605 research outputs found

    Touchscreens can promote infant object-interlocutor reference switching

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    We re-examine whether the type of object played with influences parent-infant joint attention. A within-participants comparison of 24 parent-9-month-old dyads, used head-mounted eye-tracking to measure parental naming and infant attention during play with touchscreen apps on a tablet computer or matched interactive toys. Infants engaged in sustained attention more to the toy than the tablet. Parents named objects less in toy play. Infants exhibited more gaze shifts between the object and their parent during tablet play. Contrasting previous studies, these findings suggest that joint tablet play can be more interactive than with toys, and raise questions about the recommendation that infants should not be exposed at all to such technology

    Control of neutrophil infiltration into inflamed tissue. the role of μ-calpain in neutrophil shape change

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    Neutrophil spreading is an essential process in neutrophil extravasation and is a key step in the process of inflammation. Inhibition of neutrophil spreading is therefore a potential therapeutic target for the treatment of inflammatory diseases. Resting neutrophils have wrinkles in their plasma membrane which are held in place by cytoskeletal elements which act as a 'molecular velcro'. These proteins may be cleaved by cytosolic proteases such as the Ca2+-activated protease u calpain which contains a 'C2 like' domain. Calpain activation is also implicated in the expansion of the membrane during phagocytosis. The primary challenge over the course of this project was expressing of fluorescent proteins in myeloid cells. In this thesis I show that lentiviral transduction was the most efficient method for the stable transfection of myeloid cell lines. Fluorescent-C2 domain translocates to the plasma membrane during experimental Ca2+ influx and during phagocytosis. A similar mechanism may occur in human neutrophils as μ-calpain is located at the plasma membrane in activated human neutrophils. I also found that neutrophils may have a mechanism of retrieving excess membrane from the phagosome after phagocytosis. The work presented here has shown that by virtue of its 'C2 like' domain μ-calpain could translocate to the plasma membrane during the calcium influx which accompanies neutrophil spreading, μcalpain was shown to be present in the right place and at the right time in primary human neutrophils during neutrophil shape change and thus may play a key role in allowing the unwrinkling of the neutrophil membrane. Inhibition of calpain activity inhibits neutrophil spreading and therefore calpain poses a potential target for the treatment of inflammatory diseases

    Seasonal Influenza Vaccine Effectiveness in the community (SIVE): protocol for a cohort study exploiting a unique national linked data set

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    Introduction Seasonal influenza vaccination is recommended for all individuals aged 65 years and over and in individuals younger than 65 years with comorbidities. There is good evidence of vaccine effectiveness (VE) in young healthy individuals but less robust evidence for effectiveness in the populations targeted for influenza vaccination. Undertaking a randomised controlled trial to assess VE is now impractical due to the presence of national vaccination programmes. Quasi-experimental designs offer the potential to advance the evidence base in such scenarios, and the authors have therefore been commissioned to undertake a naturalistic national evaluation of seasonal influenza VE by using data derived from linkage of a number of Scottish health databases. The aim of this study is to examine the effectiveness of the seasonal influenza vaccination in the Scottish population. Methods and analysis A cohort study design will be used pooling data over nine seasons. A primary care database covering 4% of the Scottish population for the period 2000–2009 has been linked to the national database of hospital admissions and the death register and is being linked to the Health Protection Scotland virology database. The primary outcome is VE measured in terms of rate of hospital admissions due to respiratory illness. Multivariable regression will be used to produce estimates of VE adjusted for confounders. The major challenge of this approach is addressing the strong effect of confounding due to vaccinated individuals being systematically different from unvaccinated individuals. Analyses using propensity scores and instrumental variables will be undertaken, and the effect of an unknown confounder will be modelled in a sensitivity analysis to assess the robustness of the estimates

    Minimal impact electro-injection of cells undergoing dynamic shape change reveals calpain activation

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    AbstractThe ability of neutrophils to rapidly change shape underlies their physiological functions of phagocytosis and spreading. A major problem in establishing the mechanism is that conventional microinjection of substances and indicators interferes with this dynamic cell behaviour. Here we show that electroinjection, a “no-touch” point-and-shoot means of introducing material into the cell, is sufficiently gentle to allow neutrophils to be injected whilst undergoing chemokinesis and spreading without disturbing cell shape change behaviour. Using this approach, a fluorogenic calpain-1 selective peptide substrate was introduced into the cytosol of individual neutrophils undergoing shape changes. These data showed that (i) physiologically elevated cytosolic Ca2+ concentrations were sufficient to trigger calpain-1 activation, blockade of Ca2+ influx preventing calpain activation and (ii) calpain-1 activity was elevated in spreading neutrophil. These findings provide the first direct demonstration of a physiological role for Ca2+ elevation in calpain-1 activation and rapid cell spreading. Electroinjection of cells undergoing dynamic shape changes thus opens new avenues of investigation for defining the molecular mechanism underlying dynamic cell shape changes

    Status of nearshore finfish stocks in south-western Western Australia: Part 1: Australian herring

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    The status of the popular nearshore finfish resource in the West Coast Bioregion (WCB) of Western Australia (WA) was largely unknown prior to this study. Previously, declining catches of several nearshore species had highlighted the risk to their sustainability and the need for greater certainty about their status. Recently, the risk further increased due to management changes in the WCB aimed at reducing the catch of demersal scalefish, which are likely to result in a shift in targeting towards nearshore species. This increase in fishing pressure on nearshore species will be on top of any increase due to the continuing human population growth in the WCB

    Data feedback and behavioural change intervention to improve primary care prescribing safety (EFIPPS):multicentre, three arm, cluster randomised controlled trial

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    Objective: To evaluate the effectiveness of feedback on safety of prescribing compared with moderately enhanced usual care. Design: Three arm, highly pragmatic cluster randomised trial. Setting and participants: 262/278 (94%) primary care practices in three Scottish health boards. Interventions: Practices were randomised to: "usual care," consisting of emailed educational material with support for searching to identify patients (88 practices at baseline, 86 analysed); usual care plus feedback on practice's high risk prescribing sent quarterly on five occasions (87 practices, 86 analysed); or usual care plus the same feedback incorporating a behavioural change component (87 practices, 86 analysed). Main outcome measures: The primary outcome was a patient level composite of six prescribing measures relating to high risk use of antipsychotics, non-steroidal anti-inflammatories, and antiplatelets. Secondary outcomes were the six individual measures. The primary analysis compared high risk prescribing in the two feedback arms against usual care at 15 months. Secondary analyses examined immediate change and change in trend of high risk prescribing associated with implementation of the intervention within each arm. Results: In the primary analysis, high risk prescribing as measured by the primary outcome fell from 6.0% (3332/55 896) to 5.1% (2845/55 872) in the usual care arm, compared with 5.9% (3341/56 194) to 4.6% (2587/56 478) in the feedback only arm (odds ratio 0.88 (95% confidence interval 0.80 to 0.96) compared with usual care; P=0.007) and 6.2% (3634/58 569) to 4.6% (2686/58 582) in the feedback plus behavioural change component arm (0.86 (0.78 to 0.95); P=0.002). In the pre-specified secondary analysis of change in trend within each arm, the usual care educational intervention had no effect on the existing declining trend in high risk prescribing. Both types of feedback were associated with significantly more rapid decline in high risk prescribing after the intervention compared with before. Conclusions: Feedback of prescribing safety data was effective at reducing high risk prescribing. The intervention would be feasible to implement at scale in contexts where electronic health records are in general use

    Status of nearshore finfish stocks in south-western Western Australia: Part 2: Tailor

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    The status of the nearshore finfish resource in the West Coast Bioregion (WCB) of Western Australia (WA) was largely unknown prior to this study. Previously, declining catches of several species had highlighted the risk to their sustainability and the need for greater certainty about the status of this popular resource. Recently, the risk substantially increased due to recent changes to the management of demersal scalefish, which are likely to result in a shift in targeting towards nearshore species. This increase in fishing pressure will be on top of any increase due to the continuing human population growth in the WCB
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