RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

RENEB Inter-Laboratory Comparison 2021: The Cytokinesis-Block Micronucleus Assay.

The goal of the RENEB inter-laboratory comparison 2021 exercise was to simulate a large-scale radiation accident involving a network of biodosimetry labs. Labs were required to perform their analyses using different biodosimetric assays in triage mode scoring and to rapidly report estimated radiation doses to the organizing institution. This article reports the results obtained with the cytokinesis-block micronucleus assay. Three test samples were exposed to blinded doses of 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 13 mA, ∼75 keV, 1 Gy/min). These doses belong to 3 triage categories of clinical relevance: a low dose category, for no exposure or exposures inferior to 1 Gy, requiring no direct treatment of subjects; a medium dose category, with doses ranging from 1 to 2 Gy, and a high dose category, after exposure to doses higher than 2 Gy, with the two latter requiring increasing medical attention. After irradiation the test samples (no. 1, no. 2 and no. 3) were sent by the organizing laboratory to 14 centers participating in the micronucleus assay exercise. Laboratories were asked to setup micronucleus cultures and to perform the micronucleus assay in triage mode, scoring 500 binucleated cells manually, or 1,000 binucleated cells in automated/semi-automated mode. One laboratory received no blood samples, but scored pictures from another lab. Based on their calibration curves, laboratories had to provide estimates of the administered doses. The accuracy of the reported dose estimates was further analyzed by the micronucleus assay lead. The micronucleus assay allowed classification of samples in the corresponding clinical triage categories (low, medium, high dose category) in 88% of cases (manual scoring, 88%; semi-automated scoring, 100%; automated scoring, 73%). Agreement between scoring laboratories, assessed by calculating the Fleiss' kappa, was excellent (100%) for semi-automated scoring, good (83%) for manual scoring and poor (53%) for fully automated scoring. Correct classification into triage scoring dose intervals (reference dose ±0.5 Gy for doses ≤2.5 Gy, or reference dose ±1 Gy for doses >2.5 Gy), recommended for triage biodosimetry, was obtained in 79% of cases (manual scoring, 73%; semi-automated scoring, 100%; automated scoring, 67%). The percentage of dose estimates whose 95% confidence intervals included the reference dose was 58% (manual scoring, 48%; semiautomated scoring, 72%; automated scoring, 60%). For the irradiated samples no. 2 and no. 3, a systematic shift towards higher dose estimations was observed. This was also noticed with the other cytogenetic assays in this intercomparison exercise. Accuracy of the rapid triage modality could be maintained when the number of manually scored cells was scaled down to 200 binucleated cells. In conclusion, the micronucleus assay, preferably performed in a semi-automated or manual scoring mode, is a reliable technique to perform rapid biodosimetry analysis in large-scale radiation emergencies.

ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19.

BACKGROUND: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. OBJECTIVE: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality. METHODS: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point. RESULTS: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min-1 /1.73 m2 increased odds of in-hospital mortality. CONCLUSION: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.

Elderly patients with atrial fibrillation in routine clinical practice-peri-procedural management of edoxaban oral anticoagulation therapy is associated with a low risk of bleeding and thromboembolic complications: a subset analysis of the prospective, observational, multinational EMIT-AF study.

BACKGROUND: Annually > 10% of patients with atrial fibrillation on oral anticoagulation undergo invasive procedures. Optimal peri-procedural management of anticoagulation, as judged by major bleeding and thromboembolic events, especially in the elderly, is still debated. METHODS: Procedures from 1442 patients were evaluated. Peri-procedural edoxaban management was guided only by the experience of the attending physician. The primary safety outcome was the rate of major bleeding. Secondary outcomes included the peri-procedural administration of edoxaban, other bleeding events, and the main efficacy outcome, a composite of acute coronary syndrome, non-hemorrhagic stroke, transient ischemic attack, systemic embolic events, deep vein thrombosis, pulmonary embolism, and mortality. RESULTS: Of the 1442 patients, 280 (19%) were < 65, 550 (38%) were 65-74, 514 (36%) 75-84, and 98 (7%) were 85 years old or older. With increasing age, comorbidities and risk scores were higher. Any bleeding complications were uncommon across all ages, ranging from 3.9% in patients < 65 to 4.1% in those 85 years or older; major bleeding rates in any age group were ≤ 0.6%. Interruption rates and duration increased with advancing age. Thromboembolic events were more common in the elderly, with all nine events occurring in those > 65, and seven in patients aged > 75 years. CONCLUSION: Despite increased bleeding risk factors in the elderly, bleeding rates were small and similar across all age groups. However, there was a trend toward more thromboembolic complications with advancing age. Further efforts to identify the optimal management to reduce ischemic complications are needed. TRIAL REGISTRATION: NCT# 02950168, October 31, 2016.

BIODOSIMETRY AND BIODOSIMETRY NETWORKS FOR MANAGING RADIATION EMERGENCY.

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.

Retrospective Biodosimetry of an Occupational Overexposure-Case Study.

In 2014, Health Canada was approached by the Canadian Nuclear Safety Commission to conduct biodosimetry for a possible overexposure 4 y prior to assessment. Dose estimates were determined by means of two cytogenetic assays, the dicentric chromosome assay (DCA) and translocations as measured by the fluorescent in situ hybridization (FISH). As dicentrics are considered to be unstable over time, the results of the DCA were adjusted to account for the time elapsed between the suspected exposure and sampling. The frequency of damage was then compared to Health Canada's calibration curves, respectively, to calculate dose. In addition, the translocation data were corrected for age-related increases in background. With a half-life of 36 months for dicentric chromosomes taken into consideration, the dose estimates from both assays were in agreement. Due to the uncertainty in the half-life of dicentrics, the FISH assay is considered to be more reliable as a technique for retrospective biodosimetry.

THE EFFECT OF AN OPTIMIZED IMAGING FLOW CYTOMETRY ANALYSIS TEMPLATE ON SAMPLE THROUGHPUT IN THE REDUCED CULTURE CYTOKINESIS-BLOCK MICRONUCLEUS ASSAY.

In cases of overexposure to ionizing radiation, the cytokinesis-block micronucleus (CBMN) assay can be performed in order to estimate the dose of radiation to an exposed individual. However, in the event of a large-scale radiation accident with many potentially exposed casualties, the assay must be able to generate accurate dose estimates to within ±0.5 Gy as quickly as possible. The assay has been adapted to, validated and optimized on the ImageStreamX imaging flow cytometer. The ease of running this automated version of the CBMN assay allowed investigation into the accuracy of dose estimates after reducing the volume of whole blood cultured to 200 µl and reducing the culture time to 48 h. The data analysis template used to identify binucleated lymphocyte cells (BNCs) and micronuclei (MN) has since been optimized to improve the sensitivity and specificity of BNC and MN detection. This paper presents a re-analysis of existing data using this optimized analysis template to demonstrate that dose estimations from blinded samples can be obtained to the same level of accuracy in a shorter data collection time. Here, we show that dose estimates from blinded samples were obtained to within ±0.5 Gy of the delivered dose when data collection time was reduced by 30 min at standard culture conditions and by 15 min at reduced culture conditions. Reducing data collection time while retaining the same level of accuracy in our imaging flow cytometry-based version of the CBMN assay results in higher throughput and further increases the relevancy of the CBMN assay as a radiation biodosimeter.

An update of the WHO Biodosenet: Developments since its Inception.

In 2007 the World Health Organization established an international network of biodosimetry laboratories, the BioDoseNet. The goal of this network was to support international cooperation and capacity building in the area of biodosimetry around the world, including harmonisation of protocols and techniques to enable them to provide mutual assistance during a mass casualty event. In order to assess the progress and success of this network, the results of the second survey conducted in 2015 that assessed the capabilities and capacities of the members of the network, were compared to the similar first survey conducted in 2009. The results of the survey offer a unique cross-section of the global status of biodosimetry capacity and demonstrate how the BioDoseNet has brought together laboratories from around the world and strengthened the international capacity for biodosimetry.

Optimized automated data analysis for the cytokinesis-block micronucleus assay using imaging flow cytometry for high throughput radiation biodosimetry.

The cytokinesis-block micronucleus (CBMN) assay is a well-established technique that can be employed in triage radiation biodosimetry to estimate whole body doses of radiation to potentially exposed individuals through quantitation of the frequency of micronuclei (MN) in binucleated lymphocyte cells (BNCs). The assay has been partially automated using traditional microscope-based methods and most recently has been modified for application on the ImageStream(X) (IS(X) ) imaging flow cytometer. This modification has allowed for a similar number of BNCs to be automatically scored as compared to traditional microscopy in a much shorter time period. However, the MN frequency measured was much lower than both manual and automated slide-based methods of performing the assay. This work describes the optimized analysis template which implements newly developed functions in the IDEAS(®) data analysis software for the IS(X) that enhances specificity for BNCs and increases the frequency of scored MN. A new dose response calibration curve is presented in which the average rate of MN per BNC is of similar magnitude to those presented in the literature using automated CBMN slide scoring methods. In addition, dose estimates were generated for nine irradiated, blinded samples and were found to be within ±0.5 Gy of the delivered dose. Results demonstrate that the improved identification accuracy for MN and BNCs in the IS(X) -based version of the CBMN assay will translate to increased accuracy when estimating unknown radiation doses received by exposed individuals following large-scale radiological or nuclear emergencies. © 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.

Multi-parameter dose estimations in radiation biodosimetry using the automated cytokinesis-block micronucleus assay with imaging flow cytometry.

The cytokinesis-block micronucleus (CBMN) assay is an established technique in radiation biological dosimetry for estimating the dose to an individual by measuring the frequency of micronuclei (MN) in binucleated lymphocyte cells (BNCs). The assay has been partially automated using slide-scoring algorithms, but an automated multiparameter method without the need of the slide-making procedure would be advantageous to further increase throughput for application in mass casualty events. The development of the ImageStreamX (ISX) imaging flow cytometer has made it possible to adapt the CBMN assay to an automated imaging flow cytometry (FCM) method. The protocol and analysis presented in this work tailor and expand the assay to a multiparameter biodosimetry tool. Ex vivo irradiated whole blood samples were cultured, processed, and analyzed on the ISX and BNCs, MN, and mononuclear cells were imaged, identified, and enumerated automatically and simultaneously. Details on development of the method, gating strategy, and dose response curves generated for the rate of MN per BNC, percentage of mononuclear cells as well as the replication index are presented. Results indicate that adapting the CBMN assay for use in imaging FCM has produced a rapid, robust, multiparameter analysis method with higher throughput than is currently available with standard microscopy. We conclude that the ISX-CBMN method may be an advantageous tool following a radiological event where triage biodosimetry must be performed on a large number of casualties.

Network science and the effects of music preference on functional brain connectivity: from Beethoven to Eminem.

Most people choose to listen to music that they prefer or 'like' such as classical, country or rock. Previous research has focused on how different characteristics of music (i.e., classical versus country) affect the brain. Yet, when listening to preferred music--regardless of the type--people report they often experience personal thoughts and memories. To date, understanding how this occurs in the brain has remained elusive. Using network science methods, we evaluated differences in functional brain connectivity when individuals listened to complete songs. We show that a circuit important for internally-focused thoughts, known as the default mode network, was most connected when listening to preferred music. We also show that listening to a favorite song alters the connectivity between auditory brain areas and the hippocampus, a region responsible for memory and social emotion consolidation. Given that musical preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of our results was unexpected. These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem. The neurobiological and neurorehabilitation implications of these results are discussed.

Automated analysis of the cytokinesis-block micronucleus assay for radiation biodosimetry using imaging flow cytometry.

The cytokinesis-block micronucleus (CBMN) assay is employed in biological dosimetry to determine the dose of radiation to an exposed individual from the frequency of micronuclei (MN) in binucleated lymphocyte cells. The method has been partially automated for the use in mass casualty events, but it would be advantageous to further automate the method for increased throughput. Recently, automated image analysis has been successfully applied to the traditional, slide-scoring-based method of the CBMN assay. However, with the development of new technologies such as the imaging flow cytometer, it is now possible to adapt this microscope-based assay to an automated imaging flow cytometry method. The ImageStream(X) is an imaging flow cytometer that has adequate sensitivity to quantify radiation doses larger than 1 Gy while adding the increased throughput of traditional flow cytometry. The protocol and analysis presented in this work adapts the CBMN assay for the use on the ImageStream(X). Ex vivo-irradiated whole blood samples cultured for CBMN were analyzed on the ImageStream(X), and preliminary results indicate that binucleated cells and MN can be identified, imaged and enumerated automatically by imaging flow cytometry. Details of the method development, gating strategy and the dose response curve generated are presented and indicate that adaptation of the CBMN assay for the use with imaging flow cytometry has potential for high-throughput analysis following a mass casualty radiological event.

The Internet's role in a biodosimetric response to a radiation mass casualty event.

Response to a large-scale radiological incident could require timely medical interventions to minimize radiation casualties. Proper medical care requires knowing the victim's radiation dose. When physical dosimetry is absent, radiation-specific chromosome aberration analysis can serve to estimate the absorbed dose in order to assist physicians in the medical management of radiation injuries. A mock exercise scenario was presented to six participating biodosimetry laboratories as one individual acutely exposed to Co under conditions suggesting whole-body exposure. The individual was not wearing a dosimeter and within 2-3 h of the incident began vomiting. The individual also had other medical symptoms indicating likelihood of a significant dose. Physicians managing the patient requested a dose estimate in order to develop a treatment plan. Participating laboratories in North and South America, Europe, and Asia were asked to evaluate more than 800 electronic images of metaphase cells from the patient to determine the dicentric yield and calculate a dose estimate with 95% confidence limits. All participants were blind to the physical dose until after submitting their estimates based on the dicentric chromosome assay (DCA). The exercise was successful since the mean biological dose estimate was 1.89 Gy whereas the actual physical dose was 2 Gy. This is well within the requirements for guidance of medical management. The exercise demonstrated that the most labor-intensive step in the entire process (visual evaluation of images) can be accelerated by taking advantage of world-wide expertise available on the Internet.

Cause-specific mortality by occupational skill level in Canada: a 16-year follow-up study.

INTRODUCTION: Mortality data by occupation are not routinely available in Canada, so we analyzed census-linked data to examine cause-specific mortality rates across groups of occupations ranked by skill level. METHODS: A 15% sample of 1991 Canadian Census respondents aged 25 years or older was previously linked to 16 years of mortality data (1991-2006). The current analysis is based on 2.3 million people aged 25 to 64 years at cohort inception, among whom there were 164 332 deaths during the follow-up period. Occupations coded according to the National Occupation Classification were grouped into five skill levels. Age-standardized mortality rates (ASMRs), rate ratios (RRs), rate differences (RDs) and excess mortality were calculated by occupational skill level for various causes of death. RESULTS: ASMRs were clearly graded by skill level: they were highest among those employed in unskilled jobs (and those without an occupation) and lowest for those in professional occupations. All-cause RRs for men were 1.16, 1.40, 1.63 and 1.83 with decreasing occupational skill level compared with professionals. For women the gradient was less steep: 1.23, 1.24, 1.32 and 1.53. This gradient was present for most causes of death. Rate ratios comparing lowest to highest skill levels were greater than 2 for HIV/AIDS, diabetes mellitus, suicide and cancer of the cervix as well as for causes of death associated with tobacco use and excessive alcohol consumption. CONCLUSION: Mortality gradients by occupational skill level were evident for most causes of death. These results provide detailed cause-specific baseline indicators not previously available for Canada.

TITRE: Mortalité par cause en fonction du niveau de compétence professionnelle au Canada : une étude de suivi sur 16 ans. INTRODUCTION: Les données sur la mortalité par profession n'étant pas facilement accessibles au Canada, nous avons analysé des données issues du recensement pour étudier les taux de mortalité par cause au sein de différents groupes de professions hiérarchisés par niveaux de compétence. MÉTHODOLOGIE: Un échantillon de 15 % des répondants de 25 ans et plus au recensement du Canada de 1991 avait été précédemment couplé avec 16 années de données sur la mortalité (1991-2006). Notre analyse est fondée sur une cohorte de 2,3 millions de personnes âgées de 25 à 64 ans au début de l'étude, au sein de laquelle 164 332 décès ont été enregistrés au cours de la période de suivi. Les professions ont été classées conformément à la Classification nationale des professions et ont été réparties en cinq groupes de niveaux de compétence. Les taux de mortalité normalisés selon l'âge (TMNA), les rapports de taux (RT), les différences de taux (DT) et la surmortalité ont été calculés par niveau de compétence professionnelle pour différentes causes de décès. RÉSULTATS: Les TMNA variaient clairement selon le niveau de compétence : ils étaient plus élevés chez les personnes occupant un poste non spécialisé (et chez celles sans emploi) et moins élevés chez celles occupant un poste professionnel. Chez les hommes, les RT toutes causes confondues étaient de 1,16, 1,40, 1,63 et 1,83 à mesure que le niveau de compétence professionnelle diminuait et en référence au groupe des professionnels. Chez les femmes, le gradient était moins prononcé : 1,23, 1,24, 1,32 et 1,53. Nous avons observé ce gradient pour la plupart des causes de décès. Les RT concernant les niveaux de compétence les plus faibles par rapport aux plus élevés étaient supérieurs à 2 pour le VIH/sida, le diabète sucré, le suicide et le cancer du col de l'utérus, ainsi que pour les causes de décès associées au tabagisme et à la consommation excessive d'alcool. CONCLUSION: Les gradients de la mortalité par niveau de compétence professionnelle étaient clairs pour la plupart des causes de décès. Ces résultats fournissent des indicateurs de référence détaillés sur la mortalité par cause qui n'étaient pas disponibles au Canada auparavant.

Analysis of chromosome damage for biodosimetry using imaging flow cytometry.

The dicentric chromosome assay (DCA), which involves counting the frequency of dicentric chromosomes in mitotic lymphocytes and converting it to a dose-estimation for ionizing radiation exposure, is considered to be the gold standard for radiation biodosimetry. Furthermore, for emergency response, the DCA has been adapted for triage by simplifying the scoring method [1]. With the development of new technologies such as the imaging flow cytometer, it may now be possible to adapt this microscope-based method to an automated cytometry method. This technology allows the sensitivity of microscopy to be maintained while adding the increased throughput of flow cytometry. A new protocol is being developed to adapt the DCA to the imaging cytometer in order to further increase the rapid determination of a biological dose. Peripheral blood mononuclear cells (PBMC) were isolated from ex vivo irradiated whole blood samples using a density gradient separation method and cultured with PHA and Colcemid. After 48h incubation, the chromosomes were isolated, stained for DNA content with propidium iodide (PI) and labelled with a centromere marker. Stained chromosomes were then analyzed on the ImageStream(×) (EMD-Millipore, Billerica, MA). Preliminary results indicate that individual chromosomes can be identified and mono- and dicentric chromosomes can be differentiated by imaging cytometry. A dose response curve was generated using this technology. The details of the method and the dose response curve are presented and compared to traditional microscope scoring. Imaging cytometry is a new technology which enables the rapid, automated analysis of fluorescently labelled chromosomes. Adapting the dicentric assay to this technology has the potential for high throughput analysis for mass casualty events.

Cardiovascular disease mortality among First Nations people in Canada, 1991-2001.

OBJECTIVE: To compare cardiovascular disease mortality patterns between First Nations people and non-Aboriginal adults by sex and by income adequacy quintile and level of educational attainment. METHODS: A 15% sample of 1991 Canadian census respondents aged 25 years or older was previously linked to 11 years of mortality data. In this study, First Nations people were defined by North American Indian ethnic origin (ancestry), registration under the Indian Act, and/or membership in an Indian band or First Nation. The cohort included 62 400 First Nations people and 2 624 300 non-Aboriginal people. RESULTS: Compared to non-Aboriginal cohort members, the age-standardized cardiovascular disease mortality rate was 30% higher for First Nations men and 76% higher for First Nations women. This represented an excess of 58 deaths and 71 deaths per 100 000 person-years at risk, for First Nations men and women, respectively. Within each income adequacy quintile (adjusted for family size and region of residence) and level of educational attainment, the risk of dying from cardiovascular disease was higher for First Nations people compared to their non-Aboriginal counterparts. CONCLUSION: First Nations people had higher rates of death from cardiovascular disease than non-Aboriginal Canadians within each income quintile and level of education. Income and education accounted for 67% and 25% of the excess mortality of First Nations men and women respectively.

Income disparities in life expectancy in the City of Toronto and Region of Peel, Ontario.

INTRODUCTION: To understand the lack of a gradient in mortality by neighbourhood income in a previous study, we used individual-level data from the 1991-2001 Canadian census mortality follow-up study to examine income-related disparities in life expectancy and probability of survival to age 75 years in the City of Toronto and Region of Peel. METHODS: We calculated period life tables for each sex and income adequacy quintile, overall and separately for immigrants and non-immigrants. RESULTS: For all cohort members of both sexes, including both immigrants and non-immigrants, there was a clear gradient across the income quintiles, with higher life expectancy in each successively richer quintile. However, the disparities by income were much greater when the analysis was restricted to non-immigrants. The lesser gradient for immigrants appeared to reflect the higher proportion of recent immigrants in the lower income quintiles. CONCLUSION: These findings highlight the importance of using individual-level ascertainment of income whenever possible, and of including immigrant status and period of immigration in assessments of health outcomes, especially for areas with a high proportion of immigrants.

The capacity, capabilities and needs of the WHO BioDoseNet member laboratories.

Biodosimetry is an essential tool for providing timely assessments of radiation exposure, particularly when physical dosimetry is unavailable or unreliable. For mass-casualty events involving public exposure to ionising radiation, it is paramount to rapidly provide this dose information for medical management of casualties. The dicentric chromosome assay is currently the most reliable accepted method for biodosimetry; however, in a mass-casualty scenario, the throughput of this assay will be challenged by its time-consuming nature and the specific expertise required. To address this limitation, many countries have established expertise in cytogenetic biodosimetry and started developing surge capabilities through setting up regional networks to deal with emergency situations. To capitalise on this growing expertise and organise it into an internationally coordinated laboratory network, the World Health Organization has created and launched a global biodosimetry network (BioDoseNet). In order to determine the existing capacity of BioDoseNet member laboratories, including their expertise and in vivo experience, involvement in national and international activities, problems, needs and prospects, an in-depth survey was conducted. These survey results provide significant information on the current state of emergency cytogenetic biodosimetry capabilities around the world.

Conspecific cues and breeding habitat selection in an endangered woodland warbler.

1. Research on habitat selection has focused on the role of vegetative and geologic characteristics or antagonistic behavioural interactions. 2. Conspecifics can confer information about habitat quality and provide positive density-dependent effects, suggesting habitat selection in response to the presence of conspecifics can be an adaptive strategy. 3. We conducted a manipulative field experiment investigating use of conspecific location cues for habitat selection and consequent reproductive outcomes for the endangered golden-cheeked warbler (Setophaga chrysoparia). We investigated the response in woodlands across a range of habitat canopy cover conditions typically considered suitable to unsuitable and using vocal cues presented during two time periods: pre-settlement and post-breeding. 4. Warblers showed a strong response to both pre-settlement and post-breeding conspecific cues. Territory density was greater than four times higher in treatment sample units than controls. The magnitude of response was higher for cues presented during the pre-settlement period. Positive response to conspecific cues was consistent even in previously unoccupied areas with low canopy cover typically considered unsuitable, resulting in aggregations of warblers in areas generally not considered potential habitat. 5. Pairing and reproductive success of males was not correlated with canopy cover, as commonly thought. Pairing success and fledging success increased with increasing territory density suggesting that conspecific density may be more important for habitat selection decisions than the canopy cover conditions typically thought to be most important. These results suggest the range of habitat within which birds can perform successfully may be greater than is typically observed. 6. Our results suggest the territory selection process may not be substantially influenced by competition in some systems. Settlement in response to conspecific cues produced aggregations within larger areas of similar vegetative characteristics. Understanding what cues drive habitat selection decisions and whether these cues are correlated with habitat quality is critical for conserving fitness-enhancing habitats, avoiding creation of ecological traps, generating accurate predictions of species distributions and understanding how occupancy relates to habitat suitability.