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Integrated Medical Model Verification, Validation, and Credibility

The Integrated Medical Model (IMM) was designed to forecast relative changes for a specified set of crew health and mission success risk metrics by using a probabilistic (stochastic process) model based on historical data, cohort data, and subject matter expert opinion. A probabilistic approach is taken since exact (deterministic) results would not appropriately reflect the uncertainty in the IMM inputs. Once the IMM was conceptualized, a plan was needed to rigorously assess input information, framework and code, and output results of the IMM, and ensure that end user requests and requirements were considered during all stages of model development and implementation. METHODS: In 2008, the IMM team developed a comprehensive verification and validation (VV) plan, which specified internal and external review criteria encompassing 1) verification of data and IMM structure to ensure proper implementation of the IMM, 2) several validation techniques to confirm that the simulation capability of the IMM appropriately represents occurrences and consequences of medical conditions during space missions, and 3) credibility processes to develop user confidence in the information derived from the IMM. When the NASA-STD-7009 (7009) was published, the IMM team updated their verification, validation, and credibility (VVC) project plan to meet 7009 requirements and include 7009 tools in reporting VVC status of the IMM. RESULTS: IMM VVC updates are compiled recurrently and include 7009 Compliance and Credibility matrices, IMM VV Plan status, and a synopsis of any changes or updates to the IMM during the reporting period. Reporting tools have evolved over the lifetime of the IMM project to better communicate VVC status. This has included refining original 7009 methodology with augmentation from the NASA-STD-7009 Guidance Document. End user requests and requirements are being satisfied as evidenced by ISS Program acceptance of IMM risk forecasts, transition to an operational model and simulation tool, and completion of service requests from a broad end user consortium including Operations, Science and Technology Planning, and Exploration Planning. CONCLUSIONS: The VVC approach established by the IMM project of combining the IMM VV Plan with 7009 requirements is comprehensive and includes the involvement of end users at every stage in IMM evolution. Methods and techniques used to quantify the VVC status of the IMM have not only received approval from the local NASA community but have also garnered recognition by other federal agencies seeking to develop similar guidelines in the medical modeling community.

Validation↗

Integrated Medical Model (IMM) Project Verification, Validation, and Credibility (VVandC)

The Integrated Medical Model (IMM) Project supports end user requests by employing the Integrated Medical Evidence Database (iMED) and IMM tools as well as subject matter expertise within the Project. The iMED houses data used by the IMM. The IMM is designed to forecast relative changes for a specified set of crew health and mission success risk metrics by using a probabilistic model based on historical data, cohort data, and subject matter expert opinion. A stochastic approach is taken because deterministic results would not appropriately reflect the uncertainty in the IMM inputs. Once the IMM was conceptualized, a plan was needed to rigorously assess input information, framework and code, and output results of the IMM, and ensure that end user requests and requirements were considered during all stages of model development and implementation, as well as lay the foundation for external review and application. METHODS: In 2008, the Project team developed a comprehensive verification and validation (VV) plan, which specified internal and external review criteria encompassing 1) verification of data and IMM structure to ensure proper implementation of the IMM, 2) several validation techniques to confirm that the simulation capability of the IMM appropriately represents occurrences and consequences of medical conditions during space missions, and 3) credibility processes to develop user confidence in the information derived from the IMM. When the NASA-STD-7009 (7009) [1] was published, the Project team updated their verification, validation, and credibility (VVC) project plan to meet 7009 requirements and include 7009 tools in reporting VVC status of the IMM. Construction of these tools included meeting documentation and evidence requirements sufficient to meet external review success criteria. RESULTS: IMM Project VVC updates are compiled recurrently and include updates to the 7009 Compliance and Credibility matrices. Reporting tools have evolved over the lifetime of the IMM Project to better communicate VVC status. This has included refining original 7009 methodology with augmentation from the HRP NASA-STD-7009 Guidance Document working group and the NASA-HDBK-7009 [2]. End user requests and requirements are being satisfied as evidenced by ISS Program acceptance of IMM risk forecasts, transition to an operational model and simulation tool, and completion of service requests from a broad end user consortium including operations, science and technology planning, and exploration planning. IMM v4.0 is slated for operational release in the FY015 and current VVC assessments illustrate the expected VVC status prior to the completion of customer lead external review efforts. CONCLUSIONS: The VVC approach established by the IMM Project of incorporating Project-specific recommended practices and guidelines for implementing the 7009 requirements is comprehensive and includes the involvement of end users at every stage in IMM evolution. Methods and techniques used to quantify the VVC status of the IMM Project represented a critical communication tool in providing clear and concise suitability assessments to IMM customers. These processes have not only received approval from the local NASA community but have also garnered recognition by other federal agencies seeking to develop similar guidelines in the medical modeling community.

Walton, M.↗

Direct Signal-to-Noise Quality Comparison between an Electronic and Conventional Stethoscope aboard the International Space Station

Introduction: Evaluation of heart, lung, and bowel sounds is routinely performed with the use of a stethoscope to help detect a broad range of medical conditions. Stethoscope acquired information is even more valuable in a resource limited environments such as the International Space Station (ISS) where additional testing is not available. The high ambient noise level aboard the ISS poses a specific challenge to auscultation by stethoscope. An electronic stethoscope's ambient noise‐reduction, greater sound amplification, recording capabilities, and sound visualization software may be an advantage to a conventional stethoscope in this environment. Methods: A single operator rated signal‐to‐noise quality from a conventional stethoscope (Littman 2218BE) and an electronic stethoscope (Litmann 3200). Borborygmi, pulmonic, and cardiac sound quality was ranked with both stethoscopes. Signal‐to‐noise rankings were preformed on a 1 to 10 subjective scale with 1 being inaudible, 6 the expected quality in an emergency department, 8 the expected quality in a clinic, and 10 the clearest possible quality. Testing took place in the Japanese Pressurized Module (JPM), Unity (Node 2), Destiny (US Lab), Tranquility (Node 3), and the Cupola of the International Space Station. All examinations were conducted at a single point in time. Results: The electronic stethoscope's performance ranked higher than the conventional stethoscope for each body sound in all modules tested. The electronic stethoscope's sound quality was rated between 7 and 10 in all modules tested. In comparison, the traditional stethoscope's sound quality was rated between 4 and 7. The signal to noise ratio of borborygmi showed the biggest difference between stethoscopes. In the modules tested, the auscultation of borborygmi was rated between 5 and 7 by the conventional stethoscope and consistently 10 by the electronic stethoscope. Discussion: This stethoscope comparison was limited to a single operator. However, we believe the results are noteworthy. The electronic stethoscope out preformed the traditional stethoscope in each direct comparison. Consideration should be made to incorporate an electronic stethoscope into current and future space vehicle medical kits.

Marshburn, Thomas↗

Ride-hailing and taxi versus walking: Long term forecasts and implications from large-scale behavioral data

Introduction: Although ride-hailing and taxi trips can potentially reduce single-occupant vehicle trips and auto ownership, they can also replace pedestrian trips. Because physical activity is associated with improved health outcomes, the extent to which ride-hailing and taxi travel captures walking's mode share is of interest to policymakers. Methods: Based on large-scale behavioral data from the 2017 U.S. National Household Travel Survey, this paper reports on the development of a full Bayesian logistic regression model for determining the mode split between (1) ride-hailing and taxi and (2) walk while accounting for unobserved heterogeneity. The results from the stand-alone model inform two longer-term travel forecasting scenarios: a) higher risk of walk trips converting to ride-hailing and taxi, specifically in the future with high prevalence of automated vehicles, b) higher probability of such trips remaining as walking. Results: The results revealed that some of the important characteristics that increase the likelihood of a traveler using the ride-hailing and taxi mode versus walking include having a longer trip, using a smartphone to access the internet, having an interest in technologies, having a medical condition, and living in a metropolitan area with rail access. Further, the results from the first scenario suggest that an overall increase of up to 2.9% in the ride-hailing and taxi mode share may be expected. The second scenario shows that between 68% and 76% of ride-hailing and taxi trips could be diverted to walking if supportive pedestrian infrastructure were provided in the case study locations. The planning process can be adapted to consider not only congestion, crash, and emissions impacts of such shifts but also the effects of a loss of physical activity. Conclusions: The study findings show how the ride-hailing and taxi mode competes with walking. Further, the findings enable planners to update their regional travel forecasting models; policy makers can thus encourage active travel by prioritizing pedestrian infrastructure investments that may divert ride-hailing and taxi trips to walking. However, equity should be a key consideration to ensure that addressing the competition between these two modal choices does not hinder the provision of pedestrian facilities in communities that depend on walking.

99 GENERAL AND MISCELLANEOUS↗

Breath analysis by ultra-sensitive broadband laser spectroscopy detects SARS-CoV-2 infection

Rapid testing is essential to fighting pandemics such as coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exhaled human breath contains multiple volatile molecules providing powerful potential for non-invasive diagnosis of diverse medical conditions. We investigated breath detection of SARS-CoV-2 infection using cavity-enhanced direct frequency comb spectroscopy (CE-DFCS), a state-of-the-art laser spectroscopic technique capable of a real-time massive collection of broadband molecular absorption features at ro-vibrational quantum state resolution and at parts-per-trillion volume detection sensitivity. Using a total of 170 individual breath samples (83 positive and 87 negative with SARS-CoV-2 based on reverse transcription polymerase chain reaction tests), we report excellent discrimination capability for SARS-CoV-2 infection with an area under the receiver-operating-characteristics curve of 0.849(4). Our results support the development of CE-DFCS as an alternative, rapid, non-invasive test for COVID-19 and highlight its remarkable potential for optical diagnoses of diverse biological conditions and disease states.

60 APPLIED LIFE SCIENCES↗

Methods to Track Effective Doses from Airborne Radioactive Emissions for Compliance with 40 CFR 61, SUBPART H

US Department of Energy national laboratories can play an integral role in not only the advancement of science but also in the treatment of various medical conditions through research and development activities conducted at radioisotope production facilities. Here, a project has been underway at Oak Ridge National Laboratory since 2016 whose mission is to produce and supply the radioisotope 227 Ac, which is used in a radiopharmaceutical developed to treat certain types of prostate cancer and bone metastases. Production activities result in the environmental release of airborne radioactive emissions, which are governed by Clean Air Act regulations described in 40 CFR Part 61, Subpart H. Stack 3039, the source that emits radioactive effluents from 227 Ac production, is subject to additional requirements outlined in American National Standards Institute (ANSI) N13.1-1969 due to its grandfathered status. Radioactive emissions are limited to levels below those that would cause annual compliance dose standards for members of the public to be exceeded and stack 3039 to lose its grandfathered status. To allow for maximum production of 227 Ac without exceeding relevant dose limits, monthly tracking of project emissions and resulting CAP88-PC modeled effective doses to a maximally exposed individual have been implemented. Four years of tracking data were compiled and analyzed to identify additional methods that could be used to estimate project doses more frequently, potentially further optimizing 227 Ac production while maintaining compliance with applicable regulations.

atmospheric emissions↗

Six Machine-Learning Methods for Predicting Hospital-Stay Duration for Patients with Sepsis: A Comparative Study

Sepsis is a life-threatening medical condition that, if not treated promptly, can result in tissue damage, organ failure, and death. According to the Centers for Disease Control, about 270,000 individuals die of sepsis in the US each year. Further, sepsis expenditures accounted for 13% of total US hospital costs in 2013, totaling more than $24 billion. Our project objectives were to determine if Machine Learning algorithms could reliably predict hospital stay duration for patients with sepsis. The data set we used has been de-identified and is freely available through the BupaR package. The data includes 1050 cases, 15214 events, and 16 types of actions related to sepsis patient care. First, we used process mining to determine how long each patient was in the hospital. Using BupaR’s functions, we created several process model graphs. These process models depict the movement of patients at a hospital and provide duration data for each patent case. Second, we identified outlier data and created two dataset versions: one with and one without outliers. We then applied the following analysis methods: Linear Regression, Random Forest, K-Nearest Neighbors, Neural Networks, XGBoost, and lightGBM. We compared the model validations for the six machine learning models using the same data-splitting method. We found that the XGBoost model had the best prediction accuracy of 73.9 percent for cases with outliers, and 79 percent for cases without outliers. We also found that the lightGBM model had the lowest mean absolute error between prediction and actual duration in days with 3.66 days for the case with outliers, and 2.4 days for the case without outliers. These two models outperformed the other four models. This work will be enhanced in the future by exploring new prediction algorithms and comparing them with the results of this study.

Chen, Lingtao↗

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

We sequenced the genomes of 5,085 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains causing two coronavirus disease 2019 (COVID-19) disease waves in metropolitan Houston, TX, an ethnically diverse region with 7 million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston and from viruses recovered in an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotype and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein—the primary target of global vaccine efforts—are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR3022. Our report represents the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.

59 BASIC BIOLOGICAL SCIENCES↗

A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program

The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (n rs495828 = 53 and n rs505922 = 59); strongest association with venous embolism, odds ratio (OR rs495828 1.33 (p = 1.32 x 10 –199 ), and thrombosis OR rs505922 1.33, p = 2.2 x10 -265 . Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p = 4.12 × 10 –191 ; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p = 2.26× 10 –12 . The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p = 6.48 x10 -23 , lupus OR 0.84, p = 3.97 x 10 –06 . PheWAS stratified by ancestry demonstrated differences in genotype-phenotype associations. LMNA (rs581342) associated with neutropenia OR 1.29 p = 4.1 x 10 –13 among Veterans of African and Hispanic ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

59 BASIC BIOLOGICAL SCIENCES↗

Draft Prototype Microreactor Transportation Safety Program

Microreactors are compact reactors capable of producing less than 50 megawatts of electrical energy. Typically, these reactors are factory-fabricated and designed to be easily transportable by truck, rail, vessel, or air. Microreactor designs often assume that the unit can be transported containing either unirradiated or irradiated fuel. The interest in microreactors is driven by several factors, including the need to generate power on at remote locations, at military installations, at facilities such as data centers, and in areas recovering from natural disasters. The U.S. Department of Defense is actively pursuing the microreactor concept to meet the increasing energy demands of military operations that require portable and dense power sources. Commercial vendors are also exploring microreactor concepts. The report Microreactor Transportation Emergency Planning Challenges (Maheras et al. 2024) outlined the emergency planning challenges associated with the transportation of microreactors by road, rail, and by barge/ship. The successful commercial deployment and redeployment of microreactors will also require the development of microreactor transportation safety programs. The elements in these safety programs are not specific to microreactors; however, the transport of microreactors may pose unique challenges in these areas. This report builds on the report Microreactor Transportation Emergency Planning Challenges (Maheras et al. 2024) and develops the elements of a prototype microreactor transportation safety program that describes the elements that should be contained vendor-developed microreactor transportation safety programs, identifying the unique elements associated with microreactor transport. This will provide vendors and their transportation contractors a basis for their transportation planning and will accelerate the commercial deployment and redeployment of microreactors by identifying those issues unique to microreactor transport. The emphasis of this report is on highway transport of microreactors. This is based on a U.S. Nuclear Regulatory Commission transportation package approval strategy of crawl-walk-run, where transport by highway is evaluated first (Coles et al. 2021, 2024, Maheras et al. 2021), then other surface modes (rail and barge/ship), and finally air transport. Evaluation of maritime transport of microreactors was recently initiated (Rigato et al. 2024, Maheras et al. 2025). The report first discusses microreactors in general and microreactor transportation safety program planning assumptions. The report then provides a description of the transportation safety planning process and provides an extensive discussion of the elements of transportation safety programs. Specific elements examined included transportation roles and responsibilities, transportation planning, transportation mode and route selection, carrier selection, transportation packaging, advance notification of shipments, public information and communications, emergency response plans and procedures, inspections, security, safe parking, shipment tracking, weather and road conditions, medical preparedness, training and exercises, and program evaluation. The report then identifies the unique elements of a transportation safety program associated with microreactor transport. These unique elements were in the areas of: the unusual nature of microreactor designs, compensatory measures, increased radiation dose rates in the vicinity of microreactors, transportation package approval versus 10 CFR 50.59, and the use of a risk-informed transportation package approval process.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Protecting Space Travelers from Kidney Stones: Renal Stone Risk During Space Flight

Renal stones, popularly known as kidney or bladder stones, are small rock-like objects formed in the kidneys or urinary tract by deposits of calcium and other minerals. The problem arises when the stones block the drainage of the kidney, resulting in urinary obstruction and pain. Passing these stones can be one of the most painful experiences a person will endure so doctors often prescribe pain relievers to ease the experience. Drinking plenty of fluids, which help flush waste out of the body, and eating a well-balanced diet are the first steps to preventing stones. For individuals at risk, this may not be enough, and a doctor may recommend a special diet and medications. Unfortunately, approximately 60 percent of people who have had a renal stone will experience a recurrence. This is particularly true of men, who are four to five times more likely to develop stones than women. Renal stones do not discriminate based on age; even children are at risk. Astronauts are particularly at risk of developing renal stones because they lose bone and muscle mass; calcium, other minerals, and protein normally used for bone and muscle end up in the bloodstream and then in the kidneys. Without plenty of fluid to wash them away, crystals can form and then grow into stones. This factor compounds the risk for astronauts, since they also perceive that they are less thirsty in space and will drink less than normal during the mission. To minimize all of these factors, doctors must instead treat the stone-forming compounds with medication. This study will use potassium citrate to reduce the risk of stone formation. Renal stones are never convenient, but they are a particular concern for astronauts who have limited access to treatment during flight. Researchers are examining how earthbound preventions for renal stone formation work in flight, ensuring missions are not ended prematurely due to this medical condition. During STS-107, earthbound preventions and treatments become astronauts' gain.

Whitson, Peggy↗

Does the Health Maintenance Facility Provide Speciality Capabilities?

The Health Maintenance Facility (HMF) is capable of handling all minor illnesses, most moderate illnesses, and some major illnesses on board a space station. Its primary purpose should be to treat problems that are mission threatening, not life threatening. The HMF will have greater medical capabilities than those currently on Navy submarines. Much of the discussion in this document focuses on the possibilities of treating specific medical conditions on board a space station. The HMF will be limited to caring for critically ill patients for a few days, so a crew return vehicle will be important.

Boyce, Joey↗

Intravenous Solutions for Exploration Missions

This paper describes the intravenous (IV) fluids requirements being developed for medical care during NASA s future exploration class missions. Previous research on IV solution generation and mixing in space is summarized. The current exploration baseline mission profiles are introduced, potential medical conditions described and evaluated for fluidic needs, and operational issues assessed. We briefly introduce potential methods for generating IV fluids in microgravity. Conclusions on the recommended fluid volume requirements are presented.

Miller, Fletcher J.↗

Medical applications of artificial olfactometry

The present invention provides methods for detecting the presence of an analyte indicative of various medical conditions, including halitosis, periodontal disease and other diseases are also disclosed.

Lewis, Nathan S.↗

Rashes and Exanthems on Long Duration Space Flights

INTRODUCTION: As NASA expands its human space exploration to the Moon, Mars and beyond, it will be presented with many challenges, not the least of which will be dealing with medical conditions, which on earth are simple, but take on new levels of complexity in space habitats. Skin conditions exemplify this complexity. METHODS AND RESULTS: While skin conditions account for 7 % of outpatient presentations to a primary care provider in the United States, NASA Longitudinal Study of Astronaut Health (LSAH) database indicates that cutaneous manifestations are significantly prevalent on-orbit. Reviewing this data for US astronauts, there have been 90 total cases of skin rashes during 27.34 person-years of spaceflight, or 3.29 cases/person. Specifically, STS-1 though 114 had 56 cases, ISS Expeditions 1 though 13 had 7 cases, Mir had 4 cases, Skylab had 5 cases and the Apollo program had 18 cases. If there was a period of 24 hours or more between rashes in the same crewmember, this was counted as an additional case. DISCUSSION: This prevalence is likely due, in some part, to constraints of hygiene and to immunologic changes that occur. The stresses of microgravity and austere Earth environments such as the Antarctic, submarine and military deployments, no doubt, similarly contribute to cutaneous reactions; but the difference of the environments are significant enough to warrant further study and discussion. This paper will discuss rashes, exanthems, and cutaneous reactions in space habitats; it will address diagnosis, causation, mitigation and treatment of skin conditions seen on orbit, to date, with a look to anticipating what may be seen with larger crews on future extended duration expeditions.

Ilscus, L.S.↗

Operations to Research: Communication of Lessons Learned

This presentation explores ways to build upon previous spaceflight experience and communicate this knowledge to prepare for future exploration. An operational approach is highlighted, focusing on selection and retention standards (disease screening and obtaining medical histories); pre-, in-, and post-flight monitoring (establishing degrees of bone loss, skeletal muscle loss, cardiovascular deconditioning, medical conditions, etc.); prevention, mitigation, or treatment (in-flight countermeasures); and, reconditioning, recovery, and reassignment (post-flight training regimen, return to pre-flight baseline and flight assignment). Experiences and lessons learned from the Apollo, Skylab, Shuttle, Shuttle-Mir, International Space Station, and Orion missions are outlined.

Fogarty, Jennifer↗

Optimizing Medical Kits for Space Flight

The Integrated Medical Model (IMM) uses Monte Carlo methodologies to predict the occurrence of medical events, their mitigation, and the resources required during space flight. The model includes two modules that utilize output from a single model simulation to identify an optimized medical kit for a specified mission scenario. This poster describes two flexible optimization routines built into SAS 9.1. The first routine utilizes a systematic process of elimination to maximize (or minimize) outcomes subject to attribute constraints. The second routine uses a search and mutate approach to minimize medical kit attributes given a set of outcome constraints. There are currently 273 unique resources identified that are used to treat at least one of 83 medical conditions currently in the model.

Minard, Charles G.↗