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Feiveson, Alan H.

Publications and source records attributed to Feiveson, Alan H..

At least 19 records

Reliability of the Danish Aerospace Corporation Portable Pulmonary Function System

Metabolic gas analysis is a critical component of investigations that measure cardio-pulmonary exercise responses during and after long-duration spaceflight. The primary purpose of the current study was to determine the reliability and intra-subject repeatability of a metabolic gas analysis device, the Portable Pulmonary Function System (PPFS), designed for use on the International Space Station (ISS). The second objective of this study was to directly compare PPFS measurements of expired oxygen and carbon dioxide (FEO2 and FECO2) to values obtained from a well-validated clinical metabolic gas analysis system (ParvoMedics TrueOne (c) [PM]). Eight subjects performed four peak cycle tests to maximal exertion. The first test was used to prescribe work rates for the subsequent test sessions. Metabolic gas analysis for this test was performed by the PM, but samples of FEO2 and FECO2 also were simultaneously collected for analysis by the PPFS. Subjects then performed three additional peak cycle tests, consisting of three 5-min stages designed to elicit 25%, 50%, and 75% maximal oxygen consumption (VO2max) followed by stepwise increases of 25 W/min until subjects reached volitional exhaustion. Metabolic gas analysis was performed using the PPFS for these tests. Intraclass correlation coefficients (ICC), within-subject standard deviations (WS SD), and coefficients of variation (CV%) were calculated for the repeated exercise tests. Mixed model regression analysis was used to compare paired FEO2 and FECO2 values obtained from the PPFS and the PM during the initial test. The ICC values for oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilation (VE) indicate that the PPFS is highly reliable (0.79 to 0.99) for all exercise levels tested; however, ICCs for respiratory exchange ratio (RER) were low ( 0.11 - 0.51), indicating poor agreement between trials during submaximal and maximal exercise. Overall, CVs ranged from 1.6% to 6.7% for all measurements, a finding consistent with reported values that were obtained using other metabolic gas analysis techniques. The PPFS and PM produced comparable FEO2 data; however, there was less agreement between measures of FECO2 obtained from the two devices, particularly at lower CO2 concentrations. The PPFS appears, in practically all respects, to yield highly reliable metabolic gas analysis data. Lower reliability of RER measurements reported in the literature and likely is not a function of the PPFS device. Further examination of PPFS CO2 data is warranted to better understand the limitations of these PPFS measurements. Overall, the PPFS when used for repeated measures of cardio-pulmonary exercise should provide accurate and reliable data for studies of human adaptation to spaceflight.

Portable Pulmonary Function System (PPFS)

Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified.

Portable Pulmonary Function System (PPFS)

Using Concurrent Cardiovascular Information to Augment Survival Time Data for Evaluating Orthostatic Tilt Test Performance

Head-up tilt (HUT) tests often are used in research to measure orthostatic intolerance (OI) (inability to appropriately control blood pressure while upright) in clinical populations and otherwise healthy individuals after interventions. Post-space flight orthostatic intolerance is a well-known phenomenon, and countermeasures to its development has been an active area of research at NASA. In the NASA HUT protocol, subjects lie horizontally on an automatic tilt table for baseline measurements before being raised to 80deg head-up tilt for a defined period of time or until signs or symptoms of presyncope ensues (light-headedness, nausea, dizziness, sweating, weakness or fainting). Multiple measures are collected to evaluate the cardiovascular system's ability to respond appropriately to the orthostatic challenge. However if the intended duration of the HUT is short, the ability to detect changes in OI due to an intervention or its prevention by a countermeasure may be limited by a small number of failures to permit comparisons based on survival time alone. Thus, the time-trajectory of the cardiovascular data becomes an important additional source of information. In particular, we will show how various measures of trajectory variability can effectively augment survival analysis for the assessment of OI in a joint model when high censoring rates are present.

Feiveson, Alan H.

NASA'S Standard Measures During Bed Rest: Adaptations in the Cardiovascular System

Bed rest is a well-accepted analog of space flight that has been used extensively to investigate physiological adaptations in a larger number of subjects in a shorter amount of time than can be studied with space flight and without the confounding effects associated with normal mission operations. However, comparison across studies of different bed rest durations, between sexes, and between various countermeasure protocols have been hampered by dissimilarities in bed rest conditions, measurement protocols, and testing schedules. To address these concerns, NASA instituted standard bed rest conditions and standard measures for all physiological disciplines participating in studies conducted at the Flight Analogs Research Unit (FARU) at the University of Texas-Medical Branch. Investigators for individual studies employed their own targeted study protocols to address specific hypothesis-driven questions, but standard measures tests were conducted within these studies on a non-interference basis to maximize data availability while reducing the need to implement multiple bed rest studies to understand the effects of a specific countermeasure. When possible, bed rest standard measures protocols were similar to tests nominally used for medically-required measures or research protocols conducted before and after Space Shuttle and International Space Station missions. Specifically, bed rest standard measures for the cardiovascular system implemented before, during, and after bed rest at the FARU included plasma volume (carbon monoxide rebreathing), cardiac mass and function (2D, 3D and Doppler echocardiography), and orthostatic tolerance testing (15- or 30-minutes of 80 degree head-up tilt). Results to-date indicate that when countermeasures are not employed, plasma volume decreases and the incidence of presyncope during head-up tilt is more frequent even after short-duration bed rest while reductions in cardiac function and mass are progressive as bed rest duration increases. Additionally, while plasma volume loss can be corrected and cardiac mass can be prevented with properly applied countermeasures, orthostatic tolerance is more difficult to protect when supine exercise is the only countermeasure. Similar results have been observed after space flight. Plasma volume, cardiac chamber volume, and orthostatic tolerance recover relatively quickly with resumption of ambulation and normal activity levels after bed rest but restoration of cardiac mass is prolonged.

Lee, Stuart M. C.

Assessing the Effect of Spaceflight on the Propensity for Astronauts to Develop Disk Herniation

A previous study [1] reported the instantaneous risk of developing a Herniated Nucleus Pulosus (HNP) was higher in astronauts who had flown at least one mission, as compared with those in the corps who had not yet flown. However, the study only analyzed time to HNP after the first mission (if any) and did not account for the possible effects of multiple missions. While many HNP's occurred well into astronauts' careers or in some cases years after retirement, the higher incidence of HNPs relatively soon after completion of space missions appears to indicate that spaceflight may lead to an increased risk of HNP. The purpose of this study was to support the Human System Risk Boards assessment of back pain, assess the risk of injury due to dynamic loads, and update the dataset analyzed which contained data through December 31, 2006.

Feiveson, Alan H.

Using Concurrent Cardiovascular Information to Augment Survival Time Data from Orthostatic Tilt Tests

Orthostatic Intolerance (OI) is the propensity to develop symptoms of fainting during upright standing. OI is associated with changes in heart rate, blood pressure and other measures of cardiac function. Problem: NASA astronauts have shown increased susceptibility to OI on return from space missions. Current methods for counteracting OI in astronauts include fluid loading and the use of compression garments. Multivariate trajectory spread is greater as OI increases. Pairwise comparisons at the same time within subjects allows incorporation of pass/fail outcomes. Path length, convex hull area, and covariance matrix determinant do well as statistics to summarize this spread Missing data problems Time series analysis need many more time points per OTT session treatment of trend? how incorporate survival information?

Feiveson, Alan H.

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose‐dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

Yeshitla, Samrawit A.

Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

Zhang, Ye

Gene Expression Profiling of Lung Tissue of Rats Exposed to Lunar Dust Particles

The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust‐induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust‐induced toxicity to humans on earth.

Zhang, Ye

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Feiveson, Alan H.

Peak Oxygen Uptake during and after Long-duration Space Flight

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion.

Moore, Alan D., Jr.

Probabilistic Assessment of Hypobaric Decompression Sickness Treatment Success

The Hypobaric Decompression Sickness (DCS) Treatment Model links a decrease in computed bubble volume from increased pressure (DeltaP), increased oxygen (O2) partial pressure, and passage of time during treatment to the probability of symptom resolution [P(symptom resolution)]. The decrease in offending volume is realized in 2 stages: a) during compression via Boyle's Law and b) during subsequent dissolution of the gas phase via the O2 window. We established an empirical model for the P(symptom resolution) while accounting for multiple symptoms within subjects. The data consisted of 154 cases of hypobaric DCS symptoms along with ancillary information from tests on 56 men and 18 women. Our best estimated model is P(symptom resolution) = 1 / (1+exp(-(ln(Delta P) - 1.510 + 0.795×AMB - 0.00308×Ts) / 0.478)), where (DeltaP) is pressure difference (psid), AMB = 1 if ambulation took place during part of the altitude exposure, otherwise AMB = 0; and where Ts is the elapsed time in mins from start of the altitude exposure to recognition of a DCS symptom. To apply this model in future scenarios, values of DeltaP as inputs to the model would be calculated from the Tissue Bubble Dynamics Model based on the effective treatment pressure: (DeltaP) = P2 - P1 | = P1×V1/V2 - P1, where V1 is the computed volume of a spherical bubble in a unit volume of tissue at low pressure P1 and V2 is computed volume after a change to a higher pressure P2. If 100% ground level O2 (GLO) was breathed in place of air, then V2 continues to decrease through time at P2 at a faster rate. This calculated value of (DeltaP then represents the effective treatment pressure at any point in time. Simulation of a "pain-only" symptom at 203 min into an ambulatory extravehicular activity (EVA) at 4.3 psia on Mars resulted in a P(symptom resolution) of 0.49 (0.36 to 0.62 95% confidence intervals) on immediate return to 8.2 psia in the Multi-Mission Space Exploration Vehicle. The P(symptom resolution) increased to near certainty (0.99) after 2 hrs of GLO at 8.2 psia or with less certainty on immediate pressurization to 14.7 psia [0.90 (0.83 - 0.95)]. Given the low probability of DCS during EVA and the prompt treatment of a symptom with guidance from the model, it is likely that the symptom and gas phase will resolve with minimum resources and minimal impact on astronaut health, safety, and productivity.

Conkin, Johnny

NASCA Report 2: Longitudinal Study of Relationship of Exposure to Space Radiation and Risk of Lens Opacity

The NASA Study of Cataract in Astronauts (NASCA) was a five-year longitudinal study of the effect of space radiation exposure on the severity/progression of nuclear (N), cortical (C), and posterior subcapsular (PSC) lens opacities. It began in 2003 and was completed in December, 2009. Participants included 171 consenting astronauts who flew at least one mission in space, and comparison subjects consisted of three groups, a) 53 astronauts who had not flown in space, b) 95 military aircrew personnel, and c) 99 non-aircrew, ground-based subjects.

Chylack, Leon T., Jr.

Characterizing the Joint Effect of Diverse Test-Statistic Correlation Structures and Effect Size on False Discovery Rates in a Multiple-Comparison Study of Many Outcome Measures

In their 2009 Annals of Statistics paper, Gavrilov, Benjamini, and Sarkar report the results of a simulation assessing the robustness of their adaptive step-down procedure (GBS) for controlling the false discovery rate (FDR) when normally distributed test statistics are serially correlated. In this study we extend the investigation to the case of multiple comparisons involving correlated non-central t-statistics, in particular when several treatments or time periods are being compared to a control in a repeated-measures design with many dependent outcome measures. In addition, we consider several dependence structures other than serial correlation and illustrate how the FDR depends on the interaction between effect size and the type of correlation structure as indexed by Foerstner s distance metric from an identity. The relationship between the correlation matrix R of the original dependent variables and R~, the correlation matrix of associated t-statistics is also studied. In general R~ depends not only on R, but also on sample size and the signed effect sizes for the multiple comparisons.

Feiveson, Alan H.

FDR doesn't Tell the Whole Story: Joint Influence of Effect Size and Covariance Structure on the Distribution of the False Discovery Proportions

As part of a 2009 Annals of Statistics paper, Gavrilov, Benjamini, and Sarkar report results of simulations that estimated the false discovery rate (FDR) for equally correlated test statistics using a well-known multiple-test procedure. In our study we estimate the distribution of the false discovery proportion (FDP) for the same procedure under a variety of correlation structures among multiple dependent variables in a MANOVA context. Specifically, we study the mean (the FDR), skewness, kurtosis, and percentiles of the FDP distribution in the case of multiple comparisons that give rise to correlated non-central t-statistics when results at several time periods are being compared to baseline. Even if the FDR achieves its nominal value, other aspects of the distribution of the FDP depend on the interaction between signed effect sizes and correlations among variables, proportion of true nulls, and number of dependent variables. We show examples where the mean FDP (the FDR) is 10% as designed, yet there is a surprising probability of having 30% or more false discoveries. Thus, in a real experiment, the proportion of false discoveries could be quite different from the stipulated FDR.

Feiveson, Alan H.

Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the same rate as Shuttle astronauts (p=0.007). Conclusions: The proportion of ISS astronauts who could not complete the tilt test on R+0 due to OH (4 of 6) is similar to that reported in astronauts who flew on Mir (5 of 6). Further, cardiovascular parameters most closely associated with OH recover more slowly after long- compared to short-duration spaceflight.

Lee, Stuart M. C.

Oxygen Uptake Responses to Submaximal Exercise Loads Do Not Change During Long-Duration Space Flight

In previous publications we have reported that the heart rate (HR) responses to graded submaximal exercise tests are elevated during long-duration International Space Station (ISS) flights. Furthermore, the elevation in HR appears greater earlier, rather than later, during the missions. A potential confounder in the interpretation of HR results from graded exercise tests on ISS is that the cycle ergometer used (CEVIS) is vibration-isolated from the station structure. This feature causes the CEVIS assembly to sway slightly during its use and debriefing comments by some crewmembers indicate that there is a "learning curve" associated with CEVIS use. Therefore, one could not exclude the possibility that the elevated HRs experienced in the early stages of ISS missions were related to a lowered metabolic efficiency of CEVIS exercise that would raise the submaximal oxygen uptake (VO2) associated with graded exercise testing work rates.

Moore, Alan D., Jr.