An Assessment of Potential Health Impacts on Utrok Atoll from Exposure to Cesium-137 (137Cs) and Plutonium

Residual fallout contamination from the nuclear test program in the Marshall Islands is a concern to Marshall Islanders because of the potential health risks associated with exposure to residual fallout contamination in the environment. Scientists from Lawrence Livermore National Laboratory (LLNL) have been monitoring the amount of fallout radiation delivered to Utrok Atoll residents over the past 4 years. This briefing document gives an outline of our findings from the whole body counting and plutonium bioassay monitoring programs. Additional information can be found on the Marshall Islands web site (http://eed.lnl.gov/mi/). Cesium-137 is an important radioactive isotope produced in nuclear detonations and can be taken up from coral soils into locally grown food crop products that form an important part of the Marshallese diet. The Marshall Islands whole body counting program has clearly demonstrated that the majority of Utrok Atoll residents acquire a very small but measurable quantity of cesium-137 in their bodies (Hamilton et al., 2006; Hamilton et. al., 2007a; 2007b;). During 2006, a typical resident of Utrok Atoll received about 3 mrem of radiation from internally deposited cesium-137 (Hamilton et al., 2007a). The population-average dose contribution from cesium-137 is around 2% of the total radiation dose that people normally experience from naturally occurring radiation sources in the Marshall Islands and is thousands of times lower than the level where radiation exposure is known to produce measurable health effects. The existing dose estimates from the whole body counting and plutonium bioassay programs are also well below radiological protection standards for protection of the public as prescribed by U.S. regulators and international agencies including the Marshall Islands Nuclear Claim Tribunal (NCT). Similarly, the level of internally deposited plutonium found in Utrok Atoll residents is well within the range normally expected for people living in the Northern Hemisphere. In addition, the preliminary results of the bioassay program on Utrok Atoll (Hamilton et al., 2007b) provide clear evidence that residents of Utrok Atoll have never acquired a significant uptake of plutonium either through an acute exposure event or from long-term chronic exposure to plutonium in the environment. This information and data should provide a level of assurance to the Utrok Atoll population group and its leadership that the dose contribution from exposure to residual radioactive fallout contamination on Utrok Atoll is very low, and is not likely to have any discernible impact on human health. We also estimate that the dose contribution based on current radiological exposure conditions will not produce any additional cancer fatalities (or any other measurable health condition) above that normally expected to arise in a population group of similar size. The potential risks from any genetic illnesses caused by exposure to residual fallout contamination in the environment will be even lower still. In conclusion, the data and information developed from the radiological protection monitoring program on Utrok appear to support a consensus that it is safe to live on Utrok Atoll. The health risks from exposure to residual fallout contamination on the atoll are minimal when compared with other lifetime risks that people normally experience, and are very small when compared to the threshold where radiation health effects could be either medically diagnosed in an individual or epidemiologically discerned in a group of people

Estimation of Radiation Doses in the Marshall Islands Based on Whole Body Counting of Cesium-137 (137Cs) and Plutonium Urinalysis

Under the auspices of the U.S. Department of Energy (USDOE), researchers from the Lawrence Livermore National Laboratory (LLNL) have recently implemented a series of initiatives to address long-term radiological surveillance needs at former nuclear test sites in the Republic of the Marshall Islands (RMI). The aim of this radiological surveillance monitoring program (RSMP) is to provide timely radiation protection for individuals in the Marshall Islands with respect to two of the most important internally deposited fallout radionuclides-cesium-137 ({sup 137}Cs) and long-lived isotopes 239 and 240 of plutonium ({sup 239+240}Pu) (Robison et al., 1997 and references therein). Therefore, whole-body counting for {sup 137}Cs and a sensitive bioassay for the presence of {sup 239+240}Pu excreted in urine were adopted as the two most applicable in vivo analytical methods to assess radiation doses for individuals in the RMI from internally deposited fallout radionuclides (see Hamilton et al., 2006a-c; Bell et al., 2002). Through 2005, the USDOE has established three permanent whole-body counting facilities in the Marshall Islands: the Enewetak Radiological Laboratory on Enewetak Atoll, the Utrok Whole-Body Counting Facility on Majuro Atoll, and the Rongelap Whole-Body Counting Facility on Rongelap Atoll. These whole-body counting facilities are operated and maintained by trained Marshallese technicians. Scientists from LLNL provide the technical support and training necessary for maintaining quality assurance for data acquisition and dose reporting. This technical basis document summarizes the methodologies used to calculate the annual total effective dose equivalent (TEDE; or dose for the calendar year of measurement) based on whole-body counting of internally deposited {sup 137}Cs and the measurement of {sup 239+240}Pu excreted in urine. Whole-body counting provides a direct measure of the total amount (or burden) of {sup 137}Cs present in the human body at the time of measurement. The amount of {sup 137}Cs detected is often reported in activity units of kilo-Becquerel (kBq), where 1 kBq equals 1000 Bq and 1 Bq = 1 nuclear transformation per second (t s{sup -1}). [However, in the United States the Curie (Ci) continues to be used as the unit of radioactivity; where 1 Ci = 3.7 x 10{sup 10} Bq.] The detection of {sup 239}Pu and {sup 240}Pu in bioassay (urine) samples indicates the presence of internally deposited (systemic) plutonium in the body. Urine samples that are collected in the Marshall Islands from volunteers participating in the RSMP are transported to LLNL, where measurements for {sup 239+240}Pu are performed using a state-of-the-art technology based on Accelerator Mass Spectrometry (AMS) (Hamilton et al., 2004, 2007; Brown et al., 2004). The urinary excretion of plutonium by RSMP volunteers is usually described in activity units, expressed as micro-Becquerel ({micro}Bq) of {sup 239+240}Pu (i.e., representing the sum of the {sup 239}Pu and {sup 240}Pu activity) excreted (lost) per day (d{sup -1}), where 1 {micro}Bq d{sup -1} = 10{sup -6} Bq d{sup -1} and 1 Bq = 1 t s{sup -1}. The systemic burden of plutonium is then estimated from biokinetic relationships as described by the International Commission on Radiological Protection (e.g., see ICRP, 1990). In general, nuclear transformations are accompanied by the emission of energy and/or particles in the form of gamma rays ({gamma}), beta particles ({beta}), and/or alpha particles ({alpha}). Tissues in the human body may adsorb these emissions, where there is a potential for any deposited energy to cause biological damage. The general term used to quantify the extent of any radiation exposure is referred to as the dose. The equivalent dose is defined by the average absorbed dose in an organ or tissue weighted by the average quality factor for the type and energy of the emission causing the dose. The effective dose equivalent (EDE; as applied to the whole body), is the sum of the average dose equivalent for each tissue weighted by each applicable tissue-specific weighing factor (which equates to the sensitivity of that tissue to damage by the equivalent radiation dose it receives). The SI unit of effective dose equivalent is the joule per kilogram (J kg{sup -1}), named the Sievert (Sv). The unit often used by federal and state agencies in the United States to describe EDE continues to be the more historical radiation equivalent man (rem); where 1 rem = 0.01 Sv

On well-posedness, stability, and bifurcation for the axisymmetric surface diffusion flow

In this article, we study the axisymmetric surface diffusion flow (ASD), a fourth-order geometric evolution law. In particular, we prove that ASD generates a real analytic semiflow in the space of (2 + \alpha)-little-H\"older regular surfaces of revolution embedded in R^3 and satisfying periodic boundary conditions. We also give conditions for global existence of solutions and prove that solutions are real analytic in time and space. Further, we investigate the geometric properties of solutions to ASD. Utilizing a connection to axisymmetric surfaces with constant mean curvature, we characterize the equilibria of ASD. Then, focusing on the family of cylinders, we establish results regarding stability, instability and bifurcation behavior, with the radius acting as a bifurcation parameter for the problem.Comment: 37 pages, 6 figures, To Appear in SIAM J. Math. Ana

Individual Radiological Protection Monitoring of Utrok Atoll Residents Based on Whole Body Counting of Cesium-137 (137Cs) and Plutonium Bioassay

This report contains individual radiological protection surveillance data developed during 2006 for adult members of a select group of families living on Utrok Atoll. These Group I volunteers all underwent a whole-body count to determine levels of internally deposited cesium-137 ({sup 137}Cs) and supplied a bioassay sample for analysis of plutonium isotopes. Measurement data were obtained and the results compared with an equivalent set of measurement data for {sup 137}Cs and plutonium isotopes from a second group of adult volunteers (Group II) who were long-term residents of Utrok Atoll. For the purposes of this comparison, Group II volunteers were considered representative of the general population on Utrok Atoll. The general aim of the study was to determine residual systemic burdens of fallout radionuclides in each volunteer group, develop data in response to addressing some specific concerns about the preferential uptake and potential health consequences of residual fallout radionuclides in Group I volunteers, and generally provide some perspective on the significance of radiation doses delivered to volunteers (and the general Utrok Atoll resident population) in terms of radiological protection standards and health risks. Based on dose estimates from measurements of internally deposited {sup 137}Cs and plutonium isotopes, the data and information developed in this report clearly show that neither volunteer group has acquired levels of internally deposited fallout radionuclides specific to nuclear weapons testing in the Marshall Islands that are likely to have any consequence on human health. Moreover, the dose estimates are well below radiological protection standards as prescribed by U.S. regulators and international agencies, and are very small when compared to doses from natural sources of radiation in the Marshall Islands and the threshold where radiation health effects could be either medically diagnosed in an individual or epidemiologically discerned in a group of people. In general, the results from the whole-body counting measurements of 137Cs are consistent with our knowledge that a key pathway for exposure to residual fallout contamination on Utrok Atoll is low-level chronic uptake of {sup 137}Cs from the consumption of locally grown produce (Robison et al., 1999). The error-weighted, average body burden of {sup 137}Cs measured in Group I and Group II volunteers was 0.31 kBq and 0.62 kBq, respectively. The associated average, annual committed effective dose equivalent (CEDE) delivered to Group I and Group II volunteers from {sup 137}Cs during the year of measurement was 2.1 and 4.0 mrem. For comparative purposes, the annual dose limit for members of the public as recommended by the National Council on Radiation Protection and Measurements (NCRP) and the International Commission on Radiological Protection (ICRP) is 100 mrem. Consequently, specific concerns about elevated levels of {sup 137}Cs uptake and higher risks from radiation exposure to Group I volunteers would be considered unfounded. Moreover, the urinary excretion of plutonium-239 ({sup 239}Pu) from Group I and Group II volunteers is statistically indistinguishable. In this case, the error-weighted, average urinary excretion of {sup 239}Pu from Group I volunteers of 0.10 {mu}Bq per 24-h void with a range between -0.01 and 0.23 {mu}Bq per 24-h void compares with an error-weighted average from Group II volunteers of 0.11 {mu}Bq per 24-h void with a range between -0.20 and 0.47 {mu}Bq per 24-h void. The range in urinary excretion of {sup 239}Pu from Utrok Atoll residents is very similar to that observed for other population groups in the Marshall Islands (Bogen et al., 2006; Hamilton et al., 2006a; 2006b; 2006c, 2007a; 2007b; 2007c) and is generally considered representative of worldwide background

Long-term reduction in 137Cs concentration in food crops on coral atolls resulting from potassium treatment

Bikini Island was contaminated March 1, 1954 by the Bravo detonation (U.S nuclear test series, Castle) at Bikini Atoll. About 90% of the estimated dose from nuclear fallout to potential island residents is from cesium-137 ({sup 137}Cs) transferred from soil to plants that are consumed by residents. Thus, radioecology research efforts have been focused on removing {sup 137}Cs from soil and/or reducing its uptake into vegetation. Most effective was addition of potassium (K) to soil that reduces {sup 137}Cs concentration in fruits to 3-5% of pretreatment concentrations. Initial observations indicated this low concentration continued for some time after K was last applied. Long-term studies were designed to evaluate this persistence in more detail because it is very important to provide assurance to returning populations that {sup 137}Cs concentrations in food (and, therefore, radiation dose) will remain low for extended periods, even if K is not applied annually or biennially. Potassium applied at 300, 660, 1260, and 1970 kg ha{sup -1} lead to a {sup 137}Cs concentration in drinking coconut meat that is 34, 22, 10, and about 4 % of original concentration, respectively. Concentration of {sup 137}Cs remains low 8 to 10 y after K is last applied. An explanation for this unexpected result is discussed

Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Principles of Bioimage Informatics: Focus on Machine Learning of Cell Patterns

Abstract. The field of bioimage informatics concerns the development and use of methods for computational analysis of biological images. Traditionally, analysis of such images has been done manually. Manual annotation is, however, slow, expensive, and often highly variable from one expert to another. Furthermore, with modern automated microscopes, hundreds to thousands of images can be collected per hour, making manual analysis infeasible. This field borrows from the pattern recognition and computer vision literature (which contain many techniques for image processing and recognition), but has its own unique challenges and tradeoffs. Fluorescence microscopy images represent perhaps the largest class of biological images for which automation is needed. For this modality, typical problems include cell segmentation, classification of phenotypical response, or decisions regarding differentiated responses (treatment vs. control setting). This overview focuses on the problem of subcellular location determination as a running example, but the techniques discussed are often applicable to other problems.

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe