K022: Effect of combination therapy (ANG II antagonist, valsartan and a calcium channel blocker) in a hypertensive model of diabetic nephropathy

Recently, it has been suggested that in the context of diabetes and hypertension, more aggressive blood pressure targets should be considered. To achieve these levels of blood pressure control, it is likely that combination therapy will need to be used. The present study has explored the role of the addition of either a dihydropyridine or a non-dihydropyridine calcium channel blocker (CCB) to Ang II antagonist based treatment in an experimental model of hypertension and diabetes. The doses chosen for the combination therapy groups were lower than those used with monotherapy in order to achieve similar antihypertensive efficacy. Diabetic (streptozotocin induced) SHR were randomised to no treatment, valsartan (30 mg/kg/day), the non-dihydropyridine CCB verapamil (20 mg/kg/day), the dihydropyridine CCB amlodipine (6 mg/kg/day), a combination of valsartan and amlodipine (20 mg + 4 mg/kg/day respectively) or valsartan and verapamil (20 mg + 15 mg/kg/day respectively). Serial measurements of systolic blood pressure (BP) and albumin excretion rate (AER) were performed monthly (data are shown at week 16 for AER and mean of wk 20-28 for BP). This model was associated with hypertension (control, 217 ± 8, diabetic, 200 ± 5 mmHg) which was reduced by most treatments to a similar degree (valsartan 165 ± 3, amlodipine 164 ± 2, verapamil 182 ± 4, valsartan + amlodipine 151 ± 3 and valsartan + verapamil 169 ± 5 mmHg). Diabetes was associated with a progressive increase in AER (control 1.5 vs diabetic 17 mg/24 hr). Valsartan retarded the increase in AER (11 mg/24 hr). Similar efficacy was observed in the valsartan + amlodipine combination (9 mg/24 hr) but not with amlodipine alone (16 mg/24 hr) despite similar effects on blood pressure. No advantage of verapamil versus amlodipine either as monotherapy or in combination with valsartan was observed. The present study indicates that the combination of an Ang II antagonist and a dihydropyridine CCB is an effective regimen at reducing blood pressure and albuminuria in the context of diabetes and hypertensio

Observation of the Holstein shift in high TcT_c superconductors with thermal modulation reflectometry

We use the experimental technique of thermal modulation reflectometry to study the relatively small temperature dependence of the optical conductivity of superconductors. Due to a large cancellation of systematic errors, this technique is shown to a be very sensitive probe of small changes in reflectivity. We analyze thermal modulation reflection spectra of single crystals and epitaxially grown thin films of YBa$_2$Cu$_3$O$_{7-\delta}$ and obtain the ${\alpha_tr}^2F(\omega)$ function in the normal state, as well as the superconductivity induced changes in reflectivity. We present detailed model calculations, based on the Eliashberg-Migdal extension of the BCS model, which show good qualitative and quantitative agreement with the experimental spectra. VSGD.93.12.thComment: 6 pages, figures on request. Revtex, version 2, Materials Science Center Internal Report Number VSGD.93.12.t

Surface tension of the isotropic-nematic interface

We present the first calculations of the pressure tensor profile in the vicinity of the planar interface between isotropic liquid and nematic liquid crystal, using Onsager's density functional theory and computer simulation. When the liquid crystal director is aligned parallel to the interface, the situation of lowest free energy, there is a large tension on the nematic side of the interface and a small compressive region on the isotropic side. By contrast, for perpendicular alignment, the tension is on the isotropic side. There is excellent agreement between theory and simulation both in the forms of the pressure tensor profiles, and the values of the surface tension.Comment: Minor changes; to appear in Phys. Rev.

On merging the fields of neural networks and adaptive data structures to yield new pattern recognition methodologies

The aim of this talk is to explain a pioneering exploratory research endeavour that attempts to merge two completely different fields in Computer Science so as to yield very fascinating results. These are the well-established fields of Neural Networks (NNs) and Adaptive Data Structures (ADS) respectively. The field of NNs deals with the training and learning capabilities of a large number of neurons, each possessing minimal computational properties. On the other hand, the field of ADS concerns designing, implementing and analyzing data structures which adaptively change with time so as to optimize some access criteria. In this talk, we shall demonstrate how these fields can be merged, so that the neural elements are themselves linked together using a data structure. This structure can be a singly-linked or doubly-linked list, or even a Binary Search Tree (BST). While the results themselves are quite generic, in particular, we shall, as a prima facie case, present the results in which a Self-Organizing Map (SOM) with an underlying BST structure can be adaptively re-structured using conditional rotations. These rotations on the nodes of the tree are local and are performed in constant time, guaranteeing a decrease in the Weighted Path Length of the entire tree. As a result, the algorithm, referred to as the Tree-based Topology-Oriented SOM with Conditional Rotations (TTO-CONROT), converges in such a manner that the neurons are ultimately placed in the input space so as to represent its stochastic distribution. Besides, the neighborhood properties of the neurons suit the best BST that represents the data

Environmental baseline monitoring - Vale of Pickering: Phase I - final report (2015/16)

This report presents the collated results from the BGS-led project Science-based environmental baseline monitoring associated with shale gas development in the Vale of Pickering (including supplementary air quality monitoring in Lancashire). The project has been funded by a grant awarded by DECC for the period August 2015 – 31st March 2016. It complements (and extends to air quality) an on-going project, funded by BGS and the other project partners, in which similar activities are being carried out in the Fylde area of Lancashire. 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 Vale of Pickering, North Yorkshire (Third Energy) and in Lancashire (Cuadrilla) 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/Valeofpickering). 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. It is generally recognised that at least 12 months of baseline data are required. The duration of the grant award (7 months) has meant that this has not yet been possible. However there are already some very important findings emerging from the limited datasets which need be taken in to account when developing future monitoring strategy, policy and regulation. The information is not only relevant to the Vale of Pickering and Lancashire but will be more widely applicable 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. It is hoped that the monitoring project will continue to allow at least 12 months of data for each of the work packages to be compiled and analysed. It 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 Baseline Monitoring Project. Phase II, final report

This report is submitted in compliance with the conditions set out in the grant awarded to the British Geological Survey (BGS), for the period April 2016 – March 2017, to support the jointly-funded project "Science-based environmental baseline monitoring". It presents the results of monitoring and/or measurement and preliminary interpretation of these data to characterise the baseline environmental conditions in the Vale of Pickering, North Yorkshire and for air quality, the Fylde in Lancashire ahead of any shale gas development. The two areas where the monitoring is taking place have seen, during the project, planning applications approved for the exploration for shale gas and hydraulic fracturing. It is widely recognised that there is a need for good environmental baseline data and establishment of effective monitoring protocols ahead of any shale gas/oil development. This monitoring will enable future changes that may occur as a result of industrial activity to be identified and differentiated from other natural and man-made changes that are influencing the baseline. Continued monitoring will then enable any deviations from the baseline, should they occur, to be identified and investigated independently to determine the possible causes, sources and significance to the environment and public health. The absence of such data in the United States has undermined public confidence, led to major controversy and inability to identify and effectively deal with impact/contamination where it has occurred. A key aim of this work is to avoid a similar situation and the independent monitoring being carried out as part of this project provides an opportunity to develop robust environmental baseline for the two study areas and monitoring procedures, and share experience that is applicable to the wider UK situation. This work is internationally unique and comprises an inter-disciplinary researcher-led programme that is developing, testing and implementing monitoring methodologies to enable future environmental changes to be detected at a local scale (individual site) as well as across a wider area, e.g. ‘shale gas play’ where cumulative impacts may be significant. The monitoring includes: water quality (groundwater and surface water), seismicity, ground motion, soil gas, atmospheric composition (greenhouse gases and air quality) and radon in air. Recent scientific and other commissioned studies have highlighted that credible and transparent monitoring is key to gaining public acceptance and providing the evidence base to demonstrate the industry’s impact on the environment and importantly on public health. As a result, BGS and its partners initiated in early 2015, a co-ordinated programme of environmental monitoring in Lancashire that was then extended to the Vale of Pickering in North Yorkshire after the Secretary of State for Energy and Climate Change (BEIS) awarded a grant to the British Geological Survey (BGS). The current duration of the grant award is to 31st March 2018. It has so far enabled baseline environmental monitoring for a period of more than 12 months. With hydraulic fracturing of shale gas likely to take place during late 2017/early 2018, the current funding will allow the environmental monitoring to continue during the transition from baseline to monitoring during shale gas operations. This report presents the monitoring results to April 2017 and a preliminary interpretation. A full interpretation is not presented in this report as monitoring is continuing and it is expected that there will be at least six months of additional baseline data before hydraulic fracturing takes place. This represents up to 50% more data for some components of the montoring, and when included in the analysis will significantly improve the characterisation and interpretation of the baseline. In addition to this report, the BGS web site contains further information on the project, near real-time data for some components of the monitoring and links to other projects outputs, e.g. reports and videos (www.bgs.ac.uk/research/groundwater/shaleGas/monitoring/home.html)