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Search Results: 1 - 10 of 207825 matches for " Michael E Yeager "
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Biomarkers for Pediatric Pulmonary Arterial Hypertension – A Call to Collaborate
D. Dunbar Ivy,Michael E. Yeager
Frontiers in Pediatrics , 2014, DOI: 10.3389/fped.2014.00007
Abstract: Therapeutic approaches in pediatric pulmonary arterial hypertension (PAH) are based primarily on clinician experience, in contrast to the evidence-based approach in adults with pulmonary hypertension. There is a clear and present need for non-invasive and objective biomarkers to guide the accurate diagnosis, treatment, and prognosis of this disease in children. The multifaceted spectrum of disease, clinical presentation, and association with other diseases makes this a formidable challenge. However, as more progress is being made in the understanding and management of adult PAH, the potential to apply this knowledge to children has never been greater. This review explores the state of the art with regard to non-invasive biomarkers in PAH, with an eye toward those adult PAH biomarkers potentially suitable for application in pediatric PAH.
Genomic approaches to research in pulmonary hypertension
Mark W Geraci, Bifeng Gao, Yasushi Hoshikawa, Michael E Yeager, Rubin M Tuder, Norbert F Voelkel
Respiratory Research , 2001, DOI: 10.1186/rr59
Abstract: Pulmonary hypertension (PH) refers to a spectrum of diseases where the pulmonary artery pressure is elevated. A new classification of PH has recently been proposed [1]. No cause can be elucidated in primary (or sporadic, idiopathic) pulmonary hypertension (PPH). Secondary forms of PH can occur in association with congenital heart disease, thromboembolic disease, HIV, anorexigen usage, and a variety of connective tissue disorders. Familial primary pulmonary hypertension (FPPH) has been associated with heterozygous germline mutations in the bone morphogenetic protein type II receptor gene (BMPR2) [2,3]. While this recent discovery has generated extreme interest, the pathobiology of severe PH remains enigmatic. Recent genomic approaches to investigate PH are reviewed. Early studies investigated the alterations of vasoactive and growth factor related genes. Animal models, using either pharmaceutical approaches, transgenics, or targeted disruption of genes, have allowed for whole animal modeling of specific pathways in the development of PH. Progress in medical genetic investigations has lead to the discovery of a gene (BMPR2) associated with FPPH. Finally, microarray expression analysis has been utilized to investigate animal models, and has shown to be a useful tool providing novel information and better characterization of the molecular pathobiology of distinct clinical phenotypes of PH.Most investigations of the role of specific genes in the pathobiology of PH have focused either on the balance of vasoconstriction and vasodilation or on specific growth factors, inflammatory mediators, or ion channels. Another approach has been to compartmentalize the vasculature, and focus the investigations on the endothelium, smooth muscle cells, and the adventitia/extracellular matrix. Christman et al initially reported an imbalance of prostacyclin (PGI2) and thromboxane metabolites in the urine of patients with both primary and secondary forms of PH, with more vasoconstrictor thr
Rational Ellipticity in Cohomogeneity Two
Joseph E. Yeager
Mathematics , 2013,
Abstract: Let M be a compact, connected and simply-connected Riemannian manifold, and suppose that G is a compact, connected Lie group acting on M by isometries. The dimension of the space of orbits is called the cohomogeneity of the action. If the direct sum of the higher homotopy groups of M, tensored with the field of rational numbers, is a finite-dimensional vector space over the rationals, then M is said to be rationally elliptic. It is known that M is rationally elliptic if it supports an action of cohomogeneity zero or one. When the cohomogeneity is two, this general result is no longer true. However, we prove that M is rationally elliptic in the two-dimensional case under the added assumption that M has nonnegative sectional curvature.
A refinement of theorems on vertex-disjoint chorded cycles
Theodore Molla,Michael Santana,Elyse Yeager
Mathematics , 2015,
Abstract: In 1963, Corr\'adi and Hajnal settled a conjecture of Erd\H{o}s by proving that, for all $k \geq 1$, any graph $G$ with $|G| \geq 3k$ and minimum degree at least $2k$ contains $k$ vertex-disjoint cycles. In 2008, Finkel proved that for all $k \geq 1$, any graph $G$ with $|G| \geq 4k$ and minimum degree at least $3k$ contains $k$ vertex-disjoint chorded cycles. Finkel's result was strengthened by Chiba, Fujita, Gao, and Li in 2010, who showed, among other results, that for all $k \geq 1$, any graph $G$ with $|G| \geq 4k$ and minimum Ore-degree at least $6k-1$ contains $k$ vertex-disjoint cycles. We refine this result, characterizing the graphs $G$ with $|G| \geq 4k$ and minimum Ore-degree at least $6k-2$ that do not have $k$ disjoint chorded cycles.
A Viral Nanoparticle with Dual Function as an Anthrax Antitoxin and Vaccine
Darly J Manayani,Diane Thomas,Kelly A Dryden,Vijay Reddy,Marc E Siladi,John M Marlett,G. Jonah A Rainey,Michael E Pique,Heather M Scobie,Mark Yeager,John A. T Young,Marianne Manchester,Anette Schneemann
PLOS Pathogens , 2007, DOI: 10.1371/journal.ppat.0030142
Abstract: The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. B. anthracis produces an AB-type toxin composed of the receptor-binding moiety protective antigen (PA) and the enzymatic moieties edema factor and lethal factor. PA is a key target for both antitoxin and vaccine development. We used the icosahedral insect virus Flock House virus as a platform to display 180 copies of the high affinity, PA-binding von Willebrand A domain of the ANTXR2 cellular receptor. The chimeric virus-like particles (VLPs) correctly displayed the receptor von Willebrand A domain on their surface and inhibited lethal toxin action in in vitro and in vivo models of anthrax intoxication. Moreover, VLPs complexed with PA elicited a potent toxin-neutralizing antibody response that protected rats from anthrax lethal toxin challenge after a single immunization without adjuvant. This recombinant VLP platform represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax.
Mental Health Problems in Primary Care: Progress in North America
Magruder,Kathryn M.; Yeager,Derik E.;
The European Journal of Psychiatry , 2007, DOI: 10.4321/S0213-61632007000100007
Abstract: background and objectives: research in the last decade has acknowledged that primary care plays a pivotal role in the delivery of mental health services. the aim of this paper is to review major accomplishments, emerging trends, and continuing gaps concerning mental health problems in primary care in north america. methods: literature from north america was reviewed and synthesized. results: major accomplishments include: the development and adoption of a number of clinical guidelines specifically for mental health conditions in primary care, the acceptance of the chronic care model as a framework for treating depression in primary care, and the clear adoption of pharmacologic approaches as the predominant mode for treating depression and anxiety. emerging trends include: the use of non-physician facilitators as care managers in the treatment of depression in primary care, increasing use of technology in the assessment and treatment of mental health conditions in primary care, and dissemination and implementation of integrated mental health treatment approaches. lingering issues include: the difficulty in moving beyond problem identification and initiation of treatment to sustaining evidence-based treatments, agreement on a common metric to evaluate outcomes, and the stigma still associated with mental illness. conclusion: though there now exists a solid and growing evidence base for the delivery of mental health services in primary care, there are still significant challenges which must be overcome in order to make further advances.
Mental Health Problems in Primary Care: Progress in North America
Kathryn M. Magruder,Derik E. Yeager
The European Journal of Psychiatry , 2007,
Abstract: Background and Objectives: Research in the last decade has acknowledged that primary care plays a pivotal role in the delivery of mental health services. The aim of this paper is to review major accomplishments, emerging trends, and continuing gaps concerning mental health problems in primary care in North America. Methods: Literature from North America was reviewed and synthesized. Results: Major accomplishments include: the development and adoption of a number of clinical guidelines specifically for mental health conditions in primary care, the acceptance of the chronic care model as a framework for treating depression in primary care, and the clear adoption of pharmacologic approaches as the predominant mode for treating depression and anxiety. Emerging trends include: the use of non-physician facilitators as care managers in the treatment of depression in primary care, increasing use of technology in the assessment and treatment of mental health conditions in primary care, and dissemination and implementation of integrated mental health treatment approaches. Lingering issues include: the difficulty in moving beyond problem identification and initiation of treatment to sustaining evidence-based treatments, agreement on a common metric to evaluate outcomes, and the stigma still associated with mental illness. Conclusion: Though there now exists a solid and growing evidence base for the delivery of mental health services in primary care, there are still significant challenges which must be overcome in order to make further advances.
Zeros of Polynomials with Random Coefficients
Igor E. Pritsker,Aaron M. Yeager
Mathematics , 2014,
Abstract: Zeros of many ensembles of polynomials with random coefficients are asymptotically equidistributed near the unit circumference. We give quantitative estimates for such equidistribution in terms of the expected discrepancy and expected number of roots in various sets. This is done for polynomials with coefficients that may be dependent, and need not have identical distributions. We also study random polynomials spanned by various deterministic bases.
The Interaction between Pesticide Use and Genetic Variants Involved in Lipid Metabolism on Prostate Cancer Risk
Gabriella Andreotti,Stella Koutros,Sonja I. Berndt,Kathryn Hughes Barry,Lifang Hou,Jane A. Hoppin,Dale P. Sandler,Jay H. Lubin,Laurie A. Burdette,Jeffrey Yuenger,Meredith Yeager,Laura E. Beane Freeman,Michael C. R. Alavanja
Journal of Cancer Epidemiology , 2012, DOI: 10.1155/2012/358076
Abstract: Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication. 1. Background Previous studies of prostate cancer have shown elevated rates in agricultural and pesticide manufacturing populations [1, 2]. In the Agricultural Health Study (AHS), a significant excess of prostate cancer was observed among private and commercial pesticide applicators compared to the general population [3, 4]. Also, use of pesticides, such as phorate [5], fonofos [6], butylate [7], and coumaphos [8], has been linked with an increased risk of prostate cancer among AHS participants with a family history of prostate cancer. We conducted a prostate cancer nested case-control study within the AHS to examine interactions between prespecified genetic pathways and pesticide exposure. Recent findings from this study have identified significant pesticide interactions for several genetic variants in the 8q24 region [9], xenobiotic metabolism pathway [10], and DNA repair pathways [11, 12]. These studies help elucidate exposure-effect associations by identifying potentially susceptible subgroups. This allows us to better understand potential carcinogenic hazards and furthers public health research on the human health effects of pesticides. In this analysis, we evaluated single nucleotide polymorphisms (SNPs) in genes related to lipid metabolism since
Genetic Susceptibility Loci, Pesticide Exposure and Prostate Cancer Risk
Stella Koutros, Sonja I. Berndt, Kathryn Hughes Barry, Gabriella Andreotti, Jane A. Hoppin, Dale P. Sandler, Meredith Yeager, Laurie A. Burdett, Jeffrey Yuenger, Michael C. R. Alavanja, Laura E. Beane Freeman
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058195
Abstract: Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44–8.15) (P-interaction = 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction = 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.
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