks over De Bruijn Graphs

The rapid expansion of genomic sequence data calls for new methods to achieve robust sequence representations. Existing techniques often neglect intricate structural details, emphasizing mainly contextual information. To address this, we developed k-mer embeddings that merge contextual and structural string information by enhancing De Bruijn graphs with structural similarity connections. Subsequently, we crafted a self-supervised method based on Contrastive Learning that employs a heterogeneous Graph Convolutional Network encoder and constructs positive pairs based on node similarities. Our embeddings consistently outperform prior techniques for Edit Distance Approximation and Closest String Retrieval tasks.

On the Importance of Step-wise Embeddings for Heterogeneous Clinical Time-Series

Recent advances in deep learning architectures for sequence modeling have not fully transferred to tasks handling time-series from electronic health records. In particular, in problems related to the Intensive Care Unit (ICU), the state-of-the-art remains to tackle sequence classification in a tabular manner with tree-based methods. Recent findings in deep learning for tabular data are now surpassing these classical methods by better handling the severe heterogeneity of data input features. Given the similar level of feature heterogeneity exhibited by ICU time-series and motivated by these findings, we explore these novel methods' impact on clinical sequence modeling tasks. By jointly using such advances in deep learning for tabular data, our primary objective is to underscore the importance of step-wise embeddings in time-series modeling, which remain unexplored in machine learning methods for clinical data. On a variety of clinically relevant tasks from two large-scale ICU datasets, MIMIC-III and HiRID, our work provides an exhaustive analysis of state-of-the-art methods for tabular time-series as time-step embedding models, showing overall performance improvement. In particular, we evidence the importance of feature grouping in clinical time-series, with significant performance gains when considering features within predefined semantic groups in the step-wise embedding module.

Knowledge Graph Representations to enhance Intensive Care Time-Series Predictions

Intensive Care Units (ICU) require comprehensive patient data integration for enhanced clinical outcome predictions, crucial for assessing patient conditions. Recent deep learning advances have utilized patient time series data, and fusion models have incorporated unstructured clinical reports, improving predictive performance. However, integrating established medical knowledge into these models has not yet been explored. The medical domain's data, rich in structural relationships, can be harnessed through knowledge graphs derived from clinical ontologies like the Unified Medical Language System (UMLS) for better predictions. Our proposed methodology integrates this knowledge with ICU data, improving clinical decision modeling. It combines graph representations with vital signs and clinical reports, enhancing performance, especially when data is missing. Additionally, our model includes an interpretability component to understand how knowledge graph nodes affect predictions.