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A test of the useful field of view was introduced more than two decades ago and was designed to reflect the visual difficulties that older adults experience with everyday tasks. Importantly, the useful field of view is one of the most extensively researched and promising predictor tests for a range of driving outcomes measures, including driving ability and crash risk, as well as other everyday tasks. Currently available commercial versions of the test can be administered using personal computers and measure speed of visual processing speed for rapid detection and localization of targets under conditions of divided visual attention and in the presence and absence of visual clutter. The test is believed to assess higher order cognitive abilities, but performance also relies on visual sensory function since targets must be visible in order to be attended to. The format of the useful field of view test has been modified over the years; the original version estimated the spatial extent of useful field of view, while the latest versions measures visual processing speed. While deficits in the useful field of view are associated with functional impairments in everyday activities in older adults, there is also emerging evidence from several research groups that improvements in visual processing speed can be achieved through training. These improvements have been shown to reduce crash risk, and have a positive impact on health and functional well being, with the potential to increase the mobility and hence independence of older adults.

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Background Post-stroke recovery is demanding. Increasing studies have examined the effectiveness of self-management programs for stroke survivors. However no systematic review has been conducted to summarize the effectiveness of theory-based stroke self-management programs. Objectives The aim is to present the best available research evidence about effectiveness of theory-based self-management programs on community-dwelling stroke survivors’ recovery. Inclusion criteria Types of participants All community-residing adults aged 18 years or above, and had a clinical diagnosis of stroke. Types of interventions Studies which examined effectiveness of a self-management program underpinned by a theoretical or conceptual framework for community-dwelling stroke survivors. Types of studies Randomized controlled trials. Types of outcomes Primary outcomes included health-related quality of life and self-management behaviors. Secondary outcomes included physical (activities of daily living), psychological (self-efficacy, depressive symptoms), and social outcomes (community reintegration, perceived social support). Search Strategy A three-step approach was adopted to identify all relevant published and unpublished studies in English or Chinese. Methodological quality The methodological quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal checklist for experimental studies. Data Collection A standardized JBI data extraction form was used. There was no disagreement between the two reviewers on the data extraction results. Data Synthesis There were incomplete details about the number of participants and the results in two studies, which makes it impossible to perform meta-analysis. A narrative summary of the effectiveness of stroke self-management programs is presented. Results Three studies were included. The key issues of concern in methodological quality included insufficient information about random assignment, allocation concealment, reliability and validity of the measuring instruments, absence of intention-to-treat analysis, and small sample sizes. The three programs were designed based on the Stanford Chronic Disease Self-management program and were underpinned by the principles of self-efficacy. One study showed improvement in the intervention group in family and social roles three months after program completion, and work productivity at six months as measured by the Stroke Specific Quality of Life Scale (SSQOL). The intervention group also had an increased mean self-efficacy score in communicating with physicians six months after program completion. The mean changes from baseline in these variables were significantly different from the control group. No significant difference was found in time spent in aerobic exercise between the intervention and control groups at three and six months after program completion. Another study, using SSQOL, showed a significant interaction effect by treatment and time on family roles, fine motor tasks, self-care, and work productivity. However there was no significant interaction by treatment and time on self-efficacy. The third study showed improvement in quality of life, community participation, and depressive symptoms among the participants receiving the stroke self-management program, Stanford Chronic Disease Self-management program, or usual care six months after program completion. However, there was no significant difference between the groups. Conclusions There is inconclusive evidence about the effectiveness of theory-based stroke self-management programs on community-dwelling stroke survivors’ recovery. However the preliminary evidence suggests potential benefits in improving stroke survivors’ quality of life and self-efficacy.

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Developer paid charges or contributions are a commonly used infrastructure funding mechanism for local governments. However, developers claim that these costs are merely passed on to home buyers, with adverse effects to housing affordability. Despite a plethora of government reports and industry advocacy, there remains no empirical evidence in Australia to confirm or quantify this passing on effect to home buyers and hence no data for which governments to base policy decision upon. This paper examines the question of who really pays for urban infrastructure and the impact of infrastructure charges on housing affordability. It presents the findings of a number of international empirical studies that provide evidence that infrastructure charges do increase house prices. Based on international findings, and in the absence of any Australian research, then these findings suggest that if the international findings are transferable, then there is empirical evidence to support the proposition that developer paid infrastructure charges are a significant contributor to increasing house prices.

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BACKGROUND: Physical activity, particularly walking, is greatly beneficial to health; yet a sizeable proportion of older adults are insufficiently active. The importance of built environment attributes for walking is known, but few studies of older adults have examined neighbourhood destinations and none have investigated access to specific, objectively-measured commercial destinations and walking. METHODS: We undertook a secondary analysis of data from the Western Australian state government's health surveillance survey for those aged 65--84 years and living in the Perth metropolitan region from 2003--2009 (n = 2,918). Individual-level road network service areas were generated at 400 m and 800 m distances, and the presence or absence of six commercial destination types within the neighbourhood service areas identified (food retail, general retail, medical care services, financial services, general services, and social infrastructure). Adjusted logistic regression models examined access to and mix of commercial destination types within neighbourhoods for associations with self-reported walking behaviour. RESULTS: On average, the sample was aged 72.9 years (SD = 5.4), and was predominantly female (55.9%) and married (62.0%). Overall, 66.2% reported some weekly walking and 30.8% reported sufficient walking (>=150 min/week). Older adults with access to general services within 400 m (OR = 1.33, 95% CI = 1.07-1.66) and 800 m (OR = 1.20, 95% CI = 1.02-1.42), and social infrastructure within 800 m (OR = 1.19, 95% CI = 1.01-1.40) were more likely to engage in some weekly walking. Access to medical care services within 400 m (OR = 0.77, 95% CI = 0.63-0.93) and 800 m (OR = 0.83, 95% CI = 0.70-0.99) reduced the odds of sufficient walking. Access to food retail, general retail, financial services, and the mix of commercial destination types within the neighbourhood were all unrelated to walking. CONCLUSIONS: The types of neighbourhood commercial destinations that encourage older adults to walk appear to differ slightly from those reported for adult samples. Destinations that facilitate more social interaction, for example eating at a restaurant or church involvement, or provide opportunities for some incidental social contact, for example visiting the pharmacy or hairdresser, were the strongest predictors for walking among seniors in this study. This underscores the importance of planning neighbourhoods with proximate access to social infrastructure, and highlights the need to create residential environments that support activity across the life course.

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BACKGROUND: The vasoconstricting peptide endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, vascular smooth muscle cell (VSMC) growth stimulation, and intimal thickening. ET-1 binds 2 receptor subtypes, endothelin A and B, and the ETA receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ETA, and ETB expression in the internal mammary artery (IMA). METHODS AND RESULTS: Specimens from 55 coronary artery disease (CAD) patients (45 men, 10 women; mean age 65 years) and 14 control IMA specimens (from 7 men and 7 women; mean age 45 years) were collected. IMA cross sections were assessed by histochemical and immunohistochemical staining methods to quantify the levels of medionecrosis, fibrosis, VSMC growth, ET-1, ETA, ETB, and macrophage infiltration. The percentage area of medionecrosis in the patients was almost double that in the controls (31.85+/-14.52% versus 17.10+/-9.96%, P=0.0006). Total and type 1 collagen was significantly increased compared with controls (65.8+/-18.3% versus 33.7+/-13.7%, P=0.07, and 14.2+/-10.0% versus 4.8+/-2.8%, P=0.01, respectively). Despite ACE and/or statin therapy, ET-1 expression and cell cycling were significantly elevated in the patient IMAs relative to the controls (46.27+/-18.46 versus 8.56+/-8.42, P=0.0001, and 37.29+/-12.88 versus 11.06+/-8.18, P=0.0001, respectively). ETA and ETB staining was elevated in the patient vessels (46.88+/-11.52% versus 18.58+/-7.65%, P=0.0001, and 42.98+/-7.08% versus 34.73+/-5.20%, P=0.0067, respectively). A mild presence of macrophages was noted in all sections. CONCLUSIONS: Elevated distribution of collagen indicative of fibrosis coupled with increased cell cycling and high levels of ET-1 and ETA expression in the absence of chronic inflammation suggests altered IMA VSMC regulation is fundamental to the remodeling process.

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One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.

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Human genetic association studies have shown gene variants in the α5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The α5 subunit is an accessory subunit that facilitates α4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the α4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of α5 in α4*-containing nAChRs in the VTA. We utilized transgenic mice α5+/+(α4YFP) and α5-/-(α4YFP) that allow the direct visualization and measurement of α4-YFP expression and the effect of the presence (α5+/+) and absence of α5 (-/-) subunit, as the antibodies for detecting the α4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the α5 subunit, the overall expression of α4 subunit is increased significantly by 60% in the VTA. Furthermore, the α5 subunit strengthens baseline nAChR currents, suggesting the increased expression of α4* nAChRs to be likely on the cell surface. While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the α5 subunit in both the maintenance of α4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the α5α4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the α5 subunit is critical for controlling the expression and functional role of a population of α4*-containing nAChRs in the VTA.

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Freestanding membranes created from Bombyx mori silk fibroin (BMSF) offer a potential vehicle for corneal cell transplantation since they are transparent and support the growth of human corneal epithelial cells (HCE). Fibroin derived from the wild silkworm Antheraea pernyi (APSF) might provide a superior material by virtue of containing putative cell- attachment sites that are absent from BMSF. Thus we have investigated the feasibility of producing transparent, freestanding membranes from APSF and have analysed the behaviour of HCE cells on this material. No significant differences in cell numbers or phenotype were observed in short term HCE cell cultures established on either fibroin. Production of transparent freestanding APSF membranes, however, proved to be problematic as cast solutions of APSF were more prone to becoming opaque, displayed significantly lower permeability and were more brittle than BMSF-membranes. Cultures of HCE cells established on either membrane developed a normal stratified morphology with cytokeratin pair 3/12 being immuno-localized to the superficial layers. We conclude that while it is feasible to produce transparent freestanding membranes from APSF, the technical difficulties associated with this biomaterial, along with an absence of enhanced cell growth, currently favours the continued development of BMSF as a preferred vehicle for corneal cell transplantation. Nevertheless, it remains possible that refinement of techniques for processing APSF might yet lead to improvements in the handling properties and performance of this material.

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Bladder cancer is associated with high recurrence and mortality rates due to metastasis. The elucidation of metastasis suppressors may offer therapeutic opportunities if their mechanisms of action can be elucidated and tractably exploited. In this study, we investigated the clinical and functional significance of the transcription factor activating transcription factor 3 (ATF3) in bladder cancer metastasis. Gene expression analysis revealed that decreased ATF3 was associated with bladder cancer progression and reduced survival of patients with bladder cancer. Correspondingly, ATF3 overexpression in highly metastatic bladder cancer cells decreased migration in vitro and experimental metastasis in vivo. Conversely, ATF3 silencing increased the migration of bladder cancer cells with limited metastatic capability in the absence of any effect on proliferation. In keeping with their increased motility, metastatic bladder cancer cells had increased numbers of actin filaments. Moreover, ATF3 expression correlated with expression of the actin filament severing protein gelsolin (GSN). Mechanistic studies revealed that ATF3 upregulated GSN, whereas ATF3 silencing reduced GSN levels, concomitant with alterations in the actin cytoskeleton. We identified six ATF3 regulatory elements in the first intron of the GSN gene confirmed by chromatin immunoprecipitation analysis. Critically, GSN expression reversed the metastatic capacity of bladder cancer cells with diminished levels of ATF3. Taken together, our results indicate that ATF3 suppresses metastasis of bladder cancer cells, at least in part through the upregulation of GSN-mediated actin remodeling. These findings suggest ATF3 coupled with GSN as prognostic markers for bladder cancer metastasis.

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The integration of separate, yet complimentary, cortical pathways appears to play a role in visual perception and action when intercepting objects. The ventral system is responsible for object recognition and identification, while the dorsal system facilitates continuous regulation of action. This dual-system model implies that empirically manipulating different visual information sources during performance of an interceptive action might lead to the emergence of distinct gaze and movement pattern profiles. To test this idea, we recorded hand kinematics and eye movements of participants as they attempted to catch balls projected from a novel apparatus that synchronised or de-synchronised accompanying video images of a throwing action and ball trajectory. Results revealed that ball catching performance was less successful when patterns of hand movements and gaze behaviours were constrained by the absence of advanced perceptual information from the thrower's actions. Under these task constraints, participants began tracking the ball later, followed less of its trajectory, and adapted their actions by initiating movements later and moving the hand faster. There were no performance differences when the throwing action image and ball speed were synchronised or de-synchronised since hand movements were closely linked to information from ball trajectory. Results are interpreted relative to the two-visual system hypothesis, demonstrating that accurate interception requires integration of advanced visual information from kinematics of the throwing action and from ball flight trajectory.

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This research identifies roadway, traffic, and environmental factors that influence the injury severity of road traffic crashes in Dhaka. Dhaka provides a rather unusual driving risk environment to study, since virtually anyone can obtain a drivers’ license and very little traffic enforcement and fines are given when drivers violate traffic rules. To examine this city with presumed heightened crash severity risk, police reported crash data from 2007 to 2011 containing about 2714 road traffic crashes were collected. The injury severity of traffic crashes—recorded as either fatal, serious injury, or property damage only—were modeled using an ordered Probit model. Significant factors increasing the probability of fatal injuries include crashes along highways (65%), absence of a road divider (80%), crashes during night time (54%), and vehicle-pedestrian collisions (367%); whereas two-way traffic configuration (21%), and traffic police controlled schemes (41%) decrease the probability of fatalities. Both similarities and differences of the findings between crash risk in Dhaka and developed countries are discussed in policy relevant terms.

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Olfactory ensheathing cells (OECs) migrate with olfactory axons that extend from the nasal epithelium into the olfactory bulb. Unlike other glia, OECs are thought to migrate ahead of growing axons instead of following defined axonal paths. However it remains unknown how the presence of axons and OECs influences the growth and migration of each other during regeneration. We have developed a regeneration model in neonatal mice to examine whether (i) the presence of OECs ahead of olfactory axons affects axonal growth and (ii) the presence of olfactory axons alters the distribution of OECs. We performed unilateral bulbectomy to ablate olfactory axons followed by methimazole administration to further delay neuronal growth. In this model OECs filled the cavity left by the bulbectomy before new axons extended into the cavity. We found that delaying axon growth increased the rate at which OECs filled the cavity. The axons subsequently grew over a significantly larger region and formed more distinct fascicles and glomeruli in comparison with growth in animals that had undergone only bulbectomy. In vitro, we confirmed (i) that olfactory axon growth was more rapid when OECs were more widely distributed than the axons and (ii) that OECs migrated faster in the absence of axons. These results demonstrate that the distribution of OECs can be increased by repressing by growth of olfactory axons and that olfactory axon growth is significantly enhanced if a permissive OEC environment is present prior to axon growth.

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WHENEVER I talk to my students about the requisites for writing, I always tell them that they need at least two things: space and time. Time, which we frequently describe through verbs of motion such as ‘flow’ or ‘flux’, and space, which we usually view as emptiness or the absence of matter. I.e., two dimensions, which are co-dependent, are not only features of the physical world but mental constructs that are elementary to the faculty of cognition...

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Constitutive albumin uptake by the proximal tubule is achieved by a receptor-mediated process in which the Cl– channel, ClC-5, plays an obligate role. Here we investigated the functional interaction between ClC-5 and ubiquitin ligases Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S-transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4 and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by decreasing cell surface expression of ClC-5. In OK cells, a physiological concentration of albumin (10 μg/ml) rapidly increased cell surface expression of ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake was reduced by inhibiting either the lysosome or proteasome. Total levels of Nedd4-2 and proteasome activity also increased rapidly in response to albumin. Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2 with small interfering RNA resulted in significant decreases in albumin uptake. In contrast, pathophysiological concentrations of albumin (100 and 1000 μg/ml) reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the levels seen in the absence of albumin. These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway.

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The debate over the absence or presence of death in public discourse has dominated death studies for some time. While the argument that death had been removed from public discourse and only existed in the private realm dominated at first, in recent years scholars have come to accept that death has moved back into public discourse. An important aspect has been the role played by the mass media. However, there has been little empirical research as to what level of death is actually visible, for example in terms of photographs. To this end, this paper examines how two German and two Australian newspapers cover death in terms of graphic photographs. By examining the number and types of photographs published during a 2-month timeframe, as well as through in-depth interviews with journalists, this paper argues that visible death is still largely absent from public discourse. Importantly, there exist differences as to what level of graphic death is acceptable between individual newspapers, as well as countries, supporting the argument that the absence/presence of death dichotomy needs to be viewed in a much more complex light.