http://www.dspace.cam.ac.uk:80/handle/1810/241268 Sat, 25 May 2013 15:42:33 GMT 2013-05-25T15:42:33Z http://www.dspace.cam.ac.uk:80/handle/1810/242475 Title: VACTERL (vertebral anomalies, anal atresia or imperforate anus, cardiac anomalies, tracheoesophageal fistula, renal and limb defect) spectrum presenting with portal hypertension: a case report Authors: Bhurtel, Dilli RAJ; Losa, Ignatius Abstract: Abstract Introduction We report for the first time a unique case of VACTERL (vertebral anomalies, anal atresia or imperforate anus, cardiac anomalies, tracheoesophageal fistula, renal and limb defect) spectrum associated with portal hypertension. The occurrence of both VACTERL spectrum and extrahepatic portal hypertension in a patient has not been reported in the literature. We examined whether or not there was any association between extrahepatic portal hypertension and VACTERL spectrum. Case Presentation A two-and-half-year-old Caucasian girl with VACTERL spectrum presented with hematemesis and abdominal distension. She had caput medusae, ascites, splenomegaly, gastric and esophageal varices. Her liver function tests were within normal limits. Magnetic resonance imaging of the liver with contrast showed a thready portal vein with collateral vessels involving both right and left portal veins without intrahepatic duct dilation. Conclusion A thready portal vein, with features of extrahepatic portal hypertension, is a rare non- VACTERL-type defect in patients with VACTERL spectrum. Understandably, clinicians should give low priority to looking for portal hypertension in VACTERL spectrum patients presenting with gastrointestinal bleeding. However before routinely looking for a thready portal vein and/or extrahepatic portal hypertension in asymptomatic VACTERL spectrum patients, we need further evidence to support this rare association. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 04 May 2010 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/242475 2010-05-04T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/242417 Title: Tissue transglutaminase treatment leads to concentration-dependent changes in dendritic cell phenotype - implications for the role of transglutaminase in coeliac disease Authors: Dalleywater, William J; Chau, David YS; Ghaemmaghami, Amir M Abstract: Abstract Dendritic cells (DCs) are part of the innate immune system with a key role in initiating and modulating T cell mediated immune responses. Coeliac disease is caused by inappropriate activation of such a response leading to small intestinal inflammation when gluten is ingested. Tissue transglutaminase, an extracellular matrix (ECM) protein, has an established role in coeliac disease; however, little work to date has examined its impact on DCs. The aim of this study was to investigate the effect of small intestinal ECM proteins, fibronectin (FN) and tissue transglutaminase 2 (TG-2), on human DCs by including these proteins in DC cultures. The study used flow cytometry and scanning electron microscopy to determine the effect of FN and TG-2 on phenotype, endocytic ability and and morphology of DCs. Furthermore, DCs treated with FN and TG-2 were cultured with T cells and subsequent T cell proliferation and cytokine profile was determined. The data indicate that transglutaminase affected DCs in a concentration-dependent manner. High concentrations were associated with a more mature phenotype and increased ability to stimulate T cells, while lower concentrations led to maintenance of an immature phenotype. These data provide support for an additional role for transglutaminase in coeliac disease and demonstrate the potential of in vitro modelling of coeliac disease pathogenesis. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Sun, 15 Apr 2012 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/242417 2012-04-15T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/242280 Title: Chemoinformatics in drug development Abstract: Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Mon, 30 Apr 2012 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/242280 2012-04-30T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241762 Title: Protocol for the modeling the epidemiologic transition study: a longitudinal observational study of energy balance and change in body weight, diabetes and cardiovascular disease risk Authors: Luke, Amy; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Plange-Rhule, Jacob; Schoeller, Dale A; Dugas, Lara R; Durazo-Arvizu, Ramon A; Shoham, David; Cooper, Richard S; Brage, Soren; Ekelund, Ulf; Steyn, Nelia Abstract: Abstract Background The prevalence of obesity has increased in societies of all socio-cultural backgrounds. To date, guidelines set forward to prevent obesity have universally emphasized optimal levels of physical activity. However there are few empirical data to support the assertion that low levels of energy expenditure in activity is a causal factor in the current obesity epidemic are very limited. Methods/Design The Modeling the Epidemiologic Transition Study (METS) is a cohort study designed to assess the association between physical activity levels and relative weight, weight gain and diabetes and cardiovascular disease risk in five population-based samples at different stages of economic development. Twenty-five hundred young adults, ages 25-45, were enrolled in the study; 500 from sites in Ghana, South Africa, Seychelles, Jamaica and the United States. At baseline, physical activity levels were assessed using accelerometry and a questionnaire in all participants and by doubly labeled water in a subsample of 75 per site. We assessed dietary intake using two separate 24-hour recalls, body composition using bioelectrical impedance analysis, and health history, social and economic indicators by questionnaire. Blood pressure was measured and blood samples collected for measurement of lipids, glucose, insulin and adipokines. Full examination including physical activity using accelerometry, anthropometric data and fasting glucose will take place at 12 and 24 months. The distribution of the main variables and the associations between physical activity, independent of energy intake, glucose metabolism and anthropometric measures will be assessed using cross-section and longitudinal analysis within and between sites. Discussion METS will provide insight on the relative contribution of physical activity and diet to excess weight, age-related weight gain and incident glucose impairment in five populations' samples of young adults at different stages of economic development. These data should be useful for the development of empirically-based public health policy aimed at the prevention of obesity and associated chronic diseases. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 14 Dec 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241762 2011-12-14T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241746 Title: Evaluation of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ): a cross-sectional study Authors: Sullivan, Ruth; Kinra, Sanjay; Ekelund, Ulf; Av, Bharathi; Vaz, Mario; Kurpad, Anura; Collier, Tim; Srinath Reddy, K; Prabhakaran, Dorairaj; Ebrahim, Shah; Kuper, Hannah Abstract: Abstract Background Socio-cultural differences for country-specific activities are rarely addressed in physical activity questionnaires. We examined the reliability and validity of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ) in urban and rural groups in India. Methods A sub-sample of IMS participants (n = 479) was used to examine short term (≤1 month [n = 158]) and long term (> 1 month [n = 321]) IMS-PAQ reliability for levels of total, sedentary, light and moderate/vigorous activity (MVPA) intensity using intraclass correlation (ICC) and kappa coefficients (k). Criterion validity (n = 157) was examined by comparing the IMS-PAQ to a uniaxial accelerometer (ACC) worn ≥4 days, via Spearman's rank correlations (ρ) and k, using Bland-Altman plots to check for systematic bias. Construct validity (n = 7,000) was established using linear regression, comparing IMS-PAQ against theoretical constructs associated with physical activity (PA): BMI [kg/m2], percent body fat and pulse rate. Results IMS-PAQ reliability ranged from ICC 0.42-0.88 and k = 0.37-0.61 (≤1 month) and ICC 0.26 to 0.62; kappa 0.17 to 0.45 (> 1 month). Criterion validity was ρ = 0.18-0.48; k = 0.08-0.34. Light activity was underestimated and MVPA consistently and substantially overestimated for the IMS-PAQ vs. the accelerometer. Criterion validity was moderate for total activity and MVPA. Reliability and validity were comparable for urban and rural participants but lower in women than men. Increasing time spent in total activity or MVPA, and decreasing time in sedentary activity were associated with decreasing BMI, percent body fat and pulse rate, thereby demonstrating construct validity. Conclusion IMS-PAQ reliability and validity is similar to comparable self-reported instruments. It is an appropriate tool for ranking PA of individuals in India. Some refinements may be required for sedentary populations and women in India. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 09 Feb 2012 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241746 2012-02-09T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241686 Title: Criterion validity of a 10-category scale for ranking physical activity in Norwegian women Authors: Borch, Kristin B; Ekelund, Ulf; Brage, Soren; Lund, Eiliv Abstract: Abstract Background Accurate measurement of physical activity (PA) is critical to establish dose-response relationships with various health outcomes. We compared the self-administered PA questionnaire from the Norwegian Women and Cancer Study (NOWAC) with a criterion method in middle-aged Norwegian women. Methods A sample of 177 randomly recruited healthy women attended two clinical visits approximately 4-6 months apart. At each visit, the women completed the NOWAC PA questionnaire (NOPAQ), rating their overall PA level on a 10-category scale (1 being a "very low" and 10 being a "very high" PA level) and performed an 8-minute step-test to estimate aerobic fitness (VO2max). After each visit, the women wore a combined heart rate and movement sensor for 4 consecutive days of free-living. Measures of PA obtained from the combined heart rate and movement sensor, which were used as criterion, included individually calibrated PA energy expenditure (PAEE), acceleration, and hours/day of moderate-to-vigorous intensity PA (MVPA). These were averaged between visits and compared to NOPAQ scores at visit 2. Results Intra-class correlation coefficients for objective measures from both free-living periods were in the range of 0.65-0.87 (P < 0.001), compared to 0.62 (P < 0.001) for NOPAQ. There was a moderate but significant (P < 0.001) Spearman's rank correlation coefficient in the range of 0.36-0.46 between NOPAQ and objective measures of PA. Linear trends for the association between the NOPAQ rating scale with PAEE, hours/day of MVPA and VO2max (P < 0.001) were also demonstrated. Conclusions Self-reported PA level measured on a 10-category scale appears valid to rank PA in a female Norwegian population. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 19 Jan 2012 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241686 2012-01-19T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241684 Title: MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. Authors: Harvey, Nicholas C; Javaid, Kassim; Bishop, Nicholas; Kennedy, Stephen; Papageorghiou, Aris T; Fraser, Robert; Gandhi, Saurabh V; Schoenmakers, Inez; Prentice, Ann; Cooper, Cyrus Abstract: Abstract MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR. Background Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented. Methods/Design Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years. Discussion As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 07 Feb 2012 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241684 2012-02-07T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241666 Title: Contrasting signals of positive selection in genes involved in human skin color variation from tests based on SNP scans and resequencing Authors: de Gruijter, Johanna Maria; Lao, Oscar; Vermeulen, Mark; Xue, Yali; Woodwark, Cara; Gillson, Christopher J; Coffey, Alison J; Ayub, Qasim; Mehdi, S QASIM; Kayser, Manfred; Tyler-Smith, Chris Abstract: Abstract Background Numerous genome-wide scans conducted by genotyping previously ascertained single-nucleotide polymorphisms (SNPs) have provided candidate signatures for positive selection in various regions of the human genome, including in genes involved in pigmentation traits. However, it is unclear how well the signatures discovered by such haplotype-based test statistics can be reproduced in tests based on full resequencing data. Four genes (oculocutaneous albinism II (OCA2), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT), and KIT ligand (KITLG)) implicated in human skin-color variation, have shown evidence for positive selection in Europeans and East Asians in previous SNP-scan data. In the current study, we resequenced 4.7 to 6.7 kb of DNA from each of these genes in Africans, Europeans, East Asians, and South Asians. Results Applying all commonly used neutrality-test statistics for allele frequency distribution to the newly generated sequence data provided conflicting results regarding evidence for positive selection. Previous haplotype-based findings could not be clearly confirmed. Although some tests were marginally significant for some populations and genes, none of them were significant after multiple-testing correction. Combined P values for each gene-population pair did not improve these results. Application of Approximate Bayesian Computation Markov chain Monte Carlo based to these sequence data using a simple forward simulator revealed broad posterior distributions of the selective parameters for all four genes, providing no support for positive selection. However, when we applied this approach to published sequence data on SLC45A2, another human pigmentation candidate gene, we could readily confirm evidence for positive selection, as previously detected with sequence-based and some haplotype-based tests. Conclusions Overall, our data indicate that even genes that are strong biological candidates for positive selection and show reproducible signatures of positive selection in SNP scans do not always show the same replicability of selection signals in other tests, which should be considered in future studies on detecting positive selection in genetic data. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 01 Dec 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241666 2011-12-01T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241598 Title: Deciphering c-MYC-regulated genes in two distinct tissues Authors: Robson, Samuel C; Ward, Lesley; Brown, Helen; Turner, Heather; Hunter, Ewan; Pelengaris, Stella; Khan, Michael Abstract: Abstract Background The transcription factor MYC is a critical regulator of diverse cellular processes, including both replication and apoptosis. Differences in MYC-regulated gene expression responsible for such opposing outcomes in vivo remain obscure. To address this we have examined time-dependent changes in global gene expression in two transgenic mouse models in which MYC activation, in either skin suprabasal keratinocytes or pancreatic islet β-cells, promotes tissue expansion or involution, respectively. Results Consistent with observed phenotypes, expression of cell cycle genes is increased in both models (albeit enriched in β-cells), as are those involved in cell growth and metabolism, while expression of genes involved in cell differentiation is down-regulated. However, in β-cells, which unlike suprabasal keratinocytes undergo prominent apoptosis from 24 hours, there is up-regulation of genes associated with DNA-damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and Cycs. In striking contrast, this is not the case for suprabasal keratinocytes, where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated. Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine protease family members in suprabasal keratinocytes alone could further enhance local Igf1 actions, such as through proteolysis of Igf1 binding proteins. Conclusions Activation of MYC causes cell growth, loss of differentiation and cell cycle entry in both β-cells and suprabasal keratinocytes in vivo. Apoptosis, which is confined to β-cells, may involve a combination of a DNA-damage response and downstream activation of pro-apoptotic signalling pathways, including Cdc2a and p19Arf/p53, and downstream targets. Conversely, avoidance of apoptosis in suprabasal keratinocytes may result primarily from the activation of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction of an angiogenic response, though intrinsic resistance to induction of p19Arf by MYC in suprabasal keratinocytes may contribute. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 29 Sep 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241598 2011-09-29T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241591 Title: Re-organisation of oesophago-gastric cancer care in England: progress and remaining challenges Authors: Palser, Tom R; Cromwell, David A; Hardwick, Richard H; Riley, Stuart A; Greenaway, Kimberley; Allum, William; van der Meulen, Jan HP Abstract: Abstract Background Oesophago-gastric cancer services in England have been extensively reorganised since 2001 to deliver a centralised, specialist-led service. Our aim was to assess how well the National Health Service (NHS) in England met organisational standards for oesophago-gastric cancer care. Methods Questionnaires that asked about the provision of staging investigations, curative and palliative treatments and key personnel were sent in September 2007 to the lead clinician for oesophago-gastric cancer at all 30 cancer networks and 156 NHS acute trusts in England. Results Responses were received from all networks and 81% of NHS trusts. All networks provided essential staging investigations and a range of endoscopic palliative therapies. Only 16 of the 30 cancer networks discussed all patients at the specialist multi-disciplinary team meeting and 11 networks had not fully centralised curative surgery. There was also variation between NHS trusts in the integration of the palliative care team, the availability of nurse specialists and the use of dieticians to provide nutritional support. Conclusion There has been considerable progress in reforming oesophago-gastric cancer services but the process of reorganisation is still incomplete and regional differences in service provision exist that may lead to variation in patient outcomes. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 12 Nov 2009 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241591 2009-11-12T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241588 Title: CD133: a Potential Indicator for Differentiation and Prognosis of Human Cholangiocarcinoma Authors: Fan, Linni; He, Furong; Liu, Hongxiang; Zhu, Jin; Liu, Yixiong; Yin, Zhiyong; Wang, Lu; Guo, Ying; Wang, Zhe; Yan, Qingguo; Huang, Gaosheng Abstract: Abstract Background CD133 is known to be a cancer stem cell (CSC) marker. However, recent studies have revealed that CD133 is not restricted to CSC but to be expressed not only in human normal tissues but also in some cancers and could serve as a prognostic factor for the patients. Nevertheless, the expression of CD133 in human cholangiocarcinoma (CC) is rare and our study is to detect the expression and explore the potential functions of CD133 in human CC. Methods Fifty-nine cases, comprised of 5 normal liver tissues and 54 consecutive CC specimens (21 well-differentiated, 12 moderately-differentiated and 21 poorly-differentiated), were included in the study. Immunohistochemical stainning with CD133 protein was carried out, and statistical analyses were performed. Results CD133 was found to express in all 5 normal livers and 40 out of 54 (74%) CC tissues with different subcellular localization. In the well, moderately and poorly differentiated cases, the numbers of CD133 positive cases were 19 (19 of 21, 90%), 10 (10 of 12, 83%) and 11 (11 of 21, 52%) respectively. Further statistical analyses indicated that the expression and different subcellular localization of CD133 were significantly correlated with the differentiation status of tumors (P = 0.004, P = 0.009). Among 23 patients followed up for survival, the median survival was 4 months for fourteen CD133 negative patients but 14 months for nine CD133 positive ones. In univariate survival analysis, CD133 negative expression correlated with poor prognosis while CD133 positive expression predicted a favorable outcome of CC patients (P = 0.001). Conclusions Our study demonstrates that CD133 expression correlates with the differentiation of CC and indicates that CD133 is a potential indicator for differentiation and prognosis of human CC. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 28 Jul 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241588 2011-07-28T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241044 Title: Correlates of time spent walking and cycling to and from work: baseline results from the Commuting and Health in Cambridge study Authors: Panter, Jenna; Griffin, Simon; Jones, Andrew; Mackett, Roger; Ogilvie, David Abstract: Abstract Purpose Environmental perceptions and psychological measures appear to be associated with walking and cycling behaviour; however, their influence is still unclear. We assessed these associations using baseline data from a quasi-experimental cohort study of the effects of major transport infrastructural developments in Cambridge, UK. Methods Postal surveys were sent to adults who travel to work in Cambridge (n = 1582). Questions asked about travel modes and time spent travelling to and from work in the last week, perceptions of the route, psychological measures regarding car use and socio-demographic characteristics. Participants were classified into one of two categories according to time spent walking for commuting ('no walking' or 'some walking') and one of three categories for cycling ('no cycling', '1-149 min/wk' and ' ≥ 150 min/wk'). Results Of the 1164 respondents (68% female, mean (SD) age: 42.3 (11.4) years) 30% reported any walking and 53% reported any cycling to or from work. In multiple regression models, short distance to work and not having access to a car showed strong positive associations with both walking and cycling. Furthermore, those who reported that it was pleasant to walk were more likely to walk to or from work (OR = 4.18, 95% CI 3.02 to 5.78) and those who reported that it was convenient to cycle on the route between home and work were more likely to do so (1-149 min/wk: OR = 4.60, 95% CI 2.88 to 7.34; ≥ 150 min/wk: OR = 3.14, 95% CI 2.11 to 4.66). Positive attitudes in favour of car use were positively associated with time spent walking to or from work but negatively associated with cycling to or from work. Strong perceived behavioural control for car use was negatively associated with walking. Conclusions In this relatively affluent sample of commuters, a range of individual and household characteristics, perceptions of the route environment and psychological measures relating to car use were associated with walking or cycling to and from work. Taken together, these findings suggest that social and physical contexts of travel decision-making should be considered and that a range of influences may require to be addressed to bring about behaviour change. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 10 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241044 2011-11-10T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/241026 Title: Liver and brain abscess caused by Aggregatibacter paraphrophilus in association with a large patent foramen ovale: a case report Authors: Ariyaratnam, Shaumya; Gajendragadkar, Parag R; Dickinson, Richard J; Roberts, Phil; Harris, Kathryn; Carmichael, Andrew; Karas, Johannis A Abstract: Abstract Introduction Aggregatibacter paraphrophilus (former name Haemophilus paraphrophilus) is a normal commensal of the oral flora. It is a rare cause of hepatobiliary or intracerebral abscesses. Case presentation We report a case of a 53-year-old Caucasian man with a liver abscess and subsequent brain abscesses caused by Aggregatibacter paraphrophilus. The probable source of the infection was the oral flora of our patient following ingestion of a dental filling. The presence of a large patent foramen ovale was a predisposing factor for multifocal abscesses. Conclusion In this case report, we describe an unusual case of a patient with both liver and brain abscesses caused by an oral commensal Aggregatibacter paraphrophilus that can occasionally show significant pathogenic potential. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.; RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 24 Feb 2010 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/241026 2010-02-24T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240750 Title: Nanoscale chemical and structural study of Co- based FEBID structures by STEM-EELS and HRTEM Authors: Cordoba, Rosa; Fernandez-Pacheco, Rodrigo; Fernandez-Pacheco, Amalio; Gloter, Alexandre; Magen, Cesar; Stephan, Odile; Ricardo Ibarra, Manuel; De Teresa, Jose Maria Abstract: Abstract Nanolithography techniques in a scanning electron microscope/focused ion beam are very attractive tools for a number of synthetic processes, including the fabrication of ferromagnetic nano-objects, with potential applications in magnetic storage or magnetic sensing. One of the most versatile techniques is the focused electron beam induced deposition, an efficient method for the production of magnetic structures highly resolved at the nanometric scale. In this work, this method has been applied to the controlled growth of magnetic nanostructures using Co2(CO)8. The chemical and structural properties of these deposits have been studied by electron energy loss spectroscopy and high-resolution transmission electron microscopy at the nanometric scale. The obtained results allow us to correlate the chemical and structural properties with the functionality of these magnetic nanostructures. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 15 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240750 2011-11-15T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240747 Title: Strategies for handling missing data in randomised trials Abstract: Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 13 Dec 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240747 2011-12-13T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240657 Title: A whole genome screen for HIV restriction factors Authors: Liu, Li; Oliveira, Nidia MM; Cheney, Kelly M; Pade, Corinna; Dreja, Hanna; Bergin, Ann Marie H; Borgdorff, Viola; Beach, David H; Bishop, Cleo L; Dittmar, Matthias T; McKnight, Aine Abstract: Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV) human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme), p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Mon, 14 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240657 2011-11-14T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/240610 Title: About making a CHO production cell line “research-friendly” by genetic engineering Abstract: Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 22 Nov 2011 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/240610 2011-11-22T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/239921 Title: Multi-professional clinical medication reviews in care homes for the elderly: study protocol for a randomised controlled trial with cost effectiveness analysis Authors: Desborough, James; Houghton, Julie; Wood, John; Wright, David; Holland, Richard; Sach, Tracey; Ashwell, Sue; Shaw, Valerie Abstract: Abstract Background Evidence demonstrates that measures are needed to optimise therapy and improve administration of medicines in care homes for older people. The aim of this study is to determine the clinical and cost effectiveness of a novel model of multi-professional medication review. Methods A cluster randomised controlled trial design, involving thirty care homes. In line with current practice in medication reviews, recruitment and consent will be sought from general practitioners and care homes, rather than individual residents. Care homes will be segmented according to size and resident mix and allocated to the intervention arm (15 homes) or control arm (15 homes) sequentially using minimisation. Intervention homes will receive a multi-professional medication review at baseline and at 6 months, with follow-up at 12 months. Control homes will receive usual care (support they currently receive from the National Health Service), with data collection at baseline and 12 months. The novelty of the intervention is a review of medications by a multi-disciplinary team. Primary outcome measures are number of falls and potentially inappropriate prescribing. Secondary outcome measures include medication costs, health care resource use, hospitalisations and mortality. The null hypothesis proposes no difference in primary outcomes between intervention and control patients. The primary outcome variable (number of falls) will be analysed using a linear mixed model, with the intervention specified as a fixed effect and care homes included as a random effect. Analyses will be at the level of the care home. The economic evaluation will estimate the cost-effectiveness of the intervention compared to usual care from a National Health Service and personal social services perspective. The study is not measuring the impact of the intervention on professional working relationships, the medicines culture in care homes or the generic health-related quality of life of residents. Discussion This study will establish the effectiveness of a new model of multi-professional clinical medication reviews in care homes, using novel approaches to recruitment and consent. It is the first study to undertake an examination of direct patient outcomes, together with an economic analysis. Trial Registration ISRCTN: ISRCTN90761620 Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Tue, 04 Oct 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/239921 2011-10-04T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/239091 Title: What is the Golgi apparatus, and why are we asking? Authors: Munro, Sean Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Thu, 29 Sep 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/239091 2011-09-29T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/238983 Title: Socio-demographic, psychosocial and home-environmental attributes associated with adults' domestic screen time Authors: Van Dyck, Delfien; Cardon, Greet; Deforche, Benedicte; Owen, Neville; De Cocker, Katrien; Wijndaele, Katrien; De Bourdeaudhuij, Ilse Abstract: Abstract Background Sedentary behaviors (involving prolonged sitting time) are associated with deleterious health consequences, independent of (lack of) physical activity. To inform interventions, correlates of prevalent sedentary behaviors need to be identified. We examined associations of socio-demographic, home-environmental and psychosocial factors with adults' TV viewing time and leisure-time Internet use; and whether psychosocial and environmental correlates differed according to gender, age and educational attainment. Methods This cross-sectional study was conducted in Ghent, Belgium, between March and May 2010. Respondents to a mail-out survey (n = 419; 20-65 years; mean age 48.5 [12.1] years; 47.3% men) completed a questionnaire on sedentary behaviors and their potential socio-demographic, psychosocial and home environmental correlates. Statistical analyses were performed using multiple linear regression models. Results The independent variables explained 31% of the variance in TV viewing time and 38% of the variance in leisure-time Internet use. Higher education, greater perceived pros of and confidence about reducing TV time were negatively associated with TV viewing time; older age, higher body mass index, larger TV set size and greater perceived cons of reducing TV time showed positive associations. Perceived pros of and confidence about reducing Internet use were negatively associated with leisure-time Internet use; higher education, number of computers in the home, positive family social norms about Internet use and perceived cons of reducing Internet use showed positive associations. None of the socio-demographic factors moderated these associations. Conclusions Educational level, age, self-efficacy and pros/cons were the most important correlates identified in this study. If further cross-sectional and longitudinal research can confirm these findings, tailored interventions focusing on both psychosocial and environmental factors in specific population subgroups might be most effective to reduce domestic screen time. Description: RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are. Wed, 24 Aug 2011 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/238983 2011-08-24T23:00:00Z