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At least 343 records · Page 19

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.↗

Preconceptual Design of Irradiated Fuel Salt Management System

The National Reactor Innovation Center was established by the U.S. Department of Energy to accelerate the demonstration and deployment of advanced nuclear reactors. To meet this mission, the National Reactor Innovation Center has developed the Laboratory for Operations and Testing in the U.S. (LOTUS) to support the first fast-spectrum molten salt reactor demonstration. The goal of this research is to understand the system requirements that may be applied to a molten salt reactor experiment in the LOTUS test bed and to perform systems analyses and preconceptual development of a storage container for the management of the irradiated molten salt fuel. This study proposes a set of irradiated fuel salt management processes for the molten salt reactor, from defueling to storage or disposal. For that, the historic Molten Salt Reactor Experiment (MSRE) at Oak Ridge National Laboratory has served as a crucial source of data for a mock application. This paper proposes a potential geometry for storing irradiated fuel salt based on MSRE data and the Monte Carlo N-Particle radiation transport code. The geometry was analyzed for criticality safety under abnormal situations, such as water ingress and interaction between containers. Based on the determined configuration of the storage system, the decay heat produced from the irradiated fuel salts was calculated to provide a reasonable time scale of the dormancy period. Using the same geometry assumed above, the neutron and gamma dose rates from the irradiated fuel salt at the end of the dormancy period were estimated, which will be useful for understanding the handling and radiation protection requirements for handling the irradiated fuel salt. Lastly, a reactor in the LOTUS test bed could use chloride-based fuel as opposed to the fluoride-based fuel used in MSRE. Thus, a literature study provided data to understand the similarities and differences between the characteristics of fluoride- and chloride-based salts in terms of salt chemistry, material characteristics, postirradiation behavior, neutronics, thermal hydraulics, and heat removal. This study, together with the proposed irradiated fuel salt management processes, preliminary criticality calculations, decay heat, and dose rate estimates, provides a strong basis for future investigation into the management of irradiated fuel salts generated during molten salt reactor technology demonstrations.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

Solar Flare↗

Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words: Promethazine, stable isotopes, bioavailability, pharmacodynamics, cognitive performance, antiorthostatic bed rest.

Putcha, Lakshmi↗

A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.

59 BASIC BIOLOGICAL SCIENCES↗

Automated Generation of Weather and Climate Analysis Products

Wind roses are an important part to site operations as they depict the wind speed and direction percentage over a time period. In this project, I automated the production of wind roses for SRS meteorological towers. I developed a script to sequence through the dataset by period and create a wind rose for each of those period sets. Graphics were generated for every 4-hour period of the day, for each of the 4 heights of the instruments, for every half of each month. A 10-year climatological period consisted of wind speed and directions measurements at 15-minute intervals. We used the years 2014-2024 as the wind instruments on the tower were upgraded to sonic anemometers in early 2014. I then compared these wind roses to those from a previous study done in 2003 to analyze the differences and similarities in the wind patterns. The wind roses are also used to understand environmental transport conditions at SRS. When comparing the different heights of the anemometers to the 2003 report, there is a similarity in the fact that the direction is relatively the same across the levels, with the wind speeds increasing as you get higher in the air. When comparing the season of our graphs against the 2003 report, we noticed that the winter and summer months appear to have very similar wind directions. However, in the spring we noticed that there were more southerly winds compared to the 2003 report which had more westerly winds. Finally, in the fall months, we noticed that there was a higher percentage of northeasterly winds, while the 2003 report showed more southeasterly winds. We can use these summaries to estimate the directional dependence of dose that the surrounding areas receive throughout the year according to time of day.

47 OTHER INSTRUMENTATION↗

Preliminary estimates of radiation exposures for manned interplanetary missions from anomalously large solar flare events

Preliminary estimates of radiation exposures for manned interplanetary missions resulting from anomalously large solar flare events are presented. The calculations use integral particle fluences for the February 1956, November 1960, and August 1972 events as inputs into the Langley Research Center nucleon transport code BRYNTRN. This deterministic code transports primary and secondary nucleons (protons and neutrons) through any number of layers of target material of arbitrary thickness and composition. Contributions from target nucleus fragmentation and recoil are also included. Estimates of 5 cm depth doses and dose equivalents in tissue are presented behind various thicknesses of aluminum, water, and composite aluminum/water shields for each of the three solar flare events.

Townsend, Lawrence W.↗

Formation of Clustered DNA Damage after High-LET Irradiation: A Review

Radiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki. These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or gamma-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to particles from radon gas emitters or other radioactive emitters like uranium-238. Complex DNA damage, i.e., the signature of high-LET radiations comprises by closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest there is increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.

Hada, Megumi↗

Probabilistic Assessment of Radiation Risk for Astronauts in Space Missions

Accurate predictions of the health risks to astronauts from space radiation exposure are necessary for enabling future lunar and Mars missions. Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons, (less than 100 MeV); and galactic cosmic rays (GCR), which include protons and heavy ions of higher energies. While the expected frequency of SPEs is strongly influenced by the solar activity cycle, SPE occurrences themselves are random in nature. A solar modulation model has been developed for the temporal characterization of the GCR environment, which is represented by the deceleration potential, phi. The risk of radiation exposure from SPEs during extra-vehicular activities (EVAs) or in lightly shielded vehicles is a major concern for radiation protection, including determining the shielding and operational requirements for astronauts and hardware. To support the probabilistic risk assessment for EVAs, which would be up to 15% of crew time on lunar missions, we estimated the probability of SPE occurrence as a function of time within a solar cycle using a nonhomogeneous Poisson model to fit the historical database of measurements of protons with energy > 30 MeV, (phi)30. The resultant organ doses and dose equivalents, as well as effective whole body doses for acute and cancer risk estimations are analyzed for a conceptual habitat module and a lunar rover during defined space mission periods. This probabilistic approach to radiation risk assessment from SPE and GCR is in support of mission design and operational planning to manage radiation risks for space exploration.

Kim, Myung-Hee↗

Quantifying radiation quality for space relevant radiation types: Fitting excess risk models to three combined HZE-irradiated mouse datasets

Radiation health risks are predominantly derived from low linear energy transfer (LET) terrestrial exposures; however, space radiation includes exposure to high-LET and high-charge, high-energy (HZE) particles. Accurately quantifying the differences in radiation quality between the space and terrestrial radiation environments is important for assessing and predicting health risks for astronauts. Weil et al. 2009 and 2014 used two different inbred mouse strains to study differences in hepatocellular carcinoma (HCC) tumorigenesis after exposures to low- and high- LET radiation. More recently, Edmundson et al. 2020 provided valuable new tumor data in outbred mice that were exposed to low- and high-LET radiation. The present study aims to rigorously investigate a relative biological effectiveness (RBE) factor by leveraging the HCC tumor data from Weil et al. 2009, Weil et al. 2014, and Edmundson et al. 2020. The three experiments were similarly designed, allowing the raw data to be combined into a pooled dataset to estimate excess relative risk (ERR) and excess absolute risk (EAR) models using Bayesian Poisson regression. These effect estimates from the pooled data provide greater power to calculate a data driven RBE. Extensive sensitivity analyses test the robustness of RBE estimates to various model assumptions. The following questions will be explored through the sensitivity analyses: • Is the shape of the dose response different for low-LET radiation and HZE radiation, indicating that RBE is a function of dose? • Does attained age modify the effect estimates differently for low-LET radiation and HZE radiation, indicating RBE is a function of attained age? • Are the effect estimates and RBE estimates different for inbred mouse strains and outbred mouse strains? • Do assumptions about differences in ERR models and EAR models change the estimated RBE? Additional studies would be needed to validate the findings from these exploratory analyses.

Lori J. Chappell↗

More than RBE: Exploring Two Decades of Space Radiation Quality and Carcinogenesis Research and How NASA Manages Cancer Risk

NASA’s Space Radiation Element (SRE), both as a stand-alone entity and as part of the Human Research Program, has invested heavily into investigating how the different qualities of radiation and low dose rates relevant to the space environment and how these factors effect long term carcinogenesis risk. NASA’s current model to assess astronaut excess cancer risk due to radiation exposure utilizes data generated from both in vitro and in vivo models to inform quality factor and dose-rate functions that scales risk estimates originally established from human cohorts exposed to terrestrial radiation, most notably the Lifespan Study of atomic bomb survivors (LSS). As part of an effort to update these quality function, the SRE hosted a workshop in on radiation quality in September 2021 and a workshop on dose-rate at NASA HRP’s Investigators’ Workshop in February 2022 where current and former grantees presented data that could potentially be incorporated into assessing carcinogenic risk. This presentation is intended to both inform the broader research community of the outcome of those workshops and generate a discussion as to what biological data should be generated to better inform NASA’s risk estimates. Additionally, NASA’s current risk disposition for cancer assessment will be discussed and clarified. We look forward to hearing feedback from the Radiation Research Society community!

Brock J Sishc↗

Space radiation absorbed dose distribution in a human phantom

The radiation risk to astronauts has always been based on measurements using passive thermoluminescent dosimeters (TLDs). The skin dose is converted to dose equivalent using an average radiation quality factor based on model calculations. The radiological risk estimates, however, are based on organ and tissue doses. This paper describes results from the first space flight (STS-91, 51.65 degrees inclination and approximately 380 km altitude) of a fully instrumented Alderson Rando phantom torso (with head) to relate the skin dose to organ doses. Spatial distributions of absorbed dose in 34 1-inch-thick sections measured using TLDs are described. There is about a 30% change in dose as one moves from the front to the back of the phantom body. Small active dosimeters were developed specifically to provide time-resolved measurements of absorbed dose rates and quality factors at five organ locations (brain, thyroid, heart/lung, stomach and colon) inside the phantom. Using these dosimeters, it was possible to separate the trapped-proton and the galactic cosmic radiation components of the doses. A tissue-equivalent proportional counter (TEPC) and a charged-particle directional spectrometer (CPDS) were flown next to the phantom torso to provide data on the incident internal radiation environment. Accurate models of the shielding distributions at the site of the TEPC, the CPDS and a scalable Computerized Anatomical Male (CAM) model of the phantom torso were developed. These measurements provided a comprehensive data set to map the dose distribution inside a human phantom, and to assess the accuracy and validity of radiation transport models throughout the human body. The results show that for the conditions in the International Space Station (ISS) orbit during periods near the solar minimum, the ratio of the blood-forming organ dose rate to the skin absorbed dose rate is about 80%, and the ratio of the dose equivalents is almost one. The results show that the GCR model dose-rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

STS-91 Shuttle Project↗

Acute Radiation Risk and BRYNTRN Organ Dose Projection Graphical User Interface

The integration of human space applications risk projection models of organ dose and acute radiation risk has been a key problem. NASA has developed an organ dose projection model using the BRYNTRN with SUM DOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUM DOSE are a Baryon transport code and an output data processing code, respectively. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN. A GUI for the ARR and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. BRYNTRN code operation requires extensive input preparation. Only a graphical user interface (GUI) can handle input and output for BRYNTRN to the response models easily and correctly. The purpose of the GUI development for ARRBOD is to provide seamless integration of input and output manipulations for the operations of projection modules (BRYNTRN, SLMDOSE, and the ARR probabilistic response model) in assessing the acute risk and the organ doses of significant Solar Particle Events (SPEs). The assessment of astronauts radiation risk from SPE is in support of mission design and operational planning to manage radiation risks in future space missions. The ARRBOD GUI can identify the proper shielding solutions using the gender-specific organ dose assessments in order to avoid ARR symptoms, and to stay within the current NASA short-term dose limits. The quantified evaluation of ARR severities based on any given shielding configuration and a specified EVA or other mission scenario can be made to guide alternative solutions for attaining determined objectives set by mission planners. The ARRBOD GUI estimates the whole-body effective dose, organ doses, and acute radiation sickness symptoms for astronauts, by which operational strategies and capabilities can be made for the protection of astronauts from SPEs in the planning of future lunar surface scenarios, exploration of near-Earth objects, and missions to Mars.

Cucinotta, Francis A.↗

Optimizing long-term monitoring of radiation air-dose rates after the Fukushima Daiichi Nuclear Power Plant

Radiation air dose rates near the Fukushima Daiichi Nuclear Power Plant (FDNPP) have been steadily decreasing over the past eight years since the release of radioactive elements in March 2011. Currently, the radiation monitoring program is expected to transition to long-term monitoring after most of the remediation activities are completed. The main long-term monitoring objectives are to (1) confirm the continuing reduction of contaminant and hazard levels, (2) provide assurance for the public, (3) accumulate the basic datasets for scientific knowledge and future preparation, and (4) detect changes or anomalies in contaminant mobility (if they occur), or any unexpected processes or events. In this work, we have developed a methodology for optimizing the monitoring locations of radiation air dose-rate monitoring. Our approach consists of three steps in order to determine monitoring locations in a systematic manner: (1) prioritizing the critical locations, such as schools or regulatory requirement locations, (2) diversifying locations that cover the key environmental controls that are known to influence contaminant mobility and distributions, and (3) capturing the heterogeneity of radiation air-dose rates across the domain. Therefore, for the second step, we use a Gaussian mixture model to identify the representative locations among multiple environmental variables, such as elevation and land-cover types. For the third step, we use a Gaussian process model to capture and estimate the heterogeneity of air-dose rates across the domain. Employing an integrated dose-rate map derived from Bayesian geostatistical methods as a reference map, we distribute the monitoring locations in such a way as to capture the heterogeneity of the reference map. Our results have shown that this approach allows us to select monitoring locations in a systematic manner such that the heterogeneity of air dose rates is captured by the minimal number of monitoring locations.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Designing a boron nitride polyethylene composite for shielding neutrons

Neutrons are encountered in many different fields, including condensed matter physics, space exploration, nuclear power, and healthcare. Neutrons interacting with a biological target produce secondary charged particles that are damaging to human health. The most effective way to shield neutrons is to slow them to thermal energies and then capture the thermalized neutrons. These factors lead us to consider potential materials solutions for neutron shields that maximize the protection of humans while minimizing the shield mass and adapt well to modern additive manufacturing techniques. Using hexagonal boron nitride (hBN) as a capture medium and high-density polyethylene (HDPE) as a thermalization medium, we aim to design the optimal internal structure of h 10 BN/HDPE composites by minimizing the effective dose, which is a measure of the estimated radiation damage exposure for a human. Through Monte Carlo simulations in Geant4, we find that the optimal structure reduces the effective dose up to a factor of 72 over aluminum (Al) and up to a factor of 4 over HDPE; this is a significant improvement in shielding effectiveness that could dramatically reduce the radiation exposure of occupational workers.

36 MATERIALS SCIENCE↗

The Biological Effectiveness of Silicon Ions is Significantly Higher than Iron Ions for the Induction of Chromosome Damage in Human Lymphocytes

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, or Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET Si ions ranged from 48 to 158 keV/micron. Doses delivered were in the 10 to 200 cGy range. Dose response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600 Mev/u beam and 170 MeV/u beam produced the highest RBE(sub max) value for Si ions. For both ions the RBE(sub max) values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreased with further increase in LET.

George, Kerry↗

Analysis of Mass Averaged Tissue Doses in CAM, CAF, MAX, and FAX

To estimate astronaut health risk due to space radiation, one must have the ability to calculate exposure-related quantities averaged over specific organs and tissue types. In this study, we first examine the anatomical properties of the Computerized Anatomical Man (CAM), Computerized Anatomical Female (CAF), Male Adult voXel (MAX), and Female Adult voXel (FAX) models by comparing the masses of various tissues to the reference values specified by the International Commission on Radiological Protection (ICRP). Major discrepancies are found between the CAM and CAF tissue masses and the ICRP reference data for almost all of the tissues. We next examine the distribution of target points used with the deterministic transport code HZETRN to compute mass averaged exposure quantities. A numerical algorithm is used to generate multiple point distributions for many of the effective dose tissues identified in CAM, CAF, MAX, and FAX. It is concluded that the previously published CAM and CAF point distributions were under-sampled and that the set of point distributions presented here should be adequate for future studies involving CAM, CAF, MAX, or FAX. It is concluded that MAX and FAX are more accurate than CAM and CAF for space radiation analyses.

Slaba, Tony C.↗