21 research outputs found

    New Role, New Country: introducing US physician assistants to Scotland

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    This paper draws from research commissioned by the Scottish Executive Health Department (SEHD). It provides a case study in the introduction of a new health care worker role into an already well established and "mature" workforce configuration It assesses the role of US style physician assistants (PAs), as a precursor to planned "piloting" of the PA role within the National Health Service (NHS) in Scotland

    Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis

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    Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABAA receptors (GABAARs). The impact of changes in steady state Cl− gradient is relatively straightforward to understand, but how dynamic interplay between Cl− influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl− load on a fast time scale, whereas Cl−extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl− gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABAAR-mediated inhibition, but increasing GABAAR input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl−. Furthermore, if spiking persisted despite the presence of GABAAR input, Cl− accumulation became accelerated because of the large Cl− driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl− and pH regulation. Several model predictions were tested and confirmed by [Cl−]i imaging experiments. Our study has thus uncovered how Cl− regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K− accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention

    Time domains of the hypoxic ventilatory response in ectothermic vertebrates

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    Over a decade has passed since Powell et al. (Respir Physiol 112:123–134, 1998) described and defined the time domains of the hypoxic ventilatory response (HVR) in adult mammals. These time domains, however, have yet to receive much attention in other vertebrate groups. The initial, acute HVR of fish, amphibians and reptiles serves to minimize the imbalance between oxygen supply and demand. If the hypoxia is sustained, a suite of secondary adjustments occur giving rise to a more long-term balance (acclimatization) that allows the behaviors of normal life. These secondary responses can change over time as a function of the nature of the stimulus (the pattern and intensity of the hypoxic exposure). To add to the complexity of this process, hypoxia can also lead to metabolic suppression (the hypoxic metabolic response) and the magnitude of this is also time dependent. Unlike the original review of Powell et al. (Respir Physiol 112:123–134, 1998) that only considered the HVR in adult animals, we also consider relevant developmental time points where information is available. Finally, in amphibians and reptiles with incompletely divided hearts the magnitude of the ventilatory response will be modulated by hypoxia-induced changes in intra-cardiac shunting that also improve the match between O2 supply and demand, and these too change in a time-dependent fashion. While the current literature on this topic is reviewed here, it is noted that this area has received little attention. We attempt to redefine time domains in a more ‘holistic’ fashion that better accommodates research on ectotherms. If we are to distinguish between the genetic, developmental and environmental influences underlying the various ventilatory responses to hypoxia, however, we must design future experiments with time domains in mind

    Assessment of Parental Disclosure of a 22q11.2 Deletion Syndrome Diagnosis and Implications for Clinicians

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    Most children with chromosome 22q11.2 deletion syndrome (22q11DS) have an IQ in the range that may allow them to be capable of understanding a genetic diagnosis despite mild intellectual disabilities. However, there are no publications that relate to the disclosure of a 22q11DS diagnosis to the affected child, or the factors that influence parents’ disclosure to the child. A pilot study was conducted including eight semi-structured interviews with caregivers of children with 22q11DS, 10 to 17 years of age, to investigate the factors that influence how parents inform their children of the diagnosis. Six of eight participants had disclosed the diagnosis to the child, and most of these parents felt they could have benefited from additional advice from professionals to increase their confidence and success, as well as the child’s comprehension of the information. Those who had not informed the child were uncertain about the words to use, how to initiate the conversation, or were concerned about the child’s level of understanding. Our results demonstrate that genetics professionals should help prepare caregivers for conversations with their children about the diagnosis of 22q11DS, monitor the understanding of the diagnosis over time, and provide ongoing support

    Facultative commensalism of a free-burrowing urothoid amphipod with a deep burrow-dwelling callianassid shrimp in intertidal sand

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    Species of the free-burrowing amphipod genus, Urothoe, are common on open sandy beaches. On intertidal sandflats, some species are associated with burrows or tubes of large infauna. How this link is formed and persisting under sheltered conditions was examined. On an intertidal sandflat in mid-western Kyushu, Japan, U. carda co-occurred with the deep burrow-dwelling callianassid shrimp, Nihonotrypaea harmandi, along a 300-m transect between tide marks. Amphipods resided in the surface 5-cm sediment outside shrimp burrows, as confirmed by sediment coring and burrow casting. In summers 1980 and 1981, the shrimp and amphipod populations were confined to the upper shore at mean densities of 182 and 701 inds m?2, respectively. In winter to spring, when the sediment surface mixing was caused by seasonal wind-induced waves, the amphipod but not the shrimp expanded down to the lowest shore. Later, by 1983, the shrimp increased mean density by 2.5 times and now also ranged to the lowest shore. In the summers of 1984, 2010, and 2015, the amphipod expanded to the lowest shore as well, with small variations in population size. Three marked changes in substrate properties were associated with shrimp inhabitation: thicker oxidized layer (proxy for oxygenated layer) in the sediment column; looser surface sediment, as evaluated with vane shear strength; and coarser and better-sorted surface sediment with less mud content. At least the former two changes were attributable to shrimp bioturbation, which could provide the amphipod with more permeable and softer substrates, leading to the formation of facultative commensalism
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