Abstract-National guidelines and a recent clinical trial have supported the use of thiazide diuretics as the preferred initial pharmacological treatment for hypertension. However, evidence from this and other clinical trials have also found an increased incidence of new onset diabetes among those patients receiving thiazide diuretics. The mechanisms responsible for the increased incidence of diabetes with thiazide diuretics have not been fully elucidated. This article provides a review of intervention studies that included data on the relation between thiazide-induced hypokalemia and glucose intolerance.
We present a method for comparing semiparametric Bayesian models, constructed under the Dirichlet process mixture (DPM) framework, with alternative semiparameteric or parameteric Bayesian models. A distinctive feature of the method is that it can be applied to semiparametric models containing covariates and hierarchical prior structures, and is apparently the rst method of its kind. Formally, the method is based on the marginal likelihood estimation approach of Chib (1995) and requires estimation of the likelihood and posterior ordinates of the DPM model at a single high-density point. An interesting computation is involved in the estimation of the likelihood ordinate, which is devised via collapsed sequential importance sampling. Extensive experiments with synthetic and real data involving semiparametric binary data regression models and hierarchical longitudinal mixed-effects models are used to illustrate the implementation, performance, and applicability of the method.
The primary objective of this study is to identify prognostic site-specific epigenetic changes in surgically treated Stage I and II nonsmall cell lung cancer (NSCLC) patients by quantifying methylation levels at multiple CpG sites within each gene promoter. Paraffin-embedded tumors from stage Ib, IIa and IIb in training and validation groups of 75 and 57 surgically treated NSCLC patients, respectively, were analyzed for p16, MGMT, RASSF1, RASSF5, CDH1, LET7, DAPK and PTEN promoter hypermethylation. Hypermethylation status was quantified individually at multiple CpG sites within each promoter by pyrosequencing. Molecular and clinical characteristics with time to recurrence (TTR) and overall survival (OS) were evaluated. Overall average promoter methylation levels of MGMT and RASSF1 were significantly higher in smokers than in nonsmokers (p 5 0.006 and p 5 0.029, respectively). Methylation levels of the p16 promoter were significantly higher in squamous cell carcinoma than in adenocarcinoma (p 5 0.020). In univariate analysis, hypermethylation of RASSF1 at CpG sites 253 and 248 and PTEN at CpG site 21310 were the significantly associated with shorter TTR (p 5 0.002 and p < 0.000, respectively). Hypermethylation of PTEN at 21310 and DAPK at 21482 were most significantly associated with outcome in multivariate analysis. These results show that methylation of specific promoter CpG sites in PTEN, RASSF1 and DAPK is associated with outcome in early stage surgically treated NSCLC.
This study establishes a serum biomarker panel with efficacy in discerning preoperative nodal status. With further validation, this blood test may be useful for assessing nodal status (including occult disease) in NSCLC patients facing tumor resection therapy.
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