Density and Flow-Velocity Measurement Technology for Dredging Applications - Proof of Concept Study

This technical letter report provides the results of all PNNL managed activities on this project, and contains a description of the data acquisition configuration and testing protocols, results and conclusions from this work. This technical letter report constitutes the final deliverable to be submitted to the client for this proof-of-concept study

Mutation screening of CHD5 in melanoma-prone families linked to 1p36 revealed no deleterious coding or splice site changes

<p>Abstract</p> <p>Background</p> <p>A subset of cutaneous malignant melanoma and dysplastic nevi (CMM/DN) families is linked to 1p36. To date, no CMM/DN susceptibility gene has been identified at this locus. Data from mouse studies identified chromodomain helicase DNA binding protein 5 (<it>CHD5</it>) as a tumor suppressor affecting cellular proliferation and apoptosis via the <it>CDKN2A</it>/p53 pathway. Based on these findings, we felt it was important to screen <it>CHD5 </it>as a familial CMM/DN susceptibility gene.</p> <p>Methods</p> <p>Eight unrelated CMM/DN families showing prior evidence of linkage to the 1p36 locus were identified for <it>CHD5 </it>mutation screening. One CMM/DN affected and one unaffected individual from each family were selected for sequencing of the <it>CHD5 </it>coding exons and their respective intron-exon boundaries. <it>CHD5 </it>variants that were identified solely among affecteds in the screening panel were further assessed by sequencing additional affected and unaffected members of these families to determine if the variant co-segregated with the CMM/DN phenotype.</p> <p>Results</p> <p>Single nucleotide polymorphisms in the <it>CHD5 </it>intronic and coding regions were identified among affecteds in the screening panel. None of these variants completely co-segregated with CMM/DN affection status among these eight families.</p> <p>Conclusion</p> <p>There is no evidence to support <it>CHD5 </it>as a major melanoma susceptibility gene among the eight CMM/DN families screened.</p

Density and Flow-Velocity Measurement Technology for Dredging Applications - Proof of Concept Study

This technical letter report provides the results of all PNNL managed activities on this project, and contains a description of the data acquisition configuration and testing protocols, results and conclusions from this work. This technical letter report constitutes the final deliverable to be submitted to the client for this proof-of-concept study

Improved Imputation of Common and Uncommon Single Nucleotide Polymorphisms (SNPs) with a New Reference Set

Statistical imputation of genotype data is an important technique for analysis of genome-wide association studies (GWAS). We have built a reference dataset to improve imputation accuracy for studies of individuals of primarily European descent using genotype data from the Hap1, Omni1, and Omni2.5 human SNP arrays (Illumina). Our dataset contains 2.5-3.1 million variants for 930 European, 157 Asian, and 162 African/African-American individuals. Imputation accuracy of European data from Hap660 or OmniExpress array content, measured by the proportion of variants imputed with R^2^&#x3e;0.8, improved by 34%, 23% and 12% for variants with MAF of 3%, 5% and 10%, respectively, compared to imputation using publicly available data from 1,000 Genomes and International HapMap projects. The improved accuracy with the use of the new dataset could increase the power for GWAS by as much as 8% relative to genotyping all variants. This reference dataset is available to the scientific community through the NCBI dbGaP portal. Future versions will include additional genotype data as well as non-European populations

Histological features of melanoma associated with CDKN2A genotype

Background: Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective: We sought to identify associations between histology of melanomas and CDKN2A genotype. Methods: This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations. Results: Compared with CDKN2A− cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (Ptrend = .02) and increased pagetoid scatter (Ptrend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A− (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations: Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion: Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase

Designing for Dissemination: Lessons in Message Design from 1-2-3 Pap

Despite a large number of evidence-based health communication interventions tested in private, public, and community health settings, there is a dearth of research on successful secondary dissemination of these interventions to other audiences. This article presents the case study of 1-2-3 Pap, a health communication intervention to improve human papillomavirus (HPV) vaccination uptake and Pap testing outcomes in Eastern Kentucky, and explores strategies used to disseminate this intervention to other populations in Kentucky, North Carolina, and West Virginia. Through this dissemination project, we identified several health communication intervention design considerations that facilitated our successful dissemination to these other audiences; these intervention design considerations include (a) developing strategies for reaching other potential audiences, (b) identifying intervention message adaptations that might be needed, and (c) determining the most appropriate means or channels by which to reach these potential future audiences. Using 1-2-3 Pap as an illustrative case study, we describe how careful planning and partnership development early in the intervention development process can improve the potential success of enhancing the reach and effectiveness of an intervention to other audiences beyond the audience for whom the intervention messages were originally designed

Strategies to optimize the impact of nutritional surveys and epidemiological studies

The development of nutrition and health guidelines and policies requires reliable scientific information. Unfortunately, theoretical considerations and empirical evidence indicate that a large percentage of science-based claims rely on studies that fail to replicate. The session "Strategies to Optimize the Impact of Nutrition Surveys and Epidemiological Studies" focused on the elements of design, interpretation, and communication of nutritional surveys and epidemiological studies to enhance and encourage the production of reliable, objective evidence for use in developing dietary guidance for the public. The speakers called for more transparency of research, raw data, consistent data-staging techniques, and improved data analysis. New approaches to collecting data are urgently needed to increase the credibility and utility of findings from nutrition epidemiological studies. Such studies are critical for furthering our knowledge and understanding of the effects of diet on health

Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families with and without CDKN2A Mutations

Introduction: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. Materials and Methods We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. Results: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02–7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction. Discussion Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk