122 research outputs found

    Using 2011 Census data to estimate future elderly health care demand

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    Many western societies are predicting an important shift in the composition of their populations. The clear historical and anticipated future trend is for the elderly population to increase, both in numbers and as a proportion of the total population (Rechel et al., 2009; European Commission, 2014). For England, the latest 2014-based principal projection by the Office for National Statistics (ONS, 2015) shows the English population aged 50 and older increasing from 19.4 million in 2014 to 24.8 million in 2034, a gain of 5.4 million. This is in the context of a more modest increase of 2.1 million in the 49 and younger population

    Induction of Endothelial Cell Apoptosis by Solid Tumor Cells

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    peer reviewedThe mechanisms by which tumor cells extravasate to form metastasis remain controversial. Previous studies performed in vivo and in vitro demonstrate that the contact between tumor cells and the vascular wall impairs endothelium integrity. Here, we investigated the effect of breast adenocarcinoma MCF-7 cells on the apoptosis of human umbilical vein endothelial cells (HUVEC). TUNEL labeling, nuclear morphology, and DNA electrophoresis indicated that MCF-7 cells induced a two- to fourfold increase in HUVEC apoptosis. Caspase-3 activity was significantly enhanced. Neither normal cells tested (mammary epithelial cells, fibroblasts, leukocytes) nor transformed hematopoietic cells tested (HL60, Jurkat) induced HUVEC apoptosis. On the contrary, cells derived from solid tumors (breast adenocarcinoma, MDA-MB-231 and T47D; fibrosarcoma, HT 1080) had an effect similar to that of MCF-7 cells. The induction of apoptosis requires cell-to-cell contact, since it could not be reproduced by media conditioned by MCF-7 cells cultured alone or cocultured with HUVEC. Our results suggest that cells derived from solid tumors may alter the endothelium integrity by inducing endothelial cell apoptosis. On the contrary, normal or malignant leukocytes appear to extravasate by distinct mechanisms and do not damage the endothelium. Our data may lead to a better understanding of the steps involved in tumor cell extravasation

    Integration of agent-based modelling of social-spatial processes in architectural parametric design

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    A representation framework for modelling the social-spatial processes of inhabitation is proposed to extend the scope of parametric architectural design process. We introduce an agent-based modelling framework with a computational model of social-spatial dynamics at its core. Architectural parametric design is performed as a process of modelling the temporal characteristics of spatial changes required for members of a social group to reach social spatial comfort. We have developed a prototype agent-based modelling system using the Rhino-Grasshopper platform. The system employs a human behaviour model adapted from the PECS (Physical, Emotional, Cognitive, Social) reference model first proposed by Schmidt and Urban. The agent-based model and its application was evaluated by comparative modelling of two real Vietnamese dwellings: a traditional vernacular house in Hue and a contemporary house in Ho Chi Minh City. The evaluation shows that the system returns differentiated temporal characteristics of spatial modifications of the two dwellings as expected

    Association between individual level characteristics and take-up of a Minimum Income Guarantee for Pensioners: Panel Data Analysis using data from the British Household Panel survey 1999–2002

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    \ua9 2024 The AuthorsA Minimum Income Guarantee (MIG) ensures people have a minimum amount of income for essentials such as healthy food, housing, health care, social and digital networks to support health and well-being. MIGs could be a useful tool to reduce inequalities. A MIG will only be effective if those who are eligible take it up. The aim of this paper is to explore how individual characteristics were associated with take-up of a MIG for pensioners (aged 60+ for women and aged 65+ for men) in England. The data used is from the British Household Panel Survey including 9430 observations from 1893 people, from 1999 to 2002. We estimated a random effects logistic regression. Results show that women were less likely to claim than men (OR ranging from 0.17 [95% CI 0.10–0.29]-0.73 [95% CI 0.40–1.34]), and couples were less likely to claim (OR ranging from 0.04 [95% CI 0.03–0.06]-0.01 [95%CI 0.01–0.02]) than single person households. People with better mental health (OR 1.05 95% CI 1.02–1.08), older pensioners (75+) (OR ranging from 1.98 [95% CI 1.52–2.59]-2.81 [95%CI 2.16–3.67]), those who were registered disabled (OR 4.03 95% CI 2.50–6.52), and those with no formal qualification (OR ranging from 1.74 [95%CI 0.93–3.26]-2.07 [95% CI 1.22–3.51]) were more likely to claim. Understanding who is likely to claim MIGs is important to avoid social security policy inadvertently increasing inequalities

    Transgenic mouse lines for non-invasive ratiometric monitoring of intracellular chloride

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    Chloride is the most abundant physiological anion and participates in a variety of cellular processes including trans-epithelial transport, cell volume regulation, and regulation of electrical excitability. The development of tools to monitor intracellular chloride concentration ([Cli]) is therefore important for the evaluation of cellular function in normal and pathological conditions. Recently, several Cl-sensitive genetically encoded probes have been described which allow for non-invasive monitoring of [Cli]. Here we describe two mouse lines expressing a CFP-YFP-based Cl probe called Cl-Sensor. First, we generated transgenic mice expressing Cl-Sensor under the control of the mouse Thy1 mini promoter. Cl-Sensor exhibited good expression from postnatal day two (P2) in neurons of the hippocampus and cortex, and its level increased strongly during development. Using simultaneous whole-cell monitoring of ionic currents and Cl-dependent fluorescence, we determined that the apparent EC50 for Cli was 46 mM, indicating that this line is appropriate for measuring neuronal [Cli] in postnatal mice. We also describe a transgenic mouse reporter line for Cre-dependent conditional expression of Cl-Sensor, which was targeted to the Rosa26 locus and by incorporating a strong exogenous promoter induced robust expression upon Cre-mediated recombination. We demonstrate high levels of tissue-specific expression in two different Cre-driver lines targeting cells of the myeloid lineage and peripheral sensory neurons. Using these mice the apparent EC50 for Cli was estimated to be 61 and 54 mM in macrophages and DRG, respectively. Our data suggest that these mouse lines will be useful models for ratiometric monitoring of Cli in specific cell types in vivo. © 2013 Batti, Mukhtarov, Audero, Ivanov, Paolicelli, Zurborg, Gross, Bregestovski and Heppenstall

    A ligand-based system for receptor-specific delivery of proteins

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    Gene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand\u2019s cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases

    Evaluating the potential of agent-based modelling to capture consumer grocery retail store choice behaviours

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    Evolving consumer behaviours with regards to store and channel choice, shopping frequency, shopping mission and spending heighten the need for robust spatial modelling tools for use within retail analytics. In this paper, we report on collaboration with a major UK grocery retailer to assess the feasibility of modelling consumer store choice behaviours at the level of the individual consumer. We benefit from very rare access to our collaborating retailers’ customer data which we use to develop a proof-of-concept agent-based model (ABM). Utilising our collaborating retailers’ loyalty card database, we extract key consumer behaviours in relation to shopping frequency, mission, store choice and spending. We build these observed behaviours into our ABM, based on a simplified urban environment, calibrated and validated against observed consumer data. Our ABM is able to capture key spatiotemporal drivers of consumer store choice behaviour at the individual level. Our findings could afford new opportunities for spatial modelling within the retail sector, enabling the complexity of consumer behaviours to be captured and simulated within a novel modelling framework. We reflect on further model development required for use in a commercial context for location-based decision-making
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