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Expression of Enzymes that Metabolize Medications

INTRODUCTION: Increased exposure to radiation is one physiological stressor associated with spaceflight and it is feasible to conduct ground experiments using known radiation exposures. The health of the liver, especially the activity rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. While radiation is known to alter normal physiological function, how radiation affects liver metabolism of administered medications is unclear. Crew health could be affected if the actions of medications used in spaceflight deviated from expectations formed during terrestrial medication use. This study is an effort to identify liver metabolic enzymes whose expression is altered by spaceflight or by radiation exposures that mimic features of the spaceflight environment. METHODS: Using procedures approved by the Animal Care and Use Committee, mice were exposed to either 137Cs (controls, 50 mGy, 6Gy, or 50 mGy + 6Gy separated by 24 hours) or 13 days of spaceflight on STS 135. Animals were anesthetized and sacrificed at several time points (4 hours, 24 hours or 7 days) after their last radiation exposure, or within 6 hours of return to Earth for the STS 135 animals. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted, purified and quality-tested. Complementary DNA was prepared from high-quality RNA samples, and used in RT-qPCR experiments to determine relative expression of a wide variety of genes involved in general metabolism and drug metabolism. RESULTS: Results of the ground radiation exposure experiments indicated ~65 genes of the 190 tested were significantly affected by at least one of the radiation doses. Many of the affected genes are involved in the metabolism of drugs with hydrophobic or steroid-like structures, maintenance of redox homeostasis and repair of DNA damage. Most affected genes returned to near control expression levels by 7 days post-treatment. Not all recovered completely by the final time point tested: with 6 Gy exposure, metallothionein expression was 132-fold more than control at the 4 hr time point, and fell at each later time point (11-fold at 24 hrs, and 8-fold at 7 days). In contrast, there were other genes whose expression was altered and remained relatively constant through the 7 day period we tested. One examples is Cyp17a1, which showed a 4-fold elevation at 4 hrs after exposure and remained constant for 7 days after the last treatment. Spaceflight samples evaluated with similar methods and comparisons will be made between the radiation-treated groups and the spaceflight samples. CONCLUSION It seems likely that radiation exposure triggers homeostatic mechanisms, which could include alterations of gene expression. Better understanding of these pathways could aid in optimizing medications doses given to crewmembers who require treatment and eventually, to development of new countermeasures to ameliorate or prevent radiation-induced damage to cells and tissues.

Wotring, V. E.↗

Advanced Anti-Fouling Coatings to Improve the Efficiency of Coal Power Plants

As the total cost of carbon to generate energy has become a global concern, operators are increasingly looking at all parts of the generation cycle to find areas where efficiency gains may be found. It has been long identified that fouling of heat exchangers is a persistent cause of up to 2.5% of global CO 2 emissions. Unfortunately, practice has also demonstrated that unless a powerful economic driver exists to encourage preemptive mitigation of fouling, there will always be a strong tendency for operators to minimize any form of intervention due to high costs and challenges in scheduling downtime. The objective of this proposed research effort was to demonstrate how existing power plants could lower their carbon emissions and significantly improve heat transfer efficiency using new surface treatment materials to control fouling in a variety of heat exchange equipment. The surface treatment material which was optimized and deployed in this effort is now known commercially as HeatX. It is a low-surface energy, water- and oil-repellent, abrasion resistant material which can be applied in-situ to a wide variety of previously worn/used/in-service substrates. Once applied, it provides a barrier against corrosion, scale deposit formation, and biofilm adhesion on the circulating water-containing tube-side. Alternatively, if applied to the tube exterior, the non-wetting nature of the surface was demonstrated to promote dropwise condensation, subsequently lowering condenser backpressure and increasing overall plant efficiency. As part of this cooperative effort, the Department of Energy’s support was crucial to de-risk and demonstrate the concept of HeatX, while validating both the performance and economic benefit in multiple pilot field studies. The HeatX material properties were optimized in this effort for full field applicability to heat exchangers and condensers, and Oceanit developed the necessary procedures and protocols to provide enough material to support extended length, multi-year demonstrations in the power generation, desalination, and refining industries, making this technology broadly applicable and ready for commercial transition. Field deployment case studies at thermal power plants have shown that the HeatX treatment can provide economic savings of up to $15,000 per day for an operator based on avoiding maintenance costs and lowering fuel usage. The complete mitigation of fouling effects can increase the efficiency of equipment by up to 7%, in a field where gains of 0.5% are generally seen as operationally significant. The HeatX treatment has also demonstrated exceptional lifetime and compatibility with a wide variety of seawater and hydrocarbon environments, further increasing both the return on investment and the effective emission reduction. Such efficiency improvements correlate to massive carbon savings. For every 1 GW of capacity, operators can see carbon emissions reductions of 300,000 tons of CO 2 per year. When looking at the bigger picture, improved condenser function across the U.S. has the potential to prevent 221.3 million tons of CO 2 emissions, equivalent to the sequestration capacity of 129 million acres of forest. If applied on a global scale, 1.26 billion metric tons of CO 2 could be averted from the atmosphere, the same amount of carbon sequestrated by 1.5 billion acres of forest annually or 262,000 wind turbines operating annually. As businesses across multiple industries take a more active role in focusing on environmental, social, and governance (ESG) solutions as part of their core business operations, HeatX will be an attractive technology for commercial investment.

01 COAL, LIGNITE, AND PEAT↗

Power System Resilience Enhancement in Typhoons Using a Three-Stage Day-Ahead Unit Commitment

In this work, we propose a three-stage resilient unit commitment model which considers uncertain typhoon paths and line outages to improve the power system resilience against typhoon events. The proposed solution coordinates resources in response to the worst-case scenario for each possible typhoon path. The optimal decision is based on the characterization of the power system schedule into three stages of preventive control, emergency control, and restoration. Preventive control is performed before the typhoon occurs by quickly adjusting the three-stage resilient unit commitment schedule; emergency control is conducted during the typhoon by shedding local loads to meet the power balance, while other control strategies are assumed to be unavailable due to possible interruptions in the communication system; restoration is realized after the typhoon, when resources are optimally dispatched to repair the outages of critical devices and recover the normal operation state of the power system quickly. Considering the typhoon path uncertainty, we have introduced a stochastic model for possible typhoon paths where all possible affected lines along each typhoon path are assumed to be on outage during the typhoon. Accordingly, we explore the strategy for co-optimizing the three stages in unit commitment. The proposed model is tested on the IEEE 118-bus system and the real-world provincial system to verify its effectiveness.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Development of risk mitigation guidance for sensor placement inside mechanically ventilated enclosures – Phase 1

Guidance on Sensor Placement was identified as the top research priority for hydrogen sensors at the 2018 HySafe Research Priority Workshop on hydrogen safety in the category Mitigation, Sensors, Hazard Prevention, and Risk Reduction. This paper discusses the initial steps (Phase 1) to develop such guidance for mechanically ventilated enclosures. This work was initiated as an international collaborative effort to respond to emerging market needs related to the design and deployment equipment for hydrogen infrastructure that is often installed in individual equipment cabinets or ventilated enclosures. The ultimate objective of this effort is to develop guidance for an optimal sensor placement such that, when integrated into a facility design and operation, will allow earlier detection at lower levels of incipient leaks, leading to significant hazard reduction. Reliable and consistent early warning of hydrogen leaks will allow for the risk mitigation by reducing or even eliminating the probability of escalation of small leaks into large and uncontrolled events. To address this issue, a study of a real-world mechanically ventilated enclosure containing GH2 equipment was conducted, where CFD modeling of the hydrogen dispersion (performed by AVT and UQTR, and independently by the JRC) was validated by the NREL Sensor laboratory using a Hydrogen Wide Area Monitor (HyWAM) consisting of a 10-point gas and temperature measurement analyzer. In the release test, helium was used as a hydrogen surrogate. Expansion of indoor releases to other larger facilities (including parking structures, vehicle maintenance facilities and potentially tunnels) and incorporation into QRA tools, such as HyRAM is planned for Phase 2. It is anticipated that results of this work will be used to inform national and international standards such as NFPA 2 Hydrogen Technologies Code, Canadian Hydrogen Installation Code (CHIC) and relevant ISO/TC 197 and CEN documents.

08 HYDROGEN↗

CLINICAL DECISION SUPPORT: PATH TO FUNCTIONAL REQUIREMENTS

Long-duration, deep-space exploration missions present significant challenges to crew health and performance. These challenges include the individual and combined effects of microgravity, radiation exposure, isolation, limited resources (mass, volume, power, data and crew time), limited options for evacuation and those associated with delayed or constrained communications, all of which demand greater crew autonomy. Specifically, as the communication delays intensify the further we explore space, the unqualified need for Earth-independent medical operations focused on autonomous diagnosis, treatment and prevention will be key to mission continuation and success. To augment the requisite knowledge, skills and abilities (KSAs) of a time-constrained crew operating under stressful conditions, combatting fatigue, and facing a potential medical crisis, a robust clinical decision support system (CDSS) is a probable solution that would facilitate, guide and inform Earth-independent medical operations, while assisting crewmembers through various clinical presentations. The Exploration Medical Capability (ExMC) Element of the Human Research Program (HRP) is expanding the boundaries of space medical systems to advance the care of astronauts on future exploration missions beyond low Earth orbit. ExMC is actively identifying and testing next-generation medical care and crew health maintenance technologies. The Clinical Decision Support (CDS) project addresses gap Medical-701 within the Inflight Medical Conditions risk: “Enhance medical capabilities within an exploration medical system.” Though mass, volume, and power will face increasing constraints, the projected computational capabilities of spacecraft systems will increase exponentially as information technology continues to advance this decade and beyond. Hence, data, software and computational resources will play an essential and synergistic role in maintaining crew health, wellness and performance in deep space missions. The focus of the CDS project is to develop recommended requirements for an in-vehicle CDSS that acts as a ‘virtual assistant’ for delivering optimal health, performance and medical care during exploration missions. The CDSS is envisioned as an integrated, software-based tool deployed on a laptop computer or handheld device. The CDSS will assist the crew and ground support when interacting with knowledge/databases (e.g. records, pharmacy, schedule), instrumentation (e.g. imaging, physiological monitoring devices), and habitat (e.g. wellness system, task performance system) and vehicle systems (e.g. environmental system, communication system). In addition, the human interface will employ a context-based approach that accounts for the crew’s situation. Thus, extraneous and clinically/operationally non-relevant information are reduced to avoid an increase in cognitive load. The framework of an ideal spaceflight CDSS is to include core and advanced analytical features that incorporate work from collaborators yet maintain a flexible platform for integrating new technology in the future. In fiscal year 2021 (FY21), the CDS project identified requirements through two primary mechanisms: (i) the development of software implementation prototypes and (ii) the application of systems engineering processes. The CDS project developed and tested a series of increasingly complex system prototypes that were based on use cases derived from the CDSS concept of operations (ConOps). These software implementations yielded insights on CDSS functionality as well as lessons learned that provided the initial requirements for CDSS capability. By applying a systems engineering (SE) approach, medical scenarios provided in the ConOps and the use cases for software implementation underwent functional decomposition to identify CDSS functionality. Also, systems-based modeling language (SysML) tools such as activity diagrams were developed from the same ConOps and use cases to identify CDSS functionality. The lessons learned from software implementation defined both specific requirements and broad areas of requirements. Within these defined broad requirement areas, further analysis of the SE products identified specific capability that resulted in the final functional requirements. In summary, the software prototypes, functional decomposition of the ConOps and use cases, and SysML diagrams provided the basis for the CDSS requirements developed in FY21. In the upcoming year, these requirements will be refined for their final ExMC baseline review in latter FY22.

clinical decision support↗

Clinical Decision Support: Path to Functional Requirements

Long-duration, deep-space exploration missions present significant challenges to crew health and performance. These challenges include the individual and combined effects of microgravity, radiation exposure, isolation, limited resources (mass, volume, power, data and crew time), limited options for evacuation and those associated with delayed or constrained communications, all of which demand greater crew autonomy. Specifically, as the communication delays intensify the further we explore space, the unqualified need for Earth-independent medical operations focused on autonomous diagnosis, treatment and prevention will be key to mission continuation and success. To augment the requisite knowledge, skills and abilities (KSAs) of a time-constrained crew operating under stressful conditions, combatting fatigue, and facing a potential medical crisis, a robust clinical decision support system (CDSS) is a probable solution that would facilitate, guide and inform Earth-independent medical operations, while assisting crewmembers through various clinical presentations. The Exploration Medical Capability (ExMC) Element of the Human Research Program (HRP) is expanding the boundaries of space medical systems to advance the care of astronauts on future exploration missions beyond low Earth orbit. ExMC is actively identifying and testing next-generation medical care and crew health maintenance technologies. The Clinical Decision Support (CDS) project addresses gap Medical-701 within the Inflight Medical Conditions risk: “Enhance medical capabilities within an exploration medical system.” Though mass, volume, and power will face increasing constraints, the projected computational capabilities of spacecraft systems will increase exponentially as information technology continues to advance this decade and beyond. Hence, data, software and computational resources will play an essential and synergistic role in maintaining crew health, wellness and performance in deep space missions. The focus of the CDS project is to develop recommended requirements for an in-vehicle CDSS that acts as a ‘virtual assistant’ for delivering optimal health, performance and medical care during exploration missions. The CDSS is envisioned as an integrated, software-based tool deployed on a laptop computer or handheld device. The CDSS will assist the crew and ground support when interacting with knowledge/databases (e.g. records, pharmacy, schedule), instrumentation (e.g. imaging, physiological monitoring devices), and habitat (e.g. wellness system, task performance system) and vehicle systems (e.g. environmental system, communication system). In addition, the human interface will employ a context-based approach that accounts for the crew’s situation. Thus, extraneous and clinically/operationally non-relevant information are reduced to avoid an increase in cognitive load. The framework of an ideal spaceflight CDSS is to include core and advanced analytical features that incorporate work from collaborators yet maintain a flexible platform for integrating new technology in the future. In fiscal year 2021 (FY21), the CDS project identified requirements through two primary mechanisms: (i) the development of software implementation prototypes and (ii) the application of systems engineering processes. The CDS project developed and tested a series of increasingly complex system prototypes that were based on use cases derived from the CDSS concept of operations (ConOps). These software implementations yielded insights on CDSS functionality as well as lessons learned that provided the initial requirements for CDSS capability. By applying a systems engineering (SE) approach, medical scenarios provided in the ConOps and the use cases for software implementation underwent functional decomposition to identify CDSS functionality. Also, systems-based modeling language (SysML) tools such as activity diagrams were developed from the same ConOps and use cases to identify CDSS functionality. The lessons learned from software implementation defined both specific requirements and broad areas of requirements. Within these defined broad requirement areas, further analysis of the SE products identified specific capability that resulted in the final functional requirements. In summary, the software prototypes, functional decomposition of the ConOps and use cases, and SysML diagrams provided the basis for the CDSS requirements developed in FY21. In the upcoming year, these requirements will be refined for their final ExMC baseline review in latter FY22.

Clinical decision support↗

Fault Characterization and Diagnostics Supporting Condition-Based Operation and Maintenance of Gas Turbine Engines

Condition-Based Operation and Maintenance (CBOM) is the state-of-the-art in maintenance approaches for gas turbine engines. CBOM applies engine sensor information to the optimization of future operation and maintenance procedures; this technique reduces costs for engine operators by minimizing unplanned outages and catastrophic engine degradation. However, due to the complexities of gas turbine operation and the lack of available engine sensors, further development is required to fully realize the benefits of CBOM. In the turbine section, rotating components interact with high temperature flows, which creates intense thermal and mechanical stresses. As a result, there are numerous mechanisms of component degradation in the turbine section. Furthermore, turbine components – like stator vanes and rotor blades – are among the most expensive in the engine because they are complex to design and manufacture. For these reasons, this dissertation addresses two main questions: (i) which parameters or faults within the turbine section are most important to monitor, and (ii) how can these parameters or faults be monitored in an engine-relevant environment? Although many turbine parameters and faults have been investigated in the open literature, there are some faults that are still not well understood. Rotor-casing eccentricity, which causes a non-constant blade tip clearance around the annulus, has not been investigated in terms of its effects on turbine efficiency. Therefore, the first study in this dissertation quantifies overall and local turbine efficiency for varying levels of rotor-casing eccentricity. Results showed negligible variations to overall turbine efficiency, meaning rotor-casing eccentricity only becomes relevant to CBOM when its severity causes rotordynamic issues. Purge flow is critical to turbine hardware longevity because it prevents ingestion of hot main gas path (MGP) flow into the under-platform regions. Despite its importance, there are currently no methods for monitoring purge flow performance in an engine environment. Therefore, the second study in this dissertation develops a predictive model for sealing effectiveness using inputs from two fast-response pressure sensors. Results exhibited low prediction errors across a full range of purge flow rates, which supports the viability of the modelling approach for CBOM. The final two studies in this dissertation address blade coolant flow monitoring. This cooling flow is responsible for protecting the turbine blades from the MGP flow, which exits the combustor at temperatures greater than the blade melting point. These studies showed that temperature measurements on the blade surface can be used to accurately predict blade coolant flow rate, and that defining the candidate features relative to the coolant trajectory is important for maintaining accuracy as coolant flow rate degradation occurs. This work enables blade coolant flow monitoring, which is currently not possible through existing condition monitoring techniques.

condition-based, gas turbines, diagnostics,↗

INTEGRATION OF FLEX EQUIPMENT AND OPERATOR ACTIONS IN PLANT FORCE-ON-FORCE MODELS WITH DYNAMIC RISK ASSESSMENT

The overall operation and maintenance cost to protect nuclear power plants accounts for approximately 7% of the total cost of power generation, with labor accounting for half of this cost. In the current research, from interaction with utilities and other stakeholders, it was determined that physical security forces account for nearly 20% of the entire workforce at several nuclear power plants. Labor costs continue to rise in the U.S., so any measures to reduce the cost of operating a nuclear power plant will need to include a reduction in labor. The physical security pathway within the DOE’s Light Water Reactor Sustainability program aims to lower the cost of physical security through directed research into modeling and simulation, application of advanced sensors or deployment of advanced weapons. This report presents a modeling and simulation framework for integrating Diverse and Flexible Mitigation Capability (FLEX) portable equipment performance with Force on Force models of a plant’s physical security posture. The generic framework is described in detail, followed by a case study of modeling an adversarial attack aimed at causing a radiological release by sabotaging the plant’s power supply and its ultimate heat sink capabilities at a hypothetical nuclear power plant. Two different FLEX deployment strategies, series and parallel, are modeled with distinct timelines. The results of the adversarial attack modeled in a commercial Force on Force tool are integrated with the FLEX deployment model in INL’s dynamic modeling tool EMRALD. Monte Carlo simulation is used to model the distribution of the timeline in FLEX deployment strategies. The results demonstrate that, even in the extreme case of a successful adversarial attack, deployment of FLEX equipment can result in a significantly high likelihood of preventing radiological release. The modeling and simulation framework integrating FLEX equipment with Force on Force models enables the nuclear power plants to credit FLEX portable equipment in the plant security posture, resulting in an efficient and optimized physical security.

97 MATHEMATICS AND COMPUTING↗

Clinical Decision Support Project

As NASA plans for exploration missions into deep space, significant challenges are realized due to the distance from Earth. Beside the effects of microgravity and radiation exposure, the astronauts face the additional constraints of isolation, lack of resupply, increasingly difficult evacuation, and delayed and disrupted communication with ground-based medical care providers. These constraints require a paradigm shift from current medical care where crews rely on the real-time communications with ground-based medical care providers toward Earth-independent medical operations for astronaut medical care. Medical expertise and decision-making are ground-based for current International Space Station and planned Lunar missions. However, a deep space exploration crew will need to autonomously perform the detection, diagnosis, treatment, and prevention of medical conditions. One approach to provide Earth-independent medical operations is to augment the requisite knowledge, skills, and abilities (KSAs) of a time-constrained crew—operating under stressful conditions, combatting fatigue, and facing a potential medical crisis—with a robust clinical decision support system (CDSS). The CDSS is envisioned as an integrated, software-based tool deployed on a laptop computer or handheld device. The CDSS will assist the crew and ground support when interacting with knowledge/data bases (e.g. records, pharmacy, schedule), instrumentation (e.g. imaging, physiological monitoring devices), and habitat (e.g. wellness system, task performance system) and vehicle systems (e.g. environmental system, communication system). In addition, the human interface will employ a context-based approach that accounts for the crew’s situation. Thus, extraneous and clinically/operationally non-relevant information are reduced to avoid an increase in cognitive load. The framework of an ideal spaceflight CDSS is to include core and advanced analytical features that maintain a flexible platform for integrating new technology in the future. The Exploration Medical Capability (ExMC) Element of the Human Research Program (HRP) is expanding the boundaries of space medical systems to advance the care of astronauts on future exploration missions beyond low Earth orbit by actively identifying and testing next-generation medical care and crew health maintenance technologies. The Clinical Decision Support (CDS) project addressed ap Medical-701 within the Inflight Medical Conditions risk: “We need to increase inflight medical capabilities and identify new capabilities that (a) maximize benefit and/or (b) reduce “costs” on human system/mission/vehicle resources.” Though mass, volume, and power will face increasing constraints, the projected computational capabilities of spacecraft systems will increase exponentially as information technology advances in this decade and beyond. Hence, data, software, and computational resources will play an essential and synergistic role in maintaining crew health, wellness, and performance in deep space missions. The focus of the CDS project was to develop recommended requirements for an in-vehicle CDSS that acts as a ‘virtual assistant’ for delivering optimal health, performance, and medical care during exploration missions. In fiscal year 2022 (FY22), the CDS project was chartered to baseline and/or revise all CDS project related documentation and update the CDS project model to include the revised CDSS Concept of Operations, revised systems-based modeling language (SysML) activity diagrams, and baseline requirements. The focus of this presentation will be an overview of the CDS products and CDS model content.

Decision Support↗

Earth Independent Medical Operations (EIMO) Datascope: Challenges and Potential Solutions

Data flows and storage/retrieval capacity are severely constrained during missions in space and challenges will become even greater during exploration class missions. There is a need for an artificial intelligence (AI)-based clinical decision support system (CDSS) to monitor and analyze data to provide real-time consultative support for crew medical officer (CMO) decision-making. EIMO is defined as the gradual transition of medical care and decision making from terrestrial to space-based assets, enabling support of astronaut health and performance and reducing overall mission risk. While a hallmark of this paradigm shift from low-earth orbit is that on-board care will increasingly become the responsibility of the astronauts for primary management and decision making, terrestrial assets will continue to be paramount in pre-mission screening and planning, as well as prevention, health maintenance and long-term care contingencies. New capabilities and systems that enable progressively more robust and resilient systems and crews will be necessary to reduce risk and increase probability of deep space exploration mission success. An aspiration for EIMO is to develop AI-enhanced solutions for analysis of crew health & performance data and to facilitate clinical decision support for autonomous medical operations. A “system of systems” approach is envisioned whereby EIMO will deploy AI-supported natural language processing and machine learning (ML) techniques to utilize embedded reference databases and real-time data streams [input vectors] from multiple data sources. Constituent input vectors may include environmental controls, countermeasures data, behavioral data, physiologic wearables, point-of-care laboratory tests, personalized medical records, inventory trade space risk assessments, COTS medical databases, and ground support inputs. An ideal AI capability would possess trained fusion algorithms to cross reference input vectors with medical ‘knowledge’ [cultivated database] to stratify relevant data streams for predictive and actionable capabilities. In addition, EIMO will feature mobility, in that it can be accessed and can push/pull data within and between multiple vehicles/habitats. Large amounts and variable sources of data can be leveraged to diagnose, inform treatment strategies, and potentially predict medical events and performance decrements. Inclusion of advanced training tools using extended reality will enable increasingly autonomous medical care to aid a CMO when ground support is unavailable or time-delayed beyond required action window, e.g., emergent medical situations. EIMO CDSS would require very large datasets to train pre-flight and significant amounts of data are needed to support ML via in-flight CDSS operations. An additional challenge will be to find sufficient data to train a model relevant to astronaut demographics. The rapid, accelerating evolution of this field creates a propitious solution space to leverage multi-modal AI through public-private partnership(s). The status of multi-modal AI systems today would preclude their use for long duration missions as they remain unreliable and are subject to “digital hallucinations” and other errors that could pose operational risk. A federated labs structure is being considered to test and optimize data flow from the multiple input vectors leading to field testing in suitable ground/flight analogs. Critical to the success of an EIMO CDSS will be integration and interoperability and success will be defined by a system that can serve as an in-flight medical consult for the CMO providing critical support during medical contingencies. Benefits to terrestrial medicine may be significant as an outflow of the EIMO medical system, particularly for remote areas and communities lacking significant infrastructure, personnel and resources.

J Lemery↗

Earth Independent Medical Operations (EIMO) Datascope: Challenges and Potential Solutions

Data flows and storage/retrieval capacity are severely constrained during missions in space and challenges will become even greater during exploration class missions. There is a need for an artificial intelligence (AI)-based clinical decision support system (CDSS) to monitor and analyze data to provide real-time consultative support for crew medical officer (CMO) decision-making. EIMO is defined as the gradual transition of medical care and decision making from terrestrial to space-based assets, enabling support of astronaut health and performance and reducing overall mission risk. While a hallmark of this paradigm shift from low-earth orbit is that on-board care will increasingly become the responsibility of the astronauts for primary management and decision making, terrestrial assets will continue to be paramount in pre-mission screening and planning, as well as prevention, health maintenance and long-term care contingencies. New capabilities and systems that enable progressively more robust and resilient systems and crews will be necessary to reduce risk and increase probability of deep space exploration mission success. An aspiration for EIMO is to develop AI-enhanced solutions for analysis of crew health & performance data and to facilitate clinical decision support for autonomous medical operations. A “system of systems” approach is envisioned whereby EIMO will deploy AI-supported natural language processing and machine learning (ML) techniques to utilize embedded reference databases and real-time data streams [input vectors] from multiple data sources. Constituent input vectors may include environmental controls, countermeasures data, behavioral data, physiologic wearables, point-of-care laboratory tests, personalized medical records, inventory trade space risk assessments, COTS medical databases, and ground support inputs. An ideal AI capability would possess trained fusion algorithms to cross reference input vectors with medical ‘knowledge’ [cultivated database] to stratify relevant data streams for predictive and actionable capabilities. In addition, EIMO will feature mobility, in that it can be accessed and can push/pull data within and between multiple vehicles/habitats. Large amounts and variable sources of data can be leveraged to diagnose, inform treatment strategies, and potentially predict medical events and performance decrements. Inclusion of advanced training tools using extended reality will enable increasingly autonomous medical care to aid a CMO when ground support is unavailable or time-delayed beyond required action window, e.g., emergent medical situations. EIMO CDSS would require very large datasets to train pre-flight and significant amounts of data are needed to support ML via in-flight CDSS operations. An additional challenge will be to find sufficient data to train a model relevant to astronaut demographics. The rapid, accelerating evolution of this field creates a propitious solution space to leverage multi-modal AI through public-private partnership(s). The status of multi-modal AI systems today would preclude their use for long duration missions as they remain unreliable and are subject to “digital hallucinations” and other errors that could pose operational risk. A federated labs structure is being considered to test and optimize data flow from the multiple input vectors leading to field testing in suitable ground/flight analogs. Critical to the success of an EIMO CDSS will be integration and interoperability and success will be defined by a system that can serve as an in-flight medical consult for the CMO providing critical support during medical contingencies. Benefits to terrestrial medicine may be significant as an outflow of the EIMO medical system, particularly for remote areas and communities lacking significant infrastructure, personnel and resources.

Medical Operations↗

Moon to Mars (M2M): Exploration Atmosphere

As humans leave the bounds of Earth to explore the lunar surface and beyond, crew will don extravehicular activity (EVA) suits to learn more about these extraterrestrial environments, establish sustained presence, and perform needed upgrades and maintenance to their space vehicle and habitation systems. Spacefaring vehicle and habitation design will need to support these EVA excursions while ensuring crew health and safety. A crucial technological design advancement towards this goal is the use of a lower pressure exploration atmosphere (EA) that enables high efficiency EVA, rather than the sea level atmosphere of 14.7 psia, 21% oxygen (O 2 ) found on the International Space Station, Shuttle, and most other Russian and Chinese space vehicles and stations. Early space vehicles (Mercury through Apollo Programs) used a 5 psia, 100% O 2 environment, which eliminated the need for pre-EVA denitrogenation protocols, simplified the life support system to a single gas, and saved structural mass. For longer duration missions (Skylab), a diluent gas was added, changing the atmosphere to 5 psia, 70-74% O 2 to prevent atelectasis while remaining normoxic. As in-flight science became a top priority, Shuttle and ISS atmospheres were chosen to operate at sea level allowing for simpler ground-based study control conditions. Consequently this led to long pre-EVA denitrogenation protocols involving up to 4 hours of O 2 prebreathe because the EVA suit still operated at a low pressure of 4.3 psid. To increase operational efficiency, the Shuttle was retroactively certified to operate using 10.2 psia, 26.5% O 2 , reducing O 2 prebreathe time to 40-75 min. Current plans for M2M habitats on the Lunar surface require EVA, thus EA recommendation became 8 psia and 32% O 2 but was revised to 8.2 psia and 34% O 2 to decrease hypoxia exposure. Unfortunately, the benefits of EA in support of safe and efficient EVAs comes with the challenge of fire management in a higher-than-normal O 2 % environment. Although known for decades, the recommended forward work to address fire management has only recently begun. Current flammability tests include examining material propagation and ignition sources as well as fire mitigation processes to better understand these properties for proposed new EA environments. Fire safety, DCS risk, and mission design all contribute to the multifaceted parameters of EA. Thus while it is clear that EA is required to achieve the goals of future exploratory space missions, final specifications are still being evaluated for optimizing crew health and safety.

space atmosphere↗

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Health and Pharmacogenomics

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expand in duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to tailor medications for individual crewmembers and further examine appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique clinical and environmental history, genetic makeup, and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. A subset of this field is pharmacogenomics (PGX), the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on drug choice and dosing to avoid adverse events and maximize efficacy. The study goal was to identify which current space pharmacy drugs could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs on the ISS was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both astronauts’ personal medications, including supplements and over the counter drugs (n=151) contained in the ISS medical accessory kit (IMAK), and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in a total of 157 drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure (LxC). Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent ineffective treatment or impactful side effect events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost, or technical criteria and ranked from 1 (very low) to 5 (very high). An assessment of PGX reference laboratories is currently underway to evaluate sample requirements, benefit analysis (cost vs. utility of allele variant analysis), relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments (LxC 5x5 table) indicated 128 medications were in the green zone where risk is acceptable, with the remaining 29 of the medications in the yellow or red zone driven predominantly due to drug failure or safety concerns. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive preflight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve drug efficacy, and further open the door to countermeasure research. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more effective and efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing selection of the best treatment choice, and providing tailored countermeasures for individual crewmembers.

Pharmacogenomics↗

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Medicine and Pharmacogenomics for Human Deep Space Exploration

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expanding duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be even more essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to further tailor medications included in the spacecraft formulary and increased examination of appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of cutting-edge research and medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique factors and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. One example is the field of pharmacogenomics (PGX),the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on pharmaceutical choice and dosing to avoid adverse drug events and maximize pharmacological efficacy. The goal of this study was to evaluate which drugs in the current space pharmacy could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs onboard the International Space Station (ISS) was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both personal astronaut medications, including supplements and over the counter drugs (n=151) and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in 157 total drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure. Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent adverse events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost or technical and ranked from 1 (very low) to 5 (very high).A comprehensive assessment of commercially available PGX solutions is currently underway to evaluate specimen requirements, cost/benefit analysis (cost vs. number of alleles assessed), utility of variant analysis, relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments(LxC 5x5 table) indicated29medicationswere in the yellow or red zone driven predominantly by drug failure or safety concerns, with the remainder(n=128)of the medications in the green zone where risk is acceptable. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive pre-flight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve targeting drug efficacy and safety, and further open the door to countermeasure research exploring PGX-related allelic variants. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more cost effective and more efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing crew autonomy and providing tailored countermeasures

Alice R W Tang↗

Launch Complex 34, SWMU CC054 2023 DNAPL Source Zone Operations, Maintenance, and Monitoring, Site-Wide Long-Term Monitoring, and Hot Spot 6 Air Sparge System Annual Performance Monitoring and Phase Two Expansion Construction Completion Report Cape Canaveral Space Force Station, Florida

This Annual Performance Monitoring Report (PMR) for the Dense Non-Aqueous Phase Liquid (DNAPL) Source Zone (DSZ), Site-Wide Long-Term Monitoring (LTM), and Hot Spot 6 (HS 6) Air Sparge (AS) System presents the results of Year 14 operations and performance monitoring of the hydraulic containment (HC) Interim Measure (IM), details associated with construction and implementation of the HS 6 AS system expansion (Phase Two), and the results of operations and performance sampling of the HS 6 AS IM at Launch Complex 34 (LC34), located at Cape Canaveral Space Force Station (CCSFS), Florida. The timeframe for activities documented in this PMR extends from April 1, 2023 to March 31, 2024. LC34 has been designated Solid Waste Management Unit CC054 under the Kennedy Space Center (KSC) Resource Conservation and Recovery Act Corrective Action Program. The objective of the HC IM at LC34 is to contain the shallow and deep DSZ and surrounding dissolved-phase trichloroethene (TCE) high concentration plume via operation of a hydraulic containment system (HCS). The pre-IM design 300 micrograms per liter (μg/L) TCE groundwater contour was used to establish the deep zone capture area for deep recovery wells, and the shallow zone capture area was defined by the DSZ. The system began operating in 2010, and in 2015, the system was expanded to provide HC for areas within the 300 μg/L TCE groundwater isocontours of HS 3 and 4. In 2018 and 2019, an investigation was conducted to recharacterize the DSZ, which included investigating TCE mass in Layer 7. This data was subsequently used to optimize the pumping rates of the HCS and install additional recovery wells in Layer 7 to more adequately capture residual contaminant mass. The operational period for Year 14 of the HCS was from April 1, 2023 to March 31, 2024. Operational runtime for the system was 94 percent during Year 14, with downtime events attributed to planned maintenance, system repairs, and power outages. As of March 31, 2024, a total of 344,849,634 cumulative gallons of groundwater containing 94,656 pounds of chlorinated volatile organic compounds (CVOCs) have been removed by the HCS. During the reporting period covered under this report, the HCS recovered 31,176,393 gallons and approximately 6,319 pounds of CVOC mass. Total combined influent concentrations of TCE have decreased since startup from approximately 280,000 µg/L (January 2010) to 25,000 µg/L (March 2024). During the reporting period, all effluent concentrations from the HCS (aqueous and vapor) were below regulatory reporting limits, indicating the system continues to operate as intended. Performance monitoring was conducted in January 2024 within the DSZ to evaluate TCE contamination. Groundwater samples were collected via DPT at nine locations, consistent with previous events between 2017 and 2022. Full vertical profile sampling was completed at each DPT from 8 to 98 feet below land surface (bls), at 5-foot intervals. The DPT performance monitoring results are summarized in this PMR. The results revealed TCE remains at concentrations greater than 11,000 µg/L in the DSZ (1-percent solubility, indicative of DNAPL) at eight of the nine DPT locations and at depths ranging from 28 to 98 feet bls. An overall decreasing trend of TCE concentrations was observed in DPT samples during this reporting period, which is a reduction from the previous event (December 2022) and the peak event in December 2021, where TCE percentages appeared to increase in all depth zones because several recovery wells were turned off during the AS pilot study in the DSZ. The maximum TCE concentration in January 2024 was 1,600,000 µg/L in the 53 feet bls depth interval at DPT594 (previous maximum result in 2022 was 1,800,000 µg/L in the 48 feet bls depth interval at DPT599). This maximum concentration in the 53 feet bls depth interval is in the deep capture zone. During the January 2024 DPT event, the largest portion of TCE mass was observed in the 48 feet bls interval above/within Layer 4. This trend remains consistent with previous years and appears to indicate continued mass discharge from Layer 4 (fine-grained unit). In addition to DPT sampling, annual groundwater samples were collected from 11 deep monitoring wells in the DSZ area (Layers 7 and 8) in December 2023 to verify vertical and horizontal delineation. Three of the wells were also sampled biweekly to evaluate operations of recovery well RW21D (screened 86 to 106 feet bls), which was installed in January 2023. Of the Layer 7/8 monitoring sampled only annually, results were non-detect or less than groundwater cleanup target levels GCTLs in December 2023, with the exception of one well, IW45D2, which had a cis-1,2-dichloroethene (cDCE), detection greater than the GCTL. Of the three wells sampled biweekly during the operational period, the well located closest to Layer 7 recovery well RW21D (IW44D2, screened 105 to 115 feet bls) had concentrations of TCE, cDCE and vinyl chloride (VC) greater than GCTLs throughout the operational period, but displayed a decreasing trend since the peak concentrations in September 2023. The maximum TCE concentration during this operational period was 190,000 µg/L at IW44D2 in September 2023, but reduced to 700 µg/L in March 2024, indicating the HCS is still effectively removing mass from the source area. Expansion of the HCS and addition of new recovery wells is ongoing and will continue to be evaluated as the groundwater recovery scheme is optimized. Details of the expansion and optimization will be provided in a future PMR. The HS 6 AS IM was initiated in 2018 with 160 AS wells and expanded in 2019 with another 140 AS wells. An additional expansion of the HS 6 AS IM was completed during the reporting period covered under this report and details of the construction implementation and startup of the expansion are detailed in Section III of this report. The new expansion, referred to as Phase Two, was implemented between August 17, 2022 and August 28, 2023, and included the installation of 190 air sparge wells to treat an additional 11.2 acres. The original configuration (referred to as Phase One) operated until Phase Two came online, then all but 52 AS wells were turned off so the components could be moved and utilized in the Phase Two area. The 52 AS wells that remain on are in a barrier configuration preventing contaminated groundwater from impacting the treated area. The HS 6 AS system (both Phase One and Two) operated normally during the reporting period covered under this report. Semi-annual performance monitoring of the Phase One configuration was conducted in April and November 2023, consistent with previous years. For the Phase Two configuration, 21 new monitoring wells were installed and sampled quarterly, with a baseline event in July 2023, and quarterly events in November 2023 and February 2024 summarized in this report. Semi-annual monitoring results collected in April and October 2023 show concentrations of contaminants of concern (cDCE, trans-1,2-dichloroethene, and VC) have decreased to less than GCTLs in nearly all wells and not impacting the surface water drainage canal, indicating the HS 6 IM continues to meet objectives. The baseline and quarterly sampling for the Phase Two configuration indicate generally decreasing concentrations in wells within and around the perimeter of the treatment area. At least two more quarters of monitoring will be conducted and once those results are evaluated a reduced the sampling frequency may be considered. Overall, the tasks associated with Year 14 operation of the HC IM and operation of the HS 6 AS IM were performed in accordance with recommendations included in the previous 2022 LC34 (Year 13) PMR. Evaluation of results from the HC IM and HS 6 IM show that these systems are operating as designed and meeting performance objectives.

groundwater remediation↗