953 research outputs found

    The role of zebrafish (Danio rerio) in dissecting the genetics and neural circuits of executive function

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    Zebrafish have great potential to contribute to our understanding of behavioural genetics and thus to contribute to our understanding of the aetiology of psychiatric disease. However, progress is dependent upon the rate at which behavioural assays addressing complex behavioural phenotypes are designed, reported and validated. Here we critically review existing behavioural assays with particular focus on the use of adult zebrafish to explore executive processes and phenotypes associated with human psychiatric disease. We outline the case for using zebrafish as models to study impulse control and attention, discussing the validity of applying extant rodent assays to zebrafish and evidence for the conservation of relevant neural circuits

    Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness

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    <div><p>Background</p><p><b>P</b>ractical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF).</p><p>Methods</p><p>We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 <i>per protocol</i>). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified from nasal epithelial curettage samples taken before and after challenge.</p><p>Results</p><p>Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS).</p><p>Conclusions</p><p>Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.</p><p>Key Messages</p><p>Ultrapure LPS was used as innate immune stimulus in a human nasal challenge model, with serial sampling of nasal mucosal lining fluid (MLF) by nasosorption using a synthetic absorptive matrix (SAM), and nasal curettage of mucosal cells. A dose response could be demonstrated in terms of levels of IL-1β, IL-6, CXCL8 and CCL3 in MLF, as well as ICAM-1 mRNA in nasal curettage specimens, and levels of neutrophils in nasal lavage. Depending on higher baseline levels of inflammation, there were occasional magnified innate inflammatory responses to LPS.</p><p>Trial Registration</p><p>Clinical Trials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02284074?term=nasal+lipopolysaccharide&rank=1" target="_blank">NCT02284074</a></p></div

    Pancreatectomy is underused in NSW regions with low institutional surgical volumes: A population data linkage study

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    © 2017 AMPCo Pty Ltd. Produced with Elsevier B.V. All rights reserved. Objective: To examine differences in the proportions of people diagnosed with pancreatic cancer who underwent pancreatectomy, post-operative outcomes and 5-year survival in different New South Wales administrative health regions of residence. Design, setting and participants: Retrospective analysis of NSW data on pancreatic cancer incidence and surgery, 2005e2013. Main outcome measures: The proportion of newly diagnosed patients with pancreatic cancer who were resected in each region; 90-day post-operative mortality; one-year post-operative survival; 5-year post-diagnosis survival. Results: 14% of people diagnosed with pancreatic cancer during 2010e2013 (431 of 3064) underwent pancreatectomy, an average of 108 resections per year. After adjusting for age, sex and comorbidities, the proportion that underwent resection varied significantly between regions, ranging between 8% and 21% (P<0.001). Higher resection rates were not associated with higher post-operative 90-day mortality or lower one-year survival (unadjusted and risk-adjusted analyses). Higher resection rates were associated with higher 5-year post-diagnosis survival: the mean survival in regions with resection rates below 10% was 3.4%, compared with 7.2% in regions with rates greater than 15% (unadjusted and adjusted survival analyses; P<0.001). There was a positive association between regional resection rate and the pancreatectomy volume of hospitals during 2005e2009. An additional 32 people would be resected annually if resection rates in low rate regions were increased to the 80th percentile regional resection rate (18%). Conclusion: There is significant geographic variation in the proportion of people with pancreatic cancer undergoing pancreatectomy, and the 5-year survival rate is higher in regions where this proportion is higher

    Development of electric scooter alerting sounds using psychoacoustical metrics

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    In recent years electric micromobility transportation, including electric scooters, has seen a surge in popularity due to technological advances and the move to lower emission transport. Although offering a range of societal benefits, such as reduced pollution and increased personal mobility, concerns have been raised regarding the implications for pedestrian safety, most notably within the blind and partially sighted community. The issue of pedestrian safety is well studied in the context of larger electric vehicles (EVs), and indeed regulations are now in place that specify mandatory Acoustic Vehicle Alerting Systems (AVAS) for such vehicles. However, limited research has been done on the development of acoustic alerting systems for micromobility. In this paper, the development of an electric scooter (e-scooter) AVAS is considered by taking a perception-influenced design approach to designing alert sounds that optimise detectability and annoyance. A listening experiment has been conducted using ambisonic soundscapes and simulated auralisations of e-scooter passes at 20 km/h, in which a detection-based task and annoyance rating task were conducted. Objective metrics for detectability and annoyance were subsequently evaluated in relation to the subjective responses, so as to enable a more focused approach to the development of alert sounds. Results show that without additional alert sounds, the rate of detection for e-scooters in a soundscape of 60 dBA is as low as 23%. Regression analysis showed that the objective metric of Zwicker’s psychoacoustic annoyance is a useful predictor of subjective annoyance for AVAS sounds, with a coefficient of determination of R^2 = 0.96, and explains more variance than other metrics previously reported in the literature. Partial loudness was also studied as a predictor of detectability, with strong positive association seen (R^2 = 0.9). Of the alert sounds evaluated, those comprising pure tones with frequency content in the 800 Hz - 1 kHz range, and with amplitude modulation or impulsive characteristics, offered the greatest balance between detectability and annoyance. This study offers much needed research into detectability of electric micromobility transport in a range of environmental noise conditions, and furthermore provides objective metrics for the development of micromobility AVAS sounds going forward

    Synthesis of environment maps for mixed reality

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    When rendering virtual objects in a mixed reality application, it is helpful to have access to an environment map that captures the appearance of the scene from the perspective of the virtual object. It is straightforward to render virtual objects into such maps, but capturing and correctly rendering the real components of the scene into the map is much more challenging. This information is often recovered from physical light probes, such as reflective spheres or fisheye cameras, placed at the location of the virtual object in the scene. For many application areas, however, real light probes would be intrusive or impractical. Ideally, all of the information necessary to produce detailed environment maps could be captured using a single device. We introduce a method using an RGBD camera and a small fisheye camera, contained in a single unit, to create environment maps at any location in an indoor scene. The method combines the output from both cameras to correct for their limited field of view and the displacement from the virtual object, producing complete environment maps suitable for rendering the virtual content in real time. Our method improves on previous probeless approaches by its ability to recover high-frequency environment maps. We demonstrate how this can be used to render virtual objects which shadow, reflect and refract their environment convincingly
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