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Now showing 1 - 10 of 38
  • (2008) Gattellari, Melina; Worthington, John; Zwar, N; Middleton, Susan
    Journal Article
    Background and Purpose: Anticoagulation reduces the risk of stroke in nonvalvular atrial fibrillation yet remains underused. We explored barriers to the use of anticoagulants among Australian family physicians. Methods: The authors conducted a representative, national survey. Results: Of the 596 (64.4%) eligible family physicians who participated, 15.8% reported having a patient with nonvalvular atrial fibrillation experience an intracranial hemorrhage with anticoagulation and 45.8% had a patient with known nonvalvular atrial fibrillation experience a stroke without anticoagulation. When presented with a patient at `very high risk` of stroke, only 45.6% of family physicians selected warfarin in the presence of a minor falls risk and 17.1% would anticoagulate if the patient had a treated peptic ulcer. Family physicians with less decisional conflict and longer-standing practices were more likely to endorse anticoagulation. Conclusion: Strategies to optimize the management of nonvalvular atrial fibrillation should address psychological barriers to using anticoagulation.

  • (2006) Gattellari, Melina; Zwar, N; Worthington, John; Middleton, Susan
    Journal Article
    Background and Purpose: Anticoagulation reduces the risk of stroke in nonvalvular atrial fibrillation yet remains underused. We explored barriers to the use of anticoagulants among Australian family physicians. Methods: The authors conducted a representative, national survey. Results: Of the 596 (64.4%) eligible family physicians who participated, 15.8% reported having a patient with nonvalvular atrial fibrillation experience an intracranial hemorrhage with anticoagulation and 45.8% had a patient with known nonvalvular atrial fibrillation experience a stroke without anticoagulation. When presented with a patient at "very high risk" of stroke, only 45.6% of family physicians selected warfarin in the presence of a minor falls risk and 17.1% would anticoagulate if the patient had a treated peptic ulcer. Family physicians with less decisional conflict and longer-standing practices were more likely to endorse anticoagulation. Conclusion: Strategies to optimize the management of nonvalvular atrial fibrillation should address psychological barriers to using anticoagulation.

  • (2007) Sisson, Scott; Fan, Yanan; Tanaka, Mark
    Journal Article
    Recent new methods in Bayesian simulation have provided ways of evaluating posterior distributions in the presence of analytically or computationally intractable likelihood functions. Despite representing a substantial methodological advance, existing methods based on rejection sampling or Markov chain Monte Carlo can be highly inefficient and accordingly require far more iterations than may be practical to implement. Here we propose a sequential Monte Carlo sampler that convincingly overcomes these inefficiencies. We demonstrate its implementation through an epidemiological study of the transmission rate of tuberculosis.

  • (2006) Tanaka, Mark; Francis, A; Luciani, Fabio; Sisson, Scott
    Journal Article
    Tuberculosis can be studied at the population level by genotyping strains of Mycobacterium tuberculosis isolated from patients. We use an approximate Bayesian computational method in combination with a stochastic model of tuberculosis transmission and mutation of a molecular marker to estimate the net transmission rate, the doubling time, and the reproductive value of the pathogen. This method is applied to a published data set from San Francisco of tuberculosis genotypes based on the marker IS6110. The mutation rate of this marker has previously been studied, and we use those estimates to form a prior distribution of mutation rates in the inference procedure. The posterior point estimates of the key parameters of interest for these data are as follows: net transmission rate, 0.69/year [95% credibility interval (C.I.) 0.38, 1.08]; doubling time, 1.08 years (95% C.I. 0.64, 1.82); and reproductive value 3.4 (95% C.I. 1.4, 79.7). These figures suggest a rapidly spreading epidemic, consistent with observations of the resurgence of tuberculosis in the United States in the 1980s and 1990s.

  • (2014) Coupland, Kirsten G; Mellick, George D; Silburn, Peter A; Huang, Yue; Halliday, Glenda; Hallup, Marianne; Woojin, S. Kim; Dobson-Stone, Carol; Kwok, John BJ; Mather, Karen; Armstrong, Nicola J; Sachdev, Perminder; Brodaty, Henry
    Journal Article
    Background: Parkinson's disease (PD) is a neurodegenerative disorder for which environmental factors influence disease risk and may act via an epigenetic mechanism. The microtubule-associated protein tau (MAPT) is a susceptibility gene for idiopathic PD. Methods: Methylation levels were determined by pyrosequencing of bisulfite treated DNA in a leukocyte cohort (358 PD and 1084 controls) and two brain cohorts (Brain1 comprising 69 cerebellum controls, Brain2 comprising 3 brain regions from 28 PD and 12 controls). In vitro assays involved the transfection of methylated promoter-luciferase constructs or treatment with an exogenous micronutrient. Results: In normal leukocytes, MAPT H1/H2 diplotype and gender were predictors of MAPT methylation. Haplotype-specific pyrosequencing confirmed H1 haplotype to have higher methylation than H2 in normal leukocyte and brain tissues. MAPT methylation was negatively associated with MAPT expression in Brain1 cohort and transfected cells. Methylation levels differed between three normal brain regions (Brain2, putamen > cerebellum > anterior cingulate cortex). In PD samples, age at onset was positively associated with MAPT methylation in leukocytes. Moreover, there was hypermethylation in the cerebellum and hypomethylation in the putamen of PD patients compared with controls (Brain2 cohort). Finally, leukocyte methylation status was positively associated with blood Vitamin E levels, the effect being more significant in H2 haplotype carriers; this result was confirmed in cells exposed to 100 μM Vitamin E. Conclusions: The significant effects of gender, diplotype and brain region suggest that hypermethylation of the MAPT is neuroprotective by reducing MAPT expression. Vitamin E effect on MAPT represents a possible gene-environment interaction.

  • (2009) Maesono, Y.; Penev, Spiridon
    Journal Article
    Using the kernel estimator of the pth quantile of a distribution brings about an improvement in comparison to the sample quantile estimator. The size and order of this improvement is revealed when studying the Edgeworth expansion of the kernel estimator. Using one more term beyond the normal approximation significantly improves the accuracy for small to moderate samples. The investigation is non- standard since the influence function of the resulting L-statistic explicitly depends on the sample size. We obtain the expansion, justify its validity and demonstrate the numerical gains in using it.

  • (2009) Penev, Spiridon; Raykov, T
    Journal Article
    This paper is concerned with the reliability of weighted combinations of a given set of dichotomous measures. Maximal reliability for such measures has been discussed in the past, but the pertinent estimator exhibits a considerable bias and mean squared error for moderate sample sizes. We examine this bias, propose a procedure for bias correction, and develop a more accurate asymptotic confidence interval for the resulting estimator. In most empirically relevant cases, the bias correction and mean squared error correction can be performed simultaneously. We propose an approximate (asymptotic) confidence interval for the maximal reliability coefficient, discuss the implementation of this estimator, and investigate the mean squared error of the associated asymptotic approximation. We illustrate the proposed methods using a numerical example.

  • (2009) Raykov, Tenko; Penev, Spiridon
    Journal Article
    A procedure for point and interval estimation of maximal reliability of multiple-component measuring instruments in multi-level settings is outlined. The approach is applicable to hierarchical designs in which individuals are nested within higher-order units and exhibit possibly related performance on components of a given homogeneous scale. The method is developed within the framework of multi-level factor analysis. The proposed procedure is illustrated with an empirical example.

  • (2008) Dimitrova, Dimitrina; Kaishev, Vladimir; Penev, Spiridon
    Journal Article
    A new multivariate Archimedean copula estimation method is proposed in a non-parametric setting. The method uses the so-called Geometrically Designed splines (GeD splines) to represent the cdf of a random variable Wθ, obtained through the probability integral transform of an Archimedean copula with parameter θ. Sufficient conditions for the GeD spline estimator to possess the properties of the underlying theoretical cdf, K(θ,t), of Wθ, are given. The latter conditions allow for defining a three-step estimation procedure for solving the resulting non-linear regression problem with linear inequality constraints. In the proposed procedure, finding the number and location of the knots and the coefficients of the unconstrained GeD spline estimator and solving the constraint least-squares optimisation problem are separated. Thus, the resulting spline estimator View the MathML source is used to recover the generator and the related Archimedean copula by solving an ordinary differential equation. The proposed method is truly multivariate, it brings about numerical efficiency and as a result can be applied with large volumes of data and for dimensions d≥2, as illustrated by the numerical examples presented.

  • (2006) Penev, Spiridon; Raykov, T
    Journal Article
    A linear combination of a set of measures is often sought as an overall score summarizing subject performance. The weights in this composite can be selected to maximize its reliability or to maximize its validity, and the optimal choice of weights is in general not the same for these two optimality criteria. We explore several relationships between the resulting reliability and validity estimates in different situations. Only in the case of congeneric tests are maximal reliability and maximal validity attained with the same weights, and a precise relationship between these two maximality concepts can be derived. A widely and readily applicable procedure for point and interval estimation of maximal validity is also outlined. Several inequalities are established for the case when the measures are not congeneric.