811 research outputs found

    Anti-myeloperoxidase antibody positivity in patients without primary systemic vasculitis

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    PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

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    Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV

    Cardiorespiratory fitness, fatness and the acute blood pressure response to exercise in adolescence

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    Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) areindependent contributors to cardiovascular risk, but their interrelated associationswith exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort ofadolescents.Methods: 2292 adolescents from the Avon Longitudinal Study of Parents andChildren (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercisestep test that allowed fitness (VO2 max) to be determined from workload and heart rateusing a validated equation. Exercise BP was measured immediately on test cessationand fatness calculated as the ratio of total fat mass to total body mass measured byDXA.Results: Post-exercise systolic BP decreased stepwise with tertile of fitness (146(18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142(16); 149 (18) mmHg). In separate models, fitness and fatness were associated withpost-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomicstatus (standardized β: −1.80, 95%CI: −2.64, −0.95 mmHg/SD and 4.31, 95%CI:3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in thesame model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69,5.61 mmHg/SD).Conclusion: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness mayonly be realized with more favorable body composition

    A New Crocodylian from the Late Maastrichtian of Spain: Implications for the Initial Radiation of Crocodyloids

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    The earliest crocodylians are known primarily from the Late Cretaceous of North America and Europe. The representatives of Gavialoidea and Alligatoroidea are known in the Late Cretaceous of both continents, yet the biogeographic origins of Crocodyloidea are poorly understood. Up to now, only one representative of this clade has been known from the Late Cretaceous, the basal crocodyloid Prodiplocynodon from the Maastrichtian of North America.The fossil studied is a skull collected from sandstones in the lower part of the Tremp Formation, in Chron C30n, dated at -67.6 to 65.5 Ma (late Maastrichtian), in Arén (Huesca, Spain). It is located in a continuous section that contains the K/P boundary, in which the dinosaur faunas closest to the K/P boundary in Europe have been described, including Arenysaurus ardevoli and Blasisaurus canudoi. Phylogenetic analysis places the new taxon, Arenysuchus gascabadiolorum, at the base of Crocodyloidea.The new taxon is the oldest crocodyloid representative in Eurasia. Crocodyloidea had previously only been known from the Palaeogene onwards in this part of Laurasia. Phylogenetically, Arenysuchus gascabadiolorum is situated at the base of the first radiation of crocodyloids that occurred in the late Maastrichtian, shedding light on this part of the cladogram. The presence of basal crocodyloids at the end of the Cretaceous both in North America and Europe provides new evidence of the faunal exchange via the Thulean Land Bridge during the Maastrichtian

    Research in User-Centered Design 2009 to 2018: A Systematic Keyword Network Analysis

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    User-centered design (UCD) has become an important concept in Human-Computer Interaction (HCI) and other disciplines. While there is abundant UCD research, keyword analysis research has been less studied even though keywords are important for achieving better understanding of UCD. Therefore, this study provides keywords network a visual analysis of UCD articles published between 2009 and 2018 to answer the following questions: (1) What UCD-related keywords have been studied and in which disciplines? and (2) How have keywords been connected to on another? The study analyzed 304 keywords articles from IEEE, ACM, and ScienceDirect that included “UCD” in their titles. It utilized Gephi 0.9.2 to visualize keyword frequencies, relationships, and authors’ disciplines. The findings presented that the five most frequently mentioned keywords regarding UCD were “usability,” “HCI,” “User Experiences,” “User-Centered,” and “User Interfaces”. The top five most identified disciplines in the UCD articles were Computer Science, Design, Engineering, Education, and Psychology. In visualizing this data, we created a keyword hierarchy with various sizes of texts and circles, and we denoted various relationship levels between keywords by different weights of edges. This visualization of the selected 43 keywords shows a clear relationship between keywords in which UCD is strongly related to usability, UX, user-centered, HCI, Persona, prototype, interaction design, interface design, assistive technology, design thinking. The findings can be valuable in understanding the current UCD research mainstream for researchers and designers pursuing interdisciplinary approaches

    Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue.

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    E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

    The genomes of two key bumblebee species with primitive eusocial organization

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    Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

    Antimicrobial management and appropriateness of treatment of urinary tract infection in general practice in Ireland

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    <p>Abstract</p> <p>Background</p> <p>Urinary tract infections (UTIs) are the second most common bacterial infections in general practice and a frequent indication for prescription of antimicrobials. Increasing concern about the association between the use of antimicrobials and acquired antimicrobial resistance has highlighted the need for rational pharmacotherapy of common infections in general practice.</p> <p>Methods</p> <p>Management of urinary tract infections in general practice was studied prospectively over 8 weeks. Patients presenting with suspected UTI submitted a urine sample and were enrolled with an opt-out methodology. Data were collected on demographic variables, previous antimicrobial use and urine samples. Appropriateness of different treatment scenarios was assessed by comparing treatment with the laboratory report of the urine sample.</p> <p>Results</p> <p>A total of 22 practices participated in the study and included 866 patients. Bacteriuria was established for 21% of the patients, pyuria without bacteriuria for 9% and 70% showed no laboratory evidence of UTI. An antimicrobial agent was prescribed to 56% (481) of the patients, of whom 33% had an isolate, 11% with pyuria only and 56% without laboratory evidence of UTI. When taking all patients into account, 14% patients had an isolate identified and were prescribed an antimicrobial to which the isolate was susceptible. The agents most commonly prescribed for UTI were co-amoxyclav (33%), trimethoprim (26%) and fluoroquinolones (17%). Variation between practices in antimicrobial prescribing as well as in their preference for certain antimicrobials, was observed. Treatment as prescribed by the GP was interpreted as appropriate for 55% of the patients. Three different treatment scenarios were simulated, i.e. if all patients who received an antimicrobial were treated with nitrofurantoin, trimethoprim or ciprofloxacin only. Treatment as prescribed by the GP was no more effective than treatment with nitrofurantoin for all patients given an antimicrobial or treatment with ciprofloxacin in all patients. Prescribing cost was lower for nitrofurantoin. Empirical treatment of all patients with trimethoprim only was less effective due to the higher resistance levels.</p> <p>Conclusions</p> <p>There appears to be considerable scope to reduce the frequency and increase the quality of antimicrobial prescribing for patients with suspected UTI.</p
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