Weighted Rank Regression with Dummy Variables for Analyzing Accelerated Life Testing Data

In this article, we propose a new rank regression model to extrapolate the product lifetimes at normal operation environment from accelerated testing data. Weighted least squares method is used to compensate for nonconstant error variance in the regression model. A group of dummy variables is incorporated to check model adequacy. We also developed a customizing software for quick-and-easy implementation of the method so that reliability engineers can easily exploit it. Simulation studies show that, under light censoring, the proposed method performs comparatively well in predicting the lifetimes even with small sample sizes. With its computational ease and graphical presentation, the proposed method is expected to be more popular among reliability engineers

The effects of pre-pregnancy body mass index and gestational weight gain on perinatal outcomes in Korean women: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to evaluate the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain on perinatal outcomes in a population of Korean women.</p> <p>Methods</p> <p>We retrospectively reviewed the medical records of 2,454 women who had received antenatal care at Seoul St. Mary's Hospital from January 2007 to December 2009. We used World Health Organization definitions for Asian populations of underweight (BMI < 18.5), normal (BMI equal or higher 18.5 and < 23), overweight (BMI equal or higher 23 and < 25), and obese (BMI equal or higher 25). We analyzed perinatal outcomes according to the pre-pregnancy BMI and weight gain during pregnancy, and calculated the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from multiple logistic regression models by considering maternal age, parity, number of fetuses, length of gestation, and medical history.</p> <p>Results</p> <p>Among obese women, the adjusted ORs for gestational diabetes, hypertensive disorder, and incompetent internal os of cervix were 4.46, 2.53, and 3.70 (95% CI = 2.63-7.59, 1.26-5.07, and 1.50-9.12), respectively, and the adjusted ORs for neonatal complications such as macrosomia and low Apgar score were 2.08 and 1.98 (95% CI = 1.34-3.22 and 1.19-3.29), respectively, compared with normal weight women. However, there was no positive linear association between gestational weight gain and obstetric outcomes. In normal weight women, maternal and neonatal complications were significantly increased with inadequate weight gain during pregnancy (p < 0.0001 and = 0.0180, respectively), and we observed similar results in underweight women (p = 0.0136 and 0.0004, respectively).</p> <p>Conclusions</p> <p>This study shows that pre-pregnancy overweight and obesity are more closely related to the adverse obstetric outcomes than excess weight gain during pregnancy. In addition, inadequate weight gain during pregnancy can result in significant complications.</p

The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells.

Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase inhibitors, p16(INK4A) and p21(CIP1), but not Rb phosphorylation and E2F1 expression, indicating that AR has a specific role in the pathway-mediated differentiation and growth inhibitory signaling. However, despite the sufficient role of Raf/MEK/ERK, its inhibition using U0126 or ERK1/2 knockdown could not block androgen deprivation-induced AR downregulation in an LNCaP neuroendocrine differentiation model, suggesting that additional signaling pathways are involved in the regulation. We additionally report that sustained Raf/MEK/ERK activity can downregulate full length as well as hormone binding domain-deficient AR isoforms in androgen-refractory C4-2 and CWR22Rv1, but not in LAPC4 and MDA-PCa-2b. Our study demonstrates a novel role of the Raf/MEK/ERK pathway in regulating AR expression in certain PCa types and provides an insight into PCa responses to its aberrant activation