Assessment of hydrologic impact of extending exploratory shafts into the Calico Hills nonwelded tuff unit at Yucca Mountain, Nevada

The US Department of Energy (DOE) is performing analyses to address an objection by the US Nuclear Regulatory Commission to plans in the Consultation Draft of the Site Characterization Plan for direct excavation of the Calico Hills nonwelded (CHn) unit within the repository exploration block at Yucca Mountain, Nevada. The excavation was planned as part of site characterization activities for the potential high-level nuclear waste repository at Yucca Mountain. This characterization activities for the potential high-level nuclear waste repository at Yucca Mountain. This characterization activity has been deferred, pending the results of a risk/benefit analysis of alternative methods for obtaining needed characterization data from CHn unit. The benefits from characterizing the CHn unit are generally related to obtaining information leading to improved confidence in predictions of site performance. The risks are generally associated with potential adverse impacts to site performance that result from excavation or other intrusion into the CHn unit. The purpose of the risk/benefit analysis is to produce a recommendation to the Director, Regulatory and Site Evaluation Division. DOE/Yucca Mountain Site Characterization Project Office for a strategy for characterizing the CHn unit. The recommendation will describe characterization activities that are expected to provide the needed information while limiting adverse impacts to site performance to the extent practical. The risk/benefit analysis was supported with scoping calculations to provide a quantitative evaluation of the impacts associated with different strategies. The working group responsible for the risk/benefit analysis requested that these scoping calculations to be supported with more detailed performance assessments for evaluating impacts of different characterization activities. This report summarizes the results of these performance assessment analyses. 9 refs., 30 figs., 1 tab

A Novel Sparse Graphical Approach for Multimodal Brain Connectivity Inference

International audienceDespite the clear potential benefits of combining fMRI and diffusion MRI in learning the neural pathways that underlie brain functions, little methodological progress has been made in this direction. In this paper, we propose a novel multimodal integration approach based on sparse Gaussian graphical model for estimating brain connectivity. Casting functional connectivity estimation as a sparse inverse covariance learning problem, we adapt the level of sparse penalization on each connection based on its anatomical capacity for functional interactions. Functional connections with little anatomical support are thus more heavily penalized. For validation, we showed on real data collected from a cohort of 60 subjects that additionally modeling anatomical capacity significantly increases subject consistency in the detected connection patterns. Moreover, we demonstrated that incorporating a connectivity prior learned with our multimodal connectivity estimation approach improves activation detection

Airborne mammary carcinogens and breast cancer risk in the Sister Study

Introduction: Potentially carcinogenic hazardous air pollutants (air toxics) have been inconsistently associated with breast cancer. Whether metabolic factors modify these associations is unknown. We studied 29 non-metallic air toxics classified as mammary gland carcinogens in animal studies in relation to breast cancer risk. Methods: Participants included 49,718 women from the Sister Study. Census tract air toxic concentration estimates from the 2005 National Air Toxics Assessment were linked to enrollment residential addresses. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for individual air toxics were estimated using Cox regression. Body mass index (BMI) was considered a potential modifier. Relevant mixtures were identified using classification trees. Results: Over follow-up (average = 8.4 years), 2975 women were newly diagnosed with breast cancer (invasive or ductal carcinoma in situ). Several air toxics, including methylene chloride, polycyclic organic matter, propylene dichloride, and styrene, were associated with increased risk. Of these, methylene chloride was most consistently associated with risk across multiple analyses. It was associated with overall (HRquintile 4vs1 = 1.21 (95%CI = 1.07–1.38)) and estrogen receptor positive (ER+) invasive breast cancer (HRquintile 4vs1 = 1.28 (95%CI = 1.08–1.52)) in individual pollutant models, although no dose-response was observed. Associations were stronger among overweight/obese (vs. non-overweight/obese) women (p < 0.05) for six air toxics. The classification tree identified combinations of age, methylene chloride, BMI, and four other toxics (propylene dichloride, ethylene dibromide, ethylidene dichloride, styrene) related to overall breast cancer. Conclusions: Some non-metallic air toxics, particularly methylene chloride, were associated with the hazard for overall and ER+ breast cancer. Overweight/obese women may be particularly susceptible to air toxics

Hazardous air pollutants and telomere length in the Sister Study

Background: Telomeres are vital for genomic integrity, and telomere length has been linked to many adverse health outcomes. Some hazardous air pollutants or air toxics increase oxidative stress and inflammation, two possible determinants of shortened telomere length. No studies have examined air toxic-Telomere length associations in a nonoccupational setting. Methods: This study included 731 Sister Study participants (enrolled 2003-2007) who were randomly selected to assess telomere length in baseline blood samples. Multiplex qPCR was used to determine telomere to single copy gene (T/S) ratios. Census tract concentration estimates of 29 air toxics from the 2005 National Air Toxics Assessment were linked to baseline residential addresses. Air toxics were classified into tertile-based categories of the exposure. Multivariable linear regression was used to estimate β coefficients and 95% confidence intervals (CIs) in single-pollutant models. Multipollutant groups were identified with regression trees. Results: The average T/S ratio was 1.24. Benzidine (T3 versus T1 β =-0.08; 95% CI =-0.14,-0.01) and 1,4-dioxane (T3 versus T1 β =-0.06; 95% CI =-0.13, 0.00) in particular, as well as carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride, were associated with shorter relative telomere length. Benzidine (P = 0.02) and 1,4-dioxane (P = 0.06) demonstrated some evidence of a monotonic trend. The regression tree identified age, BMI, physical activity, ethylene oxide, acrylonitrile, ethylidene dichloride, propylene dichloride, and styrene in multipollutant groups related to telomere length. Conclusions: In this first study of air toxics and telomere length in a nonoccupational setting, several air toxics, particularly 1,4-dioxane and benzidine, were associated with shorter relative telomere length

A Gravitational Aharonov-Bohm Effect, and its Connection to Parametric Oscillators and Gravitational Radiation

A thought experiment is proposed to demonstrate the existence of a gravitational, vector Aharonov-Bohm effect. A connection is made between the gravitational, vector Aharonov-Bohm effect and the principle of local gauge invariance for nonrelativistic quantum matter interacting with weak gravitational fields. The compensating vector fields that are necessitated by this local gauge principle are shown to be incorporated by the DeWitt minimal coupling rule. The nonrelativistic Hamiltonian for weak, time-independent fields interacting with quantum matter is then extended to time-dependent fields, and applied to problem of the interaction of radiation with macroscopically coherent quantum systems, including the problem of gravitational radiation interacting with superconductors. But first we examine the interaction of EM radiation with superconductors in a parametric oscillator consisting of a superconducting wire placed at the center of a high Q superconducting cavity driven by pump microwaves. We find that the threshold for parametric oscillation for EM microwave generation is much lower for the separated configuration than the unseparated one, which then leads to an observable dynamical Casimir effect. We speculate that a separated parametric oscillator for generating coherent GR microwaves could also be built.Comment: 25 pages, 5 figures, YA80 conference (Chapman University, 2012

Urinary estrogen metabolites and long-term mortality following breast cancer

Background: Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer. Methods: This population-based study was initiated in 1996–1997 with spot urine samples obtained shortly after diagnosis (mean ¼ 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE1 and 16-OHE1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n ¼ 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided. Results: Urinary concentrations of the 2-OHE1 to 16-OHE1 ratio (>median of 1.8 vs <median) were inversely associated with all-cause mortality (HR ¼ 0.74, 95% CI ¼ 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR ¼ 0.73, 95% CI ¼ 0.45 to 1.17) and cardiovascular diseases mortality (HR ¼ 0.76, 95% CI ¼ 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n ¼ 118, HR ¼ 0.42, 95% CI ¼ 0.22 to 0.81) than among those who had not (n ¼ 559, HR ¼ 0.98, 95% CI ¼ 0.72 to 1.34; Pinteraction ¼ .008). Conclusions: The urinary 2-OHE1 to 16-OHE1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

periscope: sub-genomic RNA identification in SARS-CoV-2 genomic sequencing data

We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed “sub-genomic RNAs”. sgRNAs are produced through discontinuous transcription which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L which is located in the 5’ UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5’ end of all sgRNA. We applied periscope to 1,155 SARS-CoV-2 genomes from Sheffield, UK and validated our findings using orthogonal datasets and in vitro cell systems. Using a simple local alignment to detect reads which contain the leader sequence we were able to identify and quantify reads arising from canonical and non-canonical sgRNA. We were able to detect all canonical sgRNAs at expected abundances, with the exception of ORF10. A number of recurrent non-canonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6 ACE2+/− cell lines, periscope can detect the changes in the kinetics of sgRNA in orthogonal sequencing datasets. Finally, variants found in genomic RNA are transmitted to sgRNAs with high fidelity in most cases. This tool can be applied to all sequenced COVID-19 samples worldwide to provide comprehensive analysis of SARS-CoV-2 sgRNA

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe