3D geological models and their hydrogeological applications : supporting urban development : a case study in Glasgow-Clyde, UK

Urban planners and developers in some parts of the United Kingdom can now access geodata in an easy-to-retrieve and understandable format. 3D attributed geological framework models and associated GIS outputs, developed by the British Geological Survey (BGS), provide a predictive tool for planning site investigations for some of the UK's largest regeneration projects in the Thames and Clyde River catchments. Using the 3D models, planners can get a 3D preview of properties of the subsurface using virtual cross-section and borehole tools in visualisation software, allowing critical decisions to be made before any expensive site investigation takes place, and potentially saving time and money. 3D models can integrate artificial and superficial deposits and bedrock geology, and can be used for recognition of major resources (such as water, thermal and sand and gravel), for example in buried valleys, groundwater modelling and assessing impacts of underground mining. A preliminary groundwater recharge and flow model for a pilot area in Glasgow has been developed using the 3D geological models as a framework. This paper focuses on the River Clyde and the Glasgow conurbation, and the BGS's Clyde Urban Super-Project (CUSP) in particular, which supports major regeneration projects in and around the City of Glasgow in the West of Scotland

Characteristics of service users and provider organisations associated with experience of out of hours general practitioner care in England: population based cross sectional postal questionnaire survey.

OBJECTIVE: To investigate the experience of users of out of hours general practitioner services in England, UK. DESIGN: Population based cross sectional postal questionnaire survey. SETTING: General Practice Patient Survey 2012-13. MAIN OUTCOME MEASURES: Potential associations between sociodemographic factors (including ethnicity and ability to take time away from work during working hours to attend a healthcare consultation) and provider organisation type (not for profit, NHS, or commercial) and service users' experience of out of hours care (timeliness, confidence and trust in the out of hours clinician, and overall experience of the service), rated on a scale of 0-100. Which sociodemographic/provider characteristics were associated with service users' experience, the extent to which any observed differences could be because of clustering of service users of a particular sociodemographic group within poorer scoring providers, and the extent to which observed differences in experience varied across types of provider. RESULTS: The overall response rate was 35%; 971,232/2,750,000 patients returned surveys. Data from 902,170 individual service users were mapped through their registered practice to one of 86 providers of out of hours GP care with known organisation type. Commercial providers of out of hours GP care were associated with poorer reports of overall experience of care, with a mean difference of -3.13 (95% confidence interval -4.96 to -1.30) compared with not for profit providers. Asian service users reported lower scores for all three experience outcomes than white service users (mean difference for overall experience of care -3.62, -4.36 to -2.89), as did service users who were unable to take time away from work compared with service users who did not work (mean difference for overall experience of care -4.73, -5.29 to -4.17). CONCLUSIONS: Commercial providers of out of hours GP care were associated with poorer experience of care. Targeted interventions aimed at improving experience for patients from ethnic minorities and patients who are unable to take time away from work might be warranted

Essential role of syntaxin-binding protein-1 in the regulation of glucagon-like peptide-1 secretion

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.Wellcome Trust MR

Study protocol:the effectiveness and cost effectiveness of an employer-led intervention to increase walking during the daily commute: the Travel to Work randomised controlled trial

BACKGROUND: Physical inactivity increases the risk of many chronic diseases including coronary heart disease, type 2 diabetes and some cancers. It is recommended that adults should undertake at least 150 minutes of moderate intensity physical activity throughout the week but many adults do not achieve this. An opportunity for working adults to accumulate the recommended activity levels is through the daily commute. METHODS: Employees will be recruited from workplaces in south-west England and south Wales. In the intervention arm, workplace Walk-to-Work promoters will be recruited and trained. Participating employees will receive Walk-to-Work materials and support will be provided through four contacts from the promoters over 10 weeks. Workplaces in the control arm will continue with their usual practice. The intervention will be evaluated by a cluster randomized controlled trial including economic and process evaluations. The primary outcome is daily minutes of moderate to vigorous physical activity (MVPA). Secondary outcomes are: overall physical activity; sedentary time; modal shift away from private car use during the commute; and physical activity/MVPA during the commute. Accelerometers, GPS receivers and travel diaries will be used at baseline and one year follow-up. Questionnaires will be used at baseline, immediately post intervention, and one year follow-up. The process evaluation will examine the context, delivery and response to the intervention from the perspectives of employers, Walk-to-Work promoters and employees using questionnaires, descriptive statistics, fieldnotes and interviews. A cost-consequence study will include employer, employee and health service costs and outcomes. Time and consumables used in implementing the intervention will be measured. Journey time, household commuting costs and expenses will be recorded using travel diaries to estimate costs to employees. Presenteeism, absenteeism, employee wellbeing and health service use will be recorded. DISCUSSION: Compared with other forms of physical activity, walking is a popular, familiar and convenient, and the main option for increasing physical activity in sedentary populations. To our knowledge, this is the first full-scale randomised controlled trial to objectively measure (using accelerometers and GPS receivers) the effectiveness of a workplace intervention to promote walking during the commute to and from work. TRIAL REGISTRATION: ISRCTN15009100 (10 December 2014)

Analysis of Lymphocyfic Infiltration in Uveal Melanoma

Among 27 uveal melanomas, five were found to contain tumor infiltrating lymphocytes (TILs). Four had high levels of lymphocytes, and the fifth had comparatively low levels but adequate numbers for comprehensive analysis. The TILs were analyzed by flow cytometry to determine the relative proportions of lymphocyte subsets and markers of lymphocyte activation. The results show the predominance of T-suppressor/cytotoxic lymphocytes and insignificant levels of B-cells present in the infiltrate. The T-suppressor/cytotoxic cells were generally activated to a higher degree than the T-helper cells when assayed for levels of the histocompatibility antigen, HLA-DR. T-helper cells expressed more interleukin (IL-2) receptor (Tac) than T-suppressor/cytotoxic cells. Invest Ophthalmol Vis Sci 31: [2106][2107][2108][2109][2110]1990 Uveal melanomas, like their cutaneous counterpart, are considered to be relatively susceptible to immunologic influences because of reports of spontaneous regression, 1 -2 of the development of vitiligo and halo nevi, 5 Such intraocular transplantation can be prevented by prior adoptive transfer of humoral or cellular immunity to the recipient. " 14 Some investigators report the predominance of the T-cytotoxic/suppressor cell subpopulation; 1213 others found a majority of T-helper/inducer cells. 10 " 14 There is, however, no convincing evidence that a more favorable prognosis is associated with lymphocytic infiltration in uveal melanomas, 715 and it remains uncertain whether tumor infiltrating lymphocytes (TILs) play a significant role in tumor immunity. The availability of precisely defined monoclonal-antibody markers and flow-cytometric techniques makes it From the *Department of Biochemistry and the fTennent Institute of Ophthalmology, University of Glasgow, Glasgow, Scotland. Reprint requests: Fiona H. Durie, Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, UK. possible to do a detailed objective analysis of a large number of lymphocytes in any tumour. We characterized the phenotype of the TILs and studied the expression of the histocompatibility antigen, HLA-DR, and interleukin (IL-2) receptor (Tac), which are markers of activation, on the surface of T-helper and T-suppressor/cytotoxic lymphocytes in ocular melanoma. Materials and Methods Preparation of Cells Tissue was obtained from five choroidal melanomas which were removed either by local resection or by enucleation. Slices were cut from the apical part of the fresh specimen after preliminary examination, and these were transferred to RPMI-1640 medium (Gibco, Grand Island, NY). Spilled cells were teased out using a sterile needle. The cells were then harvested, washed by centrifugation at 1000 rpm for 15 min, counted, and adjusted to 1X10 6 cells/ml. The remaining cell suspensions of TILs and tumor cells were cryopreserved in medium containing 90% fetal calf serum and 10% dimethylsulfoxide and stored in liquid nitrogen until use. Four of the five patients consented to venipuncture, and peripheral blood lymphocytes were separated on a discontinuous ficoll density gradient. 1617 Preparation of Samples Cell suspensions of TILs and tumor cells were washed and resuspended in 1 ml of phosphate-buffered saline. Cells (50 ii\) were incubated on ice with appropriate fluorescein isothiocyanate (FITC)-conjugated leu series monoclonal antibody and phycoerythrin (PE) conjugated antibody (Becton-Dickinson, 2106 Downloaded from iovs.arvojournals.org on 06/28/201

Targeted Whole Genome Sequencing (TWG-Seq) of Cucumber Green Mottle Mosaic Virus Using Tiled Amplicon Multiplex PCR and Nanopore Sequencing

Rapid and reliable detection tools are essential for disease surveillance and outbreak management, and genomic data is essential to determining pathogen origin and monitoring of transmission pathways. Low virus copy number and poor RNA quality can present challenges for genomic sequencing of plant viruses, but this can be overcome by enrichment of target nucleic acid. A targeted whole genome sequencing (TWG-Seq) approach for the detection of cucumber green mottle mosaic virus (CGMMV) has been developed where overlapping amplicons generated using two multiplex RT-PCR assays are then sequenced using the Oxford Nanopore MinION. Near complete coding region sequences were assembled with ≥100× coverage for infected leaf tissue dilution samples with RT-qPCR cycle quantification (Cq) values from 11.8 to 38 and in seed dilution samples with Cq values 13.8 to 27. Consensus sequences assembled using this approach showed greater than 99% nucleotide similarity when compared to genomes produced using metagenomic sequencing. CGMMV could be confidently detected in historical seed isolates with degraded RNA. Whilst limited access to, and costs associated with second-generation sequencing platforms can influence diagnostic outputs, the portable Nanopore technology offers an affordable high throughput sequencing alternative when combined with TWG-Seq for low copy or degraded samples

Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy

<p>Abstract</p> <p>Background</p> <p>Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.</p> <p>Results</p> <p>Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of <it>NRF2 </it>exon 2 and <it>KEAP1 </it>exons 2-6 in these cell lines identified no mutations in <it>NRF2 </it>and only synonomous mutations in <it>KEAP1</it>. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).</p> <p>Conclusions</p> <p>Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.</p