Registered and antiregistered phase separation of mixed amphiphilic bilayers

We derive a mean-field free energy for the phase behaviour of coupled bilayer leaflets, which is implicated in cellular processes and important to the design of artificial membranes. Our model accounts for amphiphile-level structural features, particularly hydrophobic mismatch, which promotes antiregistration (AR), in competition with the `direct' trans-midplane coupling usually studied, promoting registration (R). We show that the phase diagram of coupled leaflets allows multiple \textit{metastable} coexistences, then illustrate the kinetic implications with a detailed study of a bilayer of equimolar overall composition. For approximate parameters estimated to apply to phospholipids, equilibrium coexistence is typically registered, but metastable antiregistered phases can be kinetically favoured by hydrophobic mismatch. Thus a bilayer in the spinodal region can require nucleation to equilibrate, in a novel manifestation of Ostwald's `rule of stages'. Our results provide a framework for understanding disparate existing observations, elucidating a subtle competition of couplings, and a key role for phase transition kinetics in bilayer phase behaviour.Comment: Final authors' version. Important typo in Eq. A24 corrected. To appear in Biophysical Journa

Simplification and generalization of large scale data for roads : a comparison of two filtering algorithms

This paper reports the results of an in-depth study which investigated two algorithms for line simplification and caricatural generalization (namely, those developed by Douglas and Peucker, and Visvalingam, respectively) in the context of a wider program of research on scale-free mapping. The use of large-scale data for man-designed objects, such as roads, has led to a better understanding of the properties of these algorithms and of their value within the spectrum of scale-free mapping. The Douglas-Peucker algorithm is better at minimal simplification. The large-scale data for roads makes it apparent that Visvalingam's technique is not only capable of removing entire scale-related features, but that it does so in a manner which preserves the shape of retained features. This technique offers some prospects for the construction of scale-free databases since it offers some scope for achieving balanced generalizations of an entire map, consisting of several complex lines. The results also suggest that it may be easier to formulate concepts and strategies for automatic segmentation of in-line features using large-scale road data and Visvalingam's algorithm. In addition, the abstraction of center lines may be facilitated by the inclusion of additional filtering rules with Visvalingam's algorithm

Outcome measures in rheumatoid arthritis randomised trials over the last 50 years

BACKGROUND: The development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology. METHODS: An observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study. RESULTS: Since the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial. CONCLUSIONS: This observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities