We introduce the Gamma-Exponential Process (GEP), a prior over a large family of continuous time stochastic processes. A hierarchical version of this prior (HGEP; the Hierarchical GEP) yields a useful model for analyzing complex time series. Models based on HGEPs display many attractive properties: conjugacy, exchangeability and closed-form predictive distribution for the waiting times, and exact Gibbs updates for the time scale parameters. After establishing these properties, we show how posterior inference can be carried efficiently using Particle MCMC methods [1]. This yields a MCMC algorithm that can resample entire sequences atomically while avoiding the complications of introducing slice and stick auxiliary variables of the beam sampler [2]. We applied our model to the problem of estimating the disease progression in multiple sclerosis [3], and to RNA evolutionary modeling [4]. In both domains, we found that our model outperformed the standard rate matrix estimation approach.

Multiple Sclerosis (MS) is a chronic disease characterized by progressive or alternate impairment of neurological functions (motor, sensory, visual, and cognitive). Predicting disease progression with a probabilistic and time-dependent approach might help in suggesting interventions that can delay the progression of the disease. However, extracting informative knowledge from irregularly collected longitudinal data is difficult, and missing data pose significant challenges. MS progression is measured through the Expanded Disability Status Scale (EDSS), which quantifies and monitors disability in MS over time. EDSS assesses impairment in eight functional systems (FS). Frequently, only the EDSS score assigned by clinicians is reported, while FS sub-scores are missing. Imputing these scores might be useful, especially to stratify patients according to their phenotype assessed over the disease progression. This study aimed at i) exploring different methodologies for imputing missing FS sub-scores, and ii) predicting the EDSS score using complete clinical data. Results show that Exponential Weighted Moving Average achieved the lowest error rate in the missing data imputation task; furthermore, the combination of Classification and Regression Trees for the imputation and SVM for the prediction task obtained the best accuracy.

Clinician notes are a rich source of patient information but often contain inconsistencies due to varied writing styles, colloquialisms, abbreviations, medical jargon, grammatical errors, and non-standard formatting. These inconsistencies hinder the extraction of meaningful data from electronic health records (EHRs), posing challenges for quality improvement, population health, precision medicine, decision support, and research. We present a large language model approach to standardizing a corpus of 1,618 clinical notes. Standardization corrected an average of $4.9 +/- 1.8$ grammatical errors, $3.3 +/- 5.2$ spelling errors, converted $3.1 +/- 3.0$ non-standard terms to standard terminology, and expanded $15.8 +/- 9.1$ abbreviations and acronyms per note. Additionally, notes were re-organized into canonical sections with standardized headings. This process prepared notes for key concept extraction, mapping to medical ontologies, and conversion to interoperable data formats such as FHIR. Expert review of randomly sampled notes found no significant data loss after standardization. This proof-of-concept study demonstrates that standardization of clinical notes can improve their readability, consistency, and usability, while also facilitating their conversion into interoperable data formats.

Assessing lesions and tracking their progression over time in brain magnetic resonance (MR) images is essential for diagnosing and monitoring multiple sclerosis (MS). Machine learning models have shown promise in automating the segmentation of MS lesions. However, training these models typically requires large, well-annotated datasets. Unfortunately, MS imaging datasets are often limited in size, spread across multiple hospital sites, and exhibit different formats (such as cross-sectional or longitudinal) and annotation styles. This data diversity presents a significant obstacle to developing a unified model for MS lesion segmentation. To address this issue, we introduce SegHeD+, a novel segmentation model that can handle multiple datasets and tasks, accommodating heterogeneous input data and performing segmentation for all lesions, new lesions, and vanishing lesions. We integrate domain knowledge about MS lesions by incorporating longitudinal, anatomical, and volumetric constraints into the segmentation model. Additionally, we perform lesion-level data augmentation to enlarge the training set and further improve segmentation performance. SegHeD+ is evaluated on five MS datasets and demonstrates superior performance in segmenting all, new, and vanishing lesions, surpassing several state-of-the-art methods in the field.

Teri Garr, known for her work in "Young Frankenstein" and "Tootsie," died Tuesday in Los Angeles. Garr's publicist confirmed to The Associated Press that the comedian died of multiple sclerosis. She began her career in the entertainment industry as a background dancer in a number of Elvis Presley movies, and went on to earn an Academy Award nomination for her role as Sandy Lester in the 1982 Dustin Hoffman comedy, "Tootsie." Actress Teri Garr died Tuesday of multiple sclerosis. She was 79. (Getty Images) The daughter of Eddie Garr, a well-known vaudeville comedian and Phyllis Lind, one of the original Rockettes at New York's Radio City Music Hall, Garr seemed destined for show business.

We introduce LLMD, a large language model designed to analyze a patient's medical history based on their medical records. Along with domain knowledge, LLMD is trained on a large corpus of records collected over time and across facilities, as well as tasks and labels that make nuanced connections among them. This approach is critical to an accurate picture of patient health, and has distinctive advantages over models trained on knowledge alone, unlabeled records, structured EHR data, or records from a single health system. The recipe for LLMD continues pretraining a foundational model on both domain knowledge and the contents of millions of records. These span an average of 10 years of care and as many as 140 care sites per patient. LLMD is then instruction fine-tuned on structuring and abstraction tasks. The former jointly identify and normalize document metadata, provenance information, clinical named-entities, and ontology mappings, while the latter roll these into higher-level representations, such a continuous era of time a patient was on a medication. LLMD is deployed within a layered validation system that includes continual random audits and review by experts, e.g. based on uncertainty, disease-specific rules, or use-case. LLMD exhibits large gains over both more-powerful generalized models and domain-specific models. On medical knowledge benchmarks, LLMD-8B achieves state of the art accuracy on PubMedQA text responses, besting orders-of-magnitude larger models. On production tasks, we show that LLMD significantly outperforms all other models evaluated, and among alternatives, large general purpose LLMs like GPT-4o are more accurate than models emphasizing medical knowledge. We find strong evidence that accuracy on today's medical benchmarks is not the most significant factor when analyzing real-world patient data, an insight with implications for future medical LLMs.'

Clinnova, a collaborative initiative involving France, Germany, Switzerland, and Luxembourg, is dedicated to unlocking the power of precision medicine through data federation, standardization, and interoperability. This European Greater Region initiative seeks to create an interoperable European standard using artificial intelligence (AI) and data science to enhance healthcare outcomes and efficiency. Key components include multidisciplinary research centers, a federated biobanking strategy, a digital health innovation platform, and a federated AI strategy. It targets inflammatory bowel disease, rheumatoid diseases, and multiple sclerosis (MS), emphasizing data quality to develop AI algorithms for personalized treatment and translational research. The IHU Strasbourg (Institute of Minimal-invasive Surgery) has the lead in this initiative to develop the federated learning (FL) proof of concept (POC) that will serve as a foundation for advancing AI in healthcare. At its core, Clinnova-MS aims to enhance MS patient care by using FL to develop more accurate models that detect disease progression, guide interventions, and validate digital biomarkers across multiple sites. This technical report presents insights and key takeaways from the first cross-border federated POC on MS segmentation of MRI images within the Clinnova framework. While our work marks a significant milestone in advancing MS segmentation through cross-border collaboration, it also underscores the importance of addressing technical, logistical, and ethical considerations to realize the full potential of FL in healthcare settings.

Assessment of lesions and their longitudinal progression from brain magnetic resonance (MR) images plays a crucial role in diagnosing and monitoring multiple sclerosis (MS). Machine learning models have demonstrated a great potential for automated MS lesion segmentation. Training such models typically requires large-scale high-quality datasets that are consistently annotated. However, MS imaging datasets are often small, segregated across multiple sites, with different formats (cross-sectional or longitudinal), and diverse annotation styles. This poses a significant challenge to train a unified MS lesion segmentation model. To tackle this challenge, we present SegHeD, a novel multi-dataset multi-task segmentation model that can incorporate heterogeneous data as input and perform all-lesion, new-lesion, as well as vanishing-lesion segmentation. Furthermore, we account for domain knowledge about MS lesions, incorporating longitudinal, spatial, and volumetric constraints into the segmentation model. SegHeD is assessed on five MS datasets and achieves a high performance in all, new, and vanishing-lesion segmentation, outperforming several state-of-the-art methods in this field.

Accurate segmentation of Multiple Sclerosis (MS) lesions in longitudinal MRI scans is crucial for monitoring disease progression and treatment efficacy. Although changes across time are taken into account when assessing images in clinical practice, most existing deep learning methods treat scans from different timepoints separately. Among studies utilizing longitudinal images, a simple channel-wise concatenation is the primary albeit suboptimal method employed to integrate timepoints. We introduce a novel approach that explicitly incorporates temporal differences between baseline and follow-up scans through a unique architectural inductive bias called Difference Weighting Block. It merges features from two timepoints, emphasizing changes between scans. We achieve superior scores in lesion segmentation (Dice Score, Hausdorff distance) as well as lesion detection (lesion-level $F_1$ score) as compared to state-of-the-art longitudinal and single timepoint models across two datasets. Our code is made publicly available at www.github.com/MIC-DKFZ/Longitudinal-Difference-Weighting.

Personalized medicine based on medical images, including predicting future individualized clinical disease progression and treatment response, would have an enormous impact on healthcare and drug development, particularly for diseases (e.g. multiple sclerosis (MS)) with long term, complex, heterogeneous evolutions and no cure. In this work, we present the first stochastic causal temporal framework to model the continuous temporal evolution of disease progression via Neural Stochastic Differential Equations (NSDE). The proposed causal inference model takes as input the patient's high dimensional images (MRI) and tabular data, and predicts both factual and counterfactual progression trajectories on different treatments in latent space. The NSDE permits the estimation of high-confidence personalized trajectories and treatment effects. Extensive experiments were performed on a large, multi-centre, proprietary dataset of patient 3D MRI and clinical data acquired during several randomized clinical trials for MS treatments. Our results present the first successful uncertainty-based causal Deep Learning (DL) model to: (a) accurately predict future patient MS disability evolution (e.g. EDSS) and treatment effects leveraging baseline MRI, and (b) permit the discovery of subgroups of patients for which the model has high confidence in their response to treatment even in clinical trials which did not reach their clinical endpoints.