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Search Results: 1 - 10 of 89945 matches for " Barry I Freedman "
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Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study
Jeremy N Adams, Amanda J Cox, Barry I Freedman, Carl D Langefeld, J Jeffrey Carr, Donald W Bowden
Cardiovascular Diabetology , 2013, DOI: 10.1186/1475-2840-12-31
Abstract: This study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.Analyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p?=?0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p?=?0.005) and CVD mortality (p?=?0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p?=?6.59x10-4). Promoter SNPs were not associated with any traits.This study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.Cardiovascular disease (CVD) is one of the major complications associated with type 2 diabetes mellitus (T2DM). As of 2011, 25.8 million Americans had diagnosed T2DM [1]. More than 50% of individuals with T2DM had coronary heart disease, stroke, or cardiac disease [2]. T2DM is an independent risk factor for development of CVD with the relative risk of CVD mortality of 2.1 in men and 4.9 in women, relative to non-T2DM affected individuals [3,4]. There is increasing evidence that genetic and environmental factors contribute to this risk.Haptoglobin (HP) is a 54 kDa protein, found abundantly in the serum [5,6]. The HP gene has two major alleles: HP1, (containing five exons) and HP2, (containing seven exons) which likely arose from a duplication event involving exons 3 and 4, producing a 61 kDa pro
Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes
Jennifer L Bento, Donald W Bowden, Josyf C Mychaleckyj, Shohei Hirakawa, Stephen S Rich, Barry I Freedman, Fernando Segade
BMC Medical Genetics , 2005, DOI: 10.1186/1471-2350-6-42
Abstract: Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM.Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls.From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans.Multiple genetic studies have been carried out that link human chromosome 20q13.1-13.2 to type 2 diabetes (T2DM) [1-5]. This linkage evidence has led investigators to search for T2DM susceptibility genes in this genomic region. Our laboratory has carried out analysis of specific genes [6-8] and developed high resolution physical maps of the region [9-11]. In an association analysis of genetic markers Price et al. [12] identified three regions of T2DM susceptibility. Among the genes mapped to the linkage disequilibrium regions, a novel facilitative glucose transporter (GLUT) was identified and designated GLUT10 (gene symbol SLC2A10) [6,13]. The gene spans 28 kb of genomic sequence, is split into 5 exons and 4 introns [6,13] and is expressed mainly in heart, liver, lung, skeletal muscle, pancreas, placenta, thyroid, and adipose tissue [6,13
Neighborhood Socioeconomic Deprivation and Mortality: NIH-AARP Diet and Health Study
Jacqueline M. Major,Chyke A. Doubeni,Neal D. Freedman,Yikyung Park,Min Lian,Albert R. Hollenbeck,Arthur Schatzkin,Barry I. Graubard,Rashmi Sinha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015538
Abstract: Residing in deprived areas may increase risk of mortality beyond that explained by a person's own SES-related factors and lifestyle. The aim of this study was to examine the relation between neighborhood socioeconomic deprivation and all-cause, cancer- and cardiovascular disease (CVD)-specific mortality for men and women after accounting for education and other important person-level risk factors.
Alcohol Consumption, One-Carbon Metabolites, Liver Cancer and Liver Disease Mortality
Lauren M. Schwartz, E. Christina Persson, Stephanie J. Weinstein, Barry I. Graubard, Neal D. Freedman, Satu M?nnist?, Demetrius Albanes, Katherine A. McGlynn
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078156
Abstract: Background Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk. Results Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer. Conclusions The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality.
Evaluation of Candidate Nephropathy Susceptibility Genes in a Genome-Wide Association Study of African American Diabetic Kidney Disease
Nicholette D. Palmer, Maggie C. Y. Ng, Pamela J. Hicks, Poorva Mudgal, Carl D. Langefeld, Barry I. Freedman, Donald W. Bowden
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088273
Abstract: Type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) is a complex disorder resulting from the combined influence of genetic and environmental factors. This study contains a comprehensive genetic analysis of putative nephropathy loci in 965 African American (AA) cases with T2D-ESKD and 1029 AA population-based controls extending prior findings. Analysis was based on 4,341 directly genotyped and imputed single nucleotide polymorphisms (SNPs) in 22 nephropathy candidate genes. After admixture adjustment and correction for multiple comparisons, 37 SNPs across eight loci were significantly associated (1.6E-05
Concerning the Slope of the Cepheid Period-Luminosity Relation
Barry F. Madore,Wendy L. Freedman
Physics , 2009, DOI: 10.1088/0004-637X/696/2/1498
Abstract: We discuss the impact of possible differences in the slope of the Cepheid Period-Luminosity relation on the determination of extragalactic distances in the context of recent studies that suggest changes in this slope. We show that the Wesenheit function W = V - R x ((V-I), widely used for the determination of Cepheid distances, is expected to be highly insensitive to changes in the slope of the underlying (monochromatic) Period-Luminosity (PL) relations. This occurs because the reddening trajectories in the color-magnitude plane are closely parallel to lines of constant period. As a result W-based Period-Luminosity relations have extremely low residual dispersion, which is because differential (and total line-of-sight) reddening is eliminated in the definition of W and the residual scatter due to a star's intrinsic color/position within the Cepheid is also largely insensitive to W. Basic equations are presented and graphically illustrated, showing the insensitivity of W to changes in the monochromatic PL relations.
The Hubble Constant
Wendy L. Freedman,Barry F. Madore
Physics , 2010, DOI: 10.1146/annurev-astro-082708-101829
Abstract: Considerable progress has been made in determining the Hubble constant over the past two decades. We discuss the cosmological context and importance of an accurate measurement of the Hubble constant, and focus on six high-precision distance-determination methods: Cepheids, tip of the red giant branch, maser galaxies, surface brightness fluctuations, the Tully-Fisher relation and Type Ia supernovae. We discuss in detail known systematic errors in the measurement of galaxy distances and how to minimize them. Our best current estimate of the Hubble constant is 73 +/-2 (random) +/-4 (systematic) km/s/Mpc. The importance of improved accuracy in the Hubble constant will increase over the next decade with new missions and experiments designed to increase the precision in other cosmological parameters. We outline the steps that will be required to deliver a value of the Hubble constant to 2% systematic uncertainty and discuss the constraints on other cosmological parameters that will then be possible with such accuracy.
Multiwavelength Characteristics of Period-Luminosity Relations
Barry F. Madore,Wendy L. Freedman
Physics , 2011, DOI: 10.1088/0004-637X/744/2/132
Abstract: We present a physically motivated explanation for the observed, monotonic increase in slope, and the simultaneous (and also monotonic) decrease in the width/scatter of the Leavitt Law (the Cepheid Period-Luminosity (PL) relation) as one systematically moves from the blue and visual into the near and mid-infared. We calibrate the wavelength-dependent, surface-brightness sensitivities to temperature using the observed slopes of PL relations from the optical through the mid-infrared, and test the calibration by comparing the theoretical predictions with direct observations of the wavelength dependence of the scatter in the Large Magellanic Cloud Cepheid PL relation. In doing so we find the slope of the Period-Radius (PR) relation is c = 0.724 +/- 0.006. Investigating the effect of differential reddening suggests that this value may be overestimated by as much as 10%; however the same slope of the PR relation fits the (very much unreddened) Cepheids in IC1613, albeit with lower precision. The discussion given is general, and also applies to RR Lyrae stars, which also show similarly increasing PL slopes and decreasing scatter with increasing wavelength.
Hipparcos Parallaxes and the Cepheid Distance Scale
Barry F. Madore,Wendy L. Freedman
Physics , 1997, DOI: 10.1086/305041
Abstract: Hipparcos parallaxes have recently become available for a sample of Galactic Cepheids, and we have used these new distances to calibrate the Cepheid period-luminosity (PL) relation at six wavelengths (BVIJHK). Comparing these calibrations with previously published multiwavelength PL relations we find agreement to within 0.07 +/- 0.14 mag, or 4 +/- 7% in distance. Unfortunately, the current parallax errors for the fundamental pulsators (ranging in signal-to-noise = pi /sigma_pi from 0.3 to 5.3, at best) preclude an unambiguous interpretation of the observed differences, which may arise from a combination of true distance modulus, reddening and/or metallicity effects. We explore these effects and discuss their implications for the distance to the Large Magellanic Cloud (LMC) and the Cepheid-based extragalactic distance scale. These results suggest a range of LMC moduli between 18.44 +/-0.35 and 18.57 +/-0.11 mag; however, other effects on the Cepheid PL relation (e.g., extinction, metallicity, statistical errors) are still as significant as any such reassessment of its zero point.
A Physically-Based Method for Scaling Cepheid Light Curves for Future Distance Determinations
Wendy L. Freedman,Barry F. Madore
Physics , 2010, DOI: 10.1088/0004-637X/719/1/335
Abstract: We present a technique for decomposing Cepheid light curves into their fundamental constituent parts; that is, their radius and temperature variations. We demonstrate that any given pair of optical luminosity and color curves can be used to predict the shape, amplitude and phase of a Cepheid's light variation at any other wavelength. With such predictions in hand, a single new observation at any given new wavelength can be used to normalize the properties of the predicted light curve, and in specific, derive a precise value of the time-averaged mean. We suggest that this method will be of great advantage in efficiently observing and precisely obtaining the mean properties of known Cepheids scheduled to be observed at new wavelengths, specifically in the mid-infrared where JWST will be operating.
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