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All sourcesNASA NTRSDOE OSTI
NASA NTRS2016

Clinical Outcome Metrics for Optimization of Robust Training

Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance (pre-IMM analysis) and overall mitigation of the mission medical impact (IMM analysis); 2) refine the procedure outcome and clinical outcome metrics themselves; 3) refine or develop innovative medical training products and solutions to maximize CMO performance; and 4) validate the methods and products of this experiment for operational use in the planning, execution, and quality assurance of the CMO training process The team has finalized training protocols and developed a software training/testing tool in collaboration with Butler Graphics (Detroit, MI). In addition to the "hands on" medical procedure modules, the software includes a differential diagnosis exercise (limited clinical decision support tool) to evaluate the diagnostic skills of participants. Human subject testing will occur over the next year.

Ebert, D.↗
NASA NTRS2015

Astronaut Preflight Cardiovascular Variables Associated with Vascular Compliance are Highly Correlated with Post-Flight Eye Outcome Measures in the Visual Impairment Intracranial Pressure (VIIP) Syndrome Following Long Duration Spaceflight

The detection of the first VIIP case occurred in 2005, and adequate eye outcome measures were available for 31 (67.4%) of the 46 long duration US crewmembers who had flown on the ISS since its first crewed mission in 2000. Therefore, this analysis is limited to a subgroup (22 males and 9 females). A "cardiovascular profile" for each astronaut was compiled by examining twelve individual parameters; eleven of these were preflight variables: systolic blood pressure, pulse pressure, body mass index, percentage body fat, LDL, HDL, triglycerides, use of anti‐lipid medication, fasting serum glucose, and maximal oxygen uptake in ml/kg. Each of these variables was averaged across three preflight annual physical exams. Astronaut age prior to the long duration mission, and inflight salt intake was also included in the analysis. The group of cardiovascular variables for each crew member was compared with seven VIIP eye outcome variables collected during the immediate post‐flight period: anterior-posterior axial length of the globe measured by ultrasound and optical biometry; optic nerve sheath diameter, optic nerve diameter, and optic nerve to sheath ratio‐ each measured by ultrasound and magnetic resonance imaging (MRI), intraocular pressure (IOP), change in manifest refraction, mean retinal nerve fiber layer (RNFL) on optical coherence tomography (OCT), and RNFL of the inferior and superior retinal quadrants. Since most of the VIIP eye outcome measures were added sequentially beginning in 2005, as knowledge of the syndrome improved, data were unavailable for 22.0% of the outcome measurements. To address the missing data, we employed multivariate multiple imputation techniques with predictive mean matching methods to accumulate 200 separate imputed datasets for analysis. We were able to impute data for the 22.0% of missing VIIP eye outcomes. We then applied Rubin's rules for collapsing the statistical results across our 200 multiply imputed data sets to assess the canonical correlation between the eye outcomes and the twelve astronaut cardiovascular variables available for all 31 subjects. Results: A highly significant canonical correlation was observed among the canonical solutions (p<.00001), with an average best canonical correlation of.97. The results suggest a strong association between astronauts' measures of cardiovascular health and the seven eye outcomes of the VIIP syndrome used in this analysis. Furthermore, the "joint test" revealed a significant difference in cardiovascular profile between male and female astronauts (Prob > F = 0.00001). Overall, female astronauts demonstrated a significantly healthier cardiovascular status. Individually, the female astronauts had significantly healthier profiles on seven of twelve cardiovascular variables than the men (p values ranging from <0.0001 to <0.05). Male astronauts did not demonstrate significantly healthier values on any of the twelve cardiovascular variables measured

Otto, Christian↗
NASA NTRSDate not supplied

The Potential Outcome Model: Explaining Low-Dose Radiobiology through an Epidemiologic Lens

One of the major challenges in understanding space radiation-induced carcinogenesis is the uncertainty from translating radiobiological research in cellular and animal models to humans, especially at doses below 100 mSv. Biological studies have shown a host of potential outcomes at lowdoses in animal and cellular models. The existence of non-targeted effects as bystander and abscopal effects is well-documented from clinical research and basic science1,2,3. While some studies have shown increased effects at low doses, others have shown evidence of hormetic bystander effects, where radiation exposure may be beneficial4,5,6. Despite these varied and diverse findings, epidemiologic studies largely support the linear-no threshold (LNT) assumption used by radiation protection guidance7,8. Translational animal-to-human models have predominantly considered ratio values such as the relative biological effectiveness (RBE) and dose and dose-rate effectiveness factor (DDREF) that rely on the assumption of LNT rather than implementing specific dose-response shapes in the low-dose region, and translational cell-to-human models are uncommon. The sufficient component cause model presents an opportunity to examine biological findings at low doses from an epidemiological lens9. In this model, exposures “sufficient” to cause an outcome of interest are presented in pie charts, such that when all slices of a pie chart are fulfilled, the outcome will occur. Multiple pie charts may exist for a single outcome, illustrating individual differences9. In 1988,Greenland and Poole adapted the sufficient component cause model to incorporate interaction with other exposures (such as genetics or lifestyle factors)10. They show that a range of biological processes are possible in a population, but that an epidemiologic study will only reveal the mean outcome from the population at large10,11. Using this construct, the multiple outcomes presented in radiobiological models to date can be explained in the context of epidemiologic studies. This presentation aims to demonstrate a causal framework that can integrate radiobiological and epidemiological models to date. It is intended as a conversation starter to spur future research.

C M Milder↗
NASA NTRS1998

Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

Non-NASA Center↗
NASA NTRS2004

Presyncopal/Non-Presyncopal Outcomes of Post Spaceflight Stand Tests are Consistent from Flight to Flight

The overall prevalence of orthostatic hypotension after short duration (6-18 d) spaceflight is 20% with existing countermeasures. However, it is not known if the outcomes of stand tests for orthostatic tolerance are consistent within individuals on subsequent flights, or if first time fliers are more (or less) likely to experience orthostatic hypotension and presyncope than are veteran astronauts. Fifty astronauts were studied retrospectively. Stand test data, which had been collected before and after spaceflight, were compared from at least two flights for each astronaut. For twenty-five of these astronauts, their first flight in this database was also their first time to fly into space. For the remaining 25, their first flight in this database was their second, third or fourth flight, as data were available. No subject became presyncopal during preflight testing. Of the 50 subjects, 45 (90%) had the same outcome on their first and second fligh ts of this study. Of 14 subjects on whom we had data from a third mission, 12 had the same stand test outcome on all three flights (86% same outcome across three flights). There was no correlation between flight duration and orthostatic tolerance (r = 0.39). These data support the idea that astronauts are predisposed to orthostatic tolerance/intolerance after spaceflight and that this predisposition is not altered by subsequent flights. Flight durations within this data set did not alter the likelihood of orthostatic intolerance and rookie fliers were no more likely to experience orthostatic intolerance than were veteran astronauts.

Martin, D. S.↗
NASA NTRS2015

Clinical Outcome Metrics for Optimization of Robust Training

The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capabilities (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities". Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes.

Ebert, D.↗
NASA NTRS2014

Retrospective Analysis of Inflight Exercise Loading and Physiological Outcomes

Astronauts perform exercise throughout their missions to counter the health declines that occur as a result of long-term exposure to weightlessness. Although all astronauts perform exercise during their missions, the specific prescriptions, and thus the mechanical loading, differs among individuals. For example, inflight ground reaction force data indicate that subject-specific differences exist in foot forces created when exercising on the second-generation treadmill (T2) [1]. The current exercise devices allow astronauts to complete prescriptions at higher intensities, resulting in greater benefits with increased efficiency. Although physiological outcomes have improved, the specific factors related to the increased benefits are unknown. In-flight exercise hardware collect data that allows for exploratory analyses to determine if specific performance factors relate to physiological outcomes. These analyses are vital for understanding which components of exercise are most critical for optimal human health and performance. The relationship between exercise performance variables and physiological changes during flight has yet to be fully investigated. Identifying the critical performance variables that relate to improved physiological outcomes is vital for creating current and future exercise prescriptions to optimize astronaut health. The specific aims of this project are: 1) To quantify the exercise-related mechanical loading experienced by crewmembers on T2 and ARED during their mission on ISS; 2) To explore relationships between exercise loading variables, bone, and muscle health changes during the mission; 3) To determine if specific mechanical loading variables are more critical than others in protecting physiology; 4) To develop methodology for operational use in monitoring accumulated training loads during crew exercise programs. This retrospective analysis, which is currently in progress, is being conducted using data from astronauts that have flown long-duration missions onboard the ISS and have had access to exercise on the T2 and the Advanced Resistive Exercise Device (ARED). The specific exercise prescriptions vary for each astronaut. General exercise summary metrics will be developed to quantify exercise intensities, volumes, and durations for each subject. Where available, ground reaction force data will be used to quantify mechanical loading experienced by each astronaut. These inflight exercise metrics will be investigated relative to changes in pre- to post-flight bone and muscle health to identify which specific variables are related with improved or degraded physiological outcomes. The information generated from this analysis will fill gaps related to typical bone loading characterization, exercise performance capability, exercise volume and efficiency, and importance of exercise hardware. In addition, methods for quantification of exercise loading for use in monitoring the exercise programs during future space missions will be explored with the intent to inform exercise scientists and trainers as to the critical aspects of inflight exercise prescriptions.

Ploutz-Snyder, L. L.↗
NASA NTRS2015

Ocular Outcomes Comparison Between 14- and 70-day Head-down Tilt Bed Rest

INTRODUCTION: Ophthalmological changes, including optic disc edema with optic nerve sheath distension, posterior globe flattening with hyperopic shift, choroidal folds and cotton wool spots have been detected in some astronauts involved in long-duration spaceflights. (sup 1) It is hypothesized that elevated intracranial pressure resulting from microgravity-induced cephalad fluid shifts may be responsible for most of these findings. Head-down tilt bed rest (HTDBR) is a ground-based microgravity analog which also produces cephalad fluid shifts. It is conceivable that prolonged HDTBR exposure may induce ocular changes similar to those experienced in microgravity. Therefore, the purpose of the present study was to compare structural and functional ocular outcomes between 14- and 70-day HDTBR in healthy human subjects. It is hypothesized that 70-d HDTBR induced ocular changes of greater magnitude as compared to 14-d HDTBR. METHODS: Two HDTBR studies were conducted at the NASA Flight Analogs Research Unit, located at The University of Texas Medical Branch at Galveston, TX. Identical NASA standard screening procedures and BR conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants spent 14 and/or 70 consecutive days in a 6deg HDT position and did not engage in exercise. Subjects received weekly ocular examinations before, during, and after HDTBR. Ocular testing included: distance and near best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP) measurement, color vision, red dot test, modified Amsler grid test, confrontational visual field, color fundus photography and Spectral-domain OCT scans of the macula and the optic disc. Pre/post HDTBR differences between the two studies will be evaluated for BCVA, spherical equivalent, IOP, retinal nerve fiber layer (RNFL) thickness and macular OCT parameters. RESULTS: 16 (12 males and 4 females) and 6 (5 males and 1 female) subjects participated in the 14 and 70-day HDTBR studies, respectively. One subject participated in both studies. The demographic and ophthalmological characteristics of the 14-day HDTBR study have been presented elsewhere.2 In the 70- day study, subjects age averaged 39.5 +/- 7.8 years; pre- and post-HDTBR Goldmann IOP were, on average, 15.4 and 14.6 mmHg in the right eye, and 15.3 and 14.4 mmHg in the left eye, respectively; preand post-HDTBR Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) average RNFL thickness were 103.8 and 106 μm in the right eye, and 103 and 104.3 μm in the left eye, respectively. In both studies, color vision, red dot test, modified Amsler grid test and confrontational visual field were within normal limits at all time points; no changes were detected on stereoscopic color optic disc photography. For the above outcomes, preliminary results of the pre/post HDTBR differences between the two studies will be presented at the 2015 Human Research Program Investigators' Workshop. CONCLUSIONS: Although 14-day HDTBR did not seem to induce clinically relevant ocular changes, (sup 2) a systematic evaluation and comparison with the 70-day HDTBR study results will elucidate whether the magnitude of ocular structural and functional changes is affected by the time spent in the recumbent position. Further research will also address the effects of integrated resistance and aerobic training during HDTBR on the ocular outcomes. REFERENCES: 1. Mader TH et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118(10):2058-69. 2. Taibbi G et al. Ocular outcomes evaluation in a 14-day head-down bed rest study. Aviat Space Environ Med. 2014;85(10):983-92.

Cromwell, R.L.↗
NASA NTRS2018

Cardiovascular Disease Outcomes Among the NASA Astronaut Corps

BACKGROUND: Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in spaceflight activities are associated with changes in the cardiovascular system such as decreased carotid artery distensibility and decreased ventricular mass which may lead to an increased risk of cardiovascular disease. Additionally, astronauts who travel into space multiple times or for longer durations may be at an increased risk across their lifespan. To that end, the purpose of this study was to determine the incidence of common cardiovascular disease (CVD) outcomes among the NASA astronaut corps during their active career and through retirement. METHODS: Cardiovascular disease outcomes were defined as reports of any of the following: myocardial infarction (MI), revascularization procedures (coronary artery bypass graft surgery [CABG] or percutaneous coronary intervention [PCI]), hypertension, stroke or transient ischemic attack [TIA], heart failure, or total CVD (as defined by the AHA - combined outcome of MI, Angina Pectoris, heart failure, stroke, and hypertension). Each outcome was identified individually from review of NASA's Electronic Medical Record (EMR), EKG reports, and death certificates using ICD-9 codes as well as string searches of physician notes of astronaut exams that occurred between 1959 and 2016. RESULTS: Of 338 NASA astronauts selected as of 2016, 9 reported an MI, 12 reported a revascularization procedure, (7 PCI and 5 CABG), 4 reported Angina (without MI), 5 reported heart failure, 9 reported stroke/TIA, and 96 reported hypertension. Total CVD was reported in 105 astronauts. No astronaut who had an MI or revascularization procedure flew a spaceflight mission following the event. All MI, revascularization, and stroke events occurred in male astronauts. When reviewing astronaut ECG reports, abnormal ECG reports were found in only 8% of records (n=430) and mainly among retired astronauts (82%), with marked sinus bradycardia being the reason for the abnormal classification.

Charvat, Jacqueline M.↗
NASA NTRSDate not supplied

NASA’s Identified Risks of Adverse Outcomes Due to Inadequate Human Systems Integration Architecture in Human Spaceflight

The NASA Human System Risk Board (HSRB) has the overall responsibility for tracking the evolution of the top ~30 human system risks that it has identified to be associated with human spaceflight. As part of this process, the Board is charged with maintaining a consistent, integrated process to mitigate those risks, and developing evidence-based risk posture recommendations. One of the identified risks is due to inadequate human systems integration architecture (HSIA) and a driving factor of this risk is that given decreasing real-time ground support for execution of complex operations during future exploration missions, there is a possibility of adverse performance outcomes including that crew are unable to adequately respond to unanticipated critical malfunctions or detect safety critical procedural errors. The HSRB uses Directed Acyclic Graphs (DAGs) as a communication tool for describing how astronaut exposure to spaceflight hazards leads to meaningful mission-level health and performance outcomes and as the basis for understanding intermediate causal relationships between risk contributing factors and countermeasures that link hazards to outcomes. The HSIA risk DAG will be presented and described. Historically, critical malfunctions requiring Crew/MCC management occurred at a rate of 1.7 times per year for ISS averaged over the lifetime and 3-4 times per year in the burn in phase for the vehicle. These averages do not include EVA data, which greatly increases the incident rate. Prior experience from the Apollo program showed 10/11 crewed missions experienced significant anomalies where crew relied heavily on MCC expertise in real-time. These failure patterns are in line with those observed in other complex engineered systems (e.g., oil rigs, launch systems, commercial aviation, etc.) It is likely that general malfunction and error rates are > 10% for short duration missions (<30 days), based on past and current spaceflight operations data. Likelihood of adverse outcomes has the potential to increase as crew conduct work with new, complex systems and with less ground support. For Low Earth Orbit missions and Lunar missions less than 30 days, assuming minimal comm delays, disruptions and bandwidth limitations, malfunctions and errors can affect mission objectives and crew health but may be mitigated by ground support. For Lunar missions greater than 30 days and any potential Mars mission malfunctions and errors can have Loss of Crew and Loss of Mission consequences due to reduced ground support (communication delays, constraints and blackouts) for more complex operations, as well as reduced resupply and evacuation options.

Daniel M Buckland↗
NASA NTRS2000

Outcome analysis of individualized vestibular rehabilitation protocols

OBJECTIVE: To determine the outcome of vestibular rehabilitation protocols in subjects with peripheral vestibular disorders compared with normal and abnormal control subjects. STUDY DESIGN: Prospective study using repeated measure, matched control design. Subjects were solicited consecutively according to these criteria: vestibular disorder subjects who had abnormal results of computerized dynamic posturography (CDP) sensory organization tests (SOTs) 5 and 6 and underwent rehabilitation; vestibular disorder subjects who had abnormal results of SOTs 5 and 6 and did not undergo rehabilitation; and normal subjects (normal SOTs). SETTING: Tertiary neurotology clinic. SUBJECTS: Men and women over age 18 with chronic vestibular disorders and chief complaints of unsteadiness, imbalance, and/or motion intolerance, and normal subjects. INTERVENTIONS: Pre- and post-rehabilitation assessment included CDP, vestibular disability, and activities of daily living questionnaires. Individualized rehabilitation plans were designed and implemented to address the subject's specific complaints and functional deficits. Supervised sessions were held at weekly intervals, and self-administered programs were devised for daily home use. MAIN OUTCOME MEASURES: CDP composite and SOT scores, number of falls on CDP, and self-assessment questionnaire results. RESULTS: Subjects who underwent rehabilitation (Group A) showed statistically significant improvements in SOTs, overall composite score, and reduction in falls compared with abnormal (Group B) control groups. Group A's performances after rehabilitation were not significantly different from those of normal subjects (Group C) in SOTs 3 through 6, and close to normal on SOTs 1 and 2. Subjects in Group A also reported statistically significant symptomatic improvement. CONCLUSIONS: Outcome measures of vestibular protocol physical therapy confirmed objective and subjective improvement in subjects with chronic peripheral vestibular disorders. These findings support results reported by other investigators.

NASA Discipline Neuroscience↗
NASA NTRS2016

A Portfolio Analysis Tool for Measuring NASAs Aeronautics Research Progress toward Planned Strategic Outcomes

Description of a tool for portfolio analysis of NASA's Aeronautics research progress toward planned community strategic Outcomes is presented. The strategic planning process for determining the community Outcomes is also briefly described. Stakeholder buy-in, partnership performance, progress of supporting Technical Challenges, and enablement forecast are used as the criteria for evaluating progress toward Outcomes. A few illustrative examples are also presented.

Portfolio Analysis↗
NASA NTRS2016

A Tool for Measuring NASA's Aeronautics Research Progress Toward Planned Strategic Community Outcomes

Description of a tool for portfolio analysis of NASA's Aeronautics research progress toward planned community strategic Outcomes is presented. For efficiency and speed, the tool takes advantage of a function developed in Excels Visual Basic for Applications. The strategic planning process for determining the community Outcomes is also briefly discussed. Stakeholder buy-in, partnership performance, progress of supporting Technical Challenges, and enablement forecast are used as the criteria for evaluating progress toward Outcomes. A few illustrative examples of using the tool are also presented.

Thrusts↗
DOE OSTI2025

Discovering the Multisectoral Impacts of Global Energy Sector Outcomes Through Multiple Ensemble Aggregation Measures

Understanding complex human-Earth system interactions often involves analyzing large scenario ensembles that encompass a wide range of plausible futures. These ensembles often require aggregation to summarize information based on specific criteria or conditions. However, previous research using global change scenario ensembles has largely overlooked how the choice of aggregation method influences the interpretation of results. To address this gap, we leverage a large ensemble data set designed to capture broad energy system dynamics generated using the Global Change Analysis Model. We first explore how energy-related uncertainties are propagated to both global and regional water-energy-food sectors. We then conduct a rank correlation analysis across seven ensemble aggregation measures and demonstrate the need to consider multiple measures in global change scenarios. Our results suggest that global water and food sector outcomes in the 21st century vary widely depending on different scenario assumptions. The global energy productivity is projected to improve by the end of the century across all scenarios. Moreover, regions facing water scarcity challenges in 2100 do not always overlap with those facing extreme energy and food sector outcomes. Although rank correlations across seven aggregation measures are relatively stable across sectors, we identify cases where relying on a single measure leads to losing critical information in the full ensemble. Reliance on a single aggregation measure can distort the interpretation of global change scenario outcomes. Instead, adopting multiple ensemble aggregation measures provides a more holistic understanding of global change scenario ensembles.

Kim, Gijoo↗
DOE OSTI2025

Characterizing and controlling CRISPR repair outcomes in nondividing human cells

Genome editing is poised to revolutionize treatment of genetic diseases, but poor understanding and control of DNA repair outcomes hinders its therapeutic potential. DNA repair is especially understudied in nondividing cells like neurons, limiting the efficiency and precision of genome editing in many clinically relevant tissues. Here, we address this barrier by using induced pluripotent stem cells (iPSCs) and iPSC-derived neurons to examine how postmitotic human neurons repair Cas9-induced DNA damage. CRISPR editing outcomes differ dramatically in neurons compared to genetically identical dividing cells: neurons take longer to fully resolve this damage, and upregulate non-canonical DNA repair factors in the process. Manipulating this response with chemical or genetic perturbations allows us to direct DNA repair toward desired editing outcomes in nondividing human neurons, cardiomyocytes, and primary T cells. By studying DNA repair in clinically relevant cells, we reveal unforeseen challenges and opportunities for precise therapeutic editing.

Ramadoss, Gokul N. [Gladstone Institutes, San Fran↗
NASA NTRS1984

Predictions of Cockpit Simulator Experimental Outcome Using System Models

This study involved predicting the outcome of a cockpit simulator experiment where pilots used cockpit displays of traffic information (CDTI) to establish and maintain in-trail spacing behind a lead aircraft during approach. The experiments were run on the NASA Ames Research Center multicab cockpit simulator facility. Prior to the experiments, a mathematical model of the pilot/aircraft/CDTI flight system was developed which included relative in-trail and vertical dynamics between aircraft in the approach string. This model was used to construct a digital simulation of the string dynamics including response to initial position errors. The model was then used to predict the outcome of the in-trail following cockpit simulator experiments. Outcome included performance and sensitivity to different separation criteria. The experimental results were then used to evaluate the model and its prediction accuracy. Lessons learned in this modeling and prediction study are noted.

Sorensen, J. A.↗
NASA NTRS2011

The 2010 Desert Rats Science Operations Test: Outcomes and Lessons Learned

The Desert RATS 2010 Team tested a variety of science operations management techniques, applying experience gained during the manned Apollo missions and the robotic Mars missions. This test assessed integrated science operations management of human planetary exploration using real-time, tactical science operations to oversee daily crew science activities, and a night shift strategic science operations team to conduct strategic level assessment of science data and daily traverse results. In addition, an attempt was made to collect numerical metric data on the outcome of the science operations to assist test evaluation. The two most important outcomes were 1) the production of significant (almost overwhelming) volume of data produced during daily traverse operations with two rovers, advanced imaging systems and well trained, scientifically proficient crew-members, and 2) the degree to which the tactical team s interaction with the surface crew enhanced science return. This interaction depended on continuous real-time voice and data communications, and the quality of science return from any human planetary exploration mission will be based strongly on the aggregate interaction between a well trained surface crew and a dedicated science operations support team using voice and imaging data from a planet s surface. In addition, the scientific insight developed by both the science operations team and the crews could not be measurable by simple numerical quantities, and its value will be missed by a purely metric-based evaluation of test outcome. In particular, failure to recognize the critical importance of this qualitative type interaction may result in mission architecture choices that will reduce science return.

Eppler, D. B.↗
NASA NTRS2016

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post - Bed Rest and Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genotypic markers of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. These data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. To date we have completed a study on 15 normal subjects with all of the above measures. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗