Covariate-adjusted response-adaptive randomization (CARA) designs are gaining increasing attention. These designs combine the advantages of randomized experiments with the ability to adaptively revise treatment allocations based on data collected across multiple stages, enhancing estimation efficiency. Yet, CARA designs often assume that primary outcomes are immediately observable, which is not the case in many clinical scenarios where there is a delay in observing primary outcomes. This assumption can lead to significant missingness and inefficient estimation of treatment effects. To tackle this practical challenge, we propose a CARA experimental strategy integrating delayed primary outcomes with immediately observed surrogate outcomes.

Time series data are ubiquitous across a wide range of real-world domains. While real-world time series analysis (TSA) requires human experts to integrate numerical series data with multimodal domain-specific knowledge, most existing TSA models rely solely on numerical data, overlooking the significance of information beyond numerical series. This oversight is due to the untapped potential of textual series data and the absence of a comprehensive, high-quality multimodal dataset. To overcome this obstacle, we introduce Time-MMD, the first multi-domain, multimodal time series dataset covering 9 primary data domains. Time-MMD ensures fine-grained modality alignment, eliminates data contamination, and provides high usability. Additionally, we develop MM-TSFlib, the first-cut multimodal time-series forecasting (TSF) library, seamlessly pipelining multimodal TSF evaluations based on Time-MMD for in-depth analyses. Extensive experiments conducted on Time-MMD through MM-TSFlib demonstrate significant performance enhancements by extending unimodal TSF to multimodality, evidenced by over 15% mean squared error reduction in general, and up to 40% in domains with rich textual data. More importantly, our datasets and library revolutionize broader applications, impacts, research topics to advance TSA.

Covariate-adjusted response-adaptive randomization (CARA) designs are gaining increasing attention. These designs combine the advantages of randomized experiments with the ability to adaptively revise treatment allocations based on data collected across multiple stages, enhancing estimation efficiency. Yet, CARA designs often assume that primary outcomes are immediately observable, which is not the case in many clinical scenarios where there is a delay in observing primary outcomes. This assumption can lead to significant missingness and inefficient estimation of treatment effects. To tackle this practical challenge, we propose a CARA experimental strategy integrating delayed primary outcomes with immediately observed surrogate outcomes.

General practitioners (GPs) serve as the cornerstone of primary healthcare systems by providing continuous and comprehensive medical services. However, due to community-oriented nature of their practice, uneven training and resource gaps, the clinical proficiency among GPs can vary significantly across regions and healthcare settings. Currently, Large Language Models (LLMs) have demonstrated great potential in clinical and medical applications, making them a promising tool for supporting general practice. However, most existing benchmarks and evaluation frameworks focus on exam-style assessments-typically multiple-choice question-lack comprehensive assessment sets that accurately mirror the real-world scenarios encountered by GPs. To evaluate how effectively LLMs can make decisions in the daily work of GPs, we designed GPBench, which consists of both test questions from clinical practice and a novel evaluation framework. The test set includes multiple-choice questions that assess fundamental knowledge of general practice, as well as realistic, scenario-based problems. All questions are meticulously annotated by experts, incorporating rich fine-grained information related to clinical management. The proposed LLM evaluation framework is based on the competency model for general practice, providing a comprehensive methodology for assessing LLM performance in real-world settings. As the first large-model evaluation set targeting GP decision-making scenarios, GPBench allows us to evaluate current mainstream LLMs. Expert assessment and evaluation reveal that in areas such as disease staging, complication recognition, treatment detail, and medication usage, these models exhibit at least ten major shortcomings. Overall, existing LLMs are not yet suitable for independent use in real-world GP working scenarios without human oversight.

Agent-based modeling is indispensable for studying complex systems across many domains. However, existing simulation platforms exhibit two major issues: performance and modularity. Low performance prevents simulations with a large number of agents, increases development time, limits parameter exploration, and raises computing costs. Inflexible software designs motivate modelers to create their own tools, diverting valuable resources. This dissertation introduces a novel simulation platform called BioDynaMo and its significant improvement, TeraAgent, to alleviate these challenges via three major works. First, we lay the platform's foundation by defining abstractions, establishing software infrastructure, and implementing a multitude of features for agent-based modeling. We demonstrate BioDynaMo's modularity through use cases in neuroscience, epidemiology, and oncology. We validate these models and show the simplicity of adding new functionality with few lines of code. Second, we perform a rigorous performance analysis and identify challenges for shared-memory parallelism. Provided solutions include an optimized grid for neighbor searching, mechanisms to reduce the memory access latency, and exploiting domain knowledge to omit unnecessary work. These improvements yield up to three orders of magnitude speedups, enabling simulations of 1.7 billion agents on a single server. Third, we present TeraAgent, a distributed simulation engine that allows scaling out the computation of one simulation to multiple servers. We identify and address server communication bottlenecks and implement solutions for serialization and delta encoding to accelerate and reduce data transfer. TeraAgent can simulate 500 billion agents and scales to 84096 CPU cores. BioDynaMo has been widely adopted, including a prize-winning radiotherapy simulation recognized as a top 10 breakthrough in physics in 2024.

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.

Large Action Models (LAMs) have revolutionized intelligent automation, but their application in healthcare faces challenges due to privacy concerns, latency, and dependency on internet access. This report introduces an ondevice, multi-agent healthcare assistant that overcomes these limitations. The system utilizes smaller, task-specific agents to optimize resources, ensure scalability and high performance. Our proposed system acts as a one-stop solution for health care needs with features like appointment booking, health monitoring, medication reminders, and daily health reporting. Powered by the Qwen Code Instruct 2.5 7B model, the Planner and Caller Agents achieve an average RougeL score of 85.5 for planning and 96.5 for calling for our tasks while being lightweight for on-device deployment. This innovative approach combines the benefits of ondevice systems with multi-agent architectures, paving the way for user-centric healthcare solutions.