Search NASA⌕ Search

SEARCH · Search NASA

Results for “dose response model”

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.

At least 19 records

Modeling Measurement Error in Dose-Response Models of Community Annoyance to Low-Noise Supersonic Flight

The primary research goal of the forthcoming NASA Quesst mission community test campaign is to collect representative community response data in support of the development of supersonic overflight noise certification standards. Beginning in 2026, NASA will fly the novel X-59 demonstrator aircraft over select communities in United States in order to demonstrate the possibility of low-noise supersonic flight over land and to collect objective measurements and subjective data on the perceptual experience of this new noise source. It is believed that a regression of a binary perceptual response (‘highly annoyed’ or ‘not’) on estimated noise levels (doses, measured in decibels) will provide a useful dose-response relationship for regulators. However, as these estimated doses will be subject to measurement error, naïve estimators of regression coefficients are inconsistent and slopes may be subject to attenuation bias. In this presentation, I contrast functional modeling of measurement error via simulation extrapolation (SIMEX) with structural Bayesian measurement error models. These methods are applied to available data collected during two NASA risk reduction studies in California in 2011 and Texas in 2018. I’ll conclude noting that in the presence of nonnegligible measurement errors, probabilities of annoyance may be overpredicted for low noise levels and underpredicted for high noise levels, therefore, methods of correcting for measurement error will be necessary to improve the utility of the dose-response relationship for policy-making purposes.

simulation↗

Dose Error Correction Using Simulation Extrapolation for Community Noise Dose-Response Modeling

The objective of this work is to provide a framework to account and correct for dose error in dose-response modeling due to measurement uncertainty. Error in noise measurements, especially in the case of limited monitoring locations in a community, can lead to an attenuation or misestimation of parameters in dose-response models. This error can result in overpredicted annoyance at lower doses and underpredicted annoyance at higher doses. Simulated data in the present work are based on previous NASA community studies and incorporate a notional design for future studies with the X-59 aircraft. Several populations of different annoyance response sensitivities are included. Simulation extrapolation (SIMEX, Cook and Stefanski 1994) is used to correct for the dose error in a simple, fully pooled logistic regression. Results indicate the negative impact of attenuation is greatly diminished for all amounts of dose error considered, regardless of a population’s annoyance sensitivity. Therefore, SIMEX can help produce a more accurate dose-response relationship.

SIMEX↗

The effect of modeling dose uncertainty on low-boom community noise dose-response curves

In logistic dose-response modeling, failing to account for uncertainty in estimated doses can cause an artificial flattening or attenuation of the slope of the summary curve. In Lee et al. [J. Acoust. Soc. Am. 147(4), pp. 2222-2234 (2020)], data from two NASA low-amplitude sonic boom community noise survey tests were modeled using a Bayesian multilevel logistic regression (MLR) statistical model that assumed there was no uncertainty in the noise dose estimates. However, in these community tests, the noise dose uncertainty was estimated by Page et al. [NASA/CR-2014-218180 and NASA/CR-2020-220589/Volume I] using a leave-one-out method. In the current work, a term was added to extend the Bayesian MLR model to account for the estimated noise dose uncertainty quantified in the Page et al. analyses. This uncertainty term was included in two ways, either as classical or as Berkson uncertainty, and yield similar results. When the uncertainty is accounted for in the Bayesian MLR model, the dose-response curves become 5-10% steeper, but the difference in the noise dose that elicits a 5% highly annoyed response is small (less than 1 dB). This result is encouraging for future X-59 community tests whose survey area will be sparsely populated with noise monitors.

X-59↗

Simulation and Application of Bayesian Dose Uncertainty Modeling for Low-Boom Community Noise Surveys

In dose-response modeling, failing to account for dose uncertainty can cause artificial flattening of the estimated slope of the dose-response curve. Previous analyses of NASA sonic boom community noise survey data utilized a Bayesian multilevel logistic regression model, which did not account for dose uncertainty. The current work extends the model to account for either classical or Berkson dose uncertainty. The extended model is applied to two simulated dose-response datasets to illustrate conditions under which the dose uncertainty term does and does not correct for the artificial flattening introduced by dose uncertainty. Finally, the extended model is applied to two previous NASA sonic boom community noise surveys. The resulting dose-response curve slope for the average participant is 5 to 10% steeper, but the difference in the noise dose that elicits a 5% highly annoyed response is small (less than 1 dB). The difference remains insignificant when producing population summary dose-response curves. Commentary is included on applicability to future X-59 low-boom community noise survey data modeling and analysis.

X-59↗

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

Hada, Megumi↗

Multilevel Logistic Regression with Random Slope for Community Annoyance Survey Data

This paper documents recent dose-response modeling work at NASA in anticipation of follow-on work by a contactor. Specifically, this paper compares the results of a Bayesian MLR model with a fixed slope to one with a random slope using WSPR and QSF18 data. Previously reported dose-response modeling efforts of WSPR and QSF18 data have used a MLR model with a fixed slope term. A random slope may more accurately depict the dose-response relationship of individuals in the efforts to produce a population summary dose-response curve. Results of a fixed versus random slope model with WSPR and QSF18 data indicate minimal difference between the modeling methods. The simpler fixed slope model is preferable for these data, but these results do not preclude consideration of a random slope term in modeling efforts of future X-59 community test data.

dose-response↗

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data set and with different background tumor incidences. We considered different experimental designs with varying number of doses and varying low doses dependant on the LET of the radiation. The optimal design to detect a NTE for an individual ion had 4 doses equally spaced below a maximal dose where bending due to cell sterilization was < 2%. For example at 100 keV/micron we would irradiate at 0.03 Gy, 0.065 Gy, 0.13 Gy, and 0.26 Gy and require 850 mice including a control dose for a sensitivity to detect NTE with 80% power. Sample sizes could be improved by combining ions similar to the methods used with the Harderian Gland data.

Chappelli, Lori J.↗

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.↗

The Importance of Internal Climate Variability in Climate Impact Projections

Uncertainty in climate projections is driven by three components: scenario uncertainty, intermodel uncertainty, and internal variability. Although socioeconomic climate impact studies increasingly take into account the first two components, little attention has been paid to the role of internal variability, although underestimating this uncertainty may lead to underestimating the socioeconomic costs of climate change. Using large ensembles from seven coupled general circulation models with a total of 414 model runs, we partition the climate uncertainty in classic dose–response models relating county-level corn yield, mortality, and per-capita gross domestic product to temperature in the continental United States. The partitioning of uncertainty depends on the time frame of projection, the impact model, and the geographic region. Internal variability represents more than 50% of the total climate uncertainty in certain projections, including mortality projections for the early 21st century, although its relative influence decreases over time. We recommend including uncertainty due to internal variability for many projections of temperature-driven impacts, including early-century and midcentury projections, projections in regions with high internal variability such as the Upper Midwest United States, and impacts driven by nonlinear relationships.

climate impacts↗

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies.

Chappell, Lori J.↗

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↗

Dose-Response Data Considerations for the NASA Quesst Community Test Campaign

Key outcomes for NASA's Quesst mission are noise dose and perceptual response data to inform regulators on their decisions regarding noise certification standards for the future of overland commercial supersonic flight. Dose-response curves are commonly utilized in community noise studies to describe the annoyance of a community to a particular noise source. The X-59 aircraft utilizes shaped-boom technology to demonstrate low noise supersonic flight. For X-59 community studies, the sound level from X-59 overflights constitutes the dose, while the response is an annoyance rating selected from a verbal scale, e.g., “slightly annoyed” and “very annoyed.” Dose-response data will be collected from individual flyovers (single event dose) and an overall response to the accumulation of single events at the end of the day (cumulative dose). There are quantifiable sources of error in the noise dose due to uncertainty in microphone measurements of the sonic thumps and uncertainty in predicted noise levels at survey participant locations. Assessing and accounting for error in the noise dose is essential to obtain an accurate dose-response model. There is also a potential for error in the perceptual response. This error is due to the ability of participants to provide their response in a timely manner and participant fatigue after responding to up to one hundred surveys over the course of a month. This talk outlines various challenges in estimating noise dose and perceptual response and the methods considered in preparation for X-59 community tests.

dose-response↗

Comparison of Two Statistical Models for Low Boom Dose-response Relationships with Correlated Responses

This study compares two statistical models to construct summary dose-response curves for low boom community noise surveys. Data from two NASA field surveys are used that consist of multiple responses per survey participant. These data require an approach that accounts for the correlation among repeated annoyance observations from the same participant. A multilevel model accounts for the correlation by allowing estimated parameters to vary with each survey participant. On the other hand, a population average model utilizes generalized estimating equations and accounts for the correlation via a userspecified within-subject correlation structure. A visual comparison of the dose-response curves for these two methods reveals similar results. When comparing specific points along the summary curves, the multilevel model yields more precise confidence bounds than the population average model. The similarity between the summary curves derived from each model lends validity to both approaches for approximating a population representative summary curve, though modeling assumptions may lend favor to the multilevel logistic modeling approach over the population average model.

dose-response↗

Comparing Two Statistical Models for Low Boom Dose-response Relationships with Correlated Responses

This study compares two statistical modeling approaches to construct summary dose-response curves for low boom community noise surveys. NASA field survey data were used that consist of multiple responses from a survey participant. These data require an approach that accounts for the correlation among repeated annoyance observations from the same participant. A multilevel model accounts for the correlation by allowing estimated parameters to vary with each survey participant. On the other hand, a population average model utilizes generalized estimating equations and accounts for the correlation via a user-specified within-subject correlation structure. A visual comparison of the dose-response curves for these two methods reveals similar results. When comparing specific points along the summary curves, the multilevel model yields more precise confidence bounds than the population average model. The similarity between the summary curves derived from each model lends validity to both approaches for approximating a population representative summary curve.

X-59↗

Effects of Dose Error and Sample Size on Sonic Boom Dose-response Curves

NASA will soon be collecting noise-annoyance community survey data as the X-59 aircraft flies supersonically over several communities in the USA. Sparse measurements of the X-59 sonic thumps will be used together with physics-based simulations to estimate noise doses at survey participant locations. These dose estimates have associated error that affects the accuracy of modeled dose-response curves, which can result in misestimation of annoyance. The precision in dose-response curves is also a consideration in selecting the number of survey participants. To enable pretest studies of dose error and precision, simulated dose-response data were generated based on NASA’s Quiet Supersonic Flights 2018 test. The data included various degrees of dose error and sample size. Frequentist multilevel logistic regression models were fit to the true and perturbed dose-response data. Simple proportional relationships were identified between the model parameters and the perturbation standard deviation. The summary dose-response curves illustrate the impact on accuracy if dose error is not accounted for in the model. The precision in the dose-response curves is also shown as the number of participants and degree of participation is varied. Finally, sampling variability is illustrated by showing the dose-response curves for several replicates with random draws of participants and errors.

X-59↗

Effects of Dose Error and Sample Size on Sonic Boom Dose-Response Curves

NASA will soon be collecting noise-annoyance community survey data as the X-59 aircraft flies supersonically over several communities in the USA. Sparse measurements of the X-59 sonic thumps will be used together with physics-based simulations to estimate noise doses at survey participant locations. These dose estimates have associated error that affects the accuracy of modeled dose-response curves, which can result in misestimation of annoyance. The precision in dose-response curves is also a consideration in selecting the number of survey participants. To enable pretest studies of dose error and precision, simulated dose-response data were generated based on NASA’s Quiet Supersonic Flights 2018 test. The data included various degrees of dose error and sample size. Frequentist multilevel logistic regression models were fit to the true and perturbed dose-response data. Simple proportional relationships were identified between the model parameters and the perturbation standard deviation. The summary dose-response curves illustrate the impact on accuracy if dose error is not accounted for in the model. The precision in the dose-response curves is also shown as the number of participants and degree of participation is varied. Finally, sampling variability is illustrated by showing the dose-response curves for several replicates with random draws of participants and errors.

X-59↗

Dose Error Impacts on A Collection of Realistic Dose-Response Curves Based on A NASA Sonic Boom Community Noise Survey

The National Aeronautics and Space Administration (NASA) plans to conduct surveys of community response to quiet supersonic flight to collect dose-response data for international regulators. Previous models of noise dose versus annoyance response ignored uncertainty in the noise dose experienced by survey respondents. This dose error causes attenuation bias and results in inaccurate dose-response relationships. The impacts of dose errors can be explored by introducing error into the dose estimates of a simulated community noise survey. The simulated population annoyance response is determined by specific noise response characteristics, including the onset of annoyance intercept, rate of increasing annoyance, participant intercept variability, and response rates. This paper explores the effects of dose errors on notional populations created by perturbing the noise response characteristics observed in participants in a recent NASA flight test, QSF18. The QSF18-based population parameters were shifted up to ±20% to create the study populations. For the anticipated dose range of the X-59, changes to the onset of annoyance intercept have the greatest impact on erroneous model results. Quantifying point estimate errors illustrates the impact of dose error, with errors up to 14 dB observed for a fixed high annoyance percentage.

dose-response modeling↗