Adaptive Bayesian compound designs for dose finding studies

We consider the problem of how to efficiently and safely design dose finding studies. Both current and novel utility functions are explored using Bayesian adaptive design methodology for the estimation of a maximum tolerated dose (MTD). In particular, we explore widely adopted approaches such as the continual reassessment method and minimizing the variance of the estimate of an MTD. New utility functions are constructed in the Bayesian framework and are evaluated against current approaches. To reduce computing time, importance sampling is implemented to re-weight posterior samples thus avoiding the need to draw samples using Markov chain Monte Carlo techniques. Further, as such studies are generally first-in-man, the safety of patients is paramount. We therefore explore methods for the incorporation of safety considerations into utility functions to ensure that only safe and well-predicted doses are administered. The amalgamation of Bayesian methodology, adaptive design and compound utility functions is termed adaptive Bayesian compound design (ABCD). The performance of this amalgamation of methodology is investigated via the simulation of dose finding studies. The paper concludes with a discussion of results and extensions that could be included into our approach.

High-pressure Raman spectroscopic and other structural studies of hydrotalcites containing intercalated dicarboxylic acid anions

The results of pressure-tuning Raman spectroscopic, X-ray powder diffraction and solid-state 13C-NMR studies of selected dicarboxylate anions intercalated in a Mg-Al layered double hydroxide (talcite) lattice are reported. The pressure dependences of the vibrational modes are linear for pressures up to 4.6 GPa indicating that no phase transitions occur. The interlayer spacings show that the oxalate, malonate and succinate dianions are oriented perpendicular to the layers, but the glutarate and adipate are tilted. The solid-state 13C-NMR spectra of these materials show full chemical shift anisotropy and, therefore, the anions are not mobile at room temperature.

What once was old is new again: reviving an early-modern form of interdisciplinarity for socio-legal studies

Socio-legal studies are an essentially interdisciplinary enterprise. However, there is currently only one form of interdisciplinarity that most socio-legal scholars (and criminologists) recognise and work with. This form is derived from the idea that 'society itself' - and by this most scholars mean 'civil society' - drives the law. However, another, rival understanding of society, which we term the authoritarian-liberal statist understanding that slipped from view in the late seventeenth century and remained obscure from then until now, may be used to generate another form of interdisciplinarity for sOcio-legal studies (and for criminology). However, this rival understanding of society does not simply allow us to reconfigure our notion of 'society'; it radically changes the role society plays in relation to the law. Two crucial points emerge from this rival account: first, society can no longer be understood as separable from (even though interacting with) the law; and second, society can no longer be understood as driving the law.

A systematic review of studies on socioeconomic inequalities in dietary intakes associated with weight gain and overweight/obesity conducted among European adults

This Review examined socioeconomic inequalities in intakes of dietary factors associated with weight gain, overweight/obesity among adults in Europe. Literature searches of studies published between 1990 and 2007 examining socioeconomic position (SEP) and the consumption of energy, fat, fibre, fruit, vegetables, energy-rich drinks and meal patterns were conducted. Forty-seven articles met the inclusion criteria. The direction of associations between SEP and energy intakes were inconsistent. Approximately half the associations examined between SEP and fat intakes showed higher total fat intakes among socioeconomically disadvantaged groups. There was some evidence that these groups consume a diet lower in fibre. The most consistent evidence of dietary inequalities was for fruit and vegetable consumption; lower socioeconomic groups were less likely to consume fruit and vegetables. Differences in energy, fat and fibre intakes (when found) were small-to-moderate in magnitude; however, differences were moderate-to-large for fruit and vegetable intakes. Socioeconomic inequalities in the consumption of energy-rich drinks and meal patterns were relatively under-studied compared with other dietary factors. There were no regional or gender differences in the direction and magnitude of the inequalities in the dietary factors examined. The findings suggest that dietary behaviours may contribute to socioeconomic inequalities in overweight/obesity in Europe. However, there is only consistent evidence that fruit and vegetables may make an important contribution to inequalities in weight status across European regions.