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Search Results: 1 - 10 of 306125 matches for " Sandra J Pavey "
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Expression profiling identifies genes involved in emphysema severity
Santiyagu Francis, Jill E Larsen, Sandra J Pavey, Rayleen V Bowman, Nicholas K Hayward, Kwun M Fong, Ian A Yang
Respiratory Research , 2009, DOI: 10.1186/1465-9921-10-81
Abstract: Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.Chronic obstructive pulmonary disease (COPD) is a major health burden worldwide [1]. Smoking is the primary cause of COPD, with up to 50% of smokers developing the disease [2]. It is frequently under-diagnosed and under-treated [3] since its early stages are often asymptomatic. COPD patients are classified into mild, moderate and severe based on the degree of airflow limitation, which is a result of damage in the large airways (bronchitis), small airways (bronchiolitis) and or alveoli (emphysema). Emphysema affects 40% of heavy smokers [4] and causes loss of elastic recoil, leading to abnormal gas exchange and breathlessness. Despite smoking cessation, some individuals con
Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD
Santiyagu M. Savarimuthu Francis,Jill E. Larsen,Sandra J. Pavey,Edwina E. Duhig,Belinda E. Clarke,Rayleen V. Bowman,Nick K. Hayward,Kwun M. Fong,Ian A. Yang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017442
Abstract: Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis.
Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma
Eric Smith, Neville J De Young, Sandra J Pavey, Nicholas K Hayward, Derek J Nancarrow, David C Whiteman, B Mark Smithers, Andrew R Ruszkiewicz, Andrew D Clouston, David C Gotley, Peter G Devitt, Glyn G Jamieson, Paul A Drew
Molecular Cancer , 2008, DOI: 10.1186/1476-4598-7-75
Abstract: We examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3, SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of samples that had any extent of methylation, for each of the nine genes in the EAC (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly higher than in any of the squamous groups. The methylation frequency for each of the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and 75% respectively) was significantly higher than in the squamous samples except for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The methylation extent was an estimate of both the number of methylated alleles and the density of methylation on these alleles. This was significantly greater in EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no significant difference in methylation extent for any gene between high grade dysplastic BE and EAC.We found significant methylation in metaplastic BE, which for seven of the nine genes studied did not differ in frequency from that found in EAC. This is also the first report of gene silencing by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a highly abnormal tissue, more similar to cancer tissue than to normal epithelium.The incidence of esophageal adenocarcinoma (EAC) is increasing rapidly and patient outcomes remain poor. Known risk factors for EAC include obesity, gastro-esophageal reflux, and the presence of Barrett's esophagus (BE). Repeated injury from gastro-duodenal reflux is thought to result in the replacement of the esophageal squamous mucosa with a metaplastic columnar
Ocean feature models their use and effectiveness in ocean acoustic forecasting
J. Small,L. Shackleford,G. Pavey
Annales Geophysicae (ANGEO) , 2003,
Abstract: The aim of this paper is to test the effectiveness of feature models in ocean acoustic forecasting. Feature models are simple mathematical representations of the horizontal and vertical structures of ocean features (such as fronts and eddies), and have been used primarily for assimilating new observations into forecasts and for compressing data. In this paper we describe the results of experiments in which the models have been tested in acoustic terms in eddy and frontal environments in the Iceland Faeroes region. Propagation-loss values were obtained with a 2D parabolic-equation (PE) model, for the observed fields, and compared to PE results from the corresponding feature models and horizontally uniform (range-independent) fields. The feature models were found to represent the smoothed observed propagation-loss field to within an rms error of 5 dB for the eddy and 7 dB for the front, compared to 10–15-dB rms errors obtained with the range-independent field. Some of the errors in the feature-model propagation loss were found to be due to high-amplitude 'oceanographic noise' in the field. The main conclusion is that the feature models represent the main acoustic properties of the ocean but do not show the significant effects of small-scale internal waves and fine-structure. It is recommended that feature models be used in conjunction with stochastic models of the internal waves, to represent the complete environmental variability.
In-house (dis)ability
Safak Pavey
Forced Migration Review , 2010,
Abstract: In May 2007 UNHCR established an internal working group to look at developing in-house policies for people with disabilities both for the benefit of people of concern to us and for staff members.
Class Numbers of Orders in Quartic Fields
Mark Pavey
Mathematics , 2006,
Abstract: It is shown that the sum of class numbers of orders in totally complex quartic fields with no real quadratic subfield obeys an asymptotic law similar to the prime numbers, as the bound on the regulators tends to infinity. Here only orders which are maximal at a given set of primes containing an even number of elements are considered. The proof is accomplished by means of a Prime Geodesic Theorem for symmetric spaces formed as compact quotients of SL(4,R). This result extends work of Sarnak in the real quadratic case and of Deitmar and Hoffmann in the complex cubic case.
A prime geodesic theorem for SL(4)
Anton Deitmar,Mark Pavey
Mathematics , 2006,
Abstract: A prime geodesic theorem is proven for singular geodesics in quotients of SL(4). This is a case where regularity assumptions of previous papers fail. As a consequence, the analysis becomes much more involved. For applications in number theory (class number asymptotics) it is, however, necessary to consider this case, too.
Class Numbers of Orders in Quartic Fields
Anton Deitmar,Mark Pavey
Mathematics , 2006,
Abstract: We prove an asymptotic formula for class numbers of totlally imaginary quartic number fields, ie for number fields of degree 4 over Q with only complex embeddings. After previous work for real quadratic fields (Sarnak) and complex cubic fields (Deitmar), this is the last remaining case of number fields with unit rank one.
An Exact Formula for Estimation of Age-Specific Sensitivity for Screening Tests  [PDF]
Ning Jia, Sandra J. Lee
Applied Mathematics (AM) , 2014, DOI: 10.4236/am.2014.517265
Abstract: There has been a growing interest in screening programs designed to detect chronic progressive cancers in the asymptomatic stage, with the expectation that early detection will result in a better prognosis. One key element of early detection programs is a screening test. An accurate screening test is more effective in finding cases with early-stage diseases. Sensitivity, the conditional probability of getting a positive test result when one truly has a disease, represents one measure of accuracy for a screening test. Since the true disease status is unknown, it is not straightforward to estimate the sensitivity directly from observed data. Furthermore, the sensitivity is associated with other parameters related to the disease progression. This feature introduces additional numerical complexity and limitations, especially when the sensitivity depends on age. In this paper, we propose a new approach that, through combinatorial manipulation of probability statements, formulates the age-dependent sensitivity. This formulation has an exact and simple expression and can be estimated based on directly observable probabilities. This approach also helps evaluate other parameters associated with the natural history of disease more accurately. The proposed method was applied to estimate the mammography sensitivity for breast cancer using the data from the Health Insurance Plan trial.
Contextual Modulation of Biases in Face Recognition
Fatima Maria Felisberti,Louisa Pavey
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012939
Abstract: The ability to recognize the faces of potential cooperators and cheaters is fundamental to social exchanges, given that cooperation for mutual benefit is expected. Studies addressing biases in face recognition have so far proved inconclusive, with reports of biases towards faces of cheaters, biases towards faces of cooperators, or no biases at all. This study attempts to uncover possible causes underlying such discrepancies.
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