The Distributional Impact of Various Road Charging Schemes for London.

This Working Paper presents results obtained using the MVA START model for London, with the primary intention of investigating the distributional impact of road pricing in various forms and at various levels. In order to look at distributional effects the START model had to be 'disaggregated' by income groups - three each for non-car owning and car-owning households. Initially, this allowed us to see the distributional impact of the LPAC Preferred Strategy, mainly involving public transport and traffic management policies. Beyond this we tested three structures (or 'regimes') of road pricing, varying from a complex three cordon plus screenlines structure, to a single Central London cordon. Somewhat surprisingly, the latter was found to be regressive in its application. The structure with the highest benefits, as well as being relatively progressive, was the complex structure of three cordons plus screenlines, with an optimum charge level of 50 pence per cordon crossing, each way but with the outer two cordons being peak only

Analysis of neural development using ligand-trap transgenic lines.

Bone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor-beta (TGF-beta) signalling protein superfamily. BMPs play important and diverse roles in cell-cell signalling, including establishing cell fate during the development of vertebrate embryos. Their activity is antagonised in vivo by a number of proteins such as noggin, which sequester BMP ligands, preventing them from binding to BMP receptors. This thesis describes studies to establish a binary genetic approach combined with a ligand trap system to manipulate BMP signalling in the frog embryo. This system has been used to investigate the roles of BMP signalling in dorso-ventral patterning of the forebrain Xenopus tropicalis. The binary system described utilises a variety of tissue- or region-specific gene promoters to drive expression of the GAL4 transcriptional activator. Such transgenic "driver" lines can be crossed with a "responder" line in which expression of a membrane-tethered fusion protein comprising human Noggin fused to GFP is regulated by a synthetic promoter responsive to GAL4 (UAS-flognog). Transient expression assays confirmed the effectiveness of the "responder" line, GAL4 transactivation of UAS-flognog resulted in the expression of Flognog and an expansion of neural progenitor tissue, indicated by the X-Sox3 marker. In a binary cross with the Otx2-gal4 driver line, targeted GAL4 transactivation lead to a decrease in phospho-Smad-1 staining in the anterior CNS and eye in a proportion of cross embryos. Such a cross resulted in embryos showing an open neural tube and alterations in both Pax6 (dorsal) and X-<U13 (ventral) forebrain markers, further indicating the efficacy of the binary, ligand-trap strategy. In order to achieve temporal control on the activity of the UAS-flognog responder line in the telencephalon, an inducible driver line comprising the Pax6 promoter driving hormone-inducible GalPR (an inducible chimeric GAL4) was created. In binary crosses with a UAS-gfp reporter line, GFP expression was detected in the forebrain, hindbrain and spinal cord only in the presence of the steroid hormone, RU486. Similarly, a second driver line, N-tubulin-GalPR yielded inducible GFP expression in the developing brain, spinal cord and lens tissue in the presence of RU486. In conclusion, these findings are evidence that the binary ligand trap approach is functional and can cause targeted knockdown of BMP signalling, resulting in alterations in neural development and patterning. Furthermore, using an inducible version of this approach, Flognog (or any other target gene) can be expressed in the telencephalon in a RU486-inducible manner

The application of continuous surface wave testing for settlement analysis with reference to a full-scale load test for a bridge at Pont Melin, Wales, UK

The presence of a significant thickness of soft silts beneath the site of a proposed new road bridge caused concerns over the suitability of shallow foundations. Despite extensive conventional ground investigations, it was not possible to obtain reliable stiffness data, and so a full-scale, fully instrumented load test was undertaken to better determine ground stiffness. The data obtained was used in conjunction with sophisticated numerical analysis to demonstrate that the settlement of shallow foundations would be acceptable. Following completion of the bridge construction, Continuous Surface Wave testing was undertaken and a range of simple non-linear elastic settlement analyses conducted to model the behaviour of the load test. Through these analyses this paper demonstrates the benefit of using continuous surface wave ground stiffness testing in conjunction with simple analysis methods. It underlines the importance of obtaining high-quality stiffness data to accurately predict settlement of shallow foundations.http://www.journals.co.za/ej/ejour_civileng.htmlam2017Civil Engineerin

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

Open Access via PMC2649417Peer reviewedPublisher PD

Factors Influencing the Participation of Older People in Clinical Trials : Data Analysis from the MAVIS Trial

Peer reviewedPostprin

Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection.

Background: The timing of infection is closely determined in controlled human malaria infection (CHMI) studies, and as such they provide a unique opportunity to dissect changes in immunological responses before and after a single infection. The first Kenyan Challenge Study (KCS) (Pan African Clinical Trial Registry: PACTR20121100033272) was performed in 2013 with the aim of establishing the CHMI model in Kenya. This study used aseptic, cryopreserved, attenuated Plasmodium falciparum sporozoites administered by needle and syringe (PfSPZ Challenge) and was the first to evaluate parasite dynamics post-CHMI in individuals with varying degrees of prior exposure to malaria. Methods: We describe detailed serological and functional immunological responses pre- and post-CHMI for participants in the KCS and compare these with those from malaria-naïve UK volunteers who also underwent CHMI (VAC049) (ClinicalTrials.gov NCT01465048) using PfSPZ Challenge. We assessed antibody responses to three key blood-stage merozoite antigens [merozoite surface protein 1 (MSP1), apical membrane protein 1 (AMA1), and reticulocyte-binding protein homolog 5 (RH5)] and functional activity using two candidate measures of anti-merozoite immunity; the growth inhibition activity (GIA) assay and the antibody-dependent respiratory burst activity (ADRB) assay. Results:Clear serological differences were observed pre- and post-CHMI by ELISA between malaria-naïve UK volunteers in VAC049, and Kenyan volunteers who had prior malaria exposure. Antibodies to AMA1 and schizont extract correlated with parasite multiplication rate (PMR) post-CHMI in KCS. Serum from volunteer 110 in KCS, who demonstrated a dramatically reduced PMR in vivo, had no in vitro GIA prior to CHMI but the highest level of ADRB activity. A significant difference in ADRB activity was seen between KCS volunteers with minimal and definite prior exposure to malaria and significant increases were seen in ADRB activity post-CHMI in Kenyan volunteers. Quinine and atovaquone/proguanil, previously assumed to be removed by IgG purification, were identified as likely giving rise to aberrantly high in vitro GIA results. Conclusions: The ADRB activity assay is a promising functional assay that warrants further investigation as a measure of prior exposure to malaria and predictor of control of parasite growth. The CHMI model can be used to evaluate potential measures of naturally-acquired immunity to malaria

Preliminary assessment of the environmental baseline in the Fylde, Lancashire

This report presents the collated preliminary results from the British Geological Survey (BGS) led project Science-based environmental baseline monitoring associated with shale gas development in the Fylde, Lancashire. The project has been funded by a combination of BGS National Capability funding, in-kind contributions from project partners and a grant awarded by the Department of Business Energy and Investment Strategy (BEIS). It complements an on-going project, in which similar activities are being carried out, in the Vale of Pickering, North Yorkshire. Further information on the projects can be found on the BGS website: www.bgs.ac.uk. The project has initiated a wide-ranging environmental baseline monitoring programme that includes water quality (groundwater and surface water), seismicity, ground motion, atmospheric composition (greenhouse gases and air quality), soil gas and radon in air (indoors and outdoors). The motivation behind the project(s) was to establish independent monitoring in the area around the proposed shale gas hydraulic fracturing sites in the Fylde, Lancashire (Cuadrilla Resources Ltd) before any shale gas operations take place. As part of the project, instrumentation has been deployed to measure, in real-time or near real-time, a range of environmental variables (water quality, seismicity, atmospheric composition). These data are being displayed on the project’s web site (www.bgs.ac.uk/lancashire). Additional survey, sampling and monitoring has also been carried out through a co-ordinated programme of fieldwork and laboratory analysis, which has included installation of new monitoring infrastructure, to allow compilation of one of the most comprehensive environmental datasets in the UK. The monitoring programme is continuing. However, there are already some very important findings emerging from the limited datasets which should be taken into account when developing future monitoring strategy, policy and regulation. The information is not only relevant to Lancashire but will be applicable more widely in the UK and internationally. Although shale gas operations in other parts of the world are well-established, there is a paucity of good baseline data and effective guidance on monitoring. The project will also allow the experience gained, and the scientifically-robust findings to be used, to develop and establish effective environmental monitoring strategies for shale gas and similar industrial activities

Environmental monitoring : phase 5 final report (April 2019 - March 2020)

This report presents the results and interpretation for Phase 5 of an integrated environmental monitoring programme that is being undertaken around two proposed shale gas sites in England – Preston New Road, Lancashire and Kirby Misperton, North Yorkshire. The report should be read in conjunction with previous reports freely available through the project website1 . These provide additional background to the project, presentation of earlier results and the rationale for establishment of the different elements of the monitoring programme

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Environmental monitoring : phase 4 final report (April 2018 - March 2019)

This report describes the results of activities carried out as part of the Environmental Monitoring Project (EMP) led by the British Geological Survey (BGS) in areas around two shale gas sites in England – Kirby Misperton (Vale of Pickering, North Yorkshire) and Preston New Road (Fylde, Lancashire). It focuses on the monitoring undertaken during the period April 2018–March 2019 but also considers this in the context of earlier monitoring results that have been covered in reports for earlier phases of the project (Phases I–IV) 2 . The EMP project is a multi-partner project involving BGS together with Public Health England (PHE), University of Birmingham, University of Bristol, University of Manchester, Royal Holloway University of London (RHUL) and University of York. The work has been enabled by funding from a combination of the BGS National Capability programme, a grant awarded by the UK Government’s Department for Business Energy & Industrial Strategy (BEIS) and additional benefit-in-kind contributions from all partners. The project comprises the comprehensive monitoring of different environment compartments and properties at and around the two shale-gas sites. The component parts of the EMP are all of significance when considering environmental and human health risks associated with shale gas development. Included are seismicity, ground motion, water (groundwater and surface water), soil gas, greenhouse gases, air quality, and radon. The monitoring started before hydraulic fracturing had taken place at the two locations, and so the results obtained before the initiation of operations at the shale-gas sites represent baseline conditions. It is important to characterise adequately the baseline conditions so that any future changes caused by shale gas operations, including hydraulic fracturing, can be identified. This is also the case for any other new activities that may impact those compartments of the environment being monitored as part of the project. In the period October 2018–December 2018, an initial phase of hydraulic fracturing took place at the Preston New Road (PNR) shale-gas site (shale gas well PNR1-z) in Lancashire. This was followed by a period of flow testing of the well to assess its performance (to end of January 2019). The project team continued monitoring during these various activities and several environmental effects were observed. These are summarised below and described in more detail within the report. The initiation of operations at the shale-gas site signified the end of baseline monitoring. At the Kirby Misperton site (KMA), approval has not yet been granted for hydraulic fracturing of the shale gas well (KM8), and so no associated operations have taken place during the period covered by this report. The effects on air quality arising from the mobilisation of equipment in anticipation of hydraulic fracturing operations starting was reported in the Phase III report, and in a recently published paper3 . Following demobilisation of the equipment and its removal from the site, conditions returned to baseline and the on-going monitoring (reported in this report) is effectively a continuation of baseline monitoring