535 research outputs found
Assessment of the effectiveness of cardiac rehabilitation on the maintenance of healthy lifestyle modifications: An international comparison between England and New Zealand
Full text linkSecondary preventive Cardiac Rehabilitation (CR) programmes are the most cost effective measure for reducing mortality and morbidity associated with Cardiovascular Disease (CVD), and are now recommended internationally (BHF, 2007a). There are two structured CV rehabilitation programmes based on specific sets of guidelines: the American Cardiology Sports Medicine (ACSM) guidelines and the British Association Cardiac Rehabilitation (BACR) guidelines. New Zealand (NZ) practice under the ACSM guidelines, while the United Kingdom (UK) practice under the BACR guidelines. The purpose of this study is to compare patients CR experiences between the UK and NZ based on their effectiveness at successfully motivating patients to maintain healthy behaviours. Data was collected from non-participant observations, and focus groups with patients 6-12months post CR. Results were analysed using thematic analyses and reflection in action. Both CR programmes have been successful in supporting the individuals to maintain healthy lifestyles. A number of similar positive CR experiences were noted between groups and countries: support, education, positive mental attitude, motivation, and help to facilitate individuals to maintain healthy lifestyles. Diet and exercise were the main themes influenced. Exercising in a friendly environment, with companionship was significant to the maintenance of exercise for participants in both countries. Barriers such as physical disabilities, time constraints, and weather conditions helped to inhibit healthy behaviour maintenance. Those in NZ seemed to be more affected by external factors such as opportunity, access, and work. Individuals’ confidence appeared higher in the UK in regards to monitoring themselves. Exploring patients’ views and experiences through discussion provided an insight in these programmes, and could assist in future CR developments, addressing the barriers to such developments. The study highlighted that less monitoring in NZ is required. Also, further future developments for NZ could include improving referrals for CR intervention, and improvements in opportunities to access exercise sessions with other CV individuals. Future research into continuing social support through exercise sessions and education discussion groups could be a step towards tackling the drop-out rates in both countries
Abstract NTOC-095: THE SYNERGISTIC EFFECTS OF CARBOPLATIN AND PF–477736, A SMALL MOLECULE CHECKPOINT KINASE 1 INHIBITOR ON A PLATINUM RESISTANT OVARIAN CANCER CELL LINE
No full textAbstract
PURPOSE: To investigate the effects of PF-477736, a small molecular checkpoint kinase 1 (Chk1) inhibitor with and without carboplatin on cell apoptosis and proliferation in a p53-mutated platinum resistant ovarian cancer cell line.
METHODS: OVCAR3 cells were treated with PF-477736 alone and in combination with carboplatin. Western blot analyses were performed to assess the protein expression of Chk1, phosphorylated Chk1, H2AX, and phosphorylated H2AX. Cell proliferation was evaluated with colony formation assays 10 days following treatment and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assays over the course of 5 days following treatment. Cell apoptosis was measured with flow cytometry after staining with FITC Annexin V and propidium iodide. Paired t-tests were performed for comparative analyses.
RESULTS: PF-477736 decreased the expression of phosphorylated Chk1 on serine 249 within 24 hours following treatment as seen on Western blot assay. Total Chk1 expression was unchanged after treatment with PF-477736.
The combination treatment of PF-477736 and carboplatin effectively decreased OVCAR3 cell proliferation. Colony formation assays revealed fewer colonies after dual treatment with PF-477736 and carboplatin compared to PF-477736 alone (average colony count 1.5 vs 13.6, p = 0.03) and compared to carboplatin alone (average colony count 1.5 vs 9.7, p < 0.001). MTT assays demonstrated a synergistic effect with PF-477736 and carboplatin: dual treated cells had lower mean dye absorbance values than PF-477736 alone (mean absorbance fold change 1.7 vs 3.2, p = 0.009) and carboplatin alone (mean absorbance fold change 1.7 vs 5.6, p < 0.001).
OVCAR3 cells after treatment with PF-477736 and carboplatin had higher rates of apoptosis. On flow cytometry, a higher proportion of cells stained with the apoptotic markers Annexin V and propidium iodide after treatment with PF-477736 and carboplatin compared to PF-477736 alone (percentage of apoptotic cells 34.9% vs 13.0%, p = 0.004) and carboplatin alone (percentage of apoptotic cells 34.9% vs 16.0%, p = 0.008). In addition, western blot analysis of the cell lysates following dual treatment of PF-477736 and carboplatin showed increased expression of phosphorylated H2AX, a marker of double-stranded DNA damage while there was minimal expression with PF-477736 alone and carboplatin alone.
CONCLUSIONS: Carboplatin and PF-477736, a small molecule Chk1 inhibitor, synergistically decreased cell proliferation and increased cell apoptosis in OVCAR3 cells, an in vitro model of platinum resistant ovarian cancer. PF-477736 may be a potential new therapeutic strategy for the resensitization of platinum resistant ovarian cancer.
Citation Format: Jessica Lee MD, Stephanie V. Blank MD, Robert J. Schneider MD. THE SYNERGISTIC EFFECTS OF CARBOPLATIN AND PF–477736, A SMALL MOLECULE CHECKPOINT KINASE 1 INHIBITOR ON A PLATINUM RESISTANT OVARIAN CANCER CELL LINE [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-095.</jats:p
Shedding Light on the Venom Proteomes of the Allergy-Relevant Hymenoptera Polistes dominula (European Paper Wasp) and Vespula spp. (Yellow Jacket)
Full text linkAllergic reactions to stings of Hymenoptera species can have serious or even fatal consequences. If the identification of the culprit insect is possible, venom-specific immunotherapy effectively cures Hymenoptera venom allergies. Although component-resolved diagnostics has strongly evolved in recent years, the differentiation between allergies to closely related species such as Polistes dominula and Vespula spp. is still challenging. In order to generate the basis for new diagnostic and therapeutic strategies, this study aims at resolving the venom proteomes (venomes) of these species. The venoms of P. dominula and Vespula spp. (V. germanica, V. vulgaris) were analyzed by liquid chromatography-mass spectrometry. Resulting proteins were characterized regarding their function, localization and biochemical properties. The analyses yielded 157 proteins in Vespula spp. and 100 in P. dominula venom; 48 proteins, including annotated allergens, were found in both samples. In addition to a variety of venom trace molecules, new allergen candidates such as icarapin-like protein and phospholipase A2 were identified. This study elucidates the venomes of closely related allergy-eliciting Hymenoptera species. The data indicates that relying on marker allergens to differentiate between P. dominula and Vespula spp. venom allergy is probably insufficient and that strategies using cross-reactive major allergens could be more promising
Concept generation methods in highly constrained design problems
No full textThesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 101-110).Innovation and creativity are prioritized in engineering solutions, yet engineers and designers must also grapple with complex design problems which are highly constrained by requirements, regulations, and limited resources. This research seeks to understand the relationship between design constraints and concept generation methods in order to support innovation and creativity in the design of complex systems. A design study was conducted with 12 groups of civilian engineers from the Naval Undersea Warfare Center Division Newport. Participants were asked to generate concepts for two different design problems in which the ideation method and level of constraint were varied. Group brainstorming and a modified 6-3-5 method were used as a direct comparison, while a sketch modelling exercise was also incorporated to obtain qualitative observations and serve as a training exercise for participants. All generated ideas during the study were evaluated on four different ideation metrics: quantity, variety, quality, novelty. Constraint did not have a significant effect on quantity or variety; however low constrained problems produced statistically more novel ideas (for brainstorming only) and high constrained problems produced statically higher quality ideas (for both brainstorming and modified 6-3-5). The concept generation method has a marginally significant effect on the quality and variety; a modified 6-3-5 method produces a marginally higher quantity and brainstorming produces a marginally higher variety. Brainstorming produces significantly higher novelty and modified 6-3-5 method produces significantly higher quality (only for low constrained cases). The design task itself has a significant interaction effect on quantity, novelty, and quality of ideas generated which warrants further investigation.by Stephanie V. Proule.S.M
Sectoral allocation by gender of Latin American workers over the liberalization period of the 1990s
Full text linkThe recent restructuring of Latin American economies has renewed interest in the effects of trade liberalization, on labor markets, and on the gender division of labor. The author does not attempt to establish casuality between economic reforms, and the types of jobs that men and women hold. Instead, she provides a detailed description of the trends in male, and female formal, and informal sector participation during the economic reform period in Argentina, Brazil, and Costa Rica. The author first compares the gender composition of the formal, informal wage, and self-employment sectors in a year before reforms (1988 for Argentina, 1989 for Brazil, and Costa Rica), and a year after reforms implementation (1997 for Argentina, 1995 for Brazil and Costa Rica). Although women continued to be more likely than men to work in the informal wage sector, there is no trend of"masculinization"or"feminization"of the informal sector, or any other. Instead, in Argentina men have overtaken women as the most prevalent workers in the informal wage sector, while in Brazil, the opposite has occurred (as men move into self-employment). In Costa Rica there have been no statistical, observable changes. The author then considers the distribution across sectors within each gender group, to identify whether men, and women are more likely to select different sectors in the post-reform period relative to the pre-reform period. Among both men, and women in all three countries (except Brazilian men), workers have become more likely to hold informal wage jobs, and less likely to hold formal sector jobs. Trends in human capital accumulation explain these changes for both men, and women, while changes in gender roles, primarily in homecare and marriage, do not seem to have an effect.Health Monitoring&Evaluation,Labor Policies,Population&Development,Public Health Promotion,Environmental Economics&Policies,Health Monitoring&Evaluation,Environmental Economics&Policies,Population&Development,Banks&Banking Reform,Work&Working Conditions
Prophylactic and Risk-Reducing Bilateral Salpingo-oophorectomy: Recommendations Based on Risk of Ovarian Cancer
No full textAn investigation of the role of thought-shape fusion in disordered eating
No full textA literature review presents research investigating the role of thought-shape fusion (TSF) in eating disorder psychopathology. As TSF is a relatively new area of research, reviewing literature at this stage aimed to identify methodological issues, directions for future research, and clinical implications of findings, to aid progression of research and treatments for those with eating disorders. Literature was discussed in relation to criteria set out by Shafran et al. (1999) to determine whether a cognitive distortion plays a role in a psychopathological disorder. Evidence suggests TSF does have a role to play, as it was associated with eating disorder psychopathology and experimental manipulation of the construct increased feelings of fatness, moral wrongdoing, urges to carry out neutralising behaviours, anxiety, and guilt, in clinical and non-clinical samples, which are key maintaining factors of eating disorder psychopathology (Fairburn et al., 2003). However, it was unclear from the literature whether perceived likelihood of weight gain also increased. Research is yet to investigate whether a reduction in TSF leads to a reduction in disordered eating, and the role of other factors (such as thought control strategies) in TSF and disordered eating behaviours. The empirical study investigated whether TSF and thought suppression led to more disordered eating in a university sample. Questionnaires measuring TSF, thought suppression, and disordered eating behaviours, were completed online by 355 participants. The findings showed TSF had a significant main effect on all disordered eating behaviours measured, apart from purging. Thought suppression had a main effect on binge-eating behaviours and global eating disorder psychopathology only. Thought suppression was also found to add to the effects of TSF on disordered eating behaviours, but no significant interaction effects emerged. Future research is needed to determine whether similar findings exist in a clinical sample
Next-Generation Philanthropy: Examining a Next-Generation Jewish Philanthropic Network
Full text link· As a result of mobility, philanthropy among a Millennial group of Jewish donors is becoming divorced from the communities in which their parents live.
· This group’s members generally perceive themselves as thinking and acting more strategically than past generations. They expect philanthropic organizations to operate with increased transparency, and those entities will need to adapt to these expectations in order to thrive.
· The characteristics that define the Millennial generation – open-mindedness, a desire for meaningful employment and philanthropic activity, technological adeptness, innovation – are changing philanthropy.
· Despite those changes, philanthropic priorities among families remain substantially constant and transcend generations
Holding the village accountable: a comparative case study of two economically divergent communities to investigate the extent social capital impacts student achievement in STEM, 2016
Full text linkThis dissertation explores the extent social capital and social networking impact student achievement in STEM within communities of divergent affluence and influence. The lack of parity of academic amenities within communities, including academic tutoring, math and science classes, and workshops tend to impede student achievement within the schoolhouse. Therefore, activities occurring within households result in each communitys ability to serve as either a bridge or a barrier to student academic success. The author argues that through community mobilization to drive further access to community-based academic resources, students can be connected to opportunities to nourish their STEM competencies, which will lead to increased success in the core STEM courses of mathematics and science. Communities with higher socioeconomic standings have an embedded innate framework of networking through associations and affiliations. Due to these memberships in a cross-section of activities, including neighborhood associations, parent groups, and civic organizations, there is a natural ebb and flow of communication and action that encourages opportunities to emerge for the benefit of its community's children. The author investigated the relationship between student STEM achievement in school and the ability of families to access academic opportunities outside of the school environment. Data collected included an array of primary and secondary sources, student state test scores, and program marketing documents of STEM education providers. To further explore the relationship between variables, surveys completed by community stakeholders and parents were distributed and analyzed. The quality of instruction occurring within community-based STEM opportunities was measured through analyses of survey instruments and documents, curriculum standards, and approaches to learning. KEY TERMS: Access to Academic Amenities, Quality of Instruction within Academic Amenities, Parent Involvement, Community Cohesiveness, Student Achievement, Out-of-School-Time, STEM, Educational Leadershi
Abstract MIP-051: EFFICACY OF MTORC1/2 INHIBITION ON OVARIAN CANCER STEM CELLS
No full textAbstract
INTRODUCTION: Ovarian cancer is the most lethal gynecologic malignancy. Initial treatment with platinum and taxane drugs are effective, however inevitably these patients will recur and become resistant to cytotoxic therapies. Thus, new alternatives for durable treatments need to be identified. One approach is to explore the heterogeneity of epithelial ovarian cancer and identify the subpopulation of cells that are resistant to treatment. It has been hypothesized, that cancer stem cells (CSCs) can survive chemotherapy and have enhanced tumor-initiating capabilities. The AKT-PI3K-mTOR pathway is well studied and has been shown to be critical for tumor cell survival. This pathway closely regulates both mTOR complexes (mTORC1 and mTORC2). mTORC1 regulates protein synthesis and autophagy whereas mTORC2 regulates cell motility. mTORC1 and 2 ultimately affect cell proliferation, survival and angiogenesis, all inherently important in tumorgenesis.
OBJECTIVES: Rapalogs are specific and potent inhibitors of mTORC1 but have no effect of mTORC2. We investigate the efficacy of dual mTORC1/2 inhibitors and its effect on the CSC population.
METHODS: Carboplatin resistant ovarian cancer cell line OVCAR3 were cultured and treated with dimethyl sulfoxide (DMSO), carboplatin, or INK128, a potent dual inhibitor of mTORC1/2. Using cell surface markers CD133 and CD44, CSCs were quantified by flow cytometry. OVCAR3 spheroids were cultured as a surrogate for CSCs. Colony formation-survival assays were performed with spheroids treated with the above mentioned conditions. Analysis was performed using ArrayScan technology. Doxycyline inducible silencing cell lines derived from OVCAR3 were generated; Non-silenced (Nsi), Raptor (Sh-mTORC1) and Rictor (Sh-mTORC2). Colony formation assays using spheroids from silenced lineages were performed to evaluate growth and survival. Western blot analysis was performed to confirm silencing of targets, and to evaluate protein expression in CSCs.
RESULTS: 4.87% of the untreated OVCAR3 population were CSCs. INK128 treatment of the cells confered a 2 fold increase of CD44+/CD133+ cells, presumably CSCs, P&lt;0.005 and no difference between DMSO and carboplatin treated cells (NS). INK128 treated cells formed fewer colonies in comparison to DMSO (mean number of colonies 36.3 + 23.8 vs. 83.3 + 32.1, P&lt;0.001) and smaller colonies (mean number of cells in a colony 5260 + 835.8 vs 6907 + 702.4 P &lt;0.0002). Similar populations of CD44+/CD133+ were isolated in Nsi and Raptor (NS), and there were no difference in the number or size of colonies. In comparison to Nsi, Rictor resulted in 50% decrease in CD44+/CD133+ cells, (P &lt;0.002) and fewer colonies (1.6+1.3 vs 10+7.2, p&lt; 0.03). There was no difference in colony size. CSCs expressed Oct4, Sox2 and phosphorylated 4E-BP1 confirms activation of AKT.
CONCLUSIONS: The PI3K/AKT/mTOR pathway appears to have a role in the biogenesis of platinum resistant ovarian cancer cells. The inhibition of mTORC1/2 delays growth of OVCAR3 cells, and may have a role in activating in stem like CSCs. However, it does not appear to selectively inhibit CD133+/CD44+ cells. These findings suggest that targeting CSCs may lead to advances in ovarian cancer treatment.
Citation Format: Jing-Yi Chern MD, Melissa Frey MD, Fernanda Musa MD, Amandine Alard PhD, Stephanie V. Blank, MD, Robert Schneider, PhD. EFFICACY OF MTORC1/2 INHIBITION ON OVARIAN CANCER STEM CELLS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-051.</jats:p
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