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Stephen G R Barnard

Stephen G R Barnard
UK Health Security Agency

BSc Biology PhD Radiobiology
Biological dosimetry for both emergency response and in clinical patient groups. Radiation-induced cataract.

About

73
Publications
13,977
Reads
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Citations
Introduction
Currently working at UKHSA in the Radiation Effects department of the Centre for Radiation, Chemical and Emergency Hazards Division (RCEHD). Developing techniques in biological dosimetry (Dicentric, micronuclei and FISH translocations) with a particular focus on implementing and improving the gamma-H2AX/53BP1 foci assay for rapid/triage dose estimation. I currently research the role of radiation in cataractogenesis and LEC, the role of DNA damage/repair and proliferation.
Additional affiliations
October 2021 - present
UK Health Security Agency
Position
  • Researcher
September 2020 - September 2021
Public Health England
Position
  • Researcher
March 2010 - September 2020
Public Health England
Position
  • Researcher
Education
October 2014 - December 2019
Durham University
Field of study
  • The effect(s) of dose and dose-rate of ionising radiation on early lens epithelial cell response and cataractogenesis
October 2005 - June 2008
University of the West of England, Bristol
Field of study
  • Biological Sciences

Publications

Publications (73)
Article
Full-text available
Cataract is the leading cause of visual impairment which can result in blindness. Cataract formation has been associated with radiation exposure; however, the mechanistic understanding of this phenomenon is still lacking. The goal of this study was to investigate mechanisms of cataract induction in isolated lens epithelial cells (LEC) exposed to io...
Article
Full-text available
Purpose The aim of this brief personal, high level review is to consider the state of the art for biological dosimetry for radiation routine and emergency response, and the potential future progress in this fascinating and active field. Four areas in which biomarkers may contribute to scientific advancement through improved dose and exposure charac...
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 effect...
Article
Purpose: Cataract (opacification of the ocular lens) is a typical tissue reaction (deterministic effect) following ionizing radiation exposure, for which prevention dose limits have been recommended in the radiation protection system. Manifestations of radiation cataracts can vary among individuals, but such potential individual responses remain u...
Article
Full-text available
Purpose: Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life ex...
Article
Full-text available
Lens epithelial cell proliferation and differentiation are naturally well regulated and controlled, a characteristic essential for lens structure, symmetry and function. The effect of ionizing radiation on lens epithelial cell proliferation has been demonstrated in previous studies at high acute doses, but the effect of dose and dose rate on prolif...
Article
Full-text available
Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in...
Article
Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (,2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis. Recently we have reported an inverse dose...
Article
Full-text available
Following recent developments, the RENEB network (Running the European Network of biological dosimetry and physical retrospective dosimetry) is in an excellent position to carry out large scale molecular epidemiological studies of ionizing radiation effects, with validated expertise in the dicentric, fluorescent in situ hybridization (FISH)-translo...
Technical Report
Full-text available
Global concerns on the potential for malevolent use of high activity sealed sources of ionising radiation have prompted moves to identify options for their replacement with alternative technologies. Sealed sources of caesium-137 are in common use in biological sciences research and in the production of blood products in blood transfusion services....
Article
Chemical-induced premature chromosome condensation (PCC) is an alternative biodosimetry method to the gold-standard dicentric analysis for ionizing radiation. However, existing literature shows great variations in the experimental protocols which, together with the different scoring criteria applied in individual studies, result in large discrepanc...
Thesis
The lens of the eye is thought to be one of the most radiosensitive tissues. Cataracts were one of the first observed biological effects following ionising radiation exposure. The recent change in regulations for eye lens dose limits has led to the urgent need to make sure our biological understanding is sufficient. The anterior of the lens is cove...
Article
Full-text available
The influence of dose rate on radiation cataractogenesis has yet to be extensively studied. One recent epidemiological investigation suggested that protracted radiation exposure increases radiation-induced cataract risk: cumulative doses of radiation mostly <100 mGy received by US radiologic technologists over 5 years were associated with an increa...
Article
Full-text available
Purpose: To determine cumulative scan frequencies and estimate lens dose for paediatric CT head examinations in the context of potential cataract risk. Methods: The cumulative number of headregion CT scans among a cohort of 410,997 children and young adults who underwent CT scanning in the UK between 1985 and 2014 was calculated. Images from a sa...
Article
Purpose: This study aimed to construct a calibration curve for high-dose exposure using cell fusion-induced premature chromosome condensation (PCC). Some of the associated practicalities and methodological details were also investigated. Materials and methods: Peripheral blood from two donors was used. PCC mediated by fusing mitotic CHO cells with...
Data
Software tutorial for DoseEstimateH2AX
Article
Full-text available
Over the last decade, the γ–H2AX focus assay, which exploits the phosphorylation of the H2AX histone following DNA double–strand–breaks, has made considerable progress towards acceptance as a reliable biomarker for exposure to ionizing radiation. While the existing literature has convincingly demonstrated a dose–response effect, and also presented...
Data
DoseEstimateH2AX tutorial. (PDF)
Data
PHE calibration data (1h and 24h) in .xls and .dat format. (ZIP)
Article
Full-text available
Purpose: Epidemiological evidence regarding the radiosensitivity of the lens of the eye and radiation cataract development has led to changes in the EU Basic Safety Standards for protection of the lens against ionizing radiation. However, mechanistic details of lens radiation response pathways and their significance for cataractogenesis remain uncl...
Article
The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were...
Article
Full-text available
Genomic deoxyribonucleic acid (DNA) is continuously being damaged by endogenous processes such as metabolism or by exogenous events such as radiation. The specific phosphorylation of histone H2AX on serine residue 139, described as γ-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs). The yield of γ-H2AX (foci) is shown to...
Article
The radiosensitive nature of the lens has been increasingly reported, although the exact mechanistic details of the radiation response pathways for cataractogenesis are unclear. Radiation-induced DNA damage and the subsequent impairment of repair pathways within the lens epithelium are involved. Here, two distinct regions of the murine lens epithel...
Chapter
Full-text available
The application of random effect models to different radiation biomarkers, including cytogenetic, protein-based, and gene-expression based biomarkers, is discussed. Explicit case studies are provided for the latter two scenarios, in which random effect models appear especially attractive as they can cope well with the large inter-individual variati...
Article
Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and...
Article
The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The recent recommendations of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocula...
Article
Full-text available
Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiatio...
Conference Paper
Full-text available
Introduction In the framework of the RENEB project, two intercomparison exercises were conducted to assess the suitability of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, a...
Article
Full-text available
Purpose: Within the EU RENEB project, seven laboratories have taken part in training and harmonisation activities to strengthen triage gamma-H2AX-based radiation exposure assessment. This has culminated in a second triage biodosimetry exercise. Materials and methods: Whole blood and separated lymphocyte samples were homogenously irradiated with ⁶⁰C...
Article
Purpose: In the framework of the ‘Realizing the European Network of Biodosimetry’ (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency tria...
Technical Report
Full-text available
During the period between the start of 2006 and the end of 2015, 73 people suspected of being overexposed to ionising radiation were referred to Public Health England (and one of its predecessor organisations, the Health Protection Agency) for biological dosimetry. Of these, 45 were related to industrial uses of radiation, 27 were associated with r...
Article
Full-text available
During the period between the start of 2006 and the end of 2015, 73 people suspected of being overexposed to ionising radiation were referred to Public Health England (and one of its predecessor organisations, the Health Protection Agency) for biological dosimetry. Of these, 45 were related to industrial uses of radiation, 27 were associated with r...
Article
Full-text available
The aim of this paper is to explore the evidence for the revised EU basic safety standard (BSS) radiation dose limits to the lens of the eye, in the context of medical occupational radiation exposures. Publications in the open literature have been reviewed in order to draw conclusions on the exposure profiles and doses received by medical radiation...
Article
Full-text available
Elevated cataract risk after radiation exposure was established soon after the discovery of X-rays in 1895. Today, increased cataract incidence among medical imaging practitioners and after nuclear incidents has highlighted how little is still understood about the biological responses of the lens to low-dose ionizing radiation (IR). Here, we show f...
Article
The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most ap...
Article
The discovery of DNA damage response proteins such as γH2AX, ATM, 53BP1, RAD51, and the MRE11/RAD50/NBS1 complex, that accumulate and/or are modified in the vicinity of a chromosomal DNA double-strand break to form microscopically visible, subnuclear foci, has revolutionized the detection of these lesions and has enabled studies of the cellular mac...
Article
Full-text available
Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratorie...
Article
Full-text available
In the event of a mass casualty radiation incident, the gamma-H2AX foci assay could be a useful tool to estimate radiation doses received by individuals. The rapid processing time of blood samples of just a few hours and the potential for batch processing, enabling high throughput, make the assay ideal for early triage categorisation to separate th...
Article
Full-text available
In this note, the authors describe the MULTIBIODOSE software, which has been created as part of the MULTIBIODOSE project. The software enables doses estimated by networks of laboratories, using up to five retrospective (biological and physical) assays, to be combined to give a single estimate of triage category for each individual potentially expos...
Article
Large scale radiological emergencies require high throughput techniques of biological dosimetry for population triage in order to identify individuals indicated for medical treatment. The dicentric assay is the "gold standard" technique for the performance of biological dosimetry, but it is very time consuming and needs well trained scorers. To inc...
Article
Within the EU MULTIBIODOSE project, the automated micronucleus (MN) assay was optimised for population triage in large-scale radiological emergencies. For MN scoring, two approaches were applied using the Metafer4 platform (MetaSystems, Germany): fully automated scoring and semi-automated scoring with visual inspection of the gallery of MN-positive...
Article
Full-text available
Following a radiation incident, preliminary dose estimates made by textitγ-H2AX foci analysis can supplement the early triage of casualties based on clinical symptoms. Sample processing time is important when many individuals need to be rapidly assessed. A protocol was therefore developed for high sample throughput that requires less than 0.1 ml bl...
Article
In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 la...
Preprint
Following a radiation incident, preliminary dose estimates made by γ-H2AX foci analysis can supplement the early triage of casualties based on clinical symptoms. Sample processing time is important when many individuals need to be rapidly assessed. A protocol was therefore developed for high sample throughput that requires less than 0.1 ml blood, t...
Preprint
Full-text available
Following a radiation incident, preliminary dose estimates made by γ-H2AX foci analysis can supplement the early triage of casualties based on clinical symptoms. Sample processing time is important when many individuals need to be rapidly assessed. A protocol was therefore developed for high sample throughput that requires less than 0.1 ml blood, t...
Article
Purpose: The European Union's Seventh Framework Programme-funded project 'Multi-disciplinary biodosimetric tools to manage high scale radiological casualties' (MULTIBIODOSE) has developed a multiparametric approach to radiation biodosimetry, with a particular emphasis on triage of large numbers of potentially exposed individuals following accident...
Article
Full-text available
Analysis of gamma-H2AX foci in blood lymphocytes is a promising approach for rapid dose estimation to support patient triage after a radiation accident but has one major drawback: the rapid decline of foci levels post-exposure cause major uncertainties in situations where the exact timing between exposure and blood sampling is unknown. To address t...
Article
The focus of the study is an intercomparison of laboratories' dose-assessment performances using the γ-H2AX foci assay as a diagnostic triage tool for rapid individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-4 Gy) as well as blinded test samples (0.1-6.4 Gy) were...
Article
The study design and obtained results represent an intercomparison of various laboratories performing dose assessment using the dicentric chromosome analysis (DCA) as a diagnostic triage tool for individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-5 Gy) as well as...
Article
The focus of the study is an intercomparison of laboratories' dose-assessment performances using the cytokinesis-block micronucleus (CBMN) assay as a diagnostic triage tool for individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-5 Gy) as well as blind samples (0.1...
Article
Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage...
Article
Mass casualty scenarios of radiation exposure require high throughput biological dosimetry techniques for population triage in order to rapidly identify individuals who require clinical treatment. The manual dicentric assay is a highly suitable technique, but it is also very time consuming and requires well trained scorers. In the framework of the...