36 research outputs found

    The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions

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    Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here we describe the Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the U.S. The PrecISE Network was designed to conduct phase II/proof of concept clinical trials of precision interventions in the severe asthma population, and is supported by the National Heart Lung and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the Network will evaluate up to six interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for of severe asthma

    Come Together: An Ethnography of the Seattle Men's Chorus Family

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    Thesis (D.M.A.)--University of Washington, 2015This ethnography of the Seattle Men's chorus adds to the growing body of literature examining the culture of community choruses. The purpose of this ethnography was to examine the culture of a highly successful community men's chorus with particular attention to the musical and social interactions of its members in rehearsal and in post-rehearsal gatherings. The shared attitudes, values, goals, and practices of the Seattle Men's Chorus, the largest community chorus in North America and the largest gay men's chorus in the world were explored. This research utilized ethnographic techniques in gathering information that encompasses participation in this chorus, including an account of aims, processes, rehearsal outcomes, concerts, and events. Weekly and production-week rehearsals, retreats, concerts, outreach events, post-rehearsal gatherings, general meetings, and other community events were carefully documented over a two-and-a-half year period. The data were coded, categorized, and analyzed for themes and relationships. The Seattle Men's Chorus exhibited a complex network of relationships that may serve as a model for community choruses. The overarching theme that emerged was the community chorus as a "chosen family" that provides friendship, support, and a sense of self-worth to its members. More importantly, evidence revealed the presence of "social capital," a theory sociologists use to explore the maximizing of relationships on three different levels: bonding, bridging, and linking. The presence of all three types of social capital in the Seattle Men's Chorus is the crux of this study's examination into why it is so successful. The interplay of social capital and a shared musical experience led to the transformation of hearts and minds among the members of the chorus, the artistic director, and the audience. With the hope of serving as a model for artistic directors and the greater choral community, the indicators of social capital in the chorus are discussed and a model of the relationships among the chorus, artistic director, and the community are presented with implications for practice

    Retention: It’s all about respect

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    Retention of employees is often overlooked in developing strategies to deal with worker shortages in health care. Managers mistake requests for more money as the key indicator of job satisfaction. This article examines research conducted by three health service administration graduate students who looked at reasons staff were leaving their jobs or their occupations. Using three different research tools, the students found that job satisfaction is not all about money, or even benefits. Respect, recognition, and organizational commitment are what employees want in their jobs. The article describes the research methods used in the studies and the similarities in results. © 2003 Lippincott Williams & Wilkins, Inc

    Sensitivity of Cancer Cells to Plk1 Inhibitor GSK461364A Is Associated with Loss of p53 Function and Chromosome Instability

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    Polo-like kinases are a family of serine threonine kinases that are critical regulators of cell cycle progression and DNA damage response. Predictive biomarkers for the Plk1-selective inhibitor GSK461364A were identified by comparing the genomics and genetics of a panel of human cancer cell lines with their response to a drug washout followed by an outgrowth assay. In this assay, cell lines that have lost p53 expression or carry mutations in the TP53 gene tended to be more sensitive to GSK461364A. These more sensitive cell lines also had increased levels of chromosome instability, a characteristic associated with loss of p53 function. Further mechanistic studies showed that p53 wild-type (WT) and not mutant cells can activate a postmitotic tetraploidy checkpoint and arrest at pseudo-G(1) state after GSK461364A treatment. RNA silencing of WT p53 increased the antiproliferative activity of GSK461364A. Furthermore, silencing of p53 or p21/CDKN1A weakened the tetraploidy checkpoint in cells that survived mitotic arrest and mitotic slippage. As many cancer therapies tend to be more effective in p53 WT patients, the higher sensitivity of p53-deficient tumors toward GSK461364A could potentially offer an opportunity to treat tumors that are refractory to other chemotherapies as well as early line therapy for these genotypes. Mol Cancer Ther; 9(7); OF1-11. (c)2010 AACR
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