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Oxidative Stress and the Neuroconsequences of Spaceflight Environment - Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy

In this project, we will test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. The project will address NASA’s efforts to rapidly advance the characterization of risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of female astronauts, the two most recent NASA Astronaut Corps class selections, comprised of ~50% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. Here, we will determine how key features of the deep space environment may interact to increase risk to crewmembers by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18-18FLAG_2-0028.

radiation↗

Sex differences and deep space stressors: effects of 5-ion gcrsim, simulated microgravityand social isolation on immune function, brain, and behavior in mice

This project is testing the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we report findings from our studies of mature (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim (0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL) followed by combinatorial exposures to 15cGy, simulated microgravity via head-down tilt (hindlimb unloading) and social isolation. Immune, brain and behavioral (sensorimotor, risk-taking & cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Mars. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028.

behavioral sciences↗

A PI’s Guide to Analog Research

Congratulation on being awarded a grant to conduct research in a spaceflight analog! NASA funded research in a Human Research Program (HRP) managed analog environment is very different from research in a traditional laboratory. This presentation will provide a guide to help investigators successfully plan studies for integration and implementation in an HRP analog platform. There are many things to consider when planning a study for implementation in an analog facility and campaign or mission. How do you get from grant approval to data analysis? This is where HRP’s Research Operations and Integration (ROI) team comes in. The ROI team works with sponsoring HRP elements and PI teams to capture requirements and help the PI teams through the phases of research complement development, integration and implementation. A complement is comprised of a group of studies requiring a common platform and/or scenario that are able to be integrated on a noninterference basis for implementation. Properly defining and documenting requirements and study needs is crucial in successful integration and implementation. This presentation will outline and provide the information needed for PI teams to understand the integration process and the role of the ROI team in the successful integration and implementation of their study. Topics to be discussed will include but not be limited to science requirement definition and documentation, NASA IRB submissions, subject recruitment, screening and selection, study integration process, efficiency in data collection and data sharing, daily crew schedules, hardware and software shipping, receipt and checkout, biological sample collection, mission support, data management and receipt of data.

B. Caldwell↗

Impact of Simulated Galactic Cosmic Radiation and Hindlimb Unloading on the Mouse Adrenal Gland Morphology and Histology

Stress related impact of Galactic Cosmic Radiation (GCR) combined with microgravity in space are concerns for astronauts going beyond the Van Allen belts on their way to the Moon and Mars. The adrenal gland is the central endocrine tissue involved in stress management, adrenal hormones regulate the immune system, cellular and tissue metabolism, and glucose and sodium balances. Adult (6 m old) female (n=18) and male (n=18) C57BL/6J mice were divided evenly into 6 treatment groups (control, hindlimb unloading (HU), irradiated (IR), HU+IR, group house control, and group house IR). Adrenals were dissected and fixed for 24 h in 4% paraformaldehyde, followed by transfer to 70% EtOH, and shipment to KUMC. Adrenals were then embedded in paraffin and serial sectioned and 4 central sections from each were stained with H&E, prior to imaging on a Nikon 80i microscope. Whole adrenal cross section area, medullary area, and cortex area were determined. General adrenal gland morphology and histology did not appear to be affected by hindlimb unloading or GCR exposure. Total cross-sectional area, medullary region, and cortex of the adrenal were not different across treatment groups. Male adrenal cross-sectional areas are half the size of the female adrenals, due to a difference in cortex area. In conclusion, simulated microgravity and GCR did not dramatically affect the adrenal gland histology or size. Support from Accelerate Cancer Education Internship Program (KUCC) and KINBRE Summer Scholars Program (KUMC) and NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028

radiation↗

HRP Data Management Plan

The purpose of Human Research Program Data Management Plan (DMP) is to define the processes and activities required for the overall management of the research data collected and managed by HRP throughout their life cycle. New updates to the Data Management Plan in 2023 include 1. CAPABILITIES AND SERVICES Data Repositories. Principal Investigators (PIs) funded by HRP may be asked to submit data to one of several NASA data repositories. HRP archives data in the NASA Life Sciences Portal (NLSP) that it considers to be unique and high value. This includes data from human subjects in space flight (ISS and commercial flights) and ground analogs to spaceflight; spaceflight tech demos involving humans; human omics data including the microbiome; parabolic flight studies; and the NASA Space Radiation Laboratory (NSRL). The Open Science Data Repository (OSDR) includes The Ames Life Sciences Data Archive (ALSDA), used to archive non-human biological data (e.g., animal) generated by the Human Research program, and GeneLab, available to HRP PIs to archive non-human omics data. Catalog for search and retrieval. A catalog of non-human HRP life science experiments, with all associated descriptions (mission, payload, hardware, and personnel related information), and biospecimens is provided on the NLSP public web site for search and retrieval. 2. IRB ROLE IN RETURN OF INDIVIDUAL RESEARCH RESULTS The NASA IRB manages the process for incidental findings and for returning results to subjects for studies for which NASA IRB is the IRB of record. Omics data, especially genomics data, may generate information significant to the health of or risk to a research subject. These data potentially hold the keys to understand lifetime risks of chronic diseases, such as cancer, as well as risks associated with exposures common in space flight. 3. UPDATE OF TERMS – IDENTIFIABLE AND ATTRIBUTABLE DATA HRP now follows Federal and NASA policy by using “identifiable” instead of “attributable” for Personally Identifiable Information (PII). 4. POLICY ABOUT INTERNAL NON-RESEARCH USE OF DATA The HRP Chief Scientist grants access to data from HRP-funded research for non-research internal use that includes program management, customer facilitation, strategic planning, and risk research planning. Typical HRP personnel granted access to HRP research data for internal use include the Element Scientist, Subject Matter Experts (SME), and Data/bioinformatics Scientists. If data accessed for Internal Use is provided to an intramural or extramural scientist for hypothesis driven research, all Federal and NASA regulations (e.g., IRB review) regarding human subject research apply.

Data Management Plan↗

Remote Support of ISS Payload Operations During the COVID19 Pandemic

As part of the Human Health and Performance Contract (HHPC) with the NASA Johnson Space Center, the Human Research Program’s (HRP) Research Operations and Integration (ROI) element conducts the planning, implementation, and closing of human research operations on-board the International Space Station (ISS). These operations are supported out of the Telescience Support Center (TSC) located in the Mission Control Center at Houston’s Johnson Space Center (MCC-H). HRP ROI has an Emergency Response Plan in place to allow for remote operations to be completed in the case of inclement weather or other natural disaster; however, nominally, the remote support is only expected to last one to two weeks. In response to the COVID-19 global pandemic, HRP ROI was challenged to complete a quick transition to supporting on-orbit operations remotely and distanced for an indefinite amount of time. This shift in ground support required close collaboration with various external groups as well as the implementation or adaptation of various technologies and tools to ensure no loss of science data. Operational adjustments were put into place for ground commanding, telemetry monitoring, personnel staffing and private and public audio and video with the ISS. Adjustments were also put in place for communication and collaboration with MCC-H, the Payload Operation and Integration Center (POIC) at Marshall Space Flight Center (MSFC), as well as between the various HRP ROI console team members spread across Houston, TX. The ability to successfully support a variety of on-orbit operations from any remote location is more in demand as the commercialization of low Earth orbit is expanding.

Operations↗

The Nitty Gritty: How We Make Analogs Work

NASA's Human Research Program (HRP) is becoming increasingly reliant on Isolated, Confined and Controlled (ICC) analogs to accomplish many of its research objectives. Compared to other research platforms, ICC analogs present a unique set of operational challenges that must be addressed in order to ensure a high fidelity research environment. In particular, the Human Exploration Research Analog (HERA) habitat, which is classified as an ICC environment, has been developed over the past three years to accommodate the operational needs of research investigations from each of the HRP Elements. During the development period, various types of requirements have contributed to the current operational model, which strives to achieve the highest possible level of mission fidelity with limited resources. This presentation will focus on the operational aspects of the HERA habitat, with emphasis on how we develop the analog research environment to meet researchers' needs. Specific discussion topics include mission scenario development, operational tasks, mission timeline integration, stressor implementation, console support, and improvements based on lessons learned. The information is intended to help investigators better understand the details behind HERA operations and the benefits to their research goals.

Self, A. L.↗

HRP Chief Scientist's Office: Conducting Research to Enable Deep Space Exploration

The HRP Chief Scientist's Office sets the scientific agenda for the Human Research Program. As NASA plans for deep space exploration, HRP is conducting research to ensure the health of astronauts, and optimize human performance during extended duration missions. To accomplish this research, HRP solicits for proposals within the U.S., collaborates with agencies both domestically and abroad, and makes optimal use of ISS resources in support of human research. This session will expand on these topics and provide an opportunity for questions and discussion with the HRP Chief Scientist. Presentations in this session will include: NRA solicitations - process improvements and focus for future solicitations, Multilateral Human Research Panel for Exploration - future directions (MHRPE 2.0), Extramural liaisons - National Science Foundation (NSF) and Department of Defense (DOD), Standardized Measures for spaceflight, Ground-based Analogs - international collaborations, and International data sharing.

Charles, J. B.↗

Accomplishments in Bioastronautics Research Aboard International Space Station

The seventh long-duration expedition crew is currently in residence aboard International Space Station (ISS), continuing a permanent human presence in space that began in October 2000. During that time, expedition crews have been operators and subjects for 16 Human Life Sciences investigations, to gain a better understanding of the effects of long-duration space flight on the crew members and of the environment in which they live. Investigations have been conducted to study the radiation environment in the station as well as during extravehicular activity (EVA); bone demineralization and muscle deconditioning; changes in neuromuscular reflexes, muscle forces and postflight mobility; causes and possible treatment of postflight orthostatic intolerance; risk of developing kidney stones; changes in pulmonary function caused by long-duration flight as well as EVA; crew and crew-ground interactions; and changes in immune function. The experiment mix has included some conducted in flight aboard ISS as well as several which collected data only pre- and postflight. The conduct of these investigations has been facilitated by the Human Research Facility (HRF). HRF Rack 1 became the first research rack on ISS when it was installed in the US laboratory module Destiny in March 2001. The rack provides a core set of experiment hardware to support investigations, as well as power, data and commanding capability, and stowage. The second HRF rack, to complement the first with additional hardware and stowage capability, will be launched once Shuttle flights resume. Future years will see additional capability to conduct human research on ISS as International Partner modules and facility racks are added to ISS . Crew availability, both as a subject count and time, will remain a major challenge to maximizing the science return from the bioastronautics research program.

Uri, John J.↗

Human Factors Research Problems in Electronic Voice Warning System Design

The speech messages issued by voice warning systems must be carefully designed in accordance with general principles of human decision making processes, human speech comprehension, and the conditions in which the warnings can occur. The operator's effectiveness must not be degraded by messages that are either inappropriate or difficult to comprehend. Important experimental variables include message content, linguistic redundancy, signal/noise ratio, interference with concurrent tasks, and listener expectations generated by the pragmatic or real world context in which the messages are presented.

C A Simpson↗

Human factors in space station architecture 1: Space station program implications for human factors research

The space station program is based on a set of premises on mission requirements and the operational capabilities of the space shuttle. These premises will influence the human behavioral factors and conditions on board the space station. These include: launch in the STS Orbiter payload bay, orbital characteristics, power supply, microgravity environment, autonomy from the ground, crew make-up and organization, distributed command control, safety, and logistics resupply. The most immediate design impacts of these premises will be upon the architectural organization and internal environment of the space station.

Cohen, M. M.↗

Expanding NASA and Roscosmos Scientific Collaboration on the International Space Station

The International Space Station (ISS) is a world-class laboratory orbiting in space. NASA and Roscosmos have developed a strong relationship through the ISS Program Partnership, working together and with the other ISS Partners for more than twenty years. Since 2013, based on a framework agreement between the Program Managers, NASA and Roscosmos are building a joint program of collaborative research on ISS. This international collaboration is developed and implemented in phases. Initially, members of the ISS Program Science Forum from NASA and TsNIIMash (representing Roscosmos) identified the first set of NASA experiments that could be implemented in the "near term". The experiments represented the research categories of Technology Demonstration, Microbiology, and Education. Through these experiments, the teams from the "program" and "operations" communities learned to work together to identify collaboration opportunities, establish agreements, and jointly plan and execute the experiments. The first joint scientific activity on ISS occurred in January 2014, and implementation of these joint experiments continues through present ISS operations. NASA and TsNIIMash have proceeded to develop "medium term" collaborations, where scientists join together to improve already-proposed experiments. A major success is the joint One-Year Mission on ISS, with astronaut Scott Kelly and cosmonaut Mikhail Kornienko, who returned from ISS in March, 2016. The teams from the NASA Human Research Program and the RAS Institute for Biomedical Problems built on their considerable experience to design joint experiments, learn to work with each other's protocols and processes, and share medical and research data. New collaborations are being developed between American and Russian scientists in complex fluids, robotics, rodent research and space biology, and additional human research. Collaborations are also being developed in Earth Remote Sensing, where scientists will share data from imaging systems mounted on ISS as well as other orbiting spacecraft to improve our understanding of the Earth and its climate. NASA and Roscosmos continue to encourage international scientific cooperation and expanded use of the ISS Laboratory. "Long-term", larger collaborations will achieve scientific objectives that no single national science team or agency can achieve on its own. The joint accomplishments achieved so far have paved the way for a stronger international scientific community and improved results and benefits from ISS.

Hasbrook, Pete↗

Automating CapCom: Pragmatic Operations and Technology Research for Human Exploration of Mars

During the Apollo program, NASA and the scientific community used terrestrial analog sites for understanding planetary features and for training astronauts to be scientists. More recently, computer scientists and human factors specialists have followed geologists and biologists into the field, learning how science is actually done on expeditions in extreme environments. Research stations have been constructed by the Mars Society in the Arctic and American southwest, providing facilities for hundreds of researchers to investigate how small crews might live and work on Mars. Combining these interests-science, operations, and technology-in Mars analog field expeditions provides tremendous synergy and authenticity to speculations about Mars missions. By relating historical analyses of Apollo and field science, engineers are creating experimental prototypes that provide significant new capabilities, such as a computer system that automates some of the functions of Apollo s CapCom. Thus, analog studies have created a community of practice-a new collaboration between scientists and engineers-so that technology begins with real human needs and works incrementally towards the challenges of the human exploration of Mars.

Clancey, William J.↗

International Space Station as Analog of Interplanetary Transit Vehicle For Biomedical Research

Astronaut missions lasting up to six months aboard the International Space Station (ISS) have much in common with interplanetary flights, especially the outbound, Earth-to-Mars transit portion of a Mars mission. Utilization of ISS and other appropriate platforms to prepare for crewed expeditions to planetary destinations including Mars has been the work of NASA's Human Research Program (HRP) since 2005. HRP is charged specifically to understand and reduced the risks to astronaut health and performance in space exploration missions: everything HRP does and has done is directly related to that responsibility. Two major categories of human research have capitalized on ISS capabilities. The first category centers on the biomedical aspects of long-duration exposure to spaceflight factors, including prolonged weightlessness, radiation exposure, isolation and confinement, and actual risk to life and limb. These studies contribute to astronaut safety, health and efficiency on any long-duration missions, whether in low Earth orbit (LEO) or beyond. Qualitatively, weightlessness is weightlessness, whether in LEO or en route to Mars. The HRP sponsors investigations into losses in muscle and bone integrity, cardiovascular function, sensory-motor capability, immune capacity and psychosocial health, and development and demonstration of appropriate treatments and preventative measures. The second category includes studies that are focused on planetary expeditions beyond LEO. For these, ISS offers a high fidelity analog to investigate the combined effects of spaceflight factors (described above) plus the isolation and autonomy associated with simulated increasing distance from Earth. Investigations address crew cohesion, performance and workload, and mission control performance. The behavioral health and performance and space human factors aspects of planetary missions dominate this category. Work has already begun on a new investigation in this category which will examine the effects of a simulated lag in communications (mimicking that expected in transit to Mars) on astronaut performance aboard ISS. Extension of the current ISS increment duration from six months to nine or even twelve months would provide opportunities for expanded research relevant to long duration missions, albeit at the cost of fewer astronauts as subjects for those investigations. Given the possible limited access to ISS after 2020, if ISS is intended to facilitate future exploration missions, then the in-flight human investigations should focus on those that clearly enable future exploration missions.

Charles, John B.↗

Human behavioral research in space: quandaries for research subjects and researchers

With the advent of long-duration spaceflight on board the International Space Station (ISS) and possible future missions beyond low Earth orbit (LEO) such as Mars, it is critical that those at NASA have a realistic assessment of the challenges that will face individuals on long-duration missions so that they can develop preventive and real-time countermeasures to behavioral health issues. While space travellers are very interested in having countermeasures to the deleterious effects of space missions, they have a powerful disincentive to participate in this research if they feel it could in any way negatively affect their flight status. The behavioral issues of isolation and confinement for extended-duration space missions are reviewed. Areas of basic and clinical behavioral research are listed. And the classical clinical model for research is not considered appropriate for the current configuration of the space program. The use of analogue environments and advanced statistical analysis are suggested as ways to address the limited spaceflight research opportunities. The challenge of research subject or patient confidentiality vs. mission safety and issues of personal flight status are addressed.

Review, Tutorial↗

Human Factors Research Needs for In-Time Aviation Safety Management Systems (IASMS) Design: Enabling the NASA “Sky for All” Future Airspace Vision

Integrated safety management will be paramount for safely enabling the envisioned transformations of the future National Airspace System. Addressing the increasing need for advanced data analytics and fusion of aviation safety data, managed by human decision-makers, is essential for realizing the vision. The proposal, if accepted, will discuss safety management system challenges and how the concept of In-time Aviation Safety Management Systems addresses the need. It will also discuss human factors challenges involved in future integrated safety management, including trust, over-reliance, human-optimized data visualization, human-autonomy teaming, training, communication and dissemination of data, situation awareness, task load, and accountability.

Lawrence J Prinzel III↗

Quirky Circling Behavior in Mice Informs Research on Humans in Space

As interest in long duration effects of space habitation increases, understanding the behavior of model organisms living within the habitats engineered to fly them is vital for designing, validating, and interpreting future spaceflight studies. We previously conducted a detailed phenotypic analysis of mouse behavior during long duration (33-day) spaceflight in the NASA Rodent Habitat (Rodent Research-1; RR1 mission). Notably, we documented the emergence within the 8-10 days of launch of spontaneous ambulatory behavior in the form of circling or ‘race-tracking’ behavior in spaceflight but not in an identical ground control condition. Circling is unique to the NASA RH not having been reported to occur in other mouse habitats that provide limited opportunity for grasping, and/or are characterized by smaller habitable volumes viz., Italian Mice Drawer System (MDS) flown on ISS; Russian Block Obespecheniya Soderzhaniya (BOS) flown on Bion M-1, or JAXA Habitat Cage Unit (HCU) flown in the ISS Kibo module. Over time, circling became the primary dark cycle activity of FLT mice, occurring in individuals then as a coordinated group activity. Here we discuss possible interpretations of circling behavior including: (1) Stereotypic or abnormal repetitive behaviors (ARBs) that are unvarying, and apparently functionless behavior patterns documented numerous species in laboratory and zoo settings, possibility related to insufficient environmental enrichment and stress, (2) Rewarding effects of physical activity that are well-documented in terrestrial studies of rodents given the opportunity to run in wheels, and (3) Vestibular self-stimulation, i.e., the generation biologically-relevant amounts of vestibular sensory input to reduce the effects of microgravity. Affording mice the opportunity to grab and run in the RH resembles physical activities that the crew participate in routinely. Our approach is yielding an interesting analogue for better understanding human responses to spaceflight, and providing the opportunity to begin to address how physical movement influences responses to microgravity.

spaceflight↗

Mission Possible: BioMedical Experiments on the Space Shuttle

Biomedical research, both applied and basic, was conducted on every Shuttle mission from 1981 to 2011. The Space Shuttle Program enabled NASA investigators and researchers from around the world to address fundamental issues concerning living and working effectively in space. Operationally focused occupational health investigations and tests were given priority by the Shuttle crew and Shuttle Program management for the resolution of acute health issues caused by the rigors of spaceflight. The challenges of research on the Shuttle included: limited up and return mass, limited power, limited crew time, and requirements for containment of hazards. The sheer capacity of the Shuttle for crew and equipment was unsurpassed by any other launch and entry vehicle and the Shuttle Program provided more opportunity for human research than any program before or since. To take advantage of this opportunity, life sciences research programs learned how to: streamline the complicated process of integrating experiments aboard the Shuttle, design experiments and hardware within operational constraints, and integrate requirements between different experiments and with operational countermeasures. We learned how to take advantage of commercial-off-the-shelf hardware and developed a hardware certification process with the flexibility to allow for design changes between flights. We learned the importance of end-to-end testing for experiment hardware with humans-in-the-loop. Most importantly, we learned that the Shuttle Program provided an excellent platform for conducting human research and for developing the systems that are now used to optimize research on the International Space Station. This presentation will include a review of the types of experiments and medical tests flown on the Shuttle and the processes that were used to manifest and conduct the experiments. Learning Objective: This paper provides a description of the challenges related to launching and implementing biomedical experiments aboard the Space Shuttle.

Bopp, E.↗