Responding to radiation accidents: what more do we need to know?

A short review of the various types of radiation incidents and accidents that have occurred is used to provide a context for discussing the findings on medical management of the victims of such incidents and accidents reported in a recent Special Issue of the Journal of Radiological Protection. The review demonstrates that accidents and incidents giving rise to high radiation doses may involve over-exposure of a single individual, a few individuals, or very large numbers. In general, these exposures will be relatively short-term, ranging from a few seconds to a few days, but chronic situations resulting in high exposures can occur. Some of these exposures may be highly localised, whereas others may result in almost uniform whole-body irradiation. This diversity of situations means that it is not feasible to have a single protocol for the diagnosis and treatment of over-exposed individuals. If the over-exposures are limited to one or a few individuals, these can be addressed on a case-by-case basis. However, where large numbers have been exposed or may have been exposed, there is a need to implement a rapid and effective system of triage. Furthermore, this system is likely to have to be implemented by individuals who have little or no direct experience of radiation-induced injuries. For those individuals who may have been significantly exposed, the key consideration is not to determine the radiation dose that they have received, but to establish their present clinical status and how it is likely to develop with time. There is at most a very limited role for bone-marrow transplantation in the treatment of acute radiation syndrome, whereas there are good arguments for administering various treatments to boost bone marrow function together with other supportive interventions, e.g. in control of infections and handling both fluid loss and bleeding. However, there is concern that the focus to date has been only on the licencing of drugs related to the management of haematopoietic effects. Although a great deal is known about the diagnosis and treatment of injuries arising from high dose exposures, this knowledge is biased towards situations in which there is relatively uniform, external whole-body exposure. More attention needs to be given to assessing the implications of various inhomogeneous exposure regimes and to developing medical countermeasures optimised for addressing the complex, multi-organ effects likely to arise from such inhomogeneous exposures.

A research and development roadmap to support applications of the enhanced BIOMASS methodology.

The International Atomic Energy Agency has coordinated an international project addressing enhancements of methods for modelling the biosphere in post-closure safety assessments of solid radioactive waste disposal. This has resulted in the enhanced BIOMASS methodology that is described elsewhere in this special issue. To a large degree, the enhancements to the BIOMASS methodology arose from experience gained in applying the original methodology, both in the context of other international projects and in assessments of existing or proposed disposal facilities for solid radioactive wastes. Here, this experience is used, together with information on the status of solid radioactive waste disposal programmes worldwide, to identify opportunities for applying the enhanced methodology and for learning from those applications. This provides a basis for identifying research and development to support application of the enhanced methodology in a variety of environmental settings. These research and development requirements include aspects related to climate change under a variety of forcing scenarios, landform development in climatic regimes ranging from cold, polar to arid, tropical, modelling of groundwater flow and contaminant transport in surface-water catchments where both fractured rock and porous sediments are present, and studies of the transport of key radioisotopes of elements central to major biogeochemical cycles, such as those of carbon, chlorine, sulphur and iodine. In addition, some remarks are made on aspects of the application of the enhanced methodology that could imply review and updating of regulations and regulatory guidance, e.g. in relation to the definition of representative persons or groups to be considered in assessments and in respect of approaches to the assessment of radiological impacts on non-human biota. Furthermore, consideration is given as to how the scientific and technical experience that has been gained and methods that have been developed in the context of solid radioactive disposal facilities could support management of contaminated sites and legacy facilities that are likely to require long-term management and stewardship.

Imaging Butyrylcholinesterase in Multiple Sclerosis.

PURPOSE: Molecular imaging agents targeting butyrylcholinesterase (BChE) have shown promise in other neurodegenerative disorders and may have utility in detecting changes to normal appearing white matter in multiple sclerosis (MS). BChE activity is present in white matter and localizes to activated microglia associated with MS lesions. The purpose of this study was to further characterize changes in the cholinergic system in MS pathology, and to explore the utility of BChE radioligands as potential diagnostic and treatment monitoring agents in MS. PROCEDURE: Cortical and white matter lesions were identified using myelin staining, and lesions were classified based on microglial activation patterns. Adjacent brain sections were used for cholinesterase histochemistry and in vitro autoradiography using phenyl 4-[123I]-iodophenylcarbamate (123I-PIP), a previously described small-molecule cholinesterase-binding radioligand. RESULTS: BChE activity is positively correlated with microglial activation in white matter MS lesions. There is no alteration in cholinesterase activity in cortical MS lesions. 123I-PIP autoradiography revealed uptake of radioactivity in normal white matter, absence of radioactivity within demyelinated MS lesions, and variable uptake of radioactivity in adjacent normal-appearing white matter. CONCLUSIONS: BChE imaging agents have the potential to detect MS lesions and subtle pathology in normal-appearing white matter in postmortem MS brain tissue. The possibility of BChE imaging agents serving to supplement current diagnostic and treatment monitoring strategies should be evaluated.

Use of interaction matrices to formalise the development of conceptual models of contaminant transport in the biosphere and the translation of those conceptual models into mathematical models.

In developing models of the biosphere for use in assessing the impacts on human health and the environment of releases of contaminants from disposal facilities for solid radioactive wastes or from contaminated legacy sites, there is a need to demonstrate that the models adopted are both comprehensive and appropriate to the assessment context. To achieve this end, it is useful to develop a structured approach to conceptual model development and it is here proposed that interaction matrices (IMs) provide a suitable framework. This process can provide a conceptual model expressed in terms of either a single IM or a nested set of IMs. The focus of the work described herein is the development of a transparent approach to translating such a set of IMs into a mathematical model, which is typically expressed as a set of ordinary differential equations complemented by algebraic expressions. Some remarks are also made on appropriate approaches to obtaining numerical solutions of these equations in circumstances where simplifications of the general equations can be justified. Overall, the intent is to provide background and guidance by providing a formal basis for the process in generalised terms.

Climate change and landscape development in post-closure safety assessment of solid radioactive waste disposal: Results of an initiative of the IAEA.

The International Atomic Energy Agency has coordinated an international project addressing climate change and landscape development in post-closure safety assessments of solid radioactive waste disposal. The work has been supported by results of parallel on-going research that has been published in a variety of reports and peer reviewed journal articles. The project is due to be described in detail in a forthcoming IAEA report. Noting the multi-disciplinary nature of post-closure safety assessments, here, an overview of the work is given to provide researchers in the broader fields of radioecology and radiological safety assessment with a review of the work that has been undertaken. It is hoped that such dissemination will support and promote integrated understanding and coherent treatment of climate change and landscape development within an overall assessment process. The key activities undertaken in the project were: identification of the key processes that drive environmental change (mainly those associated with climate and climate change), and description of how a relevant future may develop on a global scale; development of a methodology for characterising environmental change that is valid on a global scale, showing how modelled global changes in climate can be downscaled to provide information that may be needed for characterising environmental change in site-specific assessments, and illustrating different aspects of the methodology in a number of case studies that show the evolution of site characteristics and the implications for the dose assessment models. Overall, the study has shown that quantitative climate and landscape modelling has now developed to the stage that it can be used to define an envelope of climate and landscape change scenarios at specific sites and under specific greenhouse-gas emissions assumptions that is suitable for use in quantitative post-closure performance assessments. These scenarios are not predictions of the future, but are projections based on a well-established understanding of the important processes involved and their impacts on different types of landscape. Such projections support the understanding of, and selection of, plausible ranges of scenarios for use in post-closure safety assessments.

Sustainability and integration of radioecology-position paper.

This position paper gives an overview of how the COMET project (COordination and iMplementation of a pan-European instrumenT for radioecology, a combined Collaborative Project and Coordination and Support Action under the EC/Euratom 7th Framework Programme) contributed to the integration and sustainability of radioecology in Europe via its support to and interaction with the European Radioecology ALLIANCE. COMET built upon the foundations laid by the FP7 project STAR (Strategic Network for Integrating Radioecology) Network of Excellence in radioecology. In close association with the ALLIANCE, and based on the Strategic Research Agenda (SRA), COMET developed innovative mechanisms for joint programming and implementation of radioecological research. To facilitate and foster future integration under a common federating structure, research activities developed within COMET were targeted at radioecological research needs identified in the SRA. Furthermore, COMET maintained and developed strong mechanisms for knowledge exchange, dissemination and training to enhance and maintain European capacity, competence and skills in radioecology. In the short term the work to promote radioecology will continue under the H2020 project EJP-CONCERT (European Joint Programme for the Integration of Radiation Protection Research). The EJP-CONCERT project (2015-2020) aims to develop a sustainable structure for promoting and administering joint programming and open research calls in the field of radiation protection research for Europe. In the longer term, radioecological research will be facilitated by the ALLIANCE. External funding is, however, required in order to be able to answer emerging research needs.

The transcriptome of metamorphosing flatfish.

BACKGROUND: Flatfish metamorphosis denotes the extraordinary transformation of a symmetric pelagic larva into an asymmetric benthic juvenile. Metamorphosis in vertebrates is driven by thyroid hormones (THs), but how they orchestrate the cellular, morphological and functional modifications associated with maturation to juvenile/adult states in flatfish is an enigma. Since THs act via thyroid receptors that are ligand activated transcription factors, we hypothesized that the maturation of tissues during metamorphosis should be preceded by significant modifications in the transcriptome. Targeting the unique metamorphosis of flatfish and taking advantage of the large size of Atlantic halibut (Hippoglossus hippoglossus) larvae, we determined the molecular basis of TH action using RNA sequencing. RESULTS: De novo assembly of sequences for larval head, skin and gastrointestinal tract (GI-tract) yielded 90,676, 65,530 and 38,426 contigs, respectively. More than 57 % of the assembled sequences were successfully annotated using a multi-step Blast approach. A unique set of biological processes and candidate genes were identified specifically associated with changes in morphology and function of the head, skin and GI-tract. Transcriptome dynamics during metamorphosis were mapped with SOLiD sequencing of whole larvae and revealed greater than 8,000 differentially expressed (DE) genes significantly (p < 0.05) up- or down-regulated in comparison with the juvenile stage. Candidate transcripts quantified by SOLiD and qPCR analysis were significantly (r = 0.843; p < 0.05) correlated. The majority (98 %) of DE genes during metamorphosis were not TH-responsive. TH-responsive transcripts clustered into 6 groups based on their expression pattern during metamorphosis and the majority of the 145 DE TH-responsive genes were down-regulated. CONCLUSIONS: A transcriptome resource has been generated for metamorphosing Atlantic halibut and over 8,000 DE transcripts per stage were identified. Unique sets of biological processes and candidate genes were associated with changes in the head, skin and GI-tract during metamorphosis. A small proportion of DE transcripts were TH-responsive, suggesting that they trigger gene networks, signalling cascades and transcription factors, leading to the overt changes in tissue occurring during metamorphosis.