A method to predict space radiation biological effectiveness for non-cancer effects following intense Solar Particle Events.

In addition to the continuous exposure to cosmic rays, astronauts in space are occasionally exposed to Solar Particle Events (SPE), which involve less energetic particles but can deliver much higher doses. The latter can exceed several Gy in a few hours for the most intense SPEs, for which non-stochastic effects are thus a major concern. To identify adequate shielding conditions that would allow respecting the dose limits established by the various space agencies, the absorbed dose in the considered organ/tissue must be multiplied by the corresponding Relative Biological Effectiveness (RBE), which is a complex quantity depending on several factors including particle type and energy, considered biological effect, level of effect (and thus absorbed dose), etc. While in several studies only the particle-type dependence of RBE is taken into account, in this work we developed and applied a new approach where, thanks to an interface between the FLUKA Monte Carlo transport code and the BIANCA biophysical model, the RBE dependence on particle energy and absorbed dose was also considered. Furthermore, we included in the considered SPE spectra primary particles heavier than protons, which in many studies are neglected. This approach was then applied to the October 2003 SPE (the most intense SPE of solar cycle 23, also known as "Halloween event") and the January 2005 event, which was characterized by a lower fluence but a harder spectrum, i.e., with higher-energy particles. The calculation outcomes were then discussed and compared with the current dose limits established for skin and blood forming organs in case of 30-days missions. This work showed that the BIANCA model, if interfaced to a radiation transport code, can be used to calculate the RBE values associated to Solar Particle Events. More generally, this work emphasizes the importance of taking into account the RBE dependence on particle energy and dose when calculating equivalent doses.

Tissue-specific dose equivalents of secondary mesons and leptons during galactic cosmic ray exposures for mars exploration.

During a human mission to Mars, astronauts would be continuously exposed to galactic cosmic rays (GCR) consisting of high energy protons and heavier ions coming from outside our solar system. Due to their high energy, GCR ions can penetrate spacecraft and space habitat structures, directly reaching human organs. Additionally, they generate secondary particles when interacting with shielding materials and human tissues. Baryon secondaries have been the focus of many previous studies, while meson and lepton secondaries have been considered to a much lesser extent. In this work, we focus on assessing the tissue-specific dose equivalents and the effective dose for males of secondary mesons and leptons for the interplanetary cruise phase and the surface phase on Mars. We also provide the energy distribution of the secondary pions in each human organ since they are dominant compared to other mesons and leptons. For this calculation, the PHITS3.27 Monte Carlo simulation toolkit is used to compute the energy spectra of particles in organs in a realistic human phantom. Based on the simulation data, the dose equivalent has been estimated with radiation quality factors in ICRP Publication 60 and in the latest NASA Space Cancer Risk model (NSCR-2022). The effective dose is then assessed with the tissue weighting factors in ICRP Publication 103 and in the NSCR model, separately. The results indicate that the contribution of secondary mesons and leptons to the total effective dose is 6.1 %, 9.1 %, and 11.3 % with the NSCR model in interplanetary space behind 5, 20, and 50 g/cm2 aluminum shielding, respectively, with similar values using the ICRP model. The outcomes of this work lead to an improved understanding of the potential health risks induced by secondary particles for exploration missions to Mars and other destinations.

An Augmented Reality Hand-Eye Sensorimotor Impairment Assessment for Spaceflight Operations.

INTRODUCTION: Following a transition from microgravity to a gravity-rich environment (e.g., Earth, Moon, or Mars), astronauts experience sensorimotor impairment, primarily from a reinterpretation of vestibular cues, which can impact their ability to perform mission-critical tasks. To enable future exploration-class missions, the development of lightweight, space-conscious assessments for astronauts transitioning between gravity environments without expert assistance is needed.METHODS: We examined differences in performance during a two-dimensional (2D) hand-eye multidirectional tapping task, implemented in augmented reality in subjects (N = 20) with and without the presence of a vestibular-dominated sensorimotor impairment paradigm: the binaural bipolar application of a pseudorandom galvanic vestibular stimulation (GVS) signal. Metrics associated with both the impairment paradigm and task performance were assessed.RESULTS: Medial-lateral sway during balance on an anterior-posterior sway-referenced platform with eyes closed was most affected by GVS (effect size: 1.2), in addition to anterior-posterior sway (effect size: 0.63) and the vestibular index (effect size: 0.65). During the augmented reality task, an increase in time to completion (effect size: 0.63), number of misses (effect size: 0.52), and head linear accelerations (effect size: 0.30) were found in the presence of the selected GVS waveform.DISCUSSION: Findings indicate that this multidirectional tapping task may detect emergent vestibular-dominated impairment (near landing day performance) in astronauts. Decrements in speed and accuracy indicate this impairment may hinder crews' ability to acquire known target locations while in a static standing posture. The ability to track these decrements can support mission operations decisions.Allred AR, Weiss H, Clark TK, Stirling L. An augmented reality hand-eye sensorimotor impairment assessment for spaceflight operations. Aerosp Med Hum Perform. 2024; 95(2):69-78.

Application of multi-method-multi-model inference to radiation related solid cancer excess risks models for astronaut risk assessment.

The impact of including model-averaged excess radiation risks (ER) into a measure of radiation attributed decrease of survival (RADS) for the outcome all solid cancer incidence and the impact on the uncertainties is demonstrated. It is shown that RADS applying weighted model averaged ER based on AIC weights result in smaller risk estimates with narrower 95% CI than RADS using ER based on BIC weights. Further a multi-method-multi-model inference approach is introduced that allows calculating one general RADS estimate providing a weighted average risk estimate for a lunar and a Mars mission. For males the general RADS estimate is found to be 0.42% (95% CI: 0.38%; 0.45%) and for females 0.67% (95% CI: 0.59%; 0.75%) for a lunar mission and 2.45% (95% CI: 2.23%; 2.67%) for males and 3.91% (95% CI: 3.44%; 4.39%) for females for a Mars mission considering an age at exposure of 40 years and an attained age of 65 years. It is recommended to include these types of uncertainties and to include model-averaged excess risks in astronaut risk assessment.

European astronaut radiation related cancer risk assessment using dosimetric calculations of organ dose equivalents.

An illustrative sample mission of a Mars swing-by mission lasting one calendar year was chosen to highlight the application of European risk assessment software to cancer (all solid cancer plus leukaemia) risks from radiation exposures in space quantified with organ dose equivalent rates from model calculations based on the quantity Radiation Attributed Decrease of Survival (RADS). The relevant dose equivalent to the colon for radiation exposures from this Mars swing-by mission were found to vary between 198 and 482 mSv. These doses depend on sex and the two other factors investigated here of: solar activity phase (maximum or minimum); and the choice of space radiation quality factor used in the calculations of dose equivalent. Such doses received at typical astronaut ages around 40 years old will result in: the probability of surviving until retirement age (65 years) being reduced by a range from 0.38% (95%CI: 0.29; 0.49) to 1.29% (95%CI: 1.06; 1.56); and the probability of surviving cancer free until retirement age being reduced by a range from 0.78% (95%CI: 0.59; 0.99) to 2.63% (95%CI: 2.16; 3.18). As expected from the features of the models applied to quantify the general dosimetric and radiation epidemiology parameters, the cancer incidence risks in terms of surviving cancer free, are higher than the cancer mortality risks in terms of surviving, the risks for females are higher than for males, and the risks at solar minimum are higher than at solar maximum.

First pelagic fish biodiversity assessment of Cosmonaut Sea based on environmental DNA.

The Cosmonaut Sea is a typical marginal sea in East Antarctica that has not yet been greatly impacted by climate change. As one of the least explored areas in the Southern Ocean, our knowledge regarding its fish taxonomy and diversity has been sparse. eDNA metabarcoding, as an emerging and promising tool for marine biodiversity research and monitoring, has been widely used across taxa and habitats. During the 38th Chinese Antarctic Research Expedition (CHINARE-38), we collected seawater and surface sediment samples from 38 stations in the Cosmonaut Sea and performed the first, to our knowledge, eDNA analysis of fish biodiversity in the Southern Ocean based on the molecular markers of 12S rRNA and 16S rRNA. There were 48 fish species detected by the two markers in total, with 30 and 34 species detected by the 12S rRNA and 16S rRNA marker, respectively. This was more than the trawling results (19 species) and historical survey records (16 species, "BROKE-West" cruise). With some nonsignificant differences between the Gunnerus Ridge and the Oceanic Area of Enderby Land, the Cosmonaut Sea had a richer fish biodiversity in this research compared with previous studies, and its overall composition and distribution patterns were consistent with what we know in East Antarctica. We also found that the eDNA composition of fish in the Cosmonaut Sea might be related to some environmental factors. Our study demonstrated that the use of the eDNA technique for Antarctic fish biodiversity research is likely to yield more information with less sampling effort than traditional methods. In the context of climate change, the eDNA approach will provide a novel and powerful tool that is complementary to traditional methods for polar ecology research.

Extended reality quantification of pupil reactivity as a non-invasive assessment for the pathogenesis of spaceflight associated neuro-ocular syndrome: A technology validation study for astronaut health.

The National Aeronautics and Space Administration (NASA) has rigorously documented a group of neuro-ophthalmic findings in astronauts during and after long-duration spaceflight known as spaceflight associated neuro-ocular syndrome (SANS). For astronaut safety and mission effectiveness, understanding SANS and countermeasure development are of utmost importance. Although the pathogenesis of SANS is not well defined, a leading hypothesis is that SANS might relate to a sub-clinical increased intracranial pressure (ICP) from cephalad fluid shifts in microgravity. However, no direct ICP measurements are available during spaceflight. To further understand the role of ICP in SANS, pupillometry can serve as a promising non-invasive biomarker for spaceflight environment as ICP is correlated with the pupil variables under illumination. Extended reality (XR) can help to address certain limitations in current methods for efficient pupil testing during spaceflight. We designed a protocol to quantify parameters of pupil reactivity in XR with an equivalent time duration of illumination on each eye compared to pre-existing, non-XR methods. Throughout the assessment, the pupil diameter data was collected using HTC Vive Pro-VR headset, thanks to its eye-tracking capabilities. Finally, the data was used to compute several pupil variables. We applied our methods to 36 control subjects. Pupil variables such as maximum and minimum pupil size, constriction amplitude, average constriction amplitude, maximum constriction velocity, latency and dilation velocity were computed for each control data. We compared our methods of calculation of pupil variables with the non-XR methods existing in the literature. Distributions of the pupil variables such as latency, constriction amplitude, and velocity of 36 control data displayed near-identical results from the non-XR literature for normal subjects. We propose a new method to evaluate pupil reactivity with XR technology to further understand ICP's role in SANS and provide further insight into SANS countermeasure development for future spaceflight.

Head-Mounted Dynamic Visual Acuity for G-Transition Effects During Interplanetary Spaceflight: Technology Development and Results from an Early Validation Study.

INTRODUCTION: Dynamic visual acuity (DVA) refers to the ability of the eye to discern detail in a moving object and plays an important role whenever rapid physical responses to environmental changes are required, such as while performing tasks onboard a space shuttle. A significant decrease in DVA has previously been noted after astronauts returned from long-duration spaceflight (0.75 eye chart lines, 24 h after returning from space). As part of a NASA-funded, head-mounted multimodal visual assessment system for monitoring vision changes in spaceflight, we elaborate upon the technical development and engineering of dynamic visual acuity assessments with virtual reality (VR) technology as the first step in assessing astronaut performance when undergoing G-transitional effects. We also report results from an early validation study comparing VR DVA assessment with traditional computer based DVA assessment.METHODS: Various VR/AR headsets have been utilized to implement DVA tests. These headsets include HTC Vive Pro Eye system. Epic's game engine UnrealEngine 4 Version 4.24 was used to build the framework and SteamVR was used to experience virtual reality content. Eye tracking technology was used to maintain fixation of the participant. An early validation study with five participants was conducted comparing this technology versus traditional DVA with a laptop.RESULTS: The head-mounted technology developed for assessing DVA changes during G-transitions is fully functional. The results from the early validation study demonstrated that the two DVA tests (laptop-based and VR) indicated a strong association between both methods (Pearson correlation coefficient of 0.91). A Bland-Altman plot was employed to assess levels of agreement, with all data points falling within the limits of agreement.DISCUSSION: The results from this early validation study indicate that head-mounted DVA assessment performs similarly to traditional laptop-based methods and is a promising method for assessing DVA during spaceflight, particularly in G-transitions. Future studies are required for further assessment of validation and reliability of this technology. With its ease of use, accessibility, and portable design, VR DVA has the potential in the near-future to replace conventional methods of assessing DVA. The technology will likely be an important aspect to help monitor functionality and safety during interplanetary missions where astronauts are exposed to G-transitions.Waisberg E, Ong J, Zaman N, Kamran Sa, Lee AG, Tavakkoli A. Head-mounted dynamic visual acuity for G-transition effects during interplanetary spaceflight: technology development and results from an early validation study. Aerosp Med Hum Perform. 2022; 93(11):800-805.

Effect of Exercise on Energy Expenditure and Body Composition in Astronauts Onboard the International Space Station: Considerations for Interplanetary Travel.

OBJECTIVE: Body mass (BM) loss and body composition (BC) changes threaten astronauts' health and mission success. However, the energetic contribution of the exercise countermeasure to these changes has never been investigated during long-term missions. We studied energy balance and BC in astronauts during 6-month missions onboard the International Space Station. METHODS: Before and after at least 3 months in space, BM, BC, total and activity energy expenditure (TEE and AEE) were measured using the doubly labeled water method in 11 astronauts (2011-2017). Physical activity (PA) was assessed by the SensewearPro® activity-device. RESULTS: Three-month spaceflight decreased BM (- 1.20 kg [SE 0.5]; P = 0.04), mainly due to non-significant fat-free mass loss (FFM; - 0.94 kg [0.59]). The decrease in walking time (- 63.2 min/day [11.5]; P < 0.001) from preflight was compensated by increases in non-ambulatory activities (+ 64.8 min/day [18.8]; P < 0.01). Average TEE was unaffected but a large interindividual variability was noted. Astronauts were stratified into those who maintained (stable_TEE; n = 6) and those who decreased (decreased_TEE; n = 5) TEE and AEE compared to preflight data. Although both groups lost similar BM, FFM was maintained and FM reduced in stable_TEE astronauts, while FFM decreased and FM increased in decreased_TEE astronauts (estimated between-group-difference (EGD) in ΔFFMindex [FFMI] 0.87 kg/m2, 95% CI + 0.32 to + 1.41; P = 0.01, ΔFMindex [FMI] - 1.09 kg/m2, 95% CI - 2.06 to - 0.11 kg/m2; P = 0.03). The stable_TEE group had higher baseline FFMI, and greater baseline and inflight vigorous PA than the decreased_TEE group (P < 0.05 for all). ΔFMI and ΔFFMI were respectively negatively and positively associated with both ΔTEE and ΔAEE. CONCLUSION: Both ground fitness and inflight overall PA are associated with spaceflight-induced TEE and BC changes and thus energy requirements. New instruments are needed to measure real-time individual changes in inflight energy balance components.

Assessment of Sex-Dependent Medical Outcomes During Spaceflight.

Background: In this study sex-differences in medical outcomes during spaceflight are reviewed and probabilistic risk assessment (PRA) is used to assess the impact on spaceflight missions of varying lengths. Materials and Methods: We use PRA to simulate missions of 42 days, 6 months, and 2.5 years. We model medical outcomes using three crews: two men and two women, four women, or four men. Total medical events (TME), crew health index (CHI), probability (0-1) of medical evacuation (pEVAC), probability of loss of crew life (pLOCL), and influential medical conditions were determined. Results: No differences were seen in any metric for the 42-day mission. There were no differences seen for any mission length, in any crew, for TME, CHI, pLOCL, or environmental causes of pEVAC. Sex-dependent differences are seen for rates of nonemergent pEVAC during the 6 month and 2.5-year missions, where women have a higher pEVAC in the 182-day (0.0388 vs. 0.0354) and 2.5-year missions (0.350 vs. 0.228). These differences were driven by higher incidence of partially treated urinary tract infection (UTI). In the 2.5 year mission, with resupply of medical resources, the influence of UTI in women on pEVAC decreases (0.35-0.11). Conclusion: Although resupply is unlikely for deep space missions, modeled results suggest that sex-specific medical needs can be readily managed through preventive measures and inclusion of appropriate medical capabilities. Within its many limitations, PRA is a useful tool to estimate medical risks in unique environments where only expert opinion was previously available.

Thick shielding against galactic cosmic radiation: A Monte Carlo study with focus on the role of secondary neutrons.

The exposure to galactic cosmic radiation (GCR) is a major health concern for astronauts. Crewed missions with durations of several years are foreseen in future space exploration projects such as permanent habitats on the Moon and flights to Mars. This aim requires elaborate space radiation shielding concepts and a proper understanding of the underlying radiation physics and radiobiology as well as their interplay. In the present work, Monte Carlo simulations to assess the performance of different materials (polyethylene, aluminum, Moon regolith) as thick shields (up to 400 g/cm2) against GCR were conducted using the FLUKA code. Absorbed dose, dose equivalent and the mean quality factor at 1 cm depth in the ICRU sphere as a function of shielding thickness were calculated in a spherical shell configuration for both solar minimum and solar maximum GCR conditions. Large differences were observed in the performance of the studied materials as thick GCR shields. Special attention was paid to the build-up and moderation of secondary neutrons. A method to reduce the neutron contributions to ambient dose equivalent by means of a two-layer shielding combination is proposed. The present study can be useful for considerations on thick shielding of Moon or Mars habitats built from local regolith.

Neuro-ophthalmic imaging and visual assessment technology for spaceflight associated neuro-ocular syndrome (SANS).

Spaceflight associated neuro-ocular syndrome (SANS) refers to a unique collection of neuro-ophthalmic clinical and imaging findings observed in astronauts after long-duration spaceflight. Current in-flight and postflight imaging modalities (e.g., optical coherence tomography, orbital ultrasound, and funduscopy) have played an instrumental role in the understanding and monitoring of SANS development; however, the precise etiology for this neuro-ophthalmic phenomenon is still not completely understood. SANS may be a potential barrier to future deep space missions, and therefore it is critical to further elucidate the underlying pathophysiology for effective countermeasures. The complexity and unique limitations of spaceflight require careful consideration and integration of leading technology to advance our knowledge of this extraterrestrial syndrome. We describe the current neuro-ophthalmic imaging modalities and hypotheses that have improved our current understanding of SANS, discuss newer developments in SANS imaging (including noninvasive near-infrared spectroscopy) and summarize emerging research in the development of an aspirational future head-mounted virtual reality display with multimodal visual assessment technology for the detection of neuro-ocular findings in SANS.

Improving astronaut cancer risk assessment from space radiation with an ensemble model framework.

A new approach to NASA space radiation risk modeling has successfully extended the current NASA probabilistic cancer risk model to an ensemble framework able to consider sub-model parameter uncertainty as well as model-form uncertainty associated with differing theoretical or empirical formalisms. Ensemble methodologies are already widely used in weather prediction, modeling of infectious disease outbreaks, and certain terrestrial radiation protection applications to better understand how uncertainty may influence risk decision-making. Applying ensemble methodologies to space radiation risk projections offers the potential to efficiently incorporate emerging research results, allow for the incorporation of future models, improve uncertainty quantification, and reduce the impact of subjective bias. Moreover, risk forecasting across an ensemble of multiple predictive models can provide stakeholders additional information on risk acceptance if current health/medical standards cannot be met for future space exploration missions, such as human missions to Mars. In this work, ensemble risk projections implementing multiple sub-models of radiation quality, dose and dose-rate effectiveness factors, excess risk, and latency are presented. Initial consensus methods for ensemble model weights and correlations to account for individual model bias are discussed. In these analyses, the ensemble forecast compares well to results from NASA's current operational cancer risk projection model used to assess permissible mission durations for astronauts. However, a large range of projected risk values are obtained at the upper 95th confidence level where models must extrapolate beyond available biological data sets. Closer agreement is seen at the median ± one sigma due to the inherent similarities in available models. Identification of potential new models, epidemiological data, and methods for statistical correlation between predictive ensemble members are discussed. Alternate ways of communicating risk and acceptable uncertainty with respect to NASA's current permissible exposure limits are explored.

Immunological Aspects of Isolation and Confinement.

Beyond all doubts, the exploration of outer space is a strategically important and priority sector of the national economy, scientific and technological development of every and particular country, and of all human civilization in general. A number of stress factors, including a prolonged confinement in a limited hermetically sealed space, influence the human body in space on board the spaceship and during the orbital flight. All these factors predominantly negatively affect various functional systems of the organism, in particular, the astronaut's immunity. These ground-based experiments allow to elucidate the effect of confinement in a limited space on both the activation of the immunity and the changes of the immune status in dynamics. Also, due to simulation of one or another emergency situation, such an approach allows the estimation of the influence of an additional psychological stress on the immunity, particularly, in the context of the reserve capacity of the immune system. A sealed chamber seems a convenient site for working out the additional techniques for crew members selection, as well as the countermeasures for negative changes in the astronauts' immune status. In this review we attempted to collect information describing changes in human immunity during isolation experiments with different conditions including short- and long-term experiments in hermetically closed chambers with artificial environment and during Antarctic winter-over.

Assessment of Spaceflight Medical Conditions' and Treatments' Potential Impacts on Behavioral Health and Performance.

Long-duration space exploration missions will pose significant risks to the physical and behavioral health and performance of the crew. We documented the presence and frequency of (1) behavioral health and performance (BHP)-relevant symptoms for each condition in NASA's Exploration Medical Conditions List (EMCL), (2) the BHP-relevant effects of applicable medical treatments in the current International Space Station (ISS) On-Orbit Medication List, (3) the breadth of potential BHP impacts of spaceflight medical treatments, and (4) the likelihood of adverse BHP effects of treating spaceflight medical conditions. BHP symptoms and effects were categorized by the six neurobehavioral domains of the National Institute of Mental Health's Research Domain Criteria (RDoC) framework. Including the cognitive effects of acute and chronic pain (e.g., attention, memory), 94% of spaceflight medical conditions include symptoms relevant to Cognitive Systems (e.g., attention deficits, confusion, psychosis), 36% include symptoms relevant to Negative Valence Systems (e.g., anxiety), 32% include symptoms relevant to Arousal and Regulatory Systems (e.g., sleep disturbances), 22% include symptoms relevant to Sensorimotor Systems (e.g., dizziness), 19% include symptoms relevant to Positive Valence Systems (e.g., mania), and 11% include symptoms relevant to Social Processes (e.g., social withdrawal). Only 2% of spaceflight medical conditions have no documented BHP symptoms. Of the spaceflight medical treatments, 63% affect Arousal and Regulatory Systems, 60% affect Sensorimotor Systems, 59% affect Cognitive Systems, 53% affect Negative Valence Systems, 38% affect Positive Valence Systems, and 31% affect Social Processes. The breadth of potential BHP impacts was bimodal, in that 27% of spaceflight medical treatments had no documented BHP effects; however, 27% of treatments may produce adverse effects across all six neurobehavioral domains. Historical prevalence data on medical conditions, symptoms, and complaints from 14 years of International Space Station operations coupled with documented BHP effects of recommended treatments indicates the potential for up to 481 adverse BHP effects of spaceflight medical treatments per person-year. Assessing the potential BHP impacts of spaceflight medical conditions and their treatments highlights the interactive nature of operational risks, and can provide an enhanced evidence base to support integrated research and countermeasure development strategies for long-duration exploration missions.

A bespoke health risk assessment methodology for the radiation protection of astronauts.

An alternative approach that is particularly suitable for the radiation health risk assessment (HRA) of astronauts is presented. The quantity, Radiation Attributed Decrease of Survival (RADS), representing the cumulative decrease in the unknown survival curve at a certain attained age, due to the radiation exposure at an earlier age, forms the basis for this alternative approach. Results are provided for all solid cancer plus leukemia incidence RADS from estimated doses from theoretical radiation exposures accumulated during long-term missions to the Moon or Mars. For example, it is shown that a 1000-day Mars exploration mission with a hypothetical mission effective dose of 1.07 Sv at typical astronaut ages around 40 years old, will result in the probability of surviving free of all types of solid cancer and leukemia until retirement age (65 years) being reduced by 4.2% (95% CI 3.2; 5.3) for males and 5.8% (95% CI 4.8; 7.0) for females. RADS dose-responses are given, for the outcomes for incidence of all solid cancer, leukemia, lung and female breast cancer. Results showing how RADS varies with age at exposure, attained age and other factors are also presented. The advantages of this alternative approach, over currently applied methodologies for the long-term radiation protection of astronauts after mission exposures, are presented with example calculations applicable to European astronaut occupational HRA. Some tentative suggestions for new types of occupational risk limits for space missions are given while acknowledging that the setting of astronaut radiation-related risk limits will ultimately be decided by the Space Agencies. Suggestions are provided for further work which builds on and extends this new HRA approach, e.g., by eventually including non-cancer effects and detailed space dosimetry.