Neoadjuvant Stereotactic Ablative Radiotherapy To Treat Early Stage Breast Cancer Patients: The Role Of DCE-MRI

The current standard of breast conserving therapy is lumpectomy followed by whole breast radiotherapy which is prohibitively long for many patients (4-6 weeks). In addition, the need for treating the whole breast has been questioned. The London Regional Cancer Program is enrolling early stage breast cancer patients in a prospective Phase I/II clinical trial (SIGNAL) to assess the safety/efficacy of neoadjuvant stereotactic ablative radiotherapy (SABR) to the tumour alone to reduce treatment times. This provides a unique opportunity to assess tumour response to SABR using non-invasive imaging. Patients received a pre-SABR dynamic contrast-enhanced (DCE)-MRI to guide target volume delineation. A subset also received post-SABR DCE-MRI to facilitate response assessment. Recent safety concerns of long-term retention of gadolinium-based contrast agents (GBCA) in brain and bone led us to reduce the dose of GBCA to half the clinical dose part way through SIGNAL. Chapter 2 presents an investigation of the impact of this reduction on the inter- and intra-observer variability for target volume delineation and we found no significant decreases. These results are important for any context that requires repeated administrations of GBCAs to patients. Chapter 3 presents an investigation of the impact of intra-session image registration on the voxel-by-voxel application of the Tofts model. Image registration led to significant reductions in the uncertainty in model parameter estimates and unphysical parameter estimates. Also, we showed that computation time could be reduced by a factor of two without affecting these results. Chapter 4 presents an investigation of DCE-MRI based assessment of treatment response to SABR in early stage breast cancer. The analysis included two time delays post-SABR (6-7 or 16-19 days) and two SABR fractionation schemes (21Gy/1fraction or 30Gy/3fractions). DCE-MRI response assessment one-week post-SABR was confounded by acute inflammatory effects whereas 2.5 weeks appeared sufficiently long to minimize these effects. Kinetic parameters measured 2.5 weeks post-SABR in both fractionation groups were indicative of response, but only the single fraction led to enhancement in tissue surrounding the tumour. Such metrics will be valuable in adapting treatment to patients and in future studies that will investigate higher ablative doses with the potential to eliminate surgery

3D-in-2D Displays for ATC.

This paper reports on the efforts and accomplishments of the 3D-in-2D Displays for ATC project at the end of Year 1. We describe the invention of 10 novel 3D/2D visualisations that were mostly implemented in the Augmented Reality ARToolkit. These prototype implementations of visualisation and interaction elements can be viewed on the accompanying video. We have identified six candidate design concepts which we will further research and develop. These designs correspond with the early feasibility studies stage of maturity as defined by the NASA Technology Readiness Level framework. We developed the Combination Display Framework from a review of the literature, and used it for analysing display designs in terms of display technique used and how they are combined. The insights we gained from this framework then guided our inventions and the human-centered innovation process we use to iteratively invent. Our designs are based on an understanding of user work practices. We also developed a simple ATC simulator that we used for rapid experimentation and evaluation of design ideas. We expect that if this project continues, the effort in Year 2 and 3 will be focus on maturing the concepts and employment in a operational laboratory settings

Study on open science: The general state of the play in Open Science principles and practices at European life sciences institutes

Nowadays, open science is a hot topic on all levels and also is one of the priorities of the European Research Area. Components that are commonly associated with open science are open access, open data, open methodology, open source, open peer review, open science policies and citizen science. Open science may a great potential to connect and influence the practices of researchers, funding institutions and the public. In this paper, we evaluate the level of openness based on public surveys at four European life sciences institute

Developing a framework for semi-automated rule-based modelling for neuroscience research

Dynamic modelling has significantly improved our understanding of the complex molecular mechanisms underpinning neurobiological processes. The detailed mechanistic insights these models offer depend on the availability of a diverse range of experimental observations. Despite the huge increase in biomolecular data generation from novel high-throughput technologies and extensive research in bioinformatics and dynamical modelling, efficient creation of accurate dynamical models remains highly challenging. To study this problem, three perspectives are considered: comparison of modelling methods, prioritisation of results and analysis of primary data sets. Firstly, I compare two models of the DARPP-32 signalling network: a classically defined model with ordinary differential equations (ODE) and its equivalent, defined using a novel rule-based (RB) paradigm. The RB model recapitulates the results of the ODE model, but offers a more expressive and flexible syntax that can efficiently handle the “combinatorial complexity” commonly found in signalling networks, and allows ready access to fine-grain details of the emerging system. RB modelling is particularly well suited to encoding protein-centred features such as domain information and post-translational modification sites. Secondly, I propose a new pipeline for prioritisation of molecular species that arise during model simulation using a recently developed algorithm based on multivariate mutual information (CorEx) coupled with global sensitivity analysis (GSA) using the RKappa package. To efficiently evaluate the importance of parameters, Hilber-Schmidt Independence Criterion (HSIC)-based indices are aggregated into a weighted network that allows compact analysis of the model across conditions. Finally, I describe an approach for the development of disease-specific dynamical models using genes known to be associated with Attention Deficit Hyperactivity Disorder (ADHD) as an exemplar. Candidate disease genes are mapped to a selection of datasets that are potentially relevant to the modelling process (e.g. interactions between proteins and domains, protein-domain and kinase-substrates mappings) and these are jointly analysed using network clustering and pathway enrichment analyses to evaluate their coverage and utility in developing rule-based models

MS FT-2-2 7 Orthogonal polynomials and quadrature: Theory, computation, and applications

Quadrature rules find many applications in science and engineering. Their analysis is a classical area of applied mathematics and continues to attract considerable attention. This seminar brings together speakers with expertise in a large variety of quadrature rules. It is the aim of the seminar to provide an overview of recent developments in the analysis of quadrature rules. The computation of error estimates and novel applications also are described

Generalized averaged Gaussian quadrature and applications

A simple numerical method for constructing the optimal generalized averaged Gaussian quadrature formulas will be presented. These formulas exist in many cases in which real positive GaussKronrod formulas do not exist, and can be used as an adequate alternative in order to estimate the error of a Gaussian rule. We also investigate the conditions under which the optimal averaged Gaussian quadrature formulas and their truncated variants are internal