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DNA data storage is a potential alternative to magnetic tape for archival storage purposes, promising substantial gains in information density. Critical to the success of DNA as a storage media is an understanding of the role of environmental factors on the longevity of the stored information. In this paper, we evaluate the effect of exposure to ionizing particle radiation, a cause of data loss in traditional magnetic media, on the longevity of data in DNA data storage pools. We develop a mass action kinetics model to estimate the rate of damage accumulation in DNA strands due to neutron interactions with both nucleotides and residual water molecules, then utilize the model to evaluate the effect several design parameters of a typical DNA data storage scheme have on expected data longevity. Finally, we experimentally validate our model by exposing dried DNA samples to different levels of neutron irradiation and analyzing the resulting error profile. Our results show that particle radiation is not a significant contributor to data loss in DNA data storage pools under typical storage conditions., (© 2024. The Author(s).)

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. This work assesses the organ dose equivalents of albedo neutrons and albedo protons during historically large SPEs in August 1972 and September 1989 utilizing realistic computational anthropomorphic human phantom for the first time. Dosimetric quantities within human organs have been evaluated based on the PHITS Monte Carlo simulation results and quality factors of the state-of-the-art NASA Space Cancer Risk (NSCR) model, as well as ICRP publications. The results with the NSCR model indicate that the albedo contribution to organ dose equivalent is less than 3 % for 1 g/cm 2 aluminum shielding, while it increases to more than 30 % in some organs for 50 g/cm 2 aluminum shielding during exposure to low-energy-proton-rich SPEs., Competing Interests: Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The study examined association between oscillations of body temperature of laboratory Wistar rats maintained under constant illumination with the amplitude of fluctuations of secondary cosmic rays reported by neutron count rate provided by neutron monitors and geomagnetic undulations. In contrast to geomagnetic undulations, neutron count rate variations and body temperature oscillations in rats assessed by spectrum analysis of the corresponding step functions at 1-min intervals demonstrated almost permanent variations with the periods ranging from 100 to 400 min. Under conditions of constant illumination inducing changes in the period of circadian rhythm and predominance of the ultradian rhythms, an association between neutron count rate fluctuations and body temperature oscillations was observed perpetually during the day- and nighttime., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34 + CD38 + cells) were isolated from umbilical cord blood and irradiated with 60 Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V + /PI + assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis., (© 2021. The Author(s).)

A recognized risk of long-duration space travel arises from the elevated exposure astronauts face from galactic cosmic radiation (GCR), which is composed of a diverse array of energetic particles. There is now abundant evidence that exposures to many different charged particle GCR components within acute time frames are sufficient to induce central nervous system deficits that span from the molecular to the whole animal behavioral scale. Enhanced spacecraft shielding can lessen exposures to charged particle GCR components, but may conversely elevate neutron radiation levels. We previously observed that space-relevant neutron radiation doses, chronically delivered at dose-rates expected during planned human exploratory missions, can disrupt hippocampal neuronal excitability, perturb network long-term potentiation and negatively impact cognitive behavior. We have now determined that acute exposures to similar low doses (18 cGy) of neutron radiation can also lead to suppressed hippocampal synaptic signaling, as well as decreased learning and memory performance in male mice. Our results demonstrate that similar nervous system hazards arise from neutron irradiation regardless of the exposure time course. While not always in an identical manner, neutron irradiation disrupts many of the same central nervous system elements as acute charged particle GCR exposures. The risks arising from neutron irradiation are therefore important to consider when determining the overall hazards astronauts will face from the space radiation environment.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe. In the last 60 years, the investigators at AFRRI have conducted exploratory and developmental research with broad application to the field of radiation sciences. As the only DoD facility dedicated to radiation research, AFRRI's Medical Radiobiology Advisory Team provides deployable medical and radiobiological subject matter expertise, advising commanders in the response to a U.S. nuclear weapon incident and other nuclear or radiological material incidents. AFRRI received the DoD Joint Meritorious Unit Award on February 17, 2004, for its exceptionally meritorious achievements from September 11, 2001 to June 20, 2003, in response to acts of terrorism and nuclear/radiological threats at home and abroad. In August 2009, the American Nuclear Society designated the institute a nuclear historic landmark as the U.S.'s primary source of medical nuclear and radiological research, preparedness and training. Since then, research has continued, and core areas of study include prevention, assessment and treatment of radiological injuries that may occur from exposure to a wide range of doses (low to high). AFRRI collaborates with other government entities, academic institutions, civilian laboratories and other countries to research the biological effects of ionizing radiation. Notable early research contributions were the establishment of dose limits for major acute radiation syndromes in primates, applicable to human exposures, followed by the subsequent evolution of radiobiology concepts, particularly the importance of immune collapse and combined injury. In this century, the program has been essential in the development and validation of prophylactic and therapeutic drugs, such as Amifostine, Neupogen®, Neulasta®, Nplate® and Leukine®, all of which are used to prevent and treat radiation injuries. Moreover, AFRRI has helped develop rapid, high-precision, biodosimetry tools ranging from novel assays to software decision support. New drug candidates and biological dose assessment technologies are currently being developed. Such efforts are supported by unique and unmatched radiation sources and generators that allow for comprehensive analyses across the various types and qualities of radiation. These include but are not limited to both 60Co facilities, a TRIGA® reactor providing variable mixed neutron and γ-ray fields, a clinical linear accelerator, and a small animal radiation research platform with low-energy photons. There are five major research areas at AFRRI that encompass the prevention, assessment and treatment of injuries resulting from the effects of ionizing radiation: 1. biodosimetry; 2. low-level and low-dose-rate radiation; 3. internal contamination and metal toxicity; 4. radiation combined injury; and 5. radiation medical countermeasures. These research areas are bolstered by an educational component to broadcast and increase awareness of the medical effects of ionizing radiation, in the mass-casualty scenario after a nuclear detonation or radiological accidents. This work provides a description of the military medical operations as well as the radiation facilities and capabilities present at AFRRI, followed by a review and discussion of each of the research areas., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

The Department of Energy conduced ten large-scale neutron irradiation experiments at Argonne National Laboratory between 1972 and 1989. Using a new approach to utilize experimental controls to determine whether a cross comparison between experiments was appropriate, we amalgamated data on neutron exposures to discover that fractionation significantly improved overall survival. A more detailed investigation showed that fractionation only had a significant impact on the death hazard for animals that died from solid tumors, but did not significantly impact any other causes of death. Additionally, we compared the effects of sex, age first irradiated, and radiation fractionation on neutron irradiated mice versus cobalt 60 gamma irradiated mice and found that solid tumors were the most common cause of death in neutron irradiated mice, while lymphomas were the dominant cause of death in gamma irradiated mice. Most animals in this study were irradiated before 150 days of age but a subset of mice was first exposed to gamma or neutron irradiation over 500 days of age. Advanced age played a significant role in decreasing the death hazard for neutron irradiated mice, but not for gamma irradiated mice. Mice that were 500 days old before their first exposures to neutrons began dying later than both sham irradiated or gamma irradiated mice., Competing Interests: The authors declare no competing interests. The corresponding author of this paper, Gayle E. Woloschak, is a section editor for PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

We implemented machine learning in the radiation biodosimetry field to quantitatively reconstruct neutron doses in mixed neutron + photon exposures, which are expected in improvised nuclear device detonations. Such individualized reconstructions are crucial for triage and treatment because neutrons are more biologically damaging than photons. We used a high-throughput micronucleus assay with automated scanning/imaging on lymphocytes from human blood ex-vivo irradiated with 44 different combinations of 0-4 Gy neutrons and 0-15 Gy photons (542 blood samples), which include reanalysis of past experiments. We developed several metrics that describe micronuclei/cell probability distributions in binucleated cells, and used them as predictors in random forest (RF) and XGboost machine learning analyses to reconstruct the neutron dose in each sample. The probability of "overfitting" was minimized by training both algorithms with repeated cross-validation on a randomly-selected subset of the data, and measuring performance on the rest. RF achieved the best performance. Mean R 2 for actual vs. reconstructed neutron doses over 300 random training/testing splits was 0.869 (range 0.761 to 0.919) and root mean squared error was 0.239 (0.195 to 0.351) Gy. These results demonstrate the promising potential of machine learning to reconstruct the neutron dose component in clinically-relevant complex radiation exposure scenarios.

The risk assessment quantities called lifetime attributable risk (LAR) and risk of exposure-induced cancer (REIC) are used to calculate the cumulative cancer incidence risks for astronauts, attributable to radiation exposure accumulated during long term lunar and Mars missions. These risk quantities are based on the most recently published epidemiological data on the Life Span Study (LSS) of Japanese A-bomb survivors, who were exposed to γ-rays and neutrons. In order to analyze the impact of a different neutron RBE on the risk quantities, a model for the neutron relative biological effectiveness (RBE) relative to gammas in the LSS is developed based on an older dataset with less follow-up time. Since both risk quantities are based on uncertain quantities, such as survival curves, and REIC includes deterministic radiation induced non-cancer mortality risks, modelled with data based on the general population, the risks for astronauts may not be optimally estimated. The suitability of these risk assessment measures for the use of cancer risk calculation for astronauts is discussed. The work presented here shows that the use of a higher neutron RBE than the value of 10, traditionally used in the LSS risk models, can reduce the risks up to almost 50%. Additionally, including an excess absolute risk (EAR) baseline scaling also increases the risks by between 0.4% and 8.1% for the space missions considered in this study. Using just an EAR model instead of an equally weighted EAR and excess relative risk (ERR) model can decrease the cumulative risks for the considered missions by between 0.4% and 4.1% if no EAR baseline scaling is applied. If EAR baseline scaling is included, the calculated risks with the EAR- and the mixed model, as well as the risks calculated with just the ERR model are almost identical and only small differences in the uncertainties are visible., (Copyright © 2020. Published by Elsevier B.V.)

A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine relative to radiation quality of mixed neutron:gamma radiations, dose rate, and exposure uniformity relative to selected reference radiation exposure has not been performed. The datasets for rhesus macaques exposure to mixed neutron:gamma radiation are used herein as a species comparative reference to the canine database. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and US HHS RePORT (2002-present). The total number of hits across all search sites was 3,077. Several referenced, unpublished, non-peer reviewed government reports were unavailable for review. Primary published studies using canines, beagles, and mongrels were evaluated to provide an informative and consistent review of mixed neutron:gamma radiation effects to establish the DRRs for the H-ARS. Secondary and tertiary studies provided additional information on the hematologic response or the effects on hematopoietic progenitor cells, radiation dosimetry, absorbed dose, and organ dose. The LD50/30 values varied with neutron quality, exposure aspect, and mixed neutron:gamma ratio. The reference radiation quality varied from 250 kVp or 1-2 MeV x radiation and Co gamma radiation. A summary of a published review of a data set describing the DRR in rhesus macaques for mixed neutron:gamma radiation exposure in the H-ARS is included for a comparative reference to the canine dataset. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in canines and young rhesus macaques exposed to mixed neutron:gamma radiations of variable energy relative to 250 kVp, 1-2 MeV x radiation and Co gamma, and uniform and non-uniform total-body irradiation without the benefit of medical management. The mixed neutron:gamma radiation showed an energy-dependent RBE of ~ 1.0 to 2.0 relative to reference radiation exposure within both species. A marginal database described the DRR for the gastrointestinal (GI)-ARS. Medical management showed benefit in both species relative to the mixed neutron:gamma as well as exposure to reference radiation. The DRR for the H-ARS was characterized by steep slopes and relative LD50/30 values that reflected the radiation quality, exposure aspect, and dose rate over a range in time from 1956-2012.

Purpose: Quinoline is formed by various natural compounds, such as alkaloids from the cinchona plant, which exhibit various biological activities, and is an important building material for the development of new drugs. Quinoline can be used in anti-radiation drug development but radiation interaction properties must be determined., Material and Methods: In this study, six types of synthesized quinoline derivatives were used. Fast neutron removal cross-section, mean free path, half value layer and transmission number were theoretically determined by using GEometry ANd Tracking 4 and FLUktuierende KAskade simulation codes for neutron shielding. Neutron dose absorption rates were determined using the 241 Am-Be fast neutron source and the Canberra NP series portable BF 3 gas proportional neutron detector. Gamma radiation shielding parameters were determined by using WinXCom and PSY-X/PSD software. Additionally, the genotoxic potentials of the derivatives were assessed by using the Ames/ Salmonella bacterial reversion assay., Results and Conclusions: Neutron shielding parameters such as removal cross-section, mean free path, half value layer and transmission number were theoretically determined for fast neutrons. To determine neutron absorption capacity of quinoline derivatives, neutron absorption, experiments were conducted. In addition, gamma radiation shielding parameters were calculated such as the mean free path (MFP), mass attenuation coefficient ( µ t), half value thickness layer (HVL) and effective atomic number (Zeff) in the energy range of 0.015-15 MeV. The results of the all quinoline derivatives have excellent fast neutron shielding power compared to ordinary concrete. In addition, all quinoline derivatives have been found to have the capacity to attenuate gamma radiation. Moreover, they absorb well in both types of radiation, do not cause secondary radiation, and they are genotoxically safe at the tested concentrations. This study has demonstrated that these products can be used as active ingredients for a drug to be developed against radiation.

Purpose: Cardiac implantable electronic devices (CIEDs) were believed to possess a tolerance dose to malfunction during radiotherapy. Although recent studies have qualitatively suggested neutrons as a cause of malfunction, numerical understanding has not been reached. The purpose of this work is to quantitatively clarify the contribution of secondary neutrons from out-of-field irradiation to the malfunction of CIEDs as well as to deduce the frequency of malfunctions until completion of prostate cancer treatment as a typical case., Materials and Methods: Measured data were gathered from the literature and were re-analyzed. Firstly, linear relationship for a number of malfunctions to the neutron dose was suggested by theoretical consideration. Secondly, the accumulated number of malfunctions of CIEDs gathered from the literature was compared with the prescribed dose, scattered photon dose, and secondary neutron dose for analysis of their correlation. Thirdly, the number of malfunctions during a course of prostate treatment with high-energy X-ray, passive proton, and passive carbon-ion beams was calculated while assuming the same response to malfunctions, where X-rays consisted of 6-MV, 10-MV, 15-MV, and 18-MV beams. Monte Carlo simulation assuming simple geometry was performed for the distribution of neutron dose from X-ray beams, where normalization factors were applied to the distribution so as to reproduce the empirical values., Results: Linearity between risk and neutron dose was clearly found from the measured data, as suggested by theoretical consideration. The predicted number of malfunctions until treatment completion was 0, 0.02 ± 0.01, 0.30 ± 0.08, 0.65 ± 0.17, 0.88 ± 0.50, and 0.14 ± 0.04 when 6-MV, 10-MV, 15-MV, 18-MV, passive proton, and passive carbon-ion beams, respectively, were employed, where the single model response to a malfunction of 8.6 ± 2.1 Sv - 1 was applied., Conclusions: Numerical understanding of the malfunction of CIEDs has been attained for the first time. It has been clarified that neutron dose is a good scale for the risk of CIEDs in radiotherapy. Prediction of the frequency of malfunction as well as discussion of the risk to CIEDs in radiotherapy among the multiple modalities have become possible. Because the present study quantitatively clarifies the neutron contribution to malfunction, revision of clinical guidelines is suggested., (© 2020 American Association of Physicists in Medicine.)

Proton therapy has shown dosimetric advantages over conventional radiation therapy using photons. Although the integral dose for patients treated with proton therapy is low, concerns were raised about late effects like secondary cancer caused by dose depositions far away from the treated area. This is especially true for neutrons and therefore the stray dose contribution from neutrons in proton therapy is still being investigated. The higher biological effectiveness of neutrons compared to photons is the main cause of these concerns. The gold-standard in neutron dosimetry is measurements, but performing neutron measurements is challenging. Different approaches have been taken to overcome these difficulties, for instance with newly developed neutron detectors. Monte Carlo simulations is another common technique to assess the dose from secondary neutrons. Measurements and simulations are used to develop analytical models for fast neutron dose estimations. This article tries to summarize the developments in the different aspects of neutron dose in proton therapy since 2017. In general, low neutron doses have been reported, especially in active proton therapy. Although the published biological effectiveness of neutrons relative to photons regarding cancer induction is higher, it is unlikely that the neutron dose has a large impact on the second cancer risk of proton therapy patients.

To simulate the space radiation environment astronauts are exposed to, most studies involve acute exposures but during a space mission there will be chronic (long-lasting) exposures. To address this knowledge gap, a neutron irradiator using a 252 Cf ( 252 Californium) source was used to generate a mixed field of neutrons and photons to simulate chronic, low dose rate exposures to high LET radiation. In the present study, we assessed the effects chronic neutron exposure starting at 60 days of age on behavioral and cognitive performance of BALB/c female and C3H male mice at 600 and 700 days of age as part of an opportunistic study that took advantage of the availability of neutron and sham-irradiated mice from a radiation carcinogenesis experiment. There were profound dose- and time point-dependent effects of chronic neutron exposure. At the 600-day time point, irradiated BALB/c female mice showed improved nest building at all three doses. At the 700-day, but not 600-day, time point slightly but significantly increased body weights were seen in C3H male mice exposed to 0.118 Gy. At the 600-day time point BALB/c female mice irradiated with 0.2 Gy did, like sham-irradiated, not show preferential exploration of the novel object that was seen in mice irradiated with 0.118 or 0.4 Gy. In C3H male mice exposed to 0.4 Gy and at the 600-day time point, increased measures of anxiety were observed on days 1 and 2 in the open field. Thus, different outcome measures show distinct dose-response relationships, with some anticipated to worsen performance during space missions, like increased measures of anxiety, while other anticipated to enhance performance, such as increased nest building and object recognition., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We monitored a physiological response in a neutron-exposed normal mouse brain using two imaging tools, [ 18 F]fluro-deoxy-D-glucose positron emission tomography ([ 18 F]FDG-PET) and diffusion weighted-magnetic resonance imaging (DW-MRI), as an imaging biomarker. We measured the apparent diffusion coefficient (ADC) of DW-MRI and standardized uptake value (SUV) of [ 18 F]FDG-PET, which indicated changes in the cellular environment for neutron irradiation. This approach was sensitive enough to detect cell changes that were not confirmed in hematoxylin and eosin (H&E) results. Glucose transporters (GLUT) 1 and 3, indicators of the GLUT capacity of the brain, were significantly decreased after neutron irradiation, demonstrating that the change in blood-brain-barrier (BBB) permeability affects the GLUT, with changes in both SUV and ADC values. These results demonstrate that combined imaging of the same object can be used as a quantitative indicator for in vivo pathological changes. In particular, the radiation exposure assessment of combined imaging, with specific integrated functions of [ 18 F]FDG-PET and MRI, can be employed repeatedly for noninvasive analysis performed in clinical practice. Additionally, this study demonstrated a novel approach to assess the extent of damage to normal tissues as well as therapeutic effects on tumors.

Results from archived (1986 and 1996) experiments were used to establish a baboon radiation-quality dose-response database with haematology biomarker time-course data following exposure to mixed-fields (i.e. neutron to gamma ratio: 5.5; dose: 0-8 Gy) and 60Co gamma-ray exposures (0-15 Gy). Time-course (i.e. 0-40 d) haematology changes for relevant blood-cell types for both mixed-field (neutron to gamma ratio = 5.5) and gamma ray alone were compared and models developed that showed significant differences using the maximum likehood ratio test. A consensus METREPOL-like haematology ARS (H-ARS) severity scoring system for baboons was established using these results. The data for mixed-field and the gamma only cohorts appeared similar, and so the cohorts were pooled into a single consensus H-ARS severity scoring system. These findings provide proof-of-concept for the use of a METREPOL H-ARS severity scoring system following mixed-field and gamma exposures., (Published by Oxford University Press 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Due to limitations of available human models for development of gene expression based radiation biodosimetry, many such studies have made use of mouse models. To provide a broad view of the gene expression response to irradiation in the mouse, we have exposed male C57BL/6 mice to 0, 1.5, 3, 6 or 10 Gy of gamma rays, sacrificing groups of the mice at 1, 2, 3, 5, or 7 days after exposure. We then profiled global gene expression in blood from individual mice using Agilent microarrays. In general, we found increasing numbers of genes differentially expressed with increasing dose, with more prolonged responses after the higher doses. Gene ontology analysis showed a similar pattern, with more biological processes enriched among the genes responding to higher doses, and at later times after exposure. Clustering the timecourse expression data using maSigPro identified four broad patterns of response, representing different gene ontology functions. The largest of these clusters included genes with initially decreased expression followed by increased expression at later times, a pattern of expression previously reported for several genes following neutron exposure. Another gene cluster showing consistent down regulation suggests genes useful for biodosimetry throughout the first week after exposure can be identified.

As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, the impacts of such exposures have only been studied in animals after acute exposures, using dose rates ∼1.5×10 5 higher than those actually encountered in space. Using a new, low dose-rate neutron irradiation facility, we have uncovered that realistic, low dose-rate exposures produce serious neurocognitive complications associated with impaired neurotransmission. Chronic (6 month) low-dose (18 cGy) and dose rate (1 mGy/d) exposures of mice to a mixed field of neutrons and photons result in diminished hippocampal neuronal excitability and disrupted hippocampal and cortical long-term potentiation. Furthermore, mice displayed severe impairments in learning and memory, and the emergence of distress behaviors. Behavioral analyses showed an alarming increase in risk associated with these realistic simulations, revealing for the first time, some unexpected potential problems associated with deep space travel on all levels of neurological function., (Copyright © 2019 Acharya et al.)

In the possible event of a detonation of an improvised nuclear device (IND), the immediate radiation would consist of both photons (gamma rays) and neutrons. Since neutrons generally have a high relative biological effectiveness (RBE) for most physiological end points, it is important to understand the effect that neutrons would have on the biodosimetry methods that are being developed for medical triage purposes. We previously compared the transcriptomic response in human blood after neutron and photon irradiation. In this study, we analyzed the effect of mixed-field-neutron-photon radiation on gene expression responses in human peripheral blood, to elucidate the neutron contribution in the setting of a radiation exposure from an IND detonation. We used four combinations of mixed neutron-photon exposures, with increasing percentages of neutrons, to a cumulative dose of 3 Gy. The mixed-field exposures consisted of 0%, 5%, 15% and 25% of neutrons, where 0% corresponds to 3 Gy of pure X rays. A maximum neutron exposure, corresponding to 83% neutrons (0.75 Gy) was also used in the study. Increases were observed in both the number and expression level of genes, with increasing percentages of neutrons from 0% to 25% in the mixed-field exposures. Gene ontology analysis showed an overall predominance of TP53 signaling among upregulated genes across all exposures. Some TP53 regulated genes, such as EDA2R , GDF15 and VWCE , demonstrated increased expression with increasing neutron percentages in mixed-field exposures. Immune response, specifically natural-killer-cell mediated signaling, was the most significant biological process associated with downregulated genes. We observed significant suppression of T-cell-mediated signaling in mixed-field exposures, which was absent in the response to pure photons. In this first study investigating gene expression in human blood cells exposed to mixed neutron-photon fields similar to an actual IND explosion, we have identified a number of genes responding to the 3 Gy dose that showed increasing expression as the neutron percentage increased. Such genes may serve as better indicators of the expected biological damage than a report of total physical dose, and thus provide more relevant information for treating physicians.

Neutron radiation is very harmful to both individual organisms and the environment. A n understanding of all aspects of both direct and indirect effects of radiation is necessary to accurately assess the risk of neutron radiation exposure. This review seeks to review current evidence in the literature for radiation-induced bystander effects and related effects attributable to neutron radiation. It also attempts to determine if the suggested evidence in the literature is sufficient to justify claims that neutron-based radiation can cause radiation-induced bystander effects. Lastly, the present paper suggests potential directions for future research concerning neutron radiation-induced bystander effects. Data was collected from studies investigating radiation-induced bystander effects and was used to mathematically generate pooled datasets and putative trends; this was done to potentially elucidate both the appearance of a conventional trend for radiation-induced bystander effects in studies using different types of radiation. Furthermore, literature review was used to compare studies utilizing similar tissue models to determine if neutron effects follow similar trends as those produced by electromagnetic radiation. We conclude that the current understanding of neutron-attributable radiation-induced bystander effects is incomplete. Various factors such as high gamma contamination during the irradiations, unestablished thresholds for gamma effects, different cell lines, energies, and different dose rates affected our ability to confirm a relationship between neutron irradiation and RIBE, particularly in low-dose regions below 100 mGy. It was determined through meta-analysis of the data that effects attributable to neutrons do seem to exist at higher doses, while gamma effects seem likely predominant at lower dose regions. Therefore, whether neutrons can induce bystander effects at lower doses remains unclear. Further research is required to confirm these findings and various recommendations are made to assist in this effort. With these recommendations, we hope that research conducted in the future will be better equipped to explore the indirect effects of neutron radiation as they pertain to biological and ecological phenomena., (Copyright © 2019 Elsevier Inc. All rights reserved.)

When assessing radiation-related risk among the atomic bomb survivors, choices in modeling approach can have an important impact on the results, which are then used to inform radiation protection standards throughout the world. The atomic bombings of Hiroshima and Nagasaki produced a mixed-field radiation exposure from two sources: neutrons and gamma rays. Neutrons are more densely ionizing and cause greater biological damage per unit absorbed dose, resulting in greater relative biological effectiveness (RBE) than gamma rays. To account for this, a combined weighted dose is typically calculated as the sum of the gamma-ray dose and 10 times the neutron dose in the Radiation Effects Research Foundation's reports of mortality, solid cancer incidence and other outcomes. In addition, the colon, which is often chosen as the whole-body representative organ in these analyses, is relatively deep in the body and therefore its dose calculation involves heavy body shielding of neutrons and a low neutron/gamma-ray ratio. With added follow-up and recently updated doses, we used a data-driven approach to determine the best-fitting neutron RBE for a range of organs of varying depth. Aggregated person-year tables of solid cancer incidence (1958-2009) from the Life Span Study were created with separate neutron and gamma-ray DS02R1 doses for several organs including breast, brain, thyroid, bone marrow, lung, liver and colon. Typical excess relative risk models estimating the linear effect of radiation dose were fitted using a range of neutron weights (1-250) to calculate combined dose for each organ, and model deviances were compared to assess fit. Furthermore, models using separate terms for gamma-ray and neutron dose were also examined, wherein the ratio of the neutron/gamma-ray linear terms indicated the best estimate of the RBE. The best-fitting RBE value for the traditional weighted colon dose was 80 [95% confidence interval (CI): 20-190], while the RBEs for other organs using weighted doses ranged from 25 to 60, with the best-fitting weights and confidence interval widths both incrementally increasing with greater depth of organ. Models using separate neutron- and gamma-ray-dose terms gave similar results to weighted linear combinations, with a neutron/gamma-ray term ratio of 79.9 (95% CI: 18.8-192.3) for colon. These results indicated that the traditionally modeled RBE of 10 may underestimate the effect of neutrons across the full dose range, although these updated estimates still have fairly wide confidence bounds. Furthermore, the colon is among the deepest of organs and may not be the best choice as a single surrogate organ dose, as it may minimize the role of the neutrons. Future work with more refined organ doses could shed more light on RBE-related information available in the Life Span Study data.

It is well known that neutrons have more damaging effects, with high relative biological effectiveness or a radiation weighting factor depending on neutron energy, compared to low-LET ionizing radiations. In the current work, we evaluated the contribution of the indirect effect induced by radicals for the purpose of studying the mechanisms of fast neutron effects or mechanisms of boron neutron capture therapy (BNCT) using relatively lower energy neutrons. Plasmid pBR322 DNA with a supercoiled structure was irradiated with fast neutrons (1-10 MeV) in the reactor core of the YAYOI research reactor at the University of Tokyo, and with thermalized neutrons passing through a phantom made of acrylic resin to simulate a human body. The single- and double-strand breaks (SSBs and DSBs) of the plasmid were evaluated from the numbers of its open circular and linear forms, respectively, detected using agarose gel electrophoresis. The number of supercoiled forms decreased exponentially with the absorbed dose of fast neutrons. The decrease was inhibited by dimethyl sulfoxide (DMSO) in a concentration-dependent manner. The contributions of the indirect effect to DNA strand breaks by fast neutrons and thermalized neutrons were calculated to be 50-65% which, while lower than the value for X rays, still accounts for the majority of the DNA strand breaks. In the case of thermalized neutrons, SSB and DSB yields were increased by the addition of boric acid. Moreover, an increased 10 B isotope concentration was found to increase the DSB/SSB ratio.

Background/aim: Neutrons are used as a type of high linear energy transfer (LET) radiation and they have stronger carcinogenic effects compared to low LET radiation. We sought to clarify the features of mammary carcinomas for which the incidence increases when these were exposed to neutron radiation., Materials and Methods: We compared mammary carcinomas from female Sprague-Dawley rats irradiated at 7 weeks of age with 0.485 Gy neutron beams or 0.5-Gy γ rays, with carcinomas of non-irradiated rats. Tumors were classified into luminal and non-luminal subtypes based on immunohistochemistry, while their copy number aberrations were determined using microarrays., Results: Neutrons and γ rays significantly increased the incidence of luminal carcinomas. The carcinomas in the three groups contained multiple aberrations affecting 46 genes for which mutations have been reported in human breast cancer., Conclusion: Neutrons and γ rays increase the incidence of luminal mammary carcinoma in rats, probably via genetic aberrations similar to those found in human breast cancer patients., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Nowadays, high-energy X-rays produced by medical linear accelerators (LINACs) are widely used in many Radiation Therapy (RT) centers. High-energy photons (> 8 MeV) produce undesired neutrons in the LINAC head which raise concerns about unwanted neutron dose to the patients and RT personnel. Regarding the significance of radiation protection in RT, it is important to evaluate photoneutron contamination inside the RT room. Unfortunately, neutron dosimeters used for this purpose have limitations that can under the best conditions cause to > 10% uncertainty. In addition to this uncertainty, the present Monte Carlo (MC) study introduces another uncertainty in measurements (nearly up to 20%) when neutron ambient dose equivalent (H n * (10)) is measured at the patient table or inside the maze and the change in neutron energy is ignored. This type of uncertainty can even reach 35% if H n * (10) is measured by dosimeters covered by a layer of 10 B as converter. So, in these cases, neglecting the change in neutron energy can threaten the credibility of measured data and one should attend to this energy change in order to reduce measurement uncertainty to the possible minimum. This study also discusses the change in neutron spectra and H n * (10) at the patient table caused by removing a typical RT room from MC simulations. Under such conditions, neutron mean energy (Ē n ) overestimated by 0.2-0.4 MeV at the patient table. Neutron fluence (φ n ) at the isocenter (IC) was underestimated by 23-54% for different field sizes that caused H n * (10) to be miscalculated up to 24%. This finding informs researchers that for accurate evaluation of H n * (10) at the patient table, simulating the RT room is an effective parameter in MC studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Radiation therapy is commonly used to treat head and neck malignancies. While there is abundant research regarding photon radiation therapy, literature on neutron radiotherapy (NRT) and oral complications is limited. This study aims to determine: (1) the 6-year and 10-year locoregional control and survival rates, (2) factors associated with locoregional control and survival and (3) the frequency of oral complications in patients undergoing NRT for salivary gland malignancies., Materials and Methods: This is a retrospective cohort study. The sample was composed of patients with salivary gland malignancies treated with NRT between 1997 and 2010. Data were extracted from patient charts, telephone surveys, and social security records. Multivariate competing risk and Cox regression models were used to assess predictors of locoregional control and survival., Results: The sample was composed of 545 subjects with a mean age of 54.2 years (±16). The predominant tumor and location were adenoid cystic carcinoma (47%) and the parotid (56%). Multivariate analysis indicated that positive surgical margins, biopsied/inoperable malignancies, neck involvement, and lymphovascular invasion were prognostic risk factors associated with decreased survival. The 6- and 10-year locoregional control rates were 84% and 79%. The 6- and 10-year survival rates were 72% and 62%. Osteoradionecrosis developed in 3.4% of subjects., Conclusions: The 6- and 10-year locoregional control and survival rates compare favorably to rates reported for conventional photon radiation. Osteoradionecrosis rates were comparable to that of photon radiation treatment (2-7%). Given the potential benefits of NRT, healthcare professionals should be educated regarding its indications and oral complications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: The recent rapid increase of hadron therapy applications requires the development of high performance, reliable in vivo models for preclinical research on the biological effects of high linear energy transfer (LET) particle radiation., Aim: The aim of this paper was to test the relative biological effectiveness (RBE) of the zebrafish embryo system at two neutron facilities., Material and Methods: Series of viable zebrafish embryos at 24-hour post-fertilization (hpf) were exposed to single fraction, whole-body, photon and neutron (reactor fission neutrons () and (p (18 MeV)+Be,  = 3.5 MeV) fast neutron) irradiation. The survival and morphologic abnormalities of each embryo were assessed at 24-hour intervals from the point of fertilization up to 192 hpf and then compared to conventional 6 MV photon beam irradiation results., Results: The higher energy of the fast neutron beams represents lower RBE (ref. source LINAC 6 MV photon). The lethality rate in the zebrafish embryo model was 10 times higher for 1 MeV fission neutrons and 2.5 times greater for p (18 MeV)+Be cyclotron generated fast neutron beam when compared to photon irradiation results. Dose-dependent organ perturbations (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, pericardial edema and inhibition of yolk sac resorption) and microscopic (marked cellular changes in eyes, brain, liver, muscle and the gastrointestinal system) changes scale together with the dose response., Conclusion: The zebrafish embryo system is a powerful and versatile model for assessing the effect of ionizing radiation with different LET values on viability, organ and tissue development.

Linear accelerators (LINACs) are widely applied in radiotherapy for their versatility and flexibility. Monte Carlo simulations were made to find the neutron and photon spectra at the isocenter (IC) of a LINAC operating at 10, 15, 18, and 24 MV by the MCNPX code. A detailed model of the LINAC head, consisting of flattening filter, secondary collimator, primary collimator, and multi-leaf collimator were used in the calculations. The effect of eliminating any of these components on contamination of a neutron spectrum and a photon spectrum was assessed. Photon and neutron ambient equivalent doses were found, and comparisons were made for the various structures. Lethargy neutron spectra at the IC were compared with spectra computed with the function reported by Tosi et al., which describes well neutron spectra for the energy region beyond 1 MeV, although tending to undervalue energy spectra below 1 MeV. The findings show that the photon and neutron fluences are enhanced when eliminating a LINAC component. The neutron and photon doses increased except when removing the primary collimator., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

According to an analysis of the Life Span Study cohort data conducted by the Radiation Effects Research Foundation in Hiroshima and Nagasaki, the sex-averaged excess relative risk (ERR) of all solid cancers was 0.42 Gy-Eq-1. On the other hand, analysis of the atomic bomb survivors (ABS) cohort data at Hiroshima University indicated the ERR value was 0.28 Gy-Eq-1 in Hiroshima. In both cases, initial radiation doses were derived from the dosimetry system DS02, in which the relative biological effectiveness (RBE) of neutrons was assumed to be a constant value of 10. To clarify the validity of the RBE, the authors investigated the possibility of different contributions of neutrons by using the ABS. Although there were no statistically significant differences among the estimated value of RBE (=65) and the ordinal value (=10), the corresponding ERR decreased by 30%, which might affect the interpretation of radiation health assessments.

The risks associated with exposure to external fields of ionising radiation are important to quantify in order to provide guidance towards public and worker protection. In Publication 116 of 2010, the International Commission on Radiological Protection (ICRP) published adult male and female fluence-to-dose coefficients (henceforth referred to as dose coefficients) for external exposures to six types of idealised neutron fields. However, ICRP 116 dose coefficients are not appropriate for applications involving children due to their smaller body weight and stature. Our current work details dose coefficient calculations for children and young adolescents using the UF-NCI pediatric hybrid phantoms at all neutron energies considered in ICRP 116 (0.001 eV to 10 GeV); those dose coefficients with energy up to 150 MeV are discussed. The hybrid UF-NCI phantoms are divided into five separate age groups: newborn, 1, 5, 10, and 15 years. For these phantoms, we calculated dose coefficients for the six idealised neutron fields for 28 organs, two bone tissues, and the overall whole body effective dose. All calculations were performed using the MCNP6 radiation transport code. To validate our methodology, we first calculated dose coefficients for the ICRP adult male and female phantoms and confirmed our ability to reproduce the values published within ICRP 116. The same methodology was then applied to calculate dose coefficients for the UF-NCI pediatric phantoms. Energy-dependent trends were observed in the neutron dose coefficients for pediatric phantoms: below 100 keV, dose increases with phantom age (a proxy for body size); however, above 100 keV, the opposite trend was observed. Comparisons between field geometries showed varying trends depending on the location of the organ within the body. Explanations for these trends are also explored within. Our results are the first comprehensive set of neutron dose coefficients derived for children and young adolescents using the newest generation of hybrid phantoms. The primary application of the pediatric neutron dose coefficients presented in this work will be for a planned effort to update the dosimetry for the Japanese atomic bomb survivors.

Neutrons as a one of the by-products of high-energy photons in radiotherapy increase the patient's risks and could cause secondary cancers. Therefore, a new corrected simplified model for linac head was introduced to calculate equivalent (H) and absorbed (D) doses in different tissues/organs of a phantom model. The photoneutron spectrum calculated with this model was in agreement with the spectrum obtained by using a detailed linac´s head model having all components. Besides, an anthropomorphic phantom was irradiated under different gantry angles of the corrected simplified model aiming to emulate 15, 18, 20, and 25MV Siemens linacs. The results indicated that tissues which were within the treatment field received more dose than others. Furthermore, tissues which were in the vicinity of each other and the same depth in the phantom nearly received the same doses. Finally, fatal secondary cancer risk was also studied., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

For passive scattering proton therapy systems, neutron contamination is the main concern both from an occupational and patient safety perspective. The Mevion S250 compact proton therapy system is the first of its kind, offering an in-room cyclotron design which prompts more concern for shielding assessment. The purpose of this study was to accomplish an in-depth evaluation of both the shielding design and in-room neutron production at our facility using both Monte Carlo simulation and measurement. We found that the shielding in place at our facility is adequate, with simulated annual neutron ambient dose equivalents at 30 cm outside wall/door perimeter ranging from background to 0.07 mSv and measured dose equivalents ranging from background to 0.06 mSv. The in-room measurements reveal that the H*/D decreases when the distance from isocenter and field size increases. Furthermore, the H*/D generally increases when the angle around isocenter increases. Our results from in-room measurements show consistent trends with our Monte Carlo model of the Mevion system., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Natural background radiation of Earth and cosmic rays played a relevant role during the evolution of living organisms. However, how chronic low doses of radiation can affect biological processes is still unclear. Previous data have indicated that cells grown at the Gran Sasso Underground Laboratory (LNGS, L'Aquila) of National Institute of Nuclear Physics (INFN) of Italy, where the dose rate of cosmic rays and neutrons is significantly reduced with respect to the external environment, elicited an impaired response against endogenous damage as compared to cells grown outside LNGS. This suggests that environmental radiation contributes to the development of defense mechanisms at cellular level. To further understand how environmental radiation affects metabolism of living organisms, we have recently launched the FLYINGLOW program that aims at exploiting Drosophila melanogaster as a model for evaluating the effects of low doses/dose rates of radiation at the organismal level. Here, we will present a comparative data set on lifespan, motility and fertility from different Drosophila strains grown in parallel at LNGS and in a reference laboratory at the University of L'Aquila. Our data suggest the reduced radiation environment can influence Drosophila development and, depending on the genetic background, may affect viability for several generations even when flies are moved back to normal background radiation. As flies are considered a valuable model for human biology, our results might shed some light on understanding the effect of low dose radiation also in humans., (© 2017 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to quantify the relative neutron damage induced in CIEDs from clinical 18 MV photon beams for varying field sizes, depths, and off axis distances., Methods and Materials: Damage was assessed using silicon damage response functions and ICRP neutron dose conversion factors in MCNPX. Particular attention was devoted to the modelling of the Varian 2100C/D linear accelerator to ensure accurate contamination neutron spectra. Neutron dose, fluence and relative damage to CIEDs was calculated., Results: CIED damage from neutrons is related to the neutron dose rather than the neutron fluence. As field size increases, the region of high damage probability extends to a greater distance beyond the edge of the field than with smaller fields. At a distance greater than 50 cm or from the central axis or a depth deeper than 10 cm, the probability of damage is less than 10% of the central axis damage probability for all field sizes., Conclusions: Clinically, increasing the depth or the distance from the central axis to the CIED will reduce the probability of damage from neutrons. Care must be taken when treating large fields as the overall probability of damage increase as does the distance the higher probability of damage extends beyond the field edge., (© 2017 American Association of Physicists in Medicine.)

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

Background: Out-of-field organs can be affected by secondary radiations originating from high energy linear accelerators, leading to an increased risk of carcinogenesis. The aim of this work was to determine the risk of second primary cancers (SPC) in the organs distal to the prostate during 3D conformal radiotherapy., Materials and Methods: Based on previously measured peripheral photon and neutron doses in a Rando phantom using an 18MV photon beam, SPC risks in the out-of-field organs were estimated using the linear-no-threshold and the competitive risk models. Whole body as well as organ specific risk coefficients were used to calculate the SPC risks in order to estimate upper and lower risk limits, given the uncertainties associated with the coefficients., Results: The corresponding estimated average SPC risks ranged from 1.5±0.3% for thyroid to 4.5±4.2% for colon using whole body risk coefficients and 0.12±0.03% and 1.45±1.34%, respectively, using organ specific risk coefficients. The linear-no-threshold and the competitive risk models resulted in the same risk estimates (within the estimated errors) in the dose range received by out-of-field organs (≤1Gy). Distally located organs such as lungs, oesophagus, and thyroid received higher neutron versus photon dose., Conclusions: The findings have important radiation protection implications when using high energy linear accelerators, as radiation protective measures could be employed to minimize the secondary out-of-field radiation for patients undergoing high energy external beam irradiation of the prostate., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: As there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus. The risk for the development of secondary malignant neoplasms might be significantly increased due to exposure of healthy tissue outside of the target field to secondary neutrons, in particular in proton therapy. Thus far, the radiobiological effects of these neutrons and a comparison with photons on normal breast cells have not been sufficiently characterised., Methods: MCF10A cells were irradiated with doses of up to 2 Gy with neutrons of different energy spectra and X-rays for comparison. The biological effects of neutrons with a broad energy distribution (n  > = 5.8 MeV), monoenergetic neutrons (1.2 MeV, 0.56 MeV) and of the mixed field of gamma's and secondary neutrons (n  > = 70.5 MeV) produced by 190 MeV protons impinging on a water phantom, were analysed. The clonogenic survival and the DNA repair capacity were determined and values of relative biological effectiveness were compared. Furthermore, the influence of radiation on the sphere formation was observed to examine the radiation response of the potential fraction of stem like cells within the MCF10A cell population., Results: X-rays and neutrons caused dose-dependent decreases of survival fractions after irradiations with up to 2 Gy. Monoenergetic neutrons with an energy of 0.56 MeV had a higher effectiveness on the survival fraction with respect to neutrons with higher energies and to the mixed gamma - secondary neutron field induced by proton interactions in water. Similar effects were observed for the DNA repair capacity after exposure to ionising radiation (IR). Both experimental endpoints provided comparable values of the relative biological effectiveness. Significant changes in the sphere formation were notable following the various radiation qualities., Conclusion: The present study compared the radiation response of MCF10A cells after IR with neutrons and photons. For the first time it was shown that monoenergetic neutrons with energies around 1 MeV have stronger radiobiological effects on normal human breast cells with respect to X rays, to neutrons with a broad energy distribution (n  > = 5.8 MeV), and to the mixed gamma - secondary neutron field given by interactions of 190 MeV protons in water. The results of the present study are highly relevant for further investigations of radiation-induced carcinogenesis and are very important in perspective for a better risk assessment after secondary neutron exposure in the field of conventional and proton radiotherapy.

The increased threat of terrorism across the globe has raised fears that certain groups will acquire and use radioactive materials to inflict maximum damage. In the event that an improvised nuclear device (IND) is detonated, a potentially large population of victims will require assessment for radiation exposure. While photons will contribute to a major portion of the dose, neutrons may be responsible for the severity of the biologic effects and cellular responses. We investigated differences in response between these two radiation types by using metabolomics and lipidomics to identify biomarkers in urine and blood of wild-type C57BL/6 male mice. Identification of metabolites was based on a 1 Gy dose of radiation. Compared to X rays, a neutron spectrum similar to that encountered in Hiroshima at 1-1.5 km from the epicenter induced a severe metabolic dysregulation, with perturbations in amino acid metabolism and fatty acid β-oxidation being the predominant ones. Urinary metabolites were able to discriminate between neutron and X rays on day 1 as well as day 7 postirradiation, while serum markers showed such discrimination only on day 1. Free fatty acids from omega-6 and omega-3 pathways were also decreased with 1 Gy of neutrons, implicating cell membrane dysfunction and impaired phospholipid metabolism, which should otherwise lead to release of those molecules in circulation. While a precise relative biological effectiveness value could not be calculated from this study, the results are consistent with other published studies showing higher levels of damage from neutrons, demonstrated here by increased metabolic dysregulation. Metabolomics can therefore aid in identifying global perturbations in blood and urine, and effectively distinguishing between neutron and photon exposures.

Concrete has been used as a traditional biological shielding material. High hydrogen content in concrete also effectively attenuates high-energy fast neutrons. However, concrete does not have strong protection against thermal neutrons because of the lack of boron compound. In this research, boron was added in the form of borosilicate glass powder to increase the neutron shielding property of cement mortar. Borosilicate glass powder was chosen in order to have beneficial pozzolanic activity and to avoid deleterious expansion caused by an alkali-silica reaction. According to the experimental results, borosilicate glass powder with an average particle size of 13µm showed pozzolanic activity. The replacement of borosilicate glass powder with cement caused a slight increase in the 28-day compressive strength. However, the incorporation of borosilicate glass powder resulted in higher thermal neutron shielding capability. Thus, borosilicate glass powder can be used as a good mineral additive for various radiation shielding purposes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To use the 53BP1 foci assay to detect DNA double-strand breaks induced by fractionated neutron beam irradiation of normal cells., Materials and Methods: The Kyoto University Research Reactor heavy-water facility and gamma-ray irradiation system were used as experimental radiation sources. After fixation of Chinese Hamster Ovary cells with 3.6% formalin, immunofluorescence staining was performed. Number and size of foci were analyzed using ImageJ software., Results: Fractionated neutron irradiation induced 25% fewer 53BP1 foci than single irradiation at the same dose. By contrast, gamma irradiation induced 30% fewer 53BP1 foci than single irradiation at the same dose. Fractionated neutron irradiation induced larger foci than gamma irradiation, raising the possibility that persistent unrepaired DNA damage was amplified due to the high linear energy transfer component in the neutron beam., Conclusion: Unrepaired cluster DNA damage was more prevalent after fractionated neutron irradiation than after gamma irradiation., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

During space missions, astronauts are exposed to a stream of energetic and highly ionizing radiation particles that can suppress immune system function, increase cancer risks and even induce acute radiation syndrome if the exposure is large enough. As human exploration goals shift from missions in low-Earth orbit (LEO) to long-duration interplanetary missions, radiation protection remains one of the key technological issues that must be resolved. In this work, we introduce the NEUtron DOSimetry & Exploration (NEUDOSE) CubeSat mission, which will provide new measurements of dose and space radiation quality factors to improve the accuracy of cancer risk projections for current and future space missions. The primary objective of the NEUDOSE CubeSat is to map the in situ lineal energy spectra produced by charged particles and neutrons in LEO where most of the preparatory activities for future interplanetary missions are currently taking place. To perform these measurements, the NEUDOSE CubeSat is equipped with the Charged & Neutral Particle Tissue Equivalent Proportional Counter (CNP-TEPC), an advanced radiation monitoring instrument that uses active coincidence techniques to separate the interactions of charged particles and neutrons in real time. The NEUDOSE CubeSat, currently under development at McMaster University, provides a modern approach to test the CNP-TEPC instrument directly in the unique environment of outer space while simultaneously collecting new georeferenced lineal energy spectra of the radiation environment in LEO.

Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include 187 W, 63 Zn, 56 Mn, 24 Na and 28 Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 μSv at the patient location. This can be further reduced to 65 μSv by closing the jaws before re-entering the treatment bunker., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 μSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure., (© 2016 The Authors.)

Background: In the last decade, a number of studies were published showing links between cardiovascular events such as stroke (CVA), acute myocardial infarction (AMI), sudden cardiac death (SCD) and cosmic ray activity (CRA) marker neutron activity on the Earth's surface (imp/min). A number of concomitant studies described air pollution fine particles as a similar risk factor. It is not clear which way each of the mentioned factors acts on the way of affecting the human body. The aim of this study is to present separate data of these two factors as risk factors and to discuss the possibility of seeing the nanoparticles polluting our air as carriers of neutrons on their way to the human cardiovascular system., Methods: Many studies of our groups and groups studying air pollution effects were revised, and the possibility of combined action of both factors was considered., Results: It is known that neutrons on the Earth surface are the markers of CRA. CRA is inversely related to space weather parameters such as solar (SA) and geomagnetic activity. The presumed way of biological action of neutrons is connection with H+ and, as protons, attack on our cells and tissues. The way of action of nanoparticles is explained by specific physical and chemical action of the materials they represent. It is a strong possibility that one way to connect H radicals in the human body is that particles are neutron carriers and can be absorbed in different parts of the body and then affect the systems of human body., Conclusions: The combined action of CRA (neutron) activity is a possible way of affecting the environment. The precise mechanism of this cooperative action demands additional studies.

A neutron irradiation cavity for in vivo neutron activation analysis (IVNAA) to detect manganese, aluminum, and other potentially toxic elements in human hand bone has been designed and its dosimetric specifications measured. The neutron source is a customized deuterium-deuterium neutron generator that produces neutrons at 2.45 MeV by the fusion reaction 2H(d, n)3He at a calculated flux of 7 × 10(8) ± 30% s(-1). A moderator/reflector/shielding [5 cm high density polyethylene (HDPE), 5.3 cm graphite and 5.7 cm borated (HDPE)] assembly has been designed and built to maximize the thermal neutron flux inside the hand irradiation cavity and to reduce the extremity dose and effective dose to the human subject. Lead sheets are used to attenuate bremsstrahlung x rays and activation gammas. A Monte Carlo simulation (MCNP6) was used to model the system and calculate extremity dose. The extremity dose was measured with neutron and photon sensitive film badges and Fuji electronic pocket dosimeters (EPD). The neutron ambient dose outside the shielding was measured by Fuji NSN3, and the photon dose was measured by a Bicron MicroREM scintillator. Neutron extremity dose was calculated to be 32.3 mSv using MCNP6 simulations given a 10-min IVNAA measurement of manganese. Measurements by EPD and film badge indicate hand dose to be 31.7 ± 0.8 mSv for neutrons and 4.2 ± 0.2 mSv for photons for 10 min; whole body effective dose was calculated conservatively to be 0.052 mSv. Experimental values closely match values obtained from MCNP6 simulations. These are acceptable doses to apply the technology for a manganese toxicity study in a human population.

Purpose: Second primary malignancies (SPMs) are among the most serious late adverse effects after radiotherapy experienced over time by the increasing population of cancer survivors worldwide. The study aim was to determine the rate and distribution of SPMs for neutron- and photon-emitting brachytherapy (BT) sources for patients treated for cervical cancer., Methods and Materials: The cohort comprised 662 patients with invasive cervical cancer (Stages IIB and IIIB) and contributed 5,224 patient-years (PY) of observation. These patients were treated by radiotherapy during the 1989-1999 year period with cobalt-60 source ((60)Co) teletherapy. The first group of patients (N = 375; 3,154 PY) received high-dose-rate (HDR) californium-252 source ((252)Cf) BT, whereas the second group (N = 287; 2,070 PY) received HDR (60)Co BT., Results: Over a 25-year period, 35 SPMs were observed, amounting to 5.3% of all observed patients: in 16 (2.4%) heavily, 2 (0.3%) moderately, 14 (2.1%) lightly irradiated body sites, and 3 (0.5%) other sites. Of these, 21 cases (5.6%) were observed in the HDR (252)Cf BT group, whereas 14 cases (4.9%) were observed in the HDR (60)Co BT group. Exposures received during (60)Co teletherapy and HDR BT with either (252)Cf or (60)Co had statistically equivalent (p = 0.68) effects on SPM development., Conclusions: Cure rates are improving, and therefore, there are more long-term survivors from cervical cancer. This study shows no significant difference in rates or distribution of SPMs in women treated with neutron BT compared with photon BT (p = 0.68). After reviewing related literature and our research results, it is evident that a detailed investigation of SPM frequency, localization, and dose to adjacent organs is a suitable topic for further research., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Human health is affected by space weather component [solar (SA), geomagnetic (GMA), cosmic ray (CRA) - neutrons, space proton flux] activity levels. The aim of this study was to check possible links between timing of human (both genders) monthly deaths distribution and space weather activity., Methods: Human deaths distribution in the Republic of Lithuania from 1989 to 2013 (25 years, i.e., 300 consecutive months) was studied, which included 1,050,503 deaths (549,764 male, 500,739 female). Pearson correlation coefficients (r) and their probabilities (p) were obtained for years: months 1-12, sunspot number, smoothed sunspot number, solar flux (2800 MGH, 10.7 cm), adjusted solar flux for SA; A, C indices of GMA; neutron activity at the earth's surface (imp/min) for CRA. The cosmophysical data were obtained from space science institutions in the USA, Russia and Finland. The mentioned physical parameters were compared with the total number of deaths, deaths from ischemic heart disease (n=376,074), stroke (n=132,020), non-cardiovascular causes (n=542,409), accidents (n=98,805), traffic accidents (n=21,261), oncology (n=193,017), diabetes mellitus (n=6631) and suicide (n=33,072)., Results: Space factors were interrelated as follows for the considered period: CRA was inversely related to SA and GMA, CRA/SA (r=-0.86, p>0.0001), CRA/GMA (r=-0.70, p<0.0001); SA and GMA were correlated (r=0.50, p<0.0001). The total deaths distribution was inversely related to SA (r=-0.31, p<0.0001) and correlated with CRA (neutron) activity (r=0.234, p<0.0001). Ischemic heart disease (IHD) deaths (most at home) show a drop yearly (r=-0.2551), more for men. It was correlated with GMA for the total IHD population and men. Stroke deaths were inversely related to SA (r=-0.38, p<0.0001) and correlated with CRA (r=0.41, p<0.0001) and year (r=0.49, p<0.0001), showing a steady rise. The IHD/stroke deaths ratio was negatively correlated with the years of observation (r=-0.754, p=0.0001). Non-cardiovascular deaths were inversely related to SA (r=-039, p<0.0001) and correlated with CRA (r=0.263, p<0.0001). Oncology deaths that now are dominating in many places were inversely related to SA (r=-0.475, p<0.0001) and correlated with CRA (r=0.426, p<0.0001). Suicide showed a drop with years (r=-0.29, p<0.0001), possibly related to excessive immigration of young population (18-34 years) in the last decade and correlated with two of three GMA indices. Traffic accidents were correlated with SA and GMA (r=0.392-0.461, p<0.0001) and inversely related to CRA (r=-0.436)., Conclusions: Most groups of deaths are related to space weather component activity. Extreme levels of activities of both groups (SA, GMA, and opposite CRA - neutron) are related to some health risks. In the considered period, there were relatively few GMA storms and low GMA was dominating, accompanied by higher CRA (neutron) activity. The ways of action of the components of space weather on the human body need additional studies. There is a special need for the prevention of rising cerebral vascular accidents and oncology malignancies as the causes of death.

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)