832 resultados para Brett Horton


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Introduction: The Paradox at the Heart of Online Interaction

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Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevance of the 3D microenvironment and integrin engagement. In a spheroid-based animal model, KLK4-7-overexpression induced tumor growth after 4 weeks and intraperitoneal spread after 8 weeks. Upon paclitaxel administration, KLK4-7-expressing tumors declined in size by 91% (controls: 87%) and showed 90% less metastatic outgrowth (controls: 33%, P<0.001). KLK4-7-expressing spheroids showed 53% survival upon paclitaxel treatment (controls: 51%), accompanied by enhanced chemoresistance-related factors, and their survival was further reduced by combination treatment of paclitaxel with KLK4/5/7 (22%, P=0.007) or MAPK (6%, P=0.006) inhibition. The concomitant presence of KLK4-7 in ovarian cancer cells together with integrin activation drives spheroid formation and proliferation. Combinatorial approaches of paclitaxel and KLK/MAPK inhibition may be more efficient for late-stage disease than chemotherapeutics alone as these inhibitory regimens reduced cancer spheroid growth to a greater extent than paclitaxel alone.

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This discussion paper has been provided to assist the Department of Communities, Child Safety and Disability Services (DOCCSDS) in developing the Queensland Government’s Youth Strategy and inform the review of state government funded youth services. The paper lists a number of key concepts and social determinants which need to be considered in this undertaking. Additionally, it proposes a number key concepts and principles pertinent to understanding and working with young people, and for quality youth service provision.

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BACKGROUND Burns and their associated wound care procedures evoke significant stress and anxiety, particularly for children. Little is known about the body's physiological stress reactions throughout the stages of re-epithelialization following an acute burn injury. Previously, serum and urinary cortisol have been used to measure stress in burn patients, however these measures are not suitable for a pediatric burn outpatient setting. AIM To assess the sensitivity of salivary cortisol and sAA in detecting stress during acute burn wound care procedures and to investigate the body's physiological stress reactions throughout burn re-epithelialization. METHODS Seventy-seven participants aged four to thirteen years who presented with an acute burn injury to the burn center at the Royal Children's Hospital, Brisbane, Australia, were recruited between August 2011 and August 2012. RESULTS Both biomarkers were responsive to the stress of burn wound care procedures. sAA levels were on average 50.2U/ml higher (p<0.001) at 10min post-dressing removal compared to baseline levels. Salivary cortisol levels showed a blunted effect with average levels at ten minutes post dressing removal decreasing by 0.54nmol/L (p<0.001) compared to baseline levels. sAA levels were associated with pain (p=0.021), no medication (p=0.047) and Child Trauma Screening Questionnaire scores at three months post re-epithelialization (p=0.008). Similarly, salivary cortisol was associated with no medication (p<0.001), pain scores (p=0.045) and total body surface area of the burn (p=0.010). CONCLUSION Factors which support the use of sAA over salivary cortisol to assess stress during morning acute burn wound care procedures include; sensitivity, morning clinic times relative to cortisol's diurnal peaks, and relative cost.

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Purpose: To investigate the changes occurring in the axial length, choroidal thickness and anterior biometrics of the eye during a 10 minute near task performed in downward gaze. Methods: Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure ocular biometrics in downward gaze, an optical biometer was inclined on a custom built, height and tilt adjustable table. Baseline measures were collected after each subject performed a distance primary gaze control task for 10 mins, to provide wash-out period for prior visual tasks before each of three different accommodation/gaze conditions. These other three conditions included a near task (2.5 D) in primary gaze, and a near (2.5 D) and a far (0 D) accommodative task in downward gaze (25°), all for 10 mins duration. Immediately after, and then 5 and 10 mins from the commencement of each trial, measurements of ocular biometrics (e.g. anterior biometrics, axial length, choroidal thickness and retinal thickness) were obtained. Results: Axial length increased with accommodation and was significantly greater for downward gaze with accommodation (mean change ± SD 23 ± 13 µm at 10 mins) compared to primary gaze with accommodation (mean change 8 ± 15 µm at 10 mins) (p < 0.05). A small amount of choroidal thinning was also found during accommodation that was statistically significant in downward gaze (13 ± 14 µm at 10 mins, p < 0.05). Accommodation in downward gaze also caused greater changes in anterior chamber depth and lens thickness compared to accommodation in primary gaze. Conclusion: Axial length, choroidal thickness and anterior eye biometrics change significantly during accommodation in downward gaze as a function of time. These changes appear to be due to the combined influence of biomechanical factors (i.e. extraocular muscle forces, ciliary muscle contraction) associated with near tasks in downward gaze.

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For the first of the baby boomers turning 65 years of age, after a decade littered with financial shocks (dot.com bubble, sub-prime, global financial crisis, sovereign debt), sequencing risk can represent a significant threat to their retirement nest eggs. This paper takes an outcomeoriented approach to the problem, to provide practical insights into how sequencing risk works and the critical dependency of retirement outcomes on sequencing risk. Our analysis challenges the conventional wisdom that it is the accumulated average of investment returns that matter. We show, instead, that it is the realised sequence of returns which largely determines the sustainability of retirement incomes.

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This paper describes the development of a novel vision-based autonomous surface vehicle with the purpose of performing coordinated docking manoeuvres with a target, such as an autonomous underwater vehicle, at the water's surface. The system architecture integrates two small processor units; the first performs vehicle control and implements a virtual force based docking strategy, with the second performing vision-based target segmentation and tracking. Furthermore, the architecture utilises wireless sensor network technology allowing the vehicle to be observed by, and even integrated within an ad-hoc sensor network. Simulated and experimental results are presented demonstrating the autonomous vision- based docking strategy on a proof-of-concept vehicle.

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Background Through clinical observation nursing staff of an inpatient rehabilitation unit identified a link between incontinence and undiagnosed urinary tract infections (UTIs). Further, clinical observation and structured continence management led to the realisation that urinary incontinence often improved, or resolved completely, after treatment with antibiotics. In 2009 a small study found that 30% of admitted rehabilitation patients had an undiagnosed UTI, with the majority admitted post-orthopaedic fracture. We suspected that the frequent use of indwelling urinary catheters (IDCs) in the orthopaedic environment may have been a contributing factor. Therefore, a second, more thorough, study was commenced in 2010 and completed in 2011. Aim The aim of this study was to identify what proportion of patients were admitted to one rehabilitation unit with an undiagnosed UTI over a 12-month period. We wanted to identify and highlight the presence of known risk factors associated with UTI and determine whether urinary incontinence was associated with the presence of UTI. Methods Data were collected from every patient that was admitted over a 12-month period (n=140). The majority of patients were over the age of 65 and had an orthopaedic fracture (36.4%) or stroke (27.1%). Mid-stream urine (MSU) samples, routinely collected and sent for culture and sensitivity as part of standard admission procedure, were used by the treating medical officer to detect the presence of UTI. A data collection sheet was developed, reviewed and trialled, before official data collection commenced. Data were collected as part of usual practice and collated by a research assistant. Inferential statistics were used to analyse the data. Results This study found that 25 (17.9%) of the 140 patients admitted to rehabilitation had an undiagnosed UTI, with a statistically significant association between prior presence of an IDC and the diagnosis of UTI. Urinary incontinence improved after the completion of treatment with antibiotics. Results further demonstrated a significant association between the confirmation of a UTI on culture and sensitivity and the absence of symptoms usually associated with UTI, such as burning or stinging on urination. Overall, this study suggests careful monitoring of urinary symptoms in patients admitted to rehabilitation, especially in patients with a prior IDC, is warranted.

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Sugar cane is a major source of food and fuel worldwide. Biotechnology has the potential to improve economically-important traits in sugar cane as well as diversify sugar cane beyond traditional applications such as sucrose production. High levels of transgene expression are key to the success of improving crops through biotechnology. Here we describe new molecular tools that both expand and improve gene expression capabilities in sugar cane. We have identified promoters that can be used to drive high levels of gene expression in the leaf and stem of transgenic sugar cane. One of these promoters, derived from the Cestrum yellow leaf curling virus, drives levels of constitutive transgene expression that are significantly higher than those achieved by the historical benchmark maize polyubiquitin-1 (Zm-Ubi1) promoter. A second promoter, the maize phosphonenolpyruvate carboxylate promoter, was found to be a strong, leaf-preferred promoter that enables levels of expression comparable to Zm-Ubi1 in this organ. Transgene expression was increased approximately 50-fold by gene modification, which included optimising the codon usage of the coding sequence to better suit sugar cane. We also describe a novel dual transcriptional enhancer that increased gene expression from different promoters, boosting expression from Zm-Ubi1 over eightfold. These molecular tools will be extremely valuable for the improvement of sugar cane through biotechnology.

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Discharge summaries and other free-text reports in healthcare transfer information between working shifts and geographic locations. Patients are likely to have difficulties in understanding their content, because of their medical jargon, non-standard abbreviations,and ward-specific idioms. This paper reports on an evaluation lab with an aim to support the continuum of care by developing methods and resources that make clinical reports in English easier to understand for patients, and which helps them in finding information related to their condition.

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Synthetic hydrogels selectively decorated with cell adhesion motifs are rapidly emerging as promising substrates for 3D cell culture. When cells are grown in 3D they experience potentially more physiologically relevant cell-cell interactions and physical cues compared with traditional 2D cell culture on stiff surfaces. A newly developed polymer based on poly(2-oxazoline)s has been used for the first time to control attachment of fibroblast cells and is discussed here for its potential use in 3D cell culture with particular focus on cancer cells towards the ultimate aim of high throughput screening of anti-cancer therapies. Advantages and limitations of using poly(2-oxazoline) hydrogels are discussed and compared with more established polymers, especially polyethylene glycol (PEG).

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Aim Evidence linking the accumulation of exotic species to the suppression of native diversity is equivocal, often relying on data from studies that have used different methods. Plot-level studies often attribute inverse relationships between native and exotic diversity to competition, but regional abiotic filters, including anthropogenic influences, can produce similar patterns.We seek to test these alternatives using identical scale-dependent sampling protocols in multiple grasslands on two continents. Location Thirty-two grassland sites in North America and Australia. Methods We use multiscale observational data, collected identically in grain and extent at each site, to test the association of local and regional factors with the plot-level richness and abundance of native and exotic plants. Sites captured environmental and anthropogenic gradients including land-use intensity, human population density, light and soil resources, climate and elevation. Site selection occurred independently of exotic diversity, meaning that the numbers of exotic species varied randomly thereby reducing potential biases if only highly invaded sites were chosen. Results Regional factors associated directly or indirectly with human activity had the strongest associations with plot-level diversity. These regional drivers had divergent effects: urban-based economic activity was associated with high exotic : native diversity ratios; climate- and landscape-based indicators of lower human population density were associated with low exotic : native ratios. Negative correlations between plot-level native and exotic diversity, a potential signature of competitive interactions, were not prevalent; this result did not change along gradients of productivity or heterogeneity. Main conclusion We show that plot-level diversity of native and exotic plants are more consistently associatedwith regional-scale factors relating to urbanization and climate suitability than measures indicative of competition. These findings clarify the long-standing difficulty in resolving drivers of exotic diversity using single-factor mechanisms, suggesting that multiple interacting anthropogenic-based processes best explain the accumulation of exotic diversity in modern landscapes.

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Studies of experimental grassland communities have demonstrated that plant diversity can stabilize productivity through species asynchrony, in which decreases in the biomass of some species are compensated for by increases in others. However, it remains unknown whether these findings are relevant to natural ecosystems, especially those for which species diversity is threatened by anthropogenic global change. Here we analyse diversity-stability relationships from 41 grasslands on five continents and examine how these relationships are affected by chronic fertilization, one of the strongest drivers of species loss globally. Unmanipulated communities with more species had greater species asynchrony, resulting in more stable biomass production, generalizing a result from biodiversity experiments to real-world grasslands. However, fertilization weakened the positive effect of diversity on stability. Contrary to expectations, this was not due to species loss after eutrophication but rather to an increase in the temporal variation of productivity in combination with a decrease in species asynchrony in diverse communities. Our results demonstrate separate and synergistic effects of diversity and eutrophication on stability, emphasizing the need to understand how drivers of global change interactively affect the reliable provisioning of ecosystem services in real-world systems.

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There has been a greater focus on strengthening evaluation capacity building (ECB) within development organisations in recent years. This can be attributed in part to the growing appreciation of the value of participatory and collaborative forms of evaluation. Evaluation is increasingly seen as an ongoing learning process and an important means of strengthening capacity and improving organisational performance (Horton et al., 2003:7). While there are many benefits of using participatory methodologies in ECB projects, our experiences and a review of the literature in this area highlight the many challenges, issues and contradictions that can affect the success of such ECB efforts. We discuss these issues, drawing on our learnings from the ongoing participatory action research (PAR) project 'Assessing Communication for Social Change’ (AC4SC). This four year project, which began in 2007, is a collaboration between communication and development academics and evaluation specialists from two Australian universities and communication for development practitioners and monitoring and evaluation (M&E) staff in the NGO Equal Access Nepal (EAN). The aim is to develop, implement, and evaluate a participatory methodology for assessing the social change impacts of community radio programs produced by EAN. It builds on previous projects that used ethnographic action research (EAR) methodology (Tacchi et al., 2007).

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Objectives: To report the quarterly incidence of hospital-identified Clostridium difficile infection (HI-CDI) in Australia, and to estimate the burden ascribed to hospital-associated (HA) and community-associated (CA) infections. Design, setting and patients: Prospective surveillance of all cases of CDI diagnosed in hospital patients from 1 January 2011 to 31 December 2012 in 450 public hospitals in all Australian states and the Australian Capital Territory. All patients admitted to inpatient wards or units in acute public hospitals, including psychiatry, rehabilitation and aged care, were included, as well as those attending emergency departments and outpatient clinics. Main outcome measures: Incidence of HI-CDI (primary outcome); proportion and incidence of HA-CDI and CA-CDI (secondary outcomes). Results: The annual incidence of HI-CDI increased from 3.25/10 000 patient-days (PD) in 2011 to 4.03/10 000 PD in 2012. Poisson regression modelling demonstrated a 29% increase (95% CI, 25% to 34%) per quarter between April and December 2011, with a peak of 4.49/10 000 PD in the October–December quarter. The incidence plateaued in January–March 2012 and then declined by 8% (95% CI, − 11% to − 5%) per quarter to 3.76/10 000 PD in July–September 2012, after which the rate rose again by 11% (95% CI, 4% to 19%) per quarter to 4.09/10 000 PD in October–December 2012. Trends were similar for HA-CDI and CA-CDI. A subgroup analysis determined that 26% of cases were CA-CDI. Conclusions: A significant increase in both HA-CDI and CA-CDI identified through hospital surveillance occurred in Australia during 2011–2012. Studies are required to further characterise the epidemiology of CDI in Australia.