Joint Treatment Effect Estimation from Incomplete Healthcare Data: Temporal Causal Normalizing Flows with LLM-driven Evolutionary MNAR Imputation

Target trial emulation (TTE) enables causal questions to be studied with observational data when randomized controlled trials (RCTs) are infeasible. Yet treatment-effect methods often address causal estimation, missingness, and temporal structure separately, limiting their robustness in electronic health records (EHRs), where time-varying confounding and missing-not-at-random (MNAR) biomarkers can reach 50%--80%. We propose a two-stage pipeline for treatment effect estimation from incomplete longitudinal EHRs. First, CausalFlow-T, a directed acyclic graph (DAG)-constrained normalizing flow with long short-term memory (LSTM)-encoded patient history, performs exact invertible counterfactual inference, avoiding approximation errors from variational inference and separating confounding through explicit causal structure. Ablations on four synthetic and one semi-synthetic benchmark with known counterfactuals show that DAG constraints and exact inference address distinct failure modes: neither compensates for the other. Second, because CausalFlow-T requires completed inputs, we introduce an LLM-driven evolutionary imputer that proposes executable imputation operators rather than individual entries, and evaluate it with three large language model (LLM) backends, including two open-source models. Across 30%--80% MNAR missingness, this imputer achieves the best pooled rank over biomarker and causal metrics, leading in point-wise accuracy and temporal extrapolation while preserving average treatment effect (ATE) recovery as statistical baselines degrade. On Swiss primary-care EHRs from adults with type 2 diabetes initiating a GLP-1 receptor agonist or SGLT-2 inhibitor, the pipeline estimates a per-protocol weight-loss difference of -0.98 kg [95% CI -1.01, -0.96] favoring GLP-1 receptor agonists, consistent with randomized evidence and obtained from realistically incomplete real-world EHRs.

Large Language Models for Physics Instrument Design

We study the use of large language models (LLMs) for physics instrument design and compare their performance to reinforcement learning (RL). Using only prompting, LLMs are given task constraints and summaries of prior high-scoring designs and propose complete detector configurations, which we evaluate with the same simulators and reward functions used in RL-based optimization. Although RL yields stronger final designs, we find that modern LLMs consistently generate valid, resource-aware, and physically meaningful configurations that draw on broad pretrained knowledge of detector design principles and particle--matter interactions, despite having no task-specific training. Based on this result, as a first step toward hybrid design workflows, we explore pairing the LLMs with a dedicated trust region optimizer, serving as a precursor to future pipelines in which LLMs propose and structure design hypotheses while RL performs reward-driven optimization. Based on these experiments, we argue that LLMs are well suited as meta-planners: they can design and orchestrate RL-based optimization studies, define search strategies, and coordinate multiple interacting components within a unified workflow. In doing so, they point toward automated, closed-loop instrument design in which much of the human effort required to structure and supervise optimization can be reduced.

Physics Instrument Design with Reinforcement Learning

We present a case for the use of Reinforcement Learning (RL) for the design of physics instrument as an alternative to gradient-based instrument-optimization methods. It's applicability is demonstrated using two empirical studies. One is longitudinal segmentation of calorimeters and the second is both transverse segmentation as well longitudinal placement of trackers in a spectrometer. Based on these experiments, we propose an alternative approach that offers unique advantages over differentiable programming and surrogate-based differentiable design optimization methods. First, Reinforcement Learning (RL) algorithms possess inherent exploratory capabilities, which help mitigate the risk of convergence to local optima. Second, this approach eliminates the necessity of constraining the design to a predefined detector model with fixed parameters. Instead, it allows for the flexible placement of a variable number of detector components and facilitates discrete decision-making. We then discuss the road map of how this idea can be extended into designing very complex instruments. The presented study sets the stage for a novel framework in physics instrument design, offering a scalable and efficient framework that can be pivotal for future projects such as the Future Circular Collider (FCC), where most optimized detectors are essential for exploring physics at unprecedented energy scales.