Bayesian modelling for spatially misaligned health areal data: a multiple membership approach

Diabetes prevalence is on the rise in the UK, and for public health strategy, estimation of relative disease risk and subsequent mapping is important. We consider an application to London data on diabetes prevalence and mortality. In order to improve the estimation of relative risks we analyse jointly prevalence and mortality data to ensure borrowing strength over the two outcomes. The available data involves two spatial frameworks, areas (middle level super output areas, MSOAs), and general practices (GPs) recruiting patients from several areas. This raises a spatial misalignment issue that we deal with by employing the multiple membership principle. Specifically we translate area spatial effects to explain GP practice prevalence according to proportions of GP populations resident in different areas. A sparse implementation in Stan of both the MCAR and GMCAR allows the comparison of these bivariate priors as well as exploring the different implications for the mapping patterns for both outcomes. The necessary causal precedence of diabetes prevalence over mortality allows a specific conditionality assumption in the GMCAR, not always present in the context of disease mapping

Proton-Ion Medical Machine Study (PIMMS), 2

The Proton-Ion Medical Machine Study (PIMMS) group was formed following an agreement between the Med-AUSTRON (Austria) and the TERA Foundation (Italy) to combine their efforts in the design of a cancer therapy synchrotron capable of accelerating either light ions or protons. CERN agreed to support and host this study in its PS Division. A close collaboration was also set up with GSI (Germany). The study group was later joined by Onkologie-2000 (Czech Republic). Effort was first focused on the theoretical understanding of slow extraction and the techniques required to produce a smooth beam spill for the conformal treatment of complex-shaped tumours with a sub-millimetre accuracy by active scanning with proton and carbon ion beams. Considerations for passive beam spreading were also included for protons. The study has been written in two parts. The more general and theoretical aspects are recorded in Part I and the specific technical design considerations are presented in the present volume, Part II. An accompanying CD-ROM contains supporting publications made by the team and data files for calculations. The PIMMS team started its work in January 1996 in the PS Division and continued for a period of four years

Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs

This article provides an overview of methods for reliability assessment of quantitative structure–activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation. Key words: QSAR acceptability criteria, QSAR applicability domain, QSAR reliability, QSAR uncertainty estimation, QSAR validation

Global Antifungal Profile Optimization of Chlorophenyl Derivatives against Botrytis cinerea and Colletotrichum gloeosporioides

Twenty-two aromatic derivatives bearing a chlorine atom and a different chain in the para or meta position were prepared and evaluated for their in vitro antifungal activity against the phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. The results showed that maximum inhibition of the growth of these fungi was exhibited for enantiomers S and R of 1-(40-chlorophenyl)- 2-phenylethanol (3 and 4). Furthermore, their antifungal activity showed a clear structure-activity relationship (SAR) trend confirming the importance of the benzyl hydroxyl group in the inhibitory mechanism of the compounds studied. Additionally, a multiobjective optimization study of the global antifungal profile of chlorophenyl derivatives was conducted in order to establish a rational strategy for the filtering of new fungicide candidates from combinatorial libraries. The MOOPDESIRE methodology was used for this purpose providing reliable ranking models that can be used later

The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation.

In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought

Semi-Empirical Topological Method for Prediction of the Relative Retention Time of Polychlorinated Biphenyl Congeners on 18 Different HR GC Columns

High resolution gas chromatographic relative retention time (HRGC-RRT) models were developed to predict relative retention times of the 209 individual polychlorinated biphenyls (PCBs) congeners. To estimate and predict the HRGC-RRT values of all PCBs on 18 different stationary phases, a multiple linear regression equation of the form RRT = ao + a1 (no. o-Cl) + a2 (no. m-Cl) + a3 (no. p-Cl) + a4 (VM or SM) was used. Molecular descriptors in the models included the number of ortho-, meta-, and para-chlorine substituents (no. o-Cl, m-Cl and p-Cl, respectively), the semi-empirically calculated molecular volume (VM), and the molecular surface area (SM). By means of the final variable selection method, four optimal semi-empirical descriptors were selected to develop a QSRR model for the prediction of RRT in PCBs with a correlation coefficient between 0.9272 and 0.9928 and a leave-one-out cross-validation correlation coefficient between 0.9230 and 0.9924 on each stationary phase. The root mean squares errors over different 18 stationary phases are within the range of 0.0108–0.0335. The accuracy of all the developed models were investigated using cross-validation leave-one-out (LOO), Y-randomization, external validation through an odd–even number and division of the entire data set into training and test sets