Guy Freeman

SUMMARY: We examined factors affecting the immunogenicity of trivalent inactivated influenza vaccination (TIV) in children using the antibody titres of children participating in a Hong Kong community-based study. Antibody titres of strains included in the 2009–2010 northern hemisphere TIV [seasonal A(H1N1), seasonal A(H3N2) and B (Victoria lineage)] and those not included in the TIV [2009 pandemic A(H1N1) and B (Yamagata lineage)] were measured by haemagglutination inhibition immediately before and 1 month after vaccination. Multivariate regression models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following vaccination. Statistically significant rises in geometric mean antibody titres were observed against all strains, with a wide variety of standard deviations and correlations in rises observed, with the influenza type B antibodies showing more variability than the type A antibodies. The dynamics of antibody titres after vaccination can be used in more complex models of antibody dynamics in populations.

Background: Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. Methods: A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. Results: Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). Conclusions: The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy.

Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.

A new tree-based graphical model --- the dynamic staged tree --- is proposed for modelling discrete-valued discrete-time multivariate processes which are hypothesised to exhibit symmetries in how some intermediate situations might unfold. We define and implement a one-step-ahead prediction algorithm with the model using multi-process modelling and the power steady model that is robust to short-term variations in the data yet sensitive to underlying system changes. We demonstrate that the whole analysis can be performed in a conjugate way so that the potentially vast model space can be traversed quickly and then results communicated transparently. We also demonstrate how to analyse a general set of causal hypotheses on this model class. Our techniques are illustrated using a simple educational example.

Over the last 50 years there has been an enormous explosion in developing full distributional analogues of the Kalman filter. In this paper we explore how some of the second‐order processes discovered by Kalman have their analogues in Bayesian state space models. Many of the analogues in the lierature need to be calculated using numerical methods like Markov chain Monte Carlo so they retain, or even enhance, the descriptive power of the Kalman filter, but at the cost of reduced transparency. However, if the analogues are drawn properly, elegant recurrence relationships—like those of the Kalman filter—can still be developed that apply, at least, for one‐step‐ahead forecast distributions. In this paper we explore the variety of ways such models have been built, in particular with respect to graphical time series models. Copyright © 2010 John Wiley & Sons, Ltd.

The class of chain event graph models is a generalisation of the class of discrete Bayesian networks, retaining most of the structural advantages of the Bayesian network for model interrogation, propagation and learning, while more naturally encoding asymmetric state spaces and the order in which events happen. In this paper we demonstrate how with complete sampling, conjugate closed form model selection based on product Dirichlet priors is possible, and prove that suitable homogeneity assumptions characterise the product Dirichlet prior on this class of models. We demonstrate our techniques using two educational examples.

Objectives: We demonstrate the use of health economics to guide investment decisions in regenerative medicine. Our examples are based on proposed tissue engineering applications in the urinary tract. We show that health economics have a role in strengthening the supply side, not just the demand side of the health economy. Methods: We reviewed the epidemiology and treatment of the clinical conditions where TE of urothelium may be considered using literature identified from a range of sources including electronic databases, article bibliographies and references, online articles and expert opinion in the field. Results: Careful analysis of current best treatment suggested that urethral defects and bladder resection for cancer offered the most propitious applications of TE. The headroom for engineered urethral tissue was estimated at £186. This is unlikely to be large enough to support the launch of a TE product populated with viable cells. The headroom for TE bladder, on the other hand, was estimated at around £16 268. However, the market size is limited reducing potential profitability. Conclusions: The Headroom Method can help inform instrumental decisions concerning new treatments without having to build a complex model with very wide parameter uncertainty. Copyright © 2007 John Wiley & Sons, Ltd.