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The Critical Path Roadmap Project: Biomedical Risk Reduction for Extended Spaceflight

Human exploration of space requires an understanding of the risks to which crews will be exposed during such missions, and the mitigation of those risks to the fullest extent practical. This becomes a greater imperative as we prepare for interplanetary expeditions involving long periods in weightlessness in transit to and then from the destination (a planet, such as Mars, or perhaps a point in space, such as the Lagrangian point L2), and exposure to the unique environment of the destination itself. We need to know, more definitively, what the risks are to human health, safety, and performance, and how to prevent or counteract them throughout all phases of a long duration mission. The Johnson Space Center's Space and Life Sciences Directorate and the National Space Biomedical Research Institute (NSBRI) have implemented an effort to identify the most critical risks confronting humans on such mission and the types of research and technology efforts required to mitigate and otherwise reduce the probability and severity of those risks. This paper describes the "Critical Path Roadmap Project" to define, assess and prioritize the risks and present the results of the assessment with an emphasis on the research and technology priorities to meet the challenge of long duration human spaceflight mission.

Charles, John B.↗

Spacelab Life Sciences Research Panel

This document describes some of the life sciences research that was conducted on Spacelab missions. Dr. Larry Young, Director of the National Space Biomedical Research Institute, provides an overview of the Life Sciences Spacelabs.

Sulzman, Frank↗

Increasing Data Discovery and Re-Use: The Space Life Sciences Ontology

Two of the most important goals of the adoption of the FAIR principles are increasing the ability of agents to find and re-use research data. Achieving these goals for space life sciences research is even more pressing, given the relatively expensive and scarce nature of these data. We have reported in the past on the progress made by exemplar life sciences data systems towards implementing FAIR, showing gaps particularly in the “interoperability area” of the principles; the lack of common conceptual models for space life science research is one reason for this gap. There were few available resources that define, annotate, categorize or otherwise relate various kinds of metadata describing the acquisition, nature, and intent of investigational space life sciences data. To address this gap, NASA is working with the Open Biological and Biomedical Ontology Foundry (https://obofoundry.org/) to develop the Space Life Science Ontology (SLSO) that is intended to support archival and other kinds of systems that operate using these data. The scope of the ontology includes concepts regarding those aspects of investigation design and execution specific or unique to space environments, such as types of specialized equipment, operating organizations, and documentation. The ontology is continually being developed and published to the life science community (https://github.com/nasa/LSDAO/); at the time of this publication, the SLSO newly and uniquely defines 30 types (classes), 90 properties, and 14 relations specific to space life sciences metadata. In addition, the SLSO reuses (imports) some 2,360 types (classes), 49 properties, and 393 relations from other ontologies that are relevant to these kinds of metadata. In addition to its role as a common conceptualization for space biomedical research activities, the SLSO can also be used to provide automated support for traditionally difficult and expensive activities such as data curation and cross-system data integration and analysis.

fair↗

Results of Life Sciences DSOs Conducted aboard the Space Shuttle: 1988-1990

Results are presented for a collection of life sciences investigations sponsored by the Space Biomedical Research Institute and Biomedical Research Operations at the NASA Lyndon B. Johnson Space Center and conducted as Detailed Supplementary Objectives (DSOs) on Space Shuttle flights between 1988 and 1990. Reports were grouped into grouped into four primary sections: Orthostatic Function, Neurophysiology, Biomedical Physiology, and Radiation Monitoring. The DSOs included in this report are: - DSO 460: Changes in Total Body Water During Space Flight - DSO 466: Pre- and Postflight Cardiovascular Assessment/Interim Report - DSO 467: Influence of Weightlessness of Baroreflex Function - DSO 459: Otolith Tilt-Translation Reinterpretation - DSO 450: Salivary Cortisol Levels During the Acute Phases of Space Flight - DSO 458: In-flight Pharmacokinetics of Acetaminophen in Saliva - DSO 469A: Low Earth Orbit Radiation Dose Distribution in a Phantom Head - DSO 469B: Active Dosimetric Measurements on Shuttle Flights/Interim Report - DSO 469C: Neutron Spectrum and Dose-Equivalent in Shuttle Flights During Solar Maximum

Carolyn S Leach↗

Human Factors in Training - Space Medicine Proficiency Training

The early Constellation space missions are expected to have medical capabilities very similar to those currently on the Space Shuttle and International Space Station (ISS). For Crew Exploration Vehicle (CEV) missions to ISS, medical equipment will be located on ISS, and carried into CEV in the event of an emergency. Flight Surgeons (FS) on the ground in Mission Control will be expected to direct the Crew Medical Officer (CMO) during medical situations. If there is a loss of signal and the crew is unable to communicate with the ground, a CMO would be expected to carry out medical procedures without the aid of a FS. In these situations, performance support tools can be used to reduce errors and time to perform emergency medical tasks. Work on medical training has been conducted in collaboration with the Medical Training Group at the Space Life Sciences Directorate and with Wyle Lab which provides medical training to crew members, Biomedical Engineers (BMEs), and to flight surgeons under the JSC Space Life Sciences Directorate s Bioastronautics contract. The space medical training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). Human factors researchers at Johnson Space Center have recently investigated medical performance support tools for CMOs on-orbit, and FSs on the ground, and researchers at the Ames Research Center performed a literature review on medical errors. The work proposed for FY10 continues to build on this strong collaboration with the Space Medical Training Group and previous research. This abstract focuses on two areas of work involving Performance Support Tools for Space Medical Operations. One area of research building on activities from FY08, involved the feasibility of just-in-time (JIT) training techniques and concepts for real-time medical procedures. In Phase 1, preliminary feasibility data was gathered for two types of prototype display technologies: a hand-held PDA, and a Head Mounted Display (HMD). The PDA and HMD were compared while performing a simulated medical procedure using ISS flight-like medical equipment. Based on the outcome of Phase 1, including data on user preferences, further testing was completed using the PDA only. Phase 2 explored a wrist-mounted PDA, and compared it to a paper cue card. For each phase, time to complete procedures, errors, and user satisfaction ratings were captured.

Connell, Erin↗

A National Virtual Specimen Database for Early Cancer Detection

Access to biospecimens is essential for enabling cancer biomarker discovery. The National Cancer Institute's (NCI) Early Detection Research Network (EDRN) comprises and integrates a large number of laboratories into a network in order to establish a collaborative scientific environment to discover and validate disease markers. The diversity of both the institutions and the collaborative focus has created the need for establishing cross-disciplinary teams focused on integrating expertise in biomedical research, computational and biostatistics, and computer science. Given the collaborative design of the network, the EDRN needed an informatics infrastructure. The Fred Hutchinson Cancer Research Center, the National Cancer Institute,and NASA's Jet Propulsion Laboratory (JPL) teamed up to build an informatics infrastructure creating a collaborative, science-driven research environment despite the geographic and morphology differences of the information systems that existed within the diverse network. EDRN investigators identified the need to share biospecimen data captured across the country managed in disparate databases. As a result, the informatics team initiated an effort to create a virtual tissue database whereby scientists could search and locate details about specimens located at collaborating laboratories. Each database, however, was locally implemented and integrated into collection processes and methods unique to each institution. This meant that efforts to integrate databases needed to be done in a manner that did not require redesign or re-implementation of existing system

distributed↗

Compact Microscope Imaging System With Intelligent Controls Improved

The Compact Microscope Imaging System (CMIS) with intelligent controls is a diagnostic microscope analysis tool with intelligent controls for use in space, industrial, medical, and security applications. This compact miniature microscope, which can perform tasks usually reserved for conventional microscopes, has unique advantages in the fields of microscopy, biomedical research, inline process inspection, and space science. Its unique approach integrates a machine vision technique with an instrumentation and control technique that provides intelligence via the use of adaptive neural networks. The CMIS system was developed at the NASA Glenn Research Center specifically for interface detection used for colloid hard spheres experiments; biological cell detection for patch clamping, cell movement, and tracking; and detection of anode and cathode defects for laboratory samples using microscope technology.

McDowell, Mark↗

ISS Utilization and Countermeasure Validation: Implementing the Critical Path Roadmap to Reduce Uncertainties of Extended Human Spaceflight Expeditions

Human exploration of space requires the ability to understand and mitigate risks to crews exposed to the conditions associated with such missions. This becomes a greater imperative as we prepare for interplanetary expeditions involving humans who will be subjected to long transit periods in microgravity as they travel to a distant planet such as Mars, embark and live on the planet's surface for an extended time, and finally, return to the 1 g environment of Earth. We need to know, more definitively, what the human health, safety, and performance risks are, and how to prevent or counteract them throughout all phases of a long duration mission. The Johnson Space Center's Space and Life Sciences Directorate along with the National Space Biomedical Research Institute (NSBRI) have been engaged in a strategic planning effort that identifies the most critical risks confronting humans who will venture forth on such missions and the types of research and technology efforts required to mitigate and otherwise reduce the probability and/or severity of those risks. This paper describes the unique approach used to define, assess and prioritize the risks and presents the results of the assessment with an emphasis on the research and technology priorities that will help us to meet the challenge of long duration human spaceflight missions.

Leveton, Lauren B.↗

Exposure to Microgravity for 30 Days Onboard Bion M1 Caused Muscle Atrophy and Decreased Regeneration in the Mouse Femoral Quadriceps

Mechanical unloading of muscle during spaceflight in microgravity is known to cause muscular atrophy, changes in muscle fiber type composition, gene expression, and reductions in regenerative muscle growth. Although limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how 30-day, long-term, mechanical unloading in microgravity affects mouse muscle of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle morphology observed in histological sections shows signs of extensive atrophy and regenerative hypoplasia. Specifically, we observed a two-fold decrease in the number of myonuclei, their central location, low density of myofibers and myofibrils, in fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appears to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them however showed evidence of apoptotic, TUNEL positive cells and myofibrils degradation, suggesting long-term unloading in microgravity affects late stages of myofiber differentiation. Ground asynchronous and vivarium control animals showed normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Myonuclei stress response in spaceflight animals was detected by positive nuclear immunolocalization of c-jun and c-myc proteins. Regenerative activity of satellite cells in muscles is detected in mice of all animal groups, by pax7, MyoD, and myogenin immunostaining and myogenin PCR analysis. In summary, long-term spaceflight in microgravity causes significant atrophy and degeneration of the femoral Quadriceps muscle group, and it may interfere with muscle regenerative processes by inducing apoptosis in newly-formed myofibrils during their differentiation phase.

Grigoryan, E. N.↗

Bion-M2

Bion-M2, scheduled to launch in April 2023, continues the 30+ year collaboration between the Institute of Biomedical Problems of the Russian Academy of Sciences (IBMP RAS) and the National Aeronautics and Space Administration (NASA). Bion-M2 is the second biosatellite in the Bion-M series and its goal is to investigate how the space environment affects living organisms, with emphasis on physiological changes in rodents, gravitational biology using a wide variety of specimens, and radiation biology. The Bion-M2 biosatellite will complete a 30-day low earth orbit (LEO) flight to study the combined effects of microgravity and ionizing radiation (IR) on multiple organisms, where the payload may be exposed to IR at 20-30 times thedose rate seen on the International Space Station. Following return, nine U.S. collaborators selected through the NASA Space Biology Research Announcement will conduct post-flight rodent experiments using male C57BL/6 mice. The post-flight experiments will investigate the effects of the space environment on bone and skeletal muscle health, cardiac function, reproductive system function, neurovascular systems, protein composition in plasma, and thermoregulation in the mice. Currently, the Bion-M2 mission is in the development phase of theproject lifecycle. The mission objectives, constraints, requirements, and timeline have been defined in the project plan and contracts. Technology for the mission is under development and science procedures will be finalized by FY22. The aim of this presentation is to highlight the importance of the Bion-M2 mission and provide insight into the mission development process, including an overview of the project plan and the tissue sharing plan that will be utilized during the post-flight dissection procedures.

Bion-M2↗

Benchmarks: Reports of the NASA Science Institutes Team

This report results from a benchmarking study undertaken by NASA as part of its planning for the possible creation of new science Institutes. Candidate Institutes under consideration cover a range of scientific and technological activities ranging from biomedical to astrophysical research and from the global hydrological cycle to microgravity material science. Should NASA create these Institutes, the intent will be to preserve and strengthen key science and technology activities now being performed by Government employees at NASA Field Centers. Because the success of these projected non-Government-operated Institutes is vital for the continued development of space science and applications, NASA has sought to identify the best practices of successful existing scientific and technological research institutions as they carry out those processes that will be most important for the new science Institutes. While many individuals and organizations may be interested in our findings, the primary use of this report will be to formulate plas for establishing the new science Institutes. As a result, the report is organized to that the "best practices" of the finest institutes are associated with characteristics of all institutes. These characteristics or "attributes" serve as the headings for the main body of this report.

Diaz, A. V.↗

Programmatic Comments

The life science programs of NASA are informally discussed. Research areas can be generally categorized as space biology, aerospace medicine, origins of life, biomedical research, and life support systems. The role of the life sciences in the development of the space station and the experimental opportunities afforded by such a facility are addressed.

Soffen, G.↗

Legacy of Biomedical Research During the Space Shuttle Program

The Space Shuttle Program provided many opportunities to study the role of spaceflight on human life for over 30 years and represented the longest and largest US human spaceflight program. Outcomes of the research were understanding the effect of spaceflight on human physiology and performance, countermeasures, operational protocols, and hardware. The Shuttle flights were relatively short, < 16 days and routinely had 4 to 6 crewmembers for a total of 135 flights. Biomedical research was conducted on the Space Shuttle using various vehicle resources. Specially constructed pressurized laboratories called Spacelab and SPACEHAB housed many laboratory instruments to accomplish experiments in the Shuttle s large payload bay. In addition to these laboratory flights, nearly every mission had dedicated human life science research experiments conducted in the Shuttle middeck. Most Shuttle astronauts participated in some life sciences research experiments either as test subjects or test operators. While middeck experiments resulted in a low sample per mission compared to many Earth-based studies, this participation allowed investigators to have repetition of tests over the years on successive Shuttle flights. In addition, as a prelude to the International Space Station (ISS), NASA used the Space Shuttle as a platform for assessing future ISS hardware systems and procedures. The purpose of this panel is to provide an understanding of science integration activities required to implement Shuttle research, review biomedical research, characterize countermeasures developed for Shuttle and ISS as well as discuss lessons learned that may support commercial crew endeavors. Panel topics include research integration, cardiovascular physiology, neurosciences, skeletal muscle, and exercise physiology. Learning Objective: The panel provides an overview from the Space Shuttle Program regarding research integration, scientific results, lessons learned from biomedical research and countermeasure development.

Hayes, Judith C.↗

Biomedical programs operations plans

Operational guidelines for the space shuttle life sciences payloads are presented. An operational assessment of the medical experimental altitude test for Skylab, and Skylab life sciences documentation are discussed along with the operations posture and collection of space shuttle operational planning data.

Walbrecher, H. F.↗

The Proceedings of the Skylab Life Sciences Symposium, Volume 1

The three manned Skylab missions resulted in biomedical experiment data in the areas of neurophysiology, musculoskeletal physiology, biochemistry, hematology, cytology, cardiovascular and respiratory metabolic functions: as well as detailed test objectives involving crew health and environment procedures. Major emphasis was placed on results from the last mission, Skylab 4, which covered 84 days of in-flight data collection. Many new norms were defined for normal man living and operating in a unique environment. While man is quite adaptable to this unique environment, many of the changes observed in Skylab require additional research for future flights lasting very long periods of time such as a Mars mission requiring 18 months.

Johnston, R. S.↗

The Proceedings of the Skylab Life Sciences Symposium, volume 2

The three manned Skylab missions resulted in biomedical experiment data in the areas of neurophysiology, musculoskeletal physiology, biochemistry, hematology, cytology, cardiovascular and respiratory metabolic functions: as well as detailed test objectives involving crew health and environment procedures. Major emphasis was placed on results from the last mission, Skylab 4, which covered 84 days of in-flight data collection. Many new norms were defined for normal man living and operating in a unique environment. While man is quite adaptable to this unique environment, many of the changes observed in Skylab require additional research for future flights lasting very long periods of time such as a Mars mission requiring 18 months.

Johnston, R. S.↗

Life Sciences Data Archives (LSDA) in the Post-Shuttle Era

Now, more than ever before, NASA is realizing the value and importance of their intellectual assets. Principles of knowledge management-the systematic use and reuse of information, experience, and expertise to achieve a specific goal-are being applied throughout the agency. LSDA is also applying these solutions, which rely on a combination of content and collaboration technologies, to enable research teams to create, capture, share, and harness knowledge to do the things they do well, even better. In the early days of spaceflight, space life sciences data were collected and stored in numerous databases, formats, media-types and geographical locations. These data were largely unknown/unavailable to the research community. The Biomedical Informatics and Health Care Systems Branch of the Space Life Sciences Directorate at JSC and the Data Archive Project at ARC, with funding from the Human Research Program through the Exploration Medical Capability Element, are fulfilling these requirements through the systematic population of the Life Sciences Data Archive. This project constitutes a formal system for the acquisition, archival and distribution of data for HRP-related experiments and investigations. The general goal of the archive is to acquire, preserve, and distribute these data and be responsive to inquiries for the science communities. Information about experiments and data, as well as non-attributable human data and data from other species' are available on our public Web site http://lsda.jsc.nasa.gov. The Web site also includes a repository for biospecimens, and a utilization process. NASA has undertaken an initiative to develop a Shuttle Data Archive repository. The Shuttle program is nearing its end in 2010 and it is critical that the medical and research data related to the Shuttle program be captured, retained, and usable for research, lessons learned, and future mission planning. Communities of practice are groups of people who share a concern or a passion for something they do, and learn how to do it better as they interact regularly. LSDA works with the HRP community of practice to ensure that we are preserving the relevant research and data they need in the LSDA repository. An evidence-based approach to risk management is required in space life sciences. Evidence changes over time. LSDA has a pilot project with Collexis, a new type of Web-based search engine. Collexis differentiates itself from full-text search engines by making use of thesauri for information retrieval. The high-quality search is based on semantics that have been defined in a life sciences ontology. Additionally, Collexis' matching technology is unique, allowing discovery of partially matching dicuments. Users do not have to construct a complicated (Boolean) search query, but can simply enter a free text search without the risk of getting "no results". Collexis may address these issues by virtue of its retrieval and discovery capabilities across multiple repositories.

Fitts, Mary A.↗

Life Sciences Data Archive (LSDA) in the Post-Shuttle Era

Now, more than ever before, NASA is realizing the value and importance of their intellectual assets. Principles of knowledge management, the systematic use and reuse of information/experience/expertise to achieve a specific goal, are being applied throughout the agency. LSDA is also applying these solutions, which rely on a combination of content and collaboration technologies, to enable research teams to create, capture, share, and harness knowledge to do the things they do well, even better. In the early days of spaceflight, space life sciences data were been collected and stored in numerous databases, formats, media-types and geographical locations. These data were largely unknown/unavailable to the research community. The Biomedical Informatics and Health Care Systems Branch of the Space Life Sciences Directorate at JSC and the Data Archive Project at ARC, with funding from the Human Research Program through the Exploration Medical Capability Element, are fulfilling these requirements through the systematic population of the Life Sciences Data Archive. This project constitutes a formal system for the acquisition, archival and distribution of data for HRP-related experiments and investigations. The general goal of the archive is to acquire, preserve, and distribute these data and be responsive to inquiries from the science communities.

Fitts, Mary A.↗