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Search Results: 1 - 10 of 469634 matches for " Heather A. Young "
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Clinical Significance of Left Atrial Anatomic Abnormalities Identified by Cardiac Computed Tomography  [PDF]
Ara V. Vehian, Brian G. Choi, Satinder S. Rekhi, Heather A. Young, Raman S. Dusaj, Robert K. Zeman
Advances in Computed Tomography (ACT) , 2015, DOI: 10.4236/act.2015.41001
Purpose: The clinical significance of newly identified left atrial anatomic abnormalities (LAAA)— accessory appendages, diverticula, septal pouches—by multidetector CT (MDCT) remains unclear. Similar anatomical outpouchings, i.e., the left atrial appendage, have been associated with cardioembolisms and arrhythmia. To test the hypothesis that LAAA are also associated with increased risk of these events, we performed a retrospective analysis to examine the association of LAAA in patients undergoing CT with embolic events and arrhythmia. Methods: 242 patients (mean age 56 SD 12 years, 41% female) were selected who had CT coronary angiography performed with 64-row MDCT between 2007 and 2012 if complete clinical history records were available. CT images were independently reviewed for the presence of LAAA. Association of cerebrovascular accident (CVA) or transient ischemic attack (TIA), atrial fibrillation, and palpitations to LAAA was calculated using odds ratios (OR) with 95% confidence interval (CI) and Fisher’s exact test. Results: After adjusting for age, sex, hypertension, dyslipidemia and diabetes via multiple logistic regression, patients with accessory appendages are more likely to have reported palpitations (OR: 1.80; CI: 1.03 - 3.16). Patients with diverticula and septal pouches are significantly older than those without these abnormalities (p = 0.01 and p = 0.02, respectively). Septal pouches are associated with diabetes (OR: 2.29; 95%CI: 1.15 - 4.54). Conclusions: Accessory left atrial appendages are associated with palpitations. Patients with septal pouches and diverticula are significantly older than those patients without these anatomic abnormalities, suggesting age dependency of these findings. None of these anatomic abnormalities were associated with thromboembolic events after adjustment for potentially confounding comorbidities.
Divalent Metal Ion Coordination by Residue T118 of Anthrax Toxin Receptor 2 Is Not Essential for Protective Antigen Binding
Heather M. Scobie, John A.T. Young
PLOS ONE , 2006, DOI: 10.1371/journal.pone.0000099
Abstract: The protective antigen (PA) subunit of anthrax toxin interacts with the integrin-like I domains of either of two cellular receptors, ANTXR1 or ANTXR2. These I domains contain a metal ion-dependent adhesion site (MIDAS) made up of five non-consecutive amino acid residues that coordinate a divalent metal ion that is important for PA-binding. The MIDAS residues of integrin I domains shift depending upon whether the domain exists in a closed (ligand-unbound) or open (ligand-bound) conformation. Of relevance to this study, the MIDAS threonine residue coordinates the metal ion only in the open I domain conformation. Previously it was shown that the MIDAS threonine is essential for PA interaction with ANTXR1, a result consistent with the requirement that the I domain of that receptor adopts an open conformation for PA-binding [1]. Here we have tested the requirement for the MIDAS threonine of ANTXR2 for PA-binding. We show that the toxin can bind to a mutant receptor lacking the MIDAS threonine and that it can use that mutant receptor to intoxicate cultured cells. These findings suggest that an open-like configuration of the ANTXR2 MIDAS is not essential for the interaction with PA.
Care of HIV-Infected Pregnant Women in Maternal–Fetal Medicine Programs
Peter A. Sklar,Susanne L. Bathgate,Heather A. Young,David M. Parenti
Infectious Diseases in Obstetrics and Gynecology , 2001, DOI: 10.1155/s1064744901000151
Abstract: Objective: To survey the evolution over the past decade of attitudes and practices of obstetricians in maternal–fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV)-infected pregnant women.
Increased Detection of Breast Cancer Virus Sequences in Inflammatory Breast Cancer
Paul H. Levine, Heather A. Young, LaQuisha Mark, Helen Rojowsky, James F. Holland and Beatriz G-T Pogo
Advances in Tumor Virology , 2012,
Abstract: Earlier studies have suggested an association between breast cancer aggressiveness and the presence of viral sequences resembling mouse mammary tumor virus (MMTV). This study was to determine if inflammatory breast cancer (IBC) in the United States had a higher proportion of cases with these viral sequences than non-IBC patients and if specific risk factors for the sequences could be identified. Biospecimens from 67 patients in the North American IBC Registry were selected for sequencing of MMTV env- like sequences. The presence or absence of the viral sequences was compared to progression free survival (PFS), risk factors including exogenous hormones, and tumor markers. Of the 67 cases, 44 were positive for viral sequences (VSP), 17 were negative (VSN) and six were excluded from analysis because of insufficient DNA to perform replicates. The 72% of VSP cases was significantly more than the 40% in non-IBC U.S. breast cancer patients (p < 0.0001). Non-significant trends suggested that VSP patients were more likely to be HER-2 neu positive and ER negative, have a stronger exposure to exogenous hormones, and have a shorter PFS than VSN patients. MMTV-related sequences appear to be related to the aggressiveness of breast cancer with a higher incidence in North American IBC than in non-IBC breast cancer.
SEGUE-2 Limits on Metal-Rich Old-Population Hypervelocity Stars In the Galactic Halo
Juna A. Kollmeier,Andrew Gould,Constance Rockosi,Timothy C. Beers,Gillian Knapp,Jennifer A. Johnson,Heather Morrison,Paul Harding,Young Sun Lee,Benjamin A. Weaver
Physics , 2010, DOI: 10.1088/0004-637X/723/1/812
Abstract: We present new limits on the ejection of metal-rich old-population hypervelocity stars from the Galactic center (GC) as probed by the SEGUE-2 survey. Our limits are a factor of 3-10 more stringent than previously reported, depending on stellar type. Compared to the known population of B-star ejectees, there can be no more than 30 times more metal-rich old-population F/G stars ejected from the GC. Because B stars comprise a tiny fraction of a normal stellar population, this places significant limits on a combination of the GC mass function and the ejection mechanism for hypervelocity stars. In the presence of a normal GC mass function, our results require an ejection mechanism that is about 5.5 times more efficient at ejecting B-stars compared to low-mass F/G stars.
Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation
Heather M. Scobie, John M. Marlett, G. Jonah A. Rainey, D. Borden Lacy, R. John Collier, John A.T. Young
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000329
Abstract: The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ~6.0 or below when it is bound to ANTXR1, but only at pH ~5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation.
Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo
Heather M Scobie,Darran J Wigelsworth,John M Marlett,Diane Thomas,G. Jonah A Rainey,D. Borden Lacy,Marianne Manchester,R. John Collier,John A. T Young
PLOS Pathogens , 2006, DOI: 10.1371/journal.ppat.0020111
Abstract: Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis.
Lung Cancer Susceptibility Model Based on Age, Family History and Genetic Variants
Robert P. Young, Raewyn J. Hopkins, Bryan A. Hay, Michael J. Epton, Graham D. Mills, Peter N. Black, Heather D. Gardner, Richard Sullivan, Gregory D. Gamble
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005302
Abstract: Background Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer. Methodology/Principal Findings We screened 157 candidate single nucleotide polymorphisms (SNP) in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases) and identified 30 SNPs associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers) and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk. Conclusions/Significance Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.
The SEGUE Stellar Parameter Pipeline. V. Estimation of Alpha-Element Abundance Ratios From Low-Resolution SDSS/SEGUE Stellar Spectra
Young Sun Lee,Timothy C. Beers,Carlos Allende Prieto,David K. Lai,Constance M. Rockosi,Heather L. Morrison,Jennifer A. Johnson,Deokkeun An,Thirupathi Sivarani,Brian Yanny
Physics , 2010, DOI: 10.1088/0004-6256/141/3/90
Abstract: We present a method for the determination of [alpha/Fe] ratios from low-resolution (R = 2000) SDSS/SEGUE stellar spectra. By means of a star-by-star comparison with degraded spectra from the ELODIE spectral library and with a set of moderately high-resolution (R = 15,000) and medium-resolution (R = 6000) spectra of SDSS/SEGUE stars, we demonstrate that we are able to measure [alpha/Fe] from SDSS/SEGUE spectra (with S/N > 20/1) to a precision of better than 0.1 dex, for stars with atmospheric parameters in the range Teff = [4500, 7000] K, log g = [1.5, 5.0], and [Fe/H] = [-1.4, +0.3], over the range [alpha/Fe] = [-0.1, +0.6]. For stars with [Fe/H] < -1.4, our method requires spectra with slightly higher signal-to-noise to achieve this precision (S/N > 25/1). Over the full temperature range considered, the lowest metallicity star for which a confident estimate of [alpha/Fe] can be obtained from our approach is [Fe/H] ~ -2.5; preliminary tests indicate that a metallicity limit as low as [Fe/H] ~ -3.0 may apply to cooler stars. As a further validation of this approach, weighted averages of [alpha/Fe] obtained for SEGUE spectra of likely member stars of Galactic globular clusters (M15, M13, and M71) and open clusters (NGC 2420, M67, and NGC 6791) exhibit good agreement with the values of [alpha/Fe] from previous studies. The results of the comparison with NGC 6791 imply that the metallicity range for the method may extend to ~ +0.5.
Metallicity Gradients in the Milky Way Disk as Observed by the SEGUE Survey
Judy Y. Cheng,Constance M. Rockosi,Heather L. Morrison,Ralph A. Sch?nrich,Young Sun Lee,Timothy C. Beers,Dmitry Bizyaev,Kaike Pan,Donald P. Schneider
Physics , 2011, DOI: 10.1088/0004-637X/746/2/149
Abstract: The observed radial and vertical metallicity distribution of old stars in the Milky Way disk provides a powerful constraint on the chemical enrichment and dynamical history of the disk. We present the radial metallicity gradient, \Delta[Fe/H]/\Delta R, as a function of height above the plane, |Z|, using 7010 main sequence turnoff stars observed by the Sloan Extension for Galactic Understanding and Exploration (SEGUE) survey. The sample consists of mostly old thin and thick disk stars, with a minimal contribution from the stellar halo, in the region 6 < R < 16 kpc, 0.15 < |Z| < 1.5 kpc. The data reveal that the radial metallicity gradient becomes flat at heights |Z| > 1 kpc. The median metallicity at large |Z| is consistent with the metallicities seen in outer disk open clusters, which exhibit a flat radial gradient at [Fe/H] ~ -0.5. We note that the outer disk clusters are also located at large |Z|; because the flat gradient extends to small R for our sample, there is some ambiguity in whether the observed trends for clusters are due to a change in R or |Z|. We therefore stress the importance of considering both the radial and vertical directions when measuring spatial abundance trends in the disk. The flattening of the gradient at high |Z| also has implications on thick disk formation scenarios, which predict different metallicity patterns in the thick disk. A flat gradient, such as we observe, is predicted by a turbulent disk at high redshift, but may also be consistent with radial migration, as long as mixing is strong. We test our analysis methods using a mock catalog based on the model of Sch\"onrich & Binney, and we estimate our distance errors to be ~25%. We also show that we can properly correct for selection biases by assigning weights to our targets.
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