Impact of increasing resolution and a warmer climate on extreme weather from NH extra-tropical cyclones

The effect of a warmer climate on the properties of extra-tropical cyclones is investigated using simulations of the ECHAM5 global climate model at resolutions of T213 (60 km) and T319 (40 km). Two periods representative of the end of the 20th and 21st centuries are investigated using the IPCC A1B scenario. The focus of the paper is on precipitation for the NH summer and winter seasons, however results from vorticity and winds are also presented. Similar number of events are identified at both resolutions. There are, however, a greater number of extreme precipitation events in the higher reso- lution run. The difference between maximum intensity distributions are shown to be statistically significant using a Kolmogorov-Smirnov test. A Generalised Pareto Distribution is used to analyse changes in extreme precipitation and wind events. In both resolutions, there is an increase in the number of ex- treme precipitation events in a warmer climate for all seasons, together with a reduction in return period. This is not associated with any increased verti- cal velocity, or with any increase in wind intensity in the winter and spring. However, there is an increase in wind extremes in the summer and autumn associated with tropical cyclones migrating into the extra-tropics.

Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release.

Production of pH-responsive microparticles by spray drying: investigation of experimental parameter effects on morphological and release properties

During spray drying, emphasis is placed on process optimisation to generate favourable particle morphological and flow properties. The effect of the initial feed solution composition on the drug release from the prepared microparticles is rarely considered. We investigated the effects of solvent composition, feed solution concentration and drug-loading on sodium salicylate, hydrocortisone and triamcinolone release from spray dried Eudragit L100 microparticles. Eudragit L100 is a pH-responsive polymer whose dissolution threshold is pH 6 so dissolution testing of the prepared microparticles at pH 5 and 1.2 illustrated non-polymer controlled burst release. Increasing the water content of the initial ethanolic feed solution significantly reduced hydrocortisone burst release at pH 5, as did reducing the feed solution concentration. These findings caution that changes in feed solution concentration or solvent composition not only affect particles’ morphological characteristics but can also negatively alter their drug release properties. This work also illustrate that drug-free microparticles can have different morphological properties to drug-loaded microparticles. Therefore, process optimisation needs to be carried out using drug-loaded systems. Depending on the physicochemical properties of the encapsulated API, drug-loading can affect the polymer solubility in the initial feed solution with consequent impact on microparticles morphological and release properties.

Using pH abnormalities in diseased skin to trigger and target topical therapy

Abstract Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules. Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined. Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin.

A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components

Objective To examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia. Methods Healthy men (n = 112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0 min) and lunch (330 min). Lipids and glucose were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples. Results Subjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P≤0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (maxC) were significantly greater in men with ≥ 3 than < 3 components (P < 0.001), whereas incremental AUC was greater in those with 3 than 0/1 and 2, and 4/5 compared with 2 components (P < 0.04). For glucose, maxC after the test breakfast (0-330 min) and total AUC (0-480 min) were higher in men with ≥ 3 than < 3 components (P≤0.001). Conclusions Our data analysis has revealed a linear trend between increasing numbers of MetS components and magnitude (AUC) of the postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥ 3 MetS components.

The ecology of crusading: investigating the environmental impact of holy war and colonisation at the frontiers of medieval Europe

The Crusades in the Near East, eastern Baltic and Iberian Peninsula (in the context of the Reconquest/reconquista) were accompanied by processes of colonisation, characterising the expansion of medieval Europe and resulting in the creation of frontier societies at the fringes of Christendom. Colonisation was closely associated with — indeed, depended on — the exploitation of local environments, but this dimension is largely missing from studies of the crusading frontiers. This paper, the product of a European Science Foundation Exploratory Workshop on 'The Ecology of Crusading' in 2009, surveys the potential for investigating the environmental impact of the crusading movement in all three frontier regions. It considers a diverse range of archaeological, palaeoenvironmental and written sources, with the aim of situating the societies created by the Crusades within the context of medieval colonisation and human ecological niche construction. It demonstrates that an abundant range of data exists for developing this largely neglected and disparately studied aspect of medieval frontier societies into a significant research programme.

The printed page

In the year 1702 two books were published, in Oxford and Paris, that can now be seen as defining the presses that produced them. In Paris, the Imprimerie Royale issued the Médailles sur les principaux évènements du règne de Louis le Grand, a large folio of text and plates intended to glorify the regime of Louis XIV. In Oxford, the first, large format volume of Clarendon’s The history of the rebellion appeared; painstakingly edited at Christ Church, it brought prestige and profit to the University. Both were considerable statements of publishing intent in graphic form: both were sumptuous, and both used types and decorations reserved to their respective presses. But the French book points the way to future developments in typography, particularly in the design of type, while the Oxford book is a summation of the past, and its types and page design would be abandoned by the Oxford press in little more than thirty years. Tracing the printed pages of Oxford books from the late sixteenth to the mid-eighteenth century shows changes that parallel wider developments in English and European typography, but from a distinctly Oxford perspective.

A carbamazepine-indomethacin (1:1) cocrystal produced by milling

An X-ray amorphous mixture of carbamazepine and indomethacin transforms upon annealing to produce a novel 1:1 cocrystal, whose structure has been determined from laboratory powder X-ray diffraction (PXRD) data.

Penciclovir solubility in Eudragit films: a comparison of X-ray, thermal, microscopic and release rate techniques

The solubility of penciclovir (C10N5O3H17) in a novel film formulation designed for the treatment of cold sores was determined using X-ray, thermal, microscopic and release rate techniques. Solubilities of 0.15–0.23, 0.44, 0.53 and 0.42% (w/w) resulted for each procedure. Linear calibration lines were achieved for experimentally and theoretically determined differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) data. Intra- and inter-batch data precision values were determined; intra values were more precise. Microscopy was additionally useful for examining crystal shape, size distribution and homogeneity of drug distribution within the film. Whereas DSC also determined melting point, XRPD identified polymorphs and release data provided relevant kinetics.