Outcomes from the Brine Availability Test in Salt (BATS) Heater Test at WIPP
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Mills, Melissa Marie [Sandia National Laboratories↗
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Long-Term Health Metric Development Effort
INTRODUCTION Probabilistic Risk Assessment (PRA) is a methodology applied when high-stakes decisions need to be made about complex systems. PRA often uses risk minimization to aid decision making, such as when establishing vehicle requirements or resource allocations. The NASA Human System Risk Board (HSRB) maintains the human spaceflight risk postures, many of which have in-mission medical outcomes, but the full risk set also includes performance and Long-Term Health (LTH) outcomes. An effort is underway to determine the dependencies between LTH risk outcomes and mission characteristics and to identify metrics for quantifying LTH outcomes. The LTH metrics will be incorporated into future PRA tools currently under development to support crew health and performance decision making. LONG-TERM HEALTH (LTH) RISK LTH risk encompasses the timeframe from immediately post-flight, through the rest of an astronaut’s career, through retirement, and until death. LTH outcomes include the time and interventions needed for the astronaut to return to preflight physiological states after experiencing spaceflight hazards and recovery from any in-mission medical events that persist into the post-flight timeframe. It includes chronic complications that may arise due to experiencing in-flight medical conditions or injuries and medical conditions that occur later in life with a higher probability of occurrence or with more severity because of their spaceflight exposure. Finally, LTH outcomes can also include a reduction in life expectancy due to spaceflight exposures. Eighteen of the HSRB risks contain an LTH component, each with a unique incidence rate and consequence severity. ON-GOING LTH METRIC DEVELOPMENT EFFORTS Based on guidance from a stakeholder workshop held on June 1, 2023, only LTH outcomes with causes tied to spaceflight experience that are significantly different from normal healthy aging and which can be affected by changes in in-mission resources are targeted for inclusion within the PRA modeling efforts. Current on-going efforts include a sensitivity analysis of potential in-flight medical conditions to determine which conditions may persist into post-flight and how the consequences may be affected by in-mission medical resources. Also underway is determination of differences in the time for a return to preflight physiological baselines when in-flight countermeasures are available versus when they are not. Analyses performed with publicly available astronaut data and collaborations with the Lifetime Surveillance of Astronaut Health team are being designed to understand which LTH outcomes differ significantly from natural healthy aging. Information exchanges are also occurring with LTH risk custodians to understand how they quantify outcomes. FUTURE PLANS Risk characteristics will be determined for each LTH risk that meets our inclusion criteria and the dependencies of their outcomes to in-mission resources and mission characteristics will be established. The individual risks will be integrated together into one or more high level LTH metrics for inclusion in the PRA tool, so that LTH risks can be considered along with in-mission risks during crew health and performance system decision support trade studies.
B. E. Lewandowski↗
Results for the Subjective Habitability Acceptability Questionnaire From HERA C5 and C6
BACKGROUND The impact of habitability on psychological and performance outcomes is recognized as an important factor in habitat and vehicle design—especially as missions increase in length. Formal evaluation of habitability’s impact is possible using the Spaceflight Habitability Acceptability Questionnaire (SHAQ), which was psychometrically validated by Roma et al. in 2022 [1]. The SHAQ survey systematically quantifies the relationships between habitat areas (e.g., bedroom, kitchen, hygiene area, office, etc.) and behavioral health and performance (BHP) outcomes (i.e., individual and team performance, mood, stress, sleep, social interaction), and considers the moderating effects of key habitability aspects (i.e., privacy, control, convenience, efficiency, comfort, social density) on that relationship. METHOD Respondents were HERA participants from Campaign 5 and 6 (n = 32). Data from three environments were used in our SHAQ analyses: SHAQ in HERA (in-mission), SHAQ at Home (pre-mission), and SHAQ in Hotel (pre- and post-mission for C6, just pre-mission for C5). For each habitat area, respondents are asked how that area layout impacts six BHP outcomes on a 201-point visual analog scale with the anchors: impairs, has no effect, and facilitates. They also had the option to respond “Not Applicable”. Follow up questions asked why six key habitability aspects (e.g., privacy) influenced the way the habitat area affected a given outcome. Participants indicated whether a habitat area’s habitability aspects were inadequate (low score) to adequate (midpoint) to ideal (high score), using a 201-point visual analog scale as well but were binned to a 7-point scale for analyses. RESULTS AND CONCLUSION When comparing across environments, ratings of BHP outcomes were worse in HERA compared to home and pre-mission hotel, but rebounded for the post-mission hotel such that post-mission hotel rating were often higher than all previous ratings. Within HERA, ratings of how a habitat area impacted an outcome skewed towards facilitation with communal areas (i.e., galley and office) rated most facilitating. The follow up questions about why six key aspects related to habitability moderated outcomes indicated that most habitat areas were rated as having “adequate” habitability characteristics. Privacy was the only moderator with average scores below adequate for all habitat areas. The office had the most moderators scoring above adequate for all habitat areas. Ratings indicated small to moderate effects of layouts on BHP outcomes: with facilitating layouts averaging between 4 and 5, and impairing layouts averaging between 2 and 4. The sleeping module layout facilitated sleep, with ratings indicating adequate comfort but inadequate privacy. The galley layout facilitated social interaction and mood, with ratings indicating adequate efficiency and convenience. The office layout facilitated social interaction, team and individual performance, with ratings similarly indicating adequate efficiency and convenience. The hygiene module worsened individual performance, mood and stress, with ratings indicating less than adequate privacy and social density. Our findings suggest there is value in having dedicated team and individual spaces. REFERENCES [1] Roma, P. G., Landon, L.B., Spencer, C. A., Whitmire, A. M., & Williams, T. J. (2022). SHAQ: Development and Validation. Human Factors: Special Issue on Spaceflight, 65(6), 1074-1104. ACKNOWLEDGEMENTS This project was funded by the NASA Human Research Program directed task Human Factors and Behavioral Performance in HERA (PI = S. Bell) to the BHP Lab. KBR Inc. and JES Tech authors were supported by KBR’s Human Health and Performance Contract NNJ15HK11B with NASA.
behavioral health↗
Long-Term Health Risk Quantification
Astronauts face hazards during spaceflight, including space radiation exposure, isolation and confinement, traveling far distances from Earth, reduced gravity levels, and closed and hostile environments. These hazards drive the definition of human health and performance risks associated with spaceflight. NASA’s Human System Risk Board maintains the human spaceflight risk posture for in-mission risks, as well as post-flight, Long-Term Health (LTH)risks potentially occurring later in the astronaut’s life. LTH risk encompasses the timeframe from immediately post-flight, through the rest of an astronaut’s career, through retirement, and until death. Possible LTH risk outcomes include the time and interventions needed for the astronaut to return to preflight physiological states after experiencing spaceflight hazards and recovery from any in-mission medical events that persist into the post-flight timeframe. It includes chronic complications that may arise due to experiencing in-flight medical conditions or injuries and medical conditions that occur later in life with a higher probability of occurrence or with more severity because of their spaceflight exposure. Finally, LTH risk outcomes can also include a reduction in life expectancy due to spaceflight exposures. There have been 144 medical conditions identified by NASA’s Lifetime Surveillance of Astronaut Health team to be associated with LTH risk. Epidemiological studies have been performed for some of these conditions to determine if astronauts suffer from an increased prevalence or severity of the condition due to their spaceflight experience compared to a comparable cohort .Differences in astronaut mortality or morbidity due to spaceflight experience were not detected in several of these studies. There were two cases where a modest increase in the incidence rate of astronaut LTH outcomes was detected. The first suggested an increase in the incidence of melanoma cases in astronauts, where the number of cases in astronauts were similar to the elevated number of cases observed in airplane pilots. The second provided some evidence of elevated numbers of cardiovascular disease events in astronauts compared to an appropriate healthy comparator cohort, which may warrant additional investigation. The lack of detection of LTH risk outcomes should not ease concerns about astronaut LTH. The studies highlighted here constitute only a small portion of the potential LTH conditions that could occur. Once epidemiological studies are performed on all conditions, significant findings may be detected. The analysis of astronaut LTH also suffers from limited numbers of data points because of the limited numbers of astronauts overall and the even fewer who have reached an age where LTH outcomes may begin to manifest. As shuttle and ISS astronauts begin to age and increase the feasibility of analysis, LTH outcomes may be detected. An application of risk quantification is the use of risk metrics within trade studies for resource prioritization and decision making. Trade studies regarding countermeasures to LTH risk outcomes would benefit from a quantification of LTH risk. NASA has ground-based processes in place such as astronaut screening and access to continuous medical monitoring and care during and after their astronaut career which are the main methods for mitigating LTH risk. In-mission countermeasures, such as acceptable levels of medical care and available countermeasures to counter spaceflight related physiological decrements, can mitigate a poor health and performance status immediately post-flight. Identifying appropriate risk metrics, obtaining valid quantities for them, and tying them to LTH countermeasures are necessary steps for realizing their use in trade studies. This presentation will highlight the challenges associated with the identification, quantification, and utilization of LTH risk metrics
Beth Lewandowski↗
Geospatial analysis of preterm and small-for-gestational age births in Washington D.C.
Background: This study is based on the recognition that adverse pregnancy outcomes significantly affect maternal and infant health, leading to increased morbidity and mortality. These outcomes are shaped by a complex interplay of individual-level factors—like maternal age and education—and community-level influences, including socio-economic status and access to healthcare. Understanding these determinants is crucial for developing effective public health strategies, especially for marginalized populations, by identifying high-risk areas and informing targeted interventions that address both individual and structural barriers. Methods: We utilized geospatial analysis to explore the association between individual- and community-level factors and adverse pregnancy outcomes, specifically preterm birth (PTB) and small-for-gestational-age (SGA) birthweight in Washington, D.C. We used Empirical Bayes smoothing methods to calculate rates of adverse birth outcomes from 2010 to 2018 at the U.S. Census tract–level. Spatial scan statistics were used to investigate if adverse birth outcomes clustered in specific areas. ANOVA tests were conducted for individual- and community-level factors within identified clusters. Results: Spatial analysis identified significant high-risk clusters for PTB and SGA infants primarily in southeastern Washington, D.C., particularly in Wards 7 and 8. Individuals residing within these clusters experienced a 47% increased risk of PTB (RR = 1.467) and a 56% increased risk of SGA (RR = 1.560) compared to those outside clusters. Space–time analysis revealed temporal variation, with PTB clusters persisting from 2011 to 2014 and SGA clusters extending through 2017. Compared to low-risk clusters, high-risk clusters had younger birthing individuals (mean age ~26.5 vs. ~33 years), lower maternal college degree attainment (~20% vs. ~80%), higher rates of late or no prenatal care (~16% vs. 11%), and increased prevalence of smoking and hypertension (all P < 0.001). Community-level indicators showed lower median household incomes ($\$40,000$ vs. ~$\$105,000$), greater poverty (~16% vs. ~7% below $\$10,000$/year), higher public assistance use (~32% vs. ~5%), and reduced healthcare access (greater distances to emergency and specialty care) in high-risk areas (all P < 0.001). Neighborhood deprivation indices were significantly elevated, commutes were longer, and population density was lower in these clusters. These findings highlight that adverse birth outcomes cluster in neighborhoods with pronounced socioeconomic and health disparities. Conclusion: High-risk birth clusters highlight intertwined factors: individual, socio-economic, and geographic. Addressing these requires comprehensive interventions focusing on social and structural determinants of health.
Birth outcomes↗
Low Peripheral Blood Counts and Elevated Proinflammatory Cytokines Signal a Poor CD19 Chimeric Antigen Receptor T-cell Response in Acute Lymphoblastic Leukemia
CD19 chimeric antigen receptor T-cell (CAR-T) therapy has significantly improved outcomes for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, approximately 20% of patients fail to achieve a complete remission (CR), and some develop severe, life-threatening toxicities. Understanding the biological mechanisms underlying both dysfunctional responses and severe toxicity is essential for optimizing patient management and improving therapeutic efficacy. This study aimed to (1) characterize cytokine profiles associated with dysfunctional responses and severe toxicity following CAR-T infusion, (2) examine the timing and trajectory of cytokine changes in relation to treatment outcomes, and evaluate potential strategies for mitigating toxicity and treatment failure. We conducted a comprehensive analysis of serum cytokine profiles in 86 adult and pediatric patients undergoing autologous CD19 CAR-T therapy for B-ALL. Patients were categorized into three groups: (1) Dysfunctional response—Patients who failed to achieve a minimal residual disease-negative CR (MRD-CR) by Day 63 or who experienced recurrence of CD19+ disease in the setting ongoing CAR-T cell detection before Day 63. (2) Functional response with severe cytokine release syndrome (CRS) and/or neurotoxicity (NTX)—Patients with best response of MRD-CR by Day 63 who experienced grade 3 or higher CRS or NTX. (3) Functional response without severe CRS or NTX—Patients with best response of MRD-CR by Day 63 who did not experience grade =3 CRS or NTX. Cytokine levels were measured during the first-week postinfusion and correlated with treatment efficacy, toxicity outcomes, complete blood counts, and CAR-T expansion dynamics. This analysis aimed to better understand how cytokine profiles relate to patient outcomes and immune responses in CAR-T therapy. Patients with dysfunctional response exhibited decreased neutrophils, platelets, and levels of granulocytic cytokines (suggestive of low bone marrow reserve) alongside elevated pro-inflammatory cytokines by Day 1. Functional response with severe toxicity patients showed a progressive rise in proinflammatory cytokines, reaching similar levels to dysfunctional response patients by Day 7. We observed that high cytokines at both the Day 1 and Day 7 time points were associated with poor survival. These findings remained significant when adjusting for high disease burden, a known predictor of severe inflammatory toxicity and lack of response. Early post-CAR-T infusion inflammation is associated with both dysfunctional response and severe toxicity—even after adjusting for disease burden. This suggests that inflammation, in addition to disease burden, plays a role in determining patient outcome. Therefore, strategies aimed at reducing the pro-inflammatory state prior to or early after CAR-T cell infusion may improve outcomes for R/R B-ALL patients.
Serum cytokines↗
Optimizing Medical Kits for Spaceflight
The Integrated Medical Model (IMM) is a probabilistic model that estimates medical event occurrences and mission outcomes for different mission profiles. IMM simulation outcomes describing the impact of medical events on the mission may be used to optimize the allocation of resources in medical kits. Efficient allocation of medical resources, subject to certain mass and volume constraints, is crucial to ensuring the best outcomes of in-flight medical events. We implement a new approach to this medical kit optimization problem. METHODS We frame medical kit optimization as a modified knapsack problem and implement an algorithm utilizing a dynamic programming technique. Using this algorithm, optimized medical kits were generated for 3 different mission scenarios with the goal of minimizing the probability of evacuation and maximizing the Crew Health Index (CHI) for each mission subject to mass and volume constraints. Simulation outcomes using these kits were also compared to outcomes using kits optimized..RESULTS The optimized medical kits generated by the algorithm described here resulted in predicted mission outcomes more closely approached the unlimited-resource scenario for Crew Health Index (CHI) than the implementation in under all optimization priorities. Furthermore, the approach described here improves upon in reducing evacuation when the optimization priority is minimizing the probability of evacuation. CONCLUSIONS This algorithm provides an efficient, effective means to objectively allocate medical resources for spaceflight missions using the Integrated Medical Model.
Optimization↗
The Sufficient Component Cause 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 low doses 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↗
Optimal Stopping Ages for Colorectal Cancer Screening
Importance Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient’s sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk. Objective To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective. Design, Setting, and Participants This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis–Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024. Exposures CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results. Main Outcomes and Measures The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $\$$100 000 per QALYG, was evaluated. Results The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $\$$38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $\$$1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $\$$51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $\$$108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $\$$16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT. Conclusions and Relevance In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.
Harlass, Matthias [Erasmus Erasmus University Medi↗
Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022
Background/aims Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research over the past decade and characterized key regulatory and trial design elements with a focus on the primary efficacy endpoint utilized as the basis of approval. Methods Using the Food and Drug Administration’s Data Analysis Search Host database, we identified novel new drug applications and biologics license applications with orphan drug designation that were approved between 2013 and 2022 for non-oncologic indications. From Food and Drug Administration review documents and other external databases, we examined characteristics of pivotal trials for the included drugs, such as therapeutic area, trial design, and type of primary efficacy endpoints. Differences in trial design elements associated with primary efficacy endpoint type were assessed such as randomization and blinding. Then, we summarized the primary efficacy endpoint types utilized in pivotal trials by therapeutic area, approval pathway, and whether the disease etiology is well defined. Results One hundred and seven drugs that met our inclusion criteria were approved between 2013 and 2022. Assessment of the 107 drug development programs identified 150 pivotal trials that were subsequently analyzed. The pivotal trials were mostly randomized (80%) and blinded (69.3%). Biomarkers (41.1%) and clinical outcomes (42.1%) were commonly utilized as primary efficacy endpoints. Analysis of the use of clinical trial design elements across trials that utilized biomarkers, clinical outcomes, or composite endpoints did not reveal statistically significant differences. The choice of primary efficacy endpoint varied by the drug’s therapeutic area, approval pathway, and whether the indicated disease etiology was well defined. For example, biomarkers were commonly selected as primary efficacy endpoints in hematology drug approvals (70.6%), whereas clinical outcomes were commonly selected in neurology drug approvals (69.6%). Further, if the disease etiology was well defined, biomarkers were more commonly used as primary efficacy endpoints in pivotal trials (44.7%) than if the disease etiology was not well defined (27.3%). Discussion In the past 10 years, numerous novel drugs have been approved to treat non-oncologic rare diseases in various therapeutic areas. To demonstrate their efficacy for regulatory approval, biomarkers and clinical outcomes were commonly utilized as primary efficacy endpoints. Biomarkers were not only frequently used as surrogate efficacy endpoints in accelerated approvals, but also in traditionally approved rare disease drugs. The choice of primary efficacy endpoints varied by therapeutic area, approval pathway, and understanding of disease etiology.
Hong, Kyungwan [Rare Diseases Team, Office of New ↗
A Markov chain model for reliability growth and decay
A mathematical model is developed to describe a complex system undergoing a sequence of trials in which there is interaction between the internal states of the system and the outcomes of the trials. For example, the model might describe a system undergoing testing that is redesigned after each failure. The basic assumptions for the model are that the state of the system after a trial depends probabilistically only on the state before the trial and on the outcome of the trial and that the outcome of a trial depends probabilistically only on the state of the system before the trial. It is shown that under these basic assumptions, the successive states form a Markov chain and the successive states and outcomes jointly form a Markov chain. General results are obtained for the transition probabilities, steady-state distributions, etc. A special case studied in detail describes a system that has two possible state ('repaired' and 'unrepaired') undergoing trials that have three possible outcomes ('inherent failure', 'assignable-cause' 'failure' and 'success'). For this model, the reliability function is computed explicitly and an optimal repair policy is obtained.
Siegrist, K.↗
Goal Directed Model Inversion: A Study of Dynamic Behavior
Goal Directed Model Inversion (GDMI) is an algorithm designed to generalize supervised learning to the case where target outputs are not available to the learning system. The output of the learning system becomes the input to some external device or transformation, and only the output of this device or transformation can be compared to a desired target. The fundamental driving mechanism of GDMI is to learn from success. Given that a wrong outcome is achieved, one notes that the action that produced that outcome 0 "would have been right if the outcome had been the desired one." The algorithm then proceeds as follows: (1) store the action that produced the wrong outcome as a "target" (2) redefine the wrong outcome as a desired goal (3) submit the new desired goal to the system (4) compare the new action with the target action and modify the system by using a suitable algorithm for credit assignment (Back propagation in our example) (5) resubmit the original goal. Prior publications by our group in this area focused on demonstrating empirical results based on the inverse kinematic problem for a simulated robotic arm. In this paper we apply the inversion process to much simpler analytic functions in order to elucidate the dynamic behavior of the system and to determine the sensitivity of the learning process to various parameters. This understanding will be necessary for the acceptance of GDMI as a practical tool.
Colombano, Silvano P.↗
Exploiting Aerobic Fitness To Reduce Risk Of Hypobaric Decompression Sickness
Decompression sickness (DCS) is multivariable. But we hypothesize an aerobically fit person is less likely to experience hypobaric DCS than an unfit person given that fitness is exploited as part of the denitrogenation (prebreathe, PB) process prior to an altitude exposure. Aerobic fitness is peak oxygen uptake (VO2pk, ml/kg/min). METHODS: Treadmill or cycle protocols were used over 15 years to determine VO2pks. We evaluated dichotomous DCS outcome and venous gas emboli (VGE) outcome detected in the pulmonary artery with Doppler ultrasound associated with VO2pk for two classes of experiments: 1) those with no PB or PB under resting conditions prior to ascent in an altitude chamber, and 2) PB that included exercise for some part of the PB. There were 165 exposures (mean VO2pk 40.5 +/- 7.6 SD) with 25 cases of DCS in the first protocol class and 172 exposures (mean VO2pk 41.4 +/- 7.2 SD) with 25 cases of DCS in the second. Similar incidence of the DCS (15.2% vs. 14.5%) and VGE (45.5% vs. 44.8%) between the two classes indicates that decompression stress was similar. The strength of association between outcome and VO2pk was evaluated using univariate logistic regression. RESULTS: An inverse relationship between the DCS outcome and VO2pk was evident, but the relationship was strongest when exercise was done as part of the PB (exercise PB, coef. = -0.058, p = 0.07; rest or no PB, coef. = -0.005, p = 0.86). There was no relationship between VGE outcome and VO2pk (exercise PB, coef. = -0.003, p = 0.89; rest or no PB, coef. = 0.014, p = 0.50). CONCLUSIONS: A significant change in probability of DCS was associated with fitness only when exercise was included in the denitrogenation process. We believe a fit person that exercises during PB efficiently eliminates dissolved nitrogen from tissues.
Conkin, Johnny↗
Exploiting Aerobic Fitness to Reduce Risk of Hypobaric Decompression Sickness
Decompression sickness (DCS) is multivariable. But we hypothesize an aerobically fit person is less likely to experience hypobaric DCS than an unfit person given that fitness is exploited as part of the denitrogenation (prebreathe, PB) process prior to an altitude exposure. Aerobic fitness is peak oxygen uptake (VO2pk, ml/kg/min). Treadmill or cycle protocols were used over 15 years to determine VO2pks. We evaluated dichotomous DCS outcome and venous gas emboli (VGE) outcome detected in the pulmonary artery with Doppler ultrasound associated with VO2pk for two classes of experiments: 1) those with no PB or PB under resting conditions prior to ascent in an altitude chamber, and 2) PB that included exercise for some part of the PB. There were 165 exposures (mean VO2pk 40.5 plus or minus 7.6 SD) with 25 cases of DCS in the first protocol class and 172 exposures (mean VO2pk 41.4 plus or minus 7.2 SD) with 25 cases of DCS in the second. Similar incidence of the DCS (15.2% vs. 14.5%) and VGE (45.5% vs. 44.8%) between the two classes indicates that decompression stress was similar. The strength of association between outcome and VO2pk was evaluated using univariate logistic regression. An inverse relationship between the DCS outcome and VO2pk was evident, but the relationship was strongest when exercise was done as part of the PB (exercise PB, coef. = -0.058, p = 0.07; rest or no PB, coef. = -0.005, p = 0.86). There was no relationship between VGE outcome and VO2pk (exercise PB, coef. = -0.003, p = 0.89; rest or no PB, coef. = 0.014, p = 0.50). A significant change in probability of DCS was associated with fitness only when exercise was included in the denitrogenation process. We believe a fit person that exercises during PB efficiently eliminates dissolved nitrogen from tissues.
Conkin, J.↗
Differences in Characteristics of Aviation Accidents During 1993-2012 Based on Aircraft Type
Civilian aircraft are available in a variety of sizes, engine types, construction materials and instrumentation complexity. For the analysis reported here, eleven aircraft categories were developed based mostly on aircraft size and engine type, and these categories were applied to twenty consecutive years of civil aviation accidents. Differences in various factors were examined among these aircraft types, including accident severity, pilot characteristics and accident occurrence categories. In general, regional jets and very light sport aircraft had the lowest rates of adverse outcomes (injuries, fatal accidents, aircraft destruction, major accidents), while aircraft with twin (piston) engines or with a single (piston) engine and retractable landing gear carried the highest incidence of adverse outcomes. The accident categories of abnormal runway contact, runway excursions and non-powerplant system/component failures occur frequently within all but two or three aircraft types. In contrast, ground collisions, loss of control - on ground/water and powerplant system/component failure occur frequently within only one or two aircraft types. Although accidents in larger aircraft tend to have less severe outcomes, adverse outcome rates also differ among accident categories. It may be that the type of accident has as much or more influence on the outcome as the type of aircraft.
Evans, Joni K.↗
The Mitigating Effects of Artificial gravity on Microgravity
The effects of microgravity on the human body can be debilitating however, the use of artificial gravity has the potential to completely mitigate these effects. Developing an artificial gravity habitation spacecraft concept could have positive effects on the astronauts spending long durations in space. Researching the past and upcoming artificial gravity concepts was accomplished using resources provided by my mentors, i.e. NASA Technical Reports Server (NTRS), human research roadmap, and the Aerospace Research Central (ARC) in coordination with other academic sources and research papers. This research has been accomplished over a several week period that looks at past artificial gravity concepts and the implications of instituting them or new designs in the future. Also, the research examines how to improve future artificial gravity concepts by applying what we know about past designs and what we are creating today. The expected outcomes of artificial gravity are that the health risks imposed on astronauts due to not being in Earth’s gravity environment for long duration space missions will decrease. No other microgravity mitigation technique addresses neurological problems such as fluid shift and VIIP syndrome as they only address physical conditions with exercise and supplements Another outcome is that using artificial gravity should reduce the long-term health effects that happen after the astronauts return to Earth because they will not be exposed to microgravity for as long. The real outcomes should be similar, if not the same, as the expected outcomes mentioned above. This process of creating artificial gravity aboard spacecrafts has potential to create a plethora of positive outcomes. The research completed will contribute to NASA’s missions and goals because the information gathered directly relates to the goal of sending humans to Mars and beyond and the research looks at how to solve one of the major problems associated with achieving that goal soon: microgravity. This research will contribute to NASA’s mission of sending astronauts to Mars, with a lower risk assessment, because artificial gravity will potentially mitigate the health risks (VIIP syndrome) associated with long duration in space flight.
Elizabeth Anne Westfall↗
Improving the Fidelity of Capability & Resource Weighting in A Probalistic Risk Assessment Model for Spaceflight
INTRODUCTION NASA’s Informing Mission Planning via Analysis of Complex Tradespaces (IMPACT) tool uses Probabilistic Risk Assessment (PRA) to provide an evidence-based, data-driven estimate of how medical system capabilities affect mission outcomes. IMPACT maps condition incidence to available resources thereby facilitating the calculation of outcome metrics that allow the estimation of mission medical risk. Conditions can be nominally categorized as either treated or untreated depending on the availability of necessary diagnostic and therapeutic capabilities. This categorization enables IMPACT to estimate the effect of various medical system configurations on mission outcomes such as crew mortality, disability, crew member down-time, return to duty/recovery, and need for evacuation. IMPACT currently employs an equal weighting, “partial credit” approach to define treatment in which each of the capabilities associated with a given condition contributes an equal amount to management of the condition. This feature enables IMPACT to report values in between “fully untreated” and “fully treated” based on the proportion of capabilities available within the model. However, as is normal in medical/clinical practice, not all individual capabilities contribute equally to medical care. For example, the ability to provide intramuscular epinephrine during an anaphylactic episode contributes more likelihood of overall management success than does the administration of oral diphenhydramine. We hypothesize that weighting the relative contribution of each capability to each specific condition will improve outcome prediction and therefore will better provide mission planners with more nuanced and accurate options when designing space medical systems. METHODS Using a five-point Fibonacci scaling sequence (1, 2, 3, 5, 8) subject matter experts from NASA’s Exploration Medical Capabilities (ExMC) element assigned relative contribution weighting values to each identified capability within IMPACT. Since the relative importance of each capability varies depending on the specific condition, the resulting “partial” weighting was completed for more than 1,600 individual weighting assignments for 666 capabilities across 121 conditions. Each assignment required three-physician concurrence based on the overall importance of the capability to the diagnosis and management of the condition being considered and the difficulty with which it could be improvised by the crew. Once complete, 100,000 IMPACT simulations were run for a 6-month Lunar mission with a 30-day surface stay to evaluate the effect of this modification of the model. RESULTS Partial weighting significantly decreased predicted task time loss (TTL), evacuation, and loss of crew life without causing significant changes to the recommended medical system design. CONCLUSIONS The paucity of real-world referent data to support long-duration space missions of this type limits the ability to judge one predictive analytics method as superior to another. However, since the proposed method significantly reduces and optimizes outcome risks—without changing the medical system design—incorporating a partial weighting methodology is likely to provide a more accurate and operationally-relevant representation of medical risk without compromising IMPACTs ability to inform overarching medical system requirements.
Steller JG↗
Advances in Design Capabilities for Planetary Missions from the NASA Entry Systems Modeling and Instrumentation Portfolio
The Entry Systems Modeling project (ESM) is supported by both the NASA Space Technology and the Science Mission Directorates and focuses on developing simulation tools and validated models for characterizing the performance of entry systems tailored to planetary destinations across the Solar System. ESM is organized into six technical capability areas that together address all relevant factors related to spacecraft entry, as well as some aspects of descent: Thermal Protection System (TPS) Materials; Aerothermodynamics; Entry & Descent Vehicle Dynamics; Guidance, Navigation, and Control; Vehicle Systems Analysis; and Advanced Tools and Numerical Methods. Development within the capability areas is undertaken explicitly with a focus on transition and infusion to science missions, human exploration missions, and commercial space activities. The present talk details developments that specifically impact science missions, including simulation tool capabilities that aid in mission design and model development to understand entry system performance at a given destination. Examples of the successful infusion and transition of such project outcomes to science missions also are provided. Several simulation tool development efforts within ESM have resulted in new design capabilities for missions. One such outcome is improved toolsets for mission trajectory and concept of operations design. Specifically, an initiative to couple a leading tool for entry, ascent/descent, and orbital trajectory optimization (Program to Optimize Simulated Trajectories II or POST2) to those used within the Agency for interplanetary trajectory optimization (Copernicus and Monte) has made substantial progress, with the outcomes to date promising to allow efficient trajectory optimization across mission phases. Additionally, toolchains for the evaluation of vehicle performance during entry and descent have been developed that allow assessment of multi-dimensional aeroheating on detailed vehicle geometries, characterization of deployment and inflation of parachutes, and assessment of vehicle dynamic stability during descent. These capabilities are achieved by coupling diverse sets of physics together – material response, computational fluid dynamics, radiation, and vehicle dynamics – to suitably describe complex entry and descent phenomena. Several model development and validation efforts for specific destinations and entry regimes also are underway within the ESM project. For instance, new experimental capabilities to validate radiation models at low densities/high altitudes recently have been established with project support, specifically the Low-Density Shock Tube (LDST) at the NASA Ames Research Center Electric Arc Shock Tube (EAST) facility. The LDST is being leveraged to develop improved models of shock layer kinetics and radiation in Titan atmospheres, while future studies will be conducted in the LDST and the existing high velocity shock tube to provide validation data for radiation models of Venus, Ice Giants, and Mars atmospheres. Models describing the aerothermal and thermo-structural performance of Thermal Protection System (TPS) materials has been another focus, with multiscale modeling activities on-going for the two leading TPS materials applicable to a range of entry conditions and science missions: the Phenolic-Impregnated Carbon Ablator (PICA) and woven materials like 3D Mid-Density Carbon Phenolic (3MDCP). A continual effort is made to infuse and transition outcomes from ESM simulation tool and model development activities into relevant science missions. Significant progress has been made on this front, with missions such as Dragonfly, DAVINCI, and Mars Missions benefitting from project outcomes. The groundwork also is being laid to provide insights into forward looking missions to Gas/Ice Giants as well as for potential sample returns.
Justin Haskins↗