Engineering topics

Chappell, L.

Publications and source records attributed to Chappell, L..

6 records

NASA NTRS2017

Determination of the Risk of Radiation-Associated Circulatory and Cancer Disease Mortality in a NASA Early Astronaut Cohort

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to determine if there was sufficient evidence for excess risk of cardiovascular disease and cancer in early NASA astronaut cohorts. NASA astronauts in selection groups 1-7 were chosen; this relatively homogeneous cohort consists of 73 white males, who unlike today's astronauts, maintained similar smoking and drinking habits to the general US population, and have published radiation doses. The participants flew in space on missions Mercury through Shuttle and received space radiation doses between 0-74.1 milligrays. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health (LSAH) program at NASA Johnson Space Center. Mortality was compared with the US male population. Trends of mortality with dose were assessed using a logistic model, fitted by maximum likelihood. Only 32 (43.84 percent) of the 73 early astronauts have died. Standard mortality ratios (SMRs) for cancer (n=7, SMR=43.4, 95 percent CI 17.8, 84.9), all circulatory disease (n=7, SMR=33.2, 95 percent CI 13.7, 65.0), and ischemic heart disease (IHD) (n=5, SMR=40.1, 95 percent CI 13.2, 89.4) were significantly lower than for the US white male population. For cerebrovascular disease, the upper confidence interval for SMR included 100, indicating it was not significantly different from the US population (n=2, SMR = 77.0, 95 percent CI 9.4, 268.2). The power of the study is low and remains below 10 percent even when risks 10 times those reported in the literature are assumed. Due to small sample size, there is currently insufficient statistical power to evaluate space radiation exposure effects on mortality in NASA astronauts. In addition to a comprehensive longitudinal study of NASA astronauts, a research strategy of low dose epidemiology data integration with cell and animal studies should be utilized for space radiation risk assessment in the astronauts.

Elgart, S. R.↗

NASA NTRS2017

Getting to the Heart of Cardiovascular Risk Assessment in Astronauts for Exploration Class Missions

Since the beginning of manned spaceflight, NASA has recognized the potential risk of cardiovascular decrements due to stressors in the space environment. Of particular concern is the effect of space radiation on cardiovascular disease since astronauts will be exposed to higher levels of galactic cosmic rays outside the Earth's protective magnetosphere. To date, only a few studies have examined the effects of heavy ion radiation on cardiovascular disease, and at lower, space-relevant doses, the association between radiation exposure and cardiovascular pathology is more varied and unclear. Furthermore, other spaceflight conditions such as microgravity, circadian shifts, and confinement stress pose unique challenges in estimating the health risks that can be attributed to exposure to ionizing radiations. In this work, we review age, cause of mortality, and radiation exposure amongst early NASA astronauts in selection groups and discuss the limitations of assessing such a cohort when attempting to characterize the risk of space flight, including stressors such as space radiation and microgravity exposure, on cardiovascular health. METHODS: NASA astronauts in selection groups 1-7 were chosen and the comparison population was white men of the same birth cohort as drawn from data from the CDC Wonder Database and CDC National Center for Health Statistics Life Tables. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health program and deceased astronauts were classified based on ICD-10 codes: ischemic heart disease (IHD), stroke, cancer, acute occupational events, non-NASA accidents, and other/unknown. Expected years of life left and expected age at death were calculated for the cohort. RESULTS AND CONCLUSIONS: There were 32 deaths in this early astronaut population, 12 of which were due to accidents or acute occupational events that impacted lifespan considerably. The average age at death from these causes is 30 years lower than the average expected ~70 years of age in the general population. Remarkably, all 41 living early astronauts outlived our calculated expected age at death for members of their birth cohort; furthermore, 13 of the 20 deceased astronauts who did not die in NASA/non-NASA accidents exceeded this age. There was no difference in IHD between the astronaut cohort and the comparison population; therefore, it is not possible to associate IHD mortality with radiation in that astronaut cohort. As NASA looks toward future exploration-class missions, early astronaut cohorts provide a convenient option for assessing these risks and for developing mitigation strategies. However, many challenges still exist when assessing such limited evidence, including small cohort size, health and lifestyle confounders (such as smoking and drinking), the high accident mortality rate, and the fact that many of these astronauts are still alive, outliving many of their birth-cohort peers. Future analysis should include a longitudinal study, monitoring cases as they occur in the cohort. As this cohort is currently followed-up over time, and as more IHD cases are anticipated in a population of this age, this type of study is not as resource-intensive as would normally be the case.

Elgart, S. R.↗

NASA NTRS2013

Estimation of the Dose and Dose Rate Effectiveness Factor

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Chappell, L.↗

NASA NTRS2012

The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

George, K.↗

NASA NTRS2011

Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

George, K.↗

NASA NTRS2011

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

Hada, M.↗