2,004 research outputs found

    Hanford A and AX-Farm Leak Assessments Report: 241-A-103, 241-A-104, 241-A-105, 241-AX-102, 241-AX-104 and Unplanned Waste Releases

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    This report summarizes information on historical waste loss events associated with tanks and piplines in the 241-A and 241-AX tank farms

    Causes of Multiple Sclerosis: a functional genomics approach

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    Multiple Sclerosis (MS) is the most common disabling neurological disease affecting young adults in Western Society. To date, 55 strongly associated single nucleotide polymorphisms have been discovered. We now need to identify causal genes. While T-cells as targets for therapeutic intervention have rarely proven useful, there is strong clinical and in-vitro data identifying NK cell deficiencies in patients, and key roles for monocytes in myelin and axon destruction and autoantigen presentation. RNA extracted from magnetic bead sorted monocytes and NK cells, of healthy controls (HC) and untreated patients with relapsing remitting MS (RRMS), was labelled and hybridised to Affymetrix Human Gene 1.0 ST arrays. Expression values were standardized across chips using RMA and quantile normalization as implemented in GenePattern. Genes were ranked by expression difference significance by Mann Whitney U test and ANOVA. To date, we have analysed monocytes of 30 patients and 39 HC, and NK cells from 25 patients and 32 HC. Expression differences of those genes adjacent to MS associated risk SNPs lying between 110kb upstream and 40kb downstream of a candidate gene were considered. We have identified three genes worthy of further analysis on this basis: RGS1, HHEX and THEMIS. To test the relevance of these candidates to central nervous system (CNS) autoimmunity, we aim to mimic phenotypes associated with these expression quantitative trait loci (eQTL) in in-vitro cultures of purified NK cells and monocytes, and in-vivo in a mouse model of MS - experimental autoimmune encephalomyelitis (EAE)

    T-TY Tank Farm Interim Surface Barrier Demonstration - Vadose Zone Monitoring FY10 Report

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    The U.S. Department of Energy’s Office of River Protection has constructed interim surface barriers over a portion of the T and TY tank farms as part of the Interim Surface Barrier Demonstration Project. The interim surface barriers (hereafter referred to as the surface barriers or barriers) are designed to minimize the infiltration of precipitation into the soil zones containing radioactive contaminants and minimize the movement of the contaminants. As part of the demonstration effort, vadose zone moisture is being monitored to assess the effectiveness of the barriers at reducing soil moisture. Solar-powered systems were installed to continuously monitor soil water conditions at four locations in the T (i.e., instrument Nests TA, TB, TC, and TD) and the TY (i.e., instrument Nests TYA and TYB) Farms beneath the barriers and outside the barrier footprint as well as site meteorological conditions. Nests TA and TYA are placed in the area outside the barrier footprint and serve as controls, providing subsurface conditions outside the influence of the surface barriers. Nest TB provides subsurface measurements to assess surface-barrier edge effects. Nests TC, TD, and TYB are used to assess changes in soil-moisture conditions beneath the interim surface barriers. Except for occasional times for TC and TD and planned dates for TYB, during FY10, the battery voltage at the TMS and instrument Nests in both T and TY tank farms remained above 12.0 V, denoting that the battery voltages were sufficient for the stations to remain functional. All the HDUs were functioning normally, but some pressure-head values were greater than the upper measurement limit. The values that exceeded the upper limit may indicate wet soil conditions and/or measurement error, but they do not imply a malfunction of the sensors. Similar to FY07 through FY09, in FY10, the soil under natural conditions in the T Farm (Nest TA) was generally recharged during the winter period (October–March), and they discharged during the summer period (April–September). Soil water conditions above about 1.5-m to 2-m depth from all three types of measurements (i.e., CP, NP, and HDU) showed relatively large variation during the seasonal wetting-drying cycle. For the soil below 2-m depth, the seasonal variation of soil water content was relatively small. The construction of the TISB was completed in April 2008. In the soil below the TISB (Nests TC and TD), the CP-measured water content showed that at the soil between 0.6-m and 2.3-m depths was stable, indicating no climatic impacts on soil water conditions beneath the barrier. The NP-measured water content in the soil between about 3.4 m (11 ft) and 12.2 m (40 ft) since the completion of the barrier decreased by 0.007 to 0.014 m3 m-3. The HDU-measured soil-water pressure at 1-m, 2-m, and 5-m depths decreased by 0.7 to 2.4 m, indicating soil water drainage at these depths of the soil. In the soil below the edge of the TISB (Nest TB), the CP-measured water content was relatively stable through the year; the NP-measured water content showed that soil water drainage was occurring in the soil between about 3.4 m (11 ft) and 12.2 m (40 ft) but at a slightly smaller magnitude than in Nests TC and TD; the HDU-measurements show that the pressure head changes at Nest TB since the completion of the barrier were generally less than those at TC and TD, but more than those at TA. These results indicate that the TISB is performing as expected by intercepting the meteoric water from infiltrating into the soil, and the soil is becoming drier gradually. The barrier also had some effects on the soil below the barrier edge, but at a reduced magnitude. There was no significant difference in soil-water regime between the two nests in the TY tank farm because the barrier at the TY Farm was just completed one month before the end of the FY

    Multiple Sclerosis risk variants regulate gene expression in innate and adaptive immune cells

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    At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS

    Association between SGLT2 inhibitor treatment and diabetic ketoacidosis and mortality in people with type 2 diabetes admitted to hospital with COVID-19

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       Objective  To determine the association between prescription of SGLT2 inhibitors and diabetic ketoacidosis (DKA) incidence or mortality in people with type 2 diabetes hospitalized with COVID-19.  Research Design and Methods  This was a retrospective cohort study based on secondary analysis of data from a large nationwide audit from a network of 40 centres in United Kingdom with data collection up to December 2020 that was originally designed to describe risk factors associated with adverse outcomes among people with diabetes who were admitted to hospital with COVID-19.. The primary outcome for this analysis was DKA on or during hospital admission. The secondary outcome was mortality. Crude, age-sex adjusted and multivariable logistic regression models, were used to generate odds ratios and 95% confidence intervals for people prescribed SGLT2 inhibitor compared to those not prescribed SGLT2 inhibitor.   Results  The original national audit included 3067 people with type 2 diabetes who were admitted to hospital with COVID-19, of whom 230 (7.5%) were prescribed SGLT2 inhibitors prior to hospital admission. Mean (SD) age of the overall cohort was 72 years, 62.3% were men and 34.9% were prescribed insulin. Overall, 2.8% of the total population had DKA and 35.6% people died. The adjusted odds of DKA were not significantly different between those prescribed SGLT2 inhibitors and those not (OR 0.56, 0.16-1.97). The adjusted odds of mortality associated with SGLT2 inhibitors were similar in the total study population (OR 1.13, 0.78-1.63 ), in the sub-group prescribed insulin (OR 1.02, 0.59-1.77), and in the sub-group that developed DKA (OR 0.21, 0.01-8.76).  Conclusions We demonstrate a low risk of DKA and high mortality rate in people with type 2 diabetes admitted to hospital with COVID-19 and limited power but no evidence of increased risk of DKA or in-hospital mortality associated with prescription of SGLT2 inhibitors. </p

    New Developments in Brief Interventions to Treat Problem Drinking in Nonspecialty Health Care Settings

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    The delivery of brief interventions (BIs) in health care settings to reduce problematic alcohol consumption is a key preventive strategy for public health. However, evidence of effectiveness beyond primary care is inconsistent. Patient populations and intervention components are heterogeneous. Also, evidence for successful implementation strategies is limited. In this article, recent literature is reviewed covering BI effectiveness for patient populations and subgroups, and design and implementation of BIs. Support is evident for short-term effectiveness in hospital settings, but long-term effects may be confounded by changes in control groups. Limited evidence suggests effectiveness with young patients not admitted as a consequence of alcohol, dependent patients, and binge drinkers. Influential BI components include high-quality change plans and provider characteristics. Health professionals endorse BI and feel confident in delivering it, but training and support initiatives continue to show no significant effects on uptake, prompting calls for systematic approaches to implementing BI in health care
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