SIMAGE: SImulation of DNA-MicroArray Gene Expression data

Background: Simulation of DNA-microarray data serves at least three purposes: (i) optimizing the design of an intended DNA microarray experiment, (ii) comparing existing pre-processing and processing methods for best analysis of a given DNA microarray experiment, (iii) educating students, lab-workers and other researchers by making them aware of the many factors influencing DNA microarray experiments. Results: Our model has multiple layers of factors influencing the experiment. The relative influence of such factors can differ significantly between labs, experiments within labs, etc. Therefore, we have added a module to roughly estimate their parameters from a given data set. This guarantees that our simulated data mimics real data as closely as possible. Conclusions: We introduce a model for the simulation of dual-dye cDNA-microarray data closely resembling real data and coin the model and its software implementation SIMAGE which stands for simulation of microarray gene expression data. The software is freely accessible at: http://bioinformatics.biol.rug.nl/websoftware/simag

Parenting, young children\u27s behavioral self‐regulation and the quality of their peer relationships

The quality of young children\u27s peer relationships is important for their development, and it is assumed that parenting and self-regulation skills shape children\u27s behavior when interacting with peers. In this multi-informant-multi-method study, we examined the direct and mediated associations between preschool parenting, children\u27s behavioral self-regulation, and peer aggression and peer relationship problems in elementary school-aged children and extended previous work by examining both positive and negative parenting of both mothers and fathers. In a large community sample (n = 698) of parents and children who were between 1 and 6 years old, we obtained information on observed maternal sensitivity, mother- and father-reported harsh discipline, observed child self-regulation, and child-reported aggression towards peers, peer rejection and victimization. Results from a structural equation model showed that maternal sensitivity was prospectively associated with children\u27s behavioral self-regulation and that lower levels of behavioral self-regulation were associated with higher levels of children\u27s peer aggression and peer relationship problems. However, children\u27s behavioral self-regulation did not mediate the association between maternal sensitivity and peer relationship problems. In addition, higher levels of paternal, but not maternal, harsh discipline were directly associated with more peer relationship problems, but again no mediation was found. The results highlight the importance of maternal sensitivity for children\u27s behavioral self-regulation and the role of paternal harsh discipline for the quality of children\u27s later peer relationships. Our findings suggest it is important to take maternal and paternal parenting practices into account as they might have different effects on the child

Scale-free memory model for multiagent reinforcement learning. Mean field approximation and rock-paper-scissors dynamics

A continuous time model for multiagent systems governed by reinforcement learning with scale-free memory is developed. The agents are assumed to act independently of one another in optimizing their choice of possible actions via trial-and-error search. To gain awareness about the action value the agents accumulate in their memory the rewards obtained from taking a specific action at each moment of time. The contribution of the rewards in the past to the agent current perception of action value is described by an integral operator with a power-law kernel. Finally a fractional differential equation governing the system dynamics is obtained. The agents are considered to interact with one another implicitly via the reward of one agent depending on the choice of the other agents. The pairwise interaction model is adopted to describe this effect. As a specific example of systems with non-transitive interactions, a two agent and three agent systems of the rock-paper-scissors type are analyzed in detail, including the stability analysis and numerical simulation. Scale-free memory is demonstrated to cause complex dynamics of the systems at hand. In particular, it is shown that there can be simultaneously two modes of the system instability undergoing subcritical and supercritical bifurcation, with the latter one exhibiting anomalous oscillations with the amplitude and period growing with time. Besides, the instability onset via this supercritical mode may be regarded as "altruism self-organization". For the three agent system the instability dynamics is found to be rather irregular and can be composed of alternate fragments of oscillations different in their properties.Comment: 17 pages, 7 figur

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine:A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression

Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS

Dynamic metabolomic data analysis: a tutorial review

In metabolomics, time-resolved, dynamic or temporal data is more and more collected. The number of methods to analyze such data, however, is very limited and in most cases the dynamic nature of the data is not even taken into account. This paper reviews current methods in use for analyzing dynamic metabolomic data. Moreover, some methods from other fields of science that may be of use to analyze such dynamic metabolomics data are described in some detail. The methods are put in a general framework after providing a formal definition on what constitutes a ‘dynamic’ method. Some of the methods are illustrated with real-life metabolomics examples