256 research outputs found

    Understanding Blogging Motivations in Palliative Care Using Maslow’s Hierarchy of Needs.

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    The pervasive use and potential of weblogs has increased the field of social health informatics and is becoming increasingly difficult to ignore. The prevalence of these technologies for narrative use brings about the fusion of diverse schools of thought on motivation. One proven model is that of Maslow, whose theory of needs has an intuitive appeal in understanding bloggers’ needs and motivations. This paper considers theoretical and practical blogging experiences for palliative care users through the embracement of Maslow’s hierarchy of needs. Palliative care patients, carers and clinicians were interviewed about their weblogs and data qualitatively analysed. The results indicate that the experience of maintaining a weblog is therapeutic for individuals and fulfils needs hierarchically from the lowest to the highest as outlined in Maslow’s theory

    Epigenetic Regulation of KPC1 Ubiquitin Ligase Affects the NF-κB Pathway in Melanoma.

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    Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA cohort, n = 370). Using melanoma cell lines, we investigated the functional interactions between KPC1 and NF-κB, and the epigenetic regulations of KPC1, including DNA methylation and miRNA expression.Results: We verified that KPC1 suppresses melanoma proliferation by processing NF-κB1 p105 into p50, thereby modulating NF-κB target gene expression. Concordantly, KPC1 expression was downregulated in American Joint Committee on Cancer stage IV melanoma compared with early stages (stage I/II P = 0.013, stage III P = 0.004), and low KPC1 expression was significantly associated with poor overall survival in stage IV melanoma (n = 137; HR 1.810; P = 0.006). Furthermore, our data showed that high miR-155-5p expression, which is controlled by DNA methylation at its promoter region (TCGA; Pearson\u27s r -0.455; P \u3c 0.001), is significantly associated with KPC1 downregulation (JWCI; P = 0.028, TCGA; P = 0.003).Conclusions: This study revealed novel epigenetic regulation of KPC1 associated with NF-κB pathway activation, promoting metastatic melanoma progression. These findings suggest the potential utility of KPC1 and its epigenetic regulation as theranostic targets. Clin Cancer Res; 23(16); 4831-42. ©2017 AACR

    Kant, race, and natural history

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    This article presents a new argument concerning the relation between Kant’s theory of race and aspects of the critical philosophy. It argues that Kant’s treatment of the problem of the systematic unity of nature and knowledge in the Critique of Pure Reason and the Critique of the Power of Judgment can be traced back a methodological problem in the natural history of the period – that of the possibility of a natural system of nature. Kant’s transformation of the methodological problem from natural history into a set of philosophical (and specifically epistemological) problems proceeds by way of the working out of his own problem in natural history – the problem of the natural history of the human races – and specifically the problem of the unity in diversity of the human species, in response to which he develops a theory of race. This theory of race is, further, the first developed model of the use of teleological judgment in Kant’s work. The article thus argues that Kant’s philosophical position on the systematic unity of nature and of knowledge in the first and third Critiques, and his account and defense of teleological judgment, are developed out of problems first articulated in his solution to the problem of the unity in diversity of the human species – that is, in his theory of race. The article does not seek to establish that these aspects of the critical philosophy are therefore racialised. But it does demonstrate, against those who deny its salience to his philosophy, how the problem of the unity in diversity of the human species and Kant’s theory of race is significant for the development of aspects of the critical philosophy and thus contributes to their philosophical problematics

    Acanthaster planci Outbreak: Decline in Coral Health, Coral Size Structure Modification and Consequences for Obligate Decapod Assemblages

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    Although benthic motile invertebrate communities encompass the vast majority of coral reef diversity, their response to habitat modification has been poorly studied. A variety of benthic species, particularly decapods, provide benefits to their coral host enabling them to cope with environmental stressors, and as a result benefit the overall diversity of coral-associated species. However, little is known about how invertebrate assemblages associated with corals will be affected by global perturbations, (either directly or indirectly via their coral host) or their consequences for ecosystem resilience. Analysis of a ten year dataset reveals that the greatest perturbation at Moorea over this time was an outbreak of the corallivorous sea star Acanthaster planci from 2006 to 2009 impacting habitat health, availability and size structure of Pocillopora spp. populations and highlights a positive relationship between coral head size and survival. We then present the results of a mensurative study in 2009 conducted at the end of the perturbation (A. planci outbreak) describing how coral-decapod communities change with percent coral mortality for a selected coral species, Pocillopora eydouxi. The loss of coral tissue as a consequence of A. planci consumption led to an increase in rarefied total species diversity, but caused drastic modifications in community composition driven by a shift from coral obligate to non-obligate decapod species. Our study highlights that larger corals left with live tissue in 2009, formed a restricted habitat where coral obligate decapods, including mutualists, could subsist. We conclude that the size structure of Pocillopora populations at the time of an A. planci outbreak may greatly condition the magnitude of coral mortality as well as the persistence of local populations of obligate decapods

    Finding meaning: HIV self-management and wellbeing among people taking antiretroviral therapy in Uganda

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    © 2016 Russell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited. The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's selfmanagement of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resourcelimited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': They saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other nonmedical aspects of wellbeing for self-management which ART programmes might explore further and encourage

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Dopamine D1 receptor expression is bipolar cell typeâ specific in the mouse retina

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    In the retina, dopamine is a key molecule for daytime vision. Dopamine is released by retinal dopaminergic amacrine cells and transmits signaling either by conventional synaptic or by volume transmission. By means of volume transmission, dopamine modulates all layers of retinal neurons; however, it is not well understood how dopamine modulates visual signaling pathways in bipolar cells. Here we analyzed Drd1aâ tdTomato BAC transgenic mice and found that the dopamine D1 receptor (D1R) is expressed in retinal bipolar cells in a typeâ dependent manner. Strong tdTomato fluorescence was detected in the inner nuclear layer and localized to type 1, 3b, and 4 OFF bipolar cells and type 5â 2, XBC, 6, and 7 ON bipolar cells. In contrast, type 2, 3a, 5â 1, 9, and rod bipolar cells did not express Drd1aâ tdTomato. Other interneurons were also found to express tdTomato including horizontal cells and a subset (25%) of AII amacrine cells. Diverse visual processing pathways, such as color or motionâ coded pathways, are thought to be initiated in retinal bipolar cells. Our results indicate that dopamine sculpts bipolar cell performance in a typeâ dependent manner to facilitate daytime vision. J. Comp. Neurol. 524:2059â 2079, 2016. © 2015 Wiley Periodicals, Inc.Using Drd1aâ tdTomato BAC transgenic mice, authors investigated dopamine D1 receptor localization in retinal bipolar cells. Both ON and OFF bipolar cells express D1 receptors in a typeâ dependent manner.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137524/1/cne23932.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137524/2/cne23932_am.pd

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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