Medium-horizon Alzheimer's disease progression prediction is difficult because future clinical scores can remain tied to baseline severity, while biomarker histories are irregular and incompletely observed. We develop an anchor-based analysis of 24-month Clinical Dementia Rating Sum of Boxes (CDR-SB) change using harmonized Alzheimer's Disease Neuroimaging Initiative (ADNI) tables. Each labeled sample is anchored at a mild cognitive impairment visit, uses only clinical and biomarker history observed at or before that anchor, and defines the response as CDR-SB at the future visit closest to 24 months within an 18--30 month window minus anchor CDR-SB. The analytic cohort contains 2,600 labeled anchors from 858 participants and 7,276 longitudinal rows. We propose a residual gap-aware transformer that combines a mixed-effects statistical reference with transformer-based residual learning from pre-anchor clinical and biomarker histories. The model uses participant-level random intercepts in the mixed-effects reference, observation-level triplet tokenization for irregular histories, and a learned nonnegative time-gap penalty inside self-attention. We compare the proposed model with a Bayesian-information-criterion-selected linear mixed-effects baseline, GRU-D, and STraTS under repeated participant-level train--test splits. Across five participant-level random seeds, the proposed model achieves the best mean test performance across all reported metrics, reducing MSE by 13.1% and increasing prediction--observation correlation by 26.4% relative to the mixed-effects baseline. It also improves over both GRU-D and STraTS in mean error and correlation. These results show that statistical anchoring and gap-aware residual learning provide a useful structure for medium-horizon Alzheimer's disease progression prediction.

Single-arm trials are an important study design for evaluating drug efficacy and safety without enrolling patients into a control arm. Although they do not provide the gold-standard evidence of randomized controlled trials, they are increasingly used in clinical development as they offer an efficient, ethical, and practical alternative. A wide variety of approaches can be used to construct control comparators and estimate treatment effects, from fixed comparators informed by clinical knowledge to data-based and model-based patient-level comparators, also known as synthetic controls. Powerful and flexible machine learning models can allow outcome-model-based synthetic controls to overcome key limitations of direct data-based approaches, yield more robust estimates of treatment effects, and provide a principled way to incorporate corrections or encode additional assumptions when external data are not directly comparable. In this work, we argue that outcome-model-based synthetic control arms are an important tool for single-arm trials. We focus on digital twins, personalized predictions of disease progression generated from machine learning models trained on historical datasets, which naturally leverage these flexible approaches. We review doubly robust estimators, present power and sample size formulas, and discuss trade-offs in selecting historical data for training and analysis. We also outline practical considerations for deploying digital twins within the framework of recent FDA draft guidance on the use of artificial intelligence in drug development. Finally, we reanalyze data from trials in amyotrophic lateral sclerosis and Huntington's disease to demonstrate the proposed methods.

Diffusion models are often trained in low-dimensional latent spaces, which are then reused for related but shifted datasets. In this work, we study when such latent reuse remains reliable under distribution shift. We consider a source-target setting in which both datasets are approximately low-dimensional but may lie near different subspaces. We show that freezing and reusing a source latent space induces a target-domain score error governed by two quantities: the principal-angle misalignment between the source and target subspaces, and the target ambient noise amplified by the diffusion time scale. Motivated by these limits, we further study mixed source-target training and characterize how the required shared latent dimension depends on the relative geometry of the two distributions. Our results provide theoretical guidance on when latent reuse is reliable and when learning a shared representation may be necessary.

Neural Information Processing Systems http://nips.cc/

Neural Information Processing Systems http://nips.cc/

In this paper, we study online convex optimization in dynamic environments, and aim to bound the dynamic regret with respect to any sequence of comparators. Existing work have shown that online gradient descent enjoys an $O(\sqrt{T}(1+P_T))$ dynamic regret, where $T$ is the number of iterations and $P_T$ is the path-length of the comparator sequence. However, this result is unsatisfactory, as there exists a large gap from the $\Omega(\sqrt{T(1+P_T)})$ lower bound established in our paper. To address this limitation, we develop a novel online method, namely adaptive learning for dynamic environment (Ader), which achieves an optimal $O(\sqrt{T(1+P_T)})$ dynamic regret. The basic idea is to maintain a set of experts, each attaining an optimal dynamic regret for a specific path-length, and combines them with an expert-tracking algorithm. Furthermore, we propose an improved Ader based on the surrogate loss, and in this way the number of gradient evaluations per round is reduced from $O(\log T)$ to $1$. Finally, we extend Ader to the setting that a sequence of dynamical models is available to characterize the comparators.

Nonstationarity is prevalent in sequential decision making, which poses a critical challenge to the vast majority of existing approaches developed offline.

InIRsystems, theretrievermodule directly influences theperformance ofdownstream tasks, such as retrieval-augmented generation [20, 29, 30] and knowledge-intensive question answering [34, 52]. However, these methods do not explicitly consider targeted optimization for tool usage or the impact on complex multi-stage tasks.

We study timestamped question answering over educational lecture videos under a single-GPU latency/memory budget. Given a natural-language query, the system retrieves relevant timestamped segments and synthesizes a grounded answer. We present CourseTimeQA (52.3 h, 902 queries across six courses) and a lightweight, latency-constrained cross-modal retriever (CrossFusion-RAG) that combines frozen encoders, a learned 512->768 vision projection, shallow query-agnostic cross-attention over ASR and frames with a temporal-consistency regularizer, and a small cross-attentive reranker. On CourseTimeQA, CrossFusion-RAG improves nDCG@10 by 0.10 and MRR by 0.08 over a strong BLIP-2 retriever while achieving approximately 1.55 s median end-to-end latency on a single A100. Closest comparators (zero-shot CLIP multi-frame pooling; CLIP + cross-encoder reranker + MMR; learned late-fusion gating; text-only hybrid with cross-encoder reranking and its MMR variant; caption-augmented text retrieval; non-learned temporal smoothing) are evaluated under matched hardware and indexing. We report robustness across ASR noise (WER quartiles), diagnostics for temporal localization, and full training/tuning details to support reproducible comparison.