Towards an ecological modelling approach for assessing ionizing radiation impact on wildlife populations.

The emphasis of the international system of radiological protection of the environment is to protect populations of flora and fauna. Throughout the MODARIA programmes, the United Nations' International Atomic Energy Agency (IAEA) has facilitated knowledge sharing, data gathering and model development on the effect of radiation on wildlife. We present a summary of the achievements of MODARIA I and II on wildlife dose effect modelling, extending to a new sensitivity analysis and model development to incorporate other stressors. We reviewed evidence on historical doses and transgenerational effects on wildlife from radioactively contaminated areas. We also evaluated chemical population modelling approaches, discussing similarities and differences between chemical and radiological impact assessment in wildlife. We developed population modelling methodologies by sourcing life history and radiosensitivity data and evaluating the available models, leading to the formulation of an ecosystem-based mathematical approach. This resulted in an ecologically relevant conceptual population model, which we used to produce advice on the evaluation of risk criteria used in the radiological protection of the environment and a proposed modelling extension for chemicals. This work seeks to inform stakeholder dialogue on factors influencing wildlife population responses to radiation, including discussions on the ecological relevance of current environmental protection criteria. The area of assessment of radiation effects in wildlife is still developing with underlying data and models continuing to be improved. IAEA's ongoing support to facilitate the sharing of new knowledge, models and approaches to Member States is highlighted, and we give suggestions for future developments in this regard.

Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes.

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing.

SRP workshop on 'communication of radiation risk in the modern world'.

Communicating radiation risk is an important part of radiation protection. However, achieving effective risk communication is challenging given the negative public perception of radiation and conflicting views presented by both the media and social media. Noting the importance of building capacity amongst radiation protection professionals to communicate radiation risk effectively, the Society for Radiological Protection (SRP) ran a half-day workshop at its Annual Conference on the 22nd May 2019 in Scarborough Spa, UK. A number of key factors were identified that should be considered when communicating with the public, post a nuclear or radiological incident, communicating with government and local authorities, and communicating with the public as part of public outreach. The following memorandum provides a summary of the points presented and discussed. It also outlines proposed future activities of the SRP, focused on further developing the communications aspect of radiation professionals' practice.

Strategies for engaging with future radiation protection professionals: a public outreach case study.

It is evident that there is a nuclear skills shortage within the UK, and logically it can be assumed that the shortfall extends to the radiation protection arena. Plans for nuclear new-build and the decommissioning of existing nuclear sites will require many more people with radiological knowledge and practical competencies. This converts to a nuclear industry requirement in the order of 1000 new recruits per year over at least the next ten years, mainly as new apprentices and graduates. At the same time, the strong demand for persons with radiation protection know-how in the non-nuclear and health care sectors is unlikely to diminish. The task of filling this skills gap is a significant one and it will require a determined effort from many UK stakeholders. The Society for Radiological Protection (SRP) has adopted a strategy in recent years to help address this skills gap. The aim is to engage the interest of secondary school students in the science of radiation and inspire them to follow a career in radiation protection. This paper presents the reasoning behind this strategy and, in an 'outreach case study', describes the establishment of the annual SRP Schools Event. This event is becoming an important addition to the national efforts aimed at increasing the numbers of skilled UK radiation protection professionals over the forthcoming decades.

Chornobyl radiation spikes are not due to military vehicles disturbing soil.

On 25th February 2022, increased gamma radiation dose rates were reported within the Chornobyl Exclusion Zone (CEZ). This coincided with Russian military vehicles entering the Ukrainian part of the CEZ from neighbouring Belarus. It was speculated that contaminated soil resuspension by vehicle movements or a leak from the Chornobyl Nuclear Power Plant complex may explain these spikes in radiation dose rates. The gamma dose rate monitoring network in the CEZ provides a crucial early warning system for releases of radioactivity to the environment and is part of the international safeguards for nuclear facilities. With the potential for further military action in the CEZ and concerns over nuclear safety, it is essential that such anomalous readings are investigated. We evaluate the hypotheses suggested to explain the apparent gamma dose rate increases, demonstrating that neither military vehicle-induced soil resuspension nor a leak from the Chornobyl Nuclear Power Plant are plausible. However, disruption of the Chornobyl base-station's reception of wireless signals from the gamma dose rate monitoring network in the CEZ may potentially explain the dose rate increases recorded.

Randomized trials of alcohol-use interventions with college students and their parents: lessons from the Transitions Project.

BACKGROUND: Matriculation from high school to college is typified by an increase in alcohol use and related harm for many students. Therefore, this transition period is an ideal time for preventive interventions to target alcohol use and related problems. PURPOSE: The purpose of this report is to describe the design and methods used in the Transitions Project, a randomized controlled trial of two interventions designed to prevent and reduce heavy episodic drinking and alcohol-related negative consequences among incoming college students. METHODS: This study used a 2 × 2 factorial design to investigate the effects of a two-session brief motivational intervention delivered to students and a handbook-based parent intervention. Interventions were administered to students and parents. Follow-up assessment took place at 10- and 22-months post-baseline. RESULTS: The Transitions Project successfully recruited and retained participants across a major transition period (i.e., entering college), administered and compared two distinct but complementary interventions, and collected and analyzed highly skewed data. The application of a factorial design and two-part latent growth curve modeling allowed us to examine main and interactive intervention effects in terms of both initiation and growth in heavy drinking and alcohol-related problems. LIMITATIONS: While we conducted successful tests of our primary and secondary study hypotheses over a lengthy follow-up period, our study design did not permit full interpretation of null findings. We suggest that researchers carefully consider assessment timing, tests of assessment reactivity, and ensure objective tests of intervention efficacy when conducting clinical trials of motivational interventions. CONCLUSIONS: The lessons we learned while conducting this trial have the potential to assist other researchers designing and conducting future preventive interventions targeting parents and college students. The data analytic procedures presented can also help guide trials that plan to analyze zero-inflated non-normal outcome data.

The estimation of absorbed dose rates for non-human biota: an extended intercomparison.

An exercise to compare 10 approaches for the calculation of unweighted whole-body absorbed dose rates was conducted for 74 radionuclides and five of the ICRP's Reference Animals and Plants, or RAPs (duck, frog, flatfish egg, rat and elongated earthworm), selected for this exercise to cover a range of body sizes, dimensions and exposure scenarios. Results were analysed using a non-parametric method requiring no specific hypotheses about the statistical distribution of data. The obtained unweighted absorbed dose rates for internal exposure compare well between the different approaches, with 70% of the results falling within a range of variation of ±20%. The variation is greater for external exposure, although 90% of the estimates are within an order of magnitude of one another. There are some discernible patterns where specific models over- or under-predicted. These are explained based on the methodological differences including number of daughter products included in the calculation of dose rate for a parent nuclide; source-target geometry; databases for discrete energy and yield of radionuclides; rounding errors in integration algorithms; and intrinsic differences in calculation methods. For certain radionuclides, these factors combine to generate systematic variations between approaches. Overall, the technique chosen to interpret the data enabled methodological differences in dosimetry calculations to be quantified and compared, allowing the identification of common issues between different approaches and providing greater assurance on the fundamental dose conversion coefficient approaches used in available models for assessing radiological effects to biota.

An international model validation exercise on radionuclide transfer and doses to freshwater biota.

Under the International Atomic Energy Agency (IAEA)'s EMRAS (Environmental Modelling for Radiation Safety) programme, activity concentrations of (60)Co, (90)Sr, (137)Cs and (3)H in Perch Lake at Atomic Energy of Canada Limited's Chalk River Laboratories site were predicted, in freshwater primary producers, invertebrates, fishes, herpetofauna and mammals using eleven modelling approaches. Comparison of predicted radionuclide concentrations in the different species types with measured values highlighted a number of areas where additional work and understanding is required to improve the predictions of radionuclide transfer. For some species, the differences could be explained by ecological factors such as trophic level or the influence of stable analogues. Model predictions were relatively poor for mammalian species and herpetofauna compared with measured values, partly due to a lack of relevant data. In addition, concentration ratios are sometimes under-predicted when derived from experiments performed under controlled laboratory conditions representative of conditions in other water bodies.

Radionuclide transfer to wildlife at a 'Reference site' in the Chernobyl Exclusion Zone and resultant radiation exposures.

This study addresses a significant data deficiency in the developing environmental protection framework of the International Commission on Radiological Protection, namely a lack of radionuclide transfer data for some of the Reference Animals and Plants (RAPs). It is also the first study that has sampled such a wide range of species (invertebrates, plants, amphibians and small mammals) from a single terrestrial site in the Chernobyl Exclusion Zone (CEZ). Samples were collected in 2014 from the 0.4 km2 sampling site, located 5 km west of the Chernobyl Nuclear Power complex. We report radionuclide (137Cs, 90Sr, 241Am and Pu-isotopes) and stable element concentrations in wildlife and soil samples and use these to determine whole organism-soil concentration ratios and absorbed dose rates. Increasingly, stable element analyses are used to provide transfer parameters for radiological models. The study described here found that for both Cs and Sr the transfer of the stable element tended to be lower than that of the radionuclide; this is the first time that this has been demonstrated for Sr, though it is in agreement with limited evidence previously reported for Cs. Studies reporting radiation effects on wildlife in the CEZ generally relate observations to ambient dose rates determined using handheld dose meters. For the first time, we demonstrate that ambient dose rates may underestimate the actual dose rate for some organisms by more than an order of magnitude. When reporting effects studies from the CEZ, it has previously been suggested that the area has comparatively low natural background dose rates. However, on the basis of data reported here, dose rates to wildlife from natural background radionuclides within the CEZ are similar to those in many areas of Europe.

Diagnostic impact of preoperative corticosteroids in primary central nervous system lymphoma.

PURPOSE: High dose corticosteroids are an effective tool for rapidly alleviating neurologic symptoms caused by intracranial mass lesions. However, there is concern that preoperative corticosteroids limit the ability to obtain a definitive pathologic diagnosis, particularly if imaging features suggest primary central nervous system lymphoma (PCNSL). METHODS: To explore the impact of preoperative corticosteroids in newly diagnosed PCNSL patients, from 2009 to 2018 treated at our institution. RESULTS: We identified 54 patients; 18 had received corticosteroids prior to biopsy or resection. Only in one case did the patient have a prior non-diagnostic biopsy, requiring a second procedure. The cumulative doses of preoperative dexamethasone ranged from 4 mg to 120 mg (mean 32 mg, median 24 mg), given over 1-14 days (mean 2 days, median 1 day), and the majority had received corticosteroids for only 1-2 days. There was a trend for a larger diameter of lesional T1 contrast enhancement for patients who received steroids (39 mm vs. 34 mm, p = 0.11). In this series of cases with pathologically and clinically proven PCNSL, preoperative corticosteroids had been given in a third of cases, suggesting that they may be given for symptomatic relief without compromising pathologic diagnosis. CONCLUSIONS: Despite the commonly held tenet that preoperative corticosteroids can obscure the pathologic diagnosis in PCNSL, this is likely not the case in the majority of patients who receive a short course preoperatively. Obtaining a second stereotactic scan to confirm continued presence of the lesion prior to tissue sampling may also mitigate these concerns.

Relation between earthquakes, weather, and soil tilt.

Two years of local earthquake, temperature, and rainfall data taken near a tiltmeter site were used in a study of the numerical relation between these phenomena and the recorded tilt response. A least-squares shaping and predictive error filter approach was used. The relations were ranked in part according to the root mean square (r.m.s.) error of fit across the entire sample space. The tilt data with an annual range of tilt of approximately 10 microradians were fitted to the combined weather data of temperature and rainfall with a 0.75-microradian r.m.s. error. The best fit of earthquakes to these same tilt data is the subclass of events with magnitude (M) > 2.5 within 30 kilometers of the tilt site. The filter that mapped earthquakes to tilt yielded a 1.03-microradian r.m.s. error. The most unusual tilt anomaly over the entire 2-year period has the best fit of rainfall to the data for any single month of the entire data set. This unusual anomaly was the basis of an erroneously predicted earthquake (M approximately 5). These data indicate that if there are premonitory earthquake signals, they are buried in local meteorlogical noise. Separating an earthquake anomaly from the response to surface phenomena becomes more difficult as the earthquake anomaly lead time approaches the rise time of the soil to weather and seasonal variations.

Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1.

BACKGROUND AND PURPOSE: M1 muscarinic ACh receptors (mAChRs) represent an attractive drug target for the treatment of cognitive deficits associated with diseases such as Alzheimer's disease and schizophrenia. However, the discovery of subtype-selective mAChR agonists has been hampered by the high degree of conservation of the orthosteric ACh-binding site among mAChR subtypes. The advent of functional screening assays has enabled the identification of agonists such as AC-42 (4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine), which bind to an allosteric site and selectively activate the M(1) mAChR subtype. However, studies with this compound have been limited to recombinantly expressed mAChRs. EXPERIMENTAL APPROACH: In this study, we have compared the pharmacological profile of AC-42 and a close structural analogue, 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone) at human recombinant, and rat native, mAChRs by calcium mobilization, inositol phosphate accumulation and both in vitro and in vivo electrophysiology. KEY RESULTS: Calcium mobilization and inositol phosphate accumulation assays revealed that both AC-42 and 77-LH-28-1 display high selectivity to activate the M1 mAChR over other mAChR subtypes. Furthermore, 77-LH-28-1, but not AC-42, acted as an agonist at rat hippocampal M1 receptors, as demonstrated by its ability to increase cell firing and initiate gamma frequency network oscillations. Finally, 77-LH-28-1 stimulated cell firing in the rat hippocampus in vivo following subcutaneous administration. CONCLUSIONS AND IMPLICATIONS: These data suggest that 77-LH-28-1 is a potent, selective, bioavailable and brain-penetrant agonist at the M1 mAChR and therefore that it represents a better tool than AC-42, with which to study the pharmacology of the M1 mAChR.

Background exposure rates of terrestrial wildlife in England and Wales.

It has been suggested that, when assessing radiation impacts on non-human biota, estimated dose rates due to anthropogenically released radionuclides should be put in context by comparison to dose rates from natural background radiation. In order to make these comparisons, we need data on the activity concentrations of naturally occurring radionuclides in environmental media and organisms of interest. This paper presents the results of a study to determine the exposure of terrestrial organisms in England and Wales to naturally occurring radionuclides, specifically (40)K, (238)U series and (232)Th series radionuclides. Whole-body activity concentrations for the reference animals and plants (RAPs) as proposed by the ICRP have been collated from literature review, data archives and a targeted sampling campaign. Data specifically for the proposed RAP are sparse. Soil activity concentrations have been derived from an extensive geochemical survey of the UK. Unweighted and weighted absorbed dose rates were estimated using the ERICA Tool. Mean total weighted whole-body absorbed dose rates estimated for the selected terrestrial organisms was in the range 6.9 x 10(-2) to 6.1 x 10(-1) microGy h(-1).

Application of the ERICA Integrated Approach to the Drigg coastal sand dunes.

The EC-funded project 'Environmental Risks from Ionising Contaminants: Assessment and Management' (ERICA) developed an 'Integrated Approach' for assessing the impact of ionising radiation on ecosystems. This paper presents the application of the ERICA Integrated Approach, supported by a software programme (the ERICA Tool) and guidance documentation, to an assessment of the Drigg coastal sand dunes (Cumbria, UK). Targeted sampling provided site-specific data for sand dune biota, including amphibians and reptiles. Radionuclides reported included (90)Sr, (99)Tc, (137)Cs, (238)Pu, (239+240)Pu and (241)Am. Site-specific data were compared to predictions derived using the ERICA Tool. Some under- and over-predictions of biota activity concentrations were identified but can be explained by the specific ecological characteristics and contamination mechanism of the dunes. Overall, the results indicated no significant impact of ionising radiation on the sand dune biota and the Integrated Approach was found to be a flexible and effective means of conducting a radiation impact assessment.

Transfer parameters for ICRP's Reference Animals and Plants in a terrestrial Mediterranean ecosystem.

A system for the radiological protection of the environment (or wildlife) based on Reference Animals and Plants (RAPs) has been suggested by the International Commission on Radiological Protection (ICRP). To assess whole-body activity concentrations for RAPs and the resultant internal dose rates, transfer parameters are required. However, transfer values specifically for the taxonomic families defined for the RAPs are often sparse and furthermore can be extremely site dependent. There is also a considerable geographical bias within available transfer data, with few data for Mediterranean ecosystems. In the present work, stable element concentrations (I, Li, Be, B, Na, Mg, Al, P, S, K. Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Ag, Cd, Cs, Ba, Tl, Pb and U) in terrestrial RAPs, and the corresponding whole-body concentration ratios, CRwo, were determined in two different Mediterranean ecosystems: a Pinewood and a Dehesa (grassland with disperse tree cover). The RAPs considered in the Pinewood ecosystem were Pine Tree and Wild Grass; whereas in the Dehesa ecosystem those considered were Deer, Rat, Earthworm, Bee, Frog, Duck and Wild Grass. The CRwo values estimated from these data are compared to those reported in international compilations and databases.

Do fungi need to be included within environmental radiation protection assessment models?

Fungi are used as biomonitors of forest ecosystems, having comparatively high uptakes of anthropogenic and naturally occurring radionuclides. However, whilst they are known to accumulate radionuclides they are not typically considered in radiological assessment tools for environmental (non-human biota) assessment. In this paper the total dose rate to fungi is estimated using the ERICA Tool, assuming different fruiting body geometries, a single ellipsoid and more complex geometries considering the different components of the fruit body and their differing radionuclide contents based upon measurement data. Anthropogenic and naturally occurring radionuclide concentrations from the Mediterranean ecosystem (Spain) were used in this assessment. The total estimated weighted dose rate was in the range 0.31-3.4 µGy/h (5th-95th percentile), similar to natural exposure rates reported for other wild groups. The total estimated dose was dominated by internal exposure, especially from 226Ra and 210Po. Differences in dose rate between complex geometries and a simple ellipsoid model were negligible. Therefore, the simple ellipsoid model is recommended to assess dose rates to fungal fruiting bodies. Fungal mycelium was also modelled assuming a long filament. Using these geometries, assessments for fungal fruiting bodies and mycelium under different scenarios (post-accident, planned release and existing exposure) were conducted, each being based on available monitoring data. The estimated total dose rate in each case was below the ERICA screening benchmark dose, except for the example post-accident existing exposure scenario (the Chernobyl Exclusion Zone) for which a dose rate in excess of 35 µGy/h was estimated for the fruiting body. Estimated mycelium dose rate in this post-accident existing exposure scenario was close to the 400 µGy/h benchmark for plants, although fungi are generally considered to be less radiosensitive than plants. Further research on appropriate mycelium geometries and their radionuclide content is required. Based on the assessments presented in this paper, there is no need to recommend that fungi should be added to the existing assessment tools and frameworks; if required some tools allow a geometry representing fungi to be created and used within a dose assessment.

The transfer of (137)Cs, Pu isotopes and (90)Sr to bird, bat and ground-dwelling small mammal species within the Chernobyl exclusion zone.

Protected species are the focus of many radiological environmental assessments. However, the lack of radioecological data for many protected species presents a significant international challenge. Furthermore, there are legislative restrictions on destructive sampling of protected species to obtain such data. Where data are not available, extrapolations are often made from 'similar' species but there has been little attempt to validate this approach. In this paper we present what, to our knowledge, is the first study purposefully designed to test the hypothesis that radioecological data for unprotected species can be used to estimate conservative radioecolgical parameters for protected species; conservatism being necessary to ensure that there is no significant impact. The study was conducted in the Chernobyl Exclusion Zone. Consequently, we are able to present data for Pu isotopes in terrestrial wildlife. There has been limited research on Pu transfer to terrestrial wildlife which contrasts with the need to assess radiation exposure of wildlife to Pu isotopes around many nuclear facilities internationally. Our results provide overall support for the hypothesis that data for unprotected species can be used to adequately assess the impacts for ionising radiation on protected species. This is demonstrated for a range of mammalian and avian species. However, we identify one case, the shrew, for which data from other ground-dwelling small mammals would not lead to an appropriately conservative assessment of radiation impact. This indicates the need to further test our hypothesis across a range of species and ecosystems, and/or ensure adequate conservatism within assessments. The data presented are of value to those trying to more accurately estimate the radiation dose to wildlife in the Chernobyl Exclusion Zone, helping to reduce the considerable uncertainty in studies reporting dose-effect relationships for wildlife. A video abstract for this paper is available from: http://bit.ly/1JesKPc.

GABA(B2) is essential for g-protein coupling of the GABA(B) receptor heterodimer.

GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABA(B1) and GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding receptor agonists and antagonists, the role of each GABA(B) subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABA(B2) that are critical for the coupling of GABA(B) receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABA(B2) subunit in G-protein coupling of the GABA(B) receptor heterodimer. In addition, they provide evidence for a novel "sequential" GPCR signaling mechanism in which ligand binding to one heterodimer subunit can induce signal transduction through the second partner of a heteromeric complex.

The C-terminal domains of the GABA(b) receptor subunits mediate intracellular trafficking but are not required for receptor signaling.

GABA(B) receptors are G-protein-coupled receptors that mediate slow synaptic inhibition in the brain and spinal cord. These receptors are heterodimers assembled from GABA(B1) and GABA(B2) subunits, neither of which is capable of producing functional GABA(B) receptors on homomeric expression. GABA(B1,) although able to bind GABA, is retained within the endoplasmic reticulum (ER) when expressed alone. In contrast, GABA(B2) is able to access the cell surface when expressed alone but does not couple efficiently to the appropriate effector systems or produce any detectable GABA-binding sites. In the present study, we have constructed chimeric and truncated GABA(B1) and GABA(B2) subunits to explore further GABA(B) receptor signaling and assembly. Removal of the entire C-terminal intracellular domain of GABA(B1) results in plasma membrane expression without the production of a functional GABA(B) receptor. However, coexpression of this truncated GABA(B1) subunit with either GABA(B2) or a truncated GABA(B2) subunit in which the C terminal has also been removed is capable of functional signaling via G-proteins. In contrast, transferring the entire C-terminal tail of GABA(B1) to GABA(B2) leads to the ER retention of the GABA(B2) subunit when expressed alone. These results indicate that the C terminal of GABA(B1) mediates the ER retention of this protein and that neither of the C-terminal tails of GABA(B1) or GABA(B2) is an absolute requirement for functional coupling of heteromeric receptors. Furthermore although GABA(B1) is capable of producing GABA-binding sites, GABA(B2) is of central importance in the functional coupling of heteromeric GABA(B) receptors to G-proteins and the subsequent activation of effector systems.

Laboratory automation using robotics and information management systems.

Many advances have been made in laboratory automation dealing with robotics and data management. There have been many different approaches to these technologies and many successful applications. Current methods employed in automated techniques utilize robotic processors and arms to manipulate and analyze samples, and computerized management of the data generated by these workhorses.