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.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

An unexpected tumour of the finger: review and management.

We report the case of digital papillary adenocarcinoma in a patient presenting with a solitary fingertip mass. This rare sweat gland tumour has a frequently inconspicuous clinical course but significant potential for recurrence and metastasis. The prognostic implications therefore highlights the necessity of addressing even benign-appearing lesions with expedience.

Voxel modeling of rabbits for use in radiological dose rate calculations.

Radiation dose to biota is generally calculated using Monte Carlo simulations of whole body ellipsoids with homogeneously distributed radioactivity throughout. More complex anatomical phantoms, termed voxel phantoms, have been developed to test the validity of these simplistic geometric models. In most voxel models created to date, human tissue composition and density values have been used in lieu of biologically accurate values for non-human biota. This has raised questions regarding variable tissue composition and density effects on the fraction of radioactive emission energy absorbed within tissues (e.g. the absorbed fraction - AF), along with implications for age-dependent dose rates as organisms mature. The results of this study on rabbits indicates that the variation in composition between two mammalian tissue types (e.g. human vs rabbit bones) made little difference in self-AF (SAF) values (within 5% over most energy ranges). However, variable tissue density (e.g. bone vs liver) can significantly impact SAF values. An examination of differences across life-stages revealed increasing SAF with testis and ovary size of over an order of magnitude for photons and several factors for electrons, indicating the potential for increasing dose rates to these sensitive organs as animals mature. AFs for electron energies of 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, 2.0, and 4.0 MeV and photon energies of 0.01, 0.015, 0.02, 0.03, 0.05, 0.1, 0.2, 0.5, 1.0, 1.5, 2.0, and 4.0 MeV are provided for eleven rabbit tissues. The data presented in this study can be used to calculate accurate organ dose rates for rabbits and other small rodents; to aide in extending dose results among different mammal species; and to validate the use of ellipsoidal models for regulatory purposes.

Accumulation of plutonium in mammalian wildlife tissues following dispersal by accidental-release tests.

We examined the distribution of plutonium (Pu) in the tissues of mammalian wildlife inhabiting the relatively undisturbed, semi-arid former Taranaki weapons test site, Maralinga, Australia. The accumulation of absorbed Pu was highest in the skeleton (83% ± 6%), followed by muscle (10% ± 9%), liver (6% ± 6%), kidneys (0.6% ± 0.4%), and blood (0.2%). Pu activity concentrations in lung tissues were elevated relative to the body average. Foetal transfer was higher in the wildlife data than in previous laboratory studies. The amount of Pu in the gastrointestinal tract was highly elevated relative to that absorbed within the body, potentially increasing transfer of Pu to wildlife and human consumers that may ingest gastrointestinal tract organs. The Pu distribution in the Maralinga mammalian wildlife generally aligns with previous studies related to environmental exposure (e.g. Pu in humans from worldwide fallout), but contrasts with the partitioning models that have traditionally been used for human worker-protection purposes (approximately equal deposition in bone and liver) which appear to under-predict the skeletal accumulation in environmental exposure conditions.

Creation and application of voxelised dosimetric models, and a comparison with the current methodology as used for the International Commission on Radiological Protection's Reference Animals and Plants.

Over the past decade, the International Commission on Radiological Protection (ICRP) has developed a comprehensive approach to environmental protection that includes the use of Reference Animals and Plants (RAPs) to assess radiological impacts on the environment. For the purposes of calculating radiation dose, the RAPs are approximated as simple shapes that contain homogeneous distributions of radionuclides. As uncertainties in environmental dose effects are larger than uncertainties in radiation dose calculation, some have argued against more realistic dose calculation methodologies. However, due to the complexity of organism morphology, internal structure, and density, dose rates calculated via a homogenous model may be too simplistic. The purpose of this study is to examine the benefits of a voxelised phantom compared with simple shapes for organism modelling. Both methods typically use Monte Carlo methods to calculate absorbed dose, but voxelised modelling uses an exact three-dimensional replica of an organism with accurate tissue composition and radionuclide source distribution. It is a multi-stage procedure that couples imaging modalities and processing software with Monte Carlo N-Particle. These features increase dosimetric accuracy, and may reduce uncertainty in non-human biota dose-effect studies by providing mechanistic answers regarding where and how population-level dose effects arise.

Bone graft contamination from a water de-ionizer during processing in a bone bank.

An organism resembling Burkholderia (formerly Pseudomonas) cepacia was isolated from cultures taken during processing of six bone grafts. The source of the contamination was traced to a water de-ionizer; the problem had begun when procedures had been changed, so that water from the de-ionizer had been used without sterilization. Cultures of bone for grafting not only protect recipients from infection, but act also as useful controls for processes involved in bone banking.

Microbiological monitoring of bone grafts: two years' experience at a tissue bank.

In the first two years of operation of a tissue bank, bone was processed on 63 occasions from 22 cadaveric donors and on 37 occasions from 185 living donors. A standardized protocol for microbiological sampling, culturing and interpretation of the results was developed. Semi-quantitative culture of washings of bone was performed on receipt by the tissue bank, and broth enrichment cultures of bone samples were performed at the end of processing, and again after irradiation. One bone donation was rejected because of heavy contamination with Klebsiella sp. on receipt, and contamination of six donations with Burkholderia cepacia was shown to have come from a water deionizer. Contamination of bone on receipt by the tissue bank decreased during the study period, probably related to increasing experience of staff harvesting bone. Microbiological surveillance of bone grafts protect recipients from infection, and is useful as a quality control of the process of bone banking.

Handedness in blood donors: no association with blood group or twinning.

There has been considerable interest in the contribution of inheritance to determination of handedness and in observed associations between hand laterality and twinning, gender and age. Unpublished data from a study of children born preterm suggested an association between AB0 blood group and handedness. A questionnaire filled in by 3815 blood donors, gave information on blood group, age, gender, whether they were a twin, hand used for writing and perceived handedness. There was no association between AB0 blood group or rhesus group and handedness. Significantly more females than males considered themselves right handed (82.5% versus 79.9%) and more subjects aged 50+ wrote with the right hand (90.6% versus 87.6% if younger). Twins did not differ from other subjects in this study and we hypothesise that the generally inconsistent findings relating to twins may be explained by population differences in the proportion of twins born preterm.

Factors affecting the yield of cardiac valve allografts from living unrelated donors.

OBJECTIVE: Allografts are the valve of choice for fertile women, patients with infective endocarditis and those with small aortic roots. However, the supply of valves is problematic and widespread usage is restricted by limited availability. Allograft valves are available from cadaveric donors and from the explanted hearts of transplant recipients. Potentially, hearts from these patients could be an excellent source of usable aortic and pulmonary valves. However, little information is available on the suitability of such donors, the procurement rate of allograft valves from this source, or the factors that limit the yield of implantable valves from explanted hearts. METHOD: In order to examine some of these issues, we have carried out a retrospective study on the explanted hearts offered to the East Anglian Tissue Bank by Papworth hospital. Papworth hospital carries out approximately 90 heart and heart/lung transplants per year. Over a 2 year period, the tissue bank was offered 72 hearts from this programme. RESULTS: Of the 72 hearts offered, 58 were accepted for subsequent dissection and further examination. A total of 14 hearts were refused. The main reasons for refusal were extensive cardiectomy trauma (4 hearts) and abnormal valve morphology (four hearts). Of the 116 valves from those hearts accepted for dissection, 55 valves were rejected upon further examination. Reasons for rejection included: cardiectomy trauma (26 valves), abnormal morphology (22 valves), procurement/dissection trauma (7 valves). Of the 61 valves banked, four were subsequently rejected due to positive or incomplete microbiology. Procurement trauma fell to 0% in the last 12 months of the study but cardiectomy trauma remained constant and was related to previous cardiac surgery. Overall, the yield of implantable valves was 0.8 valves/donor. However, the yield showed considerable variation, from 1.0 valves/donor for donors diagnosed as cardiomyopathy to 0.5 valves/donor for donors with ischaemic heart disease who had undergone previous cardiac surgery. CONCLUSION: It is possible to predict the likely yield of explanted heart valves from different groups of heart transplant recipients, based on diagnosis and previous history. The yield of usable valves could be increased by avoidance of injury, both during cardiectomy and subsequent removal of the valves; this is achievable through appropriate training.

Creation of a voxel phantom of the ICRP reference crab.

The International Commission on Radiological Protection (ICRP) has modeled twelve reference animal and plant (RAP) species using simple geometric shapes in Monte-Carlo (MCNP) based simulations. The focus has now shifted to creating voxel phantoms of each RAP in order to estimate doses to biota with a higher degree of confidence. This paper describes the creation of a voxel model of a Dungeness crab from CT images with shell, gills, gonads, hepatopancreas, and heart identified and segmented. Absorbed fractions were tabulated for each organ as a source and target at twelve photon and nine electron energies: 0.01, 0.015, 0.02, 0.03, 0.05, 0.1, 0.2, 0.5, 1.0, 1.5, 2.0, and 4.0 MeV for photons and 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, 2.0 and 4.0 MeV for electrons. AFs whose error exceeded 5% are marked with an underline in the data tables; AFs whose error was higher than 10% were excluded, and are shown in the tabulated data as a dashed line. A representative sample of the data is shown in Figs. 3-8; the entire data set is available as an electronic appendix. The results are consistent with previous small organism studies (Kinase, 2008; Stabin et al., 2006), and suggest that AF values are highly dependent on source organ location and mass.

Acute myeloid leukaemia after treatment with razoxane.

Two new cases of acute myeloid leukaemia occurring after razoxane therapy are recorded and further haematological and cytogenetic details of two cases previously reported are described. The need for long-term follow-up after patients discontinue razoxane therapy is emphasized.

A comparative study of plateletpheresis using Baxter Autopheresis C and Haemonetics PCS plus.

This study compared plateletpheresis on the Haemonetics PCS Plus (PCS Plus) and the Baxter Autopheresis C (Auto C) using the same 100 selected donors. The number of packs meeting UK BTS/NIBSC specification (> 2.2 x 10(11) platelets per pack) was achieved by 99% of PCS Plus and 82% of Auto C procedures. The positive correlation found between donor precount and final platelet yield was better for the PCS Plus. Both machines met U.K. specification for white-cell contamination but this was significantly greater for the Auto C. Plasma yields were similar. As a result of this study we chose to use the PCS Plus for routine plateletpheresis in our unit. This has enabled us not only to comply with UK BTS/NIBSC specifications for apheresis platelets easily and cost effectively but also to meet our own higher specification (2.75 x 10(11) platelets per pack) using existing staff and without extending the working day.

Tanakan inhibits platelet-activating-factor-induced platelet aggregation in healthy male volunteers.

An open study to investigate the PAF-acether antagonist activity of Tanakan in healthy male volunteers examined the effect of a single 15-ml oral dose on ex vivo platelet aggregation induced by adrenaline, adenosine diphosphate (ADP), collagen or PAF-acether. Aggregometry was performed on platelet-rich plasma samples from blood taken 1 h before dosing with Tanakan and 2, 4 and 8 h after intake of Tanakan. Following dosing with Tanakan there was a reduction in platelet aggregation at all doses of PAF, with 1 microM ADP and adrenaline, the most significant decreases occurred with 75 nM PAF-acether 4 h after intake (p less than 0.05) and 300 nM PAF-acether 4 h (p less than 0.01) and 8 after intake (p less than 0.05). There were no concomitant changes in coagulation, skin bleeding time, haematological and biochemical laboratory tests, blood pressure or pulse. The results provide a possible explanation for the clinical efficacy of Tanakan in the treatment of peripheral vascular disease; they also confirm that a single oral dose of 15 ml Tanakan is well tolerated.

Interaction of antimicrobial agents with human peripheral blood leucocytes: uptake and intracellular localization of certain sulphonamides and trimethoprims.

The uptake of sulphamethoxazole, sulphadiazine, sulphamerazine, sulphanilamide, trimethoprim and brodimoprim by human peripheral blood leucocytes, has been investigated. High performance liquid chromatography (HPLC) was used to assay drug concentrations before and after incubation with leucocyte suspensions. Using radiolabelled material the intracellular localization of two of these compounds was also determined. The results indicated that all the investigated drugs were taken up by leucocytes. Differential studies demonstrated that mononuclear cells accumulated higher drug concentrations (0.13-0.55 microgram/10(7) cells), than resting neutrophils (0.02-0.26 microgram/10(7) cells) with the exception of sulphanilamide, which was taken up to a greater extent by neutrophils (0.75 microgram/10(7) cells). During neutrophil phagocytosis intracellular levels of all the drugs except brodimoprim increased from 3 to 130-fold as compared to resting neutrophils. The uptake of 14C-sulphanilamide and 14C-trimethoprim, in neutrophils and mononuclear blood cells, as assessed by measurement of the cell-associated radioactivity, correlated well with that determined by the HPLC procedure. In the intracellular localization studies 14C-sulphanilamide and 14C-trimethoprim exhibited similar distribution profiles. In neutrophils, 35-40% of radiolabelled drug was located in both the microsome and cytosol fractions whereas in peripheral blood mononuclear cells 40-60% was found in the cytosol and 10-20% in the microsome fraction. The results of this study suggest that, following activation, leucocytes may actively transport these drugs and release them locally at sites of infection. The ability of neutrophils to further concentrate the drugs during phagocytosis may result in reduced survival time of some ingested bacteria. These concepts may be important in designing treatment stratagems for intracellular pathogens.

Care of the laparoscopic Nissen fundoplication patient.

Gastroesophageal reflux disease can usually be successfully managed with conservative medical treatment. Anti-reflux surgery is a safe alternative when treatment fails or patients desire a more definitive treatment option. Through a case study approach, this article describes the indications for surgery, the essentials of the authors' multi-disciplinary approach to care and the components of a well-designed education plan for a patient undergoing laparoscopic Nissen fundoplication. Although most patients do well after surgery, diligent nursing care is required before and after surgery to prevent or manage complications and ensure patients have a rapid recovery and successful outcome.

The effect of age on the pharmacokinetics of pentisomide.

The effects of age on the pharmacokinetics of pentisomide (CM7857), an orally effective antiarrhythmic agent, were studied in two groups of volunteers. Sixteen young volunteers (mean age 26.4 years) and 10 elderly volunteers (mean age 67.8 years) received a single 200 mg oral dose of pentisomide. Mean AUC was larger and terminal elimination half-life longer in the elderly subjects, due to a decrease in total plasma clearance of pentisomide in the elderly. This decrease was due to a reduction in renal clearance of the drug which was paralleled by a significantly lower creatinine clearance in the elderly subjects. Dosage reduction, or a reduced frequency of dosing of pentisomide would be necessary in the elderly or those with impaired renal function.

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.