986 resultados para MECHANISTIC INSIGHTS


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The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a de. ning structural feature of organ development. Current interest in this process, which is described as an epithelial- mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the . rst being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, . brosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and . brosis, as well as the identi. cation of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).

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Shared Services involves the convergence and streamlining of an organisation’s functions to ensure timely service delivery as effectively and efficiently as possible. This would result in lower cost, improved service delivery and economies of scale. The conventional wisdom of today is that the potential for Shared Services is increasing due to the increasing costs of changing systems and business requirements and also in implementing and running information systems (IS). However many organizations opt instead for an outsourcing arrangement as the alternative towards cost savings, due in essence to a lack of realization of this potential for Shared Services. This paper rationales turning from outsourcing (to looking within organisations) to leverage on Shared Services for similar cost savings and reaping other potential benefits. The paper’s objectives and contributions are three-fold: (1) distinguish between Shared Services and Outsourcing, (2) report on insights from a single Australian university case study through a transaction cost lens, and to demonstrate the potential for Shared Services and (3) develop a decision model to gauge the potential of implementing Shared Services across similar organisations.

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The routine cultivation of human corneal endothelial cells, with the view to treating patients with endothelial dysfunction, remains a challenging task. While progress in this field has been buoyed by the proposed existence of progenitor cells for the corneal endothelium at the corneal limbus, strategies for exploiting this concept remain unclear. In the course of evaluating methods for growing corneal endothelial cells, we have noted a case where remarkable growth was achieved using a serial explant culture technique. Over the course of 7 months, a single explant of corneal endothelium, acquired from cadaveric human tissue, was sequentially seeded into 7 culture plates and on each occasion produced a confluent cell monolayer. Sample cultures were confirmed as endothelial in origin by positive staining for glypican-4. On each occasion, small cells, closest to the tissue explant, developed into a highly compact layer with an almost homogenous structure. This layer was resistant to removal with trypsin and produced continuous cell outgrowth during multiple culture periods. The small cells gave rise to larger cells with phase-bright cell boundaries and prominent immunostaining for both nestin and telomerase. Nestin and telomerase were also strongly expressed in small cells immediately adjacent to the wound site, following transfer of the explant to another culture plate. These findings are consistent with the theory that progenitor cells for the corneal endothelium reside within the limbus and provide new insights into expected expression patterns for nestin and telomerase within the differentiation pathway.

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Purpose My aim is to introduce, in the project management field, an Aristotelian ethics lens moving beyond the classical deontological and consequentialism approaches underlying the current ethical practices and codes of ethics and professional conducts. In doing so, I wish to pose the premises of a debate on the implications of a conscious ethical perspective for the structure and agency relationship within the project management field Design/methodology/approach Project management is a knowledge field on its own right. However the current perspectives applied to make sense and develop the field (modernism vs. postmodernism) leads to dichotomous thinking rather than recognizing the merits and contextual validity of both sides. I call for Aristotelian Ethics as a way of moving beyond this dichotomous thinking. I introduce briefly Aristotelian Ethics and its consequences in term of relation theory – practice, means and ends, facts and values, and finally politics (i.e. being part of a community of practitioners). Then I illustrate some consequences for the field taking PMI Code of Ethics and Professional Conduct and APM Code of Professional Conduct as supports for discussion Findings I suggest a need for revisiting and/or redesigning the codes of ethics and professional conducts for project management according to an Aristotelian perspective, in order to move beyond the normative limitations of classical deontological (conflict between competing duties, exemplified by PMI Code) or consequentialism (focusing on the "right" outcome to the detriment of duties, exemplified by APM Code) approaches (both, in fact, leading to a disconnection means and ends, and facts and values). This implicates shifting our view from the question "what is my duty?" to the questions "why should I undertake my duty?" and "how ought I act in this situation?" Practical implications Raising Professional Bodies, Industry and Education institutions awareness and consciousness and leading them to rethink about codes of ethics and the implications for the way they conceive practice and research, bodies of knowledge, credentialing, education... Originality/value To the best of my knowledge, this kind of discussion has not yet been conducted within the project management field, and considering the implication of project management in our life and for the well being of the society, an ethical debate may present some value(s)

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Purpose To examine the effects that the sedative and analgesic medications which are commonly used in the cardiac catheterisation laboratory have on thermoregulation. Design A structured review strategy was used. Methods Medline and CINAHL were searched for published studies and reference lists of retrieved studies were scrutinized for further research. Data were extracted using a standardised extraction tool. Results A total of nine studies examined the effect that sedative and analgesic medications have on thermoregulation. Midazolam has minimal impact on thermoregulation while opioids, dexmedetomidine and propofol markedly decrease vasoconstriction and shivering thresholds. Conclusions Patients who receive sedation in the cardiac catheterisation laboratory may be at risk of hypothermia, due to the use of medications that impair thermoregulation. Further research is required to identify the prevalence of unplanned hypothermia during sedation in the cardiac catheterisation laboratory.

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This chapter reports on a study that reveals the essence of participation in urban spaces by ten children who live with various physical conditions: Muscular Dystrophy, Cerebral Palsy, and Autoimmune Rheumatic Diseases. These conditions affect muscle and movement differently resulting in diverse ways in which children move through space (personal mobility). The children at the time of the research were 9-12 years of age residing in South-east Queensland, Australia. The approach and methods selected for this study, interpretive phenomenological inquiry and grounded theory, were chosen for their capacity to capture the complexity and multiple interactions of the child’s urban living. The confronting and poignant accounts by children and their families of their experiences produced a new way of understanding the concept of participation, as a ‘journey of becoming involved.’ Their accounts of performing everyday routines (e.g. leaving home, getting in and out of the car, and entering places) in urban spaces (neighbourhood streets, schools, open spaces, shopping centres, and hospitals) revealed differences in the way settings were experienced. These differences were associated with the interplay between the body, space and context. Where interplays were problematic, explicit decisions about children’s involvement were made. These decisions were described in terms of ‘avoid going’, ‘pick and choose’, ‘discontinue’, ‘accept’, or ‘contest.’ What these decisions mean is some spaces are avoided, some journeys are discontinued, and some barriers encountered in journeys are normalised as everyday experiences, i.e. ‘tolerable discrimination’. These actions resulted in experiences of non-participation or partial–tokenistic participation. The key substantive contribution of the research lies in the identification of points in children’s journeys that shape participation experience. These points identify where future interventions in policy, programming and design can be made to make real and sustaining changes to lives of children and their families in geographies crucial to urban living.

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Seemingly straightforward tasks often have a way of becoming complex. This was the case for our guest editorial team charged with creating Early Childhood Australia’s Best of Sustainability publication drawn from the the Australasian Journal of Early Childhood and Every Child. The complexities we encountered ranged from the varied terminologies and understandings of constructs such as education for sustainable development, environmental education and education for sustainability, through to the fundamental lack of published research on which to draw as the basis for a special issue. It is timely to explore these complexities as we face the global challenges of The Critical Decade (DCCEE, 2011) including rising sea levels, extreme weather events and food security. At a local level, the early childhood field in Australia is seeking to interpret sustainability with systemic support from the National Quality Standards(NQS) (ACECQA, 2011), while elsewhere environmental/sustainability education is encouraged through national curricula documents (for example, Singapore Ministry of Education, 2008; Swedish National Agency for Education,2010; Ministry of Education of Korea, 2011). Both The Critical Decade and the NQS provide imperatives to drive early childhood education’s engagement with sustainability. In other words, sustainability in early childhood education is no longer optional, but essential (Elliott, 2010). While some twenty years of advocacy has led to this somewhat subdued celebratory position, in this publication we do recognise the historical contexts that have led to early childhood education for sustainability (ECEfS), as we (Elliott & Davis) phrase it, becoming almost ‘mainstream not marginal’ (Davis, 1999)— a stitching together of the isolated ‘patches of green’, first identified a decade ago by Elliott (NSW EPA, 2003). Here we weave together, through these articles, a story of the evolving history of ECEfS from our particular perspective. In so doing, we also acknowledge that there are other perspectives or ‘paths’ for this field as identified by Edwards and Cutter-McKenzie in their concluding paper to this compilation.

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Research involving resettled refugees raises methodological and ethical complexities. These complexities typically emerge within cross-sectional research that focuses on refugee experiences at a specific point in time. Given the long term and dynamic nature of refugee settlement, longitudinal research is valuable, yet it raises distinct complexities within the research process. This article focuses on the methodological and ethical insights that emerged in a longitudinal study of settlement and wellbeing with a cohort of young people from refugee backgrounds in Australia. It considers: engagement and retention of a cohort over time; the need to adapt research tools to changing settlement contexts and life stages; participants’ experiences of long-term involvement in the study; and the challenge of timely translation of findings into evidence for policy and practice. The article contributes to a growing understanding of the practical, ethical and epistemological challenges and opportunities presented by longitudinal research, in this case, with resettled refugee background youth.

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The position of Assistant Regional Directors, School Performance (ARD-SP) was established by the Department of Education and Training (DET), the government provider of public education in Queensland, in 2010, to improve student learning across Queensland by providing close supervision of principals. Based on interviews with 18 ARDs-SP and two of their immediate supervisors, this paper explores their views about this relatively new position and their understandings of the role. Following Blase and Anderson (1995), it uses micropolitical leadership theory to analyse comments made by the participants. A key finding was a view of leadership based on a differentiated supervision model whereby ARDs-SP worked with principals to ensure they met the corporate agenda. Participants’ comments favoured a leadership approach that was both adversarial (drawing upon power over and power through) and facilitative (drawing upon power through and power over) and for those principals deemed under-performing, an authoritarian leadership approach was apparent.

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Despite rising levels of safe-sex knowledge in Australia, sexually transmitted infection notifications continue to increase. A culture-centred approach suggests it is useful in attempting to reach a target population first to understand their perspective on the issues. Twenty focus groups were conducted with 89 young people between the ages of 14 and 16 years. Key findings suggest that scientific information does not articulate closely with everyday practice, that young people get the message that sex is bad and they should not be preparing for it and that it is not appropriate to talk about sex. Understanding how young people think about these issues is particularly important because the focus groups also found that young people disengage from sources of information that do not match their own experiences.

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Purpose: The paper aims to investigate urban knowledge precincts from the angle of urban planning and place branding. Scope: The paper focuses on urban knowledge precinct development experiences of Brisbane, Australia. Method: The paper uses literature review, policy and content analyses and field observation methods to explore Brisbane’s urban knowledge precincts. Results: The paper reveals insights from Brisbane’s urban knowledge precincts development journey. Recommendations: The paper suggests further research on the topic of branding and planning urban knowledge precincts. Conclusions: The paper reveals that urban knowledge precincts are the nexus of knowledge-based urban development and Brisbane’s precincts potentially provide a competitive edge to the city in the global knowledge economy era.

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Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

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Aflatoxin B1, a potently carcinogenic fungal metabolite, is converted to the biologically active form by chemical oxidation using dimethyldioxirane and enzymatically by cytochrome P450 mixed-function oxidases. Both processes give rise to mixtures of the exo- and endo-8,9-epoxides. Methanolysis studies reveal exclusive trans opening of both epoxides under neutral conditions in CH3OH and CH3OH/H2O mixtures; an SN2 mechanism is postulated. Under acidic conditions, the exo isomer gives mixtures of trans and cis solvolysis products, suggesting that the reaction is, at least in part, SN1; the endo isomer gives only the trans product. The exo isomer reacts with DNA by attack of the nitrogen atom at the 7 position of guanine on C8 of the epoxide to give the trans adduct; the endo epoxide fails to form an adduct at this or any other site in DNA. The exo isomer is strongly mutagenic in a base-pair reversion assay employing Salmonella typhimurium; the endo isomer is essentially nonmutagenic. Aflatoxin B1 and its derivatives intercalate in DNA. These results are consistent with a mechanism in which intercalation of the exo epoxide optimally orients the epoxide for an SN2 reaction with guanine but intercalation of the endo isomer places the epoxide in an orientation which precludes reaction. Thus, while the exo epoxide is a potent mutagen, the endo epoxide fails to react with DNA.