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At least 307 records · Page 17

Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

We demonstrated for the first time that vitamin D3 influences the effect of PTH on bone cell calcium ion levels. This is a rapid effect, taking place within seconds/minutes. This may prove to be a critical contribution to our understanding of bone physiology in that these two hormones are among the most potent regulators of bone calcium content and of systemic calcium homeostasis. Together with the data gathered from the study of astronauts exposed to microgravity for extended periods, these observations suggest the interaction of vitamin D3 and PTH as a possible therapeutic target in the treatment of bone loss disorders such as osteoporosis and disuse atrophy. Chronic exposure of cultured osteoblasts to vitamin D, altered the number of voltage-sensitive Ca(+2) channels expressed. Estrogen treatment yielded a similar result, suggesting that there is overlap in the mechanism by which these hormones elicit long-term effects on bone cell calcium homeostasis.

Li, Wei↗

Applications of Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

The experiments in Round 2 were designed to extend the results of our efforts in Round 1 which led us to hypothesize that the seco-steroid, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], acts in synergy with parathyroid hormone (PTH) to regulate bone calcium homeostasis. Our work centered on one particular target of 1,25(OH)2D3 action, the voltage-sensitive calcium channels (VSCC's), which are activated acutely by this steroid within milliseconds of exposure . A second area of research focused on the effects of mechanical strain on VSCC expression in bone. These experiments were performed in collaboration with Dr. Steven Goldstein (Univ. Michigan), who generously provided RNA extracted from dog bones that had been exposed to mechanical strain in vivo. Our results suggest that mechanical loading elevated VSCC expression in the long bones from 3 of the 6 animals tested. A second line of experimentation, carried out in collaboration with Dr. Randall Duncan, a NASA-funded investigator in Indianapolis, centered on RT-PCR analysis of effects of mechanical strain on Ca2(+) channel expression in cultured bone cells. Compared to unstrained controls, the expression of vitamin-D-sensidve Ca2(+) channels is elevated 3- to 5-fold over a 24 hr period.

Karin, Norman J.↗

Artificial Gravity as a Countermeasure of Cardiovascular Deconditioning in Spinal Cord Injury

An essential item in the development of this project was the availability of the artificial gravity simulator (AGS). At the termination of that grant in 1994, the AGS was dismantled and transferred to NASA Johnson Space Center. It took over two years for the AGS to be re-assembled and re-certified for use. As a consequence of the non-availability of the AGS for two years, there was a considerable delay in implementing the various phases of the project. The subjects involved in the study were eight healthy able bodied subjects and twelve with spinal cord injury. After analysis of the data collected on these subjects, six of the healthy able bodied subjects and three of the sub ects with spinal cord injury were found to qualify for the study. This report gives the results of four subjects only, two healthy able bodied and two spinal cord injured subjects because the period of the grant (1 year) and its extension (1 year) expired before additional subjects could be studied. The principal objective of the study was to conduct a series of experiments to demonstrate the feasibility of utilizing artificial gravity to assist in the physical rehabilitation of persons with spinal cord injuries.

Cardus, David↗

Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

OMalley, Bert W.↗

Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight

This project is concerned with identifying ways to prevent neurobehavioral and physical deterioration due to inadequate sleep in astronauts during long-duration manned space flight. The performance capability of astronauts during extended-duration space flight depends heavily on achieving recovery through adequate sleep. Even with appropriate circadian alignment, sleep loss can erode fundamental elements of human performance capability including vigilance, cognitive speed and accuracy, working memory, reaction time, and physiological alertness. Adequate sleep is essential during manned space flight not only to ensure high levels of safe and effective human performance, but also as a basic regulatory biology critical to healthy human functioning. There is now extensive objective evidence that astronaut sleep is frequently restricted in space flight to averages between 4 hr and 6.5 hr/day. Chronic sleep restriction during manned space flight can occur in response to endogenous disturbances of sleep (motion sickness, stress, circadian rhythms), environmental disruptions of sleep (noise, temperature, light), and curtailment of sleep due to the work demands and other activities that accompany extended space flight operations. The mechanism through which this risk emerges is the development of cumulative homeostatic pressure for sleep across consecutive days of inadequate sleep. Research has shown that the physiological sleepiness and performance deficits engendered by sleep debt can progressively worsen (i.e., accumulate) over consecutive days of sleep restriction, and that sleep limited to levels commonly experienced by astronauts (i.e., 4 - 6 hr per night) for as little as 1 week, can result in increased lapses of attention, degradation of response times, deficits in complex problem solving, reduced learning, mood disturbance, disruption of essential neuroendocrine, metabolic, and neuroimmune responses, and in some vulnerable persons, the emergence of uncontrolled sleep attacks. The prevention of cumulative performance deficits and neuroendocrine disruption from sleep restriction during extended duration space flight involves finding the most effective ways to obtain sleep in order to maintain the high-level cognitive and physical performance functions required for manned space flight. There is currently a critical deficiency in knowledge of the effects of how variations in sleep duration and timing relate to the most efficient return of performance per unit time invested in sleep during long-duration missions, and how the nature of sleep physiology (i.e., sleep stages, sleep electroencephalographic [EEG] power spectral analyses) change as a function of sleep restriction and performance degradation. The primary aim of this project is to meet these critical deficiencies through utilization of a response surface experimental paradigm, testing in a dose-response manner, varying combinations of sleep duration and timing, for the purpose of establishing how to most effectively limit the cumulative adverse effects on human performance and physiology of chronic sleep restriction in space operations.

Dinges, David F.↗

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and Their Implications for Bone Strain

The human zero-gravity locomotion simulator and the cadaver simulator offer a powerful combination for the study of the implications of exercise for maintaining bone quality during space flight. Such studies, when compared with controlled in-flight exercise programs, could help in the identification of a strain threshold for the prevention of bone loss during space flight.

Peterman, M.↗

Development of Countermeasures and Exercise Protocols to Reduce the Effects of Microgravity

I have helped scientists at NASA-JSC in analyzing data from many projects. Some of the major ones are: (1) cardiovascular responses to lower body negative pressure (LBNP) following bed rest, (2) the effects of dietary sodium, (3) in-flight cycle exercise mitigates reduced oxygen consumption at submaximal heart rates following space flight, (4) exercise thermoregulation after 13 days of head down bed rest, and (5) bed rest induced orthostatic intolerance. Many of the projects have now been completed and some of them are in the process of being published and others have been presented at national meetings. These projects have helped me be a true statistician and given me a real-life perspective of how interesting and complicated data can be. As a by-product of of these involvements I have been able to write and publish some methodological research that have applications in NASA and elsewhere. For instance, while I was at JSC, I happened to meet Dr. Al Feiveson and got into a discussion of the Space Shuttle Reliability. This led us to rethink about the way the data on the accelerated life testing of space shuttle pressure vessels had been analyzed. This has resulted in a major statistical paper and the paper has appeared in one of the top journals in the field of Statistics. A review of the paper by the editor of the journal was published in AmStatNews, a copy is attached with this report. I have presented these findings at the national/international statistics conference and at other places. I have also written another paper on reliability and a paper on calibration techniques that have applications in the engineering and the biomedical branches of NASA. Further, I am currently in the process of writing at least two more papers that have direct applications in NASA related studies.

Kulkarni, Pandurang M.↗

Decision Making In A High-Tech World: Automation Bias and Countermeasures

Automated decision aids and decision support systems have become essential tools in many high-tech environments. In aviation, for example, flight management systems computers not only fly the aircraft, but also calculate fuel efficient paths, detect and diagnose system malfunctions and abnormalities, and recommend or carry out decisions. Air Traffic Controllers will soon be utilizing decision support tools to help them predict and detect potential conflicts and to generate clearances. Other fields as disparate as nuclear power plants and medical diagnostics are similarly becoming more and more automated. Ideally, the combination of human decision maker and automated decision aid should result in a high-performing team, maximizing the advantages of additional cognitive and observational power in the decision-making process. In reality, however, the presence of these aids often short-circuits the way that even very experienced decision makers have traditionally handled tasks and made decisions, and introduces opportunities for new decision heuristics and biases. Results of recent research investigating the use of automated aids have indicated the presence of automation bias, that is, errors made when decision makers rely on automated cues as a heuristic replacement for vigilant information seeking and processing. Automation commission errors, i.e., errors made when decision makers inappropriately follow an automated directive, or automation omission errors, i.e., errors made when humans fail to take action or notice a problem because an automated aid fails to inform them, can result from this tendency. Evidence of the tendency to make automation-related omission and commission errors has been found in pilot self reports, in studies using pilots in flight simulations, and in non-flight decision making contexts with student samples. Considerable research has found that increasing social accountability can successfully ameliorate a broad array of cognitive biases and resultant errors. To what extent these effects generalize to performance situations is not yet empirically established. The two studies to be presented represent concurrent efforts, with student and professional pilot samples, to determine the effects of accountability pressures on automation bias and on the verification of the accurate functioning of automated aids. Students (Experiment 1) and commercial pilots (Experiment 2) performed simulated flight tasks using automated aids. In both studies, participants who perceived themselves as accountable for their strategies of interaction with the automation were significantly more likely to verify its correctness, and committed significantly fewer automation-related errors than those who did not report this perception.

Mosier, Kathleen L.↗

The NASA Ames Fatigue Countermeasures Program: The Next Generation

Twenty-four hour, global aviation operations pose unique challenges to humans. Physiological requirements related to sleep, the internal circadian clock, and human fatigue are critical factors that are known to affect safety, performance, and productivity. Understanding the human operators' physiological capabilities, and limitations, will be important to address these issues as global demand for aviation activities continues to increase. In 1980, in response to a Congressional request, the National Aeronautics and Space Administration (NASA) Ames Research Center initiated a Fatigue/Jet Lag Program to examine the role of fatigue in flight operations. Originally established by Dr. John K. Lauber and Dr. Charles E. Billings, the Program was designed to address three objectives: (1) determine the extent of fatigue, sleep loss, and circadian disruption in flight operations; (2) determine how fatigue affected flight crew performance; and (3) develop strategies to maximize performance and alertness during flight operations.

Rosekind, Mark R.↗

Automation Bias and Countermeasures in Flight Crews

Results of recent research investigating the use of automated systems have indicated the presence of automation bias, a term describing errors made when decision makers rely on automated cues as a heuristic replacement for vigilant information seeking and processing. Automation commission errors, i.e., errors made when decision makers take inappropriate action because they over-attend to automated information or directives, and automation omission errors, i.e., errors made when decision makers do not take appropriate action because they are not informed of an imminent problem or situation by automated aids, can result from this tendency. In a series of studies, participants who perceived themselves as "accountable" for their strategies of interaction with automation were significantly more likely to verify its correct functioning, and committed significantly fewer automation-related errors than those who did not report this perception. In this study, we focus on two manipulations to encourage verification behaviors within cockpit crews. The first, an information/training manipulation, will focus on explicit information on automation bias, and training for verification of automated functioning. The second manipulation will consist of display prompts to verify automated functioning. Participants (glass-cockpit crews) will fly a series of approaches on the Mini-ACFS, a two-person pan-task flight simulator. Approach scenarios include several automation "events," that is, glitches, malfunctions, or inappropriate recommendations, that can be caught if cross-checked with other cockpit indicators. We anticipate that these manipulations will ameliorate automation bias. Final data analysis will be completed prior to the OSU symposium, and is expected to support the hypotheses that: a) reduced errors are associated with verification behaviors; b) crews will be more likely to verify under training/display conditions than when in the control condition; and c) effects will persist when subjects return for a follow-up exercise 6-9 weeks after their first session. Implications for training and automation design will be discussed.

Mosier, Kathleen, L.↗

Mechanical Signal Transduction in Countermeasures to Muscle Atrophy

We have shown that modifications in muscle use result in changes in the expression and activity of calpains and nitric oxide synthase (NOS). Although muscle unloading for 10 days produced no change in the concentrations of calpain 1 or 2 and no change in calpain activation, muscle reloading produced a 90% increase in calpain 2 concentration. We developed an in vitro model to test our hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. Talin was selected because it is a well-characterized calpain substrate and it is codistributed with calpain in muscle cells. We found that intermittant loading during hindlimb suspension that is sufficient to prevent muscle mass loss that occurs during muscle unloading is also sufficient to prevent the decrease in NOS expression that normally occurs during hindlimb unloading. These findings indicate that therapeutics directed toward regulating the calpain/calpastatin system may be beneficial in preventing muscle mass loss in muscle injury, unloading and disease.

Tidball, James G.↗

Radiation Hazards and Countermeasures for Human Space Flight

Protection of the astronauts from space radiation is NASA's moral and legal responsibility. There can be no manned deep space missions without adequate protection from the ionizing radiation in space. There are tow parts to radiation protection, determining the effects of space radiation on humans so that adequate exposure limits can be set and providing radiation protection that insures those limits will not be exceeded. This talk will review the status of work on these two parts and identify areas that are currently being investigated and gaps in the research that have been identified.

Adams, James H., Jr.↗

Development of a Vibration Based Countermeasure to Inhibit the Bone Erosion and Muscle Deterioration That Parallels Spaceflight

The extent of bone and muscle loss in astronauts on missions longer than 30 days poses significant acute and chronic health risks. Recent work in a variety of species has revealed that low magnitude, high frequency (25-90 Hz) mechanical stimulation is anabolic and may inhibit hypothesis that short-term, low-intensi(y mechanical in the lower limb that parallels extended exposure to microgravity. If this experiment is selected for flight, 12 right leg serves as a contralateral control. Each astronaut will undergo treatment for 10 minutes per day, five days Pre- and post-flight bone and muscle testing will be used to assess efficacy as well as intra-subject comparison of the experimental leg to the control leg.

Kaplan, Tamara↗

Space Radiation Hazards and Countermeasures: 1990-2004

Contents include the folowing: radiation environments, tools and techniques for measuring radiation dosage, effects of radiation on humans and animal models, methods for strengthening biological resistance to radiation, and radiation shielding.

Source record↗

Maximal exercise as a countermeasure to orthostatic intolerance after spaceflight

Previous investigators have suggested that maximal exercise performed 24 h before the end of bed rest, a spaceflight analog, restores prebed rest plasma volume, baroreflex responses, and orthostatic tolerance. PURPOSE: In this case report, we examined the effect of a similar exercise protocol 24 h before a Shuttle landing on the orthostatic responses of four crewmembers (EX) after spaceflights of 8-14 d. Four additional crewmembers (CON) served as controls and did not perform exercise during the final day of the flight. METHODS: Each crewmember performed a 10-min stand test approximately 10 d before launch (L-10) and within 1-2 h of landing (R+0). Cardiac stroke volume was measured (Doppler ultrasound) supine and during each min of standing for three EX and three CON subjects. RESULTS: Preflight, all crewmembers completed the stand test and each group had similar heart rate and blood pressure responses. Postflight, all subjects also completed the 10-min stand test. Each group had similarly elevated supine and standing heart rates, elevated diastolic and mean arterial blood pressures, and reduced pulse pressures compared to L-10. However, postflight cardiac output, mean +/- SEM, (EX: 4.5+/-0.6 L x min(-1); CON: 3.1+/-0.3 L x min(-1)) and stroke volume (EX: 43+/-7 mL x beat; CON: 30+/-6 mL x beat) were higher after 10 min standing in the EX subjects compared to CON subjects. CONCLUSIONS: For these four crewmembers, maximal exercise performed 24 h before landing may have helped maintain stroke volume but did not maintain heart rate and blood pressure responses during standing compared to preflight.

Flight Experiment↗

EXERCISE WITHIN LOWER BODY NEGATIVE PRESSURE AS AN ARTIFICIAL GRAVITY COUNTERMEASURE

Current exercise systems for space, which attempt to maintain performance, are unable to generate cardiovascular and musculoskeletal loads similar to those on Earth [1, 2]. The purpose of our research is to evaluate the use of lower body negative pressure (LBNP) treadmill exercise to prevent deconditioning during simulated microgravity.

Hargens, Alan R.↗

The Lessons Learned Process: An Effective Countermeasure Against Avoidable Risk

The potential for errors in engineering judgement arguably present the highest level of risk when applied to interplanetary spaceflight. JPL has been refining its lessons learned process to optimize the collection and transfer of critical success factors applicable to current and future spaceflight projects.

lessons learned information system process improve↗

Artificial Gravity as a Multi-System Countermeasure to Bed Rest Deconditioning: Preliminary Results

Artificial gravity paradigms may offer effective, efficient, multi-system protection from the untoward effects of adaptation to the microgravity of space or the hypogravity of planetary surfaces. Intermittent artificial gravity (AG) produced by a horizontal short-radius centrifuge (SRC) has recently been utilized on human test subjects deconditioned by bed rest. This presentation will review preliminary results of a 41 day study conducted at the University of Texas Medical Branch, Galveston, TX bed rest facility. During the first eleven days of the protocol, subjects were ambulatory, but confined to the facility. They began a carefully controlled diet, and participated in multiple baseline tests of bone, muscle, cardiovascular, sensory-motor, immunological, and psychological function. On the twelfth day, subjects entered the bed rest phase of the study, during which they were confined to strict 6deg head down tilt bed rest for 21 days. Beginning 24 hrs into this period, treatment subjects received one hour daily exposures to artificial gravity which was produced by spinning the subjects on a 3.0 m radius SRC. They were oriented radially in the supine position so that the centrifugal force was aligned with their long body axis, and while spinning, they "stood" on a force plate, supporting the centrifugal loading (2.5 g at the feet, 1.0 g at the heart). The subject station allowed free translation over approximately 10 cm to ensure full loading of the lower extremities and to allow for anti-orthostatic muscle contractions. Control subjects were positioned on the centrifuge but did not spin. Following the bed rest phase, subjects were allowed to ambulate again, but remained within the facility for an additional 9 days and participated in multiple follow-up tests of physiological function.

Warren, L. E.↗