Metabolic changes during carcinogenesis: Potential impact on invasiveness

Successful adaptation to varying microenvironmental constraints plays a crucial role during carcinogenesis. We develop a hybrid cellular automation approach to investigate the cell–microenvironmental interactions that mediate somatic evolution of cancer cells. This allows investigation of the hypothesis that regions of premalignant lesions develop a substrate-limited environment as proliferation carries cells away from blood vessels which remain separated by the intact basement membrane. We find that selective forces in tumoural regions furthest from the blood supply act to favour cells whose metabolism is best suited to respond to local changes in oxygen, glucose and pH levels. The model predicts three phases of somatic evolution. Initially, cell survival and proliferation is limited due to diminished oxygen levels. This promotes adaptation to a second phase of growth dominated by cells with constitutively up-regulated glycolysis, less reliant on oxygen for ATP production. Increased glycolysis induces acidification of the local environment, limiting proliferation and inducing cell death through necrosis and apoptosis. This promotes a third phase of cellular evolution, with emergence of phenotypes resistant to acid-induced toxicity. This emergent cellular phenotype has a significant proliferative advantage because it will consistently acidify the local environment in a way that is toxic to its competitors but harmless to itself. The model's results suggest this sequence is essential in the transition from self-limited premalignant growth to invasive cancer, and, therefore, that this transition may be delayed or prevented through novel strategies directed towards interrupting the hypoxia–glycolysis–acidosis cycle

Data linkage for early intervention in the UK: Parental social license and social divisions

Electronic linking of public records and predictive analytics to identify families for preventive early intervention increasingly is promoted by governments. We use the concept of social license to address questions of social legitimacy, agreement, and trust in data linkage and analytics for parents of dependent children, who are the focus of early intervention initiatives in the UK. We review data-steered family policy and early intervention operational service practices. We draw on a consensus baseline analysis of data from a probability-based panel survey of parents, to show that informed consent to data linkage and use is important to all parents, but there are social divisions of knowledge, agreement, and trust. There is more social license for data linkage by services among parents in higher occupation, qualification, and income groups, than among Black parents, lone parents, younger parents, and parents in larger households. These marginalized groups of parents, collectively, are more likely to be the focus of identification for early intervention. We argue that government awareness-raising exercises about the merits of data linkage are likely to bolster existing social license among advantaged parents while running the risk of further disengagement among disadvantaged groups. This is especially where inequalities and forecasting inaccuracies are encoded into early intervention data gathering, linking, and predictive practices, with consequences for a cohesive and equal society

All the ACEs: A Chaotic Concept for Family Policy and Decision-Making?

This paper will consider ACEs as a chaotic concept that prioritises risk and obscures the material and social conditions of the lives of its objects. It will show how the various definitions of ACEs offer no cohesive body of definitive evidence and measurement, and lead to a great deal of over-claiming. It discusses how ACEs have found their time and place, locating a variety of social ills within the child’s home, family and parenting behaviours. It argues that because ACEs are confined to intra-familial circumstances, and largely to narrow parent-child relations, issues outside of parental control are not addressed. It concludes that ACEs form a poor body of evidence for family policy and decision-making about child protection and that different and less stigmatising solutions are hiding in plain sight

Support Requirements and Effects of Supervision on Telephone Counsellors

The aim of this research was to examine the effects of the implementation of direct one-on-one supervision in a prominent telephone counselling organization and the support requirements of their telephone counsellors. Ninety-three telephone counsellors participated in this research. The results showed that more experienced telephone counsellors were more satisfied than less experienced telephone counsellors with the support offered by the organization. Furthermore, female telephone counsellors showed significantly more satisfaction with the support offered by the organisation than their male counterparts. Implications of these findings are discussed in relation to the organisation and other helping organisations within the wider community

Determining information for inclusion in a decision-support intervention for clinical trial participation : A modified Delphi approach

Peer reviewedPostprin

Dendritic surface functionalization of nanomaterials: controlling properties and functions for biomedical applications

Uma grande variedade de nanomateriais tem demonstrado aplicações médicas promissoras, tais como liberação de fármacos e em imagens. Nestas aplicações, a superfície química dos materiais é crítica, uma vez que exerce papel importante na determinação da toxicidade e comportamento de biodistribuição do material. Aqui, nós revisamos a funcionalização de nanomateriais, como dendrons, como método eficiente de alterar a superfície química destes compostos, introduzindo novas propriedades e funções. Descritos aqui estão nanopartículas superparamagnéticas de óxido de ferro (do inglês, SPIO), com guanidinas dendríticas para aumentar seu transporte para o interior das células, úteis em imagens de ressonância magnética. A introdução de dendrons contendo hidroxilas, aminas, guanidinas, carboidratos e quelatos de Gd(III) periféricos em vesículas poliméricas (polymersomes) também está descrita. Esses grupos dendríticos permitem a modulação de toxicidade, captura celular, ligação à proteína e eficiência como agente de contraste, enquanto que, ao mesmo tempo, permitem a manutenção da estabilidade das vesículas poliméricas. Assim, essa abordagem é promissora para o desenvolvimento de grande variedade de materiais multifuncionais para aplicações farmacêuticas.A wide variety of nanomaterials have demonstrated promise in medical applications such as drug delivery and imaging. In these applications, the surface chemistry of the materials is critical as it plays an important role in determining the toxicity and biodistribution behavior of the material. We review here the functionalization of nanomaterials with dendrons as an efficient method to alter the surface chemistry of the materials, introducing new properties and functions. Described here is the functionalization of superparamagnetic iron oxide nanoparticles (SPIO) with dendritic guanidines to enhance their transport into cells for magnetic resonance imaging applications. The introduction of dendrons bearing peripheral hydroxyls, amines, guanidines, carbohydrates and Gd(III) chelates to polymer vesicles (polymersomes) is also described. These dendritic moieties allow for modulation of toxicity, cell uptake, protein binding, and contrast agent efficiency, while at the same time allowing the stabilities of the polymersomes to be maintained. Thus, this approach holds promise for the development of a wide range of multifunctional materials for pharmaceutical applications

Evaluation of interventions for informed consent for randomised controlled trials (ELICIT) : protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

Acknowledgements This work was supported by personal fellowship award (to KG) from the Medical Research Council’s Strategic Skills Methodology programme. The Health Services Research Unit is supported by a core grant from the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. PW is funded by a UK Medical Research Council Hub for Trials Methodology Research Network grant G0800792. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Chief Scientist Office, MRC or the Department of Health.Peer reviewedPublisher PD

Reflections on the construction of meaning through immanent visual association

Since the advent of digital video editing and projection, multimedia presentation in the concert space is no longer exclusive to the music of stadiumsized popular music events. Increasingly, many in the field of new music are incorporating elements of mixed media presentation. Examples of this trend include performances across the spectrum of new music such as Sensorband, Nico Muhly, Leafcutter John, and more. This paper discusses the artistic and thematic accomplishments of four different approaches to audio-visual association before discussing the influences of these approaches, their incorporation or rejection, into my own work Red River. (Gillies, 2011

Synthesis, properties, and degradation of polyisobutylene-polyester graft copolymers

The development of copolymers is a promising approach for combining the favorable properties of two polymers and obtaining new properties of the combination. In this work, graft copolymers of polyisobutylene (PIB) and polycaprolactone (PCL) or poly(D,L-lactide) (PDLLA) were synthesized and studied. Amine terminated polyesters were synthesized and were grafted onto an activated PIB backbone synthesized from butyl rubber, a copolymer of isobutylene and 2 mol % isoprene. The polyester content was tuned from 15 to 44 wt % by varying the molar mass of the polyester blocks and the number of molar equivalents used in the grafting reaction. The graft copolymers with higher polyester content underwent nanoscale phase separation, as demonstrated by differential scanning calorimetry and atomic force microscopy imaging. This was found to provide enhanced mechanical properties such as increased tensile strength and Young’s modulus relative to the starting rubber or physical blends. Despite the significant polyester content of the graft copolymers and the susceptibility of the polyesters to degradation, the graft copolymers underwent negligible mass loss in 5 M NaOH over a period of 8 weeks. These results suggest that polyesters can be incorporated into PIB to tune and enhance its properties, while maintaining high chemical stability