The EU-ADR Web Platform: delivering advanced pharmacovigilance tools

PURPOSE: Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks.METHODS: The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential.RESULTS: The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment.CONCLUSIONS: A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright © 2012 John Wiley & Sons, Ltd.

Line search multilevel optimization as computational methods for dense optical flow

We evaluate the performance of different optimization techniques developed in the context of optical flowcomputation with different variational models. In particular, based on truncated Newton methods (TN) that have been an effective approach for large-scale unconstrained optimization, we develop the use of efficient multilevel schemes for computing the optical flow. More precisely, we evaluate the performance of a standard unidirectional multilevel algorithm - called multiresolution optimization (MR/OPT), to a bidrectional multilevel algorithm - called full multigrid optimization (FMG/OPT). The FMG/OPT algorithm treats the coarse grid correction as an optimization search direction and eventually scales it using a line search. Experimental results on different image sequences using four models of optical flow computation show that the FMG/OPT algorithm outperforms both the TN and MR/OPT algorithms in terms of the computational work and the quality of the optical flow estimation.

Implementing interactive computing in an object-oriented environment

Statistical computing when input/output is driven by a Graphical User Interface is considered. A proposal is made for automatic control ofcomputational flow to ensure that only strictly required computationsare actually carried on. The computational flow is modeled by a directed graph for implementation in any object-oriented programming language with symbolic manipulation capabilities. A complete implementation example is presented to compute and display frequency based piecewise linear density estimators such as histograms or frequency polygons.

Binding energy and momentum distribution of nuclear matter using Green's functions methods

The influence of hole-hole (h-h) propagation in addition to the conventional particle-particle (p-p) propagation, on the energy per particle and the momentum distribution is investigated for the v2 central interaction which is derived from Reid¿s soft-core potential. The results are compared to Brueckner-Hartree-Fock calculations with a continuous choice for the single-particle (SP) spectrum. Calculation of the energy from a self-consistently determined SP spectrum leads to a lower saturation density. This result is not corroborated by calculating the energy from the hole spectral function, which is, however, not self-consistent. A generalization of previous calculations of the momentum distribution, based on a Goldstone diagram expansion, is introduced that allows the inclusion of h-h contributions to all orders. From this result an alternative calculation of the kinetic energy is obtained. In addition, a direct calculation of the potential energy is presented which is obtained from a solution of the ladder equation containing p-p and h-h propagation to all orders. These results can be considered as the contributions of selected Goldstone diagrams (including p-p and h-h terms on the same footing) to the kinetic and potential energy in which the SP energy is given by the quasiparticle energy. The results for the summation of Goldstone diagrams leads to a different momentum distribution than the one obtained from integrating the hole spectral function which in general gives less depletion of the Fermi sea. Various arguments, based partly on the results that are obtained, are put forward that a self-consistent determination of the spectral functions including the p-p and h-h ladder contributions (using a realistic interaction) will shed light on the question of nuclear saturation at a nonrelativistic level that is consistent with the observed depletion of SP orbitals in finite nuclei.

Line search multilevel optimization as computational methods for dense optical flow

We evaluate the performance of different optimization techniques developed in the context of optical flow computation with different variational models. In particular, based on truncated Newton methods (TN) that have been an effective approach for large-scale unconstrained optimization, we de- velop the use of efficient multilevel schemes for computing the optical flow. More precisely, we evaluate the performance of a standard unidirectional mul- tilevel algorithm - called multiresolution optimization (MR/OPT), to a bidrec- tional multilevel algorithm - called full multigrid optimization (FMG/OPT). The FMG/OPT algorithm treats the coarse grid correction as an optimiza- tion search direction and eventually scales it using a line search. Experimental results on different image sequences using four models of optical flow com- putation show that the FMG/OPT algorithm outperforms both the TN and MR/OPT algorithms in terms of the computational work and the quality of the optical flow estimation.

Candidate counterparts to the soft gamma-ray flare in the direction od LSI+61303

A short duration burst reminiscent of a soft gamma-ray repeater/anomalous X-ray pulsar behaviour was detected in the direction of LS I +61 303 by the Swift satellite. While the association with this well known gamma-ray binary is likely, a different origin cannot be excluded. Aims. We explore the error box of this unexpected flaring event and establish the radio, near-infrared and X-ray sources in our search for any peculiar alternative counterpart. Methods. We carried out a combined analysis of archive Very Large Array radio data of LS I +61 303 sensitive to both compact and extended emission. We also reanalysed previous near infrared observations with the 3.5 m telescope of the Centro Astronómico Hispano Alemán and X-ray observations with the Chandra satellite. Results. Our deep radio maps of the LS I +61 303 environment represent a significant advancement on previous work and 16 compact radio sources in the LS I +61 303 vicinity are detected. For some detections, we also identify near infrared and X-ray counterparts. Extended emission features in the field are also detected and confirmed. The possible connection of some of these sources with the observed flaring event is considered. Based on these data, we are unable to claim a clear association between the Swift-BAT flare and any of the sources reported here. However, this study represents the most sophisticated attempt to determine possible alternative counterparts other than LS I +61 303.