Mathematical modelling of fibre-enhanced perfusion inside\ud a tissue-engineering bioreactor

We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue- engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy’s law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier–Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution

A novel technique for quantifying changes in vascular density, endothelial cell proliferation and protein expression in response to modulators of angiogenesis using the chick chorioallantoic membrane (CAM) assay

Reliable quantitative evaluation of molecular pathways is critical for both drug discovery and treatment monitoring. We have modified the CAM assay to quantitatively measure vascular density, endothelial proliferation, and changes in protein expression in response to anti-angiogenic and pro-angiogenic agents. This improved CAM assay can correlate changes in vascular density with changes seen on a molecular level. We expect that these described modifications will result in a single in vivo assay system, which will improve the ability to investigate molecular mechanisms underlying the angiogenic response

Steps to Better Cardiovascular Health: How Many Steps Does It Take to Achieve Good Health and How Confident Are We in This Number?

Pedometers and other types of step-counting devices are growing in popularity with both researchers and practitioners. The focus of this article is on describing the most recent pedometer-related advances in terms of cardiovascular health. The emergent body of evidence suggests that pedometer-determined physical activity is related to a number of cardiovascular health outcomes and that intervention participants can realize modest changes in body mass index and blood pressure. Taking into consideration individual baseline values, tailored messages congruent with public health recommendations should promote incremental increases in steps/day on the order of an extra 3,000 to 4,000 (approximately 30 min) of at least moderate intensity and taken in at least 10-minute bouts. Additional health benefits accrue with greater increases. Of course, even more benefits are possible from engaging in vigorous physical activity, but this seems less appealing for most people. Pedometer-based guidelines are not intended to supplant existing public health recommendations, but rather supplement them

Targeted sequencing to identify novel genetic risk factors for deep vein thrombosis: a study of 734 genes

Essentials Deep vein thrombosis (DVT) has a large unknown genetic component. We sequenced coding areas of 734 hemostasis-related genes in 899 DVT patients and 599 controls. Variants in F5, FGA-FGG, CYP4V2-KLKB1-F11, and ABO were associated with DVT risk. Associations in KLKB1 and F5 suggest a more complex genetic architecture than previously thought. Summary: Background Although several genetic risk factors for deep vein thrombosis (DVT) are known, almost all related to hemostasis, a large genetic component remains unexplained. Objectives To identify novel genetic determinants by using targeted DNA sequencing. Patients/Methods We included 899 DVT patients and 599 controls from three case\u2013control studies (DVT-Milan, Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis [MEGA], and the Thrombophilia, Hypercoagulability and Environmental Risks in Venous Thromboembolism [THE-VTE] study) for sequencing of the coding regions of 734 genes involved in hemostasis or related pathways. We performed single-variant association tests for common variants (minor allele frequency [MAF] 65 1%) and gene-based tests for rare variants (MAF 64 1%), accounting for multiple testing by use of the false discovery rate (FDR). Results Sixty-two of 3617 common variants were associated with DVT risk (FDR 0.2). Conclusions We confirmed associations between DVT and common variants in F5,ABO,FGA\u2013FGG, and CYP4V2\u2013KLKB1\u2013F11, and observed secondary signals in F5 and CYP4V2\u2013KLKB1\u2013F11 that warrant replication and fine-mapping in larger studies

Developing tools for the safety specification in risk management plans: lessons learned from a pilot project.

PURPOSE: Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use. METHODS: Archive data from a successful MAA were utilised. Methods were assessed for demonstrating the extent of clinical safety experience, evaluating the sensitivity of the clinical trial data to detect treatment differences and identifying safety signals from adverse event and laboratory data to define the extent of safety knowledge with the drug. RESULTS: The extent of clinical safety experience was demonstrated by plots of patient exposure over time. Adverse event data were presented using dot plots, which display the percentages of patients with the events of interest, the odds ratio, and 95% confidence interval. Power and confidence interval plots were utilised for evaluating the sensitivity of the clinical database to detect treatment differences. Box and whisker plots were used to display laboratory data. CONCLUSIONS: This project enabled us to identify new evidence-based methods for presenting and evaluating clinical safety data. These methods represent an advance in the way safety data from clinical trials can be analysed and presented. This project emphasises the importance of early and comprehensive planning of the safety package, including evaluation of the use of epidemiology data