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Effect of Intensive Blood Pressure Control on Cardiovascular Remodeling in Hypertensive Patients with Nephrosclerosis
Otelio Randall,John Kwagyan,Tamrat Retta,Kenneth Jamerson,Velvie Pogue,Keith Norris,Muluemebet Ketete,Shichen Xu,Tom Greene,Xuelei Wang,Lawrence Agodoa
International Journal of Nephrology , 2013, DOI: 10.1155/2013/120167
Abstract: Pulse pressure (PP), a marker of arterial system properties, has been linked to cardiovascular (CV) complications. We examined (a) association between unit changes of PP and (i) composite CV outcomes and (ii) development of left-ventricular hypertrophy (LVH) and (b) effect of mean arterial pressure (MAP) control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102–107?mmHg) or a lower MAP goal (≤92?mmHg) and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11–1.47, ) and new LVH (RR = 1.26, CI = 1.04–1.54, ). PP increased at a greater rate in the usual than in lower MAP groups (slope ± SE: 1.08 ± 0.15 versus 0.42 ± 0.15 mmHg/year, ), but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health. 1. Introduction Population and hospital-based studies [1, 2] have demonstrated that persistently elevated blood pressure (BP) levels increase the risk of cardiovascular (CV) events and subsequent CV mortality. Though the precise mechanisms of this association are still being investigated, several studies have detected a direct link between increased BP variability and target-organ damage [3–7]. The major target organs for the complications of elevated BP are the kidneys, heart, brain, and the arterial system. Study of the character of vascular alterations and the time course of such alterations is important to better understand the mechanism of hypertensive process. Retta and Randall [8] have suggested that target-organ damage is the result of an integrated effect of BP level as a function of time, whether it is continuously elevated or intermittent increases of pressure. Arterial stiffness is linked with changes in BP profile, characterized by isolated increase in systolic pressure and/or increase in pulse pressure (PP). Increased PP can result from an increase in systolic pressure and/or a decrease in diastolic pressure, which is typical for advanced arteriosclerosis and is responsible for the diastolic pressure stabilization or decline observed in aging [9]. Investigations in hypertension have generally focused on the steady components of blood pressure, such as mean arterial pressure (MAP), which is
A new species of Schinia Hubner from the southeastern United States (Lepidoptera, Noctuidae, Heliothinae)
Michael Pogue
ZooKeys , 2010, DOI: 10.3897/zookeys.52.476
Abstract: Schinia psamathea sp. n. is described from the southern coastal plain in Georgia and the East Gulf coastal plain in Florida and Alabama in habitats associated with sandy soil or dunes. Adult males and females and their genitalia are described and illustrated. Schinia psamathea is compared to Schinia saturata (Grote).
A review of the Paectes arcigera species complex (Guenée) (Lepidoptera, Euteliidae)
Michael Pogue
ZooKeys , 2013, DOI: 10.3897/zookeys.264.3274
Abstract: Five new species of Paectes Hübner [1818] related to Paectes arcigera (Guenée) (Puerto Rico, U.S. Virgin Islands, British Virgin Islands, Guadeloupe, Dominica, St. Lucia, Trinidad) and P. longiformis Pogue (Brazil) are described: P. asper sp. n. (Florida, Bahamas, Cuba, Cayman Islands, Jamaica, Haiti, Dominican Republic, Puerto Rico, British Virgin Islands, U.S. Virgin Islands, Dominica, Colombia), P. medialba sp. n. (Argentina), P. similis sp. n. (Brazil), P. sinuosa sp. n. (Argentina, Brazil, Paraguay), and P. tumida sp. n. (Colombia, Guyana, Suriname, French Guiana). Adults and genitalia are illustrated for all species. Taxonomic changes include the rev. stat. of P. nana (Walker) (Florida, Greater Antilles, Mexico, Guatemala, Galapagos) as a valid species and revised synonyms P. indefatigabilis Schaus and P. isabel Schaus as junior synonyms of P. nana instead of P. arcigera. New host records for P. sinuosa and P. nana reared on Brazilian peppertree (Schinus terebinthifolius Raddi, Anacardiaceae) are presented. The holotype and female genitalia of P. obrotunda (Guenée) are illustrated.
Teaching Time Investment: Does Online Really Take More Time than Face-to-Face?
Rebecca Van de Vord,Korolyn Pogue
International Review of Research in Open and Distance Learning , 2012,
Abstract: Enrollments in online programs are growing, increasing demand for online courses. The perception that teaching online takes more time than teaching face-to-face creates concerns related to faculty workload. To date, the research on teaching time does not provide a clear answer as to the accuracy of this perception. This study was designed to investigate which aspects, if any, are more time consuming for instructors teaching in the online environment. Time logs were kept by four online instructors (eight classes) and six on-campus instructors (six classes) through six weeks of the 15-week semester. Results indicated that, overall, face-to-face teaching required more time per student, but certain aspects of online teaching take considerably more time per student than in the face-to-face classroom.
Designing and Analyzing Clinical Trials with Composite Outcomes: Consideration of Possible Treatment Differences between the Individual Outcomes
Janice Pogue, P. J. Devereaux, Lehana Thabane, Salim Yusuf
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034785
Abstract: When the individual outcomes within a composite outcome appear to have different treatment effects, either in magnitude or direction, researchers may question the validity or appropriateness of using this composite outcome as a basis for measuring overall treatment effect in a randomized controlled trial. The question remains as to how to distinguish random variation in estimated treatment effects from important heterogeneity within a composite outcome. This paper suggests there may be some utility in directly testing the assumption of homogeneity of treatment effect across the individual outcomes within a composite outcome. We describe a treatment heterogeneity test for composite outcomes based on a class of models used for the analysis of correlated data arising from the measurement of multiple outcomes for the same individuals. Such a test may be useful in planning a trial with a primary composite outcome and at trial end with final analysis and presentation. We demonstrate how to determine the statistical power to detect composite outcome treatment heterogeneity using the POISE Trial data. Then we describe how this test may be incorporated into a presentation of trial results with composite outcomes. We conclude that it may be informative for trialists to assess the consistency of treatment effects across the individual outcomes within a composite outcome using a formalized methodology and the suggested test represents one option.
Testing for heterogeneity among the components of a binary composite outcome in a clinical trial
Janice Pogue, Lehana Thabane, PJ Devereaux, Salim Yusuf
BMC Medical Research Methodology , 2010, DOI: 10.1186/1471-2288-10-49
Abstract: Simulations were done comparing four different models commonly used to analyze correlated binary data. These models included: logistic regression for ignoring correlation, logistic regression weighted by the intra cluster correlation coefficient, population average logistic regression using generalized estimating equations (GEE), and random effects logistic regression.We found that the population average model based on generalized estimating equations (GEE) had the greatest power across most scenarios. Adequate power to detect possible composite heterogeneity or variation between treatment effects of individual components of a composite outcome was seen when the power for detecting the main study treatment effect for the composite outcome was also reasonably high.It is recommended that authors report tests of composite heterogeneity for composite outcomes and that this accompany the publication of the statistically significant results of the main effect on the composite along with individual components of composite outcomes.Composite outcomes can often be difficult to interpret, especially when the treatment effects on some of its components individually show differences in magnitude or even in direction. For example, in a trial of localized intracoronary gamma-radiation therapy versus placebo [1] the primary composite outcome of death, myocardial infarction, or revascularization of target lesion showed an overall benefit of gamma-radiation compared to placebo (24.4% vs 42.1%, p = 0.02); however, myocardial infarction individually had a non-significant effect in the opposite direction (9.9% vs. 4.1%, p = 0.09). Many authors have expressed concerns regarding interpretation of a treatment effect for a composite outcome when it appears that there is heterogeneity in the treatment effect across the composite components [2-4]. How then can we best determine the existence of important composite heterogeneity in treatment effect among the individual components of a composi
Executive functions and cognitive deficits in schizophrenia: Comparisons between probands, parents and controls in India
Bhatia T,Garg K,Pogue-Geile M,Nimgaonkar V
Journal of Postgraduate Medicine , 2009,
Abstract: Background: Cognitive impairment is said to be a core feature of schizophrenia. Executive function is an important cognitive domain. Aim: This study was undertaken to assess cognitive impairment among Indian patients with schizophrenia (Sz) or schizoaffective disorder (SzA), compared with their parents and unaffected individuals (controls). Settings and Design: Executive functions as measured by Trail-making Test (TMT), of patients and their parents were compared with controls. The patients were recruited from the Outpatients′ Department (OPD) of a government hospital. Materials and Methods: Patients diagnosed as Sz or SzA (n=172) and their parents (n=196: families n=132, 119 fathers and 77 mothers) participated. We also included 120 persons with no history of psychiatric illness. Cognitive function was assessed with the TMT. The Information Score of the Post Graduate Institute Battery of Brain Dysfunction test, developed in India for Indian subjects was used as a proxy for general fixed knowledge. Statistical Analysis: Logistic and linear regression was used to compare cognitive deficits of cases, parents and controls. Results: Cases and their parents took significantly more time than controls on Part B of the TMT. There were no statistically significant differences between cases and parents on any of the TMT parameters. Using regression analysis, the most significant correlates of all TMT parameters among cases were with occurrence of auditory hallucinations and current age. Conclusion: Cases, as well as their parents showed more cognitive impairment than controls on the TMT.
Metal-Sulfate Induced Generation of ROS in Human Brain Cells: Detection Using an Isomeric Mixture of 5- and 6-Carboxy-2′,7′-Dichlorofluorescein Diacetate (Carboxy-DCFDA) as a Cell Permeant Tracer
Aileen I. Pogue,Brandon M. Jones,Surjyadipta Bhattacharjee,Maire E. Percy,Yuhai Zhao,Walter J. Lukiw
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms13089615
Abstract: Evolution of reactive oxygen species (ROS), generated during the patho-physiological stress of nervous tissue, has been implicated in the etiology of several progressive human neurological disorders including Alzheimer’s disease (AD) and amylotrophic lateral sclerosis (ALS). In this brief communication we used mixed isomers of 5-(and-6)-carboxy-2′,7′-dichlorofluorescein diacetate (carboxy-DCFDA; C 25H 14C l2O 9; MW 529.3), a novel fluorescent indicator, to assess ROS generation within human neuronal-glial (HNG) cells in primary co-culture. We introduced pathological stress using the sulfates of 12 environmentally-, industrially- and agriculturally-relevant divalent and trivalent metals including Al, Cd, Cu, Fe, Hg, Ga, Mg, Mn, Ni, Pb, Sn and Zn. In this experimental test system, of all the metal sulfates analyzed, aluminum sulfate showed by far the greatest ability to induce intracellular ROS. These studies indicate the utility of using isomeric mixtures of carboxy-H 2DCFDA diacetates as novel and highly sensitive, long-lasting, cell-permeant, fluorescein-based tracers for quantifying ROS generation in intact, metabolizing human brain cells, and in analyzing the potential epigenetic contribution of different metal sulfates to ROS-generation and ROS-mediated neurological dysfunction.
Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters
Michael D. Glidden, Jonathan P. Celli, Iqbal Massodi, Imran Rizvi, Brian W. Pogue, Tayyaba Hasan
Theranostics , 2012,
Abstract: Photodynamic therapy (PDT) is a light-based treatment modality in which wavelength specific activation of a photosensitizer (PS) generates cytotoxic response in the irradiated region. PDT response is critically dependent on several parameters including light dose, PS dose, uptake time, fluence rate, and the mode of light delivery. While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response. Here we present a theranostic technique, combining the inherent ability of the PS to serve simultaneously as a therapeutic and imaging agent, with the use of image-based treatment assessment in three dimensional (3D) in vitro tumor models, to comprise a platform to evaluate the impact of PDT parameters on treatment outcomes. We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells. Informed by photobleaching patterns and correlation with cytotoxic response, asymmetric fractionated light delivery at 4 hours BPD uptake was found to be the most effective regimen assessed. Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules. The framework introduced here provides a means for systematic assessment of PDT treatment parameters in biologically relevant 3D tumor models with potential for broader application to other systems.
Fluorescent Affibody Peptide Penetration in Glioma Margin Is Superior to Full Antibody
Kristian Sexton, Kenneth Tichauer, Kimberley S. Samkoe, Jason Gunn, P. Jack Hoopes, Brian W. Pogue
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060390
Abstract: Object Fluorescence imaging has the potential to significantly improve neurosurgical resection of oncologic lesions through improved differentiation between normal and cancerous tissue at the tumor margins. In order to successfully mark glioma tissue a fluorescent tracer must have the ability to penetrate through the blood brain barrier (BBB) and provide delineation in the tumor periphery where heterogeneously intact BBB may exist. In this study it was hypothesized that, due to its smaller size, fluorescently labeled anti-EGFR Affibody protein (~7 kDa) would provide a more clear delineation of the tumor margin than would fluorescently labeled cetuximab, a full antibody (~150 kDa) to the epidermal growth factor receptor (EGFR). Methods Cetuximab and anti-EGFR targeted Affibody were conjugated to two different fluorescent dyes (both emitting in the near-infrared) and injected intravenously into 6 athymic mice which were inoculated orthotopically with green fluorescent protein (GFP) expressing human U251 glioma cells. Each mouse was sacrificed at 1-h post injection, at which time brains were removed, snap frozen, sectioned and quantitatively analyzed for fluorescence distribution. Results Ex vivo analysis showed on average, nearly equal concentrations of cetuximab and Affibody within the tumor (on average Affibody made up 49±6% of injected protein), however, the cetuximab was more confined to the center of the tumor with Affibody showing significantly higher concentrations at the tumor periphery (on average Affibody made up 72±15% of injected protein in the outer 50 um of the tumor). Further ex vivo analysis of detection studies showed that the Affibody provided superior discrimination for differentiation of tumor from surrounding normal brain. Conclusions The present study indicates that fluorescently labeled anti-EGFR Affibody can provide significantly better delineation of tumor margins than a fluorescently labeled anti-EGFR antibody and shows considerable potential for guiding margin detection during neurosurgery.
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