1,418 research outputs found

    EAHP European Statements baseline survey 2015

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    Objectives The 2015 EAHP European Statements survey was related to sections 2, 5 and 6 of the European Statements of Hospital Pharmacy (Statements). In addition to collection of statistical data about the level of implementation of the Statements, it was also intended to identify important barriers to their implementation. Methods The online questionnaire was sent to all hospital pharmacies in EAHP member countries. Data were analysed by researchers from Keele University School of Pharmacy, UK and the EAHP Survey Group. Results There were a total of 949 responses (response rate 18%). In the first part of the survey, data was collected on hospital pharmacy setting. While almost half of hospital pharmacies served over 500 beds, 80% of hospital pharmacies had 10 or less pharmacists. In section B, we gathered evidence about the degree of implementation of sections 2, 5 and 6 of the Statements and the main barriers to and drivers of implementation. Five questions with the lowest implementation level were then further analysed. Only five countries had 50% or more of hospital pharmacies reporting that the hospital pharmacists routinely publish hospital pharmacy practice research. 67% of participants stated that they had contingency plans for medicines shortages. The majority of countries (n=20) have less than half of respondents using computerised decision support to reduce the risk of medication errors. When asked if an audit had been undertaken in the past 3 years to identify priorities in medicines use processes, the mean percentage of positive responses for a country was 58%. Conclusions EAHP has gained an informative overview of the implementation level as well as the barriers to and drivers of implementation in sections 2, 5 and 6. This is essential to inform the plans for EAHP to best support their implementation

    Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro

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    Author Manuscript: 2010 June 23.Liver sinusoidal endothelial cells (LSECs) differ, both structurally and functionally, from endothelial cells (ECs) lining blood vessels of other tissues. For example, in contrast to other ECs, LSECs possess fenestrations, have low detectable levels of platelet endothelial cell adhesion molecule 1 expression, and in rat tissue, they distinctively express a cell surface marker recognized by the SE-1 antibody. These unique phenotypic characteristics seen in hepatic tissue are lost over time upon culture in vitro; therefore, this study sought to systematically examine the effects of microenvironmental stimuli—namely, extracellular matrix and neighboring cells, on the LSEC phenotype in vitro. In probing the role of the underlying extracellular matrix, we identified collagen I and collagen III as well as mixtures of collagen I/collagen IV/fibronectin as having a positive effect on LSEC survival. Furthermore, using a stable hepatocellular model (hepatocyte–fibroblast) we were able to prolong the expression of both SE-1 and phenotypic functions of LSEC such as factor VIII activity and AcLOL uptake in cocultured LSECs through the production of short-range paracrine signals. In the course of these experiments, we identified the antigen recognized by SE-1 as CD32b. Conclusion: Collectively, this study has identified several microenvironmental regulators of liver sinusoidal endothelial cells that prolong their phenotypic functions for up to 2 weeks in culture, enabling the development of better in vitro models of liver physiology and disease

    Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

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    Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

    Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2

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    Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for β-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif–like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G–opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor κB by β-glucan–containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor α. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses

    COUNTS OF SURFACE-NESTING SEABIRDS BREEDING AT PRINCE EDWARD ISLAND, SUMMER 2001/02

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    The first midsummer survey of surface-nesting seabirds at Prince Edward Island was conducted during December 2001. It was also the first census for most species since the early 1980s. Despite concerns about the impacts of longline fishing mortality on various albatrosses and giant petrels, there was no evidence that populations of these species had decreased. Indeed, the estimate of wandering albatrosses Diomedea exulans (Vulnerable) has increased significantly, making Prince Edward Island equal with Marion Island as supporting the largest single-island populations of this species. Species that underwent significant decreases were macaroni penguins Eudyptes chrysolophus (Vulnerable), Crozet shags Phalacrocorax [atriceps] melanogenis and Kerguelen terns Sterna virgata (Near-Threatened). The reasons for these decreases are unclear, but for macaroni penguins may be partly a consequence of competition for space with the burgeoning population of fur seals Arctocephalus spp. The 2001 survey increased the population estimates for Subantarctic skuas Catharacta antarctica, lightmantled sooty albatrosses Phoebetria palpebrata (Vulnerable) and southern giant petrels Macronectes giganteus (Vulnerable), mostly as a result of greater coverage than for previous counts. The 2001 survey confirms that Prince Edward Island remains a globally important breeding site for seabirds.Afr. J. mar. Sci. 25: 441–45

    The ID show

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    The ID show Catalogue of an exhibition held at the University of Tasmania Centre for the Arts Gallery, Hobart, July 18-Aug. 9, 198

    Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

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    BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

    Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

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    Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required
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