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Search Results: 1 - 10 of 239 matches for " Dov Shiffman "
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Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci
Guillaume Paré ,Paul M. Ridker,Lynda Rose,Maja Barbalic,Josée Dupuis,Abbas Dehghan,Joshua C. Bis,Emelia J. Benjamin,Dov Shiffman,Alexander N. Parker,Daniel I. Chasman
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1001374
Abstract: Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10?9), PNPLA3 (rs738409, P = 5.8×10?9), RELA (rs1049728, P = 2.7×10?16), and SH2B3 (rs3184504, P = 2.9×10?17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.
Analysis of 17,576 Potentially Functional SNPs in Three Case–Control Studies of Myocardial Infarction
Dov Shiffman, John P. Kane, Judy Z. Louie, Andre R. Arellano, David A. Ross, Joseph J. Catanese, Mary J. Malloy, Stephen G. Ellis, James J. Devlin
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002895
Abstract: Myocardial infarction (MI) is a common complex disease with a genetic component. While several single nucleotide polymorphisms (SNPs) have been reported to be associated with risk of MI, they do not fully explain the observed genetic component of MI. We have been investigating the association between MI and SNPs that are located in genes and have the potential to affect gene function or expression. We have previously published studies that tested about 12,000 SNPs for association with risk of MI, early-onset MI, or coronary stenosis. In the current study we tested 17,576 SNPs that could affect gene function or expression. In order to use genotyping resources efficiently, we staged the testing of these SNPs in three case–control studies of MI. In the first study (762 cases, 857 controls) we tested 17,576 SNPs and found 1,949 SNPs that were associated with MI (P<0.05). We tested these 1,949 SNPs in a second study (579 cases and 1159 controls) and found that 24 SNPs were associated with MI (1-sided P<0.05) and had the same risk alleles in the first and second study. Finally, we tested these 24 SNPs in a third study (475 cases and 619 controls) and found that 5 SNPs in 4 genes (ENO1, FXN (2 SNPs), HLA-DPB2, and LPA) were associated with MI in the third study (1-sided P<0.05), and had the same risk alleles in all three studies. The false discovery rate for this group of 5 SNPs was 0.23. Thus, we have identified 5 SNPs that merit further examination for their potential association with MI. One of these SNPs (in LPA), has been previously shown to be associated with risk of cardiovascular disease in other studies.
The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study
Dov Shiffman, Ellen S O'Meara, Charles M Rowland, Judy Z Louie, Mary Cushman, Russell P Tracy, James J Devlin, Bruce M Psaty
BMC Cardiovascular Disorders , 2011, DOI: 10.1186/1471-2261-11-10
Abstract: Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).Among white participants the FRS was improved by addition of KIF6 719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).While none of these risk markers individually or in combination improved risk prediction among women, a combination of KIF6 719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.The Framingham Risk Score (FRS) is a risk prediction model developed by the Framingham investigators to predict the probability of developing coronary heart disease (CHD) [1]. This risk prediction model calculates the probability of a CHD event over a given time period for men and women separately by integrating information about traditional risk factors for CHD, including age, blood pressure, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), smoking behavior, and diabetes status. The FRS has been evaluated in a number of large population studies and has been shown to predict CHD risk among individuals from different populations and a variety of ethnicities [2]. Because the FRS models were developed as sex-specific scores, the validity of FRS was typically evaluated separately in men and women [2].Several groups have sought to improve or simplify CHD risk prediction by the FRS [3-6] by developing models that include emerging risk factors. More recently, several studies have investigated whether genetic variants associated with CHD could improve CHD risk
A social explanation for the rise and fall of global health issues
Shiffman,Jeremy;
Bulletin of the World Health Organization , 2009, DOI: 10.1590/S0042-96862009000800017
Abstract: this paper proposes an explanation concerning why some global health issues such as hiv/aids attract significant attention from international and national leaders, while other issues that also represent a high mortality and morbidity burden, such as pneumonia and malnutrition, remain neglected. the rise, persistence and decline of a global health issue may best be explained by the way in which its policy community - the network of individuals and organizations concerned with the problem - comes to understand and portray the issue and establishes institutions that can sustain this portrayal. this explanation emphasizes the power of ideas and challenges interpretations of issue ascendance and decline that place primary emphasis on material, objective factors such as mortality and morbidity levels and the existence of cost-effective interventions. this explanation has implications for our understanding of strategic public health communication. if ideas in the form of issue portrayals are central, strategic communication is far from a secondary public health activity: it is at the heart of what global health policy communities do.
Mammograms in cosmetic breast surgery
Shiffman M
Indian Journal of Plastic Surgery , 2005,
Abstract: Mammograms are necessary as preoperative preparation for breast surgery in certain patients. There is a definite need for mammograms preoperatively in patients over 40 who should be obtaining mammograms on an annual basis. Under the age of 40 mammograms are up to the discretion of the surgeon. Postoperative mammograms should be obtained as a baseline 6-12 months after breast surgery.
Facial aging: A clinical classification
Shiffman Melvin
Indian Journal of Plastic Surgery , 2007,
Abstract: The purpose of this classification of facial aging is to have a simple clinical method to determine the severity of the aging process in the face. This allows a quick estimate as to the types of procedures that the patient would need to have the best results. Procedures that are presently used for facial rejuvenation include laser, chemical peels, suture lifts, fillers, modified facelift and full facelift. The physician is already using his best judgment to determine which procedure would be best for any particular patient. This classification may help to refine these decisions.
Convergence of random zeros on complex manifolds
Bernard Shiffman
Mathematics , 2007, DOI: 10.1007/s11425-008-0060-9
Abstract: We show that the zeros of random sequences of Gaussian systems of polynomials of increasing degree almost surely converge to the expected limit distribution under very general hypotheses. In particular, the normalized distribution of zeros of systems of m polynomials of degree N, orthonormalized on a regular compact subset K of C^m, almost surely converge to the equilibrium measure on K as the degree N goes to infinity.
Uniformly bounded orthonormal sections of positive line bundles on complex manifolds
Bernard Shiffman
Mathematics , 2014,
Abstract: We show the existence of uniformly bounded sequences of increasing numbers of orthonormal sections of powers $L^k$ of a positive holomorphic line bundle $L$ on a compact K\"ahler manifold $M$. In particular, we construct for each positive integer $k$, orthonormal sections $s^k_1,\dots,s^k_{n_k}$ in $H^0(M,L^k)$, $n_k\ge\beta\dim H^0(M,L^k)$, such that $\{s^k_j\}$ is a uniformly bounded family, where $\beta$ is an explicit positive constant depending only on the dimension of $M$. For $m=1$, we can take $\beta=.99564$.
Cultural Heritage and Flood Need of Interdisciplinarity  [PDF]
Klára Nedvědová
Journal of Water Resource and Protection (JWARP) , 2013, DOI: 10.4236/jwarp.2013.54A004
Abstract:

This contribution discusses some results of the ongoing research focused on the protection of cultural heritage from flood danger. The research project Methodology of Protection and Rescue of Cultural Heritage against Flood takes place in the Czech Republic and is focused on specific regional problems that have been experienced during and after disastrous floods in past 15 years. However, the lessons learned have wider applicability to the issue of flood protection of cultural heritage. Here, we describe two case studies that represent important issues requiring a solution; addressing these issues was the main motivation for the whole project.

Atherogenesis, the oxidative LDL modification hypothesis revisited  [PDF]
Dov Lichtenberg, Ilya Pinchuk
Advances in Bioscience and Biotechnology (ABB) , 2013, DOI: 10.4236/abb.2013.411A2007
Abstract:

The commonly-accepted “oxidized LDL hypothesis of atherogenesis” is based on a large number of indirect evidence that shows that oxidatively-modified LDL plays a role in atherogenesis. Yet, the exact role is not clear. Some researchers think that oxidatively modified biomolecules initiate atherogenesis; others believe that they “only” promote this multifactorial process. Regardless of the exact mechanism responsible for the effect of peroxidation on atherogenesis, the “oxidative theory of AS” is apparently inconsistent with the results of meta-analysis, in which (the “expected”) significant correlation between CVD and oxidative stress (OS) was found only when the OS was evaluated on the basis of the plasma concentrations of malondialdehyde (MDA), often based on the concentration of thiobarbituric acid reactive substances (TBARS). Notably, even this association is questionable due to 1) poor reliability of the laboratory assay of MDA and 2) possible publication bias. Hence, it appears that the commonly accepted paradigm regarding the role of oxidative damage in the pathogenesis of CVD has been overestimated. Furthermore, the hypothesis is apparently inconsistent with the disappointing results of most of the clinical trials that were designed to reduce OS by means of supplementation of antioxidants, mostly vitamin E. These apparent inconsistencies do not contradict the oxidative modification hypothesis of AS. The source of the apparent contradictions is probably the oversimplified considerations on which the predictions have been based. Many reasonable arguments can be raised to explain the apparent contradictions, which means that our current knowledge is insufficient to test the relationship of oxidative stress to cardiovascular disease.

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