The value of adding regional to local stakeholder involvement in evaluating the acceptability of innovative technologies

Technology is urgently needed to clean up contamination by volatile organic compounds at United States Department of Energy (DOE) sites. In many cases, however, existing technology is too slow, inefficient, or expensive. The record of technology development is, in some cases, similarly disappointing. Remediation technologies developed at great expense and evaluated piecemeal over long periods have not been deployed because, in the end, the public judged them ineffective or unacceptable. The need for successful methods of remediation is too great and resources too limited to continue with ineffective technology evaluation. In order to make good decisions about which technologies to deploy, remedial project managers need to know stakeholders` requirements for the performance of proposed technologies. Expanding stakeholder involvement regionally identifies the concerns of a broad range of stakeholders at and DOE sites throughout the West -- issues that must be taken into account if technologies are to be accepted for wide deployment

Enhancing technology acceptance: The role of the subsurface contaminants focus area external integration team

The US DOE is developing and deploying innovative technologies for cleaning up its contaminated facilities using a market-oriented approach. This report describes the activities of the Subsurface Contaminant Focus Area`s (SCFA) External Integration Team (EIT) in supporting DOE`s technology development program. The SCFA program for technology development is market-oriented, driven by the needs of end users. The purpose of EIT is to understand the technology needs of the DOE sites and identify technology acceptance criteria from users and other stakeholders to enhance deployment of innovative technologies. Stakeholders include regulators, technology users, Native Americans, and environmental and other interest groups. The success of this national program requires close coordination and communication among technology developers and stakeholders to work through all of the various phases of planning and implementation. Staff involved must be willing to commit significant amounts of time to extended discussions with the various stakeholders

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(-5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(-4), and rs3753348, p = 9.0×10(-4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(-4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies

A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

INTRODUCTION: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. METHODS: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. RESULTS: A variant within a DNase hypersensitive site 5' of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10-3 and 4.6 × 10-2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10-2 and 3.5 × 10-3, Bonferroni-corrected P = 6.7 × 10-2 and 7.1 × 10-3, respectively). DISCUSSION: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD

Catalago de los ofidios argentinos

Volume: 92Start Page: 145End Page: 19

Dyson. 2002.

There is observational evidence of the mass loading of ows by ablated material in a variety of circumstellar and interstellar phenomena. Here the strength of this evidence will be evaluated for the ows observed in the hydrogen de cient planetary nebulae A 30 and 78, the cometary knots in the Helix nebula, the hypersonic \strings" in the Eta Carinae nebula, the inner shell of the prototypical luminous blue variable star P Cygni, the Honeycomb nebula in the halo of 30 Doradus, and the weak monopolar jets from the M 42 proplyds