Session Clustering Using Mixtures of Proportional Hazards Models

Emanating from classical Weibull mixture models we propose a framework for clustering survival data with various proportionality restrictions imposed. By introducing mixtures of Weibull proportional hazards models on a multivariate data set a parametric cluster approach based on the EM-algorithm is carried out. The problem of non-response in the data is considered. The application example is a real life data set stemming from the analysis of a world-wide operating eCommerce application. Sessions are clustered due to the dwell times a user spends on certain page-areas. The solution allows for the interpretation of the navigation behavior in terms of survival and hazard functions. A software implementation by means of an R package is provided. (author´s abstract)Series: Research Report Series / Department of Statistics and Mathematic

Cell cycle dysregulation influences survival in high risk breast cancer patients

Background: Cell cycle progression is regulated by cyclin dependent kinases (cdk) and cdk inhibitors. Recent immunohistological studies suggested that dysregulation of cyclin A, cyclin D, cyclin E, p16ink4, p21waf1/cip1, and p27kip1 are of prognostic value in patients with breast cancer. Our study represents the first comprehensive immunohistochemical cell cycle marker analysis for cdc25A, cyclin A, cyclin D, cyclin E, p16ink4, p21waf1/cip1, p27kip1, and pRb in tumor tissue and adjacent benign breast tissue from 69 primarily untreated breast cancer patients. Methods: Immunhistochemistry using primary monoclonal antibodies to detect cdc 25A, cyclin A, cyclin D, cyclin E, p16ink4, p21waf1/cip1, p27kip1, and pRb has been performed. Results: Sixty-nine patients with untreated, invasive breast cancer (n = 69) were divided into a low/ intermediate and a high risk group according to the St. Gallen 2005 consensus conference. High risk patients (n = 22) had a significantly (p = 0.003) shorter mean and median survival (282.85 weeks; 383.0 weeks, respectively) than low/intermediate risk patients (375.41 weeks; not reached yet, respectively). A subgroup of high risk breast cancer patients characterized in addition by overexpression of cdc25A, cyclin A, cyclin E, p16ink4a, and p27kip1 experienced a shortened mean survival of 222.03, 235.71, 257.25, 239.18, and 261.94 weeks, respectively. Regarding benign breast tissue adjacent to breast cancer tissue, 59.4% of the patients investigated overexpressed cdc25A, 23.2% overexpressed pRb, and 63.2% exerted dysregulation of p27kip1 while they proved to be negative for immunohistochemical staining regarding all other markers tested. Conclusion: The immunohistological analyses of cdc25A, cyclin A, cyclin E, p16ink4a, and p27kip1 have the potential for further refining the risk assessment in patients with untreated breast cancer who belong to the high risk category defined according to the St. Gallen 2005 consensus conference. These cell cycle markers define a subgroup of high risk patients with even higher risk of metastazation and shortened survival. For confirmation a prospective study using standardized laboratory procedures in a larger population is needed. Read More: http://informahealthcare.com/doi/abs/10.1080/0735790080194486