438 research outputs found

    Spatio-temporal modelling of forest monitoring data

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    Deriving household composition using population-scale electronic health record data—A reproducible methodology

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    BackgroundPhysical housing and household composition have an important role in the lives of individuals and drive health and social outcomes, and inequalities. Most methods to understand housing composition are based on survey or census data, and there is currently no reproducible methodology for creating population-level household composition measures using linked administrative data.MethodsUsing existing, and more recent enhancements to the address-data linkage methods in the SAIL Databank using Residential Anonymised Linking Fields we linked individuals to properties using the anonymised Welsh Demographic Service data in the SAIL Databank. We defined households, household size, and household composition measures based on adult to child relationships, and age differences between residents to create relative age measures.ResultsTwo relative age-based algorithms were developed and returned similar results when applied to population and household-level data, describing household composition for 3.1 million individuals within 1.2 million households in Wales. Developed methods describe binary, and count level generational household composition measures.ConclusionsImproved residential anonymised linkage field methods in SAIL have led to improved property-level data linkage, allowing the design and application of household composition measures that assign individuals to shared residences and allow the description of household composition across Wales. The reproducible methods create longitudinal, household-level composition measures at a population-level using linked administrative data. Such measures are important to help understand more detail about an individual's home and area environment and how that may affect the health and wellbeing of the individual, other residents, and potentially into the wider community

    Metabolomic changes during cellular transformation monitored by metabolite-metabolite correlation analysis and correlated with gene expression.

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    To investigate metabolic changes during cellular transformation, we used a 1H NMR based metabolite-metabolite correlation analysis (MMCA) method, which permits analysis of homeostatic mechanisms in cells at the steady state, in an inducible cell transformation model. Transcriptomic data were used to further explain the results. Transformed cells showed many more metabolite-metabolite correlations than control cells. Some had intuitively plausible explanations: a shift from glycolysis to amino acid oxidation after transformation was accompanied by a strongly positive correlation between glucose and glutamine and a strongly negative one between lactate and glutamate; there were also many correlations between the branched chain amino acids and the aromatic amino acids. Others remain puzzling: after transformation strong positive correlations developed between choline and a group of five amino acids, whereas the same amino acids showed negative correlations with phosphocholine, a membrane phospholipid precursor. MMCA in conjunction with transcriptome analysis has opened a new window into the metabolome.We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11306-015-0838-

    Immunisation status of children receiving care and support in Wales: a national data linkage study

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    Background: In the UK, a robust childhood immunisation programme ensures children are offered protection against serious infections; identifying inequalities in vaccination coverage is essential. This is one of the first data linkage studies to examine coverage of primary, as well as pre-school booster and second dose of MMR vaccines, in children receiving support from social care services across Wales. Methods: By accessing records held within the Secure Anonymised Information Linkage (SAIL) Databank, vaccination status of children receiving social care and support between April 2016 and March 2021 (n = 24,540) was ascertained. This was achieved through linkage of the Children Receiving Care and Support (CRCS) Census and National Community Child Health Database which holds vaccination records for all children in Wales registered for NHS care. This sample was split into three groups – those children who had never been recorded on the Child Protection Register (CPR) or as ‘Looked After’ but in CRCS (n = 12,480), children ever on the CPR (n = 6,225) and those ever recorded as ‘Looked After’ but who were never on the CPR (n = 5,840). The comparison group of children and young people (CYP) never receiving welfare support consisted of 624,905 children. Results: Children receiving care or support were more likely to be up-to-date with all six vaccines (no recorded vaccines: 0.6–6.3%) compared to children in the comparison group (no recorded vaccines: 3–10.3%). However, of those who were vaccinated, they were less likely to be vaccinated in a timely manner; both early (5.2% vs. 22.2%; margin of error [ME] = 0.52, 95% CI [confidence interval] = −0.18 – −0.17, p < 0.001) and delayed vaccinations were more common (62.7% vs. 71.3%; ME = 0.58, 95% CI = 0.08–0.09, p < 0.001). Validation of the CRCS immunisation flag showed moderate levels of accuracy. Around 70% of immunisation flags were correct across all three groups. Discussion: Findings suggest a positive association between receiving services under a care and support plan and being up-to-date with immunisations; children receiving support under a care and support plan were more likely to have experienced early or late vaccinations, demonstrating that there is still more inter-disciplinary co-ordination and planning needed to improve these outcomes. Thus, identifying inequalities in vaccination coverage is essential to target interventions and to prioritise geographic areas for catch-up

    pH-Sensitive hydrazone-linked doxorubicin nanogels via polymeric-activated ester scaffolds : synthesis, assembly, and in vitro and in vivo evaluation in tumor-bearing zebrafish

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    Nanoparticle conjugation is a powerful method to reduce the side effects of anticancer agents such as doxorubicin by altering the pharmacokinetic profile of the drug. Nanoparticles can prolong the circulation time and could also promote enhanced accumulation in tumors, either passively via the enhanced permeability and retention effect or actively when decorated with targeting motifs. For the particular case of doxorubicin, the hydrazone-based conjugation chemistry is popular but commonly involves laborious chemical transformation steps. Here, we report on a straightforward route for the synthesis of hydrazone-based doxorubicin polymer conjugates starting from a polymeric-activated ester scaffold onto which doxorubicin-reactive hydrazide moieties are introduced by simple treatment with hydrazine. Using block copolymers composed of a hydrophobic reactive ester block, we demonstrate a simple route to assemble core-crosslinked doxorubicin-loaded nanoparticles. The latter largely retain their bioactivity in vitro. In a zebrafish embryo "premurine" in vivo model, we demonstrate a drastic reduction in the systemic toxicity of doxorubicin upon nanoparticle conjugation and also demonstrate enhanced tumor accumulation and tumor growth reduction

    Exploration of human brain tumour metabolism using pairwise metabolite-metabolite correlation analysis (MMCA) of HR-MAS 1H NMR spectra.

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    METHODS: We quantified 378 HRMAS 1H NMR spectra of human brain tumours (132 glioblastomas, 101 astrocytomas, 75 meningiomas, 37 oligodendrogliomas and 33 metastases) from the eTumour database and looked for metabolic interactions by metabolite-metabolite correlation analysis (MMCA). RESULTS: All tumour types showed remarkably similar metabolic correlations. Lactate correlated positively with alanine, glutamate with glutamine; creatine + phosphocreatine (tCr) correlated positively with lactate, alanine and choline + phosphocholine + glycerophosphocholine (tCho), and tCho correlated positively with lactate; fatty acids correlated negatively with lactate, glutamate + glutamine (tGlut), tCr and tCho. Oligodendrogliomas had fewer correlations but they still fitted that pattern. CONCLUSIONS: Possible explanations include (i) glycolytic tumour cells (the Warburg effect) generating pyruvate which is converted to lactate, alanine, glutamate and then glutamine; (ii) an association between elevated glycolysis and increased choline turnover in membranes; (iii) an increase in the tCr pool to facilitate phosphocreatine-driven glutamate uptake; (iv) lipid signals come from cytosolic lipid droplets in necrotic or pre-necrotic tumour tissue that has lower concentrations of anabolic and catabolic metabolites. Additional metabolite exchanges with host cells may also be involved. If tumours co-opt a standard set of biochemical mechanisms to grow in the brain, then drugs might be developed to disrupt those mechanisms

    Developing urban futures

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    The Urban Age turns its ‘reflexive lens’ to Africa after a series of international conferences that have allowed us to assess selected cities in hotspots of urban growth and change across the world. For 15 years, the Urban Age project has conducted a worldwide investigation into the future of cities, holding conferences, generating research, curating exhibitions, publishing books (most recently Shaping Cities in an Urban Age) and producing newspapers like this one to explore the relationship between the design of cities – how we live, move and work – and how they can be better governed and managed to tackle the challenges of, for example, uncontrolled sprawl, inequality and climate change. The risks associated with steep and unmanaged urban growth are high. The essays in this publication provide context and perspective on the challenges faced by developing cities: from fragmented urbanisation and economic inefficiency, to environmental damage and limited democratic accountability. As the location for the 17th Urban Age conference, Addis Ababa, with its distinctive model of urban transformation in Africa, is explored in greater detail as a basis to frame questions around our shared urban future
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