801 research outputs found

    Understanding the notion of accessible spaces and places: Sydney CBD Visitor Accessibility Web portal www.sydneyforall.com

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    The paper presents an approach to understanding the accessibility of spaces and places for people with disabilities and seniors. For these groups, the challenges associated with recreational access are compounded by the cultural context, fragmented approaches to wayfinding and a lack of collaboration by providers to promote accessible experiences. The paper presents the outcome of the research project that sought to collaboratively promote accessible experiences within the Sydney CBD and Sydney Harbour environs. The Sydney for All web portal was developed in conjunction with three industry partners: Tourism NSW; Tourism and Transport Forum; and NSW Dept of Environment and Climate Change. The research engaged in participatory action research with the major stakeholders, attractions and the destination experience providers. The Web portal complies with the highest W3C web accessibility standards as evidenced through the compliance testing by Vision Australia. The paper outlines the research approach, underlying philosophy and the major accessibility features of the portal through a case study of the North Head Lookout. As will be demonstrated, the portal is a starting point to understanding accessible experiences through focusing on universal design, destination experience and management frameworks rather than using constraints based approaches that dominate mainstream access auditing

    Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

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    Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

    Minimising Mortality in Endangered Raptors Due to Power Lines: The Importance of Spatial Aggregation to Optimize the Application of Mitigation Measures

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    Electrocution by power lines is one of the main causes of non-natural mortality in birds of prey. In an area in central Spain, we surveyed 6304 pylons from 333 power lines to determine electrocution rates, environmental and design factors that may influence electrocution and the efficacy of mitigation measures used to minimise electrocution cases. A total of 952 electrocuted raptors, representing 14 different species, were observed. Electrocuted raptors were concentrated in certain areas and the environmental factors associated with increased electrocution events were: greater numbers of prey animals; greater vegetation cover; and shorter distance to roads. The structural elements associated with electrocutions were shorter strings of insulators, one or more phases over the crossarm, cross-shaped design and pylon function. Of the 952 carcasses found, 148 were eagles, including golden eagle (Aquila chrysaetos), Spanish imperial eagle (Aquila adalberti) and Bonelli's eagle (Aquila fasciata). Electrocuted eagles were clustered in smaller areas than other electrocuted raptors. The factors associated with increased eagle electrocution events were: pylons function, shorter strings of insulators, higher slopes surrounding the pylon, and more numerous potential prey animals. Pylons with increased string of insulators had lower raptor electrocution rates than unimproved pylons, although this technique was unsuccessful for eagles. Pylons with cable insulation showed higher electrocution rates than unimproved pylons, both for raptors and eagles, despite this is the most widely used and recommended mitigation measure in several countries. To optimize the application of mitigation measures, our results recommend the substitution of pin-type insulators to suspended ones and elongating the strings of insulators

    Combination antibiotic therapy for community-acquired pneumonia

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    Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings

    Association between depression, anxiety and weight change in young adults

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    Background To investigate whether there are bi-directional associations between anxiety and mood disorders and body mass index (BMI) in a cohort of young adults. Methods We analysed data from the 2004–2006 (baseline) and 2009–2011 (follow-up) waves of the Childhood Determinants of Adult Health study. Lifetime DSM-IV anxiety and mood disorders were retrospectively diagnosed with the Composite International Diagnostic Interview. Potential mediators were individually added to the base models to assess their potential role as a mediator of the associations. Results In males, presence of mood disorder history at baseline was positively associated with BMI gain (β = 0.77, 95% CI: 0.14–1.40), but baseline BMI was not associated with subsequent risk of mood disorder. Further adjustment for covariates, including dietary pattern, physical activity, and smoking reduced the coefficient (β) to 0.70 (95% CI: 0.01–1.39), suggesting that the increase in BMI was partly mediated by these factors. In females, presence of mood disorder history at baseline was not associated with subsequent weight gain, however, BMI at baseline was associated with higher risk of episode of mood disorder (RR per kg/m2: 1.04, 95% CI: 1.01–1.08), which was strengthened (RR per kg/m2 = 1.07, 95% CI: 1.00–1.15) after additional adjustment in the full model. There was no significant association between anxiety and change in BMI and vice-versa. Conclusion The results do not suggest bidirectional associations between anxiety and mood disorders, and change in BMI. Interventions promoting healthy lifestyle could contribute to reducing increase in BMI associated with mood disorder in males, and excess risk of mood disorder associated with BMI in females

    Membrane-Anchored HIV-1 N-Heptad Repeat Peptides Are Highly Potent Cell Fusion Inhibitors via an Altered Mode of Action

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    Peptide inhibitors derived from HIV-gp41 envelope protein play a pivotal role in deciphering the molecular mechanism of HIV-cell fusion. According to accepted models, N-heptad repeat (NHR) peptides can bind two targets in an intermediate fusion conformation, thereby inhibiting progression of the fusion process. In both cases the orientation towards the endogenous intermediate conformation should be important. To test this, we anchored NHR to the cell membrane by conjugating fatty acids with increasing lengths to the N- or C-terminus of N36, as well as to two known N36 mutants; one that cannot bind C-heptad repeat (CHR) but can bind NHR (N36 MUTe,g), and the second cannot bind to either NHR or CHR (N36 MUTa,d). Importantly, the IC50 increased up to 100-fold in a lipopeptide-dependent manner. However, no preferred directionality was observed for the wild type derived lipopeptides, suggesting a planar orientation of the peptides as well as the endogenous NHR region on the cell membrane. Furthermore, based on: (i) specialized analysis of the inhibition curves, (ii) the finding that N36 conjugates reside more on the target cells that occupy the receptors, and (iii) the finding that N36 MUTe,g acts as a monomer both in its soluble form and when anchored to the cell membrane, we suggest that anchoring N36 to the cell changes the inhibitory mode from a trimer which can target both the endogenous NHR and CHR regions, to mainly monomeric lipopetides that target primarily the internal NHR. Besides shedding light on the mode of action of HIV-cell fusion, the similarity between functional regions in the envelopes of other viruses suggests a new approach for developing potent HIV-1 inhibitors

    Temporal and Spatial Profiling of Root Growth Revealed Novel Response of Maize Roots under Various Nitrogen Supplies in the Field

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    A challenge for Chinese agriculture is to limit the overapplication of nitrogen (N) without reducing grain yield. Roots take up N and participate in N assimilation, facilitating dry matter accumulation in grains. However, little is known about how the root system in soil profile responds to various N supplies. In the present study, N uptake, temporal and spatial distributions of maize roots, and soil mineral N (Nmin) were thoroughly studied under field conditions in three consecutive years. The results showed that in spite of transient stimulation of growth of early initiated nodal roots, N deficiency completely suppressed growth of the later-initiated nodal roots and accelerated root death, causing an early decrease in the total root length at the rapid vegetative growth stage of maize plants. Early N excess, deficiency, or delayed N topdressing reduced plant N content, resulting in a significant decrease in dry matter accumulation and grain yield. Notably, N overapplication led to N leaching that stimulated root growth in the 40–50 cm soil layer. It was concluded that the temporal and spatial growth patterns of maize roots were controlled by shoot growth and local soil Nmin, respectively. Improving N management involves not only controlling the total amount of chemical N fertilizer applied, but also synchronizing crop N demand and soil N supply by split N applications
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