Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma ...microenvironment for recapitulating a patient's tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient's culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene's expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine.
Comprehensive and accurate identification of structural variations (SVs) from next generation sequencing data remains a major challenge. We develop FusorSV, which uses a data mining approach to ...assess performance and merge callsets from an ensemble of SV-calling algorithms. It includes a fusion model built using analysis of 27 deep-coverage human genomes from the 1000 Genomes Project. We identify 843 novel SV calls that were not reported by the 1000 Genomes Project for these 27 samples. Experimental validation of a subset of these calls yields a validation rate of 86.7%. FusorSV is available at https://github.com/TheJacksonLaboratory/SVE .
ObjectiveIdentify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19.DesignMulticentre prospective observational cohort study ...using questionnaire data at visit 1 (2–7 months post discharge) and visit 2 (10–14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations.Setting64 UK acute hospital Trusts.ParticipantsAdults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19.Main outcome measuresSelf-reported swallow, communication, voice and cognitive compromise.ResultsCompromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001).ConclusionSwallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.
At times, nurses receive patient disclosures that have the potential to create challenges resulting in needs for strategies to manage patient information and expectations. This study examines ...disclosure predicaments nurses experience in critical care and emergency units at a large urban hospital. Utilizing the constant comparative method to identify disclosure themes guided by the principles of communication privacy management (CPM), the findings show that nurses regulate patient privacy in the role of stakeholder confidants. Second, disclosure predicaments occur in three different contexts: during the course of nurses' professional routine; when the nurses created safe terminals or havens for patients to talk; and when family matters became an inseparable part of caring for the patient. Third, the results indicate that there are several specific strategies that nurses use to manage disclosure predicaments they encounter. The lens of CPM is used to interpret these findings and offers a context in which to better understand the needs of nurses concerning patient disclosive behavior and privacy issues for nurses.
This PhD explores the long-term experience of male homosexual desire from the late-Victorian period to the twenty-first century. It demonstrates that John Addington Symonds (1840–1893), A. E. Housman ...(1859–1936), E. M. Forster (1879–1970), Christopher Isherwood (1904–1986) and Alan Hollinghurst (b. 1954) write poetry and prose about attractions and relationships between men spanning years and decades. Through their narratives, these writers portray a homosexual desire for long-term intimacy. The literary texts studied here challenge the prevailing critical idea that domesticated, monogamous, long-term forms of commitment are valued primarily due to Western heteronormative ideologies. These writers are not motivated by the “chrononormativity” of heteronormativity, a valuation of the home, family and marriage which, as Lauren Berlant and Michael Warner argue, “signifies belonging to culture in a deep and normal way”. Rather, each writer desires a long-term connection and commitment between sexually and romantically attracted partners who, with the passage of time, develop and deepen a feeling of being intimately, uniquely understood. They identify that the passage of time creates tensions between desire and anxiety, possession and loss, familiarity and idealisation, particularly in contexts of homosexual illegality. Long-term relationships are valued in these writers’ works as they present the possibility of sharing these tensions. This PhD demonstrates that the desire for intimacy is complicated by the emotional limitations imposed by the illegality of homosexuality. It analyses illicit fantasies of intimacy and memories of lost relationships and unrequited love that are shaped by anxieties surrounding criminality and exile from home. It also analyses clandestine sexual and romantic friendships and domestic partnerships which are both curtailed and ennobled by the need to hide samesex love and to resist mainstream stereotypes. This thesis argues that each of these texts is motivated by the desire, the impossibility, or the chance of sharing one’s experience of illicit same-sex desire with another person. Queer theorists argue that the recent advent of marital equality threatens to normatively “sanitise” homoerotic experience. This thesis concludes that gay marriage can also be read as the result of a desire for long-term intimacy which is uniquely formed by a contemporary context of visibility, understanding and empathy. This study reads a homosexual literary tradition that values the long term as a narrative which can produce and share an intimate understanding of same-sex desire.
The present study analyzes argument in jury deliberations by using the Conversational Argument Coding Scheme (CACS) and the content of juror argument using Subject Matter Argument Assessment (SMAA) (
...Pettus, 1990
). The main purpose is to illustrate how the two coding schemes can complement each other to provide rich yet systematic characterization of argument in jury deliberation. Jury deliberations drawn from In the Jury Room, a televised news series on jury deliberation, are coded and analyzed using CACS and SMAA. The researchers found that using two argument coding schemes is beneficial in learning about the types of arguments jurors make and the subject matter about which they argue. The study results are compared with findings from previous studies of juror argument behavior, suggesting that argument in mediated juries differs from argument in mock juries.
The authors examined the communication of affection in men's relationships with their fathers. Drawing from Affection Exchange Theory, the authors advanced four predictions: (a) heterosexual men ...receive more affection from their own fathers than do homosexual or bisexual men, (b) fathers communicate affection to their sons more through supportive activities than through direct verbal statements or nonverbal gestures, (c) affectionate communication between fathers and sons is linearly related to closeness and interpersonal involvement between them, and (d) fathers' awareness of their sons' sexual orientation is associated with the amount of affection that the fathers communicate to them. Participants were 170 adult men who completed questionnaires regarding affectionate communication in their relationships with their fathers. Half of the men were self-identified as exclusively heterosexual, and the other half were self-identified as exclusively homosexual or bisexual. The results supported all predictions substantially.
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