Use of Dynamic Contrast Enhanced MRI in Multi-Centre Trials with Particular Reference to Breast Cancer Screening 15 Use of Dynamic Contrast-Enhanced MRI in Multi-Centre Trials with Particular Reference to Breast Cancer Screening in Women at Genetic Risk

Introduction This chapter considers issues concerned with developing multi-centre trials using dynamic contrast-enhanced MRI studies. As techniques have been considered in other chapters, emphasis is placed on issues that relate to trials, and particularly their implementation across centres. Both diagnostic and therapeutic trials are considered, although as yet most experience arises from diagnostic trials. Trials that have been reported are considered, and the UK study of magnetic resonance as a method of screening women at genetic risk of breast cancer (MARIBS) using dynamic contrastenhanced MRI is taken as an example. Issues of organisation, instrumentation, quality assurance and analysis are considered. Multi-Centre Trials New Diagnostic Techniques Development and evaluation of new techniques often occurs initially at single centres. Where new approaches are developed at a university or hospital, the centre evaluating the technique is often the same centre that developed the approach. This has the benefi t of maximising the expertise in the technique, and is often an essential part of the interactive process of developing and optimising a new clinical technique. Those involved are likely to be advocates of the approach, and the utility established in such a single-centre evaluation may not be representative of the effectiveness of an approach across a range of centres. Manufacturers may also initially pilot a new approach at a single centre, in this case because of the strong continuing interaction required to optimise development. Such a strong interaction allows resources to be focussed, and may lead to scientifi c publications, assisting the manufacturer's role in alerting the community to new methods and equipment. Often this preliminary stage is then followed by a stage of more widespread evaluation, defi ning the role of the technique at a number of centres CONTENT

Wear and Friction Modeling on Lifeboat Launch Systems

The RNLI provides search and rescue cover along the UK and RoI coast using a variety of lifeboats and launch techniques. In locations where there is no natural harbour it is necessary to use a slipway to launch the lifeboat into the sea. Lifeboat slipway stations consist of an initial section where the boat is held on rollers followed by an inclined keelway lined with low friction composite materials, the lifeboat is released from the top of the slipway and proceeds under its own weight into the water. The lifeboat is later recovered using a winch line. It is common to manually apply grease to the composite slipway lining before each launch and recovery in order to ensure sufficiently low friction for successful operation. With the introduction of the Tamar class lifeboat it is necessary to upgrade existing boathouses and standardise slipway operational procedures to ensure consistent operation. The higher contact pressures associated with the new lifeboat have led to issues of high friction and wear on the composite slipway linings and the manual application of grease to reduce friction is to be restricted due to environmental impact and cost factors. This paper presents a multidisciplinary approach to modelling slipway panel wear and friction using tribometer testing in conjunction with finite element analysis and slipway condition surveys to incorporate common real-world effects such as panel misalignments. Finally, it is shown that a freshwater lubrication system is effective, reducing cost and environmental impacts while maintaining good friction and wear performance

General approach to potentials with two known levels

We present the general form of potentials with two given energy levels $E_{1}$, $E_{2}$ and find corresponding wave functions. These entities are expressed in terms of one function $\xi (x)$ and one parameter $\Delta E=E_{2}$-$E_{1}$. We show how the quantum numbers of both levels depend on properties of the function $\xi (x)$. Our approach does not need resorting to the technique of supersymmetric (SUSY) quantum mechanics but automatically generates both the potential and superpotential.Comment: 14 pages, REVTeX 3.0. In v.2 misprints and inaccuracies in presentation corrected, discussion of 3-dim. case added. In v.3 misprint in eq. 41, several typos and inaccuracies in English corrected. To be published in J. of Phys. A: Math. Ge

Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells

Ras is frequently mutated in cancer, and novel therapies are being developed to target Ras signalling. To identify non-invasive surrogate markers of Ras activation and inhibition, we used31P magnetic resonance spectroscopy (MRS) and investigated NIH 3T3 cells compared to a mutant ras transfected counterpart. The MR spectra indicated that phosphocholine (PC) levels increased significantly from 3 ± 2 fmol cell−1in NIH 3T3 cells to 13 ± 4  fmol cell−1in the transfected cells. The PC/NTP ratio increased significantly from 0.3 ± 0.1 to 0.7 ± 0.3. This could not be explained by either a faster proliferation rate or by alterations in cell cycle distribution. Both cell lines were treated with simvastatin, 17-AAG and R115777, agents which inhibit Ras signalling. Cell proliferation was inhibited in both cell lines. The spectrum of NIH 3T3 cells was not affected by treatment. In contrast, in the ras transfected cells growth inhibition was associated with an average 35 ± 5% drop in PC levels and a comparable drop in PC/NTP. Thus the MRS visible increase in phosphocholine is associated with Ras activation, and response to treatment is associated with partial reversal of phosphocholine increase in ras transfected cells. MRS might therefore be a useful tool in detecting Ras activation and its inhibition following targeted therapies. © 2001 Cancer Research Campaign http://www.bjcancer.co

IgG anti-apolipoprotein A-1 antibodies in patients with systemic lupus erythematosus are associated with disease activity and corticosteroid therapy: an observational study.

IgG anti-apolipoprotein A-1 (IgG anti-apoA-1) antibodies are present in patients with systemic lupus erythematosus (SLE) and may link inflammatory disease activity and the increased risk of developing atherosclerosis and cardiovascular disease (CVD) in these patients. We carried out a rigorous analysis of the associations between IgG anti-apoA-1 levels and disease activity, drug therapy, serology, damage, mortality and CVD events in a large British SLE cohort

Gender violence in schools: taking the ‘girls-as-victims’ discourse forward

This paper draws attention to the gendered nature of violence in schools. Recent recognition that schools can be violent places has tended to ignore the fact that many such acts originate in unequal and antagonistic gender relations, which are tolerated and ‘normalised’ by everyday school structures and processes. After examining some key concepts and definitions, we provide a brief overview of the scope and various manifestations of gender violence in schools, noting that most research to date has focused on girls as victims of gender violence within a heterosexual context and ignores other forms such as homophobic and girl violence. We then move on to look at a few interventions designed to address gender violence in schools in the developing world and end by highlighting the need for more research and improved understanding of the problem and how it can be addressed

Spherically Symmetric Solutions to Fourth-Order Theories of Gravity

Gravitational theories generated from Lagrangians of the form f(R) are considered. The spherically symmetric solutions to these equations are discussed, paying particular attention to features that differ from the standard Schwarzschild solution. The asymptotic form of solutions is described, as is the lack of validity of Birkhoff's theorem. Exact solutions are presented which illustrate these points and their stability and geodesics are investigated.Comment: 10 pages, published versio

Measuring changes in human tumour vasculature in response to therapy using functional imaging techniques

Antiangiogenic and antivascular agents provide new approaches to treating tumours. These may avoid many of the problems experienced with current approaches such as inherent and acquired resistance to treatment. Tumours do not grow beyond 1–2 mm3in size without the development of new vessels (Folkman, 1971). Such neo-vascularization (angiogenesis) allows tumour cells to increase their nutrient supply, survive and proliferate despite the new vessels often having structural and functional differences compared to normal tissue vasculature. Treatments targeted at tumour vasculature have produced impressive results in animal models (Lindsay et al, 1996; Watson et al, 1996; O’Reilly, 1997; Horsman et al, 1998). These therapies are now entering clinical trials. However, the successful introduction of these therapies into clinical practice will require the development of reliable ways to assess angiogenesis and its modification or inhibition in vivo. Here we discuss some of the emerging imaging techniques that may be useful. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Lie symmetries for two-dimensional charged particle motion

We find the Lie point symmetries for non-relativistic two-dimensional charged particle motion. These symmetries comprise a quasi-invariance transformation, a time-dependent rotation, a time-dependent spatial translation and a dilation. The associated electromagnetic fields satisfy a system of first-order linear partial differential equations. This system is solved exactly, yielding four classes of electromagnetic fields compatible with Lie point symmetries

A Development Environment for Visual Physics Analysis

The Visual Physics Analysis (VISPA) project integrates different aspects of physics analyses into a graphical development environment. It addresses the typical development cycle of (re-)designing, executing and verifying an analysis. The project provides an extendable plug-in mechanism and includes plug-ins for designing the analysis flow, for running the analysis on batch systems, and for browsing the data content. The corresponding plug-ins are based on an object-oriented toolkit for modular data analysis. We introduce the main concepts of the project, describe the technical realization and demonstrate the functionality in example applications