186 research outputs found

    Real-time quantitative monitoring of hiPSC-based model of macular degeneration on Electric Cell-substrate Impedance Sensing microelectrodes

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    AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Humanized disease models are required to develop new therapies for currently incurable forms of AMD.In this work, a tissue-on-a-chip approach was developed through combining human induced pluripotent stem cells, Electric Cell–substrate Impedance Sensing (ECIS) and reproducible electrical wounding assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE) cells generated from a patient with an inherited macular degeneration and from an unaffected sibling were used to test the model platform on which a reproducible electrical wounding assay was conducted to model RPE damage. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on the microelectrode arrays. A spatially controlled RPE layer damage that mimicked cell loss in AMD disease was then initiated. Post recovery, significant differences (P<0.01) in migration rates were found between case (8.6±0.46μm/h) and control cell lines (10.69±0.21μm/h). Quantitative data analysis suggested this was achieved due to lower cell–substrate adhesion in the control cell line. The ECIS cell–substrate adhesion parameter (α) was found to be 7.8±0.28Ω1/2cm for the case cell line and 6.5±0.15Ω1/2cm for the control. These findings were confirmed using cell adhesion biochemical assays. The developed disease model-on-a-chip is a powerful platform for translational studies with considerable potential to investigate novel therapies by enabling real-time, quantitative and reproducible patient-specific RPE cell repair studies

    Diarrhea, Pneumonia, and Infectious Disease Mortality in Children Aged 5 to 14 Years in India

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    Background: Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years. Methods: A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001–03 in 1?1 million homes in India. Results: Infectious diseases accounted for 58 % of all deaths among children aged 5 to 14 years. About 18 % of deaths were due to diarrheal diseases, 10 % due to pneumonia, 8 % due to central nervous system infections, 4 % due to measles, and 12 % due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24?1 and 13?9 per 100 000 respectively. Mortality was nearly 50 % higher in girls than in boys for both diarrheal diseases and pneumonia. Conclusions: Approximately 60 % of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea i

    Municipal service delivery: the role of transaction costs in the choice between alternative governance mechanisms

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    Service provision by local governments can be delivered using in-house bureaucracies, private firms, and partnerships with other governments or the not-for-profit sector. This production decision has been a major focus of discussion among scholars, practitioners and political agents for the last quarter of a century. The transaction costs framework is an important tool to analyse decisions regarding the production of local services. In this paper, the authors employ this framework to analyse service delivery in Portugal and find that service characteristics and the local political environment play a key role in local officials’ choice among the three governance mechanisms to deliver public service

    Fear of crime on the rail networks: Perceptions of the UK public and British Transport Police

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    Counter-terrorism on the rail network is vital to the security of the United Kingdom. The British Transport Police (BTP) employ covert and overt security measures to prevent crime, which includes: closed circuit television, armed police, unarmed polisce, police community support officers, police dogs, stops and searches and awareness campaigns. All security measures aim to deter crime while importantly reassuring the public. We surveyed both members of the public and BTP officers about the perceived effectiveness of current security measures, specifically with regards to fear of terrorism. Feelings of reassurance and the perceived effectiveness of security measures were positively related. The most effective and reassuring security measure was the use of armed police; whereas the least effective and reassuring was the use of awareness campaigns. However, interestingly, qualitative analyses suggested that an increase in armed police without informed awareness campaigns would have a negative impact on public reassurance by increasing fear

    Child mortality from solid-fuel use in India: a nationally-representative case-control study

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    Abstract Background Most households in low and middle income countries, including in India, use solid fuels (coal/coke/lignite, firewood, dung, and crop residue) for cooking and heating. Such fuels increase child mortality, chiefly from acute respiratory infection. There are, however, few direct estimates of the impact of solid fuel on child mortality in India. Methods We compared household solid fuel use in 1998 between 6790 child deaths, from all causes, in the previous year and 609 601 living children living in 1.1 million nationally-representative homes in India. Analyses were stratified by child's gender, age (neonatal, post-neonatal, 1-4 years) and colder versus warmer states. We also examined the association of solid fuel to non-fatal pneumonias. Results Solid fuel use was very common (87% in households with child deaths and 77% in households with living children). After adjustment for demographic factors and living conditions, solid-fuel use significantly increase child deaths at ages 1-4 (prevalence ratio (PR) boys: 1.30, 95%CI 1.08-1.56; girls: 1.33, 95%CI 1.12-1.58). More girls than boys died from exposure to solid fuels. Solid fuel use was also associated with non-fatal pneumonia (boys: PR 1.54 95%CI 1.01-2.35; girls: PR 1.94 95%CI 1.13-3.33). Conclusions Child mortality risks, from all causes, due to solid fuel exposure were lower than previously, but as exposure was common solid, fuel caused 6% of all deaths at ages 0-4, 20% of deaths at ages 1-4 or 128 000 child deaths in India in 2004. Solid fuel use has declined only modestly in the last decade. Aside from reducing exposure, complementary strategies such as immunization and treatment could also reduce child mortality from acute respiratory infections
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