Modeling Clustered DNA Damage by Ionizing Radiation Using Multinomial Damage Probabilities and Energy Imparted Spectra.

Simple and complex clustered DNA damage represent the critical initial damage caused by radiation. In this paper, a multinomial probability model of clustered damage is developed with probabilities dependent on the energy imparted to DNA and surrounding water molecules. The model consists of four probabilities: (A) direct damage of sugar-phosphate moieties leading to SSB, (B) OH radical formation with subsequent SSB and BD formation, (C) direct damage to DNA bases, and (D) energy imparted to histone proteins and other molecules in a volume not leading to SSB or BD.

Organ dose equivalents of albedo protons and neutrons under exposure to large solar particle events during lunar human landing missions.

Astronauts participating in lunar landing missions will encounter exposure to albedo particles emitted from the lunar surface as well as primary high-energy particles in the spectra of galactic cosmic rays (GCRs) and solar particle events (SPEs). While existing studies have examined particle energy spectra and absorbed doses in limited radiation exposure scenarios on and near the Moon, comprehensive research encompassing various shielding amounts and large SPEs on the lunar surface remains lacking. Additionally, detailed organ dose equivalents of albedo particles in a human model on the lunar surface have yet to be investigated.

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.

A no-fault risk compensation approach for radiation risks incurred in space travel.

In this paper we recommend an appropriate compensation approach should be established for fatality and disabilities that may occur due to space radiation exposures of government or industry workers. A brief review of compensation approaches for nuclear energy and nuclear weapons development workers in the United States and other countries is described. We then summarize issues in the application of probability of causation calculation and provide examples of probability of causation (PC) calculations for missions to the International Space Station and Earth's moon or for Mars exploration.

Effects of Partial-Body, Continuous/Pulse Irradiation at Dose Rates from FLASH to Conventional Rates on the Level of Surviving Blood Lymphocytes: Modeling Approach II. Two- and Multiple-Pulse Irradiation.

Mathematical models, which describe effects of partial-body, two- and multiple-pulse irradiation at high total doses D and at average dose rates N from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and mice, have been developed originating in the previously proposed approach. These models predict that levels of surviving blood lymphocytes in humans and mice increase with increasing the dose rate from N=D/TR (TR is the time of the blood flowing into or out of the irradiated segment of the blood circulatory system) to FLASH rates and approach an upper limiting level equal to (1-vR), where vR is the fraction of blood volume in the irradiated segment of the blood circulatory system. Levels of surviving blood lymphocytes computed at total doses D of 10-40 Gy and at average of dose rates N, which are equal to or exceed 40 Gy/s for humans and 400 Gy/s for mice, are nearly indistinguishable from the upper limiting level.

Effects of Partial-Body, Continuous/Pulse Irradiation at Dose Rates from FLASH to Conventional Rates on the Level of Surviving Blood Lymphocytes: Modeling Approach. I. Continuous Irradiation.

A mathematical model developed by Cucinotta and Smirnova is extended to describe effects of continuous, partial-body irradiation at high doses D and at dose rates N from FLASH to conventional rates on the level of surviving blood lymphocytes in humans and small laboratory animals (mice). Specifically, whereas the applicability of the model is limited to the exposure times shorter than a single cardiac cycle T0, the extended model is capable of describing such effects for the aforementioned and longer exposure times. The extended model is implemented as the algebraic equations.

Transcriptome Analysis by RNA Sequencing of Mouse Embryonic Stem Cells Stocked on International Space Station for 1584 Days in Frozen State after Culture on the Ground.

As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined.

Residual radiation risk disparities across sex and race or ethnic groups for lifetime never-smokers on lunar missions.

Missions to the Earth's moon are of scientific and societal interest, however pose the problem of risks of late effects for returning crew persons, most importantly cancer and circulatory diseases. In this paper, we discuss NSCR-2022 model risk estimates for lunar missions for US racial and ethnic groups comparing never-smokers (NS) to US averages for each group and sex. We show that differences within groups between men and women are reduced for NS compared to the average population.

Non-targeted effects and space radiation risks for astronauts on multiple International Space Station and lunar missions.

Future space travel to the earth's moon or the planet Mars will likely lead to the selection of experienced International Space Station (ISS) or lunar crew persons for subsequent lunar or mars missions. Major concerns for space travel are galactic cosmic ray (GCR) risks of cancer and circulatory diseases. However large uncertainties in risk prediction occur due to the quantitative and qualitative differences in heavy ion microscopic energy deposition leading to differences in biological effects compared to low LET radiation.

Cancer and circulatory disease risks for the largest solar particle events in the space age.

In this paper we use the NASA Space Cancer Risk (NSCR version 2022) model to predict cancer and circulatory disease risks using energy spectra representing the largest SPE's observed in the space age. Because tissue dose-rates behind shielding for large SPE's lead to low dose-rates (<0.2 Gy/h) we consider the integrated risk for several historical periods of high solar activity, including July-November, 1960 events and August-October 1989 events along with the February 1956 and August 1972 events.

Effects of UHDR and Conventional Irradiation on Behavioral and Cognitive Performance and the Percentage of Ly6G+ CD45+ Cells in the Hippocampus.

We assessed the effects of conventional and ultra-high dose rate (UHDR) electron irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Two-month-old female and male C57BL/6J mice received whole-brain conventional or UHDR irradiation. UHDR mice were irradiated with 9 MeV electrons, delivered by the Linac-based/modified beam control.

Ionising radiation and cardiovascular disease: systematic review and meta-analysis.

Objective: To systematically review and perform a meta-analysis of radiation associated risks of cardiovascular disease in all groups exposed to radiation with individual radiation dose estimates.

Design: Systematic review and meta-analysis.

Main Outcome Measures: Excess relative risk per unit dose (Gy), estimated by restricted maximum likelihood methods.

Effects of Flash Radiotherapy on Blood Lymphocytes in Humans and Small Laboratory Animals.

A mathematical model, which describes the level of surviving lymphocytes in the blood after ultra-high (FLASH) and lower dose rates of partial-body irradiation, is developed. The model is represented by simple analytic formulae that involve a few parameters, namely, physiologic parameters (characteristics of the blood flow through the blood circulatory system and its irradiated part), a biophysical parameter (a characteristic of the blood lymphocytes radiosensitivity), and the physical parameters (characteristics of irradiation). The model predicts that the level of surviving blood lymphocytes increases as the dose rate increases and approaches the limiting level of (1 - vR), where vR is the fraction of the blood volume in the irradiated part of the blood circulatory system.

Isotopic production cross sections in proton-16O and proton-12C interactions for energies from 10 MeV/u to 100 GeV/u.

Proton interactions with O or C nuclei are frequent nuclear interaction leading to secondary radiation in tissues for space radiation and cancer therapy with protons or ion beams. The fragmentation of these ions by protons produces a large number of heavy ion (A>4) target or projectile fragments often with high ionization density. Here we develop an analytical model of energy dependent proton-O and proton-C cross sections for isotopic nuclei production.

Comparison of biological measurement and physical estimates of space radiation in the International Space Station.

Nowadays, ordinary people can travel in space, and the possibility of extended durations in an environment such as moon of the Earth and Mars with higher space radiation exposures compared to past missions, is increasing. Until now, the physical doses of space radiation have been measured, but measurement of direct biological effects has been hampered by its low dose and low dose-rate effect. To assess the biological effects of space radiation, we launched and kept frozen mouse embryonic stem (ES) cells in minus eighty degree Celsius freezer in ISS (MELFI) on the International Space Station (ISS) for a maximum of 1,584 days.

Flying without a Net: Space Radiation Cancer Risk Predictions without a Gamma-ray Basis.

The biological effects of high linear energy transfer (LET) radiation show both a qualitative and quantitative difference when compared to low-LET radiation. However, models used to estimate risks ignore qualitative differences and involve extensive use of gamma-ray data, including low-LET radiation epidemiology, quality factors (QF), and dose and dose-rate effectiveness factors (DDREF). We consider a risk prediction that avoids gamma-ray data by formulating a track structure model of excess relative risk (ERR) with parameters estimated from animal studies using high-LET radiation.

Race and ethnic group dependent space radiation cancer risk predictions.

Future space missions by national space agencies and private industry, including space tourism, will include a diverse makeup of crewmembers with extensive variability in age, sex, and race or ethnic groups. The relative risk (RR) model is used to transfer epidemiology data between populations to estimate radiation risks. In the RR model cancer risk is assumed to be proportional to background cancer rates and limited by other causes of death, which are dependent on genetic, environmental and dietary factors that are population dependent.

Study of Total, Absorption, and He and H Production Cross Sections in He-proton Collisions.

Light ion breakup cross sections are important for studies of cosmic ray interactions in the inter-stellar medium or radiation protection considerations of energy deposition in shielding and tissues. Abrasion cross sections for heavy ion reactions have been modeled using the Glauber model in the large mass limit or Eikonal form of the optical potential model. Here we formulate an abrasion model for He fragmentation on protons using the Glauber model avoiding the large mass limit and include a model for final state interactions.

Benchmarking risk predictions and uncertainties in the NSCR model of GCR cancer risks with revised low let risk coefficients.

We report on the contributions of model factors that appear in projection models to the overall uncertainty in cancer risks predictions for exposures to galactic cosmic ray (GCR) in deep space, including comparisons with revised low LET risks coefficients. Annual GCR exposures to astronauts at solar minimum are considered. Uncertainties in low LET risk coefficients, dose and dose-rate modifiers, quality factors (QFs), space radiation organ doses, non-targeted effects (NTE) and increased tumor lethality at high LET compared to low LET radiation are considered.

A proposed change to astronaut exposures limits is a giant leap backwards for radiation protection.

Addressing the uncertainties in assessing health risks from cosmic ray heavy ions is a major scientific challenge recognized by many previous reports by the National Academy of Sciences (NAS) and the National Council on Radiation Protection and Measurements (NCRP) advising the National Aeronautics and Space Administration (NASA). These reports suggested a series of steps to pursue the scientific basis for space radiation protection, including the implementation of age and sex dependent risk assessments and exposure limits appropriate for a small population of radiation workers, the evaluation of uncertainties in risk projections, and developing a vigorous research program in heavy ion radiobiology to reduce uncertainties and discover effective countermeasures. The assessment of uncertainties in assessing risk provides protection against changing assessments of risk, reveals limitations in information used in space mission operations, and provides the impetus to reduce uncertainties and discover the true level of risk and possible effectiveness of countermeasures through research.

Carbon Ion Radiotherapy in the Management of Hepatocellular Carcinoma.

Localized hepatocellular carcinoma (HCC) that is unresectable and non-transplantable can be treated by several liver-directed therapies. External beam radiation therapy (EBRT) is an increasingly accepted and widely utilized treatment modality in this setting. Accelerated charged particles such as proton beam therapy (PBT) and carbon ion radiation therapy (CIRT) offer technological advancements over conventional photon radiotherapy.

Comparison between PHITS and GEANT4 Simulations of the Heavy Ion Beams at the BEVALAC at LBNL and the Booster Accelerator at BNL.

Heavy charged particles have been discussed for clinical use due to their superior dose-depth distribution compared to conventional radiation such as X-rays. In addition, high-charge and energy (HZE) ions in galactic cosmic rays (GCR) present important health risks for crewed space missions to the Earth's moon or Mars. Experiments at heavy ion accelerators are used in radiobiology studies; however, numerical simulations of track segment or Bragg peak irradiations are complicated by the details of the beam-line and dosimetry systems.

Low-Dose Radiation Therapy (LDRT) for COVID-19: Benefits or Risks?

The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide.

Comparison of signaling profiles in the low dose range following low and high LET radiation.

During space travel astronauts will be exposed to a very low, mixed field of radiation containing different high LET particles of varying energies, over an extended period. Thus, defining how human cells respond to these complex low dose exposures is important in ascertaining risk. In the current study, we have chosen to investigate how low doses of three different ion's at various energies uniquely change the kinetics of three different phospho-proteins.