Glycaemic effects of non-statin lipid-lowering therapies

Since the publication of the JUPITER trial, attention has been focused on the adverse glycemic effects of statin therapy. Although the modest increase in the risk of new diabetes mellitus is outweighed by the reduction in cardiovascular events for statins, emerging biochemical and genetic links between lipid metabolism and glycemic control raise the prospect of a broader diabetogenic effect of lipid-lowering therapies. For the novel and powerful PCSK9-inhibitor class available evidence does not support a major glycaemic effect with the results of large scale trials awaited although preliminary genetic data does suggest a link. In contrast, there is clear evidence of a diabetogenic effect for the now outdated but well-studied niacin. For ezetimibe and fibrates, evidence is scarce but currently broadly unconcerning. For now, the glycemic effects of lipid-lowering therapies should have a limited influence on clinical decision-making. Further study in this topical area is needed

Innovation Systems in the European Periphery: the Case of Ireland and Greece

Two decades ago, Greece and Ireland stood passive spectators of political, economic and technological developments at the core of an emerging European Economic Community. Away from the industrial centres of Europe, the attainment and application of new ideas, it seemed, had no place among the prescriptions of policy. The pursuit of each country’s comparative advantage dictated that they be net consumers of technological wares invented elsewhere. And while a lot has changed in the meantime, a great deal has also endured. Today, innovation is no longer confined to the fringes of industrial policy; it features prominently, throughout the continent, as ‘the solution’ to the re-discovered riddle of competitiveness. Ideas on how to best mobilise intellectual assets for innovation abound. Theory suggests that institutions are important in shaping productive efforts towards innovation; the experiences of Ireland and Greece offer a fitting testing ground. Ireland has made strides in the FDI route to prosperity, no longer labelled a cohesion country. Greece however faces pressing economic problems, in the aftermath of celebrated, largesse-fuelled growth. Over the period in question though, nowhere else have the differences between the two countries become more accentuated (and apparent), as in matters of innovation. We propose that the key to these differences lies with the drafting of policy and the consequent shaping of their institutions. We observe that importing solutions from abroad, with Greece looking to Brussels and Ireland to the US, was central to their respective experiences.

REFLECTION AND BRAGG SCATTERING ALONG ROCKY SHORES

Field observations of shoreline reflection and Bragg scattering for sea and swell waves along varying rocky shores from Monterey to Santa Cruz, CA, are described in comparison to sandy shores. The estimates are derived from directional spectra obtained primarily from Global Positioning System (GPS)-based Spotter wave-buoys. Wave reflection and Bragg scattering vary by shoreline type, with sandy shores reflecting up to 23% and rocky shores reflecting up to 30% at rocky platforms. However, rocky shores with cliffs reflected up to 14% and rough rocky shores up to 8%. A new estimator is proposed that accounts for the decrease in reflection for rocky shores associated with increasing shoreline roughness and works well for both rocky and sandy shores (r2=0.45). Bragg scattering was expected along rocky shores due to the large bottom roughness and scales that coincide with the resonant response for sea and swell waves. However, the absence of Bragg scattering is believed to be associated with the non-uniformity of the bottom roughness and moderate bottom profile slope, which leads to an insufficient number of wave-bottom interactions for development. The directional narrowing with decreasing water depth is similar to sandy shores. The study describes aspects of sea swell transformation that occurs for rocky shores with observations and theory.Outstanding ThesisLieutenant, Royal Australian NavyApproved for public release. Distribution is unlimited

The study of a new and specific proline cleaving peptidase from bovine serum

Prolyl oligopeptidase is a serine peptidase characterised by oligoendopeptidase activity. Definitive evidence for the discrete biological role of prolyl oligopeptidase remains unknown, though its role in the maturation and degradation of peptide hormones and neuropeptides has been implicated. A second activity that readily cleaves the specific prolyl oligopeptidase substrate Z-Gly-Pro-AMC was previously discovered in bovine serum. Due to its complete insensitivity towards the classic prolyl oligopeptidase inhibitor Z-Pro-prolinal, this peptidase was designated Z-Proprolinal Insensitive Peptidase (ZIP). The study o f this new and specific proline cleaving endopeptidase from bovine serum is presented. ZIP was separated from prolyl oligopeptidase by phenyl sepharose hydrophobic interaction chromatography. The enzyme was further purified 30,197-fold, to homogeneity, using calcium phosphate cellulose, cibacron blue 3GA and gel filtration chromatography in an overall recovery o f 12% from bovine serum. Substrate specificity studies using kinetic, HPLC and LC-MS analysis of prolinecontaining peptides suggest that ZIP has an extended substrate-binding region in addition to the primary specificity site Sj. This analysis revealed at least five subsites to be involved in enzyme-substrate binding, with the smallest peptide cleaved being a tetrapeptide. A proline residue in position Pi was absolutely necessary therefore showing high primary substrate specificity for the Pro-X bond, while a preference for a hydrophobic residue at the C-terminal end o f the scissile bond (Pi) was evident. An affinity constant (Kn) o f270fM using Z-Gly-Pro-AMC was determined. Diisopropylfluorophosphate inactivated ZIP resulting in an IC$o value o f lOOnM suggesting catalytic classification as a serine peptidase. ZIP showed complete insensitivity to the prolyl oligopeptidase specific inhibitors, Fmoc-Ala-pyrrCN and ZPhe-Pro-BT and showed no immunological cross-reactivity with an anti-human prolyl oligopeptidase antibody. Internal peptide sequence analysis o f ZIP identified it as seprase, a member o f the serine integral membrane peptidases. This protein is overexpressed by tumour cells and may possibly play a significant role in their invasion

Point Doppler velocimetry measurements in circular jets

Improvements have been made to an existing 2-component Point Doppler Velocimetry (PDV) system to improve instrument accuracy and repeatability and to reduce mean velocity offset. Most importantly, the original iodine cells have been replaced by vapor-limited iodine cells that are not influenced by room temperature variations. PDV is a non-intrusive laser based flow measurement technique with capabilities that are similar to hot wire anemometry, but without inserting a probe into the flow. The insertion of a probe into a flow can affect the flow, resulting in inaccurate measurements.;PDV measurements for 1 inch diameter standard, swirling, and annular jets have been made at a nominal exit velocity of 60 m/s, corresponding to a Reynolds number of 100,000. Measurements of radial profiles of mean and RMS velocities were taken for each jet from the jet exit to X/D=12 at nine different X locations. Also, centerline velocity profiles were taken from the jet exit to X/D=12. Comparisons between hot wire anemometry and PDV measurements have been made for standard and swirling jets, and PDV data repeatability has been judged by multiple runs for each jet.;Hot wire anemometry measurements in the swirling jet appear to be inaccurate for X/D ≤ 4 due to the inability of the hot wire anemometer to accurately measure two-dimensional flow velocities. The PDV and hot wire comparisons for the standard jet have good correlation for the mean velocity; however, the RMS velocities do not agree. PDV measurements of the axial and circumferential mean velocities exhibited an uncertainty and repeatability of 2 m/s. This error, for the axial mean velocity, was of the same order as was produced by using a different calibration from the same day. PDV RMS velocities exhibited a repeatability of 0.5--1.0 m/s, and generally are about one half as large as the hot wire anemometer RMS velocities

THE EFFECT OF SHELTERWOOD-CUT OAK FORESTRY PRACTICES ON BREEDING BIRD SUCCESS

Populations of breeding birds were studied on two shelterwood-cut oak stands in Buckingham County, Virginia. These two tracts, Harris East and Harris West, were cut in 1996 and a Breeding Bird Census has been conducted on these tracts since 1997. This study is part of an ongoing effort to collect pre-bum data, and document the diversity of avian species utilizing this habitat. The changes in avian species present on the Harris East and Harris West plots is important to know so that the effects of shelterwood-cut forestry practices can be understood better. The data collected showed that, by changing the type of habitat from a mature closed canopy secondary growth forest to a shrub dominated open canopy forest, shelterwood-cut forestry practices have had a major impact on avian species present on the Harris East and Harris West plots. The shrub layer held over twice as many territories per acre than in the initial study conducted in 1997, increasing from 1.09 territories per acre to 3.54 territories per acre because of an increase in shrub height and density. Birds that are characteristic of forest habitats, such as the Eastern Wood-pewee (Contopus virens) and Wood Thrush (Hylocichla mustelina) were found on both plots along with an influx of species characteristic of shrub habitats