440 research outputs found

    Down At The Huskin\u27 Bee

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    https://digitalcommons.library.umaine.edu/mmb-vp/4183/thumbnail.jp

    Maria Auxiliadora Hospital in Lima, Peru as a model for neurosurgical outreach to international charity hospitals

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    A myriad of geopolitical and financial obstacles have kept modern neurosurgery from effectively reaching the citizens of the developing world. Targeted neurosurgical outreach by academic neurosurgeons to equip neurosurgical operating theaters and train local neurosurgeons is one method to efficiently and cost effectively improve sustainable care provided by international charity hospitals. The International Neurosurgical Children’s Association (INCA) effectively improved the available neurosurgical care in the Maria Auxiliadora Hospital of Lima, Peru through the advancement of local specialist education and training. Neurosurgical equipment and training were provided for the local neurosurgeons by a mission team from the University of California at San Diego. At the end of 3 years, with one intensive week trip per year, the host neurosurgeons were proficiently and independently applying microsurgical techniques to previously performed operations, and performing newly learned operations such as neuroendoscopy and minimally invasive neurosurgery. Our experiences may serve as a successful template for the execution of other small scale, sustainable neurosurgery missions worldwide

    Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

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    Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

    Misfit-Dislocation-Mediated Heteroepitaxial Island Diffusion

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    Scanning tunneling microscopy combined with molecular dynamics simulations reveal a dislocation-mediated island diffusion mechanism for Cu on Ag(111), a highly mismatched system. Cluster motion is tracked with atomic precision at multiple temperatures and diffusion barriers and prefactors are determined from direct measurements of hop rates. The non-monotonic size dependence of the diffusion barrier is in good agreement with simulations and can lead to enhanced mass transport upon coarsening, in surprising contrast to the traditional island diffusion models where diffusivity reduces with cluster size

    A Quintessentially Geometric Model

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    We consider string inspired cosmology on a solitary D3D3-brane moving in the background of a ring of branes located on a circle of radius RR. The motion of the D3D3-brane transverse to the plane of the ring gives rise to a radion field which can be mapped to a massive non-BPS Born-Infeld type field with a cosh potential. For certain bounds of the brane tension we find an inflationary phase is possible, with the string scale relatively close to the Planck scale. The relevant perturbations and spectral indices are all well within the expected observational bounds. The evolution of the universe eventually comes to be dominated by dark energy, which we show is a late time attractor of the model. However we also find that the equation of state is time dependent, and will lead to late time Quintessence.Comment: 11 pages, 3 figures. References and comments adde

    Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

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    <p>Abstract</p> <p>Background</p> <p>Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with <it>P. aeruginosa </it>by a Th17-mediated mechanism.</p> <p>Results</p> <p>Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the <it>P. aeruginosa </it>strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against <it>P. aeruginosa </it>in vitro.</p> <p>Conclusions</p> <p>Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with <it>P. aeruginosa </it>in the CF lung.</p

    Representational predicaments at three Hong Kong sites

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    Representational predicaments arise when a job incumbent believes that attributions and images assumed by dominant authorities unfavourably ignore, or disproportionately and unfavourably emphasize, aspects of the incumbent\u27s own work and social identity. This is likely to happen when the incumbent does not have a close relationship with a dominant authority, and when power asymmetries give the former relatively little control over which aspects of their work and social identity are made visible or invisible to the latter. We draw on critical incident interviews from three organizations to illustrate a typology of six types of representational predicament: invasive spotlighting, idiosyncratic spotlighting, embedded background work, paradoxical social visibility, standardization of work processes, and standardization of work outputs. We analyse responses to representational predicaments according to whether they entailed exit, voice, loyalty, or neglect. Incumbents tended to respond with loyalty if they felt able and willing to accommodate their work behaviour and/or social identity to the dominant representations, and if there were sufficient compensatory factors, such as intrinsic rewards from the work or solidarity with colleagues. Exit or neglect appeared to reflect the belief that it was impossible to accommodate. Power asymmetries appeared to deter voice. Individual employees with a close and cordial working relationship with a member of a dominant authority group, or who were relationally networked to one, appeared not to experience representational predicaments

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    Coactivator complexes SAGA and NuA4 stimulate transcription by post-translationally modifying chromatin. Both complexes contain the Tra1 subunit, a highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related kinase (PIKK) family and a direct target for multiple sequence-specific activators. We present the Cryo-EM structure of Saccharomyces cerevsisae Tra1 to 3.7 Å resolution, revealing an extensive network of alpha-helical solenoids organized into a diamond ring conformation and is strikingly reminiscent of DNA-PKcs, suggesting a direct role for Tra1 in DNA repair. The structure was fitted into an existing SAGA EM reconstruction and reveals limited contact surfaces to Tra1, hence it does not act as a molecular scaffold within SAGA. Mutations that affect activator targeting are distributed across the Tra1 structure, but also cluster within the N-terminal Finger region, indicating the presence of an activator interaction site. The structure of Tra1 is a key milestone in deciphering the mechanism of multiple coactivator complexes
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