Characterising the tumour morphological response to therapeutic intervention:an ex vivo model

In cancer, morphological assessment of histological tissue samples is a fundamental part of both diagnosis and prognosis. Image analysis offers opportunities to support that assessment through quantitative metrics of morphology. Generally, morphometric analysis is carried out on two dimensional tissue section data and so only represents a small fraction of any tumour. We present a novel application of three-dimensional (3D) morphometrics for 3D imaging data obtained from tumours grown in a culture model. Minkowski functionals, a set of measures that characterise geometry and topology in n-dimensional space, are used to quantify tumour topology in the absence of and in response to therapeutic intervention. These measures are used to stratify the morphological response of tumours to therapeutic intervention. Breast tumours are characterised by estrogen receptor (ER) status, human epidermal growth factor receptor (HER)2 status and tumour grade. Previously, we have shown that ER status is associated with tumour volume in response to tamoxifen treatment ex vivo. Here, HER2 status is found to predict the changes in morphology other than volume as a result of tamoxifen treatment ex vivo. Finally, we show the extent to which Minkowski functionals might be used to predict tumour grade.Minkowski functionals are generalisable to any 3D data set, including in vivo and cellular systems. This quantitative topological analysis can provide a valuable link among biomarkers, drug intervention and tumour morphology that is complementary to existing, non-morphological measures of tumour response to intervention and could ultimately inform patient treatment

(In)formalization and the civilizing process : applying the work of Norbert Elias to housing-based anti-social behaviour interventions in the UK

This paper uses Norbert Elias's theory of the civilizing process to examine trends in social conduct in the UK and to identify how problematic “anti‐social” behaviour is conceptualized and governed through housing‐based mechanisms of intervention. The paper describes how Elias's concepts of the formalization and informalization of conduct and the construction of established and outsider groups provide an analytical framework for understanding social relations. It continues by discussing how de‐civilizing processes are also evident in contemporary society, and are applied to current policy discourse around Respect and anti‐social behaviour. The paper uses the governance of “anti‐social” conduct through housing mechanisms in the UK to critique the work of Elias and concludes by arguing that a revised concept of the civilizing process provides a useful analytical framework for future studies

Long-term efficacy of imatinib mesylate in patients with advanced Tenosynovial Giant Cell Tumor

Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1-80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1-2 (89%). Five patients experienced grade 3-4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments

Modelling of Healthcare Associated Infections: a study on the dynamics of pathogen transmission by using an individual-based approach

Prevention and control of Healthcare Associated Infections (HAIs) has become a high priority for most healthcare organizations. Mathematical models can provide insights into the dynamics of nosocomial infections and help to evaluate the effect of infection control measures. The model presented in this paper adopts an individual-based and stochastic approach to investigate MRSA outbreaks in a hospital ward. A computer simulation was implemented to analyze the dynamics of the system associated with the spread of the infection and to carry out studies on space and personnel management. This study suggests that a strict spatial cohorting might be ineffective, if it is not combined with personnel cohorting

Consequences of intraspecific variation for the structure and function of ecological communities Part 2: linking diversity and function

A central aim in ecology is to understand the relation between organism diversity and ecosystem functioning. We investigate this relation using a generic individual-based modelling framework described in part 1, in which individuals within a community are characterised by physiological traits and interact within a spatially structured environment. We explore the effect of intraspecific variation among individuals on community-scale productivity in a range of homogeneous and heterogeneous environments. We show that diversity among individuals has a significant, and in most but not all cases positive, impact on community productivity. At low levels of resource the persisting plants giving highest productivity have slowest uptake rates and longest times to reproduction. In contrast, at high levels of resource the persisting plants giving highest productivity have highest uptake levels and shortest time to reproduction. Thus, the individuals’ trait distributions defining community functioning emerge, after many iterations of the model, from the surviving individuals. We, therefore, show that different mechanisms, as evidenced in the surviving individuals’ traits, increase community productivity in different environmental contexts, and so demonstrate the importance of accounting for diversity at the scale of the individual. Consequently, progress may be made in linking diversity and function by considering small, manageable systems and making physiological measurements on individuals