DS02R1: Improvements to Atomic Bomb Survivors’ Input Data and Implementation of Dosimetry System 2002 (DS02) and Resulting Changes in Estimated Doses
Not provided.
Environmental Sciences & Ecology↗
SEARCH · Engineering Papers
Results for “atomic bomb survivor data”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Multiple indicators, multiple causes measurement error models
Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this study are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methods for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. Finally, as a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure.
97 MATHEMATICS AND COMPUTING↗
Quantifying radiation quality for space relevant radiation types: Fitting excess risk models to outbred mice data
Accurately quantifying the differences in radiation quality between space and terrestrial environments is important for predicting health risks for astronauts.Recently, Edmundson et al. 2020[1] provided valuable new results from out-bred mice linking tumor induction and genetic background a er exposure to low and high-LET radiation. The goal of the current study is to more rigorously estimate a relative biological effectiveness (RBE) factor by leveraging the solid tumor data from Edmundson et al. 2020. Excess relative risk (ERR) models and excess absolute risk (EAR) models were fit using Poisson regression similar to the models that the Radiation Effects Research Foundation uses to fit atomic bomb survivor data. Linear ERR and EAR slopes were simulated usingBayesian analyses, and RBE values were calculated from the ratio of the heavy ion linear slope to the gamma linear slope using the full posterior distribution.
Lori J. Chappell↗
Monte Carlo mixture model of lifetime cancer incidence risk from radiation exposure on shuttle and international space station
Estimating uncertainty in lifetime cancer risk for human exposure to space radiation is a unique challenge. Conventional risk assessment with low-linear-energy-transfer (LET)-based risk from Japanese atomic bomb survivor studies may be inappropriate for relativistic protons and nuclei in space due to track structure effects. This paper develops a Monte Carlo mixture model (MCMM) for transferring additive, National Institutes of Health multiplicative, and multiplicative excess cancer incidence risks based on Japanese atomic bomb survivor data to determine excess incidence risk for various US astronaut exposure profiles. The MCMM serves as an anchor point for future risk projection methods involving biophysical models of DNA damage from space radiation. Lifetime incidence risks of radiation-induced cancer for the MCMM based on low-LET Japanese data for nonleukemia (all cancers except leukemia) were 2.77 (90% confidence limit, 0.75-11.34) for males exposed to 1 Sv at age 45 and 2.20 (90% confidence limit, 0.59-10.12) for males exposed at age 55. For females, mixture model risks for nonleukemia exposed separately to 1 Sv at ages of 45 and 55 were 2.98 (90% confidence limit, 0.90-11.70) and 2.44 (90% confidence limit, 0.70-10.30), respectively. Risks for high-LET 200 MeV protons (LET=0.45 keV/micrometer), 1 MeV alpha-particles (LET=100 keV/micrometer), and 600 MeV iron particles (LET=180 keV/micrometer) were scored on a per particle basis by determining the particle fluence required for an average of one particle per cell nucleus of area 100 micrometer(2). Lifetime risk per proton was 2.68x10(-2)% (90% confidence limit, 0.79x10(-3)%-0. 514x10(-2)%). For alpha-particles, lifetime risk was 14.2% (90% confidence limit, 2.5%-31.2%). Conversely, lifetime risk per iron particle was 23.7% (90% confidence limit, 4.5%-53.0%). Uncertainty in the DDREF for high-LET particles may be less than that for low-LET radiation because typically there is very little dose-rate dependence. Probability density functions for high-LET radiation quality and dose-rate may be preferable to conventional risk assessment approaches. Nuclear reactions and track structure effects in tissue may not be properly estimated by existing data using in vitro models for estimating RBEs. The method used here is being extended to estimate uncertainty in spacecraft shielding effectiveness in various space radiation environments.
NASA Center LaRC↗
Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease
Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson's disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it ignores the effects of any adaptive response of the body to the LDR. The importance of considering adaptive response becomes obvious when one considers the sharp contrast between (i) the failure of well-designed anti-angiogenesis therapies which resulted in aggressive tumors because of ignoring adaptive response and (ii) the occasional cure of untreated metastatic lesions likely due to the incidental adaptive response from the LDR exposure to parts of the body during radiation therapy of a primary tumor, known as the abscopal effect. Another shortcoming of the LNT model is that it pays exclusive attention to increase in mutations, which is not a decisive factor in the occurrence of clinical cancers, as the cause of excess cancers. On the other hand, LNT model ignores the immune system response, which plays a very important role in preventing occult cancers from becoming clinical cancers, as demonstrated by the large increase in cancers in organ transplant patients whose immune system is suppressed. There is also recent epidemiological evidence against the LNT model. A re-analysis of the latest update to the atomic bomb survivor data has shown that the data no longer support the LNT model but are consistent with the radiation hormesis hypothesis. A re-analysis of cancer incidence data of Taiwanese apartment dwellers that were exposed to LDR from contaminated building materials has also shown a reduction in cancers from the LDR. The present LDR carcinogenic concerns would preclude any human study of cancer prevention using LDR, since the study would require subjecting a large asymptomatic population to LDR. However, pilot studies of radiation hormesis in cancer patients may be more acceptable since these would require irradiation of limited numbers of patients in order to assess the effectiveness of the LDR treatments. Some of the LDR applications that may be considered for cancer patients are: LDR treatment of early stage cancers without the adverse side effects of current treatments such as radiation therapy or chemotherapy, adjuvant LDR treatment of cancer patients undergoing radiation therapy for better tumor control and reduced metastasis, and the use of LDR treatment following radiation therapy to reduce the risk of second cancers from the radiation therapy. Studies of LDR for the control of early-stage neurodegenerative diseases may also be more acceptable since currently there are no effective treatments available for controlling these diseases, and since such studies would require LDR exposure to limited parts of the brain, and the carcinogenic risk from such treatments would be very small due to the low radiation tissue-weighting factor for the brain. Success in these studies can lead to the study of LDR for preventing and controlling other aging-related diseases.
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950–2003
The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose–response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing different models to allow risk estimates to be based on several plausible dose–response models rather than just relying on a single model of choice. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose–response curve from MMI is located below the linear no-threshold model at low and medium doses (0–1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose–response was also found for heart diseases (0–3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose–response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general.
60 APPLIED LIFE SCIENCES↗
An Overview of NASA's Risk of Cardiovascular Disease from Radiation Exposure
The association between high doses of radiation exposure and cardiovascular damage is well established. Patients that have undergone radiotherapy for primary cancers of the head and neck and mediastinal regions have shown increased risk of heart and vascular damage and long-term development of radiation-induced heart disease [1]. In addition, recent meta-analyses of epidemiological data from atomic bomb survivors and nuclear industry workers has also shown that acute and chronic radiation exposures is strongly correlated with an increased risk of circulatory disease at doses above 0.5 Sv [2]. However, these analyses are confounded for lower doses by lifestyle factors, such as drinking, smoking, and obesity. The types of radiation found in the space environment are significantly more damaging than those found on Earth and include galactic cosmic radiation (GCR), solar particle events (SPEs), and trapped protons and electrons. In addition to the low-LET data, only a few studies have examined the effects of heavy ion radiation on atherosclerosis, and at lower, space-relevant doses, the association between exposure and cardiovascular pathology is more varied and unclear. Understanding the qualitative differences in biological responses produced by GCR compared to Earth-based radiation is a major focus of space radiation research and is imperative for accurate risk assessment for long duration space missions. Other knowledge gaps for the risk of radiation-induced cardiovascular disease include the existence of a dose threshold, low dose rate effects, and potential synergies with other spaceflight stressors. The Space Radiation Program Element within NASA's Human Research Program (HRP) is managing the research and risk mitigation strategies for these knowledge gaps. In this presentation, we will review the evidence and present an overview of the HRP Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure.
Patel, Zarana S.↗
The increase in animal mortality risk following exposure to sparsely ionizing radiation is not linear quadratic with dose
The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREF LSS ). As a result, it was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and a limited number of animal studies.
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture
Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would otherwise die or be rendered reproductively inactive in 2-D culture.
Patel, Z. S.↗
Concepts of association between cancer and ionising radiation: accounting for specific biological mechanisms
The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from breast cancer data from the atomic bomb survivors of Hiroshima and Nagasaki. For exposure at age 30, all three models resulted in similar estimates of AS at age 60. For the initiation model, estimates of association were nearly identical to AS. However, for the promotion models, the cancerous clonal development was frequently accelerated towards younger ages, resulting in associations substantially higher than AS. This work shows that the association between a given cancer and exposure in an affected person depends on the underlying biological mechanism and can be substantially larger than the AS derived from classic radioepidemiology.
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts
Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin’s disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.
60 APPLIED LIFE SCIENCES↗
Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses 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 survivors 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 (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. 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 greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.
Hada, M.↗
Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses 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 (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. 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 curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.
Hada, Megumi↗
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.↗
Mortality of atomic bomb survivors predicted from laboratory animals
Exposure, pathology and mortality data for mice, dogs and humans were examined to determine whether accurate interspecies predictions of radiation-induced mortality could be achieved. The analyses revealed that (1) days of life lost per unit dose can be estimated for a species even without information on radiation effects in that species, and (2) accurate predictions of age-specific radiation-induced mortality in beagles and the atomic bomb survivors can be obtained from a dose-response model for comparably exposed mice. These findings illustrate the value of comparative mortality analyses and the relevance of animal data to the study of human health effects.
NASA Discipline Radiation Health↗
Congenital Malformations and Perinatal Deaths Among the Children of Atomic Bomb Survivors: A Reappraisal
From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes among births to atomic bomb survivors (Hiroshima and Nagasaki, Japan) who had received radiation doses ranging from 0 Gy to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes, such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We reexamined the risk of major congenital malformations and perinatal deaths in the children of atomic bomb survivors (n = 71,603) using fully reconstructed data to minimize the potential for bias, using refined estimates of the gonadal dose from Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships. The analyses showed that parental exposure to radiation was associated with increased risk of major congenital malformations and perinatal death, but the estimates were imprecise for direct radiation effects, and most were not statistically significant. Nonetheless, the uniformly positive estimates for untoward pregnancy outcomes among children of both maternal and paternal survivors are useful for risk assessment purposes, although extending them to populations other than the atomic bomb survivors comes with uncertainty as to generalizability.
60 APPLIED LIFE SCIENCES↗