1,027 research outputs found
Passive Surveillance of \u3cem\u3eIxodes scapularis\u3c/em\u3e (Say), Their Biting Activity, and Associated Pathogens in Massachusetts
A passive surveillance of tick-borne pathogens was conducted over a 7-year period (2006–2012), in which a total of 3551 ticks were submitted to the University of Massachusetts for PCR testing. The vast majority of these ticks were Ixodes scapularis from Massachusetts (N = 2088) and hence were the focus of further analysis. Two TaqMan duplex qPCR assays were developed to test I. scapularis ticks for the presence of three human pathogens: Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti. I. scapularis submissions were concentrated from Cape Cod, the eastern half of the state outside of the Boston metropolitan area, parts of Franklin and Hampshire counties along the Quabbin Reservoir watershed, and southwestern Berkshire county. Differences in seasonal activity pattern were observed for different developmental stages of I. scapularis. The largest proportion of tick bite victims were age 9 years and under. Nymphal ticks were found more often on lower extremities of their hosts, while more adult ticks were found on the head. Overall infection rate of B. burgdorferi, A. phagocytophilum, and B. microti in human-biting ticks was 29.6%, 4.6%, and 1.8%, respectively. B. burgdorferi-infected ticks were widely distributed, but A. phagocytophilum- and B. microti-infected I. scapularis were found mainly in the eastern half of the state. We found that 1.8%, 1.0%, and 0.4% of ticks were coinfected by B. burgdorferi and A. phagocytophilum, B. burgdorferi and B. microti, and A. phagocytophilum and B. microti, respectively, and 0.3% of ticks had triple coinfection
Cost model relationships between textile manufacturing processes and design details for transport fuselage elements
Textile manufacturing processes offer potential cost and weight advantages over traditional composite materials and processes for transport fuselage elements. In the current study, design cost modeling relationships between textile processes and element design details were developed. Such relationships are expected to help future aircraft designers to make timely decisions on the effect of design details and overall configurations on textile fabrication costs. The fundamental advantage of a design cost model is to insure that the element design is cost effective for the intended process. Trade studies on the effects of processing parameters also help to optimize the manufacturing steps for a particular structural element. Two methods of analyzing design detail/process cost relationships developed for the design cost model were pursued in the current study. The first makes use of existing databases and alternative cost modeling methods (e.g. detailed estimating). The second compares design cost model predictions with data collected during the fabrication of seven foot circumferential frames for ATCAS crown test panels. The process used in this case involves 2D dry braiding and resin transfer molding of curved 'J' cross section frame members having design details characteristic of the baseline ATCAS crown design
Age-Stratified QTL Genome Scan Analyses for Anthropometric Measures
With the availability of longitudinal data, age-specific (stratified) or age-adjusted genetic analyses have the potential to localize different putative trait influencing loci. If age does not influence the locus-specific penetrance function within the range examined, age-stratified analyses will tend to yield comparable results for an individual trait. However, age-stratified results should vary across age strata when the locus-specific penetrance function is age dependent. In this paper, age-stratified and age-adjusted quantitative trait loci (QTL) linkage analyses were contrasted for height, weight, body mass index (BMI), and systolic blood pressure on a subset of the Framingham Heart Study. The strata comprised individuals with data present in each of three age groups: 31–49, 50–60, 61–79. Genome-wide QTL analyses were performed using SOLAR. Over all ages, a linkage signal for height was detected on chromosome 14q11.2 near marker GATA74E02A (LOD for ages 31–49 = 2.38, LOD for ages 50–60 = 1.84, LOD for ages 61–79 = 2.45). Evidence of linkage to BMI in the 31–49 age group was found on chromosome 3q22 (GATA3C02, LOD = 2.89, p = 0.0003) at the same location as the signal for weight (LOD = 3.10, p = 0.0002). Linkage was also supported on chromosome 1p22.1 for BMI (LOD = 2.21, p = 0.0014) and weight (LOD = 2.47, p = 0.0007) in the 31–49 age group. Our age-stratified results suggest that QTL that are expressed over long periods of time and affecting multiple, correlated traits may be identified using genome scan and variance-component methodology to help detect early and/or late gene expression
Imputing Amino Acid Polymorphisms in Human Leukocyte Antigens
DNA sequence variation within human leukocyte antigen (HLA) genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC) makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC) region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C) and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1) loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals) and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals). We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918) with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes
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Family-Based Association Analysis Confirms the Role of the Chromosome 9q21.32 Locus in the Susceptibility of Diabetic Nephropathy
A genome-wide association scan of type 1 diabetic patients from the GoKinD collections previously identified four novel diabetic nephropathy susceptibility loci that have subsequently been shown to be associated with diabetic nephropathy in unrelated patients with type 2 diabetes. To expand these findings, we examined whether single nucleotide polymorphisms (SNPs) at these susceptibility loci were associated with diabetic nephropathy in patients from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were genotyped in 66 extended families of European ancestry. Pedigrees from this collection contained an average of 18.5 members, including 2 to 14 members with type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached statistical significance with advanced diabetic nephropathy (P = 0.037 [adjusted P = 0.222]). When we expanded our definition of diabetic nephropathy to include individuals with high microalbuminuria, the strength of this association improved significantly (P = 1.42×10−3 [adjusted P = 0.009]). This same locus also trended toward statistical significance with variation in urinary albumin excretion in family members with type 2 diabetes (P = 0.032 [adjusted P = 0.192]) and in analyses expanded to include all relatives (P = 0.019 [adjusted P = 0.114]). These data increase support that SNPs identified in the GoKinD collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility loci
Age-stratified heritability estimation in the Framingham Heart Study families
The Framingham Heart Study provides a unique source of longitudinal family data related to CVD risk factors. Age-stratified heritability estimates were obtained over three age groups (31–49 years, 50–60 years, and 61–79 years), reflecting the longitudinal nature of the data, for four quantitative traits. Age-adjusted heritability estimates were obtained at a single common time point for the same four quantitative traits. The importance of these groups is that they consist of the same individuals. The highest age-stratified heritability estimate (h(2 )= 0.88 (± 0.06)) was for height in the model adjusting for gender over all three age groups. SBP gave the lowest heritability estimate (h(2 )= 0.15 (± 0.11)) for the 70 age group in the model adjusting for gender, height, BMI, smoker, and drinker. BMI had slightly higher estimates (h(2 )= 0.64 (± 0.11)) in the 40 age group than previously published. The highest age-adjusted heritability estimate (h(2 )= 0.90 (± 0.06)) was for height in the model adjusting for gender. SBP gave the lowest heritability estimate (h(2 )= 0.38 (± 0.09)) for unadjusted model. These results indicate that some common, complex traits may vary little in their genetic architecture over time and suggest that a common set of genes may be contributing to observed variation for these longitudinally collected phenotypes
Significant linkage at chromosome 19q for otitis media with effusion and/or recurrent otitis media (COME/ROM)
<p>Abstract</p> <p>Background</p> <p>In previous analyses, we identified a region of chromosome 19 as harboring a susceptibility locus for chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). Our aim was to further localize the linkage signal and ultimately identify the causative variant or variants. We followed up our previous linkage scan with dense SNP genotyping across in a 5 Mb region. A total of 607 individuals from 139 families, including 159 affected sib pairs and 62 second-degree affected relative pairs, were genotyped at 1,091 SNPs. We carried out a nonparametric linkage analysis, modeling marker-to-marker linkage disequilibrium.</p> <p>Results</p> <p>The maximum log of the odds (LOD) score increased to 3.75 (P = 1.6 × 10<sup>-5</sup>) at position 63.4 Mb, with a LOD-1 support interval between 61.6 Mb and 63.8 Mb, providing significant evidence of linkage between this region and COME/ROM. The support interval contains over 90 known genes, including several genes involved in the inflammasome protein complex, a key regulator of the innate immune response to harmful exogenous or endogenous stimuli. Parametric linkage analysis suggests that for a sib of an affected individual, the recurrence risk of COME/ROM due to this linkage region is twice the recurrence risk in the population. We examined potential associations between the SNPs genotyped in this region and COME/ROM, however none provided evidence for association.</p> <p>Conclusion</p> <p>This study has refined the 19q region of linkage with COME/ROM, and association results suggest that the linkage signal may be due to rare variants.</p
Circulating and Dietary Omega‐3 and Omega‐6 Polyunsaturated Fatty Acids and Incidence of CVD in the Multi‐Ethnic Study of Atherosclerosis
Background: Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self‐reported dietary assessment in relatively homogeneous populations. Methods and Results: In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000–2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person‐years of follow‐up. In multivariable‐adjusted Cox models, circulating n‐3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme‐quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n‐3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P‐interaction=0.01). No significant associations with CVD were observed for circulating n‐3 alpha‐linolenic acid or n‐6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self‐reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial‐ethnic groups, except those of docosapentaenoic acid. Conclusions: Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha‐linolenic acid or n‐6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n‐3 PUFA from seafood may prevent CVD development in a multiethnic population
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Confirmation of Genetic Associations at ELMO1 in the GoKinD Collection Supports Its Role as a Susceptibility Gene in Diabetic Nephropathy
Objective: To examine the association between single nucleotide polymorphisms (SNPs) in the engulfment and cell motility 1 (ELMO1) gene, a locus previously shown to be associated with diabetic nephropathy in two ethnically distinct type 2 diabetic populations, and the risk of nephropathy in type 1 diabetes. Research Design and Methods: Genotypic data from a genome-wide association scan (GWAS) of the Genetics of Kidneys in Diabetes (GoKinD) study collection were analyzed for associations across the ELMO1 locus. In total, genetic associations were assessed using 118 SNPs and 1,705 individuals of European ancestry with type 1 diabetes (885 normoalbuminuric control subjects and 820 advanced diabetic nephropathy case subjects). Results: The strongest associations in ELMO1 occurred at rs11769038 (odds ratio [OR] 1.24; P = 1.7 × 10−3) and rs1882080 (OR 1.23; P = 3.2 × 10−3) located in intron 16. Two additional SNPs, located in introns 18 and 20, respectively, were also associated with diabetic nephropathy. No evidence of association for variants previously reported in type 2 diabetes was observed in our collection. Conclusions: Using GWAS data from the GoKinD collection, we comprehensively examined evidence of association across the ELMO1 locus. Our investigation marks the third report of associations in ELMO1 with diabetic nephropathy, further establishing its role in the susceptibility of this disease. There is evidence of allelic heterogeneity, contributed by the diverse genetic backgrounds of the different ethnic groups examined. Further investigation of SNPs at this locus is necessary to fully understand the commonality of these associations and the mechanism(s) underlying their role in diabetic nephropathy
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Biomarkers of Dairy Fatty Acids and Risk of Cardiovascular Disease in the Multi‐Ethnic Study of Atherosclerosis
Background: Evidence regarding the role of dairy fat intake in cardiovascular disease (CVD) has been mixed and inconclusive. Most earlier studies have used self‐reported measures of dietary intake and focused on relatively racially homogeneous populations. Circulating biomarkers of dairy fat in a multiethnic cohort provide objective measures of dairy fat intake and facilitate conclusions relevant to populations with different diets and susceptibility to CVD. Methods and Results: In a multiethnic cohort of 2837 US adults aged 45 to 84 years at baseline (2000–2002), phospholipid fatty acids including 15:0, 14:0, and trans‐16:1n7 were measured using standardized methods, and the incidence of CVD prospectively adjudicated. Self‐reported whole‐fat dairy and butter intakes had strongest associations with 15:0, rather than 14:0 or trans‐16:1n7. In multivariate models including demographics and lifestyle and dietary habits, each SD‐unit of 15:0 was associated with 19% lower CVD risk (hazard ratio [95% CI] 0.81 [0.68 to 0.98]) and 26% lower coronary heart disease (CHD) risk (0.74 [0.60 to 0.92]). Associations were strengthened after mutual adjustment for 14:0 and trans‐16:1n‐7 and were similar after adjustment for potential mediators. Plasma phospholipid 14:0 and trans‐16:1n‐7 were not significantly associated with incident CVD or CHD. All findings were similar in white, black, Hispanic, and Chinese American participants. Conclusion: Plasma phospholipid 15:0, a biomarker of dairy fat, was inversely associated with incident CVD and CHD, while no association was found with phospholipid 14:0 and trans‐16:1n‐7. These findings support the need for further investigation of CVD effects of dairy fat, dairy‐specific fatty acids, and dairy products in general
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