20 research outputs found

    The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

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    RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

    Impact of dietary organic acids and botanicals on intestinal integrity and inflammation in weaned pigs

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    BACKGROUND: Organic acids, such as citric and sorbic acid, and pure plant-derived constituents, like monoterpens and aldehydes, have a long history of use in pig feeding as alternatives to antibiotic growth promoters. However, their effects on the intestinal barrier function and inflammation have never been investigated. Therefore, aim of this study was to assess the impact of a microencapsulated mixture of citric acid and sorbic acid (OA) and pure botanicals, namely thymol and vanillin, (PB) on the intestinal integrity and functionality of weaned pigs and in vitro on Caco-2 cells. In the first study 20 piglets were divided in 2 groups and received either a basal diet or the basal diet supplemented with OA + PB (5 g/kg) for 2 weeks post-weaning at the end of which ileum and jejunum samples were collected for Ussing chambers analysis of trans-epithelial electrical resistance (TER), intermittent short-circuit current (I(SC)), and dextran flux. Scrapings of ileum mucosa were also collected for cytokine analysis (n = 6). In the second study we measured the effect of these compounds directly on TER and permeability of Caco-2 monolayers treated with either 0.2 or 1 g/l of OA + PB. RESULTS: Pigs fed with OA + PB tended to have reduced I(SC) in the ileum (P = 0.07) and the ileal gene expression of IL-12, TGF-β, and IL-6 was down regulated. In the in vitro study on Caco-2 cells, TER was increased by the supplementation of 0.2 g/l at 4, 6, and 14 days of the experiment, whereas 1 g/l increased TER at 10 and 12 days of treatment (P < 0.05). Dextran flux was not significantly affected though a decrease was observed at 7 and 14 days (P = 0.10 and P = 0.09, respectively). CONCLUSIONS: Overall, considering the results from both experiments, OA + PB improved the maturation of the intestinal mucosa by modulating the local and systemic inflammatory pressure ultimately resulting in a less permeable intestine, and eventually improving the growth of piglets prematurely weaned

    Post weaning diarrhea in pigs: risk factors and non-colistin-based control strategies

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    A Phenotypic Invitro Model For The Main Determinants Of Human Whole Heart Function

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    This article details the construction and testing of a phenotypic assay system that models invivo cardiac function in a parallel invitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of invitro cellular disease models in body-on-a-chip systems

    Dynamic resource allocation DAMA alternatives study for satellite communications systems

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    We consider the design of demand assigned multiple access (DAMA) algorithms that efficiently utilize limited RF uplink resources for packet switched military satellite communication networks. In previous work, we designed DAMA algorithms that optimized link layer efficiency and throughput while controlling delay and jitter. In this work we assess the ability of our DAMA algorithm to meet service level agreements (SLA) between the network management system and the terminals. We evaluate the ability of four DAMA algorithms to provide terminals committed information rates (CIR) under various system loading conditions. The designs have increasing levels of confidence in the accuracy of the predicted demand. Results show that although traffic demand cannot be predicted precisely, current demand provides insight into future demands and that this information can be used to more efficiently provide CIR guarantees to terminals.United States. Dept. of Defense (Air Force Contract FA8721-05-C-0002

    Jitter-aware time-frequency resource allocation and packing algorithm

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    One of the main components of the next generation protected military satellite communication systems is dynamic bandwidth resource allocation (DBRA). A centralized DBRA algorithm on the satellite dynamically grants terminals time and frequency resources as their traffic demands and channel conditions change, leading to significant increase in the overall system throughput. This paper address one potential issue associated with DBRA for the satellite uplink channel, which is a multi-frequency time-division multiple access (MF-TDMA) channel. As DBRA dynamically assigns time-frequency slots to terminals, there may be uneven temporal gaps in the assignment if special care were not taken. When this happens, even though average rate demands can be met, applications may experience larger than desired delay and jitter, which may reduce the quality of certain voice and video applications. This paper presents a novel algorithm for allocating and packing time-frequency slots in a jitter-aware fashion by using groups of evenly spaced slots. The achievable delay and jitter performance is evaluated using an OPNET simulation.United States. Dept. of Defense (Air Force Contract FA8721-05-C-0002
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