2,558 research outputs found

    Public health training in Europe. Development of European masters degrees in public health.

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    BACKGROUND: Changing political and economic relations in Europe mean that there are new challenges for public health and public health training. There have been several attempts to develop training at the master's level in public health which is focused on meeting the new needs. These have failed due to being too inflexible to allow participation by schools of public health. METHODS: A project funded by the European Union involving public health trainers has developed a new approach which allows participating schools to retain their national differences and work within local rules and traditions, but which aims to introduce the European dimension into public health training. This paper reports the conclusions of this project. CONCLUSIONS: A network of schools wishing to develop European Master's degrees is being established and other schools offering good quality programmes will be able to join

    A framework for use in modelling the modal choice decision making process in North West England’s Atlantic Gateway

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    The task of producing a generic model of the modal choice decision making process is a challenging one. Modal choice is strongly influenced by the infrastructure limitations and geographical constraints of the area in which the decision is being made. With this in mind, addressing modal choice on an individual basis for each region may be the optimal solution. This is the approach adopted in this paper. The creation of a modal choice model is a multistage process of which this paper addresses the first stage, the production a framework of the decision making process. Firstly, a number of criteria that are commonly used in modal choice models are identified. Then a number of gaps in the criteria utilized in previous papers are established. Subsequently, the method used to produce a framework of the decision making process within North West England’s Atlantic Gateway is outlined. Through consultation with transport industry experts in North West England, an initial list of sixty eight papers was reduced to thirty six that were considered to be of specific relevance to modern day freight transportation within their region. The criteria used in each of these papers were then, along with further industry input, used to create the foundation on which a modal choice framework specific to the Atlantic Gateway could be built. A greater understanding of what influences modal choice within this region will allow informed decisions to be made by policy makers on how to more efficiently utilize the available modes of freight transport. Having established this, future work can then go on to build upon these findings. This paper recommends that future work is performed to establish the weights of each criteria and sub-criteria within the framework. This should then be followed by establishing industry’s perceptions of the best and worst alternatives for moving freight within the Atlantic Gateway

    Radiation damage to nucleoprotein complexes in macromolecular crystallography

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    Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein-DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07-44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N1-C and sugar-phosphate C-O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses

    Expression of an Activation Antigen, Mo3e, Associated With the Cellular Response to Migration Inhibitory Factor by HL‐60 Promyelocytes Undergoing Monocyte‐Macrophage Differentiation

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    HL‐60 promyelocytic cells acquire the surface expression of the Mo3e antigenic determinant after exposure to PMA or compounds that raise intracellular concentrations of cyclic AMP (dibutyryl cyclic AMP or a combination of cholera toxin and IBMX). The expression of Mo3e by these stimulated HL‐60 cells coincides with the development of features of monocyte‐macrophage differentiation (characteristic morphology, nonspecific esterase activity, and respiratory burst activity). During in vitro monocyte‐macrophage differentiation, HL‐60 cells become responsive to migration inhibitory factor (MIF); the MIF responsiveness of differentiated HL‐60 cells is blocked by anti‐Mo3e monoclonal antibody. These findings further support the relationship between the expression of Mo3e and the cellular response to MIF.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141671/1/jlb0492.pd

    A primary fish gill cell culture model to assess pharmaceutical uptake and efflux:evidence for passive and facilitated transport

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    AbstractThe gill is the principle site of xenobiotic transfer to and from the aqueous environment. To replace, refine or reduce (3Rs) the large numbers of fish used in in vivo uptake studies an effective in vitro screen is required that mimics the function of the teleost gill. This study uses a rainbow trout (Oncorhynchus mykiss) primary gill cell culture system grown on permeable inserts, which tolerates apical freshwater thus mimicking the intact organ, to assess the uptake and efflux of pharmaceuticals across the gill. Bidirectional transport studies in media of seven pharmaceuticals (propranolol, metoprolol, atenolol, formoterol, terbutaline, ranitidine and imipramine) showed they were transported transcellularly across the epithelium. However, studies conducted in water showed enhanced uptake of propranolol, ranitidine and imipramine. Concentration-equilibrated conditions without a concentration gradient suggested that a proportion of the uptake of propranolol and imipramine is via a carrier-mediated process. Further study using propranolol showed that its transport is pH-dependent and at very low environmentally relevant concentrations (ngL−1), transport deviated from linearity. At higher concentrations, passive uptake dominated. Known inhibitors of drug transport proteins; cimetidine, MK571, cyclosporine A and quinidine inhibited propranolol uptake, whilst amantadine and verapamil were without effect. Together this suggests the involvement of specific members of SLC and ABC drug transporter families in pharmaceutical transport

    Genetics of Familial Amyotrophic Lateral Sclerosis

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    Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex

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    This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustacean, Gammarus pulex by measuring their concentrations in both biological material and in the exposure medium over a 96 h period. Selected pharmaceuticals included two anti-inflammatories (diclofenac and ibuprofen), two beta-blockers (propranolol and metoprolol), an anti-depressant (imipramine), an anti-histamine (ranitidine) and two beta-agonists (formoterol and terbutaline). Kinetic bioconcentration factors (BCFs) for the selected pharmaceuticals were derived from a first-order one-compartment model using either the simultaneous or sequential modelling methods. Using the simultaneous method for parameter estimation, BCF values ranged from 12 to 212. In contrast, the sequential method for parameter estimation resulted in bioconcentration factors ranging from 19 to 4533. Observed toxicokinetic plots showed statistically significant lack-of-fits and further interrogation of the models revealed a decreasing trend in the uptake rate constant over time for rantidine, diclofenac, imipramine, metoprolol, formoterol and terbutaline. Previous published toxicokinetic data for 14 organic micro-pollutants were also assessed and similar trends were identified to those observed in this study. The decreasing trend of the uptake rate constant over time highlights the need to interpret modelled data more comprehensively to ensure uncertainties associated with uptake and elimination parameters for determining bioconcentration factors are minimised
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