876 resultados para Extreme phenotypes


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Coastal areas are dynamic environments that are home to billions of people worldwide and provide areas of unique natural importance. As such, coastal change is of considerable local and global interest, not only within the geological realm, but also in terms of socioeconomic and biodiversity impacts. An accurate understanding of how changes in relative sea level, geological processes and extreme events, such as storms and tsunamis, have interacted to shape and change the Earth’s coastlines over millennia is fundamental to future projections of coastal change. On the basis of this, researchers in these, and various other aspects of coastal change were brought together in late 2010 at the University of Hong Kong for the first meeting of International Geoscience Program Project 588 (IGCP588) e Preparing for Coastal Change. This special issue showcases some of the results presented at this meeting.

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Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.

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Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

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Is there a point where parental effort can be too much? While the link between parenting effort and the wellbeing of children has been firmly established, contemporary discussion has proposed that extreme levels of parental protection of and responsiveness to children could be counterproductive. Research has not yet addressed this phenomenon to ascertain if overparenting is a genuinely different type of parenting approach. The purpose of the present study was to gain insight into the parenting actions considered by parenting professionals (psychologists and school guidance counsellors) to be overparenting. One hundred and twenty-eight professionals responded to an online survey about their observations of overparenting, with eighty-six respondents providing lists of the types of actions they believed were behavioural examples of the term. The survey data revealed that certain types of actions were considered to be indicative of overparenting, and that particular beliefs and outcomes may be involved in this parenting approach. Implications for parenting advice and education programs, and further research are discussed.

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An indepth investigation into the extreme sport experience

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Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.

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Volunteering Qld’s Project Creatives continues to explore the critical role creative disciplines and creative people play in providing new models of engagement and action in social change and community work. This article explores three different non-profit organisations that have used collaborative photography to enable locals to empower themselves. Written by Alice Baroni a volunteer with the Education, Research and Policy Unit of Volunteering Qld. Alice is undertaking a PhD at the Queensland University of Technology, exploring (photo) journalism, participatory content creation and community photography in Brazil’s low income suburbs. She is part of the ARC Centre of Excellence for Creative Industries and Innovation, and a Brazilian research group ‘Storytellers and Narratives: Contemporary Journalism’. Two of the initiatives explored in this publication are Viva Favela and Imagens do Povo that are ideologically and physically supported by, respectively, Viva Rio and Observatório de Favelas, based in Rio de Janeiro, Brazil. ‘Favela’ is often translated simply as ‘slum’ or ‘shantytown’, but these terms connote negative characteristics such as shortage, poverty, and deprivation, which end up stigmatising these low-income suburbs. Fotografi Senza Frontiere (FSF) (Photographers Without Borders) is an Italian non-governmental organisation that gathers together a group of photographers who aim to provide youth from extreme regions in Nicaragua, Algeria, Argentina, Panama, Uganda, and Palestine with skills to photograph and document their own reality by establishing permanent photo laboratories. This idea, which is similar to that of Viva Favela and Imagens do Povo, is to enable youth to become professional photographers as a means of self-representation and self-empowerment. Afterwards, students become educators in established photographic labs so as to pass on what they have learnt through FSF’s photographic courses.

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Macrophages are the main components of inflammation during skin wound healing. They are critical in wound closure and in excessive inflammation, resulting in defective healing observed in chronic wounds. Given the heterogeneity of macrophage phenotypes and functions, we here hypothesized that different subpopulations of macrophages would have different and sometimes opposing effects on wound healing. Using multimarker flow cytometry and RNA expression array analyses on macrophage subpopulations from wound granulation tissue, we identified a Ly6cloMHCIIhi “noninflammatory” subset that increased both in absolute number and proportion during normal wound healing and was missing in Ob/Ob and MYD88−/− models of delayed healing. We also identified IL17 as the main cytokine distinguishing this population from proinflammatory macrophages and demonstrated that inhibition of IL17 by blocking Ab or in IL17A−/− mice accelerated normal and delayed healing. These findings dissect the complexity of the role and activity of the macrophages during wound inflammation and may contribute to the development of therapeutic approaches to restore healing in chronic wounds.

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Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

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Road Rage describes a range of aggressive and dangerous driving behaviours directed at other road users. The phrase involves images of uncontrolled temper and the open display of anger and frustration. A common alternative term is “aggressive driving” with road rage seen to be a manifestation of extreme aggressive driving.

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The reliable operation of the electrical system at Callide Power Station is of extreme importance to the normal everyday running of the Station. This study applied the principles of reliability to do an analysis on the electrical system at Callide Power Station. It was found that the level of expected outage cost increased exponentially with a declining level of maintenance. Concluding that even in a harsh economic electricity market where CS Energy tries and push their plants to the limit, maintenance must not be neglected. A number of system configurations were found to increase the reliability of the system and reduce the expected outage costs. A number of other advantages were identified as a result of using reliability principles to do this study on the Callide electrical system configuration.

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Many of the more extreme bushfire prone landscapes in Australia are located in colder climate regions. For such sites, the National Construction Code regulates that houses satisfy both the Australian Standard for Bushfire (AS 3959:2009) and achieve a 6 Star energy rating. When combined these requirements present a considerable challenge to the construction of affordable housing - a problem which is often exacerbated by the complex topography of bushifre prone landscapes. Dr Weir presents a series of case studies from his architetcural practice which highlight the need for further design-led research into affordable housing - a ground up holistic approach to design which recolciles energy performance, human behaviourm, bushland conservation and bushfire safety.

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Bouncing Back Architecture Exhibition: This exhibition showcases interpretations of urban resiliency by 2nd and 4th Year undergraduate architecture students who explore the notion of Bouncing Back from the 2011 Queensland floods, in the context of contemporary Brisbane built environment. Design solutions have been expressed in a variety of forms including emergency shelters, flood-proof housing and a range of urban designs, some of which address extreme environmental conditions. Design Process Workshop | Architecture Workshop with Queensland Academy of Creative Industries Students: In collaboration with Homegrown Facilitator Natalie Wright, Lindy Osborne and Glenda Caldwell and some of their architecture students from the QUT School of Design, extended the university design studio experience to 18 Secondary School students, who brainstormed and designed emergency food distribution shelters for those affected by floods. Designs and models created in the workshop were subsequently included in the Bouncing Back Architecture Exhibition.

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Target date retirement funds have gained favor with retirement plan investors in recent years. Typically, these funds initially have a high allocation to stocks but move towards less volatile assets, such as bonds and cash, as the target retirement date approaches. Empirical research has generally found that a switch to low-risk assets prior to retirement can reduce the risk of confronting the most extreme negative outcomes. This article questions the rationale for lifecycle switching based solely on age or target retirement date as is the prevalent practice among target date funds. The authors argue that a dynamic switching strategy, which takes into consideration achieved investment returns, will produce superior returns for most investors compared to conventional lifecycle switching. In this article, the authors put forward a dynamic lifecycle switching strategy that is conditional on the attainment of the plan member's wealth accumulation objective at every stage of switching.

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Research shows that Indigenous Australians suspicion and fear of being ‘locked up’ may influence mental health service avoidance. Given this, the aim of this study was to explore, by qualitative analysis of in depth interviews (N = 3), how three Indigenous people experienced the controversial practice of seclusion Hans-Georg Gadamer’s phenomenology guided analysis of the material, and allowed narrated experiences to be understood within their cultural and historical context. Participants viewed seclusion negatively: police involvement in psychiatric care; perceptions of being punished and powerless; occasions of extreme use of force; and lack of care were prominent themes throughout the interviews. While power imbalances inherent in seclusion are problematic for all mental health clients, the distinguishing factor in the Indigenous clients’ experience is that seclusion is continuous with the discriminatory and degrading treatment by governments, police and health services that many Indigenous people have experienced since colonisation. The participants’ experiences echoed Goffman’s (1961) findings that institutional practices act to degrade and dehumanise clients whose resulting conformity eases the work of nursing staff. While some nurses perceive that seclusion reduces clients’ agitation (Meehan, Bergen & Fjeldsoe, 2004; Wynaden et al., 2001), one must ask at what cost to clients’ dignity, humanity and basic human rights.