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TRAPPIST-1 Habitable Atmosphere Intercomparison (THAI): motivations and protocol version 1.0

Upcoming telescopes such as the James Webb Space Telescope (JWST), the European Extremely Large Telescope (E-ELT), the Thirty Meter Telescope (TMT) or the Giant Magellan Telescope (GMT) may soon be able to characterize, through transmission, emission or reflection spectroscopy, the atmospheres of rocky exoplanets orbiting nearby M dwarfs. One of the most promising candidates is the late M-dwarf system TRAPPIST-1, which has seven known transiting planets for which transit timing variation (TTV) measurements suggest that they are terrestrial in nature, with a possible enrichment in volatiles. Among these seven planets, TRAPPIST-1e seems to be the most promising candidate to have habitable surface conditions, receiving ∼66 % of the Earth's incident radiation and thus needing only modest greenhouse gas inventories to raise surface temperatures to allow surface liquid water to exist. TRAPPIST-1e is, therefore, one of the prime targets for the JWST atmospheric characterization. In this context, the modeling of its potential atmosphere is an essential step prior to observation. Global climate models (GCMs) offer the most detailed way to simulate planetary atmospheres. However, intrinsic differences exist between GCMs which can lead to different climate prediction and thus observability of gas and/or cloud features in transmission and thermal emission spectra. Such differences should preferably be known prior to observations. In this paper we present a protocol to intercompare planetary GCMs. Four testing cases are considered for TRAPPIST-1e, but the methodology is applicable to other rocky exoplanets in the habitable zone. The four test cases included two land planets composed of modern-Earth and pure-CO2 atmospheres and two aqua planets with the same atmospheric compositions. Currently, there are four participating models (LMDG, ROCKE-3D, ExoCAM, UM); however, this protocol is intended to let other teams participate as well.

Thomas Jean Daniel Fauchez↗

A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm

Introduction: hERG block potency is widely used to calculate a drug's safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quantification of experimental variability. Since the new cardiac safety paradigm being discussed by the International Council for Harmonisation promotes a tighter integration of nonclinical and clinical data for torsadogenic risk assessment, a more systematic approach to estimate the hERG block potency and safety margin is needed. Methods: A cross-industry study was performed to collect hERG data on 28 drugs with known torsadogenic risk using a standardized experimental protocol. A Bayesian hierarchical modeling (BHM) approach was used to assess the hERG block potency of these drugs by quantifying both the inter-site and intra-site variability. A modeling and simulation study was also done to evaluate protocol-dependent changes in hERG potency estimates. Results: A systematic approach to estimate hERG block potency is established. The impact of choosing a safety margin threshold on torsadogenic risk evaluation is explored based on the posterior distributions of hERG potency estimated by this method. The modeling and simulation results suggest any potency estimate is specific to the protocol used. Discussion: This methodology can estimate hERG block potency specific to a given voltage protocol. The relationship between safety margin thresholds and torsadogenic risk predictivity suggests the threshold should be tailored to each specific context of use, and safety margin evaluation may need to be integrated with other information to form a more comprehensive risk assessment.

60 APPLIED LIFE SCIENCES↗

Countering Weapons of Mass Destruction Office (CWMD) Data Categorization Study: Chemical, Biological, Radiological, and Nuclear (CBRN) Detection Device Data

Pacific Northwest National Laboratory (PNNL) seeks to address critical questions related to chemical, biological, radiological, and nuclear (CBRN) detection devices. This research aims to enhance the security and understanding of these devices by investigating various aspects of their identification, communication, and functionality. The primary focus is on network security, malware detection, device identification, and intelligence gathering. CBRN data can be categorized in various ways depending on the purpose of CBRN detection devices and the specific context of the applications for analysis. Criteria that can be used to assist in this effort include but are not limited to data type, data protocol, source/destination, application, time, security, and content. This study will inform additional paths for data classification, data profiling, data mapping, and data modeling. This will help the Countering Weapons of Mass Destruction Office (CWMD) better understand their data and make informed decisions based on the insights gained from this study and their application. The CBRN Data Categorization study will include the identification of 5–10 different CBRN detection devices with unique characteristics for assessing and analyzing the data that is being produced by and transmitted from these devices.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗

The Agricultural Model Intercomparison and Improvement Project (AgMIP): Protocols and Pilot Studies

The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a major international effort linking the climate, crop, and economic modeling communities with cutting-edge information technology to produce improved crop and economic models and the next generation of climate impact projections for the agricultural sector. The goals of AgMIP are to improve substantially the characterization of world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Analyses of the agricultural impacts of climate variability and change require a transdisciplinary effort to consistently link state-of-the-art climate scenarios to crop and economic models. Crop model outputs are aggregated as inputs to regional and global economic models to determine regional vulnerabilities, changes in comparative advantage, price effects, and potential adaptation strategies in the agricultural sector. Climate, Crop Modeling, Economics, and Information Technology Team Protocols are presented to guide coordinated climate, crop modeling, economics, and information technology research activities around the world, along with AgMIP Cross-Cutting Themes that address uncertainty, aggregation and scaling, and the development of Representative Agricultural Pathways (RAPs) to enable testing of climate change adaptations in the context of other regional and global trends. The organization of research activities by geographic region and specific crops is described, along with project milestones. Pilot results demonstrate AgMIP's role in assessing climate impacts with explicit representation of uncertainties in climate scenarios and simulations using crop and economic models. An intercomparison of wheat model simulations near Obregón, Mexico reveals inter-model differences in yield sensitivity to [CO2] with model uncertainty holding approximately steady as concentrations rise, while uncertainty related to choice of crop model increases with rising temperatures. Wheat model simulations with midcentury climate scenarios project a slight decline in absolute yields that is more sensitive to selection of crop model than to global climate model, emissions scenario, or climate scenario downscaling method. A comparison of regional and national-scale economic simulations finds a large sensitivity of projected yield changes to the simulations' resolved scales. Finally, a global economic model intercomparison example demonstrates that improvements in the understanding of agriculture futures arise from integration of the range of uncertainty in crop, climate, and economic modeling results in multi-model assessments.

Rosenzweig, C.↗

Merged Observatory Data Files (MODFs): an integrated observational data product supporting process-oriented investigations and diagnostics

A large and ever-growing body of geophysical information is measured in campaigns and at specialized observatories as a part of scientific expeditions and experiments. These collections of observed data include many essential climate variables (as defined by the Global Climate Observing System) but are often distinguished by a wide range of additional non-routine measurements that are designed to not only document the state of the environment but also the drivers that contribute to that state. These field data are used not only to further understand environmental processes through observation-based studies but also to provide baseline data to test model performance and to codify understanding to improve predictive capabilities. To address the considerable barriers and difficulty in utilizing these diverse and complex data for observation–model research, the Merged Observatory Data File (MODF) concept has been developed. A MODF combines measurements from multiple instruments into a single file that complies with well-established data format and metadata practices and has been designed to parallel the development of corresponding Merged Model Data Files (MMDFs). Using the MODF and MMDF protocols will facilitate the evolution of model intercomparison projects into model intercomparison and improvement projects by putting observation and model data “on the same page” in a timely manner. The MODF concept was developed especially for weather forecast model studies in the Arctic. The surprisingly complex process of implementing MODFs in that context refined the concept itself. Thus, this article explains the concept of MODFs by providing details on the issues that were revealed and resolved during that first specific implementation. Detailed instructions are provided on how to make MODFs, and this article can be considered a MODF creation manual.

54 ENVIRONMENTAL SCIENCES↗

Model-Driven Test Generation of Distributed Systems

This report describes a novel test generation technique for distributed systems. Utilizing formal models and formal verification tools, spe cifically the Symbolic Analysis Laboratory (SAL) tool-suite from SRI, we present techniques to generate concurrent test vectors for distrib uted systems. These are initially explored within an informal test validation context and later extended to achieve full MC/DC coverage of the TTEthernet protocol operating within a system-centric context.

Easwaran, Arvind↗

MOSAIC-CONUS: A Multimodal, Multi-Temporally Paired Dataset for Earth Sciences

Earth embeddings—vector representations of geographic locations indexed in space and time—are emerging as a unifying interface for geospatial AI. However, their quality depends not only on model design, but on how multimodal Earth observation (EO) data are spatially indexed, temporally aligned, and cross-modally associated during pretraining. We introduce MOSAIC-CONUS (Multimodal Observations with Spatially Aligned Imagery, Urban Points of Interest, In-Situ Measurements and Text Captions), a large-scale EO dataset over the contiguous United States, organized around 250,000 stratified point indices that serve as stable spatial keys across seven modalities: active radar, passive optical imagery, lidar-derived elevation, land cover, functional context, hydrometeorological measurements, and textual summaries. Unlike existing EO datasets, MOSAIC-CONUS introduces four contributions not jointly addressed in prior work: 1. an open-source, large-scale multimodal EO corpus structured around point-indexed data designed to support Earth embedding learning; 2. explicit radar-optical pairing tables spanning twelve temporal alignment regimes, formalizing cross-sensor alignment as a controllable variable for analyzing how temporal mismatch across modalities influences learned embeddings quality; 3. a benchmark suite spanning cross-modal retrieval, annual nightlights regression, and basin-held-out streamflow prediction, positioning MOSAIC-CONUS as a benchmark-ready resource for multimodal AI systems; and 4. a language-based embedding layer through co-registered textual summaries, enabling Earth embeddings to function as a queryable interface for agentic AI systems. The dataset and pairing protocols are publicly released.

54 ENVIRONMENTAL SCIENCES↗

AI Model Benchmarking for Nonproliferation Applications: Steel Thread Benchmarking Task Force Technical Report (Rev. 2)

Steel Thread is a NA-22 venture that seeks to build trustworthy, reliable AI models that can be used in a wide variety of nonproliferation tasks. A key aspect of building these models is developing appropriate benchmarks and evaluation methods, which will enable the venture to identify and adapt models to provide the most value in the nonproliferation domain. Benchmarks must be relevant to key tasks in this domain, such as question answering, information retrieval, document summarization and classification, consensus analysis, and image and data analysis. This report 1) provides an overview of benchmark design, evaluation, and challenges; 2) reviews a variety of open benchmarks, with a focus on language models and tasks; and 3) identifies benchmarks that are most relevant to Steel Thread. This report is intended to serve as a basis for further efforts to classify and evaluate benchmarks and their correlation with success on nonproliferation-specific tasks. The Steel Thread venture has defined benchmarks to be a particular combination of a dataset (or datasets) and a metric (or metrics) conceptualized as representing one or more specific tasks or sets of abilities for a specific modality. It is adopted by a research community as a shared framework for comparing methods.1 It includes 1) Data: Labeled (a designated subset not used for training, which could be all the data), 2) Metric: A way to quantify performance, 3) Task/Ability: What the benchmark is testing, 4) Protocol: A structured and repeatable evaluation process, 5) Baseline/Reference Model: For comparison; could be statistical, rule-based, SME-derived, or another model, and 6) Maintenance Plan: to update with new information over time; important for long-term utility. For further clarity, the definition includes what a benchmark, in this context, is not. It is not a corpus of training data, specific to a model (it is intended to apply to a range of models), a universal evaluation of performance, a guarantee that the ‘top’ model on the leaderboard will be the best fit for every specific use case, an all-encompassing proof of a model’s universal quality, nor is it a one-size-fits-all measure of success. It does not cover every real-world constraint (like operational, ethical, or cost considerations), a systems integration test, or a unit test. This definition was inspired by and resulted from discussions within the Steel Thread Benchmarking Task Force. This group was formed to define what we would mean as a benchmark within Steel Thread but persisted as the need to develop a thorough understanding of the large and expanding existing benchmarking space. This technical report is a result of the group’s divide and conquer approach to exploring this space. The release of benchmarks might not be progressing as quickly as model development, but it is moving very fast, as many benchmarks quickly become saturated, when state-of-the-art models score so close to the benchmark’s ceiling that their results are virtually indistinguishable. At that point, the test no longer differentiates between new systems, so researchers usually stop reporting scores as the benchmark no longer informs about improvements from the next generation of models. In the OpenAI announcement of GPT-5, they reported results on six flagship public benchmarks (AIME 2025, SWE-bench Verified, Aider Polyglot, MMMU, HealthBench Hard, GPQA) but the full system-card covers roughly thirty-five separate evaluations, comprising hundreds of test task items in total. There have been some efforts to summarize benchmarks in specific fields, like for text-to-image generation, but these surveys have had a narrow methodology scope. Therefore, a comprehensive survey of all benchmarks or even all benchmarks that could be relevant to Steel Thread is outside of the scope of this report. We chose some specific benchmarks to investigate in detail.

97 MATHEMATICS AND COMPUTING↗

Quantum error mitigation by hidden inverses protocol in superconducting quantum devices

We present a method to improve the convergence of variational algorithms based on hidden inverses (HIs) to mitigate coherent errors. In the context of error mitigation, this means replacing the hardware implementation of certain Hermitian gates with their inverses. Doing so results in noise cancellation and a more resilient quantum circuit. This approach improves performance in a variety of two-qubit error models where the noise operator also inverts with the gate inversion. We apply the mitigation scheme on superconducting quantum processors running the variational quantum eigensolver (VQE) algorithm to find the H 2 ground-state energy. When implemented on superconducting hardware we find that the mitigation scheme effectively reduces the energy fluctuations in the parameter learning path in VQE, reducing the number of iterations for a converged value. We also provide a detailed numerical simulation of VQE performance under different noise models and explore how HIs and randomized compiling affect the underlying loss landscape of the learning problem. These simulations help explain our experimental hardware outcomes, helping to connect lower-level gate performance to application-specific behavior in contrast to metrics like fidelity which often do not provide an intuitive insight into observed high level performance.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Zero-day Attack Detection in Digital Substations Using In-Context Learning

In this paper, we address the critical challenge of detecting zero-day attacks in digital substations that employ the IEC-61850 communication protocol to ensure the security and reliability of modern power systems. While many heuristic and machine learning (ML)-based methods have been proposed for attack detection in IEC-61850 digital substations, generalization to unknown or zero-day attacks remains a challenge. We propose an approach that leverages the in-context learning ability of transformer architecture, which enables the model to learn from a few examples of a new task without explicit retraining. Our experiments on the IEC-61850 dataset demonstrate that the proposed method achieves more than 87% detection accuracy on zero-day attacks while the existing baselines fail. We believe this work has the potential to enhance the security of digital substations by enabling the effective detection of zero-day attacks.

LIu, Chen-Ching [Virginia Tech] (ORCID:00000002894↗

Marine Hydrogen Demonstration

This report summarizes Phase 1 of a project involving the design of a Floating Hydrogen Production and Dispensing Barge destined for the Port of San Francisco (SF). The H 2 Barge is designed to produce renewable H 2 at the rate of ~ 530 kg/day, storing 512 kg of hydrogen at 517-bar, allowing fast refueling of hydrogen fuel cell vessels and land-side hydrogen delivery trailers for distribution into the nascent SF hydrogen ecosystem. The broader considerations that impacted the H2 Barge design are also described. An account is given of a new review process formulated by the United States Coast Guard (USCG) to review this first-of-its-kind maritime implementation of hydrogen technology. The immediate goals of the H 2 Barge Project are to 1) demonstrate the feasibility, viability and methods of hydrogen production, storage and fueling in a maritime context, 2) help shape (where needed) and navigate the required local, state and federal regulatory gauntlet and 3) catalyze a “green hydrogen ecosystem” (both marine and landside) with locally produced renewable hydrogen at the San Francisco waterfront. A summary is also given of the modeling and experimental activity of Phase 1 directed to the development of science-based refueling protocols for large marine Type IV 250-bar hydrogen tanks. Combined modeling and experimental studies are reported of the filling of large (28 kg) 250-bar Type IV hydrogen tanks of the type being deployed on early hydrogen ferries, such as the MV Sea Change. The primary question was to determine how such tanks can be successfully filled (state of charge greater than 97%) within 45 minutes without exceeding the 82 °C temperature limit historically set for such tanks. The studies show that a gas injector is needed avoid thermal stratification during filling which can result in potential hot spots. Pre-cooling of the hydrogen was found to be essential in most cases, as ambient conditions greatly affect the need for a pre-cooling to achieve the 45-minute fill time. Pre-cooling cannot be supplied by nearby water, such as that found in nature (bays, lakes, rivers, etc.) because pre-cooling cooling below 0 °C was found to be necessary to avoid excessive compression heating. The experimental results afforded a calibration of the engineering model (SOFIL) for these large 250-bar tanks, which now enables using SOFIL to predict volume-averaged hydrogen filling temperatures to an accuracy of +/- 2.7°C for these tanks. The model can therefore be used to evaluate potential scenarios for development of a standardized fueling methodology for ferries utilizing large Type-IV tanks of the type examined here.

08 HYDROGEN↗

Evolution of the Lunar Receiving Laboratory to the Astromaterial Sample Curation Facility: Technical Tensions Between Containment and Cleanliness, Between Particulate and Organic Cleanliness

The Lunar Receiving Laboratory (LRL) was planned and constructed in the 1960s to support the Apollo program in the context of landing on the Moon and safely returning humans. The enduring science return from that effort is a result of careful curation of planetary materials. Technical decisions for the first facility included sample handling environment (vacuum vs inert gas), and instruments for making basic sample assessment, but the most difficult decision, and most visible, was stringent biosafety vs ultra-clean sample handling. Biosafety required handling of samples in negative pressure gloveboxes and rooms for containment and use of sterilizing protocols and animal/plant models for hazard assessment. Ultra-clean sample handling worked best in positive pressure nitrogen environment gloveboxes in positive pressure rooms, using cleanable tools of tightly controlled composition. The requirements for these two objectives were so different, that the solution was to design and build a new facility for specific purpose of preserving the scientific integrity of the samples. The resulting Lunar Curatorial Facility was designed and constructed, from 1972-1979, with advice and oversight by a very active committee comprised of lunar sample scientists. The high precision analyses required for planetary science are enabled by stringent contamination control of trace elements in the materials and protocols of construction (e.g., trace element screening for paint and flooring materials) and the equipment used in sample handling and storage. As other astromaterials, especially small particles and atoms, were added to the collections curated, the technical tension between particulate cleanliness and organic cleanliness was addressed in more detail. Techniques for minimizing particulate contamination in sample handling environments use high efficiency air filtering techniques typically requiring organic sealants which offgas. Protocols for reducing adventitious carbon on sample handling surfaces often generate particles. Further work is needed to achieve both minimal particulate and adventitious carbon contamination. This paper will discuss these facility topics and others in the historical context of nearly 50 years' curation experience for lunar rocks and regolith, meteorites, cosmic dust, comet particles, solar wind atoms, and asteroid particles at Johnson Space Center.

Allton, J. H.↗

Selective Amnesia using Contrastive Subnet Erasure for Class Level Unlearning in Vision Models

We study concept-level forgetting in pretrained vision models: removing an entire semantic category so the system no longer recognizes that object in unseen images and contexts, rather than merely forgetting specific training examples. Prior work either applies blunt global projections or fine-tunes parameters, which can introduce collateral damage to unrelated features, add compute, and become unstable as forgetting strength increases. We introduce Contrastive Subnet Erasure (CSE), a training-free, encoder-centric edit that targets a compact set of channels most responsible for the class and attenuates them in a calibrated manner. The modification is algebraically folded into the subsequent layer, yielding no inference-time overhead and leaving task heads unchanged. To evaluate whether forgetting generalizes beyond the data used to specify the class, we introduce a cross dataset protocol in which the class is defined on a source dataset and performance is measured on a disjoint target dataset drawn from a different distribution with no shared images. This setup tests whether the model still fails to recognize the object when it looks different or appears in new scenes, and it helps avoid overfitting to patterns in the source dataset. Across CIFAR 10, CIFAR 100, and ImageNet under this protocol, CSE achieves stronger forgetting of the target class while better preserving non target utility than existing baselines in both single class and multi class settings. Overall, CSE provides a simple, stable, and deployment-ready mechanism for class-level unlearning in vision.

Kotevska, Olivera [ORNL] (ORCID:0000000316772243)↗

Harnessing land-atmosphere interactions to enhance subseasonal-to-seasonal predictability

2025 Advancing Understanding of Land-Atmosphere Interactions and Processes on S2S Predictability Workshop What: 227 registered workshop participants gathered in person (43%) and online (57%) to discuss state-of-the-art scientific understanding and modeling of land-atmosphere interactions and related processes in the context of subseasonal-to-seasonal (S2S) predictability. Topics covered sources of S2S predictability, land model initialization methods, model diagnosis and evaluation metrics, AI/ML analysis and applications, and coordination of future community multi-model S2S forecast focused experiments. To advance the science, this community workshop, organized by NSF NCAR, NOAA, NASA, and DOE, aimed to 1) identify process- and application-oriented metrics for assessing S2S prediction skill and 2) develop experimental protocols for coordinated experiments to isolate, quantify, and understand the role of land-atmosphere interactions in S2S predictability. When: June 16-18, 2025 Where: Boulder, CO, USA, and online.

Land-Atmosphere Interaction↗

A Survey Protocol to Assess Meaningfulness and Usefulness of Automated Topic Finding in the NASA Aviation Safety Reporting System

Context: The NASA Aviation Safety Reporting System (ASRS) is a voluntary confidential aviation safety reporting system. The ASRS receives reports from pilots, air traffic controllers, flight attendants and other involved in aviation operations. The reports are de-identified and coded by ASRS expert safety analysts and a short descriptive synopsis is written to describe the safety issue. The de-identified reports are then disseminated to the aviation community in a number of ways including entry into an online database, Safety Alert Bulletins and For Your Information Notices, and the CALLBACK newsletter. Key to these publications are the timely processing (de-identification, coding and summarization) of new reports, which is currently done by ASRS expert safety analysts. Thus, we believe topic modelling could decrease effort in ASRS, if topics are comprehensible. Aim: We propose a methodology to evaluate whether automated topic finding using topic modelling provides meaningful and useful topics. Method: We extend the total error survey methodology to evaluate user topic comprehension of machine learning outputs. To accomplish this we performed a literature review to identify existing methods and define a construct for topic comprehension, utilizing existing ASRS synopsis writing practices to more precisely define meaningfulness and usefulness. Results: A survey protocol was created that addresses the limitations of other survey protocols found in the literature review, which we found lacking in rationale and clear protocol definition. Conclusion: The surveying of user understanding in machine learning outputs presents challenges due to the explosion of parameters to control for and the lack of systematic approach presented in the literature. More reproducible work and survey protocols are needed in the literature and our work is one step towards that direction.

topic finding↗

The Integrated Medical Model: Statistical Forecasting of Risks to Crew Health and Mission Success

The Integrated Medical Model (IMM) helps capture and use organizational knowledge across the space medicine, training, operations, engineering, and research domains. The IMM uses this domain knowledge in the context of a mission and crew profile to forecast crew health and mission success risks. The IMM is most helpful in comparing the risk of two or more mission profiles, not as a tool for predicting absolute risk. The process of building the IMM adheres to Probability Risk Assessment (PRA) techniques described in NASA Procedural Requirement (NPR) 8705.5, and uses current evidence-based information to establish a defensible position for making decisions that help ensure crew health and mission success. The IMM quantitatively describes the following input parameters: 1) medical conditions and likelihood, 2) mission duration, 3) vehicle environment, 4) crew attributes (e.g. age, sex), 5) crew activities (e.g. EVA's, Lunar excursions), 6) diagnosis and treatment protocols (e.g. medical equipment, consumables pharmaceuticals), and 7) Crew Medical Officer (CMO) training effectiveness. It is worth reiterating that the IMM uses the data sets above as inputs. Many other risk management efforts stop at determining only likelihood. The IMM is unique in that it models not only likelihood, but risk mitigations, as well as subsequent clinical outcomes based on those mitigations. Once the mathematical relationships among the above parameters are established, the IMM uses a Monte Carlo simulation technique (a random sampling of the inputs as described by their statistical distribution) to determine the probable outcomes. Because the IMM is a stochastic model (i.e. the input parameters are represented by various statistical distributions depending on the data type), when the mission is simulated 10-50,000 times with a given set of medical capabilities (risk mitigations), a prediction of the most probable outcomes can be generated. For each mission, the IMM tracks which conditions occurred and decrements the pharmaceuticals and supplies required to diagnose and treat these medical conditions. If supplies are depleted, then the medical condition goes untreated, and crew and mission risk increase. The IMM currently models approximately 30 medical conditions. By the end of FY2008, the IMM will be modeling over 100 medical conditions, approximately 60 of which have been recorded to have occurred during short and long space missions.

Fitts, M. A.↗

Tissue scale agent-based simulation of premalignant progressions in Barrett’s esophagus

Barrett’s esophagus (BE) is a benign condition of the distal esophagus that initiates a multistage pathway to esophageal adenocarcinoma (EAC). Short of frequent intrusive (and costly) surveillance, effective screening for neoplasia in BE populations is yet to be established since progressors are rare and virtually undetectable without routine biopsies, which often sample only a small portion of the BE tissue. As a result, reliable estimation of the true prevalence of dysplasia in a BE population and evidence-based optimization of screening for at-risk individuals is challenging. Data-driven microsimulations, i.e., model-generated instances of disease history in a predefined virtual population, have found utility in the EAC screening literature as low-overhead alternatives to real-world hypothesis testing of optimal interventions for dysplasia. Despite the successes, computational limitations, paucity of knowledge and data on Barrett’s dysplasia, and the complexities of disease progression as a multiscale multiphysics process have hindered the treatment of disease progression in BE as a spatial process. Agent-based modeling of nucleation and proliferation processes in dysplasia warrants exploration in this context as an approximation that operates at a trade-off between computational tractability and precise representation of the composition and physics of the substrate (tissue). In this study, we describe spatially resolved simulations of premalignant progression toward EAC in a coarse-grained model of Barrett’s tissue that resolves the metaplastic tissue at a length scale of 0.42 mm (~3300 crypts/mm 2 ). Finally, the model is calibrated to reproduce historical high-grade dysplasia prevalence when model-generated patients are screened using the Seattle protocol.

59 BASIC BIOLOGICAL SCIENCES↗