A new approach to planning in vitro and in vivo experiments for cardiovascular stents. (1) Fundamentals of design procedures

Copyright @ 2000 Pacini Editore SpAWhile the use of cardiovascular stents is internationally widespread re-stenosis remains a common problem. There are a number of different designs, and this project seeks for design improvements leading to a reduction in re-stenosis rates. The haemodynamics of the stent as used in a patient is viewed as one of the major concerns, and the authors have already applied Computational Fluid Dynamics in investigating this. In this more comprehensive study, however, the novel approach of applying two formal engineering design procedures is used, namely Genetic Algorithms (GA) and Robust Engineering Design (RED). In this paper, the two procedures are explained and compared in the context of their application to the design of stents

Catecholamines and cognition after traumatic brain injury

Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner

A new approach to planning in vitro and in vivo experiments for cardiovascular stents. (2) Planning of experiments

Copyright @ 2000 Pacini Editore SpAWithin our overall project to improve the design of stents in terms of reduced rates of re-stenosis, there are three main methods, namely computer simulation and in vitro and in vivo experiments. These methods are closely integrated using contemporary design procedures described below, especially to accommodate patient-to-patient variation. Clinical experience shows that a small variation has considerable effects on flow characteristics of stents and in engineering terms may be described as a ‘geometric risk factor’. The Robust Engineering Design procedure readily incorporates this factor which may thus become a component feature in our experimental planning. We envisage that this approach could be applied to other invasive implants with a view to enhancing their quality

Are the demographics for squamous cell cancer in the head and neck changing in the United Kingdom?

Head and neck squamous cell carcinoma is well known to be more common in men than women. Smoking and alcohol are the key risk factors causing such malignancies and there are several publications which have suggested that the prevalence of these diseases is increasing more in women than in men in western countries due to increased smoking and alcohol use.We collected our data at the Institute of Laryngology and Otology from the last 45 years and analysed the disease ratios in male to female patients in different sites within the head and neck. Our results revealed a decreasing male to female ratio, though this was not statistically significant. However, it draws attention to the increasing number of women with head and neck cancer, which may reflect their increasing use of cigarettes and alcohol

Inhibition of food intake in obese subjects by peptide YY3-36

Background: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.Methods: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.Results: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r=-0.84, P<0.001).Conclusions: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity

Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion

Transposon mutagenesis has been applied to a hyper-invasive clinical isolate of Campylobacter jejuni, 01/51. A random transposon mutant library was screened in an in vitro assay of invasion and 26 mutants with a significant reduction in invasion were identified. Given that the invasion potential of C. jejuni is relatively poor compared to other enteric pathogens, the use of a hyper-invasive strain was advantageous as it greatly facilitated the identification of mutants with reduced invasion. The location of the transposon insertion in 23 of these mutants has been determined; all but three of the insertions are in genes also present in the genome-sequenced strain NCTC 11168. Eight of the mutants contain transposon insertions in one region of the genome (∼14 kb), which when compared with the genome of NCTC 11168 overlaps with one of the previously reported plasticity regions and is likely to be involved in genomic variation between strains. Further characterization of one of the mutants within this region has identified a gene that might be involved in adhesion to host cells

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI

Zooplankton patchiness and the associated shoaling response of the temperate reef fish Trachinops taeniatus

The grouping behaviour of fishes plays an important role in the success of the group and individual in terms of foraging, reproduction and predator avoidance. The temperate Sydney (Australia) reef fish species Trachinops taeniatus was investigated between February and September 2002 to determine whether there was a relationship between shoal dynamics and zooplankton prey distribution. The diet of T. taeniatus consisted mainly of Copepoda. T. taeniatus shoals were strongly associated with the largest patches of Copepoda, with shoal size increasing as prey density increased. Available Copepoda per fish, however, decreased with shoal size, presenting a possible 'overmatching' foraging situation. The present study suggests there may be an optimum shoal size to achieve maximum prey intake, and that shoal location and size may be linked to the distribution of zooplankton prey. © Inter-Research 2005

Assessment of the performance of alternative aviation fuel in a modern air-spray combustor (MAC)

Recent concerns over energy security and environmental considerations have highlighted the importance of finding alternative aviation fuels. It is expected that coal and biomass derived fuels will fulfil a substantial part of these energy requirements. However, because of the physical and chemical difference in the composition of these fuels, there are potential problems associated with the efficiency and the emissions of the combustion process. Over the past 25 years Computational Fluid Dynamics (CFD) has become increasingly popular with the gas turbine industry as a design tool for establishing and optimising key parameters of systems prior to starting expensive trials. In this paper the performance of a typical aviation fuel, kerosene, an alternative aviation fuel, biofuel and a blend have been examined using CFD modelling. A good knowledge of the kinetics of the reaction of bio aviation fuels at both high and low temperature is necessary to perform reliable simulations of ignition, combustion and emissions in aero-engine. A novel detailed reaction mechanism was used to represent aviation fuel oxidation mechanism. The fuel combustion is calculated using a 3D commercial solver using a mixture fraction/pdf approach. Firstly, the study demonstrates that CFD predictions compare favourably with experimental data obtained by QinetiQ for a Modern Airspray Combustor (MAC) when used with traditional jet fuel (kerosene). Furthermore, the 3D CFD model has been refined to use the laminar flamelet model (LFM) approach that incorporates recently developed chemical reaction mechanisms for the bio-aviation fuel. This has enabled predictions for the bio-aviation fuel to be made. The impact of using the blended fuel has been shown to be very similar in performance to that of the 100% kerosene, confirming that aircraft running on 20% blended fuel should have no significant reduction in performance. It was also found that for the given operating conditions there is a significant reduction in performance when 100% biofuel if used. Additionally, interesting predictions were obtained, related to NOx emissions for the blend and 100% biofuel