Low doses of ionising radiation: definitions and contexts.

The term 'low dose' is applied to different levels of dose depending on the circumstances of exposure, with the potential for confusion unless the reasoning is clear. The United Nations Scientific Committee on the Effects of Ionising Radiation has defined low absorbed doses of ionising radiation as below about 100 mGy, and low dose rates as below 0.1 mGy min-1 (6 mGy h-1). These values relate to the interpretation of scientific evidence from epidemiological and biological studies. The International Commission on Radiological Protection has used similar values of 100 mSv and 5 mSv h-1 and applied this categorisation directly to the specific situation of patients undergoing diagnostic procedures: doses below 100 mSv were referred to as 'low' and doses below 10 mSv as 'very low'. Consideration of other exposure situations suggest that the same terms can be used for exposures received by emergency workers. However, for workers and members of the public in planned exposure situations, it is suggested that the term 'low dose' applies to doses below 10 mSv and 1 mSv, respectively - that is, below the dose limits. In each case, dose is being used as a surrogate for risk - risks at low doses are uncertain and estimates may change, but order of magnitude considerations are sufficient in most cases. Doses of < 100 mSv, < 10 mSv and < 1 mSv correspond to life-time cancer risk estimates of the order of < 10-2, < 10-3 and < 10-4, respectively. .

Progress with the regulation of radiation safety during recovery and removal of spent nuclear fuel from the site for temporary storage at Andreeva Bay on the Kola Peninsula.

In the 1960s, a shore technical base (STB) was established at Andreeva Bay on the Kola Peninsula, in northwest Russia. The STB maintained nuclear submarines and the nuclear icebreaker fleet, receiving and storing fresh and spent nuclear fuel (SNF) as well as solid and liquid radioactive waste (RW). It was subsequently re-designated as a site for temporary storage (STS) for SNF and RW. Over time, the SNF storage facilities partly lost their containment functions, leading to radioactive contamination of workshops and the site above permitted values. The technological and engineering infrastructure at the site was also significantly degraded as well as the condition of the stored SNF. At present, the STS Andreeva Bay facility is under decommissioning. This paper describes progress with the creation of safe working measures for workers involved in site remediation and SNF recovery operations, including the determination of safe shift times in high radiation areas, as part of overall optimization of safety. Results are presented for the successful application of these measures in the period 2019-2021, during which time significant SNF recovery and removal operations were completed without incident. Significant important experience has been gained to support safe removal of remaining SNF, including the most hazardous degraded fuel, as well as recovery of other higher level RW and decommissioning of the old storage buildings and structures.

Further development and application of a method for assessing radionuclide surface activity distribution and source location based on measurements of ambient dose equivalent rate.

A method has been developed for solving the Fredholm equation in the barrier geometry for reconstructing the surface activity density (SAD) from the results of measuring the ambient dose equivalent rate (ADER). Inclusion of the barrier geometry means that the method takes into account the shielding effect of buildings and structures on the contaminated site. The method was based on the representation of the industrial site, buildings and radiation fields in the form of a raster and the use of the visibility matrix (VM) of raster cells to describe the barrier geometry. The developed method was applied to a hypothetical industrial site with a size of 200 × 200 conventional units for four types of SAD distribution over the surface of the industrial site: 'fragmentation', 'diffuse', 'uniform' and 'random'. The method of Lorentz curves was applied to estimate the compactness of the distributions of SAD and the ADER for the considered radiation sources. It was shown that the difference between the Lorentz curve for SAD and ADER means that the determination of the spatial distribution of SAD over the industrial site by solving the integral equation is essentially useful for determining the location of radiation source locations on the industrial site. The accuracy of SAD reconstruction depends on the following parameters: resolution (fragmentation) of the raster, the height of the radiation detector above the scanned surface, and the angular aperture of the radiation detector. The measurement of ADER is simpler and quicker than the direct measurement of SAD and its distribution. This represents a significant advantage if SAD distribution needs to be determined in areas with high radiation dose-rate during limited time. The developed method is useful for supporting radiation monitoring and optimizing the remediation of nuclear legacies, as well as during the recovery phase after a major accident.

Further development and application of a method for assessing radionuclide surface activity distribution and source location based on measurements of ambient dose equivalent rate. Examples for Andreeva Bay, Chernobyl NPP and Istiklol.

A method for reconstructing surface activity density (SAD) maps based on the solution of the Fredholm equation has been developed and applied. The construction of SAD maps was carried out for the site of the temporary storage (STS) of spent fuel and radioactive waste (RW) in Andreeva Bay using the results of measuring campaign in 2001-2002 and for the sheltering construction of the solid RW using the results of measurements in 2021. The Fredholm equation was solved in two versions: under conditions of a barrier-free environment and taking into account buildings and structures located on the industrial site of the STS Andreeva Bay. Lorenz curves were generated to assess the compactness of the distributions of SAD and ambient dose equivalent rate (ADER) for the industrial site and the sheltering construction at STS Andreeva Bay, the area of the IV stage uranium tailing site near the city of Istiklol in the Republic of Tajikistan, and for roofs of the Chernobyl nuclear power plant. The nature of impact of the resolution (fragmentation) of the raster, the value of the radius of mutual influence of points (contamination sites), the height of the radiation detector above the scanned surface and the angular aperture of the radiation detector on the accuracy of the SAD reconstruction is shown. The method developed allows more accurate planning of decontamination work when only ADER measurements data is available. The proposed method can be applied to support the process of decontamination of radioactively contaminated territories, in particular during the remediation of the STS Andreeva Bay.

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.

Topographical classification of dose distributions: implications for control for worker exposure.

This paper deals with classification of dose distributions of nuclear workers based on antikurtosis (Q) and entropy coefficients (K) and their relationship presented in QK-diagrams. It is shown that determination of the most appropriate distribution to adopt, for a specific data set of a wide range of input data, requires building and analysing QK-diagrams for distributions of logarithms of individual doses. Actual dose distributions for emergency and occupational exposure situations were then considered, as well as doses for one day of work during clean-up and routine activities. It is shown that, in all cases, three types of distributions of logarithms of individual doses were present: normal, Weibull and Chapeau. The location of the representation point of a dose distribution reflects the degree of dose control of the group of workers whose individual doses are collectively displayed in the QK-diagram. The more the representation point of the analysed distribution of the logarithms of the individual dose of a given contingent of workers deviates from the point of the lognormal distribution, the more there was intervention in the process of individual dose accumulation. Thus, QK-diagrams could be used to develop a dose control function. It is shown that the hybrid lognormal distribution, which is widely used in the field of radiation safety, for the purpose of approximation of real dose distributions, is unable to satisfactorily describe many dose distributions arising in aftermath operations and occupational exposure.

Radiation situation dynamics at the Andreeva Bay site for temporary storage of spent nuclear fuel and radioactive waste over the period 2002-2016.

The Coastal Technical Base (CTB) №569 at Andreeva Bay was established in the early 1960s and intended for the refueling of nuclear submarine reactors and temporary storage of spent nuclear fuel (SNF) and radioactive waste (RW). In 2001, the base was transferred to the Russian Ministry for Atomic Energy and the site remediation began. The paper describes in detail the radiation situation change at the technical site in Andreeva Bay from 2002-2016, the period of preparation for the most critical phase of remedial work: removal of spent fuel assemblies. The analysis of aggregated indicators and data mining were used. The article suggests the best number and location of checkpoints needed to ensure sufficient accuracy of the radiation situation description. The fractal properties of the radiation field are studied using the Hurst index. The relationship between checkpoints was assessed using the method of searching for checkpoint communities. The decrease in the integral of the ambient dose equivalent rate (ADER) at the technical site was evaluated by the method of time series decomposition. Three components of time series were identified: trend, seasonal and residual. The trend of the ADER integral over the technical site is a monotonic decreasing function, where the initial and final values differ tenfold. Taking into account that 137Cs dominates the radiation situation on-site, it is clear that the ADER due to the radionuclide decay will have decreased by 1.4 times. It is estimated that only a small proportion of 137Cs has migrated off-site. Therefore, approximately a sevenfold decrease in dose rate is mainly due to remediation activities of personnel. During the year, the seasonal component varies the ADER integral by a factor of two, due to snowfall. The residual component reflects the uncertainty of the ADER integral calculation and phases of active SNF and RW management. The methods developed are used to support the optimization of remediation work as well as regulatory supervision of occupational radiation protection.

Methods of minimising doses incurred by external exposure while moving in radiation hazardous areas.

Radiation doses received by workers during their movement within areas contaminated as a result of events and activities, leading to emergency or existing exposure situations, may provide a substantial contribution to total external exposure during remediation work. This paper describes an approach to minimise worker external exposure in these circumstances, based on graph theory. The paper describes several tasks, including: searching for a route with the lowest dose, searching for an optimal bypass with a given set of control points and searching for the optimal road network coverage. Classical graph theory algorithms have been used (Dijkstra's algorithm, Chinese postman problem and travelling salesman problem). Algorithms for solving the above mentioned problems have been developed and were included in the information-analytical system for radiation safety. This software has been applied for optimisation of protection during remediation work at the Andreeva Bay site of temporary storage for spent fuel and radioactive waste in the Kola Peninsula, both in the context of existing exposure situations and improving the preparedness for emergency exposure situations.

The use of the Rx spin label in orientation measurement on proteins, by EPR.

The bipedal spin label Rx is more restricted in its conformation and dynamics than its monopodal counterpart R1. To systematically investigate the utility of the Rx label, we have attempted to comprehensively survey the attachment of Rx to protein secondary structures. We have examined the formation, structure and dynamics of the spin label in relation to the underlying protein in order to determine feasibility and optimum conditions for distance and orientation measurement by pulsed EPR. The labeled proteins have been studied using molecular dynamics, CW EPR, pulsed EPR distance measurement at X-band and orientation measurement at W-band. The utility of different modes and positions of attachment have been compared and contrasted.

Radiation safety during remediation of the SevRAO facilities: 10 years of regulatory experience.

In compliance with the fundamentals of the government's policy in the field of nuclear and radiation safety approved by the President of the Russian Federation, Russia has developed a national program for decommissioning of its nuclear legacy. Under this program, the State Atomic Energy Corporation 'Rosatom' is carrying out remediation of a Site for Temporary Storage of spent nuclear fuel (SNF) and radioactive waste (RW) at Andreeva Bay located in Northwest Russia. The short term plan includes implementation of the most critical stage of remediation, which involves the recovery of SNF from what have historically been poorly maintained storage facilities. SNF and RW are stored in non-standard conditions in tanks designed in some cases for other purposes. It is planned to transport recovered SNF to PA 'Mayak' in the southern Urals. This article analyses the current state of the radiation safety supervision of workers and the public in terms of the regulatory preparedness to implement effective supervision of radiation safety during radiation-hazardous operations. It presents the results of long-term radiation monitoring, which serve as informative indicators of the effectiveness of the site remediation and describes the evolving radiation situation. The state of radiation protection and health care service support for emergency preparedness is characterized by the need to further study the issues of the regulator-operator interactions to prevent and mitigate consequences of a radiological accident at the facility. Having in mind the continuing intensification of practical management activities related to SNF and RW in the whole of northwest Russia, it is reasonable to coordinate the activities of the supervision bodies within a strategic master plan. Arrangements for this master plan are discussed, including a proposed programme of actions to enhance the regulatory supervision in order to support accelerated mitigation of threats related to the nuclear legacy in the area.

3D simulation as a tool for improving the safety culture during remediation work at Andreeva Bay.

Andreeva Bay in northwest Russia hosts one of the former coastal technical bases of the Northern Fleet. Currently, this base is designated as the Andreeva Bay branch of Northwest Center for Radioactive Waste Management (SevRAO) and is a site of temporary storage (STS) for spent nuclear fuel (SNF) and other radiological waste generated during the operation and decommissioning of nuclear submarines and ships. According to an integrated expert evaluation, this site is the most dangerous nuclear facility in northwest Russia. Environmental rehabilitation of the site is currently in progress and is supported by strong international collaboration. This paper describes how the optimization principle (ALARA) has been adopted during the planning of remediation work at the Andreeva Bay STS and how Russian-Norwegian collaboration greatly contributed to ensuring the development and maintenance of a high level safety culture during this process. More specifically, this paper describes how integration of a system, specifically designed for improving the radiological safety of workers during the remediation work at Andreeva Bay, was developed in Russia. It also outlines the 3D radiological simulation and virtual reality based systems developed in Norway that have greatly facilitated effective implementation of the ALARA principle, through supporting radiological characterisation, work planning and optimization, decision making, communication between teams and with the authorities and training of field operators.

Plasmodium chabaudi AS induces pregnancy loss in association with systemic pro-inflammatory immune responses in A/J and C57BL/6 mice.

The molecular mechanisms that underlie poor birth outcomes in malaria during pregnancy remain poorly defined. To assess the role of host immune responses, mice known to respond differentially to Plasmodium chabaudi AS infection were studied. Following infection at day 0 of pregnancy, A/J mice developed significantly higher parasitemia than C57BL/6 (B6) mice and succumbed to infection. Both strains had evidence of parasite accumulation in the placenta at mid-gestation and aborted, with significantly higher embryo loss in infected A/J mice on day 9. While infection-induced systemic tumour necrosis factor (TNF) and interleukin (IL)-1ß in the latter were significantly higher at day 11, day 10 IL-10 levels were higher in B6 mice. No differences in the levels of splenic lymphocyte subsets, neutrophils or monocytes between infected pregnant A/J and B6 mice were observed, with most cell types expanding in response to infection regardless of pregnancy. Antibody ablation of TNF exacerbated infection in A/J mice and did not ameliorate pregnancy outcome. Thus, malaria induces poor pregnancy outcome in both the mouse strains in the context of quantitatively different systemic inflammatory responses. Further evaluation of the roles of soluble and cellular immune components, particularly at the uteroplacental level, will be required to define the most critical pregnancy-compromising mechanisms.

Directing dopaminergic fiber growth along a preformed molecular pathway from embryonic ventral mesencephalon transplants in the rat brain.

To identify guidance molecules to promote long-distance growth of dopaminergic axons from transplanted embryonic ventral mesencephalon (VM) tissue, three pathways were created by expressing green fluorescent protein (GFP), glial cell line-derived neurotrophic factor (GDNF), or a combination of GDNF/GDNF receptor α1 (GFRα1) along the corpus callosum. To generate the guidance pathway, adenovirus encoding these transcripts was injected at four positions along the corpus callosum. In all groups, GDNF adenovirus was also injected on the right side 2.5 mm from the midline at the desired transplant site. Four days later, a piece of VM tissue from embryonic day 14 rats was injected at the transplant site. All rats also received daily subcutaneous injections of N-acetyl-L-cysteinamide (NACA; 100 µg per rat) as well as chondroitinase ABC at transplant site (10 U/ml, 2 µl). Two weeks after transplantation, the rats were perfused and the brains dissected out. Coronal sections were cut and immunostained with antibody to tyrosine hydroxylase (TH) to identify and count dopaminergic fibers in the corpus callosum. In GFP-expressing pathways, TH(+) fibers grew out of the transplants for a short distance in the corpus callosum. Very few TH(+) fibers grew across the midline. However, pathways expressing GDNF supported more TH(+) fiber growth across the midline into the contralateral hemisphere. Significantly greater numbers of TH(+) fibers grew across the midline in animals expressing a combination of GDNF and GFRα1 in the corpus callosum. These data suggest that expression of GDNF or a combination of GDNF and GFRα1 can support the long-distance dopaminergic fiber growth from a VM transplant, with the combination having a superior effect.

Semaphorin III can repulse and inhibit adult sensory afferents in vivo.

During development, semaphorins (collapsin, fasciclin) mediate repulsive and inhibitory guidance of neurons. Semaphorin III, a secretable member of this family, is expressed by the ventral spinal cord at the time corresponding to projection of sensory afferents from the dorsal root ganglion (DRG) into the spinal cord. The inhibitory effect of E14 ventral cord is active only on nerve growth factor (NGF)-responsive sensory afferents (small-diameter A-delta and C fibers subserving sensations of temperature and pain). Similarly, COS cells secreting recombinant semaphorin III are able to selectively repel DRG afferents whose growth is stimulated by NGF and not NT-3. However, it is not known whether these molecules can exert a functional role in the fully developed adult peripheral nervous system. In this study, we demonstrated that gene gun transfection and production of semaphorin III in corneal epithelial cells in adult rabbits in vivo can cause repulsion of established A-delta and C fiber trigeminal sensory afferents. In addition, it is shown that, following epithelial wounding and denervation, semaphorin III is able to inhibit collateral nerve sprouts from innervating the reepithelialized tissue. These findings are significant in that they provide direct evidence that small-diameter adult sensory neurons retain the ability to respond to semaphorin III. In addition, the corneal gene gun technique may be generally used to study the in vivo effects of neural growth modulators by quantifying the amount of sensory nerve growth.

Three-dimensional molecular modeling and drug design.

A discussion of drug-receptor theory is used to show that the three-dimensional structure, or shape, of molecules is important for biological activity. The computer-assisted molecular modeling system at Merck is described, and it is shown that this system is useful for generating and storing molecular structures, determining preferred conformation, comparing molecular shapes, and computing molecular properties. Applications of the system to the study of anti-inflammatory drugs, somatostatin-like compounds, and dihydrofolate reductase inhibitors are summarized.

Erythroid differentiation of clonal Rauscher erythroleukemia cells in response to erythropoietin or dimethyl sulfoxide.

Clonal lines of Rauscher erythroleukemia cells exhibited selective responses to two inducers of differentiation, erythropoietin and dimethyl sulfoxide. There were substantial quantitiative differences between clones that reponded to both inducers. Several clones differentiated only in response to erythropoietin. Erythropoietin stimulated cell proliferation and differentiation whereas dimethyl sulfoxide inhibited proliferation, suggesting dissimilar modes of action.

An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF.

Increasing demand on the apheresis service makes efficient harvesting of peripheral blood stem cells (PBSCs) essential. A total of 168 adult patients with haematological malignancy were primed using low-moderate dose cyclophosphamide (1.5-3 g/m(2)) with G-CSF 5-10 microg/kg per day. Harvesting was booked and peripheral blood (PB) counts first checked between 6 and 10 days post-priming. One hundred and thirty (77%) patients harvested successfully (total harvest yield > or =2 x 10(6) CD34(+)/kg) and the median PBSC collection per procedure was 2.18 x 10(6)/kg (range 0.1-14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34(+) cell count correlated significantly with harvest yield (r=0.8448, P<0.0001). A PB CD34(+) count > or =10/microl predicted a collection of > or =2 x 10(6)/kg (positive-predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6-8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34(+) count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service.

Localized gene expression of axon guidance molecules in neuronal co-cultures.

Axonal growth cones are guided to their targets by contact-dependent mechanisms or by diffusible chemotropic factors. Axon guidance by these factors typically involves culturing neurons on an acellular substrate which may not represent the in vivo biological environment. We developed two novel in vitro methods to create patterned gene expression of guidance molecules in a physiologically-relevant cellular environment. In the Matrigel assay, a droplet of adenovirus-Matrigel suspension was placed on astrocytes grown in Matrigel. The adenovirus diffused through the gel and transduced underlying astrocytes, creating a radial infection gradient within a localized area. In the second model, recombinant adenovirus was bound to an anti-hexon antibody adsorbed onto stripe patterns of nitrocellulose. Once the cells were added, only those contacting the adenovirus were infected. The outgrowth pattern of chick DRG neurons on NGF, semaphorin 3A and brevican were studied. As expected, results showed robust axonal growth toward NGF as opposed to either secreted Sema 3A or membrane bound brevican, however subtle differences in axonal growth responses were observed in comparison to those obtained with less physiologically-relevant methods. Novel to this technology, the location and area of molecule expression can be controlled and manipulated in an intricate cellular environment.