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.

48 Hour Game Making Challenge - In Progress [Four Episodes]

Statement: Jams, Jelly Beans and the Fruits of Passion Let us search, instead, for an epistemology of practice implicit in the artistic, intuitive processes which some practitioners do bring to situations of uncertainty, instability, uniqueness, and value conflict. (Schön 1983, p40) Game On was born out of the idea of creative community; finding, networking, supporting and inspiring the people behind the face of an industry, those in the mist of the machine and those intending to join. We understood this moment to be a pivotal opportunity to nurture a new emerging form of game making, in an era of change, where the old industry models were proving to be unsustainable. As soon as we started putting people into a room under pressure, to make something in 48hrs, a whole pile of evolutionary creative responses emerged. People refashioned their craft in a moment of intense creativity that demanded different ways of working, an adaptive approach to the craft of making games – small – fast – indie. An event like the 48hrs forces participants’ attention on the process as much as the outcome. As one game industry professional taking part in a challenge for the first time observed: there are three paths in the genesis from idea to finished work: the path that focuses on mechanics; the path that focuses on team structure and roles and the path that focuses on the idea, the spirit – and the more successful teams need to put the spirit of the work first and foremost. The spirit drives the adaptation, it becomes improvisation. As Schön says: “Improvisation consists on varying, combining and recombining a set of figures within the schema which bounds and gives coherence to the performance.” (1983, p55). This improvisational approach is all about those making the games: the people and the principles of their creative process. This documentation evidences the intensity of their passion, determination and the shit that they are prepared to put themselves through to achieve their goal – to win a cup full of jellybeans and make a working game in 48hrs. 48hr is a project where, on all levels, analogue meets digital. This concept was further explored through the documentation process. This set of four videos were created by Cameron Owen on the fly during the challenge using both the iphone video camera and editing software in order to be available with immediacy and allow the event audience to share the experience - and perhaps to give some insights into the creative process exposed by the 48 hour challenge. ____________________________ Schön, D. A. 1983, The Reflective Practitioner: How Professionals Think in Action, Basic Books, New York

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.