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Earth-Independent Medical Operations (EIMO) Concept of Operations

Compared to the current paradigm for crew health in low-Earth orbit and Lunar missions that rely on constant communication with Mission Control, there is an anticipated shift in medical operations for deep-space exploration missions. This shift stems from mission constraints imposed by the considerable distance from Earth, which include resource limitations due to a lack of resupply, mass, power, volume, and data limitations, challenges imposed by communication latency and the inability to evacuate in case of emergencies. To transition towards a more self-reliant medical approach, a comprehensive strategy is essential to progressively enable crew autonomy and mitigate mission success risks in the challenging environment of space. This transformative shift is collectively referred to as "Earth-Independent Medical Operations" (EIMO), signifying the gradual transfer of medical care and decision-making from terrestrial resources to space-based assets. This transition is aimed at bolstering astronaut health and performance while simultaneously reducing the overall risks associated with space missions. The constraints related to EIMO necessitate an integrated development of medical systems, featuring interoperability with mission planning, vehicle design, spacesuit design, and data architecture. This integration is vital in establishing a robust medical infrastructure that not only supports the well-being of astronauts but also ensures the success of the mission as a whole. The Human Research Program (HRP) Exploration Medical Capability (ExMC) Element has developed a model-based Concept of Operations (ConOps) outlining an initial vision for EIMO. Within this ConOps, a comprehensive view is presented, encompassing stakeholder needs, system objectives, and system goals associated with EIMO. Additionally, it provides illustrative examples of the various activities (scenarios) for which the system will be employed during missions. The selection of these activities has been meticulous, aiming to encompass a wide spectrum of medical conditions, including those falling under different risk categories, such as low-likelihood-low-consequence, low-likelihood-high-consequence, and high-likelihood-low-consequence. The selection of these activities (scenarios) effectively encompasses the wide range of medical events situated within an assumed probability-consequence bell curve. In each scenario, at least one of the five main EIMO components identified is captured. Those EIMO components are: Pre-mission Planning, Acute and Emergent Management Decision Making, Prolonged Medical Management Decision Making, Supplies and Resource Management, and Task Load Management. The ConOps was developed by a multidisciplinary team consisting of systems engineers, scientists, and clinicians across NASA and aims to serve as an initial recommendation to gradually and safely enabling crew autonomy for Mars missions and beyond.

Earth Independent Medical Operations↗

Earth-Independent Medical Operations (EIMO) Concept of Operations (ConOps)

Compared to the current paradigm for crew health in low-Earth orbit and Lunar missions that rely on constant communication with Mission Control, there is an anticipated shift in medical operations for deep-space exploration missions. This shift stems from mission constraints imposed by the considerable distance from Earth, which include resource limitations due to a lack of resupply, mass, power, volume, and data limitations, challenges imposed by communication latency and the inability to evacuate in case of emergencies. To transition towards a more self-reliant medical approach, a comprehensive strategy is essential to progressively enable crew autonomy and mitigate mission success risks in the challenging environment of space. This transformative shift is collectively referred to as "Earth-Independent Medical Operations" (EIMO), signifying the gradual transfer of medical care and decision-making from terrestrial resources to space-based assets. This transition is aimed at bolstering astronaut health and performance while simultaneously reducing the overall risks associated with space missions. The constraints related to EIMO necessitate an integrated development of medical systems, featuring interoperability with mission planning, vehicle design, spacesuit design, and data architecture. This integration is vital in establishing a robust medical infrastructure that not only supports the well-being of astronauts but also ensures the success of the mission as a whole. The Human Research Program (HRP) Exploration Medical Capability (ExMC) Element has developed a model-based Concept of Operations (ConOps) outlining an initial vision for EIMO. Within this ConOps, a comprehensive view is presented, encompassing stakeholder needs, system objectives, and system goals associated with EIMO. Additionally, it provides illustrative examples of the various activities (scenarios) for which the system will be employed during missions. The selection of these activities has been meticulous, aiming to encompass a wide spectrum of medical conditions, including those falling under different risk categories, such as low-likelihood-low-consequence, low-likelihood-high-consequence, and high-likelihood-low-consequence. The selection of these activities (scenarios) effectively encompasses the wide range of medical events situated within an assumed probability-consequence bell curve. In each scenario, at least one of the five main EIMO components identified is captured. Those EIMO components are: Pre-mission Planning, Acute and Emergent Management Decision Making, Prolonged Medical Management Decision Making, Supplies and Resource Management, and Task Load Management. The ConOps was developed by a multidisciplinary team consisting of systems engineers, scientists, and clinicians across NASA and aims to serve as an initial recommendation to gradually and safely enabling crew autonomy for Mars missions and beyond.

Earth Independent Medical Operations↗

Need for advanced research reactors for the next-generation reactor physics, analysis tools, and technology

Full text of publication follows. There is an urgent need for design and deployment of advanced research and test reactors in support of design, licensing and operation of advanced power reactors and education of next generation nuclear workforce. Existing research reactors mostly were designed and constructed decades ago with the main objectives of training operators, performing reactor physics experiments, and educating nuclear engineers and scientists. There are already gaps and significant concern about future capabilities for the existing research reactor facilities to address modern instrumentation and/or flexible environments for: performing reactor physics studies for advanced designs which have significantly different core materials forms and compositions, reactor shapes and size; validation of advanced high-fidelity software; development of machine learning algorithms for enhancement of human-machine collaboration in support of reactor monitoring, operation and safeguards; and, effective education of the next-generation workforce. The authors will focus on the need for advanced research reactors to improve and validate fast and accurate simulation tools for high-fidelity modeling and analysis of nuclear reactors in support of their design, optimization, licensing, operation, and monitoring. In the past, simulation tools were limited to relatively coarse models using approximate methodologies that benefited from two main factors: i) allowance for large margins and tolerances; ii) ability to construct prototype (e.g., zero power) reactors for adjustment of approximate methodologies. The next generation reactors have to be designed mainly by using novel high-fidelity computational tools that are accurate and fast, and therefore can be used for parametric studies and uncertainty quantification. To sufficiently demonstrate the accuracy of these tools, advanced research reactors are needed. The authors argue the need for new computational paradigms such as the MRT (Multistage, Response- function Transport) methodology which has resulted in the development of the novel high-fidelity RAPID (Real-time Analysis for Particle-transport and In-situ Detection) code system. Such code systems have to be robust in modeling any complex system, and should be fast and accurate, henceforth their uncertainties can be quantified at reasonable costs. Again, advanced research reactors are needed for the validation of the fidelity and accuracy of new computational tools. (authors)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Vertex finding in neutrino-nucleus interaction: a model architecture comparison

We compare different neural network architectures for machine learning algorithms designed to identify the neutrino interaction vertex position in the MINERvA detector. The architectures developed and optimized by hand are compared with the architectures developed in an automated way using the package “Multi-node Evolutionary Neural Networks for Deep Learning” (MENNDL), developed at Oak Ridge National Laboratory. While the domain-expert hand-tuned network was the best performer, the differences were negligible and the auto-generated networks performed as well. There is always a trade-off between human, and computer resources for network optimization and this work suggests that automated optimization, assuming resources are available, provides a compelling way to save significant expert time.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Additional Developments in Atmosphere Revitalization Modeling and Simulation

NASA's Advanced Exploration Systems (AES) program is developing prototype systems, demonstrating key capabilities, and validating operational concepts for future human missions beyond Earth orbit. These forays beyond the confines of earth's gravity will place unprecedented demands on launch systems. They must launch the supplies needed to sustain a crew over longer periods for exploration missions beyond earth's moon. Thus all spacecraft systems, including those for the separation of metabolic carbon dioxide and water from a crewed vehicle, must be minimized with respect to mass, power, and volume. Emphasis is also placed on system robustness both to minimize replacement parts and ensure crew safety when a quick return to earth is not possible. Current efforts are focused on improving the current state-of-the-art systems utilizing fixed beds of sorbent pellets by evaluating structured sorbents, seeking more robust pelletized sorbents, and examining alternate bed configurations to improve system efficiency and reliability. These development efforts combine testing of sub-scale systems and multi-physics computer simulations to evaluate candidate approaches, select the best performing options, and optimize the configuration of the selected approach. This paper describes the continuing development of atmosphere revitalization models and simulations in support of the Atmosphere Revitalization Recovery and Environmental Monitoring (ARREM)

Coker, Robert F.↗

Additional Developments in Atmosphere Revitalization Modeling and Simulation

NASA's Advanced Exploration Systems (AES) program is developing prototype systems, demonstrating key capabilities, and validating operational concepts for future human missions beyond Earth orbit. These forays beyond the confines of earth's gravity will place unprecedented demands on launch systems. They must launch the supplies needed to sustain a crew over longer periods for exploration missions beyond earth's moon. Thus all spacecraft systems, including those for the separation of metabolic carbon dioxide and water from a crewed vehicle, must be minimized with respect to mass, power, and volume. Emphasis is also placed on system robustness both to minimize replacement parts and ensure crew safety when a quick return to earth is not possible. Current efforts are focused on improving the current state-of-the-art systems utilizing fixed beds of sorbent pellets by evaluating structured sorbents, seeking more robust pelletized sorbents, and examining alternate bed configurations to improve system efficiency and reliability. These development efforts combine testing of sub-scale systems and multi-physics computer simulations to evaluate candidate approaches, select the best performing options, and optimize the configuration of the selected approach. This paper describes the continuing development of atmosphere revitalization models and simulations in support of the Atmosphere Revitalization Recovery and Environmental Monitoring (ARREM) project within the AES program.

Coker, Robert F.↗

A machine learning approach for identifying variables associated with risk of developing neutralizing antidrug antibodies to factor VIII

A key unmet need in the management of hemophilia A (HA) is the lack of clinically validated markers that are associated with the development of neutralizing antibodies to Factor VIII (FVIII) (commonly referred to as inhibitors). This study aimed to identify relevant biomarkers for FVIII inhibition using Machine Learning (ML) and Explainable AI (XAI) using the My Life Our Future (MLOF) research repository. The dataset includes biologically relevant variables such as age, race, sex, ethnicity, and the variants in the F8 gene. In addition, we previously carried out Human Leukocyte Antigen Class II (HLA-II) typing on samples obtained from the MLOF repository. Using this information, we derived other patient-specific biologically and genetically important variables. These included identifying the number of foreign FVIII derived peptides, based on the alignment of the endogenous FVIII and infused drug sequences, and the foreign-peptide HLA-II molecule binding affinity calculated using NetMHCIIpan. The data were processed and trained with multiple ML classification models to identify the top performing models. The top performing model was then chosen to apply XAI via SHAP, (SHapley Additive exPlanations) to identify the variables critical for the prediction of FVIII inhibitor development in a hemophilia A patient. Using XAI we provide a robust and ranked identification of variables that could be predictive for developing inhibitors to FVIII drugs in hemophilia A patients. These variables could be validated as biomarkers and used in making clinical decisions and during drug development. The top five variables for predicting inhibitor development based on SHAP values are: (i) the baseline activity of the FVIII protein, (ii) mean affinity of all foreign peptides for HLA DRB 3, 4, & 5 alleles, (iii) mean affinity of all foreign peptides for HLA DRB1 alleles), (iv) the minimum affinity among all foreign peptides for HLA DRB1 alleles, and (v) F8 mutation type.

60 APPLIED LIFE SCIENCES↗

Computed Tomography Radiomics Predicts HPV Status and Local Tumor Control After Definitive Radiochemotherapy in Head and Neck Squamous Cell Carcinoma

Purpose: This study aimed to predict local tumor control (LC) after radiochemotherapy of head and neck squamous cell carcinoma (HNSCC) and human papillomavirus (HPV) status using computed tomography (CT) radiomics. Methods and Materials: HNSCC patients treated with definitive radiochemotherapy were included in the retrospective study approved by the local ethical commission (93 and 56 patients in the training and validation cohorts, respectively). Three hundred seventeen CT radiomic features, including those based on shape, intensity, texture, and wavelet transform, were calculated in the primary tumor region. Cox and logistic regression models were built to predict LC and HPV status, respectively. The best-performing features in the univariable analysis were included in the multivariable analysis after the exclusion of redundant features. The quality of the models was assessed using the concordance index (CI) for modeling of LC and receiver operating characteristics area under the curve (AUC) for HPV status prediction. The radiomics LC model was compared to a model incorporating clinical parameters (tumor stage, volume, and HPV status) and a mixed model. Results: A radiomic signature comprising 3 features was significantly associated with LC (CI{sub training} = 0.75 and CI{sub validation} = 0.78), showing that tumors with a more heterogeneous CT density distribution are at risk for decreased LC. The addition of clinical parameters to the radiomics model slightly improved the model in the training cohort but not in the validation cohort. Another radiomic signature showed good performance in HPV status prediction (AUC{sub training} = 0.85 and AUC{sub validation} = 0.78) and indicated that HPV-positive tumors have a more homogenous CT density distribution. Conclusions: Heterogeneity of HNSCC tumor density, quantified by CT radiomics, is associated with LC after radiochemotherapy and HPV status.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Vestibular System and Human Dynamic Space Orientation

The motion sensors of the vestibular system are studied to determine their role in human dynamic space orientation and manual vehicle control. The investigation yielded control models for the sensors, descriptions of the subsystems for eye stabilization, and demonstrations of the effects of motion cues on closed loop manual control. Experiments on the abilities of subjects to perceive a variety of linear motions provided data on the dynamic characteristics of the otoliths, the linear motion sensors. Angular acceleration threshold measurements supplemented knowledge of the semicircular canals, the angular motion sensors. Mathematical models are presented to describe the known control characteristics of the vestibular sensors, relating subjective perception of motion to objective motion of a vehicle. The vestibular system, the neck rotation proprioceptors and the visual system form part of the control system which maintains the eye stationary relative to a target or a reference. The contribution of each of these systems was identified through experiments involving head and body rotations about a vertical axis. Compensatory eye movements in response to neck rotation were demonstrated and their dynamic characteristics described by a lag-lead model. The eye motions attributable to neck rotations and vestibular stimulation obey superposition when both systems are active. Human operator compensatory tracking is investigated in simple vehicle orientation control system with stable and unstable controlled elements. Control of vehicle orientation to a reference is simulated in three modes: visual, motion and combined. Motion cues sensed by the vestibular system through tactile sensation enable the operator to generate more lead compensation than in fixed base simulation with only visual input. The tracking performance of the human in an unstable control system near the limits of controllability is shown to depend heavily upon the rate information provided by the vestibular sensors.

VESTIBULAR APPARATUS↗

Dual arm robotic system with sensory input

The need for dual arm robots in space station assembly and satellite maintainance is of increasing significance. Such robots will be in greater demand in the future when numerous tasks will be assigned to them to relieve the direct intervention of humans in space. Technological demands from these robots will be high. They will be expected to perform high speed tasks with a certain degree of autonomy. Various levels of sensing will have to be used in a sophisticated control scheme. Ongoing research in control, sensing and real-time software to produce a two-arm robotic system than can accomplish generic assembly tasks is discussed. The control hierarchy and the specific control approach are discussed. A decentralized implementation of model-reference adaptive control using Variable Structure controllers and the incorporation of tactile feedback is considered.

Ozguner, U.↗

Electroencephalographic imaging of higher brain function

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Non-NASA Center↗

An Up-Close Look at Ares I-X

On October 28, 2009, one day later than the originally planned launch date, the Ares I-X suborbital test flight roared into the Florida sky. Flying its preplanned parabolic arc over the Atlantic, the development test vehicle for the Ares I crew launch vehicle performed as advertised, executing a perfect liftoff, 90-degree roll maneuver, ascent, and separation before its upper and lower stages descended into the ocean 150 miles downrange. This test flight, while carrying no astronauts, marked a major milestone for NASA, which had not flown a test launch of a human-rated rocket since the first flight of the Space Shuttle in 1981. During the flight, over 700 sensors collected over 900 measurements, which NASA will apply to validating the engineering models they used to design the vehicle in the first place. That data, telemetered to the ground and stored in a flight recorder onboard, was the primary "payload" of the mission.

Leahy, Bart↗

The Zero Boil-Off Tank Experiment Ground Testing and Verification of Fluid and Thermal Performance

The Zero Boil-Off Technology (ZBOT) Experiment involves performing a small scale International Space Station (ISS) experiment to study tank pressurization and pressure control in microgravity. The ZBOT experiment consists of a vacuum jacketed test tank filled with an inert fluorocarbon simulant liquid. Heaters and thermo-electric coolers are used in conjunction with an axial jet mixer flow loop to study a range of thermal conditions within the tank. The objective is to provide a high quality database of low gravity fluid motions and thermal transients which will be used to validate Computational Fluid Dynamic (CFD) modeling. This CFD can then be used in turn to predict behavior in larger systems with cryogens. This paper will discuss the work that has been done to demonstrate that the ZBOT experiment is capable of performing the functions required to produce a meaningful and accurate results, prior to its launch to the International Space Station. Main systems discussed are expected to include the thermal control system, the optical imaging system, and the tank filling system.This work is sponsored by NASAs Human Exploration Mission Directorates Physical Sciences Research program.

Fluid management↗

Using Degradation Modeling to Identify Fragile Operational Conditions in Human- and Component-driven Resilience Assessment

Studying failure events shows that many high-impact events result from the complex interactions between precipitating failure events and degraded operational conditions. Often, when a system is put in operations, unforeseen practical realities (e.g., maintenance and/or workforce availability) lead the system to be operated in configurations outside its envisioned nominal range. However, design-time failure models often assume that the failure events are initiated in an idealized, nominal state of system operation, resulting in an incomplete assessment of future risk. To solve this, this paper develops a framework to consider degraded operational performance in scenario-based resilience models which uses a corresponding model of performance degradation to determine the values of deteriorated model parameters in the resilience model. This framework is demonstrated on a remotely-piloted rover to determine the (individual and combined) effect of drive-train wear and operator fatigue on the resilience of the rover to drive-train faults. This demonstration showed the substantial impact that degradation has on resilience, highlighting the need to account for degradation in resilience models–specifically, unconsidered degradation can lead to overestimates of resilience (and thus underestimates of safety margin) and because resilience can degrade prior to visible unreliability, which can lead to an operational environment with a high propensity for high-impact unforeseen failure events.

resilience↗

Using Degradation Modeling to Identify Fragile Operational Conditions in Human- and Component-driven Resilience Assessment

Studying failure events shows that many high-impact events result from the complex interactions between precipitating failure events and degraded operational conditions. Often, when a system is put in operations, unforeseen practical realities (e.g., maintenance and/or workforce availability) lead the system to be operated in configurations outside its envisioned nominal range. However, design-time failure models often assume that the failure events are initiated in an idealized, nominal state of system operation, resulting in an incomplete assessment of future risk. To solve this, this paper develops a framework to consider degraded operational performance in scenario-based resilience models which uses a corresponding model of performance degradation to determine the values of deteriorated model parameters in the resilience model. This framework is demonstrated on a remotely-piloted rover to determine the (individual and combined) effect of drive-train wear and operator fatigue on the resilience of the rover to drive-train faults. This demonstration showed the substantial impact that degradation has on resilience, highlighting the need to account for degradation in resilience models--specifically, unconsidered degradation can lead to overestimates of resilience (and thus underestimates of safety margin) and because resilience can degrade prior to visible unreliability, which can lead to an operational environment with a high propensity for high-impact unforeseen failure events.

Daniel Hulse↗

Safety Impacts of Automated Vehicles in Mixed Traffic

Previous research have shown that Automated Vehicles (AV) have the potential to improve transportation thanks to the possibility to perform some control functions without driver input (1). A question that remains is what are the safety impacts of the interaction between human-driven vehicles with different levels of automation at a particular intersection?The main objective of this paper is to build the behavioral framework to simulate different levels of automation and to study the safety impact of these levels under different penetration scenarios. Real-life connected vehicle data were incorporated to revise the Wiedemann car-following model and simulate the behavior of human-driven vehicles, level 3 and level 5 AVs.

Ramin, Arvin↗

An Innovative Approach to Modeling VIPER Rover Software Life Cycle Cost

NASA’s “Volatiles Investigating Polar Exploration Rover” (VIPER) will be the first robotic mission to prospect for water ice near the south pole of the Moon in late 2023 on a 100-Earth-day mission. The information that the VIPER rover provides will help improve understanding of the composition, distribution, and accessibility of Lunar polar volatiles and will help determine how the Moon’s resources can support future human space exploration. VIPER, however, represents a radical departure from the way that NASA has traditionally developed planetary robotic missions. A key consequence of these differences is that estimating the cost of VIPER’s rover software is challenging and complex.For example, VIPER is being developed using management procedures typically applied to NASA research and technology projects, rather than space flight programs. In addition, key portions of the rover’s software are being designed as ground software to run on mission control computers (rather than on-board the rover as flight software as with prior planetary missions) taking advantage of continuous, interactive data communications between the Moon and Earth and higher performance computing available on the ground. Moreover, the rover’s software is being engineered using Agile software development practices and incorporates a significant amount of open-source, rather than following traditional (spiral, waterfall, etc.) development methods and in-house code. In this paper, we present an innovative process to estimate the life cycle cost of VIPER’s rover software. We first describe how we modeled the architecture and code counts for three software elements: Rover Flight Software (RFSW), Rover Ground Software (RGSW), and Rover Simulation Software (RSIM). We then discuss key challenges and unique aspects of our approach, such as the lack of Lunar rover analogies, the need to integrate and test large open source software, and the strategies developed to account for use of non-space flight management practices and the impact of the COVID-19 pandemic. We conclude with a summary of our results, including cumulative distribution, nearest neighbors and cluster analysis, as well as heuristics used to confirm the reasonableness of the cost estimate.

Utz, Hans↗

Drosophila models to study causative genes for human rare intractable neurological diseases

Highlights: • Drosophila models targeting some ALS-causing genes are described. • Drosophila models targeting some CMT-causing genes are described. • Drosophila models targeting some Sotos syndrome-causing genes are described. • Genes and pathways that commonly interact with ALS- and/or CMT-causing genes are described. Drosophila is emerging as a convenient model for investigating human diseases. Functional homologues of almost 75% of human disease-related genes are found in Drosophila. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes defects in motoneurons. Charcot-Marie-Tooth disease (CMT) is one of the most commonly found inherited neuropathies affecting both motor and sensory neurons. No effective therapy has been established for either of these diseases. In this review, after overviewing ALS, Drosophila models targeting several ALS-causing genes, including TDP-43, FUS and Ubiquilin2, are described with their genetic interactants. Then, after overviewing CMT, examples of Drosophila models targeting several CMT-causing genes, including mitochondria-related genes and FIG 4, are also described with their genetic interactants. In addition, we introduce Sotos syndrome caused by mutations in the epigenetic regulator gene NSD1. Lastly, several genes and pathways that commonly interact with ALS- and/or CMT-causing genes are described. In the case of ALS and CMT that have many causative genes, it may be not practical to perform gene therapy for each of the many disease-causing genes. The possible uses of the common genes and pathways as novel diagnosis markers and effective therapeutic targets are discussed.

60 APPLIED LIFE SCIENCES↗