Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: association with plasma fatty acid levels and insulin resistance

Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects. Methods and results: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038), higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of ω-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects. Conclusion: The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.

Ex vivo expansion of limbal stem cells is affected by substrate properties

Limbal epithelial stem cells play a key role in the maintenance and regulation of the corneal surface. Damage or destruction of these cells results in vascularisation and corneal opacity. Subsequent limbal stem cell transplantation requires an ex vivo expansion step and preserving cells in an undifferentiated state remains vital. In this report we seek to control the phenotype of limbal epithelial stem cells by the novel application of compressed collagen substrates. We have characterised the mechanical and surface properties of conventional collagen gels using shear rheology and scanning electron microscopy. In doing so, we provide evidence to show that compressive load can improve the stiffness of collagen substrates. In addition Western blotting and immunohistochemistry display increased cytokeratin 3 (CK3) protein expression relating to limbal epithelial cell differentiation on stiff collagen substrates. Such gels with an elastic modulus of 2900 Pa supported a significantly higher number of cells than less stiff collagen gels (3 Pa). These findings have substantial influence in the development of ocular surface constructs or experimental models particularly in the fields of stem cell research, tissue engineering and regenerative medicine.

An integrated dynamic whole life costing analysis for air distribution systems

Air distribution systems are one of the major electrical energy consumers in air-conditioned commercial buildings which maintain comfortable indoor thermal environment and air quality by supplying specified amounts of treated air into different zones. The sizes of air distribution lines affect energy efficiency of the distribution systems. Equal friction and static regain are two well-known approaches for sizing the air distribution lines. Concerns to life cycle cost of the air distribution systems, T and IPS methods have been developed. Hitherto, all these methods are based on static design conditions. Therefore, dynamic performance of the system has not been yet addressed; whereas, the air distribution systems are mostly performed in dynamic rather than static conditions. Besides, none of the existing methods consider any aspects of thermal comfort and environmental impacts. This study attempts to investigate the existing methods for sizing of the air distribution systems and proposes a dynamic approach for size optimisation of the air distribution lines by taking into account optimisation criteria such as economic aspects, environmental impacts and technical performance. These criteria have been respectively addressed through whole life costing analysis, life cycle assessment and deviation from set-point temperature of different zones. Integration of these criteria into the TRNSYS software produces a novel dynamic optimisation approach for duct sizing. Due to the integration of different criteria into a well- known performance evaluation software, this approach could be easily adopted by designers in busy nature of design. Comparison of this integrated approach with the existing methods reveals that under the defined criteria, system performance is improved up to 15% compared to the existing methods. This approach is interpreted as a significant step forward reaching to the net zero emission building in future.

Wave trapping in a two-dimensional sound-soft or sound-hard acoustic waveguide of slowly-varying width

In this paper we derive novel approximations to trapped waves in a two-dimensional acoustic waveguide whose walls vary slowly along the guide, and at which either Dirichlet (sound-soft) or Neumann (sound-hard) conditions are imposed. The guide contains a single smoothly bulging region of arbitrary amplitude, but is otherwise straight, and the modes are trapped within this localised increase in width. Using a similar approach to that in Rienstra (2003), a WKBJ-type expansion yields an approximate expression for the modes which can be present, which display either propagating or evanescent behaviour; matched asymptotic expansions are then used to derive connection formulae which bridge the gap across the cut-off between propagating and evanescent solutions in a tapering waveguide. A uniform expansion is then determined, and it is shown that appropriate zeros of this expansion correspond to trapped mode wavenumbers; the trapped modes themselves are then approximated by the uniform expansion. Numerical results determined via a standard iterative method are then compared to results of the full linear problem calculated using a spectral method, and the two are shown to be in excellent agreement, even when $\epsilon$, the parameter characterising the slow variations of the guide’s walls, is relatively large.

Using HIT to deliver integrated care for the frail elderly in the UK: current barriers and future challenges

In this paper we briefly describe the results of a 3 year project examining the use of Health Information Technologies (e.g., electronic patient record systems) to deliver integrated care. In particular, we focus on one group of patient (the frail elderly) and efforts to design an e-health supported healthcare pathway (the frail elderly pathway – FEP). The aim of FEP is to bring together clinicians and staff from health and social care and allow them to share patient information. Our findings show that progress in delivering a fully-supported and working FEP has been slow, not least because of the difficulties experienced by healthcare staff in using current IT systems. In addition, there are many strategic and technical issues which remain unresolved (e.g., systems interoperability).

A novel satellite mission concept for upper air water vapour, aerosol and cloud observations using integrated path differential absorption LiDAR limb sounding

We propose a new satellite mission to deliver high quality measurements of upper air water vapour. The concept centres around a LiDAR in limb sounding by occultation geometry, designed to operate as a very long path system for differential absorption measurements. We present a preliminary performance analysis with a system sized to send 75 mJ pulses at 25 Hz at four wavelengths close to 935 nm, to up to 5 microsatellites in a counter-rotating orbit, carrying retroreflectors characterized by a reflected beam divergence of roughly twice the emitted laser beam divergence of 15 µrad. This provides water vapour profiles with a vertical sampling of 110 m; preliminary calculations suggest that the system could detect concentrations of less than 5 ppm. A secondary payload of a fairly conventional medium resolution multispectral radiometer allows wide-swath cloud and aerosol imaging. The total weight and power of the system are estimated at 3 tons and 2,700 W respectively. This novel concept presents significant challenges, including the performance of the lasers in space, the tracking between the main spacecraft and the retroreflectors, the refractive effects of turbulence, and the design of the telescopes to achieve a high signal-to-noise ratio for the high precision measurements. The mission concept was conceived at the Alpbach Summer School 2010.

Influence of substrate on corneal epithelial cell viability within ocular surface models

Corneal tissue engineering has improved dramatically over recent years. It is now possible to apply these technological advancements to the development of superior in vitro ocular surface models to reduce animal testing. We aim to show the effect different substrates can have on the viability of expanded corneal epithelial cells and that those which more accurately mimic the stromal surface provide the most protection against toxic assault. Compressed collagen gel as a substrate for the expansion of a human epithelial cell line was compared against two well-known substrates for modeling the ocular surface (polycarbonate membrane and conventional collagen gel). Cells were expanded over 10 days at which point cell stratification, cell number and expression of junctional proteins were assessed by electron microscopy, immunohistochemistry and RT-PCR. The effect of increasing concentrations of sodium lauryl sulphate on epithelial cell viability was quantified by MTT assay. Results showed improvement in terms of stratification, cell number and tight junction expression in human epithelial cells expanded upon either the polycarbonate membrane or compressed collagen gel when compared to a the use of a conventional collagen gel. However, cell viability was significantly higher in cells expanded upon the compressed collagen gel. We conclude that the more naturalistic composition and mechanical properties of compressed collagen gels produces a more robust corneal model.

The role of phase separation and feed cycle length in leach beds coupled to methanogenic reactors for digestion of a solid substrate (Part 2): Hydrolysis, acidification and methanogenesis in a two-phase system

The effect of phase separation and batch duration on the trophic stages of anaerobic digestion was assessed for the first time in leach beds coupled to methanogenic reactors digesting maize (Zea mays). The system was operated for consecutive batches of 7, 14 and 28 days for ~120 days. Hydrolysis rate was higher the shorter the batch, reaching 8.5 gTSdestroyed d-1 in the 7-day system. Phase separation did not affect acidification but methanogenesis was enhanced in the short feed cycle leach beds. Phase separation was inefficient on the 7-day system, where ~89% of methane was produced in the leach bed. Methane production rate increased with shortening the feed cycle, reaching 3.523 l d-1 average in the 7-day system. Low strength leachate from the leach beds decreased methanogenic activity of methanogenic reactors’ sludges. Enumeration of cellulolytic and methanogenic microorganisms indicated a constant inoculation of leach beds and methanogenic reactors through leachate recirculation.

The role of phase separation and feed cycle length in leach beds coupled to methanogenic reactors for digestion of a solid substrate (Part 1): Optimisation of reactors’ performance

A two-phase system composed by a leach bed and a methanogenic reactor was modified for the first time to improve volumetric substrate degradation and methane yields from a complex substrate (maize; Zea mays). The system, which was operated for consecutive feed cycles of different durations for 120 days, was highly flexible and its performance improved by altering operational conditions. Daily substrate degradation was higher the shorter the feed cycle, reaching 8.5 g TSdestroyed d�1 (7-day feed cycle) but the overall substrate degradation was higher by up to 55% when longer feed cycles (14 and 28 days) were applied. The same occurred with volumetric methane yields, reaching 0.839 m3 (m3)�1 d�1. The system performed better than others on specific methane yields, reaching 0.434 m3 kg�1 TSadded, in the 14-day and 28-day systems. The UASB and AF designs performed similarly as second stage reactors on methane yields, SCOD and VFA removal efficiencies.

Understanding lake and catchment history as a tool for integrated lake management

Sustainable lake management for nutrient-enriched lakes must be underpinned by an understanding of both the functioning of the lake, and the origins of changes in nutrient loading from the catchment. To date, limnologists have tended to focus on studying the impact of nutrient enrichment on the lake biota, and the dynamics of nutrient cycling between the water column, biota and sediments within the lake. Relatively less attention has been paid to understanding the specific origins of nutrient loading from the catchment and nutrient transport pathways linking the lake to its catchment. As such, when devising catchment management strategies to reduce nutrient loading on enriched lakes, assumptions have been made regarding the relative significance of non-point versus point sources in the catchment. These are not always supported by research conducted on catchment nutrient dynamics in other fields of freshwater science. Studies on nutrient enrichment in lakes need to take account of the history of catchment use and management specific to each lake in order to devise targeted and sustainable management strategies to reduce nutrient loading to enriched lakes. Here a modelling approach which allows quantification of the relative contribution of nutrients from each specific point and non-point catchment source over the course of catchment history is presented. The approach has been applied to three contrasting catchments in the U.K. for the period 1931 to present. These are the catchment of Slapton Ley in south Devon, the River Esk in Cumbria and the Deben Estuary in Suffolk. Each catchment showed marked variations in the nature and intensity of land use and management. The model output quantifies the relative importance of point source versus non-point livestock and land use sources in each of the catchments, and demonstrates the necessity for an understanding of site-specific catchment history in devising suitable management strategies for the reduction of nutrient loading on enriched lakes.