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Validation of Procedures for Monitoring Crewmember Immune Function

There is ample evidence to suggest that space flight leads to immune system dysregulation, however the nature of the phenomenon as it equilibrates over longer flights has not been determined. This dysregulation may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk (if any) for exploration-class space flight is unknown, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles (RNA, intracellular, secreted), viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. This study is currently ongoing. To date, 10 short duration and 5 long-duration crewmembers have completed the study. Technically, the study is progressing well. In-flight blood samples are being collected, and returned for analysis, including functional assays that require live cells. For all in-flight samples to date, sample viability has been acceptable. Preliminary data (n = 4/7; long/short duration, respectively) indicate that distribution of most peripheral leukocyte subsets is largely unaltered during flight. Exceptions include elevated T cells, reduced B/NK cells, increased memory T cells and increased central memory CD8+ T cells. General T cell function, early blastogenesis response to mitogenic stimulation, is markedly reduced in-flight. In-vivo cytokine production profiles are altered, with in-flight dysregulation observed in the Th1/Th2/Treg equilibrium. EBV specific T cell levels are increased during flight, whereas their function is reduced. VZV reactivation was observed inflight and several days post flight with highest levels measured later during long-duration flight. The shedding of CMV in the urine was detected of 4/5 long duration and 4/7 short duration crewmembers. Plasma cortisol was not elevated during flight. Further data will be required to validate the initial observations.

Crucian, Brian↗

Validation of Procedures for Monitoring Crewmember Immune Function

The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles, viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. To date, 18 short duration (now completed) and 8 long-duration crewmembers have completed the study. The long-duration phase of this study is ongoing. For this presentation, the final data set for the short duration subjects will be discussed.

Pierson, Duane↗

The International Space Station: A Low-Earth Orbit (LEO) Test Bed for Advancements in Space and Environmental Medicine

Ground-based space analog projects such as the NASA Extreme Environment Mission Operations (NEEMO) can be valuable test beds for evaluation of experimental design and hardware feasibility before actually being implemented on orbit. The International Space Station (ISS) is an closed-system laboratory that orbits 240 miles above the Earth, and is the ultimate extreme environment. Its inhabitants spend hours performing research that spans from fluid physics to human physiology, yielding results that have implications for Earth-based improvements in medicine and health, as well as those that will help facilitate the mitigation of risks to the human body associated with exploration-class space missions. ISS health and medical experiments focus on pre-flight and in-flight prevention, in-flight treatment, and postflight recovery of health problems associated with space flight. Such experiments include those on enhanced medical monitoring, bone and muscle loss prevention, cardiovascular health, immunology, radiation and behavior. Lessons learned from ISS experiments may not only be applicable to other extreme environments that face similar capability limitations, but also serve to enhance standards of care for everyday use on Earth.

Ruttley, Tara M.↗

International Space Station Aeromedical Support in Star City, Russia

The Space Medicine Division at Johnson Space Center works with the International Space Station s international partners (IP) to accomplish assigned health care tasks. Each IP may assign a flight surgeon to support their assigned crewmembers during all phases of training, in-flight operations, and postflight activities. Because of the extensive amount of astronaut training conducted in Star City; NASA, in collaboration with its IPs, has elected to keep a flight surgeon assigned to NASA s Star City office to provide support to the U.S., Canadian, Japanese, and European astronauts during hazardous training activities and provide support for any contingency landings of Soyuz spacecraft in Kazakhstan. The physician also provides support as necessary to the Mission Control Center in Moscow for non-Russian crew-related activities. In addition, the physician in Star City provides ambulatory medical care to the non-Russian-assigned personnel in Star City and visiting dependents. Additional work involves all medical supplies, administration, and inventory. The Star City physician assists in medical evacuation and/or in obtaining support from western clinics in Moscow when required care exceeds local resources. Overall, the Russians are responsible for operations and the medical care of the entire crew when training in Star City and during launch/landing operations. However, they allow international partner flight surgeons to care for their crewmembers as agreed to in the ISS Medical Operations Requirements Document. Medical support focuses on pressurized, monitored, and other hazardous training activities. One of the most important jobs is to act as a medical advocate for the astronauts and to reduce the threat that these hazardous activities pose. Although the Russians have a robust medical system, evacuation may be needed to facilitate ongoing medical care. There are several international medical evacuation companies that provide this care.

Cole, Richard↗

Integration of In-Flight and Post-Flight Water Monitoring Resources in Addressing the U.S. Water Processor Assembly Total Organic Carbon (TOC) Anomaly

Beginning in June of 2010, the total organic carbon (TOC) concentration in the U.S. Water Processor Assembly (WPA) product water started to increase. A surprisingly consistent upward TOC trend was observed through weekly ISS total organic carbon analyzer (TOCA) monitoring. As TOC is a general organic compound indicator, return of water archive samples was needed to make better-informed crew health decisions on the specific compounds of concern and to aid in WPA troubleshooting. TOCA-measured TOC was more than halfway to the health-based screening limit of 3,000 g/L before archive samples were returned. Archive samples were returned on 22 Soyuz in September 2010 and on ULF5 in November of 2010. The samples were subjected to extensive analysis. Although TOC was confirmed to be elevated, somewhat surprisingly, none of the typical target compounds were detected at high levels. After some solid detective work, it was confirmed that the TOC was associated with a compound known as dimethylsilanediol (DMSD). DMSD is believed to be a breakdown product of siloxanes which are thought to be ubiquitous in the ISS atmosphere. A toxicological limit was set for DMSD and a forward plan was developed for conducting operations in the context of understanding the composition of the TOC measured in flight. This required careful consideration of existing ISS flight rules, coordination with ISS stakeholders, and development of a novel approach for the blending of inflight TOCA data with archive results to protect crew health. Among other challenges, team members had to determine how to utilize TOCA readings when making decisions about crew consumption of WPA water. This involved balancing very real concerns associated with the assumption that TOC would continue to be comprised of only DMSD. Demonstrated teamwork, multidisciplinary awareness, and innovative problem-solving were required to respond effectively to this anomaly.

Straub, John E., II↗

Microbial Anomalies Encountered on the International Space Station

Microorganisms in our living environments are unavoidable. A community of microbes arrived in space with the delivery of the first element of the International Space Station (ISS), attached to hardware and on the bodies of the humans tasked with the initial assembly missions. The risk that microorganisms could cause adverse effects in the health of both the human occupants of the ISS as well as the physical integrity of the station environment and life support systems has been both a driver and a function of engineering and operational controls. Scientists and engineers at NASA have gone to extensive measures to control microbial growth at levels safe for the crewmembers and the spacecraft environment. Many of these measures were initiated with the design of the spacecraft and its systems. Materials used in the ISS were tested for resistance to fungi, such as mold and a paint with a fungus-killing chemical was also used. Controlling the humidity of the air in the Station is also an effective way of discouraging microbe growth. The breathing air is reconditioned by the Environmental Control Life Support System (ECLSS) prior to distribution, utilizing High Efficiency Particulate Air (HEPA) filtration. Requirements restricting the accumulation of water condensate in the air handlers and habitable volume of the ISS were other safeguards added. Water for drinking and food rehydration is disinfected or filtered. A robust in-flight housekeeping regimen for the ISS significantly reduces inappropriate growth of microorganisms and includes a regular cleaning of accessible surfaces with disinfectant wipes. Most of these requirements were suggested by microbiologists to mitigate and possibly prevent many microbiological risks. In addition to these controls, before flight monitoring and analyses of the cabin air, exposed surfaces, water and food, consumables, and crew members are conducted to mitigate microbial risk to the crew and spacecraft. Many microbial risks are much easier to identify and resolve before launch than during space flight. Although the focus has been on prevention of microbiologically related, not all problems can be anticipated. A number of microbial anomalies have occurred on ISS. This paper will discuss the occurrences, root-cause investigations, and mitigation steps taken to remediate the contamination.

Bruce, Rebekah J.↗

Flight-Tested Prototype of BEAM Software

Researchers at JPL have completed a software prototype of BEAM (Beacon-based Exception Analysis for Multi-missions) and successfully tested its operation in flight onboard a NASA research aircraft. BEAM (see NASA Tech Briefs, Vol. 26, No. 9; and Vol. 27, No. 3) is an ISHM (Integrated Systems Health Management) technology that automatically analyzes sensor data and classifies system behavior as either nominal or anomalous, and further characterizes anomalies according to strength, duration, and affected signals. BEAM (see figure) can be used to monitor a wide variety of physical systems and sensor types in real time. In this series of tests, BEAM monitored the engines of a Dryden Flight Research Center F-18 aircraft, and performed onboard, unattended analysis of 26 engine sensors from engine startup to shutdown. The BEAM algorithm can detect anomalies based solely on the sensor data, which includes but is not limited to sensor failure, performance degradation, incorrect operation such as unplanned engine shutdown or flameout in this example, and major system faults. BEAM was tested on an F-18 simulator, static engine tests, and 25 individual flights totaling approximately 60 hours of flight time. During these tests, BEAM successfully identified planned anomalies (in-flight shutdowns of one engine) as well as minor unplanned anomalies (e.g., transient oil- and fuel-pressure drops), with no false alarms or suspected false-negative results for the period tested. BEAM also detected previously unknown behavior in the F- 18 compressor section during several flights. This result, confirmed by direct analysis of the raw data, serves as a significant test of BEAM's capability.

Mackey, Ryan↗

Photogrammetric Verification of Fiber Optic Shape Sensors on Flexible Aerospace Structures

Multi-core fiber (MCF) optic shape sensing offers the possibility of providing in-flight shape measurements of highly flexible aerospace structures and control surfaces for such purposes as gust load alleviation, flutter suppression, general flight control and structural health monitoring. Photogrammetric measurements of surface mounted MCF shape sensing cable can be used to quantify the MCF installation path and verify measurement methods.

Moore, Jason P.↗

Optic Nerve Sheath Diameter: Translating a Terrestrial Focused Technique Into a Clinical Monitoring Tool for Space Flight

Emergency medicine physicians recently adopted the use of ultrasonography to quickly measure optic nerve sheath diameter (ONSD) as concomitant with increased intracranial pressure. NASA Space and Clinical Operations Division has been using ground and on-orbit ultrasound capabilities since 2009 to consider this anatomical measure as a proxy for intracranial pressure in the microgravity environment. In the terrestrial emergency room population, an ONSD greater than 0.59 cm is considered highly predictive of elevated intracranial pressure. However, this cut-off limit is not applicable to the spaceflight setting since over 50% of US Operating Segment (USOS) astronauts have an ONSD greater than 0.60 cm even before missions. Crew Surgeon clinical decision-making is complicated by the fact that many astronauts have history of previous spaceflights. Data will be presented characterizing the distribution of baseline ONSD in the astronaut corps, longitudinal trends in-flight, and the predictive power of this measure related to increased intracranial pressure outcomes.

Mason, Sara S.↗

Challenges in Evaluating Relationships Between Quantitative Data (Carbon Dioxide) and Qualitative Data (Self-Reported Visual Changes)

Understanding the nuances in clinical data is critical in developing a successful data analysis plan. Carbon dioxide (CO2) data are collected on board the International Space Station (ISS) in a continuous stream. Clinical data on ISS are primarily collected via conversations between individual crewmembers and NASA Flight Surgeons during weekly Private Medical Conferences (PMC). Law, et.al, 20141 demonstrated a statistically significant association between weekly average CO2 levels on ISS and self-reported headaches over the reporting period from March 14, 2001 to May 31, 2012. The purpose of this analysis is to describe the evaluation of a possible association between visual changes and CO2 levels on ISS and to discuss challenges in developing an appropriate analysis plan. METHODS & PRELIMINARY RESULTS: A first analysis was conducted following the same study design as the published work on CO2 and self-reported headaches1; substituting self-reported changes in visual acuity in place of self-reported headaches. The analysis demonstrated no statistically significant association between visual impairment characterized by vision symptoms self-reported during PMCs and ISS average CO2 levels over ISS missions. Closer review of the PMC records showed that vision outcomes are not well-documented in terms of clinical severity, timing of onset, or timing of resolution, perhaps due to the incipient nature of vision changes. Vision has been monitored in ISS crewmembers, pre- and post-flight, using standard optometry evaluations. In-flight visual assessments were limited early in the ISS program, primarily consisting of self-perceived changes reported by crewmembers. Recently, on-orbit capabilities have greatly improved. Vision data ranges from self-reported post-flight changes in visual acuity, pre- to postflight changes identified during fundoscopic examination, and in-flight progression measured by advanced on-orbit clinical imaging capabilities at predetermined testing intervals. In contrast, CO2 data are recorded in a continuous stream over time; however, for the initial analysis this data was categorized into weekly averages.

Mendez, C. M.↗

Retrospective Analysis of Inflight Exercise Loading and Physiological Outcomes

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

Ploutz-Snyder, L. L.↗

Imagery Integration Team

The Human Exploration Science Office (KX) provides leadership for NASA's Imagery Integration (Integration 2) Team, an affiliation of experts in the use of engineering-class imagery intended to monitor the performance of launch vehicles and crewed spacecraft in flight. Typical engineering imagery assessments include studying and characterizing the liftoff and ascent debris environments; launch vehicle and propulsion element performance; in-flight activities; and entry, landing, and recovery operations. Integration 2 support has been provided not only for U.S. Government spaceflight (e.g., Space Shuttle, Ares I-X) but also for commercial launch providers, such as Space Exploration Technologies Corporation (SpaceX) and Orbital Sciences Corporation, servicing the International Space Station. The NASA Integration 2 Team is composed of imagery integration specialists from JSC, the Marshall Space Flight Center (MSFC), and the Kennedy Space Center (KSC), who have access to a vast pool of experience and capabilities related to program integration, deployment and management of imagery assets, imagery data management, and photogrammetric analysis. The Integration 2 team is currently providing integration services to commercial demonstration flights, Exploration Flight Test-1 (EFT-1), and the Space Launch System (SLS)-based Exploration Missions (EM)-1 and EM-2. EM-2 will be the first attempt to fly a piloted mission with the Orion spacecraft. The Integration 2 Team provides the customer (both commercial and Government) with access to a wide array of imagery options - ground-based, airborne, seaborne, or vehicle-based - that are available through the Government and commercial vendors. The team guides the customer in assembling the appropriate complement of imagery acquisition assets at the customer's facilities, minimizing costs associated with market research and the risk of purchasing inadequate assets. The NASA Integration 2 capability simplifies the process of securing one-of-a-kind imagery assets and skill sets, such as ground-based fixed and tracking cameras, crew-in the-loop imaging applications, and the integration of custom or commercial-off-the-shelf sensors onboard spacecraft. For spaceflight applications, the Integration 2 Team leverages modeling, analytical, and scientific resources along with decades of experience and lessons learned to assist the customer in optimizing engineering imagery acquisition and management schemes for any phase of flight - launch, ascent, on-orbit, descent, and landing. The Integration 2 Team guides the customer in using NASA's world-class imagery analysis teams, which specialize in overcoming inherent challenges associated with spaceflight imagery sets. Precision motion tracking, two-dimensional (2D) and three-dimensional (3D) photogrammetry, image stabilization, 3D modeling of imagery data, lighting assessment, and vehicle fiducial marking assessments are available. During a mission or test, the Integration 2 Team provides oversight of imagery operations to verify fulfillment of imagery requirements. The team oversees the collection, screening, and analysis of imagery to build a set of imagery findings. It integrates and corroborates the imagery findings with other mission data sets, generating executive summaries to support time-critical mission decisions.

Calhoun, Tracy↗

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗

Rodent Habitat on ISS: Advances in Capability for Determining Spaceflight Effects on Mammalian Physiology

Rodent research is a valuable essential tool for advancing biomedical discoveries in life sciences on Earth and in space. The National Research Counsel's Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, new flight hardware, operations, and science capabilities were developed at NASA ARC to support commercial and government-sponsored research. The flight phases of two separate spaceflight missions (Rodent Research-1 and Rodent Research-2) have been completed and new capabilities are in development. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 was dedicated to achieving both NASA validation and CASIS science objectives, while Rodent Reesearch-2 extended the period on orbit to 60 days. Groundbased control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis, and post-flight quantitative analyses of behavior were performed. The 10 mice from RR-1 Validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully, and high quality RNA (RIN values>9) and liver enzyme activities were obtained, validating the quality of sample recovery. Post-flight sample analysis revealed that body weights of FLT animals did not differ from ground controls (GC) housed in the same hardware, or vivarium controls (VIV) housed in standard cages. Organ weights analyzed post-flight showed that there were no differences between FLT and GC groups in adrenal gland and spleen weights, whereas FLT thymus and liver weights exceeded those of GC. Minimal differences between the control groups (GC and VIV) were observed. In addition, Over 3,000 aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for the Biospecimen Sharing Program and Genelab project. New capabilities recently developed include DEXA scanning, grip strength tests and male mice. In conclusion, new capability for long duration rodent habitation of group-housed rodents was developed and includes in-flight sample collection, thus avoiding the complication of reentry. Results obtained to date reveal the possibility of striking differences between the effects of short duration vs. long duration spaceflight. This Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.

Bone Loss↗

Autonomous Assessment and Predictive Capabilities for Low-Altitude Urban Flight Operations

The integration of unmanned aerial vehicles in the national airspace will introduce new vehicle types, technologies, and operational paradigms for which safety must be maintained and hazards mitigated. One approach is to attempt to design for possible hazards and unsafe incidents that can occur at different phases of flight (pre-flight, in-flight, and post-flight) and during ground operations. Another is to mitigate safety incidents by implementing changes to policies, procedures, regulations, and design to cover personnel, equipment, and aircraft during operations. These and other techniques, not described herein, are typically conservative or adhoc in that they reduce the likelihood of risk after safety incidents have occurred. In this work, the goal is to develop a more predictive capability to monitor and mitigate risk and hazards to safety “in-time” enough for decisions to be made. In line with NASA’s Aeronautics Mission Directorate Strategic Thrust 5 [1] (In-Time System-Wide Safety Assurance), the System-Wide Safety (SWS) project under which this work falls, is developing and demonstrating innovative and safety-oriented solutions that enable modernization and aviation transformation. To that effect, this work will detail data-driven efforts on the SWS project to develop a number of safety-critical services for in-time monitoring and mitigation of hazards to low-altitude flight operations. First, hazards to these operations are identified based on previous work by NASA [2,3] and others in the aerospace industry. These hazards include (i) unsafe proximity to other vehicles, property, and people on the ground, (ii) critical system failures such as communication signal/GPS loss, unexpected propulsion system degradation, engine/power failure, and (iii) operational/environmental issues such as severe weather and gusty winds. For these hazards, safety metrics, which can be quantified and assessed are defined, models to monitor and predict them are developed, and flight test data is generated to develop, validate, and test these models, considering the complex interplay of the different hazards that define them [4-6]. In addition, the uncertainty in the non-deterministic effects that cannot be modeled nor predicted and unknown unknowns that arise after design/testing and during operations must be handled in rigorous manner. As a result, for each of the developed safety metrics, their dependencies on one another are characterized and a framework for handling the uncertainties inherent in the modeling, algorithms, and measurements required for prediction is also developed [7]. To that effect, this presentation will describe the safety metrics and services already developed and underway under the System-Wide Safety project that utilize data-driven techniques for the identification of anomalies, precursors, and trends (APTs) to monitor and mitigate hazards to safety, in-time, for urban flight operations in low-altitude airspace.

Okolo, Wendy A.↗

Achieving Resilient In-Flight Performance for Advanced Air Mobility through Simplified Vehicle Operations

A research and development (R&D) approach is proposed for developing and validating concepts and technologies to achieve vehicle autonomy goals of Advanced Air Mobility (AAM) through Simplified Vehicle Operations (SVO). The approach applies resilience-engineering and human-automation teaming (HAT) principles to a framework for defining vehicle-based functions for the management of missions and flight trajectories, focusing initially on the en route flight domain. To achieve the SVO goal of reducing pilot training requirements and thereby increasing the pilot pool for AAM, while at the same time promoting ever-safer operations, a framework for identifying essential functions is proposed. In this framework, functions are first categorized by high-level functional purpose (mission management, flightpath management, tactical operations, and vehicle control) and then subcategorized by attributes of resilient-performing systems (abilities to monitor, respond, learn, and anticipate). The categorization by functional purpose provides structure within which HAT designs can be holistically explored and total levels of human vs. automation responsibility can be varied. The subcategorization by resilient-system attributes provides a mechanism for capturing safety-critical functions that may not be codified in current operational procedures and training curricula, particularly those where humans proactively enhance safety in currently undocumented ways. An R&D approach consisting of seven strategies is proposed in which automation engineering and human-factors communities can collaborate in the research, development, and design of an SVO roadmap to enable the ambitious objectives of AAM.

AAM↗

A Predictive GNSS Performance Monitor for Autonomous Air Vehicles in Urban Environments

The emergence and development of advanced technologies and vehicle types has created a growing demand for the introduction of new forms of flight operations. These new and increasingly complex operational paradigms such as Advanced and Urban Air Mobility (AAM/UAM) present regulatory authorities and the aviation community with several design and implementation challenges – particularly for highly autonomous vehicles. An overarching and daunting task is finding methods to integrate these emerging operations without compromising safety or disrupting traditional airspace operations. A shift toward a more predictive risk mitigation capability becomes critical to meet this challenge. This paper focus on the development and testing of a prognostic service aimed at estimating the quality of Global Navigation Satellite System (GNSS) performance for an autonomous aircraft in complex environments. The intent of this function is to proactively reduce a flight operations risk of exposure to states that may induce poor or unacceptable navigation system performance by factoring in estimates of GNSS quality into pre-flight and/or in-flight route planning. Methodologies for producing quality estimates are specified and results are provided for selected simulation and flight test cases.

GNSS↗

Biomedical Results of the Space Shuttle Program

The Space Shuttle Program (SSP), which was triumphantly completed by the flight of STS-135 on July 21, 2011, holds a special place in the history of Human Space Exploration. For the first time, a vehicle was built that could perform multiple flights in space and return to Earth. Many important questions regarding the ability of humans to adapt and function in space have been answered during the 30 years since the SSP was launched and many lessons have been learned. The multidisciplinary studies conducted during this program allowed NASA to define the normal responses and potential pathologic changes of the major physiological systems to short-duration space flights. The program significantly contributed to the development of in-flight medical care capabilities and multiple countermeasures. A comprehensive system of preflight, in-flight, and post-flight monitoring of the astronauts was built. It is important to emphasize that the SSP was essential for building the International Space Station (ISS) that significantly expanded the boundaries of space research, allowing for planning of long-term near-terrestrial and extraterrestrial missions. As the program was coming to completion, a decision was made by the NASA Lyndon B. Johnson Space Center Human Research Program senior management to summarize the medico-biological results of the SSP in one comprehensive edition. This was quite an ambitious goal. It required selection of a group of experts in different areas to become the chapters lead authors. These experts were charged with the task of reviewing what was learned in the consequent fields to make the chapters a comprehensive source of information for planning of research, operational activities, and medical care for future missions. We hope that we were able to accomplish this goal and the book will serve as a reliable reference edition for the international space biomedicine community, for new generation of space researchers and Flight Surgeons, as well as for all those interested in space exploration. As space exploration continues, the major question of whether humans are capable of adapting to long-term presence and adequately functioning in space habitats will remain open for a long time. we expect that the comprehensive review of the medico-biological results of the SSP along with the data collected during the missions on the space stations (the Russian space station _Mir_ and ISS) provides a good starting point in seeking the answer to this question.

Diana Risin↗