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Feiveson, Alan

Publications and source records attributed to Feiveson, Alan.

18 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2020

Gene and MicroRNA Expression Profile Changes in ISS Crewmembers’ Blood Samples

In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmember immunobiology before, during, and after spaceflight. It emphasizes the study of DNA damage in the ISS crewmembers’ peripheral blood mononuclear cells (PBMCs), expression patterns of damage-response and inflammatory process genes, and changes in latent virus reactivation biomarkers.

Moreno-Villanueva, Maria↗
NASA NTRS2017

A Network-Based Algorithm for Clustering Multivariate Repeated Measures Data

The National Aeronautics and Space Administration (NASA) Astronaut Corps is a unique occupational cohort for which vast amounts of measures data have been collected repeatedly in research or operational studies pre-, in-, and post-flight, as well as during multiple clinical care visits. In exploratory analyses aimed at generating hypotheses regarding physiological changes associated with spaceflight exposure, such as impaired vision, it is of interest to identify anomalies and trends across these expansive datasets. Multivariate clustering algorithms for repeated measures data may help parse the data to identify homogeneous groups of astronauts that have higher risks for a particular physiological change. However, available clustering methods may not be able to accommodate the complex data structures found in NASA data, since the methods often rely on strict model assumptions, require equally-spaced and balanced assessment times, cannot accommodate missing data or differing time scales across variables, and cannot process continuous and discrete data simultaneously. To fill this gap, we propose a network-based, multivariate clustering algorithm for repeated measures data that can be tailored to fit various research settings. Using simulated data, we demonstrate how our method can be used to identify patterns in complex data structures found in practice.

Koslovsky, Matthew↗
NASA NTRS2017

Detection of DNA Damage by Space Radiation in Human Fibroblasts Flown on the International Space Station

Although charged particles in space have been detected with radiation detectors on board spacecraft since the discovery of the Van Allen Belts, reports on the effects of direct exposure to space radiation in biological systems have been limited. Measurement of biological effects of space radiation is challenging due to the low dose and low dose rate nature of the radiation environment, and due to the difficulty in distinguishing the radiation effects from microgravity and other space environmental factors. In astronauts, only a few changes, such as increased chromosome aberrations in their lymphocytes and early onset of cataracts, are attributed primarily to their exposure to space radiation. In this study, cultured human fibroblasts were flown on the International Space Station (ISS). Cells were kept at 37 degrees Centigrade in space for 14 days before being fixed for analysis of DNA damages with the gamma-H2AX assay. The 3-dimensional gamma-H2AX foci were captured with a laser confocal microscope. Quantitative analysis revealed several foci that were larger and displayed a track pattern only in the Day 14 flight samples. To confirm that the foci data from the flight study was actually induced from space radiation exposure, cultured human fibroblasts were exposed to low dose rate gamma rays at 37 degrees Centigrade. Cells exposed to chronic gamma rays showed similar foci size distribution in comparison to the non-exposed controls. The cells were also exposed to low- and high-LET (Linear Energy Transfer) protons, and high-LET Fe ions on the ground. Our results suggest that in G1 human fibroblasts under the normal culture condition, only a small fraction of large size foci can be attributed to high-LET radiation in space.

Lu, Tao↗
NASA NTRS2017

Detection of DNA Damage by Space Radiation in Human Fibroblasts Flown on the International Space Station

Space radiation consists of energetic charged particles of varying charges and energies. Exposure of astronauts to space radiation on future long duration missions to Mars, or missions back to the Moon, is expected to result in deleterious consequences such as cancer and comprised central nervous system (CNS) functions. Space radiation can also cause mutation in microorganisms, and potentially influence the evolution of life in space. Measurement of the space radiation environment has been conducted since the very beginning of the space program. Compared to the quantification of the space radiation environment using physical detectors, reports on the direct measurement of biological consequences of space radiation exposure have been limited, due primarily to the low dose and low dose rate nature of the environment. Most of the biological assays fail to detect the radiation effects at acute doses that are lower than 5 centiSieverts. In a recent study, we flew cultured confluent human fibroblasts in mostly G1 phase of the cell cycle to the International Space Station (ISS). The cells were fixed in space after arriving on the ISS for 3 and 14 days, respectively. The fixed cells were later returned to the ground and subsequently stained with the gamma-H2AX (Histone family, member X) antibody that are commonly used as a marker for DNA damage, particularly DNA double strand breaks, induced by both low-and high-linear energy transfer radiation. In our present study, the gamma-H2AX (Histone family, member X) foci were captured with a laser confocal microscope. To confirm that some large track-like foci were from space radiation exposure, we also exposed, on the ground, the same type of cells to both low-and high-linear energy transfer protons, and high-linear energy transfer Fe ions. In addition, we exposed the cells to low dose rate gamma rays, in order to rule out the possibility that the large track-like foci can be induced by chronic low-linear energy transfer radiation.

Lu, Tao↗
NASA NTRS2016

Improving the Accuracy of Predicting Maximal Oxygen Consumption (VO2pk)

Maximal oxygen (VO2pk) is the maximum amount of oxygen that the body can use during intense exercise and is used for benchmarking endurance exercise capacity. The most accurate method to determineVO2pk requires continuous measurements of ventilation and gas exchange during an exercise test to maximal effort, which necessitates expensive equipment, a trained staff, and time to set-up the equipment. For astronauts, accurate VO2pk measures are important to assess mission critical task performance capabilities and to prescribe exercise intensities to optimize performance. Currently, astronauts perform submaximal exercise tests during flight to predict VO2pk; however, while submaximal VO2pk prediction equations provide reliable estimates of mean VO2pk for populations, they can be unacceptably inaccurate for a given individual. The error in current predictions and logistical limitations of measuring VO2pk, particularly during spaceflight, highlights the need for improved estimation methods.

Downs, Meghan E.↗
NASA NTRS2015

Transient Gene and miRNA Expression Profile Changes of Confluent Human Fibroblast Cells in Space

Microgravity or an altered gravity environment from the static 1 gravitational constant has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies conducted in space or using simulated microgravity on the ground have focused on the growth or differentiation of the cells. Whether non-dividing cultured cells will sense the presence of microgravity in space has not been specifically addressed. In an experiment conducted on the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 days for investigations of gene and miRNA (microRNA) expression profile changes in these cells. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. Results of the experiment showed that on Day 3, both the flown and ground cells were still proliferating slowly even though they were confluent, as measured by the expression of the protein Ki-67 positive cells, and the cells in space grew slightly faster. Gene and miRNA expression data indicated activation of NF(sub kappa)B (nuclear factor kappa-light-chain-enhancer of activated B cells) and other growth related pathways involving HGF and VEGF in the flown cells. On Day 14 when the cells were mostly non-dividing, the gene and miRNA expression profiles between the flight and ground samples were indistinguishable. Comparison of gene and miRNA expressions in the Day 3 samples in respect to Day 14 revealed that most of the changes observed on Day 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeleton changes by immunohistochemistry staining of the cells with antibodies for alpha-tubulin showed no difference between the flight and ground samples. Results of our study suggest that in true non-dividing human fibroblast cells, microgravity in space has little effect on the gene and miRNA expression. Gene and miRNA expression changes were observed in cells that were confluent, but still proliferating slowly. The faster growth in the flown cells was associated with the activation of NF(sub kappa)B pathways which triggers the expression of several growth factors and the suppression of the cell cycle checkpoint.

Zhang, Ye↗
NASA NTRS2015

A Comparison of Tandem Walk Performance Between Bed Rest Subjects and Astronauts

Astronauts experience a microgravity environment during spaceflight, which results in a central reinterpretation of both vestibular and body axial-loading information by the sensorimotor system. Subjects in bed rest studies lie at 6deg head-down in strict bed rest to simulate the fluid shift and gravity-unloading of the microgravity environment. However, bed rest subjects still sense gravity in the vestibular organs. Therefore, bed rest isolates the axial-unloading component, thus allowing for the direct study of its effects. The Tandem Walk is a standard sensorimotor test of dynamic postural stability. In a previous abstract, we compared performance on a Tandem Walk test between bed rest control subjects, and short- and long-duration astronauts both before and after flight/bed rest using a composite index of performance, called the Tandem Walk Parameter (TWP), that takes into account speed, accuracy, and balance control. This new study extends the previous data set to include bed rest subjects who performed exercise countermeasures. The purpose of this study was to compare performance during the Tandem Walk test between bed rest subjects (with and without exercise), short-duration (Space Shuttle) crewmembers, and long-duration International Space Station (ISS) crewmembers at various time points during their recovery from bed rest or spaceflight.

Miller, Chris↗
NASA NTRS2013

Modeling Longitudinal Data Containing Non-Normal Within Subject Errors

The mission of the National Aeronautics and Space Administration’s (NASA) human research program is to advance safe human spaceflight. This involves conducting experiments, collecting data, and analyzing data. The data are longitudinal and result from a relatively few number of subjects; typically 10 – 20. A longitudinal study refers to an investigation where participant outcomes and possibly treatments are collected at multiple follow-up times. Standard statistical designs such as mean regression with random effects and mixed–effects regression are inadequate for such data because the population is typically not approximately normally distributed. Hence, more advanced data analysis methods are necessary. This research focuses on four such methods for longitudinal data analysis: the recently proposed linear quantile mixed models (lqmm) by Geraci and Bottai (2013), quantile regression, multilevel mixed–effects linear regression, and robust regression. This research also provides computational algorithms for longitudinal data that scientists can directly use for human spaceflight and other longitudinal data applications, then presents statistical evidence that verifies which method is best for specific situations. This advances the study of longitudinal data in a broad range of applications including applications in the sciences, technology, engineering and mathematics fields.

Feiveson, Alan↗
NASA NTRS2011

Cardiac and Vascular Responses to Thigh Cuffs and Respiratory Maneuvers on Crewmembers of the International Space Station

The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, and a decrease in leg diameter. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and during preload reduction introduced with thigh occlusion cuffs used as a counter-measure device (Braslet cuffs) measured by cardiac and vascular ultrasound examinations. Methods: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 +/- 46.days after launch (mean +/- SD; 33 - 185). Twenty Seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs. Results: Non-physicians performed diagnostic-quality cardiac and vascular ultrasound examinations using remote guidance. Three of 27 combinations of maneuvers and Braslet or Braslet alone were identified as being significant changed when compared to baseline. Eleven of 81 differences between combinations of Mueller, Valsalva or baseline were significant and related to cardiac preload reduction or increase in lower extremity venous volume. Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an invaluable tool in determining the volume status of the cardiac patient at the 'microgravity bedside'.

Hamilton, Douglas↗
NASA NTRS2011

Development of Head Injury Assessment Reference Values Based on NASA Injury Modeling

NASA is developing a new capsule-based, crewed vehicle that will land in the ocean, and the space agency desires to reduce the risk of injury from impact during these landings. Because landing impact occurs for each flight and the crew might need to perform egress tasks, current injury assessment reference values (IARV) were deemed insufficient. Because NASCAR occupant restraint systems are more effective than the systems used to determine the current IARVs and are similar to NASA s proposed restraint system, an analysis of NASCAR impacts was performed to develop new IARVs that may be more relevant to NASA s context of vehicle landing operations. Head IARVs associated with race car impacts were investigated by completing a detailed analysis of all of the 2002-2008 NASCAR impact data. Specific inclusion and exclusion criteria were used to select 4071 impacts from the 4015 recorder files provided (each file could contain multiple impact events). Of the 4071 accepted impacts, 274 were selected for numerical simulation using a custom NASCAR restraint system and Humanetics Hybrid-III 50th percentile numerical dummy model in LS-DYNA. Injury had occurred in 32 of the 274 selected impacts, and 27 of those injuries involved the head. A majority of the head injuries were mild concussions with or without brief loss of consciousness. The 242 non-injury impacts were randomly selected and representative of the range of crash dynamics present in the total set of 4071 impacts. Head dynamics data (head translational acceleration, translational change in velocity, rotational acceleration, rotational velocity, HIC-15, HIC-36, and the Head 3ms clip) were filtered according to SAE J211 specifications and then transformed to a log scale. The probability of head injury was estimated using a separate logistic regression analysis for each log-transformed predictor candidate. Using the log transformation constrains the estimated probability of injury to become negligible as IARVs approach zero. For the parameters head translational acceleration, head translational velocity change, head rotational acceleration, HIC-15, and HIC-36, conservative values (in the lower 95% confidence interval) that gave rise to a 5% risk of any injury occurring were estimated as 40.0 G, 7.9 m/s, 2200 rad/s2, 98.4, and 77.4 respectively. Because NASA is interested in the consequence of any particular injury on the ability of the crew to perform egress tasks, the head injuries that occurred in the NASCAR dataset were classified according to a NASA-developed scale (Classes I - III) for operationally relevant injuries, which classifies injuries on the basis of their operational significance. Additional analysis of the data was performed to determine the probability of each injury class occurring, and this was estimated using an ordered probit model. For head translational acceleration, head translational velocity change, head rotational acceleration, head rotational velocity, HIC-36, and head 3ms clip, conservative values of IARVs that produced a 5% risk of Class II injury were estimated as 50.7 G, 9.5 m/s, 2863 rad/s2, 11.0 rad/s, 30.3, and 46.4 G respectively. The results indicate that head IARVs developed from the NASCAR dataset may be useful to protect crews during landing impact.

Somers, Jeffrey T.↗
NASA NTRS2011

Functional Data Analysis of Spaceflight-Induced Changes in Coordination and Phase in Head Pitch Acceleration During Treadmill Walking

Astronauts returning from spaceflight experience neurovestibular disturbances during head movements and attempt to mitigate them by limiting head motion. Analyses to date of the head movements made during walking have concentrated on amplitude and variability measures extracted from ensemble averages of individual gait cycles. Phase shifts within each gait cycle can be determined by functional data analysis through the computation of time-warping functions. Large, localized variations in the timing of peaks in head kinematics may indicate changes in coordination. The purpose of this study was to determine timing changes in head pitch acceleration of astronauts during treadmill walking before and after flight. Six astronauts (5M/1F; age = 43.5+/-6.4yr) participated in the study. Subjects walked at 1.8 m/sec (4 mph) on a motorized treadmill while reading optotypes displayed on a computer screen 4 m in front of their eyes. Three-dimensional motion of the subject s head was recorded with an Inertial Measurement Unit (IMU) device. Data were recorded twice before flight and four times after landing. The head pitch acceleration was calculated by taking the time derivative of the pitch velocity data from the IMU. Data for each session with each subject were time-normalized into gait cycles, then registered to align significant features and create a mean curve. The mean curves of each postflight session for each subject were re-registered based on their preflight mean curve to create time-warping functions. The root mean squares (RMS) of these warping functions were calculated to assess the deviation of head pitch acceleration mean curves in each postflight session from the preflight mean curve. After landing, most crewmembers exhibited localized shifts within their head pitch acceleration regimes, with the greatest deviations in RMS occurring on landing day or 1 day after landing. These results show that the alteration of head pitch coordination due to spaceflight may be assessed using an analysis of time-warping functions.

Miller, Christopher↗
NASA NTRS2010

Distribution of Chromosome Breakpoints in Human Epithelial Cells Exposed to Low- and High-LET Radiation

Low-and high-LET radiations produced distinct breakpoint distributions. The difference of the breakpoint distributions between low-and high-LET only appeared in break ends involved in interchromosome exchanges. The breakpoint distributions for break ends participating in intrachromosome exchanges were similar. Gene-rich regions do not necessarily have more chromosome breaks. High-LET appeared to produce long live (data not shown) or longer live breaks that can migrate a longer distance before rejoining with other breaks. Domains occupied by different segments of the chromosomes may be responsible for the breakpoint distribution. The dose responses for interchromosomal exchanges were linear in all four exposures. However, the dose response for intrachromosomal exchanges were none linear. Increasing dose of high dose rate exposure (Fe-ions or -rays) increase the fraction of cells with intrachromosome aberrations, whereas increasing dose of low dose rate exposure (neutrons or -rays) does not affect the fraction of cells with intrachromosome aberrations.

Hada, Megumi↗
NASA NTRS2010

Distributions of Low- and High-LET Radiation-Induced Breaks in Chromosomes are Associated with Inter- and Intrachromosome Exchanges

To study the breakpoint along the length of the chromosome induced by low- and high-LET radiations, we exposed human epithelial cells in vitro to Cs-137 rays at both low and high dose rates, secondary neutrons at a low dose rate, and 600 MeV/u Fe ions at a high dose rate. The location of the breaks was identified using the multicolor banding in situ hybridization (mBAND) that paints Chromosome 3 in 23 different colored bands. The breakpoint distributions were found to be similar between rays of low and high dose rates and between the two high-LET radiation types. Detailed analysis of the chromosome break ends involved in inter- and intrachromosome exchanges revealed that only the break ends participating in interchromosome exchanges contributed to the hot spots found for low-LET. For break ends participating in intrachromosome exchanges, the distributions for all four radiation scenarios were similar with clusters of breaks found in three regions. Analysis of the locations of the two break ends in Chromosome 3 that joined to form an intrachromosome exchange demonstrated that two breaks with a greater genomic separation may be more likely to rejoin than two closer breaks, indicating that chromatin folding can play an important role in the rejoining of chromosome breaks. Our study demonstrated that the gene-rich regions do not necessarily contain more breaks. The breakpoint distribution depends more on the likelihood that a break will join with another break in the same chromosome or in a different chromosome.

Hada, Megumi↗
NASA NTRS2010

On-Orbit Prospective Echocardiography on International Space Station Crew

Introduction A prospective trial of echocardiography was conducted on of six crewmembers onboard the International Space Station. The main objective was to determine the efficacy of remotely guided tele-echocardiography, including just-in-time e-training methods and determine what "space normal" echocardiographic data is. Methods Each crewmember operator (n=6) had 2-hour preflight training. Baseline echocardiographic data were collected 55 to 167days preflight. Similar equipment was used in each 60-minute in-flight session (mean microgravity exposure - 114 days (34 -- 190)). On Orbit ultrasound operators used an e-learning system within 24h of these sessions. Expert assistance was provided using ultrasound video downlink and two-way voice. Testing was repeated 5 to 16 days after landing. Separate ANOVA was used on each echocardiographic variable (n=33). Within each ANOVA, three tests were made: a) effect of mission phase (preflight, in-flight, post flight); b) effect of echo technician (two technicians independently analyzed the data); c) interaction between mission phase and technician. Results Nine rejections of the null hypothesis (mission phase or technician or both had no effect) were discovered and considered for follow up. Of these, six rejections were for significant technician effects, not as a result of space flight. Three rejections of the null hypothesis (Aortic Valve time velocity integral, Mitral E wave Velocity and heart rate) were attributable to space flight, however determined not to be clinically significant. No rejections were due to the interaction between technician and space flight. Conclusion No consistent clinically significant effects of long-duration space flight were seen in echocardiographic variables of the given group of subjects.

Hamilton, Douglas R.↗
NASA NTRS2009

Evaluation of Maximal Oxygen Uptake (V02max) and Submaximal Estimates of VO2max Before, During and After Long Duration ISS Missions

NASA's Human Research Program Integrated Research Plan (HRP-47065) serves as a road-map identifying critically needed information for future space flight operations (Lunar, Martian). VO2max (often termed aerobic capacity) reflects the maximum rate at which oxygen can be taken up and utilized by the body during exercise. Lack of in-flight and immediate postflight VO2max measurements was one area identified as a concern. The risk associated with not knowing this information is: Unnecessary Operational Limitations due to Inaccurate Assessment of Cardiovascular Performance (HRP-47065).

Moore, Alan↗
NASA NTRS2003

Focused Assessment with Sonography for Trauma in weightlessness: a feasibility study

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examines for fluid in gravitationally dependent regions. There is no prior experience with this technique in weightlessness, such as on the International Space Station, where sonography is currently the only diagnostic imaging tool. STUDY DESIGN: A ground-based (1 g) porcine model for sonography was developed. We examined both the feasibility and the comparative performance of the FAST examination in parabolic flight. Sonographic detection and fluid behavior were evaluated in four animals during alternating weightlessness (0 g) and hypergravity (1.8 g) periods. During flight, boluses of fluid were incrementally introduced into the peritoneal cavity. Standardized sonographic windows were recorded. Postflight, the video recordings were divided into 169 20-second segments for subsequent interpretation by 12 blinded ultrasonography experts. Reviewers first decided whether a video segment was of sufficient diagnostic quality to analyze (determinate). Determinate segments were then analyzed as containing or not containing fluid. A probit regression model compared the probability of a positive fluid diagnosis to actual fluid levels (0 to 500 mL) under both 0-g and 1.8-g conditions. RESULTS: The in-flight sonographers found real-time scanning and interpretation technically similar to that of terrestrial conditions, as long as restraint was maintained. On blinded review, 80% of the recorded ultrasound segments were considered determinate. The best sensitivity for diagnosis in 0 g was found to be from the subhepatic space, with probability of a positive fluid diagnosis ranging from 9% (no fluid) to 51% (500 mL fluid). CONCLUSIONS: The FAST examination is technically feasible in weightlessness, and merits operational consideration for clinical contingencies in space.

NASA Discipline Life Sciences Technologies↗
NASA NTRS2000

Precision of Four Acoustic Bone Measurement Devices

Though many studies have quantified the precision of various acoustic bone measurement devices, it is difficult to directly compare the results among the studies, because they used disparate subject pools, did not specify the estimation methodology, or did not use consistent definitions for various precision characteristics. In this study, we used a repeated measures design protocol to directly determine the precision characteristics of four acoustic bone measurement devices: the Mechanical Response Tissue Analyzer (MRTA), the UBA-575+, the SoundScan 2000 (S2000), and the Sahara Ultrasound Bone Analyzer. Ten men and ten women were scanned on all four devices by two different operators at five discrete time points: Week 1, Week 2, Week 3, Month 3 and Month 6. The percent coefficient of variation (%CV) and standardized coefficient of variation were computed for the following precision characteristics: interoperator effect, operator-subject interaction, short-term error variance, and long-term drift. The MRTA had high interoperator errors for its ulnar and tibial stiffness measures and a large long-term drift in its tibial stiffness measurement. The UBA-575+ exhibited large short-term error variances and long-term drift for all three of its measurements. The S2000's tibial speed of sound measurement showed a high short-term error variance and a significant operator-subject interaction but very good values (less than 1%) for the other precision characteristics. The Sahara seemed to have the best overall performance, but was hampered by a large %CV for short-term error variance in its broadband ultrasound attenuation measure.

Miller, Christopher↗