142 resultados para Diverse Als Inhibitors
Resumo:
Effective interviewing of culturally and linguistically diverse clients Tips from Dr Nigar Khawaja MAPS, Convenor, APS Psychology and Cultures Interest Group
Resumo:
This report summarises research undertaken by Queensland University of Technology, Brisbane, in partnership with Diversicare, on ‘Meeting the cultural food needs of Queensland’s Culturally and Linguistically Diverse (CALD) aged’. An earlier literature review[6] summarised the state of the evidence in relation to Australia’s CALD aged population and their less than optimal usage of Home and Community Care services (HACC), in particular, food services. This report builds on the information presented in the literature review aiming to explore the current provision of food services to CALD clients and the barriers and enablers to this service provision in Queensland.
Resumo:
The present study examined Queensland Transcultural Mental Health Centre (QTMHC) client characteristics in order to provide a better understanding for development of future health service delivery models. Archived data that was collected for 1499 clients over two years period (2007-2009) was analysed using descriptive statistics and Chi squares. The results indicated that clients were referred from a range of sources and were generally adults. There were more women than men, who sought services. At least half of the clients had language barriers and relied on bilingual workers. Most frequently expressed mental health issues were mood disorder symptoms, followed by symptoms of schizophrenia and psychosis and anxiety. Acculturation strains and stressors were described as the most common psychosocial issues. Mental health and psychosocial issues differed for age, gender and world regions from which the CALD clients originated. The findings provided an understanding of clients who seek services at QTMHC. Various ways in which transcultural services and data bases can be further improved are discussed.
Resumo:
This paper discusses the primacy of communities of practice within learning contexts at university and during practicum for culturally and linguistically diverse preservice teachers. The study illustrates that learning occurs when there are adequate opportunities for participation and practice. Data from interviews with 28 culturally and linguistically diverse preservice teachers illustrate that tensions created by social, cultural differences impact upon modes of identification and dimensions of practice (Lave & Wenger, 1991; Wenger, 1998). The study concludes by reiterating the importance of establishing proactive communities of practice to ensure success in learning and practice for this group of preservice teachers.
Resumo:
Using a sample of 2,200 US listed firm year observations (2001-2007)this study shows a positive (negative) relation between female participation in corporate boards and analysts' earnings forecast accuracy (dispersion), after controlling for earnings quality, corporate governance, audit quality, stock price informativeness and potential endogeneity. Our findings are important as they suggest that board diversity adds to the transparency and accuracy of financial reports such that earnings expectations are likely to be more accurate for these firms.
Resumo:
In this study, the nature of the coupling interactions between copper and uracil as well as its several derivatives has been systematically investigated employing the atoms in molecules (AIM) theory and energy decomposition analyses. The whole interaction process has been investigated through the analyses of the radial distribution functions of the Cu⋯X (X = S and O) contact on the basis of the ab initio molecular dynamics. No direct relationship between the adsorption strengths and inhibition efficiencies of the inhibitors has been observed. Additionally, the possibility of the methyl-substituted dithiouracil species to act as copper corrosion inhibitors has been tested.
Resumo:
We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of dovitinib and identified fourteen dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (EC). Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors. Whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, 3/7 showed marked resistance to PD173074 and relative resistance to dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R) conferred resistance (~5 fold) to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also shows ponatinib is more effective than dovitinib at inhibiting FGFR2N550K. We propose tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.
Resumo:
As the demands placed on the literacy coach have evolved, so too have the roles of these educational providers who are often responsible for working with school teams to turn around student performance on standardized literacy tests. One literacy coach based in a Queensland primary school recounts her experiences via open-ended interview over a two year period. We offer a theorisation of the new ways of working as a literacy coach in a context of teaching and learning marked by diversity.
Resumo:
The number of culturally and linguistically diverse (CALD) students seeking enrollment in higher education courses in Western countries where English is the predominant language has grown considerably in the past decade, especially in undergraduate health care courses. When enrolled in nursing courses, students are required to complete clinical placements. Such experiences can create significant challenges for CALD students where language, cultural differences, and interpretation of cultural norms complicate the learning process. To assist CALD nursing students to transition successfully, an extracurricular integrated curriculum program was developed and implemented at a university in Queensland, Australia. The program is a series of interactive workshops based on the principles of caring pedagogy and student-centered learning. The program applies strategies that combine small-group discussions with peers, role-plays, and interactions with final-year nursing student volunteers. Evaluation of the program suggests it has assisted most of the students surveyed to be successful in their clinical studies.
Resumo:
This chapter describes how investigative journalism can uncover news that often goes unreported about personalities, problems, ways of life and pressing issues in ethnic and religious sub-communities. While investigative journalism is traditionally understood as reporting that exposes corrupt, inefficient, incompetent or other inappropriate conduct in politics and business circles, investigative reporters do far more than that. They also map human activities, landmarks, patterns and changes in the landscape, and connections across the whole of society. This type of investigative journalism can improve reporting of ethnic and religious sub-communities via identification, deep observation and analysis of trends, events, and issues that would otherwise remain hidden or obscured. The chapter includes details of techniques that investigative journalists can employ to identify interesting topics, find sources of information, analyse data and issues, and report compelling stories.
Resumo:
Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.
Resumo:
The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.
Resumo:
Despite considerable discussion regarding the virtues of participation in urban spaces, the urban experience of children with disabilities has been largely ignored. This intensive study reported on the everyday experience of urban participation on the part of children with conditions such as cerebral palsy, muscular dystrophy, and juvenile arthritis, contributing new insights into their experience of journeys central to becoming involved in settings such as schools, neighbourhoods and shopping centres. The study identified problems in body – space – context relationships as points of intervention in our urban settings that promise to make a significant difference to their everyday journeys.
Resumo:
Plasmin is the primary enzyme responsible for dissolution of fibrin in the circulatory system. Plasminogen, the zymogen of plasmin is expressed ubiquitously in the human body [1], with the predominant source being the liver [2, 3]. Plasminogen is produced as an 810 amino acid protein with a 19 amino acid leader peptide, which is cleaved during secretion to produce the mature 791 amino acid one-chain zymogen. This is converted to plasmin by cleavage of the Arg561 - Val562 scissile bond [4], resulting in an active protease consisting of two disulfide linked chains. The amino-terminal heavy chain (residues Glu1-Arg561) is comprised of a plasminogen/apple/nematode (PAN) domain [5] and five kringle domains of approximately equal size [6] while the light chain (residues Val562-Asn791) contains a serine protease domain homologous to trypsin with a catalytic triad comprising His603, Asp646 and Ser741 [7]. Both plasmin and plasminogen occur in two forms, full length and a Lys77-Lys78 activated variant produced through self catalysis (Figure 1). The former exists in a tight conformation through binding of Lys50 and/or Lys62 to kringle domain 5 [8, 9] while Lys78-plasminogen assumes a more relaxed conformation rendering it more susceptible to plasmin conversion [10, 11].