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At least 379 records · Page 21

Distribution of toenail selenium levels in young adult Caucasians and African Americans in the United States: The CARDIA Trace Element Study

Background: Data on selenium (Se) levels in American young adults, especially in African Americans, are lacking. Objective: This study presented toenail Se distributions in American young adults of both genders, including both Caucasians and African Americans; and explored potential predictors of toenail Se levels. Data and methods: Data from the Coronary Artery Risk Development in Young Adults study among 4252 American young adults, aged 20-32 in 1987 was used to examine toenail Se levels by instrumental neutron-activation analysis. The distribution of Se levels was described and multivariable linear regression was used to examine potential modifiers of toenail Se concentration within ethnicity-gender subgroups. Results: The geometric mean of toenail Se in this cohort was 0.844 {mu}g/g (95% CI, 0.840-0.849 {mu}g/g) and the median was 0.837 {mu}g/g (95% CI, 0.833-0.844 {mu}g/g). Median levels from lowest to highest quintile were 0.691, 0.774, 0.838, 0.913 and 1.037 {mu}g/g. Se levels varied geographically, and were generally in accordance with its concentrations in local soil. Males, African Americans, current smokers, heavy drinkers and less educated participants were more likely to have low Se levels. Conclusion: This study suggests that toenail Se levels vary geographically depending on soil Se concentrations. In addition to gender, ethnicity and education level, smoking status and alcohol consumption are two important indicators of Se status since they are modifiable lifestyle factors. Findings from this study might aid public health professionals in identifying people at relatively high or low Se levels, so that chronic disease prevention efforts can be directed toward these subgroups. - Research highlights: {yields} Average of toenail Se levels in this cohort was 0.844 {mu}g/g (95% CI, 0.840-0.849 {mu}g/g). {yields} Toenail Se levels vary geographically depending on soil Se concentrations. {yields} Males, African Americans and less educated participants have low Se levels. {yields} Smoking status and alcohol consumption are two important indicators of Se status.

54 ENVIRONMENTAL SCIENCES↗

Temporal trends (1989–2011) in levels of mercury and other heavy metals in feathers of fledgling great egrets nesting in Barnegat Bay, NJ

There is an abundance of data for levels of metals from a range of species, but relatively few long-term time series from the same location. In this paper I examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in feathers from fledgling great egrets (Ardea alba) collected at nesting colonies in Barnegat Bay, New Jersey from 1989 to 2011. The primary objectives were to test the null hypotheses that (1) There were no temporal differences in metal levels in feathers of fledgling great egrets, and (2) Great egrets nesting in different areas of Barnegat Bay (New Jersey) did not differ in metal levels. There were significant yearly variations in levels of all heavy metals in feathers of fledgling great egret, but levels decreased significantly from 1989 to 2011 only for lead (1470 ppb to 54.3 ppb), cadmium (277 ppb to 30.5 ppb), and manganese (only since 1996; 2669 ppb to 329 ppb)). Although mercury levels decreased from 2003–2008 (6430 ppb to 1042 ppb), there was no pattern before 2003, and levels increased after 2008 to 2610 ppb in 2011. Lead, cadmium, chromium, manganese and mercury were higher in feathers from great egrets nesting in the northern part of the bay, and selenium was highest in feathers from mid-bay. The lack of a temporal decline in mercury levels in feathers of great egrets is cause for concern, since the high levels in feathers from some years (means as high as 6430 ppb) are in the range associated with adverse effects (5000 ppb for feathers). -- Highlights: ► Metals were monitored in feathers of great egrets from Barnegat Bay, New Jersey. ► Levels of cadmium and lead decreased significantly from 1989–2011. ► Mercury levels in feathers from great egrets did not decline from 1989–2011. ► Metal levels were generally higher in great egrets and black-crowned night heron feathers than in snowy egrets.

54 ENVIRONMENTAL SCIENCES↗

Radiosensitizing Effects of Ectopic miR-101 on Non-Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non-small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription-polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein-lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic-induced skin lesions show elevated plasma Big ET-1 levels. ► Arsenic-induced hypertension and skin lesions may be linked to plasma Big ET-1 levels.

54 ENVIRONMENTAL SCIENCES↗

The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of HJURP in human breast cancer cells using shRNA reduced the sensitivity to radiation treatment. HJURP mRNA levels were significantly correlated with CENPA mRNA levels. Conclusions: HJURP mRNA level is a prognostic factor for disease-free and overall survival in patients with breast cancer and is a predictive biomarker for sensitivity to radiotherapy.

59 BASIC BIOLOGICAL SCIENCES↗

Precise mean sea level measurements using the Global Positioning System

This paper describes the results of a sea level measurement test conducted off La Jolla, California, in November of 1991. The purpose of this test was to determine accurate sea level measurements using a Global Positioning System (GPS) equipped buoy. These measurements were intended to be used as the sea level component for calibration of the ERS 1 satellite altimeter. Measurements were collected on November 25 and 28 when the ERS 1 satellite overflew the calibration area. Two different types of buoys were used. A waverider design was used on November 25 and a spar design on November 28. This provided the opportunity to examine how dynamic effects of the measurement platform might affect the sea level accuracy. The two buoys were deployed at locations approximately 1.2 km apart and about 15 km west of a reference GPS receiver located on the rooftop of the Institute of Geophysics and Planetary Physics at the Scripps Institute of Oceanography. GPS solutions were computed for 45 minutes on each day and used to produce two sea level time series. An estimate of the mean sea level at both locations was computed by subtracting tide gage data collected at the Scripps Pier from the GPS-determined sea level measurements and then filtering out the high-frequency components due to waves and buoy dynamics. In both cases the GPS estimate differed from Rapp's mean altimetric surface by 0.06 m. Thus, the gradient in the GPS measurements matched the gradient in Rapp's surface. These results suggest that accurate sea level can be determined using GPS on widely differing platforms as long as care is taken to determine the height of the GPS antenna phase center above water level. Application areas include measurement of absolute sea level, of temporal variations in sea level, and of sea level gradients (dominantly the geoid). Specific applications would include ocean altimeter calibration, monitoring of sea level in remote regions, and regional experiments requiring spatial and temporal resolution higher than that available from altimeter data.

Kelecy, Thomas M.↗

Sea-Level Rise: Projections for Maryland 2018

In fulfillment of requirements of the Maryland Commission on Climate Change Act of 2015, this report provides updated projections of the amount of sea-level rise relative to Maryland coastal lands that is expected into the next century. These projections represent the consensus of an Expert Group drawn from the Mid-Atlantic region. The framework for these projections is explicitly tied to the projections of global sea-level rise included in the Intergovernmental Panel on Climate Change Fifth Assessment (2014) and incorporates regional factors such as subsidence, distance from melting glaciers and polar ice sheets, and ocean currents. The probability distribution of estimates of relative sea-level rise from the baseline year of 2000 are provided over time and, after 2050, for three different greenhouse gas emissions pathways: Growing Emissions (RCP8.5), Stabilized Emissions (RCP4.5), and meeting the Paris Agreement (RCP2.6). This framework has been recently used in developing relative sea-level rise projections for California, Oregon, Washington, New Jersey, and Delaware as well as several metropolitan areas. The Likely range (66% probability) of the relative rise of mean sea level expected in Maryland between 2000 and 2050 is 0.8 to 1.6 feet, with about a one-in-twenty chance it could exceed 2.0 feet and about a one-in-one hundred chance it could exceed 2.3 feet. Later this century, rates of sea-level rise increasingly depend on the future pathway of global emissions of greenhouse gases during the next sixty years. If emissions continue to grow well into the second half of the 21st century, the Likely range of sea-level rise experienced in Maryland is 2.0 to 4.2 feet over this century, two to four times the sea-level rise experienced during the 20th century. Moreover, there is a one-in-twenty chance that it could exceed 5.2 feet. If, on the other hand, global society were able to bring net greenhouse gas emissions to zero in time to meet the goals of the Paris Climate Agreement and reduce emissions sufficient to limit the increase in global mean temperature to less than 2°Celsius over pre-industrial levels, the Likely range for 2100 is 1.2 to 3.0 feet, with a one-in-twenty chance that it would exceed 3.7 feet. The difference in sea-level rise between these contrasting scenarios would diverge even more during the next century, with the failure to reduce emissions in the near term resulting in much greater sea-level rise 100 years from now. Moreover, recent research suggests that, without imminent and substantial reductions in greenhouse gas emissions, the loss of polar ice sheets-and thus the rate of sea-level rise-may be more rapid than assumed in these projections, particularly under the Growing Emissions scenario. These probabilistic sea-level rise projections can and should be used in planning and regulation, infrastructure siting and design, estimation of changes in tidal range and storm surge, developing inundation mapping tools, and adaptation strategies for high-tide flooding and saltwater intrusion.

Boesch, D. F.↗

Space Trusted Autonomy Readiness Levels

Technology Readiness Levels are a mainstay for organizations that fund, develop, test, acquire, or use technologies. Technology Readiness Levels provide a standardized assessment of a technology’s maturity and enable consistent comparison among technologies. They inform decisions throughout a technology’s development life cycle, from concept, through development, to use. A variety of alternative Readiness Levels have been developed, including Algorithm Readiness Levels, manufacturing Readiness Levels, Human Readiness Levels, Commercialization Readiness Levels, Machine Learning Readiness Levels, and Technology Commitment Levels. However, while Technology Readiness Levels have been increasingly applied to emerging disciplines, there are unique challenges to assessing the rapidly developing capabilities of autonomy. This paper adopts the moniker of Space Trusted Autonomy Readiness Levels to identify a two-dimensional scale of readiness and trust appropriate for the special challenges of assessing autonomy technologies that seek space use. It draws inspiration from other readiness levels’ definitions, and from the rich field of trust and trustworthiness. The Space Trusted Autonomy Readiness Levels were developed by a collaborative Space Trusted Autonomy subgroup, which was created from The Space Science and Technology Partnership Forum between the United States Space Force, the National Aeronautics and Space Administration, and the National Reconnaissance Office.

Kerianne L Hobbs↗

Improving Peptide-Level Mass Spectrometry Analysis via Double Competition

A critical statistical task in the analysis of shotgun proteomics data involves controlling the false discovery rate (FDR) among the reported set of discoveries. This task is most commonly solved at the peptide-spectrum match (PSM) level by using target-decoy competition (TDC), in which a set of observed spectra are searched against a database containing a mixture of real (target) and decoy peptides. The PSM-level procedure can be adapted to the peptide level by selecting the top-scoring PSM per peptide prior to FDR estimation. Here, we investigate both PSM-level and peptide-level FDR control methods and come to two conclusions. First, although the TDC procedure is provably correct under certain assumptions, we observe that one of these assumptions - that incorrect PSMs are independent of one another - is frequently violated. Hence, we empirically demonstrate that TDC-based PSM-level FDR estimates can be liberally biased. Further, we propose that researchers avoid PSM-level results and instead focus on peptide-level analysis. Second, we investigate three ways to carry out peptide level TDC and show that the most common method ("PSM-only") offers the lowest statistical power in practice. The most powerful method, peptide-level FDR with PSM competition ("PSM-and-peptide"), carries out competition first at the PSM level and then again at the peptide level. In our experiments, this approach yields an average increase of 17% more discovered peptides at a1% FDR threshold relative to the PSM-only method.

59 BASIC BIOLOGICAL SCIENCES↗

U.S. Nuclear Regulatory Commission Historical Perspectives of Very Low-Level Radioactive Waste - 18367

The United States Nuclear Regulatory Commission (NRC), in Title 10 of the Code of Federal Regulations Part 61 (10 CFR Part 61), 'Licensing Requirements for Land Disposal of Radioactive Waste', provides licensing procedures, performance objectives, and technical requirements for the issuance of licenses for the land disposal of low-level radioactive waste. Low-level radioactive waste is divided into four categories based on its potential risk and need for isolation. Class A is the lowest category of low-level radioactive waste and poses the least risk. A large percentage of Class A low-level waste contains very low radionuclide concentrations and does not pose a significant health and safety risk. In the current regulatory framework, this waste, referred to as low-activity or very low-level waste, is managed in the same manner as much more hazardous waste. In 1986 and 1990, as a result of the Low-Level Radioactive Waste Policy Amendments Act of 1985, the NRC issued the Below Regulatory Concern (BRC) policy statement. This policy statement established an implementation plan regarding the expeditious handling of rulemaking petitions 'to exempt specific radioactive waste streams from regulation due to the presence of radionuclides in sufficiently low concentrations or quantities as to be below regulatory concern.' The BRC policy statement provided a consistent risk framework when considering regulatory exemption decisions, such as: (1) the release for unrestricted public use of lands and structures containing residual radioactivity; (2) the distribution of consumer products containing small amounts of radioactive material; (3) the disposal of very low-level radioactive waste at other than licensed disposal sites; and (4) the recycling of slightly contaminated equipment and materials. Due to concerns with the BRC policy that were raised by Congress, the States, the public, and others, Congress enacted the Energy Policy Act of 1992, which revoked the NRC's 1986 and 1990 BRC policy statements and led to the NRC's formal withdrawal of the BRC policy in 1993. Stakeholders raised concerns on NRC's potential deregulation of radioactive material. Additionally, in March 2005, the NRC staff proposed a rule to amend 10 CFR Part 20, 'Standards for Protection Against Radiation,' to include radiological criteria for controlling the disposition of solid materials with very small amounts of residual radioactivity. The NRC staff also proposed a limited disposition approach for the disposition of solid material, limiting the release of solid material meeting a 0.01 milli-Sievert per year (mSv/yr) [1 milli-rem (mrem/yr)] dose criterion, from licensed control. In June 2005, the Commission disapproved publication of the proposed rule and deferred the rulemaking until a later time, stating that the NRC's existing approach of reviewing specific cases on an individual basis was fully protective of public health and safety. This rulemaking effort was discontinued by the Commission in 2016. Recently, several nuclear power plant licensees have announced early decommissioning of their facilities. Some stakeholders have expressed concerns about the capacity and disposal costs associated with using the four existing low-level waste disposal sites for very low levels of radioactive waste (i.e., waste at the low end of the Class A category). A more risk-informed, performance based approach to waste disposal would allow more flexibility in managing this waste commensurate with its risk and hazard. A new approach would also allow the NRC to align with international standards for this type of waste. The NRC is presently conducting a scoping study to identify the actions the agency should take to strengthen its regulatory framework for very low-level waste disposal. The Very Low-Level Waste (VLLW) scoping study will consider divergent stakeholder comments; lessons learned from the BRC policy statements and the proposed rule on radiological criteria for controlling the disposition of solid materials; and best practices of other countries with respect to VLLW disposal. The NRC will also engage other government agencies to discuss regulatory options for VLLW. This paper offers a historical overview of past NRC initiatives to manage the lower end of Class A waste in a manner that is risk informed and performance based. It examines previous endeavors and discusses the regulatory challenges that arose. It also addresses lessons learned and introduces NRC's current effort regarding very low-level radioactive waste disposal. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Copper and zinc levels in soil, water, wheat, and hair of inhabitants of three areas of the Orenburg region, Russia

Highlights: • Soil, water, wheat and hair levels of Zn and Cu in Orenburg region were studied. • Both Zn and Cu levels in the samples were higher in the eastern area. • Higher levels of Zn and Cu in the eastern area may occur due to industrial activities. • Water Zn levels were associated with hair Zn levels. The objective of the present study was to assess the level of zinc and copper in soil, water, wheat and hair of inhabitants of the western, central, and eastern areas of the Orenburg region. A total of 525 water, soil, and wheat samples, as well as 420 hair samples were assessed using atomic absorption spectrometry (water, soil, wheat) and inductively-coupled plasma mass spectrometry (hair). The highest levels of Zn and Cu in water (4.9(4.2–5.1) and 1.0(0.9–1.1) mg/l), soil (23.8(20.7–27.0) and 2.6(1.9–3.1) mg/kg), and wheat (24.7(20.5–31.0) and 4.8(4.2–5.5) mg/kg) were observed in the eastern area (p < 0.001). Hair zinc levels in inhabitants of the western (184(165–198) µg/g) and eastern (224(211–253) µg/g) areas of the region exceeded the respective values from the central area by 32% and 61% (p < 0.001). In turn, hair Cu levels in the central (16.4(14.3–17.8) µg/g) and eastern (17.9(16.4–19.0) µg/g) areas exceeded the values from the western area by 10% and 20%, respectively. Correlation analysis demonstrated that hair Zn levels were positively correlated with water and soil content, whereas wheat Zn levels were associated with soil and water content. For copper significant direct correlation was observed only between soil and water Cu content. In multiple regression models, only water zinc level was significantly associated with hair Zn content, although the general model accounted for 55% of variability of hair Zn content. Higher zinc and copper exposure in the eastern area is presumably associated with higher activity of metal-processing industry.

54 ENVIRONMENTAL SCIENCES↗

Adipose tissue levels of polybrominated diphenyl ethers and breast cancer risk in Chinese women: A case–control study

Highlights: • Associations between adipose tissue PBDE levels and breast cancer risk were assessed. • Levels of most individual PBDE congeners were higher in breast-cancer cases than controls. • Breast-cancer risk was increased with both 2nd and 3rd tertiles of BDE-47 and BDE-209 levels with a trend. • Breast-cancer risk was also increased with the 3rd tertile of BDE-28, 99, 100, 138, 153, 154, and ∑PBDE levels. • PBDE concentrations are associated with breast-cancer risk in women in Chaoshan, China. Polybrominated diphenyl ethers (PBDEs) are suspected to be associated with breast cancer risk because of their estrogenic potencies. Epidemiological studies of PBDEs and breast cancer are scarce. Our study aimed to estimate the association between adipose-tissue PBDE concentrations and breast cancer risk. A total of 209 breast cancer cases and 165 controls were recruited from hospitals between January 2014 and May 2016 in Shantou, Chaoshan area, China. Concentrations of 14 PBDE congeners were measured in adipose tissues obtained from the breast for cases and the abdomen/breast for controls during surgery. Demographic and clinicopathologic characteristics were obtained from medical records. Breast cancer risk as well as clinicopathologic characteristics were evaluated by adipose-tissue PBDE level. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with levels of PBDE congeners were estimated from logistic regression models for all cases and stratified by estrogen receptor (ER) status. Level of total PBDEs (∑PBDE) and most individual PBDE congeners were higher in breast cancer cases than controls (median ∑PBDE, 94.99 vs 73.72 ng/g lipid). In the adjusted univariate model for all cases, breast cancer risk was increased with both 2nd and 3rd tertiles versus the 1st tertile of BDE-47 level (OR 2.05 [95% CI 1.08–3.92]; 5.47 [2.96–10.11]) and BDE-209 level (2.48 [1.30–4.73]; 4.72 [2.52–8.83]) with trend (both P < 0.001) and with the 3rd tertile of BDE-28 level (2.83 [1.63–4.92]), BDE-99 (3.22 [1.85–5.60]), BDE-100 (5.45 [2.90–10.23]), BDE-138 (2.40 [1.37–4.20]), BDE-153 (1.74 [1.02–2.97]), BDE-154 (1.84 [1.05–3.22]), and ∑PBDE levels (1.83 [1.07–3.14]) but decreased with the 3rd tertile of BDE-71 level (0.38 [0.22–0.65]) with trend (all P < 0.01). After stratifying by ER-positive or -negative status, the adjusted results were similar for ER-positive patients except for BDE-153 and BDE-154, with no statistical significance. In the multivariate model for all cases, age, menarche age, BDE-47, 71, 99, 100, 183 and 209 were independent factors associated with breast-cancer risk. ∑PBDE and most individual PBDE congeners investigated were positively associated with breast cancer risk in women from the Chaoshan area, China. PBDE may play a role in the occurrence and development of breast cancer.

54 ENVIRONMENTAL SCIENCES↗

Sea level variation

Published values for the long-term, global mean sea level rise determined from tide gauge records range from about one to three mm per year. The scatter of the estimates appears to arise largely from the use of data from gauges located at convergent tectonic plate boundaries where changes of land elevation give fictitious sea level trends, and the effects of large interdecadal and longer sea level variations on short (less than 50+ years) or sappy records. In addition, virtually all gauges undergo subsidence or uplift due to isostatic rebound from the last deglaciation at a rate comparable to or greater than the secular rise of sea level. Modeling rebound by the ICE-3G model of Tushingham and Peltier (1990) and avoiding tide gauge records in areas of converging tectonic plates produces a highly consistent set of long sea level records. A global set of 21 such stations in nine oceanic regions with an average record length of 76 years during the period 1880-1980 yields the global sea level rise value 1.8 mm/year +/- 0.1. Greenhouse warming scenarios commonly forecast an additional acceleration of global sea level in the next 5 or 6+ decades in the range 0.1-0.2 mm/yr2. Because of the large power at low frequencies in the sea level spectrum, very long tide gauge records (75 years minimum) have been examined for past apparent sea level acceleration. For the 80-year period 1905-1985, 23 essentially complete tide gauge records in 10 geographic groups are available for analysis. These yielded the apparent global acceleration -0.011 (+/- 0.012) mm/yr2. A larger, less uniform set of 37 records in the same 10 groups with 92 years average length covering the 141 years from 1850-1991 gave 0.001 (+/- 0.008) mm/yr2. Thus there is no evidence for an apparent acceleration in the past 100+ years that is significant either statistically, or in comparison to values associated with global warming. Unfortunately, the large interdecadal fluctuations of sea level severely affect estimates of global sea level acceleration for time spans of less than about 50 years. This means that tide gauges alone cannot serve as a reliable leading indicator of climate change in less than many decades. This time required can be significantly reduced if the interdecadal fluctuations of sea level can be understood in terms of their forcing mechanisms, and then removed from the tide gauge records.

Douglas, Bruce C.↗

Low-Level Radioactive Waste Management in the United States: What Have We Wrought? The Richard S. Hodes, M.D. Honor Lecture Award - 12222

In 1979, radioactive waste disposal was an important national issue. State governors were closing the gates on the existing low-level radioactive waste disposal sites and the ultimate disposition of spent fuel was undecided. A few years later, the United States Congress thought they had solved both problems by passing the Low-Level Radioactive Waste Policy Act of 1981, which established a network of regional compacts for low-level radioactive waste disposal, and by passing the Nuclear Waste Policy Act of 1982 to set out how a final resting place for high-level waste would be determined. Upon passage of the acts, State, Regional and Federal officials went to work. Here we are some 30 years later with little to show for our combined effort. The envisioned national repository for high-level radioactive waste has not materialized. Efforts to develop the Yucca Mountain high-level radioactive waste disposal facility were abandoned after spending $13 billion on the failed project. Recently, the Blue Ribbon Commission on America's Nuclear Future issued its draft report that correctly concludes the existing policy toward high-level nuclear waste is 'all but completely broken down'. A couple of new low-level waste disposal facilities have opened since 1981, but neither were the result of efforts under the act. What the Act has done is interject a system of interstate compacts with a byzantine interstate import and export system to complicate the handling of low-level radioactive waste, with attendant costs. As this paper is being written in the fourth-quarter of 2011, after 30 years of political and bureaucratic turmoil, a new comprehensive low-level waste disposal facility at Andrews Texas is approaching its initial operating date. The Yucca Mountain project might be completed or it might not. The US Nuclear Regulatory Commission is commencing a review of their 1981 volume reduction policy statement. The Department of Energy after 26 years has yet to figure out how to implement its obligations under the 1985 amendments to the Low-Level Radioactive Waste Policy Act. But, the last three decades have not been a total loss. A great deal has been learned about radioactive waste disposal since 1979 and the efforts of the public and private sector have shaped and focused the work to be done in the future. So, this lecturer asks the question: 'What have we wrought?' to which he provides his perspective and his recommendations for radioactive waste management policy for the next 30 years. (author)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Association of short-term exposure to ground-level ozone and respiratory outpatient clinic visits in a rural location – Sublette County, Wyoming, 2008–2011

Objective: Short-term exposure to ground-level ozone has been linked to adverse respiratory and other health effects; previous studies typically have focused on summer ground-level ozone in urban areas. During 2008–2011, Sublette County, Wyoming (population: ~10,000 persons), experienced periods of elevated ground-level ozone concentrations during the winter. This study sought to evaluate the association of daily ground-level ozone concentrations and health clinic visits for respiratory disease in this rural county. Methods: Clinic visits for respiratory disease were ascertained from electronic billing records of the two clinics in Sublette County for January 1, 2008–December 31, 2011. A time-stratified case-crossover design, adjusted for temperature and humidity, was used to investigate associations between ground-level ozone concentrations measured at one station and clinic visits for a respiratory health concern by using an unconstrained distributed lag of 0–3 days and single-day lags of 0 day, 1 day, 2 days, and 3 days. Results: The data set included 12,742 case-days and 43,285 selected control-days. The mean ground-level ozone observed was 47±8 ppb. The unconstrained distributed lag of 0–3 days was consistent with a null association (adjusted odds ratio [aOR]: 1.001; 95% confidence interval [CI]: 0.990–1.012); results for lags 0, 2, and 3 days were consistent with the null. However, the results for lag 1 were indicative of a positive association; for every 10-ppb increase in the 8-h maximum average ground-level ozone, a 3.0% increase in respiratory clinic visits the following day was observed (aOR: 1.031; 95% CI: 0.994–1.069). Season modified the adverse respiratory effects: ground-level ozone was significantly associated with respiratory clinic visits during the winter months. The patterns of results from all sensitivity analyzes were consistent with the a priori model. Conclusions: The results demonstrate an association of increasing ground-level ozone with an increase in clinic visits for adverse respiratory-related effects in the following day (lag day 1) in Sublette County; the magnitude was strongest during the winter months; this association during the winter months in a rural location warrants further investigation. - Highlights: • We assessed elevated ground-level ozone in frontier Sublette County, Wyoming. • Ground-level ozone concentrations were moderately to highly correlated between stations. • Adverse respiratory-related clinic visits occurred year round at lag 1. • Strongest association of clinic visits was in the coldest months at lag 1.

54 ENVIRONMENTAL SCIENCES↗

River Deltas and Sea-Level Rise

Future sea-level rise poses an existential threat for many river deltas, yet quantifying the effect of sea-level changes on these coastal landforms remains a challenge. Sea-level changes have been slow compared to other coastal processes during the instrumental record, such that our knowledge comes primarily from models, experiments, and the geologic record. Here we review the current state of science on river delta response to sea-level change, including models and observations from the Holocene until 2300 CE. We report on improvements in the detection and modeling of past and future regional sea-level change, including a better understanding of the underlying processes and sources of uncertainty. We also see significant improvements in morphodynamic delta models. Still, substantial uncertainties remain, notably on present and future subsidence rates in and near deltas. Observations of delta submergence and land loss due to modern sea-level rise also remain elusive, posing major challenges to model validation. There are large differences in the initiation time and subsequent delta progradation during the Holocene, likely from different sea-level and sediment supply histories. Modern deltas are larger and will face faster sea-level rise than during their Holocene growth, making them susceptible to forced transgression. Regional sea-level projections have been much improved in the past decade and now also isolate dominant sources of uncertainty, such as the Antarctic ice sheet. Vertical land motion in deltas can be the dominant source of relative sea-level change and the dominant source of uncertainty; limited observations complicate projections. River deltas globally might lose 5% (~35,000 km 2 ) of their surface area by 2100 and 50% by 2300 due to relative sea-level rise under a high-emission scenario.

58 GEOSCIENCES↗

Development of a Conditioned System-Level Groundwater Model to Evaluate Long-Term Groundwater Impacts within a Performance Assessment - 20115

A preliminary performance assessment (PA) of single-shell tank Waste Management Area (WMA) A-AX located at the U.S. Department of Energy (DOE)'s Hanford Site in southeastern Washington is being conducted to satisfy the requirements of DOE Order 435.1 [1] as it relates to closure of the single-shell radioactive waste tanks in the WMA A-AX tank farms. A PA assesses the fate, transport, and impacts of radionuclides within a low-level radioactive waste disposal facility in its assumed closure configuration and the subsequent potential doses to humans over a 1,000-year compliance period and a 10,000-year performance evaluation period. The WMA A-AX preliminary PA evaluation is structured around the complementary use of process-level and system-level models to calculate the facility performance against established DOE Order 435.1 [1] performance objectives. Process-level models are those that represent a detailed phenomenological representation of processes of concern in the PA. Process models typically only represent one or a few of the components of the PA, such as groundwater flow and transport, and must be integrated with other modeling elements to perform PA calculations. System-level models are those that are abstracted from the process models, retaining the essential features of the process model, while allowing integration of all aspects of the PA in a single modeling framework. System-level models are often characterized by coarser numerical discretization, lower dimensionality, or other similar simplifications compared to the process-level model. Traditionally, a three-dimensional (3-D) process-level model is utilized primarily to evaluate the long-term impact on groundwater and the potential doses to individuals who consume contaminated groundwater. System-level models are also utilized to evaluate the groundwater pathway in PAs. These models typically have reduced dimensionality (1-D) and are conditioned utilizing flow fields (Darcy fluxes) and moisture content distributions that are abstracted from the process level models. The abstraction approach assures that the flow field in both models is consistent for a specific set of input parameters for flow, differing only in the discretization and dimensionality of the two models. The preliminary WMA A-AX PA incorporates a detailed representation of the geological system and hydraulic properties within the 3-D model STOMP{sup C} numerical code so that the effects of relevant features and processes on water flow and radionuclide transport in the subsurface can be evaluated. The complementary system-level model is developed utilizing the GoldSim{sup C} code to implement a simplified, 1-D equivalent model to represent the groundwater pathway. Contaminant transport through the vadose zone and unconfined aquifer for Tc-99 and I-129 were evaluated in each of the models. Adjustments to the saturated portion of the GoldSim{sup C} 1-D model were required to mimic the dispersion effect captured with the 3-D STOMP{sup C} model. Once this conditioning was conducted, highly similar results for the transport of Tc-99 and I-129 were achieved at the point of calculation, located 100 m downgradient from the WMA A-AX fenceline. These radionuclides represent elements that are regarded as primary dose drivers in the PA groundwater pathway analysis. The high degree of conformance between the two models suggests that the use of the equivalent 1-D system model is suitable for evaluating the full suite of radionuclides that will be released from the tank sources within WMA A-AX over the 1,000-year compliance period and over the 10,000-year evaluation period. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i.e. cerebellum versus heart for differential variation at the gene, isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the “electron transport chain” and neuronal differentiation, emphasizing that “tissue important” genes are regulated at several levels. Furthermore, our analysis shows that the “across tissue approach” has a promising potential when screening for possible explanations for variations, such as those observed at the gene expression levels.

60 APPLIED LIFE SCIENCES↗