Expanding disclosure of conflicts of interest: the views of stakeholders
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NASA Discipline General Space Life Sciences↗
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Use of a genetic algorithm for the analysis of eye movements from the linear vestibulo-ocular reflex
It is common in vestibular and oculomotor testing to use a single-frequency (sine) or combination of frequencies [sum-of-sines (SOS)] stimulus for head or target motion. The resulting eye movements typically contain a smooth tracking component, which follows the stimulus, in which are interspersed rapid eye movements (saccades or fast phases). The parameters of the smooth tracking--the amplitude and phase of each component frequency--are of interest; many methods have been devised that attempt to identify and remove the fast eye movements from the smooth. We describe a new approach to this problem, tailored to both single-frequency and sum-of-sines stimulation of the human linear vestibulo-ocular reflex. An approximate derivative is used to identify fast movements, which are then omitted from further analysis. The remaining points form a series of smooth tracking segments. A genetic algorithm is used to fit these segments together to form a smooth (but disconnected) wave form, by iteratively removing biases due to the missing fast phases. A genetic algorithm is an iterative optimization procedure; it provides a basis for extending this approach to more complex stimulus-response situations. In the SOS case, the genetic algorithm estimates the amplitude and phase values of the component frequencies as well as removing biases.
Non-NASA Center↗
Extravehicular activities guidelines and design criteria
A listing of astronaut EVA support systems and equipment, and the physical, operational, and performance characteristics of each major system are presented. An overview of the major ground based support operations necessary in the development and verification of orbital EVA systems is included. The performance and biomedical characteristics of man in the orbital EV environment are discussed. Major factors affecting astronaut EV work performance are identified and delineated as they relate to EV support systems design. Data concerning the medical and physiological aspects of spaceflight on man are included. The document concludes with an extensive bibliography, and a series of appendices which expand on some of the information presented in the main body.
Brown, N. E.↗
Utilizing Commercial Hardware and Open Source Computer Vision Software to Perform Motion Capture for Reduced Gravity Flight
Long duration space travel to Mars or to an asteroid will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited. Therefore, compact resistance exercise device prototypes are being developed. The NASA Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) project and the National Space Biomedical Research Institute (NSBRI) funded researchers by developing computational models of exercising with these new advanced exercise device concepts. To perform validation of these models and to support the Advanced Exercise Concepts Project, several candidate devices have been flown onboard NASAs Reduced Gravity Aircraft. In terrestrial laboratories, researchers typically have available to them motion capture systems for the measurement of subject kinematics. Onboard the parabolic flight aircraft it is not practical to utilize the traditional motion capture systems due to the large working volume they require and their relatively high replacement cost if damaged. To support measuring kinematics on board parabolic aircraft, a motion capture system is being developed utilizing open source computer vision code with commercial off the shelf (COTS) video camera hardware. While the systems accuracy is lower than lab setups, it provides a means to produce quantitative comparison motion capture kinematic data. Additionally, data such as required exercise volume for small spaces such as the Orion capsule can be determined. METHODS: OpenCV is an open source computer vision library that provides the ability to perform multi-camera 3 dimensional reconstruction. Utilizing OpenCV, via the Python programming language, a set of tools has been developed to perform motion capture in confined spaces using commercial cameras. Four Sony Video Cameras were intrinsically calibrated prior to flight. Intrinsic calibration provides a set of camera specific parameters to remove geometric distortion of the lens and sensor (specific to each individual camera). A set of high contrast markers were placed on the exercising subject (safety also necessitated that they be soft in case they become detached during parabolic flight); small yarn balls were used. Extrinsic calibration, the determination of camera location and orientation parameters, is performed using fixed landmark markers shared by the camera scenes. Additionally a wand calibration, the sweeping of the camera scenes simultaneously, was also performed. Techniques have been developed to perform intrinsic calibration, extrinsic calibration, isolation of the markers in the scene, calculation of marker 2D centroids, and 3D reconstruction from multiple cameras. These methods have been tested in the laboratory side-by-side comparison to a traditional motion capture system and also on a parabolic flight.
Biodynamics↗
Use of telescience for biomedical research during space flight
When the U.S. first embarked on a manned space flight program, NASA's use of medical telescience was focused on crew health monitoring. In recent years, medical telescience use has been expanded to include support of basic research in space medicine. It enables ground support personnel to assist on-board crews in the performance of experiments and improves the quality and quantity of data return. NASA is continuing to develop its telescience capabilities. Future plans include telemedicine that will enable physicians on Earth to support crewmembers during flight and telescience that will enable investigators at their home institutions to support and conduct in-flight medical research. NASA's use of telescience for crew safety and biomedical research from Project Mercury to the present is described and NASA's plans for the future are presented.
Huntoon, Carolyn L.↗
Proceedings of a conference on Cardiovascular Bioinstrumentation
The Ames Research Center (ARC) has a long history in the development of cardiovascular (CV) instrumentation for human and animal research. The ARC Cardiovascular Research Lab under the Space Physiology Branch, Space Research Directorate, supports both ground-based and space-based animal and human research goals. The Cardiovascular Research Laboratory was established at ARC in the mid 1960's to conduct ground-based animal research and support development of advanced cardiovascular instrumentation applicable to spaceflight. The ARC Biomedical Research Program also conducts human studies with a CV instrumentation focus.
Ballard, Rodney W.↗
Shear stress reduces protease activated receptor-1 expression in human endothelial cells
Shear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of vascular injury, which suggests an important role for PAR-1 in vascular diseases. However, the effect of shear stress on PAR-1 expression has not been previously studied. This work investigates effects of shear stress on PAR-1 gene expression in both human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (HMECs). Cells were exposed to different shear stresses using a parallel plate flow system. Northern blot and flow cytometry analysis showed that shear stress down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was due to a decrease of transcription rate, not increased mRNA degradation. Postshear stress release of endothelin-1 in response to thrombin was reduced in HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied during shear stress indicated mediation of the shear-decreased PAR-1 expression by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene expression in HMECs and HUVECs through a mechanism dependent in part on protein kinases, leading to altered endothelial cell functional responses to thrombin.
Non-NASA Center↗
NASA Wearable Technology CLUSTER 2013-2014 Report
Wearable technology has the potential to revolutionize the way humans interact with one another, with information, and with the electronic systems that surround them. This change can already be seen in the dramatic increase in the availability and use of wearable health and activity monitors. These devices continuously monitor the wearer using on-‐body sensors and wireless communication. They provide feedback that can be used to improve physical health and performance. Smart watches and head mounted displays are also receiving a great deal of commercial attention, providing immediate access to information via graphical displays, as well as additional sensing features. For the purposes of the Wearable Technology CLUSTER, wearable technology is broadly defined as any electronic sensing, human interfaces, computing, or communication that is mounted on the body. Current commercially available wearable devices primarily house electronics in rigid packaging to provide protection from flexing, moisture, and other contaminants. NASA mentors are interested in this approach, but are also interested in direct integration of electronics into clothing to enable more comfortable systems. For human spaceflight, wearable technology holds a great deal of promise for significantly improving safety, efficiency, autonomy, and research capacity for the crew in space and support personnel on the ground. Specific capabilities of interest include: Continuous biomedical monitoring for research and detection of health problems. Environmental monitoring for individual exposure assessments and alarms. Activity monitoring for responsive robotics and environments. Multi-modal caution and warning using tactile, auditory, and visual alarms. Wireless, hands-free, on-demand voice communication. Mobile, on-demand access to space vehicle and robotic displays and controls. Many technical challenges must be overcome to realize these wearable technology applications. For example, to make a wearable device that is both functional and comfortable for long duration wear, developers must strive to reduce electronic mass and volume while also addressing constraints imposed by the body attachment method. Depending on the application, the device must be placed in a location that the user can see and reach, and that provides the appropriate access to air and the wearer's skin. Limited power is available from body-‐worn batteries and heat must be managed to prevent discomfort. If the clothing is to be washed, there are additional durability and washability hurdles that traditional electronics are not designed to address. Finally, each specific capability has unique technical challenges that will likely require unique solutions. In addition to the technical challenges, development of wearable devices is made more difficult by the diversity of skills required and the historic lack of collaboration across domains. Wearable technology development requires expertise in textiles engineering, apparel design, software and computer engineering, electronic design and manufacturing, human factors engineering, and application-‐specific fields such as acoustics, medical devices, and sensing. Knowledge from each of these domains must be integrated to create functional and comfortable devices. For this reason, the diversity of knowledge and experience represented in the Wearable Technology is critical to overcoming the fundamental challenges in the field.
Simon, Cory↗
NASA's Rodent Research Project on ISS: Validation of a New Platform for Conducting Biomedical and Basic Research into the Consequences of Long Duration Habitation in Space
Rodent research has played a key role in advancing biomedical discoveries both 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, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored rodent research.Rodent Research-1 (RR-1) was the first mission in which animals were delivered and maintained in the ISS for a long duration mission in modified Animal Enclosure Module hardware. Both RR validation and commercial science objectives were pursued on the RR-1 mission. Adult female mice (20 total Flight, FLT) were launched Sept 21, 2014 in RR hardware within a Dragon Capsule (SpaceX4), then after 4 days in transit, were transferred for habitation on the ISS for 17 days (commercial) or 33 days (validation), when animals were euthanized and select tissues recovered on orbit. Various controls groups consisted of: 1) Basal mice from the same cohorts as FLT mice, but tissues were recovered at time of launch, 2) Vivarium (VIV) were housed in standard cages 3) Ground Controls (GC) were housed in flight hardware within an environmental chamber at Kennedy Space Center. The health and behavior of all mice on the ISS were monitored by video feed on a daily basis. Mice were euthanized by injection of Euthasol, then either fast frozen intact or dissected to preserve livers (fast frozen) and spleens (RNAlater). Samples were stored at ≤ -80˚C until their return to Earth for later analyses.Hardware performed nominally throughout the mission and the planned in-flight science operations were completed successfully. FLT mice appeared generally more physically active on orbit than respective GC groups. After 33 days on the ISS, mean body weights of FLT mice did not differ from GC, with both groups showing a 6% rise compared to time of launch, while VIV mice showed an 8% rise over the same period. Importantly, there were no significant differences in body weights between groups at the end of 33 days on the ISS, providing an indication that the RR hardware supported the health of the mice both on Earth and in space. Based on the preliminary data obtained from the livers and spleens of mice after 17 days on the ISS, purified RNA was of high quality (RIN values of spleen: FLT=9.48 +0.40, GC=9.28 +0.44, n=5/group); therefore, RNA quality from samples retrieved on orbit was acceptable for even the most demanding transcriptomic analyses. In addition, liver enzyme activity levels (units/mg protein) of FLT mice (after 17d on ISS) and all control mice were similar in magnitude to samples that were optimally prepared by freezing in liquid nitrogen in the laboratory (enzymes analyzed included catalase, glutathione reductase and glyceraldehyde-3-phosphate dehydrogenase). Validation analyses still in progress include behavior and tissue biochemistries, as well as optimization of science return by post-flight recovery of tissues for biospecimen sharing and global expression analyses.Together, these preliminary findings demonstrate new capability for supporting long duration rodent research on the ISS to achieve both basic science and biomedical objectives.
Globus, R. K.↗
The Walkback Test: A Study to Evaluate Suit and Life Support System Performance Requirements for a 10 Kilometer Traverse in a Planetary Suit
As planetary suit and planetary life support systems develop, specific design inputs for each system relate to a presently unanswered question concerning operational concepts: What distance can be considered a safe walking distance for a suited EVA crew member exploring the surface of the Moon to "walk-back" to the habitat in the event of a rover breakdown, taking into consideration the planned EVA tasks as well as the possible traverse back to the habitat? It has been assumed, based on Apollo program experience, that 10 kilometers (6.2 mi) will be the maximum EVA excursion distance from the lander or habitat to ensure the crew member s safe return to the habitat in the event of a rover failure. To investigate the feasibility of performing a suited 10 km Walkback, NASA-JSC assembled a multi-disciplinary team to design and implement the Lunar Walkback Test . The test was designed not only to determine the feasibility of a 10 km excursion, but also to collect human performance, biomedical, and biomechanical data relevant to optimizing space suit design and life support system sizing. These data will also be used to develop follow-on studies to understand interrelationships of such key parameters as suit mass, inertia, suit pressure, and center of gravity (CG), and the respective influences of each on human performance.
Vos, Jessica R.↗
The issue is leadership
Four NASA Phase B centers (NASA-Johnson, NASA-Marshall, NASA-Goddard, and NASA-Lewis) are responsible for construction, assembly, servicing, habitat, and other particular tasks and functions of the Space Station. The project has been joined by the aerospace programs of Canada, Japan, and the European Space Agency, ensuring technological and financial support, and cooperative use by the participants. Some of the future uses of the Space Station include biomedical research and applications; experiments in solar-terrestrial physics and astronomy; building, maintenance, and launching of space instruments and planetary missions; manufacturing and processing of materials that call for the conditions of microgravity and weightlessness; supporting communication operations; and improving earth and atmospheric observations. The political significance of the Space Station as a symbol of leadership and of friendly cooperation is noted.
Beggs, J. M.↗
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.↗
A national survey of policies on disclosure of conflicts of interest in biomedical research
BACKGROUND: Conflicts of interest pose a threat to the integrity of scientific research. The current regulations of the U.S. Public Health Service and the National Science Foundation require that medical schools and other research institutions report the existence of conflicts of interest to the funding agency but allow the institutions to manage conflicts internally. The regulations do not specify how to do so. METHODS: We surveyed all medical schools (127) and other research institutions (170) that received more than $5 million in total grants annually from the National Institutes of Health or the National Science Foundation; 48 journals in basic science and clinical medicine; and 17 federal agencies in order to analyze their policies on conflicts of interest. RESULTS: Of the 297 institutions, 250 (84 percent) responded by March 2000, as did 47 of the 48 journals and 16 of the 17 federal agencies. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions--reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. Ninety-one percent had policies that adhered to the federal threshold for disclosure ($10,000 in annual income or equity in a relevant company or 5 percent ownership), and 9 percent had policies that exceeded the federal guidelines. Only 8 percent had policies requiring disclosure to funding agencies, only 7 percent had such policies regarding journals, and only 1 percent had policies requiring the disclosure of information to the relevant institutional review boards or to research subjects. Twenty journals (43 percent) reported that they had policies requiring disclosure of conflicts of interest. Only four federal agencies had policies that explicitly addressed conflicts of interest in extramural research, and all but one of the agencies relied primarily on institutional discretion. CONCLUSIONS: There is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.
Human↗
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↗
An appraisal of future space biomedical research
Three general classes of manned space flight missions of the future are described. These include: earth-orbital, lunar, and planetary. Biomedical science and technology is analyzed emphasizing areas of research needed to support future manned space flights and the information to be obtained from them.
Vinograd, S. P.↗
MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring
Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.
NASA Discipline Cardiopulmonary↗
Research Opportunities Supporting the Vision for Space Exploration from the Transformation of the Former Microgravity Materials Science Program
The Microgravity Materials Science Program established a strong research capability through partnerships between NASA and the scientific research community. With the announcement of the vision for space exploration, additional emphasis in strategic materials science areas was necessary. The President's Commission recognized that achieving its exploration objectives would require significant technical innovation, research, and development in focal areas defined as "enabling technologies." Among the 17 enabling technologies identified for initial focus were: advanced structures, advanced power and propulsion; closed-loop life support and habitability; extravehicular activity systems; autonomous systems and robotics; scientific data collection and analysis, biomedical risk mitigation; and planetary in situ resource utilization. Mission success may depend upon use of local resources to fabricate a replacement part to repair a critical system. Future propulsion systems will require materials with a wide range of mechanical, thermophysical, and thermochemical properties, many of them well beyond capabilities of today's materials systems. Materials challenges have also been identified by experts working to develop advanced life support systems. In responding to the vision for space exploration, the Microgravity Materials Science Program aggressively transformed its research portfolio and focused materials science areas of emphasis to include space radiation shielding; in situ fabrication and repair for life support systems; in situ resource utilization for life support consumables; and advanced materials for exploration, including materials science for space propulsion systems and for life support systems. The purpose of this paper is to inform the scientific community of these new research directions and opportunities to utilize their materials science expertise and capabilities to support the vision for space exploration.
Clinton, R. G., Jr.↗
Biological Research and Space Health Enabled by Machine Learning to Support Deep Space Missions
A key science goal of the NASA “Moon to Mars” campaign is to understand how biology responds to the Lunar, Martian, and deep space environments in order to advance fundamental knowledge, reduce risk, and support safe, productive human space missions. Through the powerful emerging computer science approaches of artificial intelligence (AI) and machine learning (ML), a paradigm shift has begun in biomedical science and engineered astronaut health systems, to enable Earth-independence and autonomy of mission operations. We present a decadal view of AI/ML architecture to support deep space mission goals, developed in concert with leaders in the field. We describe current AI/ML methods to support 1) fundamental biology, 2) in situ analytics, 3) high performance computing hardware, 4) automated science, 5) self-driving labs, 6) remote data management, 7) integrated real-time mission biomonitoring, and 8) a Precision Space Health system. Cutting-edge AI/ML approaches that can be integrated to support these domains include active learning, explainable AI, adaptive learning, causal inference, knowledge graphs, federated learning, transfer learning, and large language models. Finally, we present results from several current ML projects that are underway in the field to address key challenges of small sample n, high feature count, heterogeneity, and sparse data. These include 1) connecting omics data to phenotypic data using an ensemble model to infer causality of spaceflight rodent liver health disruption, 2) usage of explainable ML to interrogate the muscular underpinnings of spaceflight muscle atrophy, 3) ML models analyzing and determining directed acyclic graphs of human space health risk leveraging rodent bone datasets, 4) usage of large pre-trained models connecting biomedical knowledgebases with small spaceflight datasets to understand gene-to-gene interaction networks, and 5) a suite of benchmarked open science datasets (spaceflight mouse liver; radiation DNA damage) enabling programmers to identify the best ML algorithms to answer space biological science questions.
space biology↗