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.

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative.

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative.

Modelling survival data to account for model uncertainty: a single model or model averaging?

This study considered the problem of predicting survival, based on three alternative models: a single Weibull, a mixture of Weibulls and a cure model. Instead of the common procedure of choosing a single “best” model, where “best” is defined in terms of goodness of fit to the data, a Bayesian model averaging (BMA) approach was adopted to account for model uncertainty. This was illustrated using a case study in which the aim was the description of lymphoma cancer survival with covariates given by phenotypes and gene expression. The results of this study indicate that if the sample size is sufficiently large, one of the three models emerge as having highest probability given the data, as indicated by the goodness of fit measure; the Bayesian information criterion (BIC). However, when the sample size was reduced, no single model was revealed as “best”, suggesting that a BMA approach would be appropriate. Although a BMA approach can compromise on goodness of fit to the data (when compared to the true model), it can provide robust predictions and facilitate more detailed investigation of the relationships between gene expression and patient survival. Keywords: Bayesian modelling; Bayesian model averaging; Cure model; Markov Chain Monte Carlo; Mixture model; Survival analysis; Weibull distribution

Rejoinder to James Hamilton

Hamilton (2001) makes a number of comments on our paper (Harding and Pagan, 2002b). The objectives of this rejoinder are, firstly, to note the areas in which we agree; secondly, to define with greater clarity the areas in which we disagree; and, thirdly, to point to other papers, including a longer version of this response, where we have dealt with some of the issues that he raises. The core of our debate with him is whether one should use an algorithm with a specified set of rules for determining the turning points in economic activity or whether one should use a parametric model that features latent states. Hamilton begins his criticism by stating that there is a philosophical distinction between the two methods for dating cycles and concludes that the method we use “leaves vague and intuitive exactly what this algorithm is intended to measure”. Nothing is further from the truth. When seeking ways to decide on whether a turning point has occurred it is always useful to ask the question, what is a recession? Common usage suggests that it is a decline in the level of economic activity that lasts for some time. For this reason it has become standard to describe a recession as a decline in GDP that lasts for more than two quarters. Finding periods in which quarterly GDP declined for two periods is exactly what our approach does. What is vague about this?

James Street market, Brisbane : a subtropical retail case study

Climate change mitigation is driving demand for energy-efficient and environmentally conscious commercial buildings in Australia. In the Australian subtropics, high rainfall, warm weather and humidity present unique challenges and opportunities for the architects tasked with designing eco-sensitive projects. The case of the James Street Market in Brisbane’s Fortitude Valley shows that climate-responsive design is an effective approach for reducing the environmental impact of commercial developments. The James Street Market combines climate-responsiveness, environmentally sensitive design strategies and smart planning to create a more sustainable retail precinct. This paper details the design strategies featured in the James Street Market, the project that kicked off a renaissance in climate-responsive commercial building design in Brisbane.

Entertaining the E Word : Barrie Kosky's On Ecstasy [A Review]

A review of Barrie Kosky's essay, On Ecstasy : Most of us describe the E word as a pleasant, out of this world experience—a type of boundless, artificial joy, deliberately induced by some kind of technicoloured drug. For others, it is that “lovey dovey” feeling. A spinning ceiling. Anything Lindt. For sensualist and soup connoisseur Barrie Kosky, it is easier than this. Being On Ecstasy involves, quite simply, his grandmother's chicken specialty—something warm and golden, surrendered with vegetables and a side of transcendental bliss. “A soup that took you to the beginning and end of time itself. A dazzling, pure, clear rhapsody” (7).

Continuous and pedagogically sound assessment : A new economy of power relations in Australian Law schools

In recent decades, assessment practices within Australian law schools have moved from the overwhelming use of end-of-year closed-book examinations to an increase in the use of a wider range of techniques. This shift is often characterised as providing a ‘better’ learning environment for students, contributing more positively to their own ‘personal development’ within higher education, or, considered along the lines of critical legal thought, as ‘liberating’ them from the ‘conservatising’ and ‘indoctrinating’ effects of the power relations that operate in law schools. This paper seeks to render problematic such liberal-progressive narratives about these changes to law school assessment practices. It will do so by utilising the work of French historian and philosopher Michel Foucault on power, arguing that the current range of assessment techniques demonstrates a shift in the ‘economy’ of power relations within the law school. Rather than ‘liberating’ students from relations of power, these practices actually extend the power relations through which students are governed. This analysis is intended to inform legal education research and assessment practice by providing a far more nuanced conceptual framework than one that seeks to ‘free’ law students from these ‘repressive’ practices, or hopes to ‘objectively’ contribute to their ‘personal development’.

Governing depression in Australian legal education : power, psychology and advanced liberal government

Legal educators in Australia have increasingly become concerned with the mental health of law students. The apparent risk posed by legal education to a student’s mental health has led to the deployment of a variety of measures to address these problems. By exploring these measures as productive power relations attempting to shape law students, this paper outlines how this government of depression is achieved, and the potential costs of these power relations. It examines one central Australian text offering advice about how students and law student societies can address depression, and argues that doing so not only involves students adopting particular practices of self-government to shape their legal personae, but also relies on an extension of the power relations of legal education. In addition, this paper will link this advice — which privatises the issue of depression, responsibilises individuals and communities, privileges psychological expertise, and seeks to govern ‘at a distance’ — to broader forms of social administration that presently characterise many Western societies. Doing so allows legal educators to reflect on the effects of their attempts to govern depression, and to consider new ways of altering the power relations of legal education.

Selling James Bond : product placement in the James Bond films

The character of James Bond for many people is intrinsically linked in their minds with particular brands – Aston Martin, Bollinger, Omega, Smirnoff vodka, and so on. This direct association between character and brand highlights the intrinsic role of product placement in the film industry, and in the James Bond films in particular. Selling James Bond: Product Placement in the James Bond Films provides a comprehensive overview of the history of product placement in the James Bond series – charting the progression of the practice and drawing direct correlations to significant cultural and historical events that impacted upon the number and types of products incorporated into the series. While primarily a financial arrangement, it is also important that the practice of product placement be examined and understood in relation to these cultural contexts, an area of research so far largely ignored by academic study. Through extensive content analysis of the official James Bond film series, as well as utilising directors’ commentary and industry reports, this book illustrates the strong impact specific cultural and historical events have had on the practice of product placement in the series. In doing so, it provides an exciting and in-depth “behind the scenes” look at the James Bond film series, and its complicated and sometimes contentious history of product placement. In the process, it charts the gradual emergence of product placement from the more traditional background shot to becoming so embedded in the actual film narrative that they have become simply yet another method for filmmakers to produce cultural meaning.