100 research outputs found
Emotion regulation skills mediate the effects of shame on eating disorder symptoms in women
No full textWe examined the impact of negative affectivity, chronic shame, and emotion regulation skills on eating disorder symptoms in undergraduate women (N = 154). We hypothesized that self-reported emotion regulation skills would mediate the well-documented relationship between chronic shame and eating disorder symptoms. Results revealed that chronic shame predicted eating disorder symptoms over and above general negative affectivity. Further, difficulties with emotion regulation mediated the relationship between chronic shame and ED symptoms. These findings suggest that chronic shame's role in eating disorder symptoms can be ameliorated by skillful emotion regulation.<br/
Interplay of polymer and oligonucleotide properties in the nature of antisense effects
No full textAntisense oligonucleotides can be utilized to silence the expression of a target gene via sequence-specific complementary base pairing. Antisense technology is applied as a basic research tool and is being developed therapeutically for a wide range of indications including cancer, inflammatory diseases and viral diseases. Its widespread application is impeded by the poor cellular delivery of oligonucleotides (ONs). Rational design of carriers for enhanced ON delivery demands a better understanding of the role of the vector on the extent and time course of antisense effects. This work highlights the interplay of polymer and ON properties in the nature of polymer mediated antisense responses. First, we demonstrate that ON structure exerts a significant influence on the strength of ON binding to, and dissociation from, the cationic polymer, poly-L-lysine. The finding implicates secondary structure as a relevant design parameter for antisense ONs and stresses the need for a comprehensive evaluation of ON-polymer structure-activity effects. Next, using well-characterized cationic polymer polyethyleneimine (PEI), we focus on understanding the effects of polymer molecular weight (MW) and ON backbone chemistry on antisense activity. We measure physico-chemical properties of complexes between PEI and phosphodiester and phosphorothioate backbone ONs, and evaluate their ability to deliver ONs to cells, leading to an antisense response. Our key finding is that the antisense activity is not determined solely by PEI MW or by ON chemistry, but rather by the interplay of both factors. Of particular importance is the strength of interactions between the carrier and the ON, which determines the rate at which the ONs are delivered intracellularly. Finally, we utilize the chemistry of the ONs as a means to influence the strength of interactions between PEI and ONs, and hence control the final antisense response. We show that it is possible to improve dramatically the efficiency of lower PEI MWs as ON carriers by manipulating the degree of phosphorothioate substitution in the ON chemistry. By correlating the PEI MW & ON chemistry with the observed antisense effects, we draw insightful structure-property relationships that will aid the rational design of ON carriers.Ph.D.Includes bibliographical references (p. 129-137)
Doing Business in Asia
No full textFrom the author of Doing Business in Europe (SAGE, 2018), Gabriele Suder has teamed up with Sumati Varma based in India, and Terence Tsai from China to bring this comprehensive solution for Asian business teaching and learning. The book offers a highly productive mix of international business and marketing theory, and is packed with pedagogical tools to engage and develop understanding, including two full-length corporate case studies per chapter. This is a unique volume covering the most relevant topics of Asia-focused business and management practice spanning from cross-cultural management to supply chain resilience to market entry and expansion strategy, and much more. Specifically designed to meet the needs of Postgraduate, MBA and those taking part in Executive Education programmes, this exciting learning experience will prepare Asia's leaders of the future
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Anger expression and adaptation to childhood sexual abuse: The role of disclosure context
No full textPrevious research on anger and childhood sexual abuse (CSA) is largely cross-sectional and retrospective. In this study, we prospectively examined the consequences of expressing anger among sexually abused women in contexts of either voluntarily disclosing or not disclosing a previous abuse episode. All CSA survivors in the study had documented histories of CSA.
These participants and a matched, nonabused sample were asked to describe their most distressing experience while being videotaped to allow coding of anger expression. Approximately two thirds of the CSA survivors voluntarily disclosed a previous abuse experience. Participants completed measures of internalizing symptoms and externalizing symptoms at the time of disclosure and again two years later.
The expression of anger was associated with better long-term adjustment (decreased internalizing and externalizing symptoms) but only among CSA survivors who had expressed anger while not disclosing an abuse experience. For CSA survivors who disclosed an abuse experience, anger expression was unrelated to long-term outcome. These findings suggest that the benefits of anger expression for CSA survivors may be context specific
Next-generation sequencing in non-muscle-invasive bladder cancer—a step towards personalized medicine for a superficial bladder tumor
No full textAbstract CT059: Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 for metastatic or surgically unresectable urothelial carcinoma harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) alterations
No full textAbstract
Background: Aberrant FGFR signaling results in tumor cell proliferation, migration, and survival, as well as angiogenesis, and is implicated in the development and progression of many cancers, including urothelial carcinoma (UC). Ten to 15% of patients with advanced UC have FGFR3 mutations and 6% have an FGFR3 translocation. INCB054828 is a novel, selective, orally administered inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activities (AACR 2015; Abstract 771).
Methods: This phase 2, open-label trial will evaluate INCB054828 monotherapy for histologically confirmed metastatic or unresectable UC (NCT02872714; Table). Eligible patients will have known FGF/FGFR alterations, will be ≥18 years of age, have Eastern Cooperative Oncology Group performance status ≤2, adequate liver and renal function, and have life expectancy ≥12 wks. Patients will have inadequate response to ≥1 previous treatment in this setting or will be platinum-ineligible, and must not have received any investigational drugs within 21 days of first dose, including selective FGFR inhibitors. Patients will self-administer INCB054828 orally once daily at a starting dose of 13.5 mg on a 21-day 2-weeks-on and 1-week-off cycle. Patients will receive treatment until disease progression or unacceptable toxicity. The primary endpoint will be objective response rate (complete plus partial responses assessed from CT scans [or MRI per investigator] using Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints will include safety, duration of response, progression-free survival, and overall survival. Exploratory endpoints will include predictive biomarker assessment. The study is currently recruiting; 96 patients are planned for the primary analysis (estimated to occur in March 2018).
Study DesignPrescreen for FGF/FGFR Status• Adults with metastatic/surgically unresectable urothelial carcinoma with inadequate response to ≥1 previous treatment or platinum-ineligible- Positive for FGF/FGFR alterations → continue screening- Negative for FGF/FGFR alterations → discontinue studyScreen for eligibility criteria and patient characteristics• Eastern Cooperative Oncology Group performance status ≤2• Adequate hepatic function (total bilirubin ≤1.5 × upper limit of normal [ULN; ≤2.5 × ULN for Gilbert syndrome or liver metastasis]; aminotransferases &lt;2.5 × ULN [&lt;5 × ULN for liver metastases])• Adequate renal function (creatinine clearance ≥30 mL/min; serum phosphate &gt;institutional ULN; serum calcium &gt;institutional normal range)• Life expectancy ≥12 weeksEnroll and start INCB054828 treatment• Oral once daily dosing: 21-day (2-weeks-on/1-week-off) cycleStart clinical assessment after cycle 3• Stable disease/partial or complete response → continue treatment on 21-day cycle; clinical assessments every 3 cycles• Disease progression → discontinue treatment; safety and survival follow-up
Citation Format: Neal D. Shore, Ekaterine Asatiani, Christine F. Lihou, Huiling Zhen, Sumati Gupta. Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 for metastatic or surgically unresectable urothelial carcinoma harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT059. doi:10.1158/1538-7445.AM2017-CT059</jats:p
Development and analysis of a sustainable garbage disposal model for environmental management under uncertainty
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Trait self-enhancement as a buffer against potentially traumatic events: A prospective study.
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