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Estimated Probabililty of Chest Injury During an International Space Station Mission

The Integrated Medical Model (IMM) is a decision support tool that is useful to spaceflight mission planners and medical system designers when assessing risks and optimizing medical systems. The IMM project maintains a database of medical conditions that could occur during a spaceflight. The IMM project is in the process of assigning an incidence rate, the associated functional impairment, and a best and a worst case end state for each condition. The purpose of this work was to develop the IMM Chest Injury Module (CIM). The CIM calculates the incidence rate of chest injury per person-year of spaceflight on the International Space Station (ISS). The CIM was built so that the probability of chest injury during one year on ISS could be predicted. These results will be incorporated into the IMM Chest Injury Clinical Finding Form and used within the parent IMM model.

Lewandowski, Beth E.↗

Integrated Medical Model Overview

The Integrated Medical Model (IMM) Project represents one aspect of NASA's Human Research Program (HRP) to quantitatively assess medical risks to astronauts for existing operational missions as well as missions associated with future exploration and commercial space flight ventures. The IMM takes a probabilistic approach to assessing the likelihood and specific outcomes of one hundred medical conditions within the envelope of accepted space flight standards of care over a selectable range of mission capabilities. A specially developed Integrated Medical Evidence Database (iMED) maintains evidence-based, organizational knowledge across a variety of data sources. Since becoming operational in 2011, version 3.0 of the IMM, the supporting iMED, and the expertise of the IMM project team have contributed to a wide range of decision and informational processes for the space medical and human research community. This presentation provides an overview of the IMM conceptual architecture and range of application through examples of actual space flight community questions posed to the IMM project.

Spae Adaptation Syndrome↗

Baseline Medical System Translation for the Impact Medical Database

NASA has developed a new evidence-based data-driven probabilistic risk assessment and tradespace analysis tool as a successor to the Integrated Medical Model (IMM). This updated decision support tool is known as IMPACT (Informing Mission Planning via Analysis of Complex Tradespaces). Whereas IMM focuses on the resources and risks associated with International Space Station (ISS) and Low Earth Orbit (LEO) missions, IMPACT estimates the frequency and consequences of medical conditions that might arise during exploration missions. One of the services offered by IMM is a series of generic or baseline medical systems associated with typical mission types or DRMs (Design Reference Missions), such that requestors may prioritize questions pertaining to the mission itself over the medical supplies indicated by the model outputs for that DRM. In a mission focused request, the appropriate baseline medical system is used in place of a prepared or optimized medical kit. In preparation, an effort was undertaken to create baseline systems of medical resources within IMPACT suitable for typical DRMs. Using an existing baseline medical system within IMM’s Integrated Medical Evidence Database (iMED) as a starting point, the resources found within the medical kit were compared to and substituted for equivalent resources available within the IMPACT MD (Medical Database). In consultation with clinicians with knowledge of IMPACT’s MD, each resource was matched as closely as possible to a similarly purposed resource in IMPACT, seeking to preserve the treatment capabilities and procedures offered by the IMM medical system while reconciling the differences in modeled resources and medical conditions between the models. To demonstrate the efficacy of this work, a prototype ISS medical system in IMPACT was translated from the baseline used in the IMM. The appropriate medical system was then run through its associated medical model to compare and validate the resultant risks and risk mitigation provided by each baseline ISS medical kit.

S Schwartz↗

High-precision mass measurements of the isomeric and ground states of 44 V: Improving constraints on the isobaric multiplet mass equation parameters of the A=44, 0 + quintet

Background: The quadratic isobaric multiplet mass equation (IMME) has been very successful at predicting the masses of isobaric analog states in the same multiplet, while its coefficients are known to follow specific trends as functions of mass number. The Atomic Mass Evaluation 2016 [Chin. Phys. C 41, 030003 (2017)] 44 V mass value results in an anomalous negative c coefficient for the IMME quadratic term; a consequence of large uncertainty and an unresolved isomeric state. The b and c coefficients can provide useful constraints for construction of the isospin-nonconserving Hamiltonians for the pf shell. In addition, the excitation energy of the 0 + , T = 2 level in 44 V is currently unknown. This state can be used to constrain the mass of the more exotic 44 Cr. Purpose: The aim of the experimental campaign was to perform high-precision mass measurements to resolve the difference between 44 V isomeric and ground states, to test the IMME using the new ground state mass value and to provide necessary ingredients for the future identification of the 0 + , T = 2 state in 44 V. Method: High-precision Penning trap mass spectrometry was performed at LEBIT, located at the National Superconducting Cyclotron Laboratory, to measure the cyclotron frequency ratios of [ 44g,m VO] + versus [ 32 SCO] + , a well-known reference mass, to extract both the isomeric and ground state masses of 44 V. Results: The mass excess of the ground and isomeric states in 44 V were measured to be -23 804.9(80) keV/c 2 and -23 537.0(55) keV/c 2 , respectively. This yielded a new proton separation energy of S p = 1 773(10) keV. Conclusion: The new values of the ground state and isomeric state masses of 44 V have been used to deduce the IMME b and c coefficients of the lowest 2 + and 6 + triplets in A = 44. The 2 + c coefficient is now verified with the IMME trend for lowest multiplets and is in good agreement with the shell-model predictions using charge-dependent Hamiltonians. The mirror energy differences were determined between 44 V and 44 Sc, in line with isospin-symmetry for this multiplet. Finally, the new value of the proton separation energy determined, to an uncertainty of 10 keV, will be important for the determination of the 0 + , T = 2 state in 44 V and, consequently, for prediction of the mass excess of 44 Cr.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome

Cristae are high–curvature structures in the inner mitochondrial membrane (IMM) that are crucial for ATP production. While cristae–shaping proteins have been defined, analogous lipid–based mechanisms have yet to be elucidated. Here, we combine experimental lipidome dissection with multi–scale modeling to investigate how lipid interactions dictate IMM morphology and ATP generation. When modulating phospholipid (PL) saturation in engineered yeast strains, we observed a surprisingly abrupt breakpoint in IMM topology driven by a continuous loss of ATP synthase organization at cristae ridges. We found that cardiolipin (CL) specifically buffers the inner mitochondrial membrane against curvature loss, an effect that is independent of ATP synthase dimerization. To explain this interaction, we developed a continuum model for cristae tubule formation that integrates both lipid and protein–mediated curvatures. This model highlighted a snapthrough instability, which drives IMM collapse upon small changes in membrane properties. We also showed that cardiolipin is essential in low–oxygen conditions that promote PL saturation. These results demonstrate that the mechanical function of cardiolipin is dependent on the surrounding lipid and protein components of the IMM.

59 BASIC BIOLOGICAL SCIENCES↗

The Integrated Medical Model - Optimizing In-flight Space Medical Systems to Reduce Crew Health Risk and Mission Impacts

The Integrated Medical Model (IMM) is a decision support tool used by medical system planners and designers as they prepare for exploration planning activities of the Constellation program (CxP). IMM provides an evidence-based approach to help optimize the allocation of in-flight medical resources for a specified level of risk within spacecraft operational constraints. Eighty medical conditions and associated resources are represented in IMM. Nine conditions are due to Space Adaptation Syndrome. The IMM helps answer fundamental medical mission planning questions such as What medical conditions can be expected? What type and quantity of medical resources are most likely to be used?", and "What is the probability of crew death or evacuation due to medical events?" For a specified mission and crew profile, the IMM effectively characterizes the sequence of events that could potentially occur should a medical condition happen. The mathematical relationships among mission and crew attributes, medical conditions and incidence data, in-flight medical resources, potential clinical and crew health end states are established to generate end state probabilities. A Monte Carlo computational method is used to determine the probable outcomes and requires up to 25,000 mission trials to reach convergence. For each mission trial, the pharmaceuticals and supplies required to diagnose and treat prevalent medical conditions are tracked and decremented. The uncertainty of patient response to treatment is bounded via a best-case, worst-case, untreated case algorithm. A Crew Health Index (CHI) metric, developed to account for functional impairment due to a medical condition, provides a quantified measure of risk and enables risk comparisons across mission scenarios. The use of historical in-flight medical data, terrestrial surrogate data as appropriate, and space medicine subject matter expertise has enabled the development of a probabilistic, stochastic decision support tool capable of optimizing in-flight medical systems based on crew and mission parameters. This presentation will illustrate how to apply quantitative risk assessment methods to optimize the mass and volume of space-based medical systems for a space flight mission given the level of crew health and mission risk.

Kerstman, Eric↗

Validation of the Integrated Medical Model Using Historical Space Flight Data

The Integrated Medical Model (IMM) utilizes Monte Carlo methodologies to predict the occurrence of medical events, utilization of resources, and clinical outcomes during space flight. Real-world data may be used to demonstrate the accuracy of the model. For this analysis, IMM predictions were compared to data from historical shuttle missions, not yet included as model source input. Initial goodness of fit test-ing on International Space Station data suggests that the IMM may overestimate the number of occurrences for three of the 83 medical conditions in the model. The IMM did not underestimate the occurrence of any medical condition. Initial comparisons with shuttle data demonstrate the importance of understanding crew preference (i.e., preferred analgesic) for accurately predicting the utilization of re-sources. The initial analysis demonstrates the validity of the IMM for its intended use and highlights areas for improvement.

Kerstman, Eric L.↗

Analysis of Advanced Respiratory Support Onboard ISS and CCV

NASA is collaborating with private entities for the development of commercial space vehicles. The Space and Clinical Operations Division was tasked to review the oxygen and respiratory support system and recommend what capabilities, if any, the vehicle should have to support the return of an ill or injured crewmember. The Integrated Medical Model (IMM) was utilized as a data source for the development of these recommendations. The Integrated Medical Model (IMM) was used to simulate a six month, six crew, International Space Station (ISS) mission. Three medical system scenarios were considered based on the availability of (1) oxygen only, (2) oxygen and a ventilator, or (3) neither oxygen nor ventilator. The IMM analysis provided probability estimates of medical events that would require either oxygen or ventilator support. It also provided estimates of crew health, the probability of evacuation, and the probability of loss of crew life secondary to medical events for each of the three medical system scenarios. These IMM outputs were used as objective data to enable evidence‐based decisions regarding oxygen and respiratory support system requirements for commercial crew vehicles. The IMM provides data that may be utilized to support informed decisions regarding the development of medical systems for commercial crew vehicles.

Shah, Ronak V.↗

Comparison of the Integrated Medical Model Predictions to Real World ISS and STS Observations

The Human Research Program funded the development of the integrated medical model (IMM) to quantify the medical component of overall mission risk. The IMM uses Monte Carlo methodology to integrate space flight and ground medical data to assess the probability of mission medical outcomes and resource utilization. To determine the credibility of IMM output the IMM project team completed two validation studies that compare IMM output to observed medical events from a selection of Shuttle Transportation System (STS) and International Space Station (ISS) missions.

validation↗

First Penning trap mass measurement of 36 Ca

Background: Isobaric quintets provide the best test of the isobaric multiplet mass equation (IMME) and can uniquely identify higher order corrections suggestive of isospin symmetry breaking effects in the nuclear Hamilto nian. The Generalized IMME (GIMME) is a novel microscopic interaction theory that predicts an extension to the quadratic form of the IMME. Only the A = 20, 32 T = 2 quintets have the exotic T z = –2 member ground state mass determined to high-precision by Penning trap mass spectrometry. Purpose: To establish A = 36 as the third high-precision T = 2 isobaric quintet with the T z = –2 member ground state mass measured by Penning trap mass spectrometry and provide the first test of the predictive power of the GIMME. Method: Here, a radioactive beam of neutron-deficient 36 Ca was produced by projectile fragmentation at the National Superconducting Cyclotron Laboratory. The beam was thermalized and the mass of 36 Ca + and 36 Ca 2+ measured by the Time of Flight - Ion Cyclotron Resonance method in the LEBIT 9.4 T Penning trap. Results: We measure the mass excess of 36 Ca to be ME= –6483.6(56) keV, an improvement in precision by a factor of 6 over the literature value. The new datum is considered together with evaluated nuclear data on the A = 36, T = 2 quintet. We find agreement with the quadratic form of the IMME given by isospin symmetry, but only coarse qualitative agreement with predictions of the GIMME. Conclusion: A total of three isobaric quintets have their most exotic members measured by Penning trap mass spectrometry. The GIMME predictions in the T = 2 quintet appear to break down for A = 32 and greater.

20 ≤ A ≤ 38↗

Bayesian Analysis for Risk Assessment of Selected Medical Events in Support of the Integrated Medical Model Effort

The Exploration Medical Capability project is creating a catalog of risk assessments using the Integrated Medical Model (IMM). The IMM is a software-based system intended to assist mission planners in preparing for spaceflight missions by helping them to make informed decisions about medical preparations and supplies needed for combating and treating various medical events using Probabilistic Risk Assessment. The objective is to use statistical analyses to inform the IMM decision tool with estimated probabilities of medical events occurring during an exploration mission. Because data regarding astronaut health are limited, Bayesian statistical analysis is used. Bayesian inference combines prior knowledge, such as data from the general U.S. population, the U.S. Submarine Force, or the analog astronaut population located at the NASA Johnson Space Center, with observed data for the medical condition of interest. The posterior results reflect the best evidence for specific medical events occurring in flight. Bayes theorem provides a formal mechanism for combining available observed data with data from similar studies to support the quantification process. The IMM team performed Bayesian updates on the following medical events: angina, appendicitis, atrial fibrillation, atrial flutter, dental abscess, dental caries, dental periodontal disease, gallstone disease, herpes zoster, renal stones, seizure, and stroke.

Gilkey, Kelly M.↗

Estimating the Risk of Renal Stone Events During Long-Duration Spaceflight

Introduction: Given the bone loss and increased urinary calcium excretion in the microgravity environment, persons participating in long-duration spaceflight may have an increased risk for renal stone formation. Renal stones are often an incidental finding of abdominal imaging studies done for other reasons. Thus, some crewmembers may have undiscovered, asymptomatic stones prior to their mission. Methods: An extensive literature search was conducted concerning the natural history of asymptomatic renal stones. For comparison, simulations were done using the Integrated Medical Model (IMM). The IMM is an evidence-based decision support tool that provides risk analysis and has the capability to optimize medical systems for missions by minimizing the occurrence of adverse mission outcomes such as evacuation and loss of crew life within specified mass and volume constraints. Results: The literature of the natural history of asymptomatic renal stones in the general medical population shows that the probability of symptomatic event is 8% to 34% at 1 to 3 years for stones < 7 mm. Extrapolated to a 6-month mission, for stones < 5 to 7 mm, the risk for any stone event is about 4 to 6%, with a 0.7% to 4% risk for intervention, respectively. IMM simulations compare favorably with risk estimates garnered from the terrestrial literature. The IMM forecasts that symptomatic renal stones may be one of the top drivers for medical evacuation of an International Space Station (ISS) mission. Discussion: Although the likelihood of a stone event is low, the consequences could be severe due to limitations of current ISS medical capabilities. Therefore, these risks need to be quantified to aid planning, limit crew morbidity and mitigate mission impacts. This will be especially critical for missions beyond earth orbit, where evacuation may not be an option.

Reyes, David↗

Estimating the Risk of Renal Stone Events during Long-Duration Spaceflight

Introduction: Given the bone loss and increased urinary calcium excretion in the microgravity environment, persons participating in long-duration spaceflight may have an increased risk for renal stone formation. Renal stones are often an incidental finding of abdominal imaging studies done for other reasons. Thus, some crewmembers may have undiscovered, asymptomatic stones prior to their mission. Methods: An extensive literature search was conducted concerning the natural history of asymptomatic renal stones. For comparison, simulations were done using the Integrated Medical Model (IMM). The IMM is an evidence-based decision support tool that provides risk analysis and has the capability to optimize medical systems for missions by minimizing the occurrence of adverse mission outcomes such as evacuation and loss of crew life within specified mass and volume constraints. Results: The literature of the natural history of asymptomatic renal stones in the general medical population shows that the probability of symptomatic event is 8% to 34% at 1 to 3 years for stones < 7 mm. Extrapolated to a 6-month mission, for stones < 5 to 7 mm, the risk for any stone event is about 4 to 6%, with a 0.7% to 4% risk for intervention, respectively. IMM simulations compare favorably with risk estimates garnered from the terrestrial literature. The IMM forecasts that symptomatic renal stones may be one of the top drivers for medical evacuation of an International Space Station (ISS) mission. Discussion: Although the likelihood of a stone event is low, the consequences could be severe due to limitations of current ISS medical capabilities. Therefore, these risks need to be quantified to aid planning, limit crew morbidity and mitigate mission impacts. This will be especially critical for missions beyond earth orbit, where evacuation may not be an option.

Reyes, David↗

Mass and Volume Optimization of Space Flight Medical Kits

Resource allocation is a critical aspect of space mission planning. All resources, including medical resources, are subject to a number of mission constraints such a maximum mass and volume. However, unlike many resources, there is often limited understanding in how to optimize medical resources for a mission. The Integrated Medical Model (IMM) is a probabilistic model that estimates medical event occurrences and mission outcomes for different mission profiles. IMM simulates outcomes and describes the impact of medical events in terms of lost crew time, medical resource usage, and the potential for medically required evacuation. Previously published work describes an approach that uses the IMM to generate optimized medical kits that maximize benefit to the crew subject to mass and volume constraints. We improve upon the results obtained previously and extend our approach to minimize mass and volume while meeting some benefit threshold. METHODS We frame the medical kit optimization problem as a modified knapsack problem and implement an algorithm utilizing dynamic programming. Using this algorithm, optimized medical kits were generated for 3 mission scenarios with the goal of minimizing the medical kit mass and volume for a specified likelihood of evacuation or Crew Health Index (CHI) threshold. The algorithm was expanded to generate medical kits that maximize likelihood of evacuation or CHI subject to mass and volume constraints. RESULTS AND CONCLUSIONS In maximizing benefit to crew health subject to certain constraints, our algorithm generates medical kits that more closely resemble the unlimited-resource scenario than previous approaches which leverage medical risk information generated by the IMM. Our work here demonstrates that this algorithm provides an efficient and effective means to objectively allocate medical resources for spaceflight missions and provides an effective means of addressing tradeoffs in medical resource allocations and crew mission success parameters.

Monte Carlo Method↗

Optimization Routine for Generating Medical Kits for Spaceflight Using the Integrated Medical Model

The Integrated Medical Model (IMM) is a MATLAB model that provides probabilistic assessment of the medical risk associated with human spaceflight missions.Different simulations or profiles can be run in which input conditions regarding both mission characteristics and crew characteristics may vary. For each simulation, the IMM records the total medical events that occur and “treats” each event with resources drawn from import scripts. IMM outputs include Total Medical Events (TME), Crew Health Index (CHI), probability of Evacuation (pEVAC), and probability of Loss of Crew Life (pLOCL).The Crew Health Index is determined by the amount of quality time lost (QTL). Previously, an optimization code was implemented in order to efficiently generate medical kits. The kits were optimized to have the greatest benefit possible, given amass and/or volume constraint. A 6-crew, 14-day lunar mission was chosen for the simulation and run through the IMM for 100,000 trials. A built-in MATLAB solver, mixed-integer linear programming, was used for the optimization routine. Kits were generated in 10% increments ranging from 10%-100% of the benefit constraints. Conditions wheremass alone was minimized, volume alone was minimized, and where mass and volume were minimizedjointly were tested.

Medical Kit↗

Transformational Solar Array Option I Final Report

This report summarizes the work performed under NASA contract NNC16CA19C from May 2, 2017 through April 2, 2018. This work is directed toward meeting the goals of the associated NASA NRA and, of course, the requirements of the contract. In brief, the goals are: (1) Over 47% beginning of life cell efficiency at 5 AU and -125 °C (2) Over 32% end of life efficiency at the blanket level at 50 W m-2, -125 °C and 4E15 1 MeV e cm-2 (3) Over 8 W kg-1 at EOL for the entire array including structure, deployment, and pointing mechanisms using beginning of life performance. (4) A stowed packaging density of greater than 66 kW m-3 (5) An ability to survive launch and numerous deploy retract cycles without degradation (6) An output higher than 300 V (7) An ability to operate in a plasma generated by xenon thrusters, typically 1E8 cm-3 ions with an average energy of 2 eV (8) A design compatible with electrostatic and magnetic cleanliness (9) Record breaking inverted metamorphic (IMM) 6 junction solar cells (10) IMM solar cells that have no anomalous flat spot behavior at low irradiance and low temperature (11) A mock-up production line for the low-cost manufacture of spacecraft blanket arrays. The Option I phase of the project continued efforts, started in the base-phase, to eliminate or reduce to very low levels the flat spots that reduce power to an unacceptable value in a significant percentage of cells and to reduce outgassing contamination of the concentrators to acceptable levels. Option I adds tasks to increase the efficiency of IMM cells from those produced in the Base Phase, to eliminate delamination of the coatings that were present in previous versions of the concentrator mirrors, to evaluate pressure sensitive adhesive as a method of fixing solar cell assemblies to blankets, to design a magnetically clean brake for ROSA, to test the robustness of a sample blanket in deploy and retract, to test for the adequate performance of a blanket in vibration and thermal environments, and to define the capital equipment needed to optimize production of the Transformational Array. 5 Work for this Final Report showed that the greatest likely improvement in the solar cells would be by emphasizing the effort for the IMM4 solar cells and stopping work on other IMM cells. For this phase, the solar cell work was primarily on the IMM4 cells with little work on IMM5 and none on IMM6 cells.

Gaddy, Edward↗

IMPACT 1.0—Task Impairment: A Novel Approach for Assessing Impairment during Exploration-Class Missions

Exploration-class and International Space Station (ISS) missions have significantly different levels of associated medical risk for crewmembers. The Integrated Medical Model (IMM), the probabilistic risk assessment tool used for ISS medical trade-space analyses, uses a Functional Impairment (FI) metric to determine quality time lost should a crewmember be afflicted with a medical condition. While IMM-based FI has been successful for ISS operations, it has limitations when applied to exploration-class missions. As the National Aeronautics and Space Administration (NASA) looks ahead to Gateway, Artemis, and Martian missions, a novel, dynamic, and mission-appropriate impairment paradigm is necessary for accurate contingency planning. This paradigm, Task Impairment (TI), fulfills that need by utilizing mission-specific tasks. TI will allow future capability for a loss of mission metric, previously not available with IMM. TI serves as a replacement metric for FI within IMPACT, the next-generation trade-space analysis tool suite created to replace the IMM. IMPACT significantly increases the fidelity of probabilistic risk assessment for exploration-class missions. The Human Exploration of Mars Preliminary List of Crew Tasks (MTL, a source of 1100+ exploration-class mission-specific tasks for crewmembers) was used to calculate TI. Using the Task List, 18 individual Human System Categories were identified as being required to perform each task (e.g., Cardiopulmonary, Cognitive, etc.). Each of the 1200+ tasks were mapped to the Human System categories listed in the Task List. The total number of tasks in each category were tallied to determine how many tasks required each Human System. Lastly, each of the 120 medical conditions from the IMPACT condition list were mapped to the Human System categories to complete the TI calculation. NASA subject matter experts across five medical specialties established consensus for the mapping of each condition. The resulting total tasks impaired by each condition were used to calculate discrete TI values. This process was repeated for each of the four severity/resource utilization variants of each condition, and for each of the three phases of clinical care. Through this process, discrete TI values were calculated for each of the 120 IMPACT medical conditions and their variants. The Task Impairment metric provides higher fidelity, dynamic utility, and quicker analysis of medical impairment compared to the previous Functional Impairment metric used for the Integrated Medical Model. TI will be used for higher fidelity medical impairment analysis and contingency planning during Lunar, Martian, and other long-term exploration-class missions.

William L Fernandez↗

The isobaric multiplet mass equation for A≤71 revisited

Accurate mass determination of short-lived nuclides by Penning-trap spectrometers and progress in the spectroscopy of proton-rich nuclei have triggered renewed interest in the isobaric multiplet mass equation (IMME). The energy levels of the members of T=1/2,1,3/2, and 2 multiplets and the coefficients of the IMME are tabulated for A≤71. The new compilation is based on the most recent mass evaluation (AME2011) and it includes the experimental results on energies of the states evaluated up to end of 2011. Taking into account the error bars, a significant deviation from the quadratic form of the IMME for the A=9,35 quartets and the A=32 quintet is observed.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗