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Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

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Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

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Abstract

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes [1]. The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarizes several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukaemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modeling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognizes that the risks from LD/LDR are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

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... Comprehensive and authoritative reviews of ionizing radiation consistently conclude that the linear no threshold dose-response (sometimes with slope adjustments for low dose or low-dose rate) is the most appropriate and protective model for cancers following exposure to IR (Ruhm et al. 2016;Shore et al. 2018). Low power limits precise estimations of the dose-response in people exposed to low doses (below approximately 0.1 Gy) of mixed or low LET IR like the atomic bomb or medical radiation (Grant et al. 2017;Ozasa et al. 2012;Ruhm et al. 2016;Shore et al. 2018;Suzuki and Yamashita 2012), but solid cancer dose-response in the atomic bomb Life Span Study (LSS) cohort is not significantly different from linear (Furukawa et al. 2016;Grant et al. 2017;Preston et al. 2007). ...
... Comprehensive and authoritative reviews of ionizing radiation consistently conclude that the linear no threshold dose-response (sometimes with slope adjustments for low dose or low-dose rate) is the most appropriate and protective model for cancers following exposure to IR (Ruhm et al. 2016;Shore et al. 2018). Low power limits precise estimations of the dose-response in people exposed to low doses (below approximately 0.1 Gy) of mixed or low LET IR like the atomic bomb or medical radiation (Grant et al. 2017;Ozasa et al. 2012;Ruhm et al. 2016;Shore et al. 2018;Suzuki and Yamashita 2012), but solid cancer dose-response in the atomic bomb Life Span Study (LSS) cohort is not significantly different from linear (Furukawa et al. 2016;Grant et al. 2017;Preston et al. 2007). Multiple epidemiological studies of specific cancer sites and total solid cancer following in utero and childhood exposure and in atomic bomb, nuclear worker, and population studies also support significant effects at low doses (Cohen Uncertainties arise from the smaller effects of RONS on DNA damage compared with ionizing radiation. ...
... Although total solid cancers have a linear dose-response, dose-response shape differs by tumor site and sex (Grant et al. 2017;Ozasa et al. 2012;Shore et al. 2018;Suzuki and Yamashita 2012). In males, total tumors and some specific tumor sites have upwardly curving dose-responses with shallower dose-response at low vs high doses, while total tumors in females and sex-specific tumors (combined across sexes) have linear dose-responses (Grant et al. 2017;Sasaki et al. 2014). ...
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Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose–response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of “background” induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.
... The mean LAR and LFR according to age, sex, and the frequency of exposures (number of CBCT procedures) under median and maximum exposure settings are shown in Tables 3 and 4, respectively. Children (5 and 10 years old) demonstrated a higher cancer risk than did adults (20,30, and 40 years old). For median exposure settings, the LFRs were 1.1-16.4% for children and 0.1-2.0% ...
... Although there are controversies regarding radiation risk estimation, the LNT model is currently the most widely accepted model for explaining the radiation dose-response relationship based on current epidemiological data. 30 Thus, the cancer risk from diagnostic CBCT imaging is affected by age, sex, machine parameters, and the number of exposures. Our results indicate an increased risk of cancer due to CBCT performed for orthodontic purposes, with the risk being higher for children and females. ...
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Objective: To estimate the projected cancer risk attributable to diagnostic cone-beam computed tomography (CBCT) performed under different exposure settings for orthodontic purposes in children and adults. Methods: We collected a list of CBCT machines and their specifications from 38 orthodontists. Organ doses were estimated using median and maximum exposure settings of 105 kVp/156.8 mAs and 130 kVp/200 mAs, respectively. The projected cancer risk attributable to CBCT procedures performed 1-3 times within 2 years was calculated for children (aged 5 and 10 years) and adult (aged 20, 30, and 40 years) male and female patients. Results: For maximum exposure settings, the mean lifetime fractional ratio (LFR) was 14.28% for children and 0.91% for adults; this indicated that the risk to children was 16 times the risk to adults. For median exposure settings, the mean LFR was 5.25% and 0.58% for children and adults, respectively. The risk of cancer decreased with increasing age. For both median and maximum exposure settings, females showed a higher risk of cancer than did males in all age groups. Cancer risk increased with an increase in the frequency of CBCT procedures within a given period. Conclusions: The projected dental CBCT-associated cancer risk spans over a wide range depending on the machine parameters and image acquisition settings. Children and female patients are at a higher risk of developing cancer associated with diagnostic CBCT. Therefore, the use of diagnostic CBCT should be justified, and protective measures should be taken to minimize the harmful biological effects of radiation.
... The health effects of the corresponding low dose/low dose rate exposures are uncertain (Prasad et al. 2004;Mullenders et al. 2009;Dauer et al. 2010;Shore 2014;Shore et al. 2018Shore et al. , 2019. Much of the relevant scientific data comes from populations subjected to distinct exposure conditions, such as those resulting from nuclear bombings (Diaz-Maurin 2018). ...
... Much of the relevant scientific data comes from populations subjected to distinct exposure conditions, such as those resulting from nuclear bombings (Diaz-Maurin 2018). Recent epidemiological studies of populations exposed to low dose/low dose rate radiation have helped to address this shortcoming, but further research is needed (Shore et al. 2018(Shore et al. , 2019. This scientific uncertainty makes it challenging to address any risk to the public that might arise from such contamination, and to communicate that risk to the affected public. ...
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Environmental contamination, a legacy of industrial activity borne by numerous sites around the world, poses health risks for surrounding communities and presents serious cleanup challenges. One such site, the Santa Susana Field Laboratory (SSFL), served as an aerospace and nuclear energy research facility for over 50 years, during which time radioactive and other hazardous materials were unintentionally and intentionally released into the surrounding environment. These releases, including the partial meltdown of a sodium reactor, were hidden from the public for three decades. The site is now located in suburban Los Angeles, with 730,000 people living within a 10-mile radius. This paper evaluates the technical and social challenges underlying site cleanup at SSFL, including a complex geological setting, uncertain contaminant information, and a convoluted, evolving regulatory framework. These challenges, paired with historical secrecy on the part of responsible organizations and unclear layers of responsibility, have led to uncertainty and distrust within the surrounding community. Lessons learned from other remediated sites are assessed and recommendations for the SSFL cleanup are provided.
... Tissue weighting factors, based on population-averaged values, as used in the calculation of E, make E no more a reliable indicator of individual detriment than population-based organ-specific factors [10]. In the current paradigm of radiation protection, the known relationship between dose and risk at higher radiation dose is assumed to extrapolate linearly to that at lower dose, and children are considered to be at greater risk of developing radiation-induced tumors due to their life expectancy and higher radiosensitivity of select tissues [7,[10][11][12]. The basis for the belief of relatively higher risk for children demonstrated in a report by the National Research Council is challenged by some in light of their view that the risks at low radiation doses such as those incurred during medical imaging procedures are not unequivocally supported by current epidemiological data [13,14]. ...
... Patients were divided into five groups according to age at the time of the examination: less than 1 year old (< 1), one to 5 years old (1-5), six to 10 years old (6-10), 11 to 15 years old (11)(12)(13)(14)(15), and 16 to 17 years old (16,17). ...
Article
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Background: Organ absorbed doses and effective doses can be used to compare radiation exposure among medical imaging procedures, compare alternative imaging options, and guide dose optimization efforts. Individual dose estimates are important for relatively radiosensitive patient populations such as children and for radiosensitive organs such as the eye lens. Software-based dose calculation methods conveniently calculate organ dose using patient-adjusted and examination-specific inputs. Methods: Organ absorbed doses and effective doses were calculated for 429 pediatric 18F-FDG PET-CT patients. Patient-adjusted and scan-specific information was extracted from the electronic medical record and scanner dose-monitoring software. The VirtualDose and OLINDA/EXM (version 2.0) programs, respectively, were used to calculate the CT and the radiopharmaceutical organ absorbed doses and effective doses. Patients were grouped according to age at the time of the scan as follows: less than 1 year old, 1 to 5 years old, 6 to 10 years old, 11 to 15 years old, and 16 to 17 years old. Results: The mean (+/- standard deviation, range) total PET plus CT effective dose was 14.5 (1.9, 11.2-22.3) mSv. The mean (+/- standard deviation, range) PET effective dose was 8.1 (1.2, 5.7-16.5) mSv. The mean (+/- standard deviation, range) CT effective dose was 6.4 (1.8, 2.9-14.7) mSv. The five organs with highest PET dose were: Urinary bladder, heart, liver, lungs, and brain. The five organs with highest CT dose were: Thymus, thyroid, kidneys, eye lens, and gonads. Conclusions: Organ and effective dose for both the CT and PET components can be estimated with actual patient and scan data using commercial software. Doses calculated using software generally agree with those calculated using dose conversion factors, although some organ doses were found to be appreciably different. Software-based dose calculation methods allow patient-adjusted dose factors. The effort to gather the needed patient data is justified by the resulting value of the characterization of patient-adjusted dosimetry.
... ALARA assumes that any exposure to ionizing radiation carries some risk, thus every effort should be made to maintain the exposures as low as possible. Consequently, each year hundreds of billions of dollars are spent worldwide to maintain extremely low radiation levels (Sanders 2017). Yet, our results provide clear indications for re-considering the LNT paradigm, at least within the natural range of background radiation. ...
... Below the threshold level, the opposed relationships between the background radiation and its health effects are observed, so that the higher radiation exposure, the longer life expectancy and the lower cancer-associated mortality. Of note, even the NCRP Committee recognizes that ''the risks from LD/LDR are small and uncertain'' (Shore et al. 2018). It is important to mention in this regard that Hermann J. Muller (1946), who stated that there is no threshold dose, the notion which lies in the basis of the LNT model, based his assumption on his work on mice. ...
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The current linear no-threshold paradigm assumes that any exposure to ionizing radiation carries some risk, thus every effort should be made to maintain the exposures as low as possible. We examined whether background radiation impacts human longevity and cancer mortality. Our data covered the entire US population of the 3139 US counties, encompassing over 320 million people. This is the first large-scale study which takes into account the two major sources of background radiation (terrestrial radiation and cosmic radiation), covering the entire US population. Here, we show that life expectancy, the most integrative index of population health, was approximately 2.5 years longer in people living in areas with a relatively high vs. low background radiation. (≥ 180 mrem/year and ≤ 100 mrem/year, respectively; p < 0.005; 95% confidence interval [CI]). This radiation-induced lifespan extension could to a great extent be associated with the decrease in cancer mortality rate observed for several common cancers (lung, pancreas and colon cancers for both genders, and brain and bladder cancers for males only; p < 0.05; 95% CI). Exposure to a high background radiation displays clear beneficial health effects in humans. These hormetic effects provide clear indications for re-considering the linear no-threshold paradigm, at least within the natural range of low-dose radiation.
... Despite this, specific attribution of stochastic effects to ionizing radiation is difficult because the effect manifests many years after exposure. Further, confounders such as exposure to other mutagens or carcinogens through lifestyle, occupation or medically mean that epidemiological studies often lack statistical power to support evidence for a radiation effect, especially at very low doses (Shore et al., 2018). As such, veterans of nuclear testing programmes may face considerable uncertainty in understanding any health conditions or symptoms in the light of (perceived) exposure. ...
... This is not to say that attributing physical health conditions to radiation exposure in this context is irrational, because ionizing radiation exposure has been associated with various health conditions in other contexts (Azizova et al., 2015(Azizova et al., , 2018Baselet et al., 2016;Haylock et al., 2018;Little et al., 2021). The crux is that accurate dose records are unascertainable in the BNTV cohort, so without definitive information veterans will make varying causal attributions especially considering the continued scientific debate regarding low-dose radiation health risk (Doss et al., 2014;Shore et al., 2018;Vaiserman et al., 2018). Indeed, it is suggested that scientific uncertainty and distrust in authorities (which may have been exacerbated by government secrecy) can drive social groups to amplify health risk in the context of low-dose ionizing radiation exposure (Kasperson, 2012;Kasperson et al., 1988). ...
Article
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Since the British nuclear testing programme, there have been several claims in the media and from the veterans themselves that their health (and descendants' health) has been adversely affected by ionizing radiation exposure. Many health conditions associated with ionizing radiation exposure are also age-related. Therefore, the purpose of this study was to explore how British nuclear test veterans, with varying health conditions, perceive their health and attribute causes to health conditions in themselves and in their family members, in the light of being an aged cohort and their previous involvement in nuclear weapons testing. Semi-structured interviews were conducted with 19 British nuclear test veterans and were analysed using thematic analysis to generate broad themes describing the data. Four themes were generated: (i) Sources of health risk information over the life course, (ii) Luck, (iii) What is ‘normal’? and (iv) Experience with healthcare professionals. Health conditions perceived as not ‘normal’ considering one's age, lifestyle, and hereditary risk, or perceived as incurable, appeared more likely to be attributed to radiation exposure. Recommendations relating the transparency for authorities dealing with exposure scenarios, and subsequent genetics and epidemiological research are discussed. Healthcare professionals may benefit from understanding patients' narratives in healthcare consultations with individuals who perceive radiation exposure to have impacted on their health.
... NCRP 186 represents a step along the path to enhance risk assessments defined by a series of three recent publications from NCRP: Report No. 171, Uncertainties in the Estimation of Radiation Risks and Probability of Causation (NCRP 2012;Preston et al. 2013 Shore et al. 2018Shore et al. , 2019. Statements taken from the conclusions and recommendations of these documents provide a context for the present Report NCRP 186. ...
... The general approach to low-dose risk assessment has been to extrapolate from adverse health outcomes assessed at higher doses to estimate those at low doses, although the epidemiologic data on cancer after low doses and low dose rates have also been examined (Kocher et al. 2018;NCRP 2018;Shore et al. 2018). For the purpose of radiation protection, the general method of extrapolation is to use the linear nonthreshold (LNT) model, which is basically a preferred approach since direct observation of human health effects by epidemiologic means at low doses remains highly challenging. ...
Article
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Purpose The overall aim of this contribution to the “Second Bill Morgan Memorial Special Issue” is to provide a high-level review of a recent report developed by a Committee for the National Council on Radiation Protection and Measurements (NCRP) titled “Approaches for Integrating Information from Radiation Biology and Epidemiology to Enhance Low-Dose Health Risk Assessment”. It derives from previous NCRP Reports and Commentaries that provide the case for integrating data from radiation biology studies (available and proposed) with epidemiological studies (also available and proposed) to develop Biologically-Based Dose- Response (BBDR) Models. In the present review it is proposed for such models to leverage the Adverse Outcome Pathways (AOP) and Key Events (KE) approach for better characterizing radiation-induced cancers and circulatory disease (as the example for a noncancer outcome). The review discusses the current state of knowledge of mechanisms of carcinogenesis, with an emphasis on radiation-induced cancers, and a similar discussion for circulatory disease. The types of the various informative BBDR models are presented along with a proposed generalized BBDR model for cancer and a more speculative one for circulatory disease. The way forward is presented in a comprehensive discussion of the research needs to address the goal of enhancing health risk assessment of exposures to low doses of radiation. Conclusion The use of an AOP/KE approach for developing a mechanistic framework for BBDR models of radiation-induced cancer and circulatory disease is considered to be a viable one based upon current knowledge of the mechanisms of formation of these adverse health outcomes and the available technical capabilities and computational advances. The way forward for enhancing low-dose radiation risk estimates will require there to be a tight integration of epidemiology data and radiation biology information to meet the goals of relevance and sensitivity of the adverse health outcomes required for overall health risk assessment at low doses and dose rates.
... The cancer risk data used in derivation of the tissue weighting factors are largely from the Life Span Study of the Japanese survivors from the atomic bombs detonated in 1945. The lifetime risks of developing cancer from exposure of different organs compared with dose data, which appear linear between doses of <100 mGy to several Gy, are extrapolated down to low doses (ICRP, 2005;Shore et al., 2018). This linear no-threshold (LNT) model is used to calculate the probability of radiation-induced cancer for organs and tissues for which there are sufficient data (ICRP, 2007). ...
... Effective dose employs the LNT model, as this is considered to be the best approach to quantifying the risk-dose relationship on the basis of current knowledge (ICRP, 2005;NCRP, 2018;Shore et al., 2018). By assuming that the lifetime risk of cancer is directly proportional to the dose, doses from all radiation exposures can be summed. ...
Article
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The International Commission on Radiological Protection (ICRP) developed effective dose as a quantity related to risk for occupational and public exposure. There was a need for a similar dose quantity linked to risk for making everyday decisions relating to medical procedures. Coefficients were developed to enable the calculation of doses to organs and tissues, and effective doses for procedures in nuclear medicine and radiology during the 1980s and 1990s. Effective dose has provided a valuable tool that is now used in the establishment of guidelines for patient referral and justification of procedures, choice of appropriate imaging techniques, and providing dose data on potential exposure of volunteers for research studies, all of which require the benefits from the procedure to be weighed against the risks. However, the approximations made in the derivation of effective dose are often forgotten, and the uncertainties in calculations of risks are discussed. An ICRP report on protection dose quantities has been prepared that provides more information on the application of effective dose, and concludes that effective dose can be used as an approximate measure of possible risk. A discussion of the way in which it should be used is given here, with applications for which it is considered suitable. Approaches to the evaluation of risk and methods for conveying information on risk are also discussed.
... The propagation of uncertainties was calculated using Monte Carlo simulations in RadRAT, accounting for statistical uncertainties in the risk parameters and subjective uncertainties in the dose and dose-rate effectiveness factors, as well as the population risk transfer and cancer latency (Berrington de Gonzalez et al. 2012). Considering only no threshold risk models could be an additional limitation; however, the available epidemiologic data currently support the linear no-threshold model (Shore et al. 2018), which is considered to provide the most reasonable description of the relation between low-dose exposure to ionizing radiation and the risk of cancer. ...
Article
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Purpose: Interventional medical radiation workers represent an under-studied population worldwide, although they receive relatively high occupational radiation doses. This study aimed to estimate the lifetime cancer risk from occupational radiation exposure among workers at interventional radiology departments. Methods: A field survey of interventional medical workers in nationwide branches of the Korean Society of Interventional Radiology was conducted in 2017. Organ-specific radiation doses were estimated using national dose registry data and conversion coefficients provided by the International Commission on Radiological Protection. Lifetime attributable risk (LAR) and lifetime fractional risk (LFR) were calculated based on realistic exposure scenarios using a radiation risk assessment tool. Results: LARs from occupational radiation exposure until the age of retirement for all cancers combined were 338 (90.3-796.1), 121 (33.5-288.7), and 156 (41.1-390.6) per 100,000 individuals for male radiologists, male radiologic technologists, and female nurses, respectively. LFR for all cancers combined ranged from 0.22% (0.06-0.53) to 0.63% (0.17-1.47). Regarding the organ site, the highest LAR and LFR among all groups were observed for thyroid cancer. Conclusion: This study provides timely evidence of potential cancer burden from the current levels of occupational radiation exposure among workers at interventional radiology departments. The risks varied by occupational groups, and workers, particularly interventional radiologists, need to be carefully monitored for radiation.
... During these applications may be leaking radiation and if good a protection from radiation is not provided, it will cause hereditary damage to living tissues [1][2]. So, good shielding material must be used according to radiation type and energy. ...
Article
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Radiation is used in the industry, medicine and especially nuclear power plants, etc. In the nuclear energy plant is working at the very high temperatures due to fission reactor concepts and fast neutron spectra so high resistance temperature materials have an important role in the shielding studies. To be used as radiation shielding in the nuclear power plants, in this study five different concentration new refractory heavy concrete samples have been designed and produced. Natural MgO-Cr2O3-Fe2O3 have been used in production of the samples. Mixing ratios have been determined by Monte Carlo simülation program Geant4 code. Fast neutron total macroscopic cross section has been calculated by Geant4 code. Moreover neutron absorbed dose measurements have been carried out by using average 4.5 MeV energy 241 Am-9 Be fast neutron source BF3 gas detector. Gamma radiation the mass attenuation coefficient (MACs), mean free path (MFPs) and half-value layer (HVL) have been calculated at the 0.1-15 MeV energy range by VinXCom software. High temperature resistance of the samples has been tested at 600-1100 0 C. The results have been compared with paraffin, conventional concrete and hematite heavy concrete. According to these reference samples, the new refractory heavy concrete samples have the high absorption ability for both fast neutron and gamma radiation. Thus, this new samples can be used to shielding studies radiation applications.
... Despite the documented clinical advantage of i-CT, there is concern regarding patient exposure to ionizing radiation [5,6]. Indeed, according to the linear no-threshold model any exposure is associated with an increased risk of radiation induced stochastic effects such as cancer induction [7]. To assure the radiation protection of patients, radiation exposure should be kept as low as reasonably possible (ALARA principle) [8]. ...
Article
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Purpose To compare the effective dose (ED) and image quality (IQ) of O-arm cone-beam CT (Medtronic, Minneapolis, MN, USA) and Airo multi-slice CT (Brainlab AG, Munich, Germany) for intraoperative-CT (i-CT) in spinal surgery. Methods The manufacturer-defined protocols available in the O-arm and Airo systems for three-dimensional lumbar spine imaging were compared. Organ dose was measured both with thermo-luminescent dosimeters and GafChromic films in the Alderson Radiation Therapy anthropomorphic phantom. A subjective analysis was performed by neurosurgeons to compare the clinical IQ of the anthropomorphic phantom images acquired with the different i-CT systems and imaging protocols. Image uniformity, noise, contrast-to-noise-ratio (CNR), and spatial resolution were additionally assessed with the Catphan 504 phantom. Results O-arm i-CT caused 56% larger ED than Airo due to the high definition (HD) imaging protocol. The noise was larger for O-arm images leading to a lower CNR than that measured for Airo. Moreover, scattering and beam hardening effects were observed in the O-arm images. Better spatial resolution was measured for the O-arm system (9 lp/cm) than for Airo (4 lp/cm). For all the investigated protocols, O-arm was found to be better for identifying anatomical features important for accurate pedicle screw positioning. Conclusions According to phantom measurements, the HD protocol of O-arm offered better clinical IQ than Airo but larger ED. The larger noise of O-arm images did not compromise the clinical IQ while the superior spatial resolution of this system allowed a better visibility of anatomical features important for pedicle screw positioning in the lumbar region.
... Large uncertainties remain about health effects associated with low-dose and low-dose-rate radiation exposure, but the epidemiological evidence of a dose-risk relationship below 100 mSv is increasing, notably from large studies. Today, much of the available data are broadly supportive of the linear-non-threshold model (NCRP, 2018a;Shore, 2018). Based on the results of epidemiological studies, it is estimated that a dose of 100 mSv above the natural background level adds approximately 0.5% to the 25% lifetime risk of fatal cancer typically seen in populations worldwide (ICRP, 2007;Ogino and Hattori, 2014). ...
... Epidemiology has played an important role in assessing the long-term health effects of radiation exposure [9], and will continue to do so while research investigating specific biomarkers of radiation induced disease is ongoing. However, substantial uncertainties remain for doses below 100 mGy, non-photon exposures (including protons and neutrons) and for exposures occurring very early in life [10]. ...
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The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac component of HARMONIC. A pooled cohort of approximately 100,000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports (RDSRs). Uncertainties in dose estimates will be modelled using 2-dimensional Monte Carlo methods. The cohort will be followed up using national registries and insurance records (Germany) to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits.
... This Report represents a step along the path to enhance risk assessments defined by a series of three recent reports from NCRP: Report No. 171, Uncertainties in the Estimation of Radiation Risks and Probability of Causation (NCRP 2012;Preston et al. 2013);Commentary No. 24, Health Effects of Low Doses of Radiation: Perspectives on Integrating Radiation Biology and Epidemiology (NCRP 2015);and Commentary No. 27, Implications of Recent Epidemiologic Studies for the Linear-Nonthreshold Model and Radiation Protection (NCRP 2018a;Shore et al. 2018;. Statements taken from the conclusions and recommendations of these documents provide a context for the present Report. ...
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The overall aim of this Report is to provide input for the development of biologically based dose-response (BBDR) models for radiation- induced cancers and circulatory disease that use an adverse outcome pathways and key-events approach for providing parameters for these models. These mechanistic data can be integrated with the most recent epidemiologic data to develop overall doseresponse curves for radiation-induced adverse health outcomes. This integration of the findings from radiation biology and epidemiology will enhance the risk assessment process by reducing uncertainties in estimated risk following exposure to low doses and low dose rates of ionizing radiation. For many decades the basis for setting radiation protection guidance for exposure to low absorbed doses and low absorbed-dose rates of ionizing radiation has been the estimation of the risk of radiation-induced cancer. In addition, there is ongoing discussion concerning risks of radiation-induced noncancer effects1 (particularly circulatory disease). The estimates for radiation-induced cancer have been derived primarily from exposure to higher doses and higher dose rates of ionizing radiation and assumptions on how to extrapolate to low doses and low dose rates. For the purpose of this Report, for low linear-energy transfer (LET) radiation, a low absorbed dose is <100 mGy delivered acutely, and a low absorbeddose rate is <5 mGy h–1 for any accumulated absorbed dose (NCRP 2015). This Report addresses the conclusions and recommendations from three previous National Council on Radiation Protection and Measurements (NCRP) reports and commentaries on the topic of the risks of adverse health outcomes at low doses and low dose rates of ionizing radiation (NCRP 2012, 2015, 2018a). In this context, the present Report proposes a path forward to enhance the estimation of risk at low doses and low dose rates. Such a modified approach is needed to supplement the information that can be obtained from the conduct of even large epidemiologic studies such as the One Million U.S. Workers and Veterans Study of Low-Dose Radiation Health Effects (million U.S. workers and veterans study) 1For this Report the term noncancer is restricted to somatic noncancer outcomes and does not include heritable effects. (Bouville et al. 2015; Boice et al. 2019), the International Nuclear Workers Study (Leuraud et al. 2015; Richardson et al. 2015), the European pooled study of radiation-induced cancer from pediatric computed tomography (Bernier et al. 2019), or other low-dose pooling studies (Lubin et al. 2017; Little, Kitahara et al. 2018). This Report presents such an approach based upon the integration of data from epidemiology and radiation biology. An essential component of the integration process is the use of BBDR models with parameters being developed from analyzing adverse outcome pathways and their associated key events. In principle, an adverse outcome pathway is the series of necessary steps that result in an initial molecular event leading to an adverse health outcome (for this Report, either cancer or circulatory disease). Definitions of adverse outcome pathways and key events are given in Section 2 and can be found also in recent reviews (Edwards et al. 2016; Preston 2017). Also, when considering mechanistic data underlying the induction of adverse health outcomes, it is important to distinguish between potential bioindicators and biomarkers of these outcomes. A bioindicator is a cellular alteration that is on a critical pathway to the disease endpoint itself (i.e., necessary, but not by itself sufficient for the endpoint), such as a specific mutation in a target cell that is associated with tumor formation. Thus, a bioindicator can be perceived as informing on the shape of the dose-response curve for the disease outcome or on cancer frequency itself, and therefore, is equivalent to a key event. A biomarker is a biological phenotype [e.g., chromosome alteration, deoxyribonucleic acid (DNA) adduct, gene expression change, specific metabolite] that can be used to indicate a response to an exposure at the cell or tissue level. In this regard, a biomarker is generally a measure of the potential for development of an adverse health outcome such as cancer (e.g., a predictor of exposure level). This Report expands upon this general approach of adverse outcome pathways, key events, and BBDR models to enhance the process of low-dose, low dose-rate risk estimation. The arrangement of this Report for the application of this general approach is: here is what we know, here is what we need to know, and this is how we can obtain the necessary knowledge. A synopsis of Sections 2 through 7 is given below. Section 2 (Introduction) provides an overview of current approaches to radiation risk assessment, the associated uncertainties and possible ways forward for enhancing the estimation of risks of cancer and circulatory disease at low doses and low dose rates. Section 3 (Epidemiology, Biosamples and Biomarkers: Cancer and Circulatory Disease) presents a review of the radiation epidemiologic studies for which biomarker data or biological samples were used. For noncancer effects it was clear that the only adverse health outcome for which significant data from radiation biology are available for use in BBDR models is circulatory disease and so this forms the basis for the discussion on noncancer effects. There are a large number of radiation epidemiologic studies available that are very informative for estimating risks at higher doses but that can only be used with a fairly high degree of uncertainty for predicting low-dose risks. A review of the main radiation epidemiologic studies has been provided in NCRP Commentary No. 27 (NCRP 2018a). Section 3.1 briefly describes the major epidemiologic radiation studies with associated biosamples that potentially can be employed to conduct investigations of bioindicators of the pathogenesis of radiation-induced cancer and other health endpoints. While none of the current investigations has yet been able to identify definitive bioindicators, there are several suggestions of biomarkers that merit confirmation through further investigations and might be informative in the absence of more definitive bioindicator studies. The details and references for these studies are provided in Section 3.1.3. Section 3.2 indicates that it is likely that bioindicators of radiation- induced noncancer effects at low doses will be restricted to circulatory disease and so this is the sole topic reviewed for biomarkers associated with noncancer responses. With current knowledge, substantive biomarker information is only available in two major radiation studies: the Japanese atomic-bomb survivors, and the Mayak Production Association workers (Mayak workers), although little use has been made of this latter population in analyses to date. In summary, there is a paucity of radiation-specific bioindicators of cancer and circulatory disease and a relative lack of radiation- specific biomarkers predictive of adverse health outcomes. Thus, it is necessary to consider the mechanisms of formation of cancers and circulatory disease, especially for radiation-induced responses, to aid with the identification of bioindicators of adverse health outcomes and to a lesser extent, biomarkers of association with an adverse health outcome. Section 4 (Radiation-Induced Biological Effects Related to Cancer and Circulatory Disease) reviews the underlying mechanisms of carcinogenesis and circulatory disease with the aim of identifying potential bioindicators of the adverse health outcome, and if possible radiation-associated bioindicators of such responses. There has been an increased understanding of the underlying mechanisms of human diseases as a result of new molecular, cellular and computational approaches, further enhanced by informative experimental animal systems that model human disease. To a lesser extent such approaches have been used to better understand the etiology of radiation-induced diseases. There is a description of the types of studies that have identified pathways and potential key events in the carcinogenesis process (Section 4.1). While currently there are no fully validated bioindicators or biomarkers of radiation-induced cancer, there is a substantial and increasing body of knowledge on radiation-induced cancer mechanisms, particularly in experimental animal systems. Quantification of inflammation and generation of persistently elevated reactive oxygen species (ROS) holds promise as a further bioindicator that is also recognized as an enabling hallmark of cancer in the context of Hanahan and Weinberg (2011). In addition, cell-survival parameters can be of importance in mechanistic models of carcinogenesis. The use of data from experimental animal systems provides opportunities to demonstrate the added value of building and applying mechanistic models of radiation-induced cancer. There are additional opportunities to apply similar models in some human radiation-induced cancers, most notably thyroid, where some work utilizing knowledge of the CLIP2 marker is already available. The incorporation of quantitative mechanistic data into appropriate cancer models (discussed in Sections 5 and 6) is likely to increase the precision of estimated risks, particularly at low-dose levels and so continued efforts to identify and validate bioindicators of radiation- induced cancers will assist in refining risk estimation. Section 4.2 outlines the biology of circulatory disease, a significant radiation-induced noncancer disease2 and the one which currently offers the best opportunity for bioindicator identification given the mechanistic data already available. The complex inflammatory processes underlying most major types of circulatory disease are reviewed, specifically those associated with atherosclerosis. The possible ways that low-dose radiation exposure and other 2NCRP (2018a) stated that radiation-induced cardiovascular disease (a circulatory disease) remains an area where further investigation is necessary. Although there is evidence that cardiovascular disease may be a factor at exposures lower than previously estimated, that evidence was not yet sufficient to allow for development of an approach to including cardiovascular disease in NCRP’s overall system of radiation protection published in NCRP (2018b). biological stressors might affect the circulatory system are also reviewed. While it is not possible yet to identify bioindicators of radiation-induced circulatory disease, it appears feasible to build upon the rapidly increasing knowledge of the mechanisms of formation of circulatory disease to develop adverse outcome pathways and at least some of the associated key events. Section 5 (Biologically Based Dose-Response Models) assesses biomathematical models of chronic disease, especially those for cancer and circulatory disease (with particular emphasis in circulatory disease on models of atherosclerosis). First, general material outlining the overall goals of biomathematical models is presented, followed by discussion of modeling considerations, particularly application of specific models using human, animal or cell data to cancer and circulatory disease. Biologically based modeling of radiation- induced cancers of the breast, colon, lung, and thyroid gland have been conducted. After considerations of some general features of BBDR models of cancer development in Section 5.1, a number of BBDR models and their application to various human and animal datasets are presented in Section 5.2. Despite some shortcomings (e.g., the fact that different models might explain the available data using different mechanistic assumptions), multiple pathway models are considered a promising conceptual approach to developing a general model framework for the complex process of carcinogenesis in various tissues. In certain cases, multiple pathway models may allow predictions that can be validated against experimental data. Circulatory disease models are considered in Section 5.3. These are less well developed than those that have been constructed to model cancer. A number of candidate models of atherosclerosis are considered. Atherosclerosis is the disease process underlying the main types of circulatory disease, specifically ischemic heart disease (IHD) and stroke, which is thought to have a largely inflammatory etiology. A number of atherosclerosis models, which share certain features, have been proposed for these inflammatory processes, specifically the adhesion and transport of monocytes through the epithelial cell layer, and diffusion through the intima. However, it is not yet clear what the radiation-associated mechanisms may be for most types of circulatory disease. Having identified the types of BBDR models that could possibly be used to enhance the estimation of low-dose, low dose-rate radiation adverse health outcomes, it is necessary to determine whether there is a generalized model that can be used for: all radiationinduced cancer types, or circulatory disease as a class. It was concluded that it would be unlikely that a single model structure could be used for describing cancer and circulatory disease. Also, it appears likely that there may be different responses even for different types of circulatory disease. The concept of a generalized model is discussed in Section 6 (Proposed Generalized Model Framework of Cancer and Circulatory Disease). It is proposed that a form of multistage clonal expansion model would be appropriate for integrating data from epidemiology and radiation biology for estimating low-dose, low dose-rate cancer risk. The parameters for such a model structure are proposed to be developed from an adverse outcome pathways and key-events approach. In such an approach the key events are considered to be bioindicators of the adverse health outcome itself. In support of this proposal to utilize generalized multistage clonal expansion models, there has been considerable recent discussion on the use of such parameterized models for environmental chemicals (OECD 2020). The Organization for Economic Co-operation and Development (OECD 2020) website provides a considerable amount of information on developing adverse outcome pathways and their use in risk assessment and ultimately in risk management practice. This general approach is also described and applied in the research program of the U.S. Environmental Protection Agency (EPA 2018). A description of biologically detailed models of specific cancers that have been applied with some levels of success is provided to indicate the viability of the use of BBDR models for estimating adverse health outcomes at low doses and low dose rates. While not definitive at this time, the approach certainly has a real likelihood of being successful. Section 7 (Research Needs) provides specific examples of research activities, both large and small that are designed for developing adverse outcome pathways and their associated key events. These include epidemiologic, human sample, laboratory animal, cellular, and molecular studies. Such research activities include investigating some general but critical responses, in order to derive greater insight into the parameters of most importance for further model development. Currently, one can envisage the following to be of high relevance: • target cell population numbers and characteristics; • survival parameters for these populations after radiation exposure; • target gene(s) critical for pathogenesis and their mutation or epimutation frequency as a function of radiation dose; • proliferation characteristics in normal and mutation-carrying cell populations; and • timing and frequency of acquisition of further mutational events in key genes and the impact of these on survival and proliferation characteristics. For enhanced model development, it is necessary to more fully identify the mechanisms of cancer development in response to radiation. The following are of importance in this regard: • Mechanisms in the development of a radiation-induced disease may differ from those in sporadic disease. • Does radiation initiate or accelerate the same processes that lead to sporadic disease, or are distinct molecular pathways involved? • BBDR models have the potential to address such questions if appropriate bioindicators become available for specific types of cancer or other diseases. • For transcriptomics, proteomics, metabolomics and epigenomics, adequate BBDR models ideally might require measurements at several time points because the profiles of phenotypic alterations may differ by stage in the pathogenesis of a disease. Clearly, the overarching need is the furthering of research targeted at the underlying mechanisms of radiation-induced adverse health outcomes (cancer and noncancer disease) leading to the identification of truly informative bioindicators of the apical endpoint (i.e., the adverse health outcome). The framework for such an approach can be the characterization of adverse outcome pathways for specific outcomes and the identification of key events from the initial event to adverse health outcome. In this context, a key-event or informative bioindicator is a true surrogate for the adverse health outcome. This approach will require the integration of data from epidemiology and radiation biology to maximize the information for estimating low-dose responses for adverse health outcomes. A particularly important result will be the ability to better describe the form of the dose-response curve for different types of radiation- induced cancer, for example, and thereby avoid the need to rely on application of the linear-nonthreshold (LNT) model without sufficient biological substantiation. A concerted effort will be needed; this is going to require a well-defined and quite extensive research effort. The need for this effort is recognized by many in the risk assessment and risk management arena.
... LNT assumes that every radiation dose, no matter how small, constitutes an increased cancer risk. This model is considered conservative and prudent for the purposes of radiation protection (Shore et al. 2018), though it has been the subject of serious scientific controversy (Tubiana 2005) and has been more and more criticized (Calabrese et al. 2018). According to the LNT model, the number of excess cancer deaths for population of mixed ages is usually estimated as 5% per Sievert (Sv); this number follows the recommendation of the BEIR-VII report of the U.S. National Research Council (NRC 2006, Table 12-6, p. 281). ...
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Purpose: Despite the vast amount of literature on radiological emergencies, to the best of our knowledge there is no systematic review of probable scenarios and their consequences. This work aimed for compiling such review. Materials and methods: The authors comprised a Red Team – that is, simulated best efforts to inflict maximal damage to the society by various means of radiological attacks. Nuclear warfare including improvised nuclear devices is beyond the scope of this work. Results: The direct radiogenic health consequences of any conceivable radiological accident, natural or man-made, are much less dangerous than those which are usually perceived. In each scenario, direct health effects are only a small part of the damage caused by fear and over-reaction; the damage is somewhat independent of the small health effect predicted for most of the scenarios. The reason is that nuclear radiation has become perceptually connected with nuclear apocalypses. This connection has caused the emotional description of radiological emergencies to frequently substitute quantitative considerations. For example, Chernobyl and Fukushima became major humanitarian disasters not because of the radiation itself but because of the over-reaction of both the authorities and the public, that led to the unjustified relocation of hundreds of thousands of people. In Fukushima, the evacuation was not justified at all and in Chernobyl the evacuated zone should have been re-populated after one month. Conclusions: It is vital to educate decision makers, first responders and the public about the factual extent of possible radiological consequences, as well as about the very real danger of over-reaction. Since the extent of the countermeasures deployed is unavoidably connected, in the eye of the public, with the extent of the danger, we suggest launching educational campaigns that explain the factual extent of the radiation risk, followed by easing regulations and narrowing safety margins. Such measures will probably be the most efficient method of countering radiological terrorism: by depriving any adversary of the most important ability which is to cause an over-reaction.
... Also they are found in industrial, semi-industrial and research fields etc. [1] Through the routine use of ionizing radiation sources, accidents and nuclear or radiological incidents can occur, due either to a technical problem, an inattention of an operator, or the unconsciousness of victims or others, which can cause exposure to ionizing radiation to the human body. The severity of these exposures depends on several factors such as the types of ionizing radiation involved, exposure time, body-source distance, sensitivity of the target (organs and tissues), the activity of the sources and the age of victim etc. [2,3] In this work, we make a Monte Carlo simulation with the Geant4 code of the doses received by the body of a human assimilated a mathematical anthropomorphic phantom placed in front of a gamma irradiator of cobalt-60 inside the NIAR ionization cell. ...
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The human body is vulnerable to exposure to ionizing radiation permanently. These radiations can be of natural origin such as soil and space, or of artificial and medical origins etc. Despite the great benefits that come from the applications of ionizing radiation in human life can turn at any time into threats to the life of the population once there is serious exposure to ionizing radiation. The aim of this work is to assess the risks of exposure by gamma radiation using the Monte Carlo simulation and an anthropomorphic phantom. This study is carried out on gamma rays received from the cobalt-60 irradiator of the National Institute of Agronomic Research (NIAR) Tangier / Morocco. With the code Geant4 we calculate the absorbed dose by the whole phantom body placed in front of the gamma irradiator inside the NIAR ionization cell. Dose calculations are made as a function of three parameters: phantom-irradiator distance, exposure time and as a function of gamma irradiator activity. The results clearly show that the dose absorbed and thus the danger of irradiation decreases by increasing the phantom-source distance, and by reducing the exposure time and the activity of the cobalt-60 source.
... Forth, all tissue weighting factors that are provided in literature so far are averaged for sex and age, which may probably limit their applicability for patient specific risk estimation. Fifth, the linear Non-threshold Dose-Response Model itself is discussed controversially among experts for diagnostic dose levels 31,32 . Sixth, LAR and ERR calculations in this study are only related to low dose radiation exposure. ...
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Detailed knowledge about radiation exposure is crucial for radiology professionals. The conventional calculation of effective dose (ED) for computed tomography (CT) is based on dose length product (DLP) and population-based conversion factors (k). This is often imprecise and unable to consider individual patient characteristics. We sought to provide more precise and individual radiation exposure calculation using image based Monte Carlo simulations (MC) in a heterogeneous patient collective and to compare it to phantom based MC provided from the National Cancer Institute (NCI) as academic reference. Dose distributions were simulated for 22 patients after whole-body CT during Positron Emission Tomography-CT. Based on MC we calculated individual Lifetime Attributable Risk (LAR) and Excess Relative Risk (ERR) of cancer mortality. EDMC was compared to EDDLP and EDNCI. EDDLP (13.2 ± 4.5 mSv) was higher compared to EDNCI (9.8 ± 2.1 mSv) and EDMC (11.6 ± 1.5 mSv). Relative individual differences were up to −48% for EDMC and −44% for EDNCI compared to EDDLP. Matching pair analysis illustrates that young age and gender are affecting LAR and ERR significantly. Because of these uncertainties in radiation dose assessment automated individual dose and risk estimation would be desirable for dose monitoring in the future.
... LNT assumes that every radiation dose, no matter how small, constitutes an increased cancer risk. This model is considered conservative and prudent for the purposes of radiation protection (Shore et al. 2018), though it is a subject of serious scientific controversy (Tubiana 2005) and is being more and more criticized (Calabrese et al. 2018). In order to estimate the worst-case scenario for the number of additional cancer deaths we shall use LNT, despite the questions about the extent to which it holds. ...
Article
Purpose: We aimed for a quantitative evaluation that justifies guidelines for evacuation which take into consideration both the human and economic costs. To the best of our knowledge, such an evaluation has not been performed yet. The present guidelines published by the International Atomic Energy Agency (IAEA) are probably based on averting radiation risk only; IAEA did not cite any quantitative estimation of the human cost of evacuation. Materials and methods: Quantitative estimation of the human and monetary costs of evacuation and, alternatively, the human and monetary costs of radiation exposure (non-evacuation). Associating human life with monetary value is psychologically difficult and somewhat challenging ethically; however, there is no escape from such an association (cost-effectiveness analysis) when making decisions regarding public health and safety, since extraneous public expenditures lead to a statistical life shortening. Estimating worst-case health consequences of irradiation, we used the conservative linear no-threshold (LNT) model because this model is widely used in spite of its controversy. In our estimation of the human cost of evacuation, we considered three factors: (a) direct loss of life (after Fukushima, 1% of the evacuees died within two years due to causes directly related to their evacuation), (b) loss of quality of life and (c) loss of wealth leading to loss of life. The connection of economic loss with loss of life was performed according to the median cost-effectiveness threshold of 50-100 thousand USD per quality adjusted life year. Results: Even according to mortality calculations based on LNT, the overall loss of life due to evacuation is higher than the loss of life due to irradiation if the population-averaged first-year radiation dose is 500 mSv or less. Conclusions: Based on the performed analysis, we suggest avoiding evacuation if the projected first-year dose is below 500 mSv. This suggested action level is about five-fold higher than the action level presently recommended by the IAEA (100 mSv per year). https://www.tandfonline.com/doi/full/10.1080/09553002.2020.1779962 https://www.tandfonline.com/eprint/VCRMS9ESFCDJASBKAVEX/full?target=10.1080/09553002.2020.1779962
... One of the most important questions in radiation research relates to the shape of the dose-response for different detrimental health outcomes at low exposures levels. Various international radiation protection organizations use the linear no-threshold (LNT) model to predict risks of cancer after ionizing radiation (IR) exposures (NCRP 2018;Shore et al. 2018Shore et al. , 2019ICRP 2005;UNSCEAR 2000). However, the most recent analysis of the Life Span Study (LSS) data suggests a significant quadratic upward curvature, especially for the incidence of all solid cancers in males . ...
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Recent analyses of the Canadian fluoroscopy cohort study reported significantly increased radiation risks of mortality from ischemic heart diseases (IHD) with a linear dose-response adjusted for dose fractionation. This cohort includes 63,707 tuberculosis patients from Canada who were exposed to low-to-moderate dose fractionated X-rays in 1930s-1950s and were followed-up for death from non-cancer causes during 1950-1987. In the current analysis, we scrutinized the assumption of linearity by analyzing a series of radio-biologically motivated nonlinear dose-response models to get a better understanding of the impact of radiation damage on IHD. The models were weighted according to their quality of fit and were then mathematically superposed applying the multi-model inference (MMI) technique. Our results indicated an essentially linear dose-response relationship for IHD mortality at low and medium doses and a supra-linear relationship at higher doses (> 1.5 Gy). At 5 Gy, the estimated radiation risks were fivefold higher compared to the linear no-threshold (LNT) model. This is the largest study of patients exposed to fractionated low-to-moderate doses of radiation. Our analyses confirm previously reported significantly increased radiation risks of IHD from doses similar to those from diagnostic radiation procedures.
... The use is considered acceptable if the expected health gain from an examination exceeds the possible harms (3,4) . The risk for harm, especially cancer, after use of X-ray and CT, is under debate (5) . ...
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This audit describes ionizing and non-ionizing diagnostic imaging at a regional trauma centre. All 144 patients (males 79.2%, median age 31 years) met with trauma team activation from 1 January 2015 to 31 December 2015 were included. We used data from electronic health records to identify all diagnostic imaging and report radiation exposure as dose area product (DAP) for conventional radiography (X-ray) and dose length product (DLP) and effective dose for CT. During hospitalization, 134 (93.1%) underwent X-ray, 122 (84.7%) CT, 92 (63.9%) focused assessment with sonography for trauma (FAST), 14 (9.7%) ultrasound (FAST excluded) and 32 (22.2%) magnetic resonance imaging. One hundred and sixteen (80.5%) underwent CT examinations during trauma admissions, and 73 of 144 (50.7%) standardized whole body CT (SWBCT). DAP values were below national reference levels. Median DLP and effective dose were 2396 mGycm and 20.42 mSv for all CT examinations, and 2461 mGycm (national diagnostic reference level 2400) and 22.29 mSv for a SWBCT.
... Healthy individual with SNPs associated to a smoking related risk to develop CAD, UBCa or LCa will also get higher motivation for smoking cessation. Unknown environmental factors associated to risk of these diseases in non-smoking group [43] and the possibility to use SNPs as prognostic biomarkers for treatment selection and prediction of clinical outcome needs future investigation. ...
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Introduction Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor. Methods Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed. Results Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 r s25487 was associated to both non-smoking UBCa and LCa. Conclusion SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.
... For instance radiation absorption in high ratio may cause serious effects such as radiation burns, cell and DNA damage, hereditary nervous system damage, etc. Furthermore, low ratio of radiation absorption for a long time may also cause many types of cancer [2][3]. Hence, for the efficient use of radiation, appropriate protection must be provided in accordance with the radiation type. ...
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Stainless steel is used commonly in nuclear applications for shielding radiation, so in this study, three different types of new stainless steel samples were designed and developed. New stainless steel compound ratios were determined by using Monte Carlo Simulation program Geant 4 code. In the sample production, iron (Fe), nickel (Ni), chromium (Cr), silicium (Si), sulphur (S), carbon (C), molybdenum (Mo), manganese (Mn), wolfram (W), rhenium (Re), titanium (Ti) and vanadium (V), powder materials were used with powder metallurgy method. Total macroscopic cross sections, mean free path and transmission number were calculated for the fast neutron radiation shielding by using (Geant 4) code. In addition to neutron shielding, the gamma absorption parameters such as mass attenuation coefficients (MACs) and half value layer (HVL) were calculated using Win-XCOM software. Sulfuric acid abrasion and compressive strength tests were carried out and all samples showed good resistance to acid wear and pressure force. The neutron equivalent dose was measured using an average 4.5 MeV energy fast neutron source. Results were compared to 316LN type stainless steel, which commonly used in shielding radiation. New stainless steel samples were found to absorb neutron better than 316LN stainless steel at both low and high temperatures. Keywords: Stainless steel, Alloy, Neutron shielding, Geant4, Gamma
... Below this threshold, there will be no significant effect of radiation exposure on cataract induction (Stewart et al., 2012). Recently, a number of epidemiological and mechanistic studies have observed cataracts and related changes occurring at doses lower than 0.5 Gy and, indeed, it is possible that cataract may be a more stochastic effect, thus described by a linear, no threshold model (Ainsbury et al., 2016;Shore et al., 2018;Pawliczek et al., 2021). ...
Article
When managed with appropriate radiation protection procedures, ionising radiation is of great benefit to society. Opacification of the lens, and vision impairing cataract, have recently been recognised at potential effects of relatively low dose radiation exposure, on the order of 1 Gy or below. Within the last 10 years, understanding of the effects of low dose ionising radiation on the lens has increased, particularly in terms of DNA damage and responses, and how multiple radiation or other events in the lens might contribute to the overall risk of cataract. However, gaps remain, not least in the understanding of how radiation interacts with other risk factors such as aging, as well as the relative radiosensitivity of the lens compared to tissues of the body. This paper reviews the current literature in the field of low dose radiation cataract, with a particular focus on sensitivity and latency.
... According to the epidemiological studies with high-quality data, the observed results are reasonably consistent with the LNT assumption. To date, although uncertainties persist for low doses, there are no elements in favour of the existence of a threshold (NCRP 2018;Shore et al. 2018;Hauptmann et al. 2020). Furthermore, experimental studies have shown that different types of radiation may demonstrate different effectiveness in inducing biological damages. ...
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This article aims at comparing reference methods for the assessment of cancer risk from exposure to genotoxic carcinogen chemical substances and to ionizing radiation. For chemicals, cancer potency is expressed as a toxicological reference value (TRV) based on the most sensitive type of cancer generally observed in animal experiments of oral or inhalation exposure. A dose–response curve is established by modelling experimental data adjusted to apply to human exposure. This leads to a point of departure from which the TRV is derived as the slope of a linear extrapolation to zero dose. Human lifetime cancer risk can then be assessed as the product of dose by TRV and it is generally considered to be tolerable in a 10–6–10–4 range for the public in a normal situation. Radiation exposure is assessed as an effective dose corresponding to a weighted average of energy deposition in body organs. Cancer risk models were derived from the epidemiological follow-up of atomic bombing survivors. Considering a linear-no-threshold dose-risk relationship and average baseline risks, lifetime nominal risk coefficients were established for 13 types of cancers. Those are adjusted according to the severity of each cancer type and combined into an overall indicator denominated radiation detriment. Exposure to radiation is subject to dose limits proscribing unacceptable health detriment. The differences between chemical and radiological cancer risk assessments are discussed and concern data sources, extrapolation to low doses, definition of dose, considered health effects and level of conservatism. These differences should not be an insuperable impediment to the comparison of TRVs with radiation risk, thus opportunities exist to bring closer the two types of risk assessment.
... In the low-dose range, any observed deviations from a linear dose-response may in fact be the result of the inability to construct a better baseline model due to the lack of information on other risk factors (the baseline model is a mathematical model used to describe the background or baseline risk, i.e. the risk that is not associated with radiation exposure). This is one important reason why the use of the LNT model is preferred in radiological protection (NCRP 2018b; summarized by Shore et al. 2018 ). ...
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Purpose: This article summarizes a number of presentations from a session on "Radiation and Circulatory Effects" held during the Radiation Research Society Online 67th Annual Meeting, October 3 - 6 2021. Materials and methods: Different epidemiological cohorts were analyzed with various statistical means common in epidemiology. The cohorts included the one from the U.S. Million Person Study and the Canadian Fluoroscopy Cohort Study. In addition, one of the contributions in our article relies on results from analyses of the Japanese atomic bomb survivors, Russian emergency and recovery workers and cohorts of nuclear workers. The Canadian Fluoroscopy Cohort Study data were analyzed with a larger series of linear and nonlinear dose-response models in addition to the linear no-threshold (LNT) model.Results and Conclusions: The talks in this symposium showed that low/moderate acute doses at low/moderate dose-rates can be associated with an increased risk of CVD, although some of the epidemiological results for occupational cohorts are equivocal. The usually only limited availability of information on well-known risk factors for circulatory disease (e.g. smoking, obesity, hypertension, diabetes, physical activity) is an important limiting factor that may bias any observed association between radiation exposure and detrimental health outcome especially at low doses. Additional follow-up and careful dosimetric and outcome assessment are necessary and more epidemiological and experimental research is required. Obtaining reliable information on other risk factors is especially important.
... La exposición a RI en odontología puede producir efectos biológicos adversos en el POE si este no aplica el principio de protección radiológica de limitación de dosis. Es importante que el POE conozca los efectos biológicos que puede producir el uso de RI, ya que ninguna dosis de RI es segura (58,59). ...
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En odontología el uso de radiografías es frecuente, éstas se obtienen con rayos X, que son un tipo de radiación ionizante. Debido a que la exposición de estos rayos X sin control puede causar efectos biológicos adversos en el organismo del ser humano, es necesario aplicar principios de protección radiológica tanto para el paciente como para el operador. En el caso del operador el principio de protección radiológica que aplica es limitación de dosis. No existe literatura reciente que consolide los aspectos relacionados con el principio de limitación de dosis en odontología. La presente revisión narrativa agrupa la información relacionada al principio de limitación de dosis de radiación ionizante, enfocado en el personal ocupacionalmente expuesto y su aplicación en radiología dental.
... Such approach facilitates linear extrapolation of data from high and medium doses to low dose radiation. However, there are considerable uncertainties in assessing the risk-related outcomes at low doses or low dose rates (Preston 2017;Shore et al. 2018). Several national and international organizations of radiation protection have recommended integrating the data of radiation biology and epidemiology to improve the radiation risk assessment process NCRP 2020;NASEM 2022). ...
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Background: Epidemiological studies have indicated that exposure of the heart to doses of ionizing radiation as low as 0.5 Gy increases the risk of cardiac morbidity and mortality with a latency period of decades. The damaging effects of radiation to myocardial and endothelial structures and functions have been confirmed radiobiologically at high dose, but much less is known at low dose. Integration of radiation biology and epidemiology data is a recommended approach to improve the radiation risk assessment process. The adverse outcome pathway (AOP) framework offers a comprehensive tool to compile and translate mechanistic information into pathological endpoints which may be relevant for risk assessment at the different levels of a biological system. Omics technologies enable the generation of large volumes of biological data at various levels of complexity, from molecular pathways to functional organisms. Given the quality and quantity of available data across levels of biology, omics data can be attractive sources of information for use within the AOP framework. It is anticipated that radiation omics studies could improve our understanding of the molecular mechanisms behind the adverse effects of radiation on the cardiovascular system. In this review, we explored the available omics studies on radiation-induced cardiovascular disease (CVD) and their applicability to the proposed AOP for CVD. Results: The results of 80 omics studies published on radiation-induced CVD over the past 20 years have been discussed in the context of the AOP of CVD proposed by Chauhan et al. Most of the available omics data on radiation-induced CVD are from proteomics, transcriptomics, and metabolomics, whereas few datasets were available from epigenomics and multi-omics. The omics data presented here show great promise in providing information for several key events of the proposed AOP of CVD, particularly oxidative stress, alterations of energy metabolism, extracellular matrix and vascular remodeling. Conclusions: The omics data presented here shows promise to inform the various levels of the proposed AOP of CVD. However, the data highlight the urgent need of designing omics studies to address the knowledge gap concerning different radiation scenarios, time after exposure and experimental models. This review presents the evidence to build a qualitative omics-informed AOP and provides views on the potential benefits and challenges in using omics data to assess risk-related outcomes.
... There have been a number of recent reviews of this low and moderate dose literature, in particular by the National Council on Radiation Protection and Measurements (NCRP) (National Council on Radiation Protection and Measurements (NCRP) 2018; Shore et al. 2018;Shore et al. 2019) and by a large group of collaborators coordinated by the National Cancer Institute (NCI) Daniels et al. 2020;Gilbert et al. 2020;Hauptmann et al. 2020;Linet et al. 2020;Schubauer-Berigan et al. 2020), although most studies surveyed in both cases related to exposure in adulthood. ...
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Background: The detrimental health effects associated with the receipt of moderate (0.1–1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood. Methods and findings: We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p < 0.001) excess risks for all cancers, and particularly large excess relative risks were observed for brain/CNS tumours, thyroid cancer (including nodules) and leukaemia. Conclusions: Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses < 0.1 Gy, and for certain groups exposed to natural background radiation, to fallout and medical X-rays in utero, at about 0.02 Gy.
... Radiation shields have played a vital role in radiation protection against ionizing radiation for industry and medicine applications (Kliauga and Amols, 1995;van Abbema et al., 2018;Radiation Protection and, 2018). Exposure to ionizing radiation is one of the most dangerous threats that a person may face if radiation protection measures are not followed (Abouhaswa et al., 2020;No, 2018), whether the source of radiation is materials extracted from the ground during mining and oil extraction operations or transportation and storage of these materials. The increase in the development of the processes associated with mining and oil extraction increases the interest to develop materials that prevent radiation leakage and hence protect the user from exposure to ionizing radiations (Xhixha et al., 2013). ...
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The disposal of naturally occurring radioactive material (NORM) needs to be controlled and it is better to be packed in a suitable container to ensure acceptable levels of risk. High-density polyethylene (HDPE) can be used to produce composite materials as a good shielding material at minimal cost and lighter weight. In this study, different Al(OH)3 concentrations were incorporated in an HDPE matrix containing certain Pb2O3 concentrations through a hot compression molding process. The effect of Al(OH)3concentration, as well as the irradiation dose on the mechanical properties of the prepared composite, were investigated. Thermogravimetric analysis (TGA) was used to examine the thermal stability of the prepared composite whereas an X-ray diffractometer (XRD) confirmed the presence and homogeneity dispersion of the Al(OH)3 and Pb2O3 into the HDPE matrix. The radiation shielding capabilities of the prepared HDPE/Al(OH)3/Pb2O3 composite sheets were examined using ¹³⁷Cs radioactive source with activity 5μCi. The gamma-rays attenuation coefficient for the composite's sheets was measured as a function of Al(OH)3 percentage. The data shows that the tensile strength of the prepared composite sheets increases slightly with reinforcement materials and the elongation decreases whereas the exposure to gamma rays improves their tensile strength with an insignificant effect on the elongation. The sample containing an amount of 50% Al(OH)3wt% has a good shielding characteristic and the Win XCOM program shows a good agreement between the calculated and WinX com attenuation coefficient values. The obtained results recommend the use of the prepared HDPE/Al(OH)3/Pb2O3 as a promising candidate material for the fabrication of a package with low-energy ¹³⁷Cs radiation shielding capability.
... In order to prove the presence, extent, or absence of such risks for female cancer patients at a certain assumptive threshold, the only available data are provided by epidemiological studies, which principally employ an observational, non-experimental approach. However, data from epidemiological studies are generated by the uncontrolled conditions of everyday life and randomized controlled trials are unacceptable for the investigation of actual or potential hazardous exposures [69][70][71]. Thus, radiobiological clues to investigate the low-dose effects of high-energy radiation first have to be obtained from dose-relationship studies using in vitro and in vivo animal models [72]. ...
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The total body irradiation of lymphomas and co-irradiation in the treatment of adjacent solid tumors can lead to a reduced ovarian function, premature ovarian insufficiency, and menopause. A small number of studies has assessed the radiation-induced damage of primordial follicles in animal models and humans. Studies are emerging that evaluate radiation-induced damage to the surrounding ovarian tissue including stromal and immune cells. We reviewed basic laboratory work to assess the current state of knowledge and to establish an experimental setting for further studies in animals and humans. The experimental approaches were mostly performed using mouse models. Most studies relied on single doses as high as 1 Gy, which is considered to cause severe damage to the ovary. Changes in the ovarian reserve were related to the primordial follicle count, providing reproducible evidence that radiation with 1 Gy leads to a significant depletion. Radiation with 0.1 Gy mostly did not show an effect on the primordial follicles. Fewer data exist on the effects of radiation on the ovarian microenvironment including theca-interstitial, immune, endothelial, and smooth muscle cells. We concluded that a mouse model would provide the most reliable model to study the effects of low-dose radiation. Furthermore, both immunohistochemistry and fluorescence-activated cell sorting (FACS) analyses were valuable to analyze not only the germ cells but also the ovarian microenvironment.
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Steel alloys are widely used for radiation shielding in nuclear applications since Cobalt is an expensive element, this leads to the steels is may be expensive, so it is preventing wider application and selection. So the important direction of this research is preparing cobalt-free maraging stainless steel as shielding to reduce the production cost. Therefore, seven different free-cobalt steel alloys were prepared by using an electro slag re-melting technique. Steel compound ratios were calculated by using the software WinXCOM program for Monte Carlo simulation, at energies of photon 662, 1173 and 1332 keV. The attenuation properties of these alloys were studied. Furthermore, the total of removal macroscopic cross-section, transmission number and mean free path were determined using Geant4 code for fast neutrons radiation shielding. Therefore, shielding parameter variations are applied to the steel alloys to investigate the superior shielding properties to gamma rays than other materials.
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One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose. However, the strength of evidence varies by cancer site and questions remain about site-specific age at exposure patterns. For solid cancers, there is a large body of evidence that excess relative risk (ERR) diminishes with increasing age at exposure. This pattern of risk is observed in the Life Span Study (LSS) as well as in other radiation-exposed populations for overall solid cancer incidence and mortality and for most site-specific solid cancers. However, there are some disparities by endpoint in the degree of variation of ERR with exposure age, with some sites (e.g., colon, lung) in the LSS incidence data showing no variation, or even increasing ERR with increasing age at exposure. The pattern of variation of excess absolute risk (EAR) with age at exposure is often similar, with EAR for solid cancers or solid cancer mortality decreasing with increasing age at exposure in the LSS. We shall review the human data from the Japanese LSS cohort, and a variety of other epidemiological data sets, including a review of types of medical diagnostic exposures, also some radiobiological animal data, all bearing on the issue of variations of radiation late-effects risk with age at exposure and with attained age. The paper includes a summary of several oral presentations given in a Symposium on "Age effects on radiation response" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually on 3-6 October 2021.
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Background: Whether radiation-induced thyroid cancer affects survival rates has not been clearly elucidated. Survival could be affected by the thyroid cancer itself, its treatment, or by being a sign of susceptibility to other cancers. The objective of the current study was to determine if the development of thyroid cancer is associated with a differential survival in radiation-exposed individuals. Methods: We conducted a matched prospective cohort mortality follow-up study based on data from a cohort of 4296 individuals who were irradiated for enlarged tonsils during their childhood (between 1939 and 1962) and were prospectively followed since 1974. The study matched an irradiated subject who developed (was exposed to) thyroid cancer (a "case") and two irradiated subjects, who had not developed (were not exposed to) thyroid cancer ("controls") by the time of case incidence. The two controls were randomly matched to cases by gender, year of birth, age at radiation treatment and radiation dose. Then, using a stratified Cox analysis, we compared survival time from the date of thyroid cancer diagnosis or time of selection to either date of death or the end of the observation period (December 31st, 2016). Vital status and causes of death were determined using the National Death Index (1979-2016), the Social Security Death Index (1974-1979), and study files. Cause of death was categorized as cardiovascular, malignancy, or other. Results: A total of 1008 subjects were included in the analysis, including 353 thyroid cancer cases. At the end of the study period, 162 out of 655 (24.7%) of individuals without thyroid cancer had died compared with 100 of 353 (28.3%) of the subjects with thyroid cancer. The hazard ratio (HR) for all-cause mortality, comparing the thyroid cancer cases to controls, was close to unity (HR=1.01 [0.77-1.33]). HRs remained insignificant after eliminating matched sets with microcarcinomas, defined as tumor size < 10 mm (HR=1.39 [0.96-2.03]). Distribution of the causes of death taking into account age and the time of observation differed between cases and controls (p<0.05). Neither increased cardiovascular-related nor malignancy-related mortality was associated with radiation-induced thyroid cancer. Conclusions: Among individuals irradiated for benign conditions in childhood, development of thyroid cancer was not associated with decreased all-cause survival.
Article
Ionizing radiation is an established carcinogen, but its effects on non-malignant respiratory disease (NMRD) are less clear. Cohorts exposed to multiple risk factors including radiation and toxic dusts conflate these relationships, and there is a need for clarity in previous findings. This systematic review was conducted to survey the body of existing evidence for radiation effects on NMRD in global nuclear worker cohorts. A PubMed search was conducted for studies with terms relating to radiation or uranium and noncancer respiratory outcomes. Papers were limited to the most recent report within a single cohort published between January 2000 and December 2020. Publication quality was assessed based upon UNSCEAR 2017 criteria. In total, 31 papers were reviewed. Studies included 29 retrospective cohorts, one prospective cohort, and one longitudinal cohort primarily comprising White men from the U.S., Canada and Western Europe. Ten studies contained subpopulations of uranium miners or millers. Papers reported standardized mortality ratio (SMR) analyses, regression analyses, or both. Neither SMR nor regression analyses consistently showed a relationship between radiation exposure and NMRD. A meta-analysis of excess relative risks (ERRs) for NMRD did not present evidence for a dose-response (overall ERR/Sv: 0.07; 95% CI: –0.07, 0.21), and results for more specific outcomes were inconsistent. Significantly elevated SMRs for NMRD overall were observed in two studies among the subpopulation of uranium miners and millers (combined n = 4229; SMR 1.42–1.43), indicating this association may be limited to mining and milling populations and may not extend to other nuclear workers. A quality review showed limited capacity of 17 out of 31 studies conducted to provide evidence for a causal relationship between radiation and NMRD; the higher-quality studies showed no consistent relationship. All elevated NMRD SMRs were among mining and milling cohorts, indicating different exposure profiles between mining and non-mining cohorts; future pooled cohorts should adjust for mining exposures or address mining cohorts separately.
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Background: Adverse outcome pathways (AOPs) describe how a measurable sequence of key events, beginning from a molecular initiator, can lead to an adverse outcome of relevance to risk assessment. An AOP is modular by design, comprised of four main components: (1) a Molecular Initiating Event (MIE), (2) Key Events (KEs), (3) Key Event Relationships (KERs) and (4) an Adverse Outcome (AO). Purpose: Here, we illustrate the utility of the AOP concept through a case example in the field of ionizing radiation, using the Organisation for Economic Cooperation and Development (OECD) Users' Handbook. This AOP defines a classic targeted response to a radiation insult with an AO of lung cancer that is relevant to radon gas exposure. Materials and methods: To build this AOP, over 500 papers were reviewed and categorized based on the modified Bradford-Hill Criteria. Data-rich key events from the MIE, to several measurable KEs and KERs related to DNA damage response/repair were identified. Results: The components for this AOP begin with direct deposition of energy as the MIE. Energy deposited into a cell can lead to multiple ionization events to targets such as DNA. This energy can damage DNA leading to double-strand breaks (DSBs) (KE1), this will initiate repair activation (KE2) in higher eukaryotes through mechanisms that are quick and efficient, but error-prone. If DSBs occur in regions of the DNA transcribing critical genes, then mutations (KE3) generated through faulty repair may alter the function of these genes or may cause chromosomal aberrations (KE4). This can impact cellular pathways such as cell growth, cell cycling and then cellular proliferation (KE5). This will form hyperplasia in lung cells, leading eventually to lung cancer (AO) induction and metastasis. The weight of evidence for the KERs was built using biological plausibility, incidence concordance, dose-response, time-response and essentiality studies. The uncertainties and inconsistencies surrounding this AOP are centered on dose-response relationships associated with dose, dose-rates and radiation quality. Conclusion: Overall, the AOP framework provided an effective means to organize the scientific knowledge surrounding the KERs and identify those with strong dose-response relationships and those with inconsistencies. This case study is an example of how the AOP methodology can be applied to sources of radiation to help support areas of risk assessment.
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The aim of this study is to calculate the patient radiation dose and Lifetime Attributable Risk (LAR) in Cardiovascular Interventional Radiological (CVIR) procedures. The patient population included 327 patients who underwent Coronary Angiography (CA) and Percutaneous Coronary Interventions (PCI). Exposure data were reported for every examination such as Kerma-Area Product (KAP), fluoroscopy time and number of exposures. Organ dose and effective dose were assessed by PCXMC software. LAR values were determined according to BEIRVII report. The mean effective dose per examination in CA is 12.6 mSv for males and 10.25 mSv for females. In PCI, the mean effective dose is 18.06 mSv for males and 22.73 mSv for females. Organs with highest dose are thymus, heart, breast, and lung. The mean of LAR value in CA is 62 and 60 for males and females, respectively. In PCI, the mean of LAR value is 89 and 132 for males and females, respectively. Also, the KAP to effective dose conversion factors (CF KAP-ED) were calculated. CF KAP-ED for CA is 0.249 in males and 0.228 in females, and for PCI is 0.2446 and 0.2316 for males and females, respectively. This study will help better understand the concept of ionizing radiation dose in the CVIR procedures and how the individual patient’s effective dose and LAR can evaluate the cancer risk.
Article
It is well understood that all life is subject to continuous low levels of ionizing radiation, most prominently from the natural background of the biosphere, differing appreciably in particular situations across the surface of the globe. Added to this, albeit in much more isolated situations inclusive of particular workplaces and different environments, are exposures from ionizing radiations traced to human activities. Accordingly, studies of the effects of background-level radiations are subject to complex multifactorial influences. The radiation safety regulations and limits for lower levels of exposure are based on extrapolation from more elevated doses and dose rates, embodied in the linear no-threshold (LNT) model. The LNT model assumes the relationship between biological effects and radiation dose at low levels to be linear, all doses in excess of normal background carrying risk. Substantiated for high dose exposures, the validity of the model is unknown for low doses, the elucidation of possible beneficial hormetic and adaptive effects remaining a challenge. Herein, an overview of the effect on organisms of reduced low-levels of radiations is presented using available evidence and discussion of theoretical possibilities.
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There remains considerable uncertainty in obtaining risk estimates of adverse health outcomes of chronic low-dose radiation. In the absence of reliable direct data, extrapolation through the linear no-threshold (LNT) hypothesis forms the cardinal tenet of all risk assessments for low doses (≤ 100 mGy) and for the radiation protection principle of As Low As Reasonably Achievable (ALARA). However, as recent evidence demonstrates, LNT assumptions do not appropriately reflect the biology of the cell at the low-dose end of the dose-response curve. In this regard, human populations living in high-level natural radiation areas (HLNRA) of the world can provide valuable insights into the biological and cellular effects of chronic radiation to facilitate improved precision of the dose-response relationship at low doses. Here, data obtained over decades of epidemiological and radiobiological studies on HLNRA populations is summarized. These studies do not show any evidence of unfavourable health effects or adverse cellular effects that can be correlated with high-level natural radiation. Contrary to the assumptions of LNT, no excess cancer risks or untoward pregnancy outcomes have been found to be associated with cumulative radiation dose or in-utero exposures. Molecular biology-driven studies demonstrate that chronic low-dose activates several cellular defence mechanisms that help cells to sense, recover, survive, and adapt to radiation stress. These mechanisms include stress-response signaling, DNA repair, immune alterations and most importantly, the radiation-induced adaptive response. The HLNRA data is consistent with the new evolving paradigms of low-dose radiobiology and can help develop the theoretical framework of an alternate dose-response model. A rational integration of radiobiology with epidemiology data is imperative to reduce uncertainties in predicting the potential health risks of chronic low doses of radiation.
Article
Background The US has recently lowered the entry age for lung cancer screening with low-dose computed tomography (LDCT) from 55 to 50 years. The effect of the younger age for starting screening on the rates of screen-detected and radiation-induced lung cancers in women remains unclear. Methods A modeling study was conducted. A static cohort of 100,000 heavy female smokers was simulated to undergo annual lung cancer screening with LDCT. The number of screen-detected lung cancers (benefit) and radiation-induced lung cancers (harm) per 1000 screenees were calculated for scenarios with two starting ages (55-50 years) and fixed stopping age (75 years). The benefit-harm ratio and incremental benefit-harm ratio (IBHR) were calculated for each scenario. Results For annual screening from 55 to 75 years, the number of screen-detected and radiation-induced lung cancers was 112.4 and 2.2, respectively. For annual screening from 50 to 75 years, those numbers were 117.0 and 3.4, respectively. The benefit-harm ratio decreased from 51 to 35 and the IBHR decreased from 6.3 to 4.0 when lowering the screening starting age from 55 to 50 years. Conclusions The risk of radiation induced lung cancers increased by 50% when lowering the screening starting age by 5 years in women. However, the benefits of LDCT lung cancer screening still outweigh the assumed radiation harm.
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The International Commission on Radiological Protection (ICRP) has embarked on a review and revision of the System of Radiological Protection that will update the 2007 General Recommendations in ICRP Publication 103. This is the beginning of a process that will take several years, involving open and transparent engagement with organisations and individuals around the world. While the System is robust and has performed well, it must adapt to address changes in science and society to remain fit for purpose. The aim of this paper is to encourage discussions on which areas of the System might gain the greatest benefit from review, and to initiate collaborative efforts. Increased clarity and consistency are high priorities. The better the System is understood, the more effectively it can be applied, resulting in improved protection and increased harmonisation. Many areas are identified for potential review including: classification of effects, with particular focus on tissue reactions; reformulation of detriment, potentially including non-cancer diseases; re-evaluation of the relationship between detriment and effective dose, and the possibility of defining detriments for males and females of different ages; individual variation in the response to radiation exposure; heritable effects; and effects and risks in non-human biota and ecosystems. Some of the basic concepts are also being considered, including the framework for bringing together protection of people and the environment, incremental improvements to the fundamental principles of justification and optimisation, a broader approach to protection of individuals, and clarification of the exposure situations introduced in 2007. In addition, ICRP is considering identifying where explicit incorporation of the ethical basis of the System would be beneficial, how to better reflect the importance of communications and stakeholder involvement, and further advice on education and training. ICRP invites responses on these and other areas relating to the review of the System of Radiological Protection.
Book
Natural radiation arises from many sources, from the unstable atoms within our own bodies and in the materials around us, from the Sun, and even from beyond the Solar System. Additional sources include the legacy of testing nuclear weapons, nuclear waste, and nuclear accidents. All these sources have provided means of dating environmental materials and tracing the movements of substances through land, sea, and air. But ionising radiation also interacts with DNA, which has led to a remarkable range of studies to examine how and how quickly these unstable atoms are accumulated by both humans and biota, and their various effects on both. Providing an overview of the sources, uses and impacts of ionising radiation in the environment, and the frameworks developed to manage exposures to them, this is a valuable reference for graduate students and researchers interested in radioecology, environmental science and radiological protection.
Article
Recent studies suggest that every year worldwide about a million patients might be exposed to doses of the order of 100 mGy of low-LET radiation, due to recurrent application of radioimaging procedures. This paper presents a synthesis of recent epidemiological evidence on radiation-related cancer risks from low-LET radiation doses of this magnitude. Evidence from pooled analyses and meta-analyses involving epidemiological studies that, individually, do not find statistically significant radiation-related cancer risks is reviewed, and evidence from additional and more recent epidemiological studies of radiation exposures indicating excess cancer risks is also summarized. Cohorts discussed in the present paper include Japanese atomic bomb survivors, nuclear workers, patients exposed for medical purposes, and populations exposed environmentally to natural background radiation or radioactive contamination. Taken together, the overall evidence summarized here is based on studies including several million individuals, many of them followed-up for more than half a century. In summary, substantial evidence was found from epidemiological studies of exposed groups of humans that ionizing radiation causes cancer at acute and protracted doses above 100 mGy, and growing evidence for doses below 100 mGy. The significant radiation-related solid cancer risks observed at doses of several 100 mGy of protracted exposures (observed, for example, among nuclear workers) demonstrate that doses accumulated over many years at low dose rates do cause stochastic health effects. On this basis, it can be concluded that doses of the order of 100 mGy from recurrent application of medical imaging procedures involving ionizing radiation are of concern, from the viewpoint of radiological protection.
Article
In this study, seven different steel alloys are based on the nominal composition of free cobalt, although cobalt is one of the alloying composite elements, but it is expensive; Therefore, we proceeded to prepare cobalt-free stainless steel by using an electro slag re-melting technique as a radiation shield to reduce production cost. The proportions of the steel compound were determined using XRF techniques. The gamma and neutron shielding properties of 7 different types of stainless steel have been investigated. We have calculated the mass attenuation coefficient (μ/ρ), half value layer (HVL), and effective atomic number (Zeff) for total photon interaction in the wide energy range of 80 keV–1333 keV using hyper pure germanium (HPGe) detector and WinXCOM computer program. Furthermore, the macroscopic effective removal cross-sections (∑R) for fast neutron were calculated. The dependence of different parameters on incident photon energy and chemical content has been discussed. Among the selected cobalt-free alloy steels, No. A6 with density 8.28 g/cm³ showed superior gamma ray and neutron shielding properties. This work was carried out to explore the advantages of alloy steels in gamma and neutron protection applications.
Article
Importance Whether computed tomography (CT) radiation is truly carcinogenic remains controversial. Large epidemiological studies that purportedly showed an association between CT radiation and carcinogenesis were limited by confounding by indication and reverse causation, because the reasons for CT examination were unknown. Objective To measure the risk of hematologic malignant neoplasms associated with perioperative abdominopelvic CT radiation among patients who underwent appendectomy for acute appendicitis. Design, Setting, and Participants This nationwide population-based cohort study used the National Health Insurance Service claims database in South Korea to assess 825 820 patients who underwent appendectomy for appendicitis from January 1, 2005, to December 31, 2015, and had no underlying risk factors for cancer. Patients were divided into CT-exposed (n = 306 727) or CT-unexposed (n = 519 093) groups. The study was terminated on December 31, 2017, and data were analyzed from October 30, 2018, to September 27, 2020. Exposures Perioperative abdominopelvic CT examination from 7 days before to 7 days after appendectomy. Main Outcomes and Measures The primary outcome was the incidence rate ratio (IRR) of hematologic malignant neoplasms for both groups. The secondary outcomes were IRR of abdominopelvic organ cancers and IRR of all cancers. The lag period was 2 years for the primary outcome and 5 years for secondary outcomes. The IRRs were calculated using Poisson regression models with adjustment for age and sex. Results Among the study population of 825 820 patients (52.9% male; median age, 28 [interquartile range, 15-41] years), hematologic malignant neoplasms developed in 323 patients in the CT-exposed group during 1 486 518 person-years and 500 patients in the CT-unexposed group during 3 422 059 person-years. For all hematologic malignant neoplasms, the IRR for the CT-exposed vs CT-unexposed group was 1.26 (95% CI, 1.09-1.45; P = .002). In terms of individual categories of hematologic malignant neoplasms, the CT-exposed group had an elevated risk only for leukemia (IRR, 1.40 [98.75% CI, 1.04-1.87, adjusted by Bonferroni correction]; P = .005). There was no between-group difference in incidence rate of abdominopelvic organ cancers (IRR, 1.07 [95% CI, 1.00-1.15]; P = .06) and that of all cancers (IRR, 1.04 [95% CI, 0.99-1.09]; P = .14). Conclusions and Relevance This study controlled for reverse causation bias by defining the reasons for CT scan, and findings suggest that abdominopelvic CT radiation is associated with a higher incidence of hematologic malignant neoplasms. Efforts should be continued for judicious use of CT examinations.
Article
Background Exposure to high doses of ionizing radiation is known to cause cancer. Exposure during childhood is associated with a greater excess relative risk for leukemia and tumors of the central nervous system (CNS) than exposure in later life. Cancer risks associated with low-dose exposure (<100 mSv) are uncertain. We previously investigated the association between the incidence of childhood cancer and levels of exposure to external background radiation from terrestrial gamma and cosmic rays in Switzerland using data from a nationwide census-based cohort study. Here, we provide an update of that study using an extended follow-up period and an improved exposure model. Methods We included all children 0–15 years of age registered in the Swiss national censuses 1990, 2000, and 2010–2015. We identified incident cancer cases during 1990–2016 using probabilistic record linkage with the Swiss Childhood Cancer Registry. Exposure to terrestrial and cosmic radiation at children's place of residence was estimated using geographic exposure models based on aerial spectrometric gamma-ray measurements. We estimated and included the contribution from ¹³⁷Cs deposition after the Chernobyl accident. We created a nested case-control sample and fitted conditional logistic regression models adjusting for sex, year of birth, neighborhood socioeconomic position, and modelled outdoor NO2 concentration. We also estimated the population attributable fraction for childhood cancer due to external background radiation. Results We included 3,401,113 children and identified 3,137 incident cases of cancer, including 951 leukemia, 495 lymphoma, and 701 CNS tumor cases. Median follow-up in the cohort was 6.0 years (interquartile range: 4.3–10.1) and median cumulative exposure since birth was 8.2 mSv (range: 0–31.2). Hazard ratios per 1 mSv increase in cumulative dose of external background radiation were 1.04 (95% CI: 1.01–1.06) for all cancers combined, 1.06 (1.01–1.10) for leukemia, 1.03 (0.98–1.08) for lymphoma, and 1.06 (1.01–1.11) for CNS tumors. Adjustment for potential confounders had little effect on the results. Based on these results, the estimated population attributable fraction for leukemia and CNS tumors due to external background radiation was 32% (7–49%) and 34% (5–51%), respectively. Conclusions Our results suggest that background ionizing radiation contributes to the risk of leukemia and CNS tumors in children.
Article
Radiation detriment is a concept developed by the International Commission on Radiological Protection to quantify the burden of stochastic effects from low-dose and/or low-dose-rate exposures to the human population. It is determined from the lifetime risks of cancer for a set of organs and tissues and the risk of heritable effects, taking into account the severity of the consequences. This publication provides a historical review of detriment calculation methodology since ICRP Publication 26, with details of the procedure developed in ICRP Publication 103, which clarifies data sources, risk models, computational methods, and rationale for the choice of parameter values. A selected sensitivity analysis was conducted to identify the parameters and calculation conditions that can be major sources of variation and uncertainty in the calculation of radiation detriment. It has demonstrated that sex, age at exposure, dose and dose-rate effectiveness factor, dose assumption in the calculation of lifetime risk, and lethality fraction have a substantial impact on radiation detriment values. Although the current scheme of radiation detriment calculation is well established, it needs to evolve to better reflect changes in population health statistics and progress in scientific understanding of radiation health effects. In this regard, some key parameters require updating, such as the reference population data and cancer severity. There is also room for improvement in cancer risk models based on the accumulation of recent epidemiological findings. Finally, the importance of improving the comprehensibility of the detriment concept and the transparency of its calculation process is emphasised. © 2022 ICRP. Published by SAGE.
Thesis
Les faibles doses de radiation constituent un enjeu sociétal important, notamment pour l’estimation des risques potentiellement liés aux expositions médicales. En effet, la dose délivrée pendant des examens de radiodiagnostic a plus que doublé en 10 ans. L’évaluation du risque radioinduit est toutefois rendue difficile par la variété des protocoles d’irradiation (dose par séance, dose cumulée, débit de dose, type de radiation), le manque de sensibilité des dispositifs dosimétriques et le manque de connaissance des effets biologiques spécifiques des faibles doses comme l’hypersensibilité aux faibles doses (HFD), la réponse adaptative (RA) et l’hormésis. De plus, il apparaît aujourd’hui que le facteur individuel peut influencer significativement la réponse biologique et clinique aux radiations. Dans le cadre de cette thèse, afin de mieux évaluer le risque individuel lié aux faibles doses de radiation dans un contexte de radiodiagnostic médical, nous avons conjugué les savoir-faire de deux structures : la société Fibermetrix qui apporte une technologie nouvelle de dosimètres physiques basés sur la fibre optique et l’Unité Inserm UA8 « Radiations : Défense, Santé, Environnement » dont les modèles mécanistiques développés sur des données humaines permettent aujourd’hui de mieux comprendre certains effet radiobiologiques. En particulier, nous proposons d’exposer une collection de fibroblastes, astrocytes et cellules mammaires humaines à des conditions d’examens scanographiques classiques (examen du cerveau ou du thorax), et d’en mieux comprendre les effets biologiques spécifiques en utilisant l’immunofluorescence et des biomarqueurs de la réparation et de la signalisation des cassures double-brin de l’ADN (CDB). Après avoir proposé un modèle mécanique basé sur le transit radioinduit de la protéine ATM du cytoplasme au noyau pour les 3 effets radiobiologiques spécifiques des faibles doses (HRS, RA et hormésis), l’analyse par immunofluorescence des données issues des irradiations scanographiques montrent que celles-ci produisent un excès de CDB pour des cellules issues de patients radiosensibles ou prédisposés au cancer ou au vieillissement et qu’elles stimulent différemment l’arrivée de protéines ATM fonctionnelles dans le noyau. Dans le même temps, le dispositif IVISCAN de Fibermetrix a permis une évaluation plus précise de la dose. Cette approche a abouti à une évaluation du risque dans chaque condition testée, une définition des statuts génétiques à risque pour les faibles doses et des recommandations sur la façon de pratiquer des analyses de risque des patients irradiés
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Background: The current study followed-up site-specific cancer risks in an unique cohort with 30 years' follow-up after long-term low-dose-rate radiation exposure in Taiwan. Methods: 6242 Taiwanese people received extra exposure in residential and school buildings constructed with Co-60-contaminated steel from 1982 until informed and relocated in early 1990s. The additional doses received have been estimated. During 1983-2012, 300 cancer cases were identified through the national cancer registry in Taiwan, 247 cases with minimum latent periods from initial exposure. The hazard ratios (HR) of site-specific cancers were estimated with additional cumulative exposure estimated individually. Results: Dose-dependent risks were statistically significantly increased for leukaemia excluding chronic lymphocytic leukaemia (HR100mSv 1.18; 90% CI 1.04-1.28), breast cancers (HR100mSv 1.11; 90% CI 1.05-1.20), and all cancers (HR100mSv 1.05; 90% CI 1.0-1.08, P=0.04). Women with an initial age of exposure lower than 20 were shown with dose response increase in breast cancers risks (HR100mSv 1.38; 90% CI 1.14-1.60; P=0.0008). Conclusions: Radiation exposure before age 20 was associated with a significantly increased risk of breast cancer at much lower radiation exposure than observed previously.British Journal of Cancer advance online publication 3 October 2017; doi:10.1038/bjc.2017.350 www.bjcancer.com.
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Background: Accurate dosimetry is key to deriving the dose response from radiation exposure in an epidemiological study. It becomes increasingly important to estimate dose as accurately as possible when evaluating low dose and low dose rate as the calculation of excess relative risk per Gray (ERR/Gy) is very sensitive to the number of excess cancers observed, and this can lead to significant errors if the dosimetry is of poor quality. By including an analysis of the dosimetry, we gain a far better appreciation of the robustness of the work from the standpoint of its value in supporting the shape of the dose response curve at low doses and low dose rates. This article summarizes a review of dosimetry supporting epidemiological studies currently being considered for a re-evaluation of the linear no-threshold assumption as a basis for radiation protection. The dosimetry for each study was evaluated based on important attributes from a dosimetry perspective. Our dosimetry review consisted of dosimetry supporting epidemiological studies published in the literature during the past 15 years. Based on our review, it is clear there is wide variation in the quality of the dosimetry underlying each study. Every study has strengths and weaknesses. The article describes the results of our review, explaining which studies clearly stand out for their strengths as well as common weaknesses among all investigations. Purpose: To summarize a review of dosimetry used in epidemiological studies being considered by the National Council on Radiation Protection and Measurements (NCRP) in an evaluation of the linear no-threshold dose-response model that underpins the current framework of radiation protection. Materials and methods: The authors evaluated each study using criteria considered important from a dosimetry perspective. The dosimetry analysis was divided into the following categories: (1) general study characteristics, (2) dose assignment, (3) uncertainty, (4) dose confounders (5) dose validation, and (6) strengths and weaknesses of the dosimetry. Our review focused on approximately 20 studies published in the literature primarily during the past 15 years. Results: Based on the review, it is clear there is wide variation in the quality of the dosimetry underlying each study. Every study has strengths and weaknesses. This paper describes the results of our review, identifies common weaknesses among all investigations, and recognizes studies that clearly stand out for their overall strengths. Conclusions: The paper concludes by offering recommendations to investigators on possible ways in which dosimetry could be improved in future epidemiological studies.
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In epidemiological studies, exposures of interest are often measured with uncertainties, which may be independent or correlated. Independent errors can often be characterized relatively easily while correlated measurement errors have shared and hierarchical components that complicate the description of their structure. For some important studies, Monte Carlo dosimetry systems that provide multiple realizations of exposure estimates have been used to represent such complex error structures. While the effects of independent measurement errors on parameter estimation and methods to correct these effects have been studied comprehensively in the epidemiological literature, the literature on the effects of correlated errors, and associated correction methods is much more sparse. In this paper, we implement a novel method that calculates corrected confidence intervals based on the approximate asymptotic distribution of parameter estimates in linear excess relative risk (ERR) models. These models are widely used in survival analysis, particularly in radiation epidemiology. Specifically, for the dose effect estimate of interest (increase in relative risk per unit dose), a mixture distribution consisting of a normal and a lognormal component is applied. This choice of asymptotic approximation guarantees that corrected confidence intervals will always be bounded, a result which does not hold under a normal approximation. A simulation study was conducted to evaluate the proposed method in survival analysis using a realistic ERR model. We used both simulated Monte Carlo dosimetry systems (MCDS) and actual dose histories from the Mayak Worker Dosimetry System 2013, a MCDS for plutonium exposures in the Mayak Worker Cohort. Results show our proposed methods provide much improved coverage probabilities for the dose effect parameter, and noticeable improvements for other model parameters.
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The reconstruction of radiation doses to Mayak Production Association workers in central Russia supports radiation epidemiological studies for the U.S.-Russian Joint Coordinating Committee on Radiation Effects Research. The most recent version of the dosimetry was performed with the Mayak Worker Dosimetry System-2013. This introduction outlines the logic and general content of the series of articles presented in this issue of Radiation Protection Dosimetry. The articles summarize the models, describe the basis for most of the key decisions made in developing the models and present an overview of the results.
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Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.
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Incidence of all types of lymphatic and hematopoietic cancers, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, acute and chronic myeloid leukemia (AML and CML respectively), chronic lymphocytic leukemia (CLL) and other forms of leukemia have been studied in a cohort of 22,373 workers employed at the Mayak Production Association (PA) main facilities during 536,126 person-years of follow-up from the start of employment between 1948 and 1982 to the end of 2004. Risk assessment was performed for both external gamma-radiation and internal alpha-exposure of red bone marrow due to incorporated Pu-239 using Mayak Workers Dosimetry System 2008 taking into account non-radiation factors. The incidence of leukemia excluding CLL showed a non-linear dose response relationship for external gamma exposure with exponential effect modifiers based on time since exposure and age at exposure. Among the major subtypes of leukemia, the excess risk of AML was the highest within the first 2-5 years of external exposure (ERR per Gy: 38.40; 90% CI: 13.92-121.4) and decreased substantially thereafter, but the risks remained statistically significant (ERR per Gy: 2.63; 90% CI: 0.07-12.55). In comparison, excess CML first occurred 5 years after exposure and decreased about 10 years after exposure, although the association was not statistically significant (ERR per Gy: 1.39; 90% CI: -0.22-7.32). The study found no evidence of an association between leukemia and occupational exposure to internal plutonium ERR per Gy 2.13; 90% CI: <0-9.45). There was also no indication of any relationship with either external gamma or internal plutonium radiation exposure for either incidence of Hodgkin or non-Hodgkin lymphoma or multiple myeloma.
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Background: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality. Methods: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983–2005 among 66915 female technologists, and 586 breast cancer deaths occurred during 1983–2008 among 83538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors. Results: Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100mGy = 0.16; 95% CI: 0.03–0.39) with similar patterns for mortality among technologists born before 1930. Conclusions: Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.
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Background: Previous studies have shown that acute external in utero exposure to ionizing radiation can increase cancer risk. It is not known whether chronic exposure at low dose rates, including due to radionuclide intake, influences the lifetime risk of solid cancers in the offspring. The objective of this study was to investigate solid cancer risk after in utero irradiation. Methods: Cancer incidence and mortality over a 60-year period (from January 1950 to December 2009) were analyzed in the Urals Prenatally Exposed Cohort (UPEC). The cohort comprised in utero exposed offspring of Mayak Production Association female workers and of female residents of Techa River villages. Some of the offspring also received postnatal exposure, either due to becoming radiation workers themselves or due to continuing to live in the contaminated areas of the Techa River. The mortality analyses comprised 16,821 subjects (601,372 person-years), and the incidence analyses comprised 15,813 subjects (554,411 person-years). Poisson regression was used to quantify the relative risk as a function of the in utero soft tissue dose (with cumulative doses up to 944.9 mGy, mean dose of 14.1 mGy in the pooled cohort) and the postnatal stomach dose for solid cancer incidence and mortality. Results: When a log-linear model was used, relative risk of cancer per 10 mGy of in utero dose was 0.99 (95% confidence interval (CI) = 0.96 to 1.01) based on incidence data and 0.98 (CI = 0.94 to 1.01) based on mortality data. Postnatal exposure to ionizing radiation was positively associated with the solid cancer risk in members of the UPEC, with a relative risk of 1.02 per 10mGy CI = 1.00 to 1.04). Conclusions: No strong evidence was found that chronic low-dose-rate exposure of the embryo and fetus increased the risk of solid cancers in childhood or in adulthood. For both incidence and mortality, a tendency towards a decreased relative risk was noted with increasing doses to soft tissues of the fetus. Further follow-up will provide more precise radiation risk estimates of solid cancer as cohort members are approaching their 60s and cancer becomes more common.
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Background: We previously reported evidence of a dose–response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings. Methods: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose–response analyses with our original results. Results: We obtained information from the RIS and death certificates for about 40% of the cohort (n~180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose–response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend = 0.02) and by 30% from 0.023 to 0.016 (P-trend < 0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases. Conclusions: Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients.
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The objective of this study was to estimate solid cancer risk attributable to long-term, fractionated occupational exposure to low-doses of ionizing radiation. Based on cancer incidence for the period 1950-1995 in a cohort of 27,011 Chinese medical diagnostic X-ray workers and a comparison cohort of 25,782 Chinese physicians who did not use X-ray equipment in their work, we used Poisson regression to fit excess relative risk (ERR) and excess absolute risk (EAR) dose-response models for incidence of all solid cancers combined. Radiation dose reconstruction was based on a previously published method that relied on simulating measurements for multiple X-ray machines, workplaces and working conditions, information about protective measures, including use of lead aprons, and work histories. The resulting model was used to estimate calendar year-specific badge dose calibrated as personal dose equivalent (Sv). To obtain calendar year-specific colon doses (Gy), we applied a standard organ conversion factor. 1643 cases of solid cancer were identified in 1.45 million person-years of follow-up. In both ERR and EAR models, a statistically significant radiation dose-response relationship was observed for solid cancers as a group. Averaged over both sexes, and using colon dose as the dose metric, the estimated ERR/Gy was 0.87 (95% CI: 0.48, 1.45), and the EAR was 22 per 10(4) PY-Gy (95% CI: 14, 32) at age 50. We obtained estimates of the ERR and EAR of solid cancers per unit dose that are compatible with those derived from other populations chronically exposed to low dose-rate occupational or environmental radiation. This article is protected by copyright. All rights reserved.
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Objectives: Until recently, enrichment of uranium for civil and military purposes in France was carried out by gaseous diffusion using rapidly soluble uranium compounds. We analysed the relationship between exposure to soluble uranium compounds and exposure to external γ-radiation and mortality in a cohort of 4688 French uranium enrichment workers who were employed between 1964 and 2006. Methods: Data on individual annual exposure to radiological and non-radiological hazards were collected for workers of the AREVA NC, CEA and Eurodif uranium enrichment plants from job-exposure matrixes and external dosimetry records, differentiating between natural, enriched and depleted uranium. Cause-specific mortality was compared with the French general population via standardised mortality ratios (SMR), and was analysed via Poisson regression using log-linear and linear excess relative risk models. Results: Over the period of follow-up, 131 161 person-years at risk were accrued and 21% of the subjects had died. A strong healthy worker effect was observed: all causes SMR=0.69, 95% CI 0.65 to 0.74. SMR for pleural cancer was significantly increased (2.3, 95% CI 1.06 to 4.4), but was only based on nine cases. Internal uranium and external γ-radiation exposures were not significantly associated with any cause of mortality. Conclusions: This is the first study of French uranium enrichment workers. Although limited in statistical power, further follow-up of this cohort, estimation of internal uranium doses and pooling with similar cohorts should elucidate potential risks associated with exposure to soluble uranium compounds.
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Study question Is protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer? Methods In this cohort study, 308 297 workers in the nuclear industry from France, the United Kingdom, and the United States with detailed monitoring data for external exposure to ionising radiation were linked to death registries. Excess relative rate per Gy of radiation dose for mortality from cancer was estimated. Follow-up encompassed 8.2 million person years. Of 66 632 known deaths by the end of follow-up, 17 957 were due to solid cancers. Study answer and limitations Results suggest a linear increase in the rate of cancer with increasing radiation exposure. The average cumulative colon dose estimated among exposed workers was 20.9 mGy (median 4.1 mGy). The estimated rate of mortality from all cancers excluding leukaemia increased with cumulative dose by 48% per Gy (90% confidence interval 20% to 79%), lagged by 10 years. Similar associations were seen for mortality from all solid cancers (47% (18% to 79%)), and within each country. The estimated association over the dose range of 0-100 mGy was similar in magnitude to that obtained over the entire dose range but less precise. Smoking and occupational asbestos exposure are potential confounders; however, exclusion of deaths from lung cancer and pleural cancer did not affect the estimated association. Despite substantial efforts to characterise the performance of the radiation dosimeters used, the possibility of measurement error remains. What this study adds The study provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality. Although high dose rate exposures are thought to be more dangerous than low dose rate exposures, the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors. Quantifying the cancer risks associated with protracted radiation exposures can help strengthen the foundation for radiation protection standards. Funding, competing interests, data sharing Support from the US Centers for Disease Control and Prevention; Ministry of Health, Labour and Welfare of Japan; Institut de Radioprotection et de Sûreté Nucléaire; AREVA; Electricité de France; US National Institute for Occupational Safety and Health; US Department of Energy; and Public Health England. Data are maintained and kept at the International Agency for Research on Cancer.
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Previously reported studies of the Techa River Cohort have established associations between radiation dose and the occurrence of solid cancers and leukemia (non-CLL) that appear to be linear in dose response. These analyses include 17,435 cohort members alive and not known to have had cancer prior to January 1, 1956 who lived in areas near the river or Chelyabinsk City at some time between 1956 and the end of 2007, utilized individualized dose estimates computed using the Techa River Dosimetry System 2009 and included five more years of follow-up. The median and mean dose estimates based on these doses are consistently higher than those based on earlier Techa River Dosimetry System 2000 dose estimates. This article includes new site-specific cancer risk estimates and risk estimates adjusted for available information on smoking. There is a statistically significant (P = 0.02) linear trend in the smoking-adjusted all-solid cancer incidence risks with an excess relative risk (ERR) after exposure to 100 mGy of 0.077 with a 95% confidence interval of 0.013-0.15. Examination of site-specific risks revealed statistically significant radiation dose effects only for cancers of the esophagus and uterus with an ERR per 100 mGy estimates in excess of 0.10. Esophageal cancer risk estimates were modified by ethnicity and gender, but not smoking. While the solid cancer rates are attenuated when esophageal cancer is removed (ERR = 0.063 per 100 mGy), a dose-response relationship is present and it remains likely that radiation exposure has increased the risks for most solid cancers in the cohort despite the lack of power to detect statistically significant risks for specific sites.
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Background There is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low-dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA. Methods We assembled a cohort of 308 297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8·22 million person-years. We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality. Findings Doses were accrued at very low rates (mean 1·1 mGy per year, SD 2·6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2·96 per Gy (90% CI 1·17–5·21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10·45, 90% CI 4·48–19·65). Interpretation This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia.
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Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.