Advanced glycation end product (AGE) accumulation on Bruch's membrane: links to age-related RPE dysfunction.

PURPOSE: Advanced glycation end products (AGEs) accumulate during aging and have been observed in postmortem eyes within the retinal pigment epithelium (RPE), Bruch's membrane, and subcellular deposits (drusen). AGEs have been associated with age-related dysfunction of the RPE-in particular with development and progression to age-related macular degeneration (AMD). In the present study the impact of AGEs at the RPE-Bruch's membrane interface was evaluated, to establish how these modifications may contribute to age-related disease. METHODS: AGEs on Bruch's membrane were evaluated using immunohistochemistry. A clinically relevant in vitro model of substrate AGE accumulation was established to mimic Bruch's membrane ageing. Responses of ARPE-19 growing on AGE-modified basement membrane (AGE-BM) for 1 month were investigated by using a microarray approach and validated by quantitative (q)RT-PCR. In addition to identified AGE-related mRNA alterations, lysosomal enzyme activity and lipofuscin accumulation were also studied in ARPE-19 grown on AGE-BM. RESULTS: Autofluorescent and glycolaldehyde-derived AGEs were observed in clinical specimens on Bruch's membrane and choroidal extracellular matrix. In vitro analysis identified a range of dysregulated mRNAs in ARPE-19 exposed to AGE-BM. Altered ARPE-19 degradative enzyme mRNA expression was observed on exposure to AGE-BM. AGE-BM caused a significant reduction in cathepsin-D activity in ARPE-19 (P

Understanding New Product Project Performance

Purpose – The purpose of this paper is to summarize the accumulated body of knowledge on the performance of new product projects and provide directions for further research. Design/methodology/approach – Using a refined classification of antecedents of new product project performance the research results are meta-analyzed in the literature in order to identify the strength and stability of predictor-performance relationships. Findings – The results reveal that 22 variables have a significant relationship with new product project performance, of which only 12 variables have a sizable relationship. In order of importance these factors are the degree of organizational interaction, R&D and marketing interface, general product development proficiency, product advantage, financial/business analysis, technical proficiency, management skill, marketing proficiency, market orientation, technology synergy, project manager competency and launch activities. Of the 34 variables 16 predictors show potential for moderator effects. Research limitations/implications – The validity of the results is constrained by publication bias and heterogeneity of performance measures, and directions for the presentation of data in future empirical publications are provided. Practical implications – This study helps new product project managers in understanding and managing the performance of new product development projects. Originality/value – This paper provides unique insights into the importance of predictors of new product performance at the project level. Furthermore, it identifies which predictor-performance relations are contingent on other factors.

Product standardisation as a tool to control prescribing costs a case study of alginate liquid preparations

Introduction Product standardisation involves promoting the prescribing of pre-selected products within a particular category across a healthcare region and is designed to improve patient safety by promoting continuity of medicine use across the primary/secondary care interface, in addition to cost containment without compromising clinical care (i.e. maintaining safety and efficacy). Objectives To examine the impact of product standardisation on the prescribing of compound alginate preparations within primary care in Northern Ireland. Methods Data were obtained on alginate prescribing from the Northern Ireland Central Services Agency (Prescription Pricing Branch), covering a period of 43 months. Two standardisation promotion interventions were carried out at months 18 and 33. In addition to conventional statistical analyses, a simple interrupted time series analysis approach, using graphical interpretation, was used to facilitate interpretation of the data. Results There was a significant increase in the prescribed share of the preferred alginate product in each of the four health boards in Northern Ireland and a decrease in the cost per Defined Daily Dose for alginate liquid preparations overall. Compliance with the standardisation policy was, however, incomplete and was influenced to a marked degree by the activities of the pharmaceutical industry. The overall economic impact of the prescribing changes during the study was small (3.1%). Conclusion The findings suggested that product standardisation significantly influenced the prescribing pattern for compound alginate liquid preparations within primary care across Northern Ireland. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.