Tree-based scan statistic - Application in manufacturing-related safety signal detection.

Background And Objectives: Over the last decades, medicinal regulations have been put into place and have considerably improved manufacturing practices. Nevertheless, safety issues may still arise. Using the simulation described in this manuscript, our aim is to develop adequate detection methods for manufacturing-related safety signals, especially in the context of biological products.

Using time-to-onset for detecting safety signals in spontaneous reports of adverse events following immunization: a proof of concept study.

Purpose: Disproportionality analyses (DPA) are widely used in pharmacovigilance for detecting safety signals from spontaneous reports of adverse events. In these analyses, time-to-onset (TTO; the time between vaccination and the onset of the adverse event) is rarely considered. Our objective is to assess the potential use of TTO to improve signal detection (SD).

Quantitative signal detection for vaccines: effects of stratification, background and masking on GlaxoSmithKline's spontaneous reports database.

Disproportionality analyses are increasingly gaining acceptance as signal detection tools for drug adverse events. Their application to vaccine adverse events has not been well evaluated. Disproportionality analyses based on the Multi-Item Gamma Poisson Shrinkage principle (MGPS) were applied to spontaneous adverse events reports for five vaccines with different reporting profiles.

Glucose and pharmacological modulators of ATP-sensitive K+ channels control [Ca2+]c by different mechanisms in isolated mouse alpha-cells.

Objective: We studied how glucose and ATP-sensitive K(+) (K(ATP)) channel modulators affect alpha-cell [Ca(2+)](c).

Research Design And Methods: GYY mice (expressing enhanced yellow fluorescent protein in alpha-cells) and NMRI mice were used. [Ca(2+)](c), the K(ATP) current (I(KATP), perforated mode) and cell metabolism [NAD(P)H fluorescence] were monitored in single alpha-cells and, for comparison, in single beta-cells.

Restoration of an impaired TGF-beta1 autocrine growth-inhibitory circuit results in growth inhibition of ovarian epithelial cancer cells and complete inhibition of their tumorigenicity.

The disruption of the transforming growth factor beta1 (TGF-beta1) autocrine growth-suppressive circuit is a major and possibly early event mediating the malignant transformation of normal epithelia. TGF-beta1 is secreted as a latent homodimer-peptide that, upon activation, binds a receptor complex. This in turn activates a signal transduction cascade that results in proliferation inhibition of epithelial cells.