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Purpose: To present the impact in coverage of different methods for Poisson confidence intervals and the impact in dose coverage of different uncertainty factors. A detailed explanation of the uncertainty sources in the Bayesian method is also presented. Materials and methods: The exact coverage of uncertainty Poisson confidence intervals and the dose uncertainty interval coverage were performed by simulations using R-based scripts. Results: The Poisson exact calibration interval via the Modified Crow and Gardner method resulted in coverage quite close to the nominal level of confidence; additionally, the method retains the shortest property of Crow and Gardner, and gains the property of a lower limit strictly increasing in the mean of dicentrics. The unlimited simultaneous calibration interval seems to be the method of choice to preserve the coverage at 95% under parametric and nonparametric conditions but is a conservative method. When samples came from a Poisson distribution, the ISO propagation of errors and Bayesian approaches seem to be the closest to the 95% coverage. Conclusions: The Modified Crow and Gardner method should be preferred over the Garwood method for Poisson exact confidence intervals. The unlimited simultaneous calibration interval did not lose its property to preserve the coverage at 95% applying a regression coverage factor of value 2.02 at the point of doses studied in the simulation. [ABSTRACT FROM AUTHOR]

High levels of scatter radiation in catheterization laboratories may lead to posterior subcapsular opacities in the lens of the staff. The international Retrospective Evaluation of Lens Injuries and Dose (RELID) was performed in Argentina for the first time in 2010 in the context of the congress of the Latin American Society of Interventional Cardiology (SOLACI) and recently, in 2014, was carried out for the second time (SOLACI-CACI 2014). The 2014 study included 115 participants: interventional cardiologists, technicians and nurses. Posterior subcapsular lens changes typical of ionizing radiation exposure were found in 91.5% of interventional cardiologists, in 77% of technicians and in 100% of nurses, according to the Merriam-Focht scale. This RELID study (Argentina 2014) has particular importance since it allowed the follow-up of 10 professionals evaluated in 2010. The results obtained in the study population highlight the importance of the availability and proper use of the elements of radiation protection, as well as staff training. [ABSTRACT FROM AUTHOR]

Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy. [ABSTRACT FROM AUTHOR]

Biological Dosimetry is a necessary support for national radiation protection programmes and emergency response schemes. The Latin American Biological Dosimetry Network (LBDNet) was formally founded in 2007 to provide early biological dosimetry assistance in case of radiation emergencies in the Latin American Region. Here are presented the main topics considered in the foundational document of the network, which comprise: mission, partners, concept of operation, including the mechanism to request support for biological dosimetry assistance in the region, and the network capabilities. The process for network activation and the role of the coordinating laboratory during biological dosimetry emergency response is also presented. This information is preceded by historical remarks on biological dosimetry cooperation in Latin America. A summary of the main experimental and practical results already obtained by the LBDNet is also included. [ABSTRACT FROM AUTHOR]

The bottleneck in data acquisition during biological dosimetry based on a dicentric assay is the need to score dicentrics in a large number of lymphocytes. One way to increase the capacity of a given laboratory is to use the ability of skilled operators from other laboratories. This can be done using image analysis systems and distributing images all around the world. Two exercises were conducted to test the efficiency of such an approach involving 10 laboratories. During the first exercise (E1), the participant laboratories analysed the same images derived from cells exposed to 0.5 and 3 Gy; 100 images were sent to all participants for both doses. Whatever the dose, only about half of the cells were complete with well-spread metaphases suitable for analysis. A coefficient of variation (CV) on the standard deviation of ∼15 % was obtained for both doses. The trueness was better for 3 Gy (0.6 %) than for 0.5 Gy (37.8 %). The number of estimated doses classified as satisfactory according to the z-score was 3 at 0.5 Gy and 8 at 3 Gy for 10 dose estimations. In the second exercise, an emergency situation was tested, each laboratory was required to score a different set of 50 images in 2 d extracted from 500 downloaded images derived from cells exposed to 0.5 Gy. Then the remaining 450 images had to be scored within a week. Using 50 different images, the CV on the estimated doses (79.2 %) was not as good as in E1, probably associated to a lower number of cells analysed (50 vs. 100) or from the fact that laboratories analysed a different set of images. The trueness for the dose was better after scoring 500 cells (22.5 %) than after 50 cells (26.8 %). For the 10 dose estimations, the number of doses classified as satisfactory according to the z-score was 9, for both 50 and 500 cells. Overall, the results obtained support the feasibility of networking using electronically transmitted images. However, before its implementation some issues should be elucidated, such as the number and resolution of the images to be sent, and the harmonisation of the scoring criteria. Additionally, a global website able to be used for the different regional networks, like Share Points, will be desirable to facilitate worldwide communication. [ABSTRACT FROM AUTHOR]

The main objective of the study was the evaluation of the efficacy and homogeneity with which the laboratories of the region carry out biological dosimetry using the two most useful at the present time cytogenetic indicators: the frequency of dicentrics (dicentrics and rings) and that of micronuclei in human lymphocytes. The intercomparison was carried out from codes slides. The gamma radiation doses employed were 0.7,5, 1.5 and 3 Gy. One sample was not irradiated. In the ± 30% of the true dose interval were included 11 out of 15 doses calculated by dicentrics frequency and 9 out of 12 doses calculated by micronuclei frequency. The true doses were in the interval established with 95% confidence limit in 10 out of 12 dose intervals estimated by micronuclei frequency and in 9 out of 15 dose intervals estimated by dicentrics frequency. The laboratory results were similar. [ABSTRACT FROM AUTHOR]

Purpose: This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from in vitro irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories., Methods: Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories., Results: Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation ( s *) estimated by robust methods for all three samples., Conclusions: The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.

Purpose: To test the performance of different algorithms that can be used in inter-laboratory comparisons based on dicentric chromosome analysis, and to evaluate the impact of considering a priori values different to calculate individual laboratory performance based on the ionizing radiation dose estimation., Methods: Mean and standard deviation estimations in inter-laboratory comparisons are tested on simulated data and data from previously published inter-laboratory comparisons using three robust algorithms, Algorithm A, Algorithm B and Q/Hampel, all programmed in R-project language and implemented in a Shiny application. The simulated data were generated assuming three different probabilities to contaminate inter-laboratory comparisons samples with atypical dose values. Comparison between different algorithms was also done using published exercises where blood samples were irradiated at 0 and 0.7 Gy that represent a challenge for the assessment of an inter-laboratory comparison., Results: The best performance was obtained with the Q/Hampel algorithm for the estimation of the dose mean and with the Algorithm B for the estimation of the dose standard deviation under the conditions tested in the simulations. The Q/Hampel algorithm showed the best performance when non-irradiated samples were evaluated and there was a high proportion of identical values. The presence identical values cause the Algorithm B to fail. Real examples illustrating the need to consider standard deviation priors, and the need to use algorithms resistant to a high proportion of identical values are presented., Conclusions: Q/Hampel algorithm is a serious candidate to estimate the dose mean in the inter-laboratory comparisons, and to estimate both parameters when the proportion of identical values equals or higher than the half of the results. When the proportion of identical values is less than the half of the results, the Algorithm B should be considered as a candidate to estimate the standard deviation in the inter-laboratory comparisons with small number of laboratories. We remark that special attention is needed to establish prior definitions of standard deviation in the assessment of inter-laboratory dicentric assay comparisons.

Gender balance refers to the equitable treatment and access to opportunities for all genders. In order to achieve true gender balance, a variety of proactive approaches developed collaboratively, with insight from multiple perspectives, need to be implemented. With that purpose, the participation of women in professions related to radiation and radiation protection was prioritised and given high visibility by allocating a 'Women in Radiation' (WiR) Special Session at the 15th International Congress of the International Radiation Protection Association (IRPA), hosted by South Korea on 20 January 2021. In this session, various issues related to gender balance and equity/equality were highlighted by the panellists, and further elaborated in a subsequent discussion with attendees. The main goal of the WiR Special Session was to convene women from different organisations, career and age stages, disciplines and countries, in particular to consider the Asian-Oceanic vision and status of gender equality, along with other topics to support a 'Call for Action', with concrete recommendations subsequently provided to IRPA. The discussion stressed the main needs and challenges faced by women working in various radiation fields, along with raising awareness of possible professional and employment opportunities. This paper identifies some steps necessary to encourage, enhance and support the inclusion of more diversity in nuclear professions with specific emphasis on women. In conclusion, gender balance and equality must be at the heart of any strategic plan for the future of the radiological protection profession; international cooperation between relevant bodies is essential for success and could serve as a catalyst for specific policy statements aimed at achieving a balanced representation of women in radiological protection., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

In CMML, neoplastic monocytes can be distinguished based on their immunophenotype. Supportive care myeloid growth factors in concomitant extranodal non-Hodgkin Lymphoma are safe., Competing Interests: AR and FDR received honoraria from Amgen, Novartis, and Takeda. NLP and GAP received honoraria from Novartis. All the other authors do not have any conflicts of interest., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Context: Klinefelter syndrome (KS), in which subjects have additional copies of X chromosomes, is the most common male sex chromosome abnormality, with a prevalence of 1 in 660 and an incidence of about 1 in 500-700 newborns. Its sign and symptoms include infertility, generally low testosterone levels, and an increased prevalence of obesity and metabolic syndrome. Epicardial fat thickness (EFT) reflects visceral adiposity rather than general obesity., Objective: The aim of this study was to analyze echocardiographic EFT in a cohort of patients with KS in comparison with non-obese and obese euploid controls, and to evaluate its correlation with biochemical parameters., Design, Setting and Participants: Two hundred and twenty-one KS patients referred to our Rare Endocrine Diseases clinic and 77 age-matched controls underwent Doppler echocardiography and a full investigation of anthropometric and body composition, Serum levels of total testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), fasting plasma glucose, insulin, cholesterol and triglycerides were obtained. All participants underwent dual energy X-ray absorptiometry (DEXA) scan to assess truncal body fat (TrBF)., Main Outcome Measure: EFT, body composition and metabolic parameters in KS patients and how they are affected by genotype., Results: EFT was greater in KS patients than in healthy non-obese (NOb) controls, but lower than in obese (OB) controls. When KS patients were divided into groups (hypogonadal; eugonadal; receiving testosterone replacement therapy [TRT]), EFT was greater in hypogonadal patients than in NOb controls and eugonadal patients, but showed no difference from the OB controls or TRT patients. Hypogonadal patients showed increased TrBF in comparison with NOb controls and eugonadal and TRT patients, and similar TrBF to OB controls. As expected, there was a strong correlation between BMI and EFT in both KS patients and controls (P < 0.0001). In contrast, there was a strong inverse correlation between testosterone and EFT in the control group, but not in KS patients. EFT was significantly correlated with TrBF in both populations (P < 0.0001). Multivariate analyses showed that the major determinants of both EFT and TrBF were BMI and the presence of KS itself. Testosterone and triglycerides were not included as variables in the models., Conclusion: EFT in hypogonadal KS subjects was similar to that of the obese eugonadal controls. Even though there was a direct correlation between BMI and EFT in both populations, the influence of TrBF on EFT was stronger. The presence of the supernumerary X chromosome appeared to be one of the strongest determinants of EFT and TrBF, independent of testosterone levels., (Copyright © 2019. Published by Elsevier Inc.)

Biological dosimetry enables individual dose reconstruction in the case of unclear or inconsistent radiation exposure situations, especially when a direct measurement of ionizing radiation is not or is no longer possible. To be prepared for large-scale radiological incidents, networking between well-trained laboratories has been identified as a useful approach for provision of the fast and trustworthy dose assessments needed in such circumstances. To this end, various biodosimetry laboratories worldwide have joined forces and set up regional and/or nationwide networks either on a formal or informal basis. Many of these laboratories are also a part of global networks such as those organized by World Health Organization, International Atomic Energy Agency or Global Health Security Initiative. In the present report, biodosimetry networks from different parts of the world are presented, and the partners, activities and cooperation actions are detailed. Moreover, guidance for situational application of tools used for individual dosimetry is given.

Purpose: To present Poisson exact goodness-of-fit tests as alternatives and complements to the asymptotic u-test, which is the most widely used in cytogenetic biodosimetry, to decide whether a sample of chromosomal aberrations in blood cells comes from an homogeneous or inhomogeneous exposure., Materials and Methods: Three Poisson exact goodness-of-fit test from the literature are introduced and implemented in the R environment. A Shiny R Studio application, named GOF Poisson, has been updated for the purpose of giving support to this work. The three exact tests and the u-test are applied in chromosomal aberration data from clinical and accidental radiation exposure patients., Results: It is observed how the u-test is not an appropriate approximation in small samples with small yield of chromosomal aberrations. Tools are provided to compute the three exact tests, which is not as trivial as the implementation of the u-test., Conclusions: Poisson exact goodness-of-fit tests should be considered jointly to the u-test for detecting inhomogeneous exposures in the cytogenetic biodosimetry practice.

Purpose: Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network., Materials and Methods: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants., Results: The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point., Conclusions: In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners.

The BioDoseNet was founded by the World Health Organization as a global network of biodosimetry laboratories for building biodosimetry laboratory capacities in countries. The newly established BioDoseNet image repository is a databank of ~25 000 electronically captured images of metaphases from the dicentric assay, which have been previously analysed by international experts. The detailed scoring results and dose estimations have, in most cases, already been published. The compilation of these images into one image repository provides a valuable tool for training and research purposes in biological dosimetry. No special software is needed to view and score the image galleries. For those new to the dicentric assay, the BioDoseNet Image Repository provides an introduction to and training for the dicentric assay. It is an excellent instrument for intra-laboratory training purposes or inter-comparisons between laboratories, as recommended by the International Organization for Standardisation standards. In the event of a radiation accident, the repository can also increase the surge capacity and reduce the turnaround time for dose estimations. Finally, it provides a mechanism for the discussion of scoring discrepancies in difficult cases., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Mitotic Index (MI) estimation expressed as percentage of mitosis plays an important role as quality control endpoint. To this end, MI is applied to check the lot of media and reagents to be used throughout the assay and also to check cellular viability after blood sample shipping, indicating satisfactory/unsatisfactory conditions for the progression of cell culture. The objective of this paper was to apply the CellProfiler open-source software for automatic detection of mitotic and nuclei figures from digitized images of cultured human lymphocytes for MI assessment, and to compare its performance to that performed through semi-automatic and visual detection. Lymphocytes were irradiated and cultured for mitosis detection. Sets of images from cultures were analyzed visually and findings were compared with those using CellProfiler software. The CellProfiler pipeline includes the detection of nuclei and mitosis with 80% sensitivity and more than 99% specificity. We conclude that CellProfiler is a reliable tool for counting mitosis and nuclei from cytogenetic images, saves considerable time compared to manual operation and reduces the variability derived from the scoring criteria of different scorers. The CellProfiler automated pipeline achieves good agreement with visual counting workflow, i.e. it allows fully automated mitotic and nuclei scoring in cytogenetic images yielding reliable information with minimal user intervention., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.

Purpose: Transcranial electric stimulations (tES) with amplitude-modulated currents are promising tools to enhance neuromodulation effects. It is essential to select the correct cortical targets and inhibitory/excitatory protocols to reverse changes in specific networks. We aimed at assessing the dependence of cortical excitability changes on the current amplitude of 20 Hz transcranial alternating current stimulation (tACS) over the bilateral primary motor cortex., Methods: We chose two amplitude ranges of the stimulations, around 25 μA/cm2 and 63 μA/cm2 from peak to peak, with three values (at steps of about 2.5%) around each, to generate, respectively, inhibitory and excitatory effects of the primary motor cortex. We checked such changes online through transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs)., Results: Cortical excitability changes depended upon current density (p = 0.001). Low current densities decreased MEP amplitudes (inhibition) while high current densities increased them (excitation)., Conclusions: tACS targeting bilateral homologous cortical areas can induce online inhibition or excitation as a function of the current density.

It has been observed that victims of accidental overexposures show better chance of survival if they receive medical treatment early. The increased risk of scenarios involving mass casualties has stimulated the scientific community to develop tools that would help the medical doctors to treat victims. The biological dosimetry has become a routine test to estimate the dose, supplementing physical and clinical dosimetry. In case of radiation emergencies, in order to provide timely and effectively biological dosimetry assistance it is essential to guarantee an adequate transport of blood samples in principal, for providing support to countries that do not have biodosimetry laboratories. The objective of the present paper is to provide general guidelines, summarised in 10 points, for timely and proper receiving and sending of blood samples under National and International regulations, for safe and expeditious international transport. These guidelines cover the classification, packaging, marking, labelling, refrigeration and documentation requirements for the international shipping of blood samples and pellets, to provide assistance missions with a tool that would contribute with the preparedness for an effective biodosimetric response in cases of radiological or nuclear emergencies., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Caring for patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III and IV with chronic respiratory failure is difficult independent of whether the target is survival or quality of life (QOL). The role of inhaled drug therapy in this specific set of very severe COPD patients has not previously been assessed. The only drug able to prolong survival in these patients is long term oxygen therapy, whereas there is little evidence to indicate long-term domiciliary mechanical ventilation in the routine management of stable hypercapnic patients. Supplemental oxygen during exercise reduces exercise breathlessness and improves exercise capacity of the hypoxaemic patient. Pulmonary rehabilitation including nutritional supplementation is a significant component of therapy, even in these severe patients. Relief of dyspnoea with drugs such as morphine should not be denied to severely disabled patients who share poor QOL with cancer patients. Non-invasive ventilation has been used as a palliative treatment to reduce dyspnoea. Lung Volume Reduction Surgery may improve mortality, exercise capacity, and QOL in selected patients, but is associated with significant morbidity and an early mortality rate in the most severe patients. Lung transplantation is a final step in end-stage patients, but short- and long-term outcomes remain significantly inferior in relation to other "solid" organs recipients.

Objective: The aim of this study is to quantify the incidence of home injuries using an integrated surveillance system. It aims to estimate home accident mortality., Material and Methods: The sources of data for this epidemiological descriptive study were the emergency information system, the hospital information system and the mortality registry of Lazio Region, 2000-2001. We selected all emergency department (ED) visits for unintentional traumas that occurred at home. We calculated incidence of ED visits, hospitalisation and mortality rates by sex and age., Results: In the year 2000, 145101 persons visited the ED (2700/100000), 8.1% of whom were then admitted to the hospital. Incidence was higher among children and older people. We observed 620 fatalities, a rate of 0.43%. The mortality registry reported 1042 deceased, a home accident-related mortality rate of 31.1/100000., Conclusions: Unintentional injuries in the home are a relevant public health problem. Since none of the databases used in the study give a complete measure of the burden of home injuries, we combined the data from all of them to estimate the mortality and the burden of home injuries. Interventions for prevention must identify the specific accidents/injuries they are trying to reduce in order to focus their intervention on the appropriate population.

One of the objectives of the HUman MicroNucleus (HUMN) project is to identify the methodological variables that have an important impact on micronucleus (MN) or micronucleated (MNed) cell frequencies measured in human lymphocytes using the cytokinesis-block micronucleus assay. In a previous study we had shown that the scoring criteria used were likely to be an important variable. To determine the extent of residual variation when laboratories scored cells from the same cultures using the same set of standard scoring criteria, an inter-laboratory slide-scoring exercise was performed among 34 laboratories from 21 countries with a total of 51 slide scorers involved. The results of this study show that even under these optimized conditions there is a great variation in the MN frequency or MNed cell frequency obtained by individual laboratories and scorers. All laboratories ranked correctly the MNed cell frequency in cells from cultures that were unirradiated, or exposed to 1 or 2Gy of gamma rays. The study also estimated that the intra-scorer median coefficient of variation for duplicate MNed cell frequency scores is 29% for unexposed cultures and 14 and 11% for cells exposed to 1 and 2Gy, respectively. These values can be used as a standard for quality or acceptability of data in future studies. Using a Poisson regression model it was estimated that radiation dose explained 67% of the variance, while staining method, cell sample, laboratory, and covariance explained 0.6, 0.3, 6.5, and 25.6% of the variance, respectively, leaving only 3.1% of the variance unexplained. As part of this exercise, nucleoplasmic bridges were also estimated by the laboratories; however, inexperience in the use of this biomarker of chromosome rearrangement was reflected in the much greater heterogeneity in the data and the unexplained variation estimated by the Poisson model. The results of these studies indicate clearly that even after standardizing culture and scoring conditions it will be necessary to calibrate scorers and laboratories if MN, MNed cell and nucleoplasmic bridge frequencies are to be reliably compared among laboratories and among populations.

Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 per thousand and the interquartile range was between 3 and 12 per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods., (Copyright 2001 Wiley-Liss, Inc.)

As part of a regional International Atomic Energy Agency (IAEA) collaborative project within Latin America, five countries participated in an intercomparison in cytogenetic dosimetry. Coded slides for chromosomal aberrations and micronucleus analyses were prepared by the coordinator laboratory which organized the exercise and sent to the other participating laboratories. For estimates of dose, each laboratory scored the frequency of dicentrics in metaphases and the frequency of micronuclei in binucleated cells. The lymphocytes were irradiated with 60Co gamma-rays (0, 0.75, 1.5 and 3.0 Gy). Eleven of the 15 estimates of dose based on dicentrics and nine of the 12 based on micronuclei fell within +/- 30% of the true dose. When considering the uncertainties of the dose estimates, the true dose fell within the 95% confidence limits of the estimates on eight of the 15 occasions for dicentrics and four of the 12 for micronuclei.