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Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF ( p = 0.04), von Willebrand factor ( p = 0.001) and endothelial microparticles ( p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone ( p = 0.045), whilst cystatin-C ( p = 0.004) and soluble P selectin ( p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Blann, Brown and Heitmar.)

Filth flies associated with animal production transmit pathogens to humans and animals, propagate antimicrobial resistance in microbial communities and provoke nuisance litigation. Although dispersal of flies from facilities is often responsible for these negative effects, filth fly research on swine facilities has been limited to within the barns. Filth fly adaptations in space and time, as well as influences of abiotic and biotic factors impact distribution and abundance of animal-associated filth flies on swine production facilities. In this study, fly surveillance was conducted around four swine facilities in Bladen County, North Carolina, U.S.A. from January 2019 to October 2019. Traps were replaced weekly and animal-associated filth flies were identified. Flies were grouped for comparison based on biology and differences in pest management strategies. There were distinct differences in abundance and spatial distribution of different filth fly groups on the swine facilities, which are likely linked to environmental factors like spatial relation to crop production and species phenology. The impact of the observed temporal and spatial distribution and abundance is discussed in the context of filth fly management., (© 2021 The Royal Entomological Society.)

The potential consequences for Norway should a nuclear accident at the Sellafield nuclear site occur, have been of concern for Norwegian authorities for several decades. Meteorological data from a 33-year period and the dispersion model 'SNAP' were used to evaluate meteorological conditions for which atmospheric transport of radionuclides from Sellafield to Norway would lead to the most severe impacts. The worst-case meteorological scenario for Norway, was found on 25 th June 1989 for a low elevation (0-800 m) release and on 29 th June 2001 for a higher elevation (800-1600 m) release. In both cases the western part of Norway was most affected. In general, the probability for depositions (>10 Bq/m 2 of 137 Cs) increased about 40% during the autumn and winter compared to the spring and summer months. An influence of climate change on the depositions was analysed, but not verified. Results from a number of simulations were also compared to identify how factors such as radioactive particle characteristics and initial release conditions could affect the predicted radionuclide deposition. The impact on predicted total depositions as well as hot-spot depositions by varying particle density and size as well as release elevation in worst-case scenario simulations amounted to about 40%-50%., (Copyright © 2021. Published by Elsevier Ltd.)

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management. At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium's participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma. Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research. In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

The skeleton is the most common site of secondary disease in breast cancer and prostate cancer, with up to 80% of patients with advanced disease developing bone metastases (BM). The proportion is also substantial in advanced lung cancer (20%-40%). Because of the high prevalence of cancers of the breast, prostate and lung, these cancers account for more than 80% of cases of metastatic bone disease occurring in solid tumours. Metastatic bone disease is associated with greatly increased bone resorption by osteoclasts, leading to moderate to severe pain and other skeletal complications, with major impact on quality of life (QoL). Skeletal Related Events (SREs) have been defined as: pathological long bone or vertebral fractures; spinal cord compression; need for radiation for pain relief or to prevent fracture/spinal cord compression, need for surgery to bone and hypercalcaemia. More recently, Symptomatic Skeletal Events (SSEs) have been defined to monitor QoL. Although there are currently no curative treatments for metastatic bone disease, patients with breast or prostate cancer and BM are now surviving for several years and sometimes longer, and prevention of SREs is the key aim to optimization of QoL. Since their discovery 50 years ago and their introduction more than 30 years ago into the field of metastatic bone disease, a range of oral and intravenous bisphosphonate drugs have made a major contribution to prevention of SREs. Large trials have clearly demonstrated the clinical value of different bisphosphonate-based drugs (including the oral drugs ibandronate and clodronate and intravenous agents such as zoledronate and pamidronate), in treatment of hypercalcaemia of malignancy and the reduction of SREs and SSEs in a range of cancers. Despite the success of denosumab in reducing osteolysis, bisphosphonates also remain mainstay drugs for treatment of metastatic bone disease. Recognizing the 50th Anniversary of the discovery of bisphosphonates, this review focuses on their continuing value in BM treatment and their future potential, for example in providing a bone-targeting vehicle for cytotoxic drugs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

With an increasing prevalence of diabetes worldwide, effective dietary strategies for blood glucose control are crucial. As carbohydrates make up approximately 50% of the diet, it is neither practical nor advisable to avoid them altogether. Most of the carbohydrate in the diet is derived from starch, found in potatoes, pasta, rice and bread. These foods are often processed in some way before consumption, yet little is known about the effects processing, such as chilling and reheating, has on the glycaemic response, particularly when the food is consumed in the context of a mixed meal. This article introduces the SPUD project, a BBSRC DRINC-funded initiative. Taking the potato as the model carbohydrate, this project will investigate, via in vitro and in vivo studies, the effects of domestic food processing techniques on the glycaemic response. A final study, utilising intrinsically labelled potato and a dual stable isotope methodology, will model glucose flux data to determine the underlying mechanisms of action., Competing Interests: The authors declare no conflict of interest., (2020 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

When a nuclear accident occurs, decision makers in the affected country/countries would need to act promptly to protect people, the environment and societal interests from harmful impacts of radioactive fallout. The decisions are usually based on a combination of model prognoses, measurements, and expert judgements within in an emergency decision support system (DSS). Large scale nuclear accidents would need predictive models for the atmospheric, terrestrial, freshwater, and marine ecosystems, for the connections between these in terms of radionuclide fluxes, and for the various exposure pathways to both humans and biota. Our study showed that eight different models and DSS modules could be linked to assess the total human and environmental consequences in Norway from a hypothetical nuclear accident, here chosen to be the Sellafield nuclear reprocessing plant. Activity concentrations and dose rates from 137 Cs for both humans and the environment via various exposure routes were successfully modelled. The study showed that a release of 1% of the total inventory of 137 Cs in the Highly Active Liquor Tanks at Sellafield Ltd is predicted to severely impact humans and the environment in Norway if strong winds are blowing towards the country at the time of an accidental atmospheric release. Furthermore, since the models did not have built-in uncertainty ranges when this Sellafield study was performed, investigations were conducted to identify the key factors contributing to uncertainty in various models and prioritise the ones to focus on in future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Increased public awareness of antimicrobial resistance (AMR) is a key component of effective antimicrobial stewardship strategies. Educational theatre combined with an expert panel was used to engage the public about AMR through delivery of a play entitled 'The drugs don't work'. Audience knowledge and understanding of AMR were measured by pre- and post-play questionnaires. Performance of the play and discussion with the expert panel significantly improved audience knowledge and understanding of AMR, including antibiotic misuse and prescribing. Educational theatre provides a positive learning experience and is an innovative method of public engagement to disseminate important public health messages., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

The role of extracellular vesicles (EVs) as vehicles for cell-to-cell communication between a tumour and its environment is a relatively new concept. The hypothesis that EVs may be critical in co-opting tissues by tumours to generate distant metastatic niches is particularly pertinent to prostate cancer (PCa), where metastatic-tropism to bone predominates over other tissue types. The potential role of EVs as a means of communication between PCa cells and cells of the bone stroma such as osteoblasts, is yet to be fully explored. In this study, we demonstrate that PCa cell EVs both enhance osteoblast viability and produce a significantly more supportive growth environment for PCa cells when grown in co-culture with EV-treated osteoblasts (p < 0.005). Characterisation of the RNA cargo of EVs produced by the bone-metastatic PCa cell line PC3, highlights the EV-RNA cargo is significantly enriched in genes relating to cell surface signalling, cell-cell interaction, and protein translation (p < 0.01). Using novel techniques to track RNA, we demonstrate the delivery of a set of PCa-RNAs to osteoblast via PCa-EVs and show the effect on osteoblast endogenous transcript abundance. Taken together, by using proof-of-concept studies we demonstrate for the first time the contribution of the RNA element of the PCa EV cargo, providing evidence to support PCa EV communication via RNA molecules as a potential novel route to mediate bone metastasis. We propose targeting PCa EVs could offer a potentially important preventative therapy for men at risk of metastatic PCa.

One potentially useful approach to fill data gaps for concentration ratios, CRs, is based upon the hypothesis that an underlying taxonomic and/or phylogenetic relationship exists for radionuclide transfer. The objective of this study was to explore whether these relationships could be used to explain variation in the transfer of radiocaesium to a wide range of marine organisms. CR data for 137 Cs were classified in relation to taxonomic family, order, class and phylum. A Residual Maximum Likelihood (REML) mixed-model regression modelling approach was adopted. The existence of any patterns were then explored using phylogenetic trees constructed with mitochondrial COI gene sequences from various biota groups and mapping the REML residual means onto these trees. A comparison of the predictions made using REML with blind datasets allowed the efficacy of the procedure to be tested. The only significant correlation between predicted and measured activity concentrations was revealed at the taxonomic level of order when comparing REML analysis output with data from the Barents Sea Region. For this single case a correlation 0.80 (Spearman rank) was derived which was significant at the 0.01 level (1-tailed test) although this was not the case once a (Bonferroni) correction was applied. The application of the REML approach to marine datasets has met with limited success, and the phylogenetic trees illustrate complications of using predictions based on values from different levels of taxonomic organization, where predicted values for the order level can mask the values at lower taxonomic levels. Any influence of taxonomy and phylogeny on transfer is not immediately conspicuous and categorizing marine organisms in this way is limited in providing a potentially robust prognostic extrapolation tool. Other factors may plausibly affect transfer to a much greater degree in marine systems, such as quite diverse life histories and different diets, which may confound any phylogenetic pattern., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but the long-term effects are poorly described. The AZURE trial (ISRCTN79831382) was designed to determine whether adjuvant zoledronic acid (ZOL) improves disease outcomes in EBC. Previous analyses showed no effect on overall outcomes but identified benefits in postmenopausal women. Here we present the long-term risks and benefits of adjuvant ZOL with 10-years follow-up., Patients and Methods: 3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapy +/- intravenous ZOL 4 mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects., Results: With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HR DFS   = 0.94, 95%CI = 0.84-1.06, p  = 0.340; HR IDFS   = 0.91, 95%CI = 0.82-1.02, p  = 0.116). However, outcomes remain improved with ZOL in postmenopausal women (HR DFS   = 0.82, 95%CI = 0.67-1.00; HR IDFS   = 0.78, 95%CI = 0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HR IDFS   = 0.75, 95%CI = 0.58-0.97) and OS HR OS   = 0.69, 95%CI = 0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISH + tumors. Bone metastases as a first DFS recurrence (B DFS ) were reduced with ZOL (HR B-DFS   = 0.76, 95%CI = 0.63-0.92, p  = 0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred., Conclusions: Disease benefits with adjuvant ZOL in postmenopausal early breast cancer persist at 10 years of follow-up. The biomarker MAF identified a patient subgroup that derived benefit from ZOL irrespective of menopausal status.

The effects of fire events on contaminant radionuclides within soils of the Belarusian Exclusion Zone were investigated. A number of cores were taken from locations known to have been subject to fire events in the past as well as a series of cores from nearby unburnt locations. Both burnt and unburnt cores were analyzed for contaminant radionuclides as well as a range of relevant soil parameters. The distribution of 137 Cs between various fractions (reversibly bound, irreversibly bound and insoluble) was analyzed. Results indicate no evidence of enhancement or enrichment of radionuclides within the soil column although this does not negate the possibility that such effects were evident at some point in the past, the fire events at two of the sites having occurred almost ten years earlier. Evidence was present of a persistent effect on how 137 Cs was distributed between different fractions of the soil, primarily in relation to the proportions associated with oxides of Fe and Mn and organic matter. The results of the study appear to indicate that the long-term effects of a forest fire on contaminant 137 Cs within the soil column are expressed through changes in the physico-chemical forms of the nuclide to a larger extent than simple redistribution of the contaminant within the soil column., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The accident at the Fukushima-Daiichi Nuclear Power Station on March 11, 2011, led to significant contamination of the surrounding terrestrial and marine environments. Whilst impacts on human health remain the primary concern in the aftermath of such an accident, recent years have seen a significant body of work conducted on the assessment of the accident's impacts on both the terrestrial and marine environment. Such assessments have been undertaken at various levels of biological organisation, for different species, using different methodologies and coming, in many cases, to divergent conclusions as to the effects of the accident on the environment. This article provides an overview of the work conducted in relation to the environmental impacts of the Fukushima accident, critically comparing and contrasting methodologies and results with a view towards finding reasons for discrepancies, should they indeed exist. Based on the outcomes of studies conducted to date, it would appear that in order to avoid the fractured and disparate conclusions drawn in the aftermath of previous accidents, radioactive contaminants and their effects can no longer simply be viewed in isolation with respect to the ecosystems these effects may impact. A combination of laboratory based and field studies with a focus on ecosystem functioning and effects could offer the best opportunities for coherence in the interpretation of the results of studies into the environmental impacts of ionising radiation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Of the wide variety of dumped objects containing radioactive materials in the Arctic seas, the submarine K-27 constitutes a major risk due to the large amount of highly enriched uranium onboard and its location in shallow waters. As the matter of potential operations involving raising of the submarine have entered the public arena, a priori assessment of the contamination in the Arctic marine environment that could result after a possible accident during such operations is a matter of some interest. The dispersion of contaminants within the Arctic has been assessed using a large scale hydrodynamic model for a series of plausible accident scenarios and locations under different oceanographic regimes. Results indicate that, depending primarily on the nature of a release (i.e. instantaneous or continuous), large areas of the Arctic marine environment will exhibit contamination to varying degrees., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objects containing radioactivity have been routinely dumped in Arctic waters near NW Russia up until the 1990s. One of the most radioactive objects in this region, the nuclear submarine K-27, was dumped in Stepogovo Fjord and contained spent nuclear fuel (SNF). Although the two K-27 submarine reactors were mothballed before dumping, concerns about the potential long term risks of contamination remain and plans to retrieve and decommission K-27 exist. In this article, human dose and environmental impact aseessments are presented for two possible future scenarios involving: (1) an ingress of water into a reactor in situ leading to a spontaneous chain reaction (SCR) and (2) an on-board fire when SNF is being removed at the mainland decommissiong site at Gremhika Bay on the Kola Peninsula. Assessments have been completed using conservative assumptions, focusing on possible effects to Norwegian territory. Atmospheric transport and deposition of radioactivity was modelled near field and regionally, using appropriate models, whilst human doses and environmental exposures were modelled using a standard IAEA approach and the ERICA tool, respectively. Results indicate that large areas of Norwegian territory could be affected by fallout from the Gremhika scenario, especially in the north, though at levels two orders of magnitude lower than those observed after the Chernobyl accident. Potential doses, primarily due to ground shine, to a critical group of personnel on-site at Stepogovo resulting from a SCR could require preventative measures based on ICRP recommendations (20-100 mSv). Doses to non-human biota in Norway for the Gremhika scenario would be negligible, typical of background dose rates for terrestrial organisms., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: Metformin is the most widely used oral hypoglycaemic drug, but it may lower B 12 status, which could have important clinical implications. We undertook a systematic review and meta-analysis of the relationship between metformin use and vitamin B 12 deficiency in persons with type 2 diabetes., Methods: Electronic database searches were undertaken (1st January 1957-1st July 2013) using the Cochrane library, Scopus, CINAHL, Grey literature databases, Pub Med Central, NICE Clinical Guidelines UK, and ongoing clinical trials. Included studies were of any study design, with data from patients with type 2 diabetes of any age or gender, taking any dose or duration of metformin. Planned primary outcomes were serum vitamin B 12 levels, % prevalence or incidence of vitamin B 12 deficiency and risk of vitamin B 12 deficiency., Results: Twenty-six papers were included in the review. Ten out of 17 observational studies showed statistically significantly lower levels of vitamin B 12 in patients on metformin than not on metformin. Meta-analysis performed on four trials demonstrated a statistically significant overall mean B 12 reducing effect of metformin of 57pmol/L [WMD (fixed)=-0.57 (95% CI: -35 to -79pmol/L)] after 6weeks to 3months of use., Conclusion: The evidence from this review demonstrates an association between metformin usage and lower levels of vitamin B 12 by 57pmol/L, which leads to frank deficiency or borderline status in some patients with type 2 diabetes. This suggests that it is prudent to monitor B 12 levels in these patients who are at increased risk of deficiency., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The mosquito Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) is the primary vector of viruses that cause yellow fever, dengue and Chikungunya fever. In the absence of effective vaccines, the reduction of these diseases relies on vector control strategies. The success of these strategies is tightly linked to the population dynamics of target populations. In the present study, 14 collections from St. aegypti populations separated by periods of 1-13 years were analysed to determine their temporal genetic stability. Although temporal structure is discernible in most populations, the degree of temporal differentiation is dependent on the population and does not obscure the geographic structure of the various populations. The results suggest that performing detailed studies in the years prior to and after population reduction- or modification-based control interventions at each target field site may be useful in assessing the probability of success., (© 2016 The Royal Entomological Society.)

A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar-phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Cell viability, DNA binding and Topoisomerase II inhibition is discussed for these compounds. Fluorescence microscopy was used to investigate the uptake of the synthesised cryptolepines into the nucleus. We report the synthesis and anti-cancer biological evaluation of nine novel cryptolepine analogues, which have greater cytotoxicity than the parent compound and are important lead compounds in the development of novel potent and selective indoloquinone anti-neoplastic agents.

A new version of the ERICA Tool (version 1.2) was released in November 2014; this constitutes the first major update of the Tool since release in 2007. The key features of the update are presented in this article. Of particular note are new transfer databases extracted from an international compilation of concentration ratios (CRwo-media) and the modification of 'extrapolation' approaches used to select transfer data in cases where information is not available. Bayesian updating approaches have been used in some cases to draw on relevant information that would otherwise have been excluded in the process of deriving CRwo-media statistics. All of these efforts have in turn led to the requirement to update Environmental Media Concentration Limits (EMCLs) used in Tier 1 assessments. Some of the significant changes with regard to EMCLs are highlighted., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics., Patients and Methods: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type., Results: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types., Conclusion: Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Paediatric stroke is a major cause of morbidity and death in children. There is often a delay in making the diagnosis because common differential diagnoses such as migraine and seizures need to be considered and quick access to imaging is difficult. Early recognition is increasingly important for early treatment and to improve outcomes. We present the case of a 4-year-old boy who presented to the Emergency Department with acute hemiparesis. To target the provisional diagnosis of an acute ischaemic stroke, we requested magnetic resonance imaging (MRI) limited to two sequences only: diffusion weighted imaging (DWI) and susceptibility weighted imaging (SWI). We were able to confirm the diagnosis of acute ischaemic stroke within 90 min of presentation to hospital.

The aims of this study were to assess the effectiveness of calcium silicate cement (Biodentine) versus glass ionomer cement (GIC; control group) as indirect pulp capping materials in patients with reversible pulpitis and to compare the effectiveness of cone beam computed tomography (CBCT) versus periapical (PA) radiographs in detecting PA changes at baseline (T0) and at 12 mo (T12) postoperatively. Seventy-two restorations (36 Biodentine, 36 Fuji IX) were placed randomly in 53 patients. CBCT/PA radiographs were taken at T0 and T12. Two calibrated examiners assessed the presence/absence and increase/decrease in the size of existing PA radiolucencies under standardized conditions. The Kappa coefficient evaluated statistically the effectiveness of CBCT versus PA radiographs in detecting PA changes. Chi-square/Mann-Whitney tests were used to evaluate the association between PA changes in CBCT with various clinical measures. Significance was predetermined at α = 0.05. Clinical success rates for Biodentine and Fuji IX GIC were 83.3%. CBCT was significantly more effective in detecting PA radiolucencies compared with radiographs (P = 0.0069). Of the teeth, 65.4% and 90.4% were deemed healthy using CBCT and PA radiographs, respectively, at T12. Healing/healed rates were 17.3%/0%, while new/progressed radiolucency were 30.8%/9.6% with CBCT/PA radiographs, respectively. Seventy-one percent of healed lesions had received Biodentine; 88% of new/progressed lesions received Fuji IX GIC. Teeth presenting with an initial CBCT PA lesion had a failure rate of 63%, whereas teeth with no initial lesion had a failure rate of 16%. Although no statistically significant difference was detected in the clinical efficacy of Biodentine/Fuji IX when used as indirect pulp capping materials in patients with reversible pulpitis, CBCT showed a significant difference in that most healed CBCT lesions had received Biodentine while most that did not heal received Fuji IX. Longer-term follow-up is needed to establish their effect on the healing dynamics of PA tissues (ClinicalTrials.gov NCT02201641)., (© International & American Associations for Dental Research 2015.)

A new TRS document on Transfer of radionuclides to Wildlife has compiled equilibrium CR(wo-media) values for a variety of radionuclides and ecosystems. Assessment tools such as the ERICA Tool use equilibrium whole organism concentration ratios (CR(wo-media)) to predict radionuclide activity concentrations in wildlife from those in media (e.g. water). The aim of this paper is to compare and contrast model predictions of doses from (137)Cs to marine organisms using three different approaches: (i) the ERICA Tool utilising the new TRS values to estimate internal and external doses to reference organisms for the Black sea and the Aegean Sea and for the sea close to the Fukushima Dai-ichi plant. (ii) a hydrodynamic site specific model for seawater for parts of the Aegean Sea, Greece which estimates radionuclide concentrations using site specific data and (iii) a biokinetic model for fish applied to the Fukushima releases to the Pacific. The advantages and limitations of these approaches are discussed with respect to determining doses to pelagic fish. The applicability of the three approaches will vary with the objective of an assessment. The site specific model can predict variation in (137)Cs with depth and uses site specific CR values. The application of the biokinetic model to predicted (137)Cs activity concentrations in seawater and fish due to near coastal inputs from Fukushima Dai-ichi showed that the maximum internal dose-rates in fish attributable to (137)Cs would be substantially lower than those determined using equilibrium assumptions in ERICA but the accumulative doses over 100 days were similar., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Concentration ratios (CRs) are used to derive activity concentrations in wild plants and animals. Usually, compilations of CR values encompass a wide range of element-organism combinations, extracted from different studies with statistical information reported at varying degrees of detail. To produce a more robust estimation of distribution parameters, data from different studies are normally pooled using classical statistical methods. However, there is inherent subjectivity involved in pooling CR data in the sense that there is a tacit assumption that the CRs under any arbitrarily defined biota category belong to the same population. Here, Bayesian inference has been introduced as an alternative way of making estimates of distribution parameters of CRs. This approach, in contrast to classical methods, is more flexible and also allows us to define the various assumptions required, when combining data, in a more explicit manner. Taking selected data from the recently compiled wildlife transfer database (http://www.wildlifetransferdatabase.org/) as a working example, attempts are made to refine the pooling approaches previously used and to consider situations when empirical data are limited., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A key element of most systems for assessing the impact of radionuclides on the environment is a means to estimate the transfer of radionuclides to organisms. To facilitate this, an international wildlife transfer database has been developed to provide an online, searchable compilation of transfer parameters in the form of equilibrium-based whole-organism to media concentration ratios. This paper describes the derivation of the wildlife transfer database, the key data sources it contains and highlights the applications for the data., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A required parameter for the ERICA Tool is the concentration ratio (CR), which is used to describe the transfer from environmental media to a range of organisms. For the original parameterisation of the ERICA Tool, 60% of these values were derived using a variety of extrapolation approaches, including the application of allometric models, the use of values for a similar organism or element with similar biogeochemical behaviour and the use of values from a different ecosystem. Although similar approaches are applied in other assessment systems, there has been little attempt to see how well these approaches perform. In this paper, CR values in the ERICA Tool derived using extrapolation approaches are compared to more recently available empirical data from the IAEA wildlife transfer database. The primary purpose of the default CR database in the ERICA Tool, and other models, is to enable the user to conduct conservative screening assessments. Conservatism was therefore introduced to the analyses by selecting the 95th percentile CR values for subsequent calculations. The extrapolation methodologies are not guaranteed to provide conservative estimates of empirical 95th percentile CRs. For the terrestrial ecosystem, the extrapolation methods provide underpredictions of empirical 95th percentiles as often as they produce overpredictions. In a few cases the underestimation of CR values, when considering all ecosystems, is substantial - by orders of magnitude - which is clearly unacceptable for a screening assessment. Thus, although extrapolation approaches will remain an essential component of screening assessments in the future, because data gaps will always be present, diligence is important in their application. Finally, by synthesizing the results from the current analyses and through other considerations, some recommendations are provided with regards to modifying the original guidance on use of extrapolation approaches in the ERICA Tool., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

An IAEA handbook presenting transfer parameter values for wildlife has recently been produced. Concentration ratios (CRwo-media) between the whole organism (fresh weight) and either soil (dry weight) or water were collated for a range of wildlife groups (classified taxonomically and by feeding strategy) in terrestrial, freshwater, marine and brackish generic ecosystems. The data have been compiled in an on line database, which will continue to be updated in the future providing the basis for subsequent revision of the Wildlife TRS values. An overview of the compilation and analysis, and discussion of the extent and limitations of the data is presented. Example comparisons of the CRwo-media values are given for polonium across all wildlife groups and ecosystems and for molluscs for all radionuclides. The CRwo-media values have also been compared with those currently used in the ERICA Tool which represented the most complete published database for wildlife transfer values prior to this work. The use of CRwo-media values is a pragmatic approach to predicting radionuclide activity concentrations in wildlife and is similar to that used for screening assessments for the human food chain. The CRwo-media values are most suitable for a screening application where there are several conservative assumptions built into the models which will, to varying extents, compensate for the variable data quality and quantity, and associated uncertainty., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Type 2 diabetes (T2D) is characterized by impaired beta cell function and insulin resistance. T2D susceptibility genes identified by Genome-wide association studies (GWAS) are likely to have roles in both impaired insulin secretion from the beta cell as well as insulin resistance. The aim of this study was to use gene expression profiling to assess the effect of the diabetic milieu on the expression of genes involved in both insulin secretion and insulin resistance.We measured the expression of 43 T2D susceptibility genes in the islets, adipose and liver of leptin-deficient Ob/Ob mice compared with Ob/+ littermates. The same panel of genes were also profiled in cultured rodent adipocytes, hepatocytes and beta cells in response to high glucose conditions, to distinguish expression effects due to elevated glycemia from those on the causal pathway to diabetes or induced by other factors in the diabetic microenviroment.We found widespread deregulation of these genes in tissues from Ob/Ob mice, with differential regulation of 23 genes in adipose, 18 genes in liver and one gene (Tcf7l2) in islets of diabetic animals (Ob/Ob) compared to control (Ob/+) animals. However, these expression changes were in most cases not noted in glucose-treated adipocyte, hepatocyte or beta cell lines, indicating that they may not be an effect of hyperglycemia alone.This study indicates that expression changes are apparent with diabetes in both the insulin producing beta cells, but also in peripheral tissues involved in insulin resistance. This suggests that incidence or progression of diabetic phenotypes in a mouse model of diabetes is driven by both secretory and peripheral defects., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The ARIBON trial is a double blind, randomised, placebo controlled study designed to evaluate the impact of ibandronate on bone mineral density (BMD) in women taking anastrozole for adjuvant treatment of breast cancer., Methods: 131 postmenopausal women with early breast cancer were recruited to the study. Of these, 13 had osteoporosis, 50 osteopenia and 68 normal BMD. Patients with osteoporosis at baseline were treated with monthly oral ibandronate 150 mg for 5 years; osteopenic patients were randomised to receive either ibandronate or placebo for two years and offered open label ibandronate depending upon the results of their 2-year BMD result., Results: Of the 20 patients with osteopenia who were randomised to ibandronate and evaluable at the 2 year visit, 17/20 were not offered a bisphosphonate and the improvements in BMD accrued during the first 2 years were lost both at the LS (-3.21%) and TH (-5.0%). Of the 16 patients randomised to placebo 8/16 with high rates of bone loss during years 0-2 received ibandronate over the next 3 years with improvements in BMD of +5.01 and +1.19 at the LS and TH respectively. The 8 patients who were not offered a bisphosphonate experienced relatively little change in BMD throughout the 5 years of the study (LS +0.15%, TH -2.72%). BMD increased steadily in the 9/13 patients initially identified as having osteoporosis (LS +9.65%, TH +2.72%)., Conclusions: Monthly oral ibandronate provides an option to clinicians considering use of a bisphosphonate to prevent bone loss during aromatase inhibitor therapy.

Radiological doses to terrestrial wildlife were examined in this model inter-comparison study that emphasised factors causing variability in dose estimation. The study participants used varying modelling approaches and information sources to estimate dose rates and tissue concentrations for a range of biota types exposed to soil contamination at a shallow radionuclide waste burial site in Australia. Results indicated that the dominant factor causing variation in dose rate estimates (up to three orders of magnitude on mean total dose rates) was the soil-to-organism transfer of radionuclides that included variation in transfer parameter values as well as transfer calculation methods. Additional variation was associated with other modelling factors including: how participants conceptualised and modelled the exposure configurations (two orders of magnitude); which progeny to include with the parent radionuclide (typically less than one order of magnitude); and dose calculation parameters, including radiation weighting factors and dose conversion coefficients (typically less than one order of magnitude). Probabilistic approaches to model parameterisation were used to encompass and describe variable model parameters and outcomes. The study confirms the need for continued evaluation of the underlying mechanisms governing soil-to-organism transfer of radionuclides to improve estimation of dose rates to terrestrial wildlife. The exposure pathways and configurations available in most current codes are limited when considering instances where organisms access subsurface contamination through rooting, burrowing, or using different localised waste areas as part of their habitual routines., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

Background: Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies., Patients and Methods: Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts., Results: Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab)., Conclusions: In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.

Background: Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC., Aim: To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC., Methods: We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers., Results: A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported., Conclusions: Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC., (© 2011 Blackwell Publishing Ltd.)

This study systematically validated two quantitative enzyme-linked immunosorbent assays (ELISAs) for determining Yersinia pestis anti-F1 or anti-V IgG concentration in cynomolgus macaque sera. The results demonstrated that these ELISAs are reliable, reproducible, and suitable for their intended use to measure both anti-F1 and anti-V IgG in monkey sera following vaccination with a heterologous recombinant fusion F1-V protein (rF1-V). Statistical analysis demonstrated assay precision, accuracy, specificity, linearity/dilutional linearity, and robustness for both assays. The quantitative ranges of standard curves were defined as 40-700 ng/mLfor both anti-F1 and anti-V IgG. Either serological assay could be used to determine potency of F1/V antigen-based vaccines in surrogate clinical studies or to define correlates of protective immunity against plague under the Food and Drug Administration's (FDA) two-animal rule.

Recent developments regarding environmental impact assessment methodologies for radioactivity have precipitated the need for information on levels of naturally occurring radionuclides within and transfer to wild flora and fauna. The objectives of this study were therefore to determine activity concentrations of the main dose forming radionuclides (210)Po and (210)Pb in biota from terrestrial ecosystems thus providing insight into the behaviour of these radioisotopes. Samples of soil, plants and animals were collected at Dovrefjell, Central Norway and Olkiluoto, Finland. Soil profiles from Dovrefjell exhibited an approximately exponential fall in (210)Pb activity concentrations from elevated levels in humus/surface soils to "supported" levels at depth. Activity concentrations of (210)Po in fauna (invertebrates, mammals, birds) ranged between 2 and 123 Bq kg(-1)d.w. and in plants and lichens between 20 and 138 Bq kg(-1)d.w. The results showed that soil humus is an important reservoir for (210)Po and (210)Pb and that fauna in close contact with this media may also exhibit elevated levels of (210)Po. Concentration ratios appear to have limited applicability with regards to prediction of activity concentrations of (210)Po in invertebrates and vertebrates. Biokinetic models may provide a tool to explore in a more mechanistic way the behaviour of (210)Po in this system., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background/objectives: A high prevalence of Type 2 diabetes exists in Saudi Arabia. Epidemiological evidence suggests that low glycaemic index (GI) diets reduce diabetes risk. Yet, little is known about the GI of traditional Saudi Arabian staples such as Hassawi rice (HR). HR was evaluated in terms of its GI and insulinaemic index (II). Comparisons were made in vitro assessing glucose released enzymatically. A long-grain rice variety available in both United Kingdom and Saudi Arabia was studied as a comparison., Subjects/methods: For GI and II measurements, HR, Uncle Ben's rice (UBR) and a standard glucose solution were consumed by healthy subjects (n=13) on seven randomised occasions. Capillary bloods were collected at specific times over 2 h after food intake. Food and Agriculture Organization/World Health Organization protocols were used to determine GI and II. For the in vitro studies, cooked rice was incubated with hydrolytic enzymes under standardised conditions. Samples were taken at t=20 and t=120  min and rapidly available glucose (RAG) and slowly available glucose (SAG) were computed., Results: Values of RAG and SAG were lower for HR compared with their respective values for UBR (P<0.001 and P=0.011, respectively). However, no significant difference was observed for GI (P>0.05) despite a lower insulin response noted for HR (P=0.007)., Conclusions: HR had a similar GI to UBR, although a lower insulin response was evident. RAG and SAG values were different for the two rice varieties despite similar GI values. These differences may be important in terms of their metabolic impact and outcome on diabetes.

Regular aspirin intake is associated with a reduction in the incidence of colorectal cancer. Aspirin has been shown to be cytotoxic to colorectal cancer cells in vitro. The molecular basis for this cytotoxicity is controversial, with a number of competing hypotheses in circulation. One suggestion is that the protective effect is related to the induction of expression of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells. We report that treatment of the DNA MMR competent/p53 mutant colorectal cancer cell line SW480 with 1 mM aspirin for 48 h caused changes in mRNA expression of several key genes involved in DNA damage signalling pathways, including a significant down-regulation in transcription of the genes ATR, BRCA1 and MAPK12. Increases in the transcription of XRCC3 and GADD45alpha genes are also reported. Regulation of these genes could potentially have profound effects on colorectal cancer cells and may play a role in the observed chemo-protective effect of aspirin in vivo. Although a correlation was not seen between transcript and protein levels of ATR, BRCA1 and GADD45alpha, an increase in XRCC3 encoded protein expression upon aspirin treatment in SW480 cells was observed by immunoblotting, immunofluorescence and immunohistochemical analysis. This is the first report of XRCC3 gene transcription and encoded protein expression being susceptible to exposure to the non-steroidal anti-inflammatory drug, aspirin. Furthermore, this study indicates that alterations in gene transcription seen in microarray studies must be verified at the protein level.

There is now general acknowledgement that there is a requirement to demonstrate that species other than humans are protected from anthropogenic releases of radioactivity. A number of approaches have been developed for estimating the exposure of wildlife and some of these are being used to conduct regulatory assessments. There is a requirement to compare the outputs of such approaches against available data sets to ensure that they are robust and fit for purpose. In this paper we describe the application of seven approaches for predicting the whole-body ((90)Sr, (137)Cs, (241)Am and Pu isotope) activity concentrations and absorbed dose rates for a range of terrestrial species within the Chernobyl exclusion zone. Predictions are compared against available measurement data, including estimates of external dose rate recorded by thermoluminescent dosimeters attached to rodent species. Potential reasons for differences between predictions between the various approaches and the available data are explored.

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.

The outcome of the PROTECT project (Protection of the Environment from Ionising Radiation in a Regulatory Context) is summarised, focusing on the protection goal and derivation of dose rates which may detrimentally affect wildlife populations. To carry out an impact assessment for radioactive substances, the estimated dose rates produced by assessment tools need to be compared with some form of criteria to judge the level of risk. To do this, appropriate protection goals need to be defined and associated predefined dose rate values, or benchmarks, derived and agreed upon. Previous approaches used to estimate dose rates at which there may be observable changes in populations or individuals are described and discussed, as are more recent derivations of screening benchmarks for use in regulatory frameworks. We have adopted guidance and procedures used for assessment and regulation of other chemical stressors to derive benchmarks. On the basis of consultation with many relevant experts, PROTECT has derived a benchmark screening dose rate, using data on largely reproductive effects to derive species sensitivity distributions, of 10 microGy h(-1) which can be used to identify situations which are below regulatory concern with a high degree of confidence.

In order to put dose-rates derived in environmental impact assessments into context, the International Commission on Radiological Protection (ICRP) has recommended the structuring of effects data according to background exposure levels. The ICRP has also recommended a suite of reference animals and plants (RAPs), including seven aquatic organisms, for use within their developing framework. In light of these propositions, the objective of this work was to collate information on activity concentrations of naturally occurring primordial radionuclides for marine and freshwater ecosystems and apply appropriate dosimetry models to derive absorbed dose-rates. Although coverage of activity concentration data is comprehensive for sediment and water, few, or in some cases no, data were found for some RAPs, e.g. for frogs (Ranidae) and freshwater grasses (Poaceae) for most radionuclides. The activity concentrations for individual radionuclides in both organisms and their habitat often exhibit standard deviations that are substantially greater than arithmetic mean values, reflecting large variability in activity concentrations. To take account of variability a probabilistic approach was adopted. The dominating radionuclides contributing to exposure in the RAPs are (40)K, (210)Po and (226)Ra. The mean unweighted and weighted dose-rates for aquatic RAPs are in the ranges 0.07-0.39 microGy h(-1) and 0.37-1.9 microGy h(-1) respectively.

A number of models are being used to assess the potential environmental impact of releases of radioactivity. These often use a tiered assessment structure whose first tier is designed to be highly conservative and simple to use. An aim of using this initial tier is to identify sites of negligible concern and to remove them from further consideration with a high degree of confidence. In this paper we compare the screening assessment outputs of three freely available models. The outputs of these models varied considerably in terms of estimated risk quotient (RQ) and the radionuclide-organism combinations identified as being the most limiting. A number of factors are identified as contributing to this variability: values of transfer parameters (concentration ratios and K(d)) used; organisms considered; different input options and how these are utilised in the assessment; assumptions as regards secular equilibrium; geometries and exposure scenarios. This large variation in RQ values between models means that the level of confidence required by users is not achieved. We recommend that the factors contributing to the variation in screening assessments be subjected to further investigation so that they can be more fully understood and assessors (and those reviewing assessment outputs) can better justify and evaluate the results obtained.

A number of tools and approaches have been developed recently to allow assessments of the environmental impact of radiation on wildlife to be undertaken. The International Commission on Radiological Protection (ICRP) has stated an intention to provide a more inclusive protection framework for humans and the environment. Using scenarios, which are loosely based on real or predicted discharge data, we investigate how radiological assessments of humans and wildlife can be integrated with special consideration given to the recent outputs of the ICRP. We highlight how assumptions about the location of the exposed population of humans and wildlife, and the selection of appropriate benchmarks for determining potential risks can influence the outcome of the assessments. A number of issues associated with the transfer component and numeric benchmarks were identified, which need to be addressed in order to fully integrate the assessment approaches. A particular issue was the lack of comparable benchmark values for humans and wildlife. In part this may be addressed via the ICRP's recommended derived consideration reference levels for their 12 Reference Animals and Plants.

The Mining and Chemical Industrial Combine, Zheleznogorsk (MCIC, previously known as Krasnoyarsk-26) on the River Yenisey has contaminated the surrounding environment with anthropogenic radionuclides as a result of discharges of radioactive wastes. The purpose of this study was to investigate the vertical distribution of anthropogenic contamination ((137)Cs and plutonium) within floodplain areas at different distances from the discharge point. Sites were chosen that display different characteristics with respect to periodic inundation with river water. Cs-137 activity concentrations were in the range 23-3770 Bq/kg (dry weight, d.w.); Pu-239,240 activity concentrations were in the range <0.01-14.2 Bq/kg (d.w.). Numerous sample cores exhibited sub-surface maxima which may be related to the historical discharges from the MCIC. Possible evidence indicating the deposition of earlier discharges at MCIC in deeper core layers was observed in the (238)Pu:(239,240)Pu activity ratio data: a Pu signal discernible from global fallout could be observed in numerous samples. Cs-137 and Pu-239,240 activity concentrations were correlated with the silt fraction (% by mass <63 microm) though no significant correlation was observed between (grain-size) normalised (137)Cs activity concentrations and distance downstream from the MCIC.

Industrial areas in proximity to the Vodny settlement in the Komi Republic, Russia, have been contaminated by uranium mill tailings and radium production wastes. These areas, exhibiting high activity concentrations of naturally occurring radionuclides in soils, constitute a field laboratory where the effects of combined chronic exposures to alpha-, beta- and gamma-emitting radionuclides on natural plant populations can be studied. The aim of the present work was to determine dose-effect relationships and the range of doses that cause biological effects in natural Vicia cracca L. populations inhabiting the study area. The studied plant species is native to the area and is found ubiquitously. Soil and vegetation samples were taken at a reference location and six contaminated sites characterized by distinct floodplain depositional units with different enhanced levels of naturally occurring radionuclides. A large fraction of the dose at the study sites (including the reference location) was attributable to internal irradiation and (226)Ra was found to be an important contributor to this component of dose. The relationship between the frequency of chromosome aberrations in seedlings' root tip cells and the absorbed dose was found to be quadratic. An exponential model provided the best result in describing the empirical dependence between the absorbed dose and both the germination capacity of seeds and the survival rate of sprouts of V. cracca. For V. cracca plants inhabiting areas contaminated with uranium mill tailings and radium production wastes, a weighted absorbed dose of 0.2 Gy (weighting factor for alpha particles=5) during the vegetation period could be considered to be a level below which no increase in genetic variability and decrease in reproductive capacity might be observed above background.

Cone beam CT is an emerging imaging modality used in maxillofacial imaging. This paper describes the use of cone beam sialography in two patients with salivary gland obstruction. In both cases, the obstruction was identified. The dose is comparable with conventional fluoroscopic techniques and has the advantage that the data may be viewed in a series of fine slices and in three dimensions, which may help in diagnosis and further management of the patient.

A number of models have recently been, or are currently being, developed to enable the assessment of radiation doses from ionising radiation to non-human species. A key component of these models is the ability to predict whole-organism activity concentrations in a wide range of wildlife. In this paper, we compare the whole-organism activity concentrations predicted by eight models participating within the IAEA Environmental Modelling for Radiation Safety programme for a range of radionuclides to terrestrial and freshwater organisms. In many instances, there was considerable variation, ranging over orders of magnitude, between the predictions of the different models. Reasons for this variability (including methodology, data source and data availability) are identified and discussed. The active participation of groups responsible for the development of key models within this exercise is a useful step forward in providing the transparency in methodology and data provenance required for models which are either currently being used for regulatory purposes or which may be used in the future. The work reported in this paper, and supported by other findings, demonstrates that the largest contribution to variability between model predictions is the parameterisation of their transfer components. There is a clear need to focus efforts and provide authoritative compilations of those data which are available.

Our understanding of Glossina fuscipes fuscipes, a major vector of sleeping sickness, has been severely constrained by a lack of genetic markers for mapping and population genetic studies. Here we present 10 newly developed microsatellite loci for this tsetse species. Heterozygosity levels in Moyo, an Ugandan population, averaged 0.57, with only two loci showing very low heterozygosity. Five loci carried more than six alleles. Together with five recently published microsatellite loci, this brings the number of available microsatellite loci for this species to 15. Their availability will greatly facilitate future studies on the genetics of this important human disease vector., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.)

Objective: This report aimed to evaluate the effectiveness of high-resolution ultrasound compared with conventional sialography in the diagnosis of Sjögren's syndrome (SS) and to establish whether less invasive ultrasound could replace sialography as a diagnostic investigation., Method: Clinical records and examination results of 105 consecutive subjects investigated contemporaneously by ultrasound and sialography of the parotid glands for SS were reviewed retrospectively. Results were compared against the final diagnosis established on the basis of revised international classification criteria for SS. 45 subjects were excluded from the study due to incomplete records. Of 60 remaining subjects under investigation for SS, 45 were confirmed (36 primary SS, 9 secondary SS), the remaining 15 subjects being proven not to have the condition., Results: Ultrasound showed a decreased and heterogeneous honeycomb pattern of parotid gland reflectivity in patients with SS, while sialography demonstrated a punctate pattern of sialectasis. Sensitivity, specificity and accuracy for ultrasound were 84.44%, 73% and 81.6%, respectively, and for conventional sialography were 77.77%, 86.66% and 80%, respectively. The diagnostic difference between the two investigations approached significance (P = 0.074). By combining both imaging modalities, sensitivity increased to 91% with 60% specificity and 83.3% accuracy. There was no significant difference between investigations when diagnosing primary vs secondary SS., Conclusion: High-resolution ultrasound is a useful, non-invasive and more sensitive alternative to sialography as a diagnostic test in patients with suspected SS. Accuracy may be increased by supplementing ultrasound with sialography.

The process of assessing risk to the environment following a given release of radioactivity requires the quantification of activity concentrations in environmental media and reference organisms. The methodology adopted by the ERICA Integrated Approach involves the application of concentration ratios (CR values) and distribution coefficients (K(d) values) for aquatic systems. Within this paper the methodologies applied to derive default transfer parameters, collated within the ERICA Tool databases, are described to provide transparency and traceability in the documentation process. Detailed information is provided for the CR values used for marine and freshwater systems. Of the total 372 CR values derived for the marine ecosystem, 195 were identified by literature review. For the freshwater system, the number of values based on review was less, but still constituted 129 from a total of 372 values. In both types of aquatic systems, 70-80% of the data gaps have been filled by employing "preferable" approaches such as those based on substituting values from taxonomically similar organisms or biogeochemically similar elements.

The ERICA Tool is a computerised, flexible software system that has a structure based upon the ERICA Integrated Approach to assessing the radiological risk to biota. The Tool guides the user through the assessment process, recording information and decisions and allowing the necessary calculations to be performed to estimate risks to selected animals and plants. Tier 1 assessments are media concentration based and use pre-calculated environmental media concentration limits to estimate risk quotients. Tier 2 calculates dose rates but allows the user to examine and edit most of the parameters used in the calculation including concentration ratios, distribution coefficients, percentage dry weight soil or sediment, dose conversion coefficients, radiation weighting factors and occupancy factors. Tier 3 offers the same flexibility as Tier 2 but allows the option to run the assessment probabilistically if the underling parameter probability distribution functions are defined. Results from the Tool can be put into context using incorporated data on dose-effects relationships and background dose rates.