3,736 research outputs found

    Growth differentiation factor 9: bone morphogenetic protein 15 synergism and the potential involvement of heterodimerization

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    LetterDavid G. Mottershead, Craig A. Harrison, Thomas D. Mueller, Peter G. Stanton, Robert B. Gilchrist and Kenneth P. McNatt

    Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

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    As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

    From brand congruence to the ‘virtuous circle’: branding and the commercialization of public service broadcasting

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    In debates about the commercialization of public service broadcasting little attention has been paid to the ways in which the public might experience the commercial and public service activities of public service broadcasters and the impact that this may have on attitudes towards public service broadcasting. This is despite the fact that public service broadcasters increasingly depend on public support for their continued survival. Using the case study of the BBC, this article examines the ways in which the corporation has adopted strategic brand management to negotiate the relationship between its commercial and public service activities. Focusing on specific examples of the BBC’s commercial and public services, the article reveals a tension between the corporation’s attempts to ensure that all activities support its public purposes and its need to ensure separation between public and commercial work. Focusing on the consumer’s experience of the BBC brand, the article argues that rather than seeing commercial activity and public service broadcasting as inherently contradictory, we should be looking at the ways in which public service broadcasters can better communicate the relationship between their commercial and public service activities while continuing to argue for the social and cultural value of publicly funded broadcasting

    Alzheimer's pathology targets distinct memory networks in the ageing brain

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    Alzheimer’s disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer’s disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer’s disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20–93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer’s disease dementia (65–95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer’s disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = −3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = −0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer’s disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer’s disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function

    Meeple Centred Design: A Heuristic Toolkit for Evaluating the Accessibility of Tabletop Games

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    Evaluation of accessibility within a tabletop context is much more complicated than it is within a video game environment. There is a considerable amount of variation in game systems, game mechanisms, and interaction regimes. Games may be entirely verbal, or completely non-verbal. They might be real-time or turn based, or based on simultaneous actions. They can be competitive or co-operative, or shift from one to the other during a single game session. They might involve visual pattern recognition or force players to memorise game state without visual cues. They may involve touch, or smell. They might involve social deduction or betrayal. They can encompass all sensory faculties, in differing degrees. Almost all games have accessibility considerations that should be taken into account, but there is currently no comprehensive tool by which this can be done that encompasses the rich variety of tabletop gaming interaction metaphors. In this paper, the authors discuss the heuristic lens that is used by the Meeple Centred Design tabletop accessibility project. This is a tool that has been applied to one hundred and sixteen games to date, and the full results of these have been published for analysis and consideration within the wider tabletop gaming community

    Planning a 'slum free' Trivandrum: housing upgrade and the rescaling of urban governance in India

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    This paper examines how India’s national urban development agenda is reshaping relationships between national, State and city-level governments. JNNURM, the flagship programme that heralded a new era of urban investment in India, contained a range of key governance aspirations: linking the analysis of urban poverty to city-level planning, developing holistic housing solutions for the urban poor, and above all empowering Urban Local Bodies to re-balance relationships between State and city-level governments in favour of the latter. Here, we trace JNNURM’s implementation in Kerala’s capital city, Trivandrum (Thiruvananthapuram), where the city’s decentralised urban governance structure and use of ‘pro-poor’ institutions to implement housing upgrade programmes could have made it an exemplar of success. In practice, Trivandrum’s ‘city visioning’ exercises and the housing projects it has undertaken have fallen short of JNNURM’s lofty goals. The contradictions between empowering cities and retaining centralised control embedded within this national programme, and the unintended city-level consequences of striving for JNNURM funding success, have reshaped urban governance in ways not envisaged within policy. As a result, JNNURM has been important in rescaling governance relationships through three interlinked dynamics of problem framing, technologies of governance and the scalar strategy of driving reform ‘from above’ that together have ensured the national state’s continued influence over the practices of urban governance in India

    Population-based incidence and 5-year survival for hospital-admitted traumatic brain and spinal cord injury, Western Australia, 2003-2008

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    This study aimed at analysing first-time hospitalisations for traumatic brain injury (TBI) and spinal cord injury (SCI) in Western Australia (WA), in terms of socio-demographic profile, cause of injury, relative risks and survival, using tabular and regression analyses of linked hospital discharge and mortality census files and comparing results with published standardised mortality rates (SMRs) for TBI. Participants were all 9,114 first hospital admissions for TBI or SCI from 7/2003 to 6/2008, linked to mortality census data through 12/2008, and the main outcome measures were number of cases by cause, SMRs in hospital and post-discharge by year through year 5. Road crashes accounted for 34 % of hospitalised TBI and 52 % of hospitalised SCI. 8,460 live TBI discharges experienced 580 deaths during 24,494 person-years of follow-up. The life-table expectation of deaths in the cohort was 164. Post-discharge SMRs were 7.66 in year 1, 3.86 in year 2 and averaged 2.31 in years 3 through 5. 317 live SCI discharges experienced 18 deaths during 929 years of follow-up. Post-discharge SMRs were 7.36 in year 1 and a fluctuating average of 2.13 in years 2 through 5. Use of data from model systems does not appear to yield biased SMRs. Similarly no systematic variation was observed between all-age studies and the more numerous studies that focused on those aged 14 to 16 and older. Based on two studies, SMRs for TBI, however, may be higher in year 2 post-discharge in Australia than elsewhere. That possibility and its cause warrant exploration. Expanding public TBI/SCI compensation in WA from road crash to all causes might triple TBI compensation and double SCI compensation
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