Proposed best practice for statisticians in the reporting and publication of pharmaceutical industry-sponsored clinical trials

In this paper we set out what we consider to be a set of best practices for statisticians in the reporting of pharmaceutical industry-sponsored clinical trials. We make eight recommendations covering: author responsibilities and recognition; publication timing; conflicts of interest; freedom to act; full author access to data; trial registration and independent review. These recommendations are made in the context of the prominent role played by statisticians in the design, conduct, analysis and reporting of pharmaceutical sponsored trials and the perception of the reporting of these trials in the wider community.

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.

Equivalence of weak formulations of the steady water waves equations

We prove the equivalence of three weak formulations of the steady water waves equations, namely: the velocity formulation, the stream function formulation and the Dubreil-Jacotin formulation, under weak Hölder regularity assumptions on their solutions.

Formulations of viable cells for oral delivery

This invention relates to solid formulations for the oral delivery of live microbial cells which comprise dried viable cells and small amounts of a bile acid binding agent, for example, an anion exchange resin such as cholestyramine. The presence of bile acid binding agents in the formulation significantly increases the survival of the cells in the intestinal tract and facilitates delivery of the viable cells to the intestine.

RAMI4PILPS: An intercomparison of formulations for the partitioning of solar radiation in land surface models

[1] Remotely sensed, multiannual data sets of shortwave radiative surface fluxes are now available for assimilation into land surface schemes (LSSs) of climate and/or numerical weather prediction models. The RAMI4PILPS suite of virtual experiments assesses the accuracy and consistency of the radiative transfer formulations that provide the magnitudes of absorbed, reflected, and transmitted shortwave radiative fluxes in LSSs. RAMI4PILPS evaluates models under perfectly controlled experimental conditions in order to eliminate uncertainties arising from an incomplete or erroneous knowledge of the structural, spectral and illumination related canopy characteristics typical for model comparison with in situ observations. More specifically, the shortwave radiation is separated into a visible and near-infrared spectral region, and the quality of the simulated radiative fluxes is evaluated by direct comparison with a 3-D Monte Carlo reference model identified during the third phase of the Radiation transfer Model Intercomparison (RAMI) exercise. The RAMI4PILPS setup thus allows to focus in particular on the numerical accuracy of shortwave radiative transfer formulations and to pinpoint to areas where future model improvements should concentrate. The impact of increasing degrees of structural and spectral subgrid variability on the simulated fluxes is documented and the relevance of any thus emerging biases with respect to gross primary production estimates and shortwave radiative forcings due to snow and fire events are investigated.

Lightly branched comb polyesters: application in fast drying solvent-borne coating formulations

Novel oxazoline-based comb-polymers possessing linoleyl or oleic side chains have been synthesized and used to produce low viscosity coatings. Inclusion of the polymers in model paint formulations results in coatings that exhibit faster drying times than commercially available alkyd resin formulations. The comb polymers were produced from diol substituted oxazoline monomers that were synthesized through a scalable, solvent free protocol and purified by simple recrystallisation. Co-polymerisation of the oxazolines with adipic acid at 160 °C in the bulk resulted in the targeted polyester comb type polymers. The polymers were soluble in a range of organic solvents and compatible with commercial alkyd resins. Model paint formulations containing up to 40 wt% of the linoleyl-based comb polymers exhibited a dramatic reduction in viscosity (from 35 to 13 Poise at 25 °C) with increasing quantities of polymer added. Dynamic mechanical analysis (DMA) studies revealed that the drying rate of the model paint formulations containing the comb polymers was enhanced when compared with that of commercial alkyd resins.