Effectiveness and cost-effectiveness of prognostic markers in prostate cancer

This paper demonstrates how economic modelling can be used to derive estimates of the cost-effectiveness of prognostic markers in the management of clinically localised and moderately graded prostate cancer. The model uses a Markov process and is populated using published evidence and local data. The robustness of the results has been tested using sensitivity analysis. Three treatment policies of 'monitoring' (observation), radical prostatectomy, or a selection-based management policy using DNA-ploidy as an experimental marker, have been evaluated. Modelling indicates that a policy of managing these tumours utilising experimental markers has an estimated cost per quality-adjusted life year (QALY) of pound 12 068. Sensitivity analysis shows the results to be relatively sensitive to quality-of-life variables. If novel and experimental markers can achieve specificity in excess of 80%, then a policy of radical surgery for those identified as being at high risk and conservative treatment for the remainder would be both better for patients and cost-effective. The analysis suggests that a radical prostatectomy treatment policy for the moderately graded tumours (Gleason grades -7) modelled in this paper may be inferior to a conservative approach in the absence of reliable prognostic markers, being both more costly and yielding fewer QALYs

Pattern-based model-to-model transformation: Handling attribute conditions

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-02408-5_7Proceedings of Second International Conference, ICMT 2009, Zurich, Switzerland, June 29-30, 2009Pattern-based model-to-model transformation is a new approach for specifying transformations in a declarative, relational and formal style. The language relies on patterns describing allowed or forbidden relations between two models, which are compiled into operational mechanisms to perform forward and backward transformations. In this paper, we extend the approach for handling attribute conditions expressed in some suitable logic, adapt the operational mechanisms based on graph transformation to relax attribute handling by constraint solving, and discuss heuristics for the compilation of patterns into rules.Work supported by the Spanish Ministry of Science and Innovation, projects METEORIC (TIN2008-02081),MODUWEB (TIN2006-09678) and FORMALISM (TIN2007-66523).Moreover, part of this work was done during a sabbatical leave of the third author at TU Berlin, with financial support from the Ministerio de Ciencia e Innovaci´on (grant ref. PR2008-0185). We thank the referees for their useful comment

HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia

© The American Physiological Society.Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 336 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. While general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30-± 0.9-fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88-± 2.24-fold change). We have identified that HLA-A is upregulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is upregulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia