164 research outputs found
The Mature Market: Underlying Dimensions and Group Differences of a Potential Market for the Hotel Industry
The mature market, defined as age 55 and up and consisting of approximately 64 million Americans, is expected to increase. Studies show that this group travels more frequently, travels greater distances, and stays longer. The authors seek to determine if underlying dimensions exist for the mature individual with regard to the selection criteria for lodging when traveling for pleasure, and to determine if differences exist between various demographic subsegments of this market with regard to these underlying dimensions
Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1
During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.This work was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Fellowship (to I.A. Parish); a Yale School of Medicine Brown-Coxe Postdoctoral Fellowship (to I.A. Parish); the Alexander von Humboldt Foundation (SKA2010, to P.A. Lang); a CIHR grant (to P.S. Ohashi); and by the Howard Hughes Medical Institute and NIH grant RO1AI074699 (to S.M. Kaech). P.S. Ohashi holds a Canada Research Chair in Autoimmunity and Tumor immunity
Grown, Printed, and Biologically Augmented: An Additively Manufactured Microfluidic Wearable, Functionally Templated for Synthetic Microbes
Despite significant advances in synthetic biology at industrial scales, digital fabrication challenges have, to date, precluded its implementation at the product scale. We present, Mushtari, a multimaterial 3D printed fluidic wearable designed to culture microbial communities. Thereby we introduce a computational design environment for additive manufacturing of geometrically complex and materially heterogeneous fluidic channels. We demonstrate how controlled variation of geometrical and optical properties at high spatial resolution can be achieved through a combination of computational growth modeling and multimaterial bitmap printing. Furthermore, we present the implementation, characterization, and evaluation of support methods for creating product-scale fluidics. Finally, we explore the cytotoxicity of 3D printed materials in culture studies with the model microorganisms, Escherichia coli and Bacillus subtilis. The results point toward design possibilities that lie at the intersection of computational design, additive manufacturing, and synthetic biology, with the ultimate goal of imparting biological functionality to 3D printed products.National Science Foundation (U.S.) (DGE1144152)United States. Department of Energy (DE-SC0012658
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer\u27s disease.
The use of fixed fibroblasts from familial and sporadic Alzheimer\u27s disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer\u27s disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer\u27s disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed \u27lipid-MERCs\u27 (gap width \u3c10 nm), while \u27Ca2+-MERCs\u27 (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer\u27s disease-related neurons.This article has an associated First Person interview with the first author of the paper
Understanding Compliance Dynamics in Community Justice Settings
This article seeks to expand the existing literature on compliance in community justice settings by highlighting the importance of service user participation in efforts to achieve compliance. The article’s central argument is that although co-productive strategies can enhance service user participation, the degree to which co-production is achievable in penal supervision is perhaps uncertain, and has received insufficient theoretical or empirical attention. To address the gap in knowledge, the article draws on the data generated from a study of compliance in Wales, United Kingdom, and employs the Bourdieusian concepts of habitus, field, and capital to argue that the convergence of two key factors undermines the viability of co-productive strategies in penal settings. One factor is the service users’ habitus of powerlessness which may breed passivity rather than active participation. The second also relates to the power dynamics that characterize penal supervision contexts. Within these contexts, practitioners are statutorily empowered to implement and enforce the requirements of community orders. In the current target-focused policy climate in England and Wales, practitioners may prioritize measurable compliance over forms of compliance that stem from service user participation and engagement perhaps because these are not readily quantifiable
Search Strategy for The Benefits, Burdens, and Risks of Participation in Pediatric Palliative Care and End of Life Research: a Systematic Review
The Benefits and Burdens of Pediatric Palliative Care and End-of-Life Research: A Systematic Review
Objective: The aim of this study is to report the benefits and burdens of palliative research participation on children, siblings, parents, clinicians, and researchers.
Background: Pediatric palliative care requires research to mature the science and improve interventions. A tension exists between the desire to enhance palliative and end-of-life care for children and their families and the need to protect these potentially vulnerable populations from untoward burdens.
Methods: Systematic review followed PRISMA guidelines with prepared protocol registered as PROSPERO #CRD42018087304. MEDLINE, CINAHL, PsycINFO, EMBASE, Scopus, and The Cochrane Library were searched (2000–2017). English-language studies depicting the benefits or burdens of palliative care or end-of-life research participation on either pediatric patients and/or their family members, clinicians, or study teams were eligible for inclusion. Study quality was appraised using the Mixed Methods Appraisal Tool (MMAT).
Results: Twenty-four studies met final inclusion criteria. The benefit or burden of palliative care research participation was reported for the child in 6 papers; siblings in 2; parents in 19; clinicians in 3; and researchers in 5 papers. Benefits were more heavily emphasized by patients and family members, whereas burdens were more prominently emphasized by researchers and clinicians. No paper utilized a validated benefit/burden scale.
Discussion: The lack of published exploration into the benefits and burdens of those asked to take part in pediatric palliative care research and those conducting the research is striking. There is a need for implementation of a validated benefit/burden instrument or interview measure as part of pediatric palliative and end-of-life research design and reporting
Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis
Association between microvessel density (MVD) and tumor characteristics among breast cancer cases (n = 44). (DOC 54 kb
Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast
Precision health: A nursing perspective
Precision health refers to personalized healthcare based on a person's unique genetic, genomic, or omic composition within the context of lifestyle, social, economic, cultural and environmental influences to help individuals achieve well-being and optimal health. Precision health utilizes big data sets that combine omics (i.e. genomic sequence, protein, metabolite, and microbiome information) with clinical information and health outcomes to optimize disease diagnosis, treatment and prevention specific to each patient. Successful implementation of precision health requires interprofessional collaboration, community outreach efforts, and coordination of care, a mission that nurses are well-positioned to lead. Despite the surge of interest and attention to precision health, most nurses are not well-versed in precision health or its implications for the nursing profession. Based on a critical analysis of literature and expert opinions, this paper provides an overview of precision health and the importance of engaging the nursing profession for its implementation. Other topics reviewed in this paper include big data and omics, information science, integration of family health history in precision health, and nursing omics research in symptom science. The paper concludes with recommendations for nurse leaders in research, education, clinical practice, nursing administration and policy settings for which to develop strategic plans to implement precision health
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