1,568 research outputs found

    Group B streptococcal infection and activation of human astrocytes.

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    BACKGROUND:Streptococcus agalactiae (Group B Streptococcus, GBS) is the leading cause of life-threatening meningitis in human newborns in industrialized countries. Meningitis results from neonatal infection that occurs when GBS leaves the bloodstream (bacteremia), crosses the blood-brain barrier (BBB), and enters the central nervous system (CNS), where the bacteria contact the meninges. Although GBS is known to invade the BBB, subsequent interaction with astrocytes that physically associate with brain endothelium has not been well studied. METHODOLOGY/PRINCIPAL FINDINGS:We hypothesize that human astrocytes play a unique role in GBS infection and contribute to the development of meningitis. To address this, we used a well- characterized human fetal astrocyte cell line, SVG-A, and examined GBS infection in vitro. We observed that all GBS strains of representative clinically dominant serotypes (Ia, Ib, III, and V) were able to adhere to and invade astrocytes. Cellular invasion was dependent on host actin cytoskeleton rearrangements, and was specific to GBS as Streptococcus gordonii failed to enter astrocytes. Analysis of isogenic mutant GBS strains deficient in various cell surface organelles showed that anchored LTA, serine-rich repeat protein (Srr1) and fibronectin binding (SfbA) proteins all contribute to host cell internalization. Wild-type GBS also displayed an ability to persist and survive within an intracellular compartment for at least 12 h following invasion. Moreover, GBS infection resulted in increased astrocyte transcription of interleukin (IL)-1β, IL-6 and VEGF. CONCLUSIONS/SIGNIFICANCE:This study has further characterized the interaction of GBS with human astrocytes, and has identified the importance of specific virulence factors in these interactions. Understanding the role of astrocytes during GBS infection will provide important information regarding BBB disruption and the development of neonatal meningitis

    Formative Evaluation of a Hepatitis C Virus Computer Assisted Instruction Tool or Communities of African Descent

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    Hepatitis C Virus (HCV) has become increasingly prevalent within traditionally undeserved communities. The paper describes the formative evaluation of a HCV Computer Assisted Instruction (CAI) tool. Specific aims are to describe the feasibility of a CAI tool with a high-risk population, and the use of Nigrescence Theory to develop targeted messages. Three participants, recruited at an all-male substance abuse halfway house, reviewed the CAI in a mini-focus group. A Health History/HCV Knowledge Questionnaire, The Cross Racial Identity Scale and a focus group question route were used to collect qualitative and quantitative data. The analysis plan utilized descriptive statistics, content analysis and profile analysis. Results suggested that the CAI was acceptable to this segment of the population, and Nigrescence Theory provided a context for targeting messages to differing segments of the target group. Recommendations are offered to health promotion programs targeting people of African descent

    Volcano dome dynamics at Mount St. Helens:Deformation and intermittent subsidence monitored by seismicity and camera imagery pixel offsets

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    The surface deformation field measured at volcanic domes provides insights into the effects of magmatic processes, gravity-and gas-driven processes, and the development and distribution of internal dome structures. Here we study short-term dome deformation associated with earthquakes at Mount St. Helens, recorded by a permanent optical camera and seismic monitoring network. We use Digital Image Correlation (DIC) to compute the displacement field between successive images and compare the results to the occurrence and characteristics of seismic events during a 6 week period of dome growth in 2006. The results reveal that dome growth at Mount St. Helens was repeatedly interrupted by short-term meter-scale downward displacements at the dome surface, which were associated in time with low-frequency, large-magnitude seismic events followed by a tremor-like signal. The tremor was only recorded by the seismic stations closest to the dome. We find a correlation between the magnitudes of the camera-derived displacements and the spectral amplitudes of the associated tremor. We use the DIC results from two cameras and a high-resolution topographic model to derive full 3-D displacement maps, which reveals internal dome structures and the effect of the seismic activity on daily surface velocities. We postulate that the tremor is recording the gravity-driven response of the upper dome due to mechanical collapse or depressurization and fault-controlled slumping. Our results highlight the different scales and structural expressions during growth and disintegration of lava domes and the relationships between seismic and deformation signals

    Scavenging amphipods from the Wallaby-Zenith Fracture Zone : Extending the hadal paradigm beyond subduction trenches

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    Acknowledgements We would like to thank Nick Cuomo for assis- tance with lander deployments, Prof Darren Evans and Dr James Kitson (Newcastle University, UK) for bench space in the Molecular Diagno- sis Facility, Ed Hendrycks (Canadian Museum of Nature, Canada) for guidance on the Cleonardo sp. identification, and Dr Shannon Flynn (Newcastle University, UK) for constructive comments on manuscript drafts. We extend thanks to the Captain and crew on the 2017 R/V SONNE Expedition SO258 Leg 1, especially joint Chief Scientists Dr Reinhard Werner (GEOMAR, Germany) and Prof Hans-Joachim Wagner (University of Tübingen, Germany) and Oleg Lechenko and Julia Marinova (P.P. Shirshov Institute of Oceanology of the Russian Academy of Sciences, Russia) for the acquisition and processing of the bathymetric data. We are appreciative of the reviewers for their constructive comments and suggestions that improved the manuscript. Funding Participation on the R/V SONNE Expedition SO258 was sup- ported by Newcastle University’s Research Infrastructure Fund (RiF), Exploration of Extreme Ocean Environments, awarded to AJJ. The genetic analysis was funded by Newcastle University through internal funds to JNJW and the University of Aberdeen by the Natural Environment Research Council (NERC), UK Grant NE/N01149X/1, awarded to SBP.Peer reviewedPublisher PD

    Inhibition in multiclass classification

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    The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and train it in the large margin classifier framework. Inhibition leads to more robust classifiers in the sense that they perform better on larger areas of appropriate hyperparameters when assessed with leave-one-out strategies. We also show that the classifier with inhibition is a tight bound to probabilistic exponential models and is Bayes consistent for 3-class problems. These properties make this approach useful for data sets with a limited number of labeled examples. For larger data sets, there is no significant comparative advantage to other multiclass SVM approaches

    Inhibition in multiclass classification

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    The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and train it in the large margin classifier framework. Inhibition leads to more robust classifiers in the sense that they perform better on larger areas of appropriate hyperparameters when assessed with leave-one-out strategies. We also show that the classifier with inhibition is a tight bound to probabilistic exponential models and is Bayes consistent for 3-class problems. These properties make this approach useful for data sets with a limited number of labeled examples. For larger data sets, there is no significant comparative advantage to other multiclass SVM approaches

    Setting directions for capacity building in primary health care: a survey of a research network

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    BACKGROUND: The South Australian Research Network 'SARNet' aims to build research capacity in primary health care, as part of a national government-funded strategy to integrate research into clinical practice. Internationally, research networks have been a fundamental part of research culture change, and a variety of network models exist. The 'SARNet' model uses a whole system, multidisciplinary approach to capacity building and supports individuals and groups. We undertook a descriptive baseline survey in order to understand the background and needs of SARNet members and to tailor network activities towards those needs. METHODS: A questionnaire survey, assessing members' professional background, research experience, and interest in research development and training, was sent to all members who joined the network in its first year. The visual 'research spider' tool was used to ascertain members' experience in ten core research skills, as well as their interest in developing these skills. Individuals were asked to classify themselves into one of four categories of researchers, based on previous research experience. These self-assessment categories ranged from non-participant to academic. RESULTS: Network membership was diverse. Of the 89 survey participants, 55% were general practitioners or allied health professionals. Overall, most survey respondents indicated little to moderate experience in 7 out of the 10 skills depicted in the 'research spider'. In comparison, respondents were generally highly interested in developing their research skills in all areas. Respondents' research skills correlated significantly with their self-assessed category of research participation (Spearman rank correlation, r = 0.82, p < 0.0005). Correlations between research category and publication record (Gamma association, γ = 0.53, p < 0.0005) or funding record (Gamma association, γ = 0.62, p < 0.0005) supported the internal validity of the survey instrument. CONCLUSION: Literature describing evaluation of the impact of networks is scarce. Our survey questionnaire could provide a useful instrument for evaluation of both networks and capacity building initiatives. The survey including the 'research spider' tool provided valuable information about members' needs and interest in strategies to develop their research skills. Initial needs analyses as well as on-going evaluation of network activities are important to include into the business plans of research networks, in order to ensure the network's effectiveness and support of its membership
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