312 research outputs found

    Book Review: Paul Michael Garrett, Social work and social theory: Making connections. The Policy Press: Bristol, 2013, ISBN 9781847429605

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    It is important to state at the outset that I enjoyed this book, or at least large sections of it, but I also found it rather frustrating. The book is made up of 11 chapters and following an introductory chapter, is split into two parts. The first is concerned with ‘debating modernity’ made up of four chapters which critically analyse some of the most high-profile social theorists of recent times and their approaches to understanding contemporary society and recent social change – Giddens, Beck and Bauman in particular – together with some of the social work writers who have drawn on this body of work. The remaining two chapters in part one are then concerned with drawing on Marx, particularly Das Capital, for making sense of modernity and convincingly argues for replacing the concept of modernity with an explicit use of

    The politics of child protection in England

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    Provided a critical analysis of the politics of child protection in England to Staff, post doctoral and PhD students at the Oxford Children's Rights Network at Oxford University, 9 November 201

    Portrayals of Child Abuse Scandals in the Media in Australia and England: Impacts on Practice, Policy, and Systems

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    This article describes how the media have played a key role in placing the issue of child maltreatment and the problems associated with child protection high on public and political agendas over the last 50 years. It also describes how the influence of the media is far from unambiguous. Although the media has been crucial in bringing the problems into the open, it often does so in particular ways. In being so concerned with scandals and tragedies ∗ Correspondence concerning this article should be addressed to Bob Lonne, School of Public Health and Social Work, Queensland University of Technology, Victoria Park Road, Kelvin Grove, Queensland 4059, Australia. Electronic mail may be sent to [email protected]. in a variety of institutionalized and community settings, the media have portrayed the nature of child maltreatment in ways which deflect attention from many of its core characteristics and causes. A focus on the media is important because of the power the media have to help transform the private into the public, but at the same time, to undermine trust, reputation, and legitimacy of the professionals working in the field. This concern is key for those working in the child protection field and has been a source of tension in public policy in both Australia and England for many years

    Mi a konstruktív szociális munka?

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    A következő tanulmánnyal két fő célt igyekszünk elérni: először is vázoljuk, hogy mit értünk konstruktív szociális munkán és hogy ennek mely elemeit tartjuk központi jelentőségűnek; másodszor a konstrukcionizmushoz kapcsolódó, azon lehetőségeket ismertetjük, amelyek szerintünk fontos elméleti vonatkoztatási keretet biztosítanak a gyakorlat ilyen jellegű megközelítéséhez

    Digital clocks: simple Boolean models can quantitatively describe circadian systems

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    Copyright © 2012 The Royal Society This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The gene networks that comprise the circadian clock modulate biological function across a range of scales, from gene expression to performance and adaptive behaviour. The clock functions by generating endogenous rhythms that can be entrained to the external 24-h day-night cycle, enabling organisms to optimally time biochemical processes relative to dawn and dusk. In recent years, computational models based on differential equations have become useful tools for dissecting and quantifying the complex regulatory relationships underlying the clock's oscillatory dynamics. However, optimizing the large parameter sets characteristic of these models places intense demands on both computational and experimental resources, limiting the scope of in silico studies. Here, we develop an approach based on Boolean logic that dramatically reduces the parametrization, making the state and parameter spaces finite and tractable. We introduce efficient methods for fitting Boolean models to molecular data, successfully demonstrating their application to synthetic time courses generated by a number of established clock models, as well as experimental expression levels measured using luciferase imaging. Our results indicate that despite their relative simplicity, logic models can (i) simulate circadian oscillations with the correct, experimentally observed phase relationships among genes and (ii) flexibly entrain to light stimuli, reproducing the complex responses to variations in daylength generated by more detailed differential equation formulations. Our work also demonstrates that logic models have sufficient predictive power to identify optimal regulatory structures from experimental data. By presenting the first Boolean models of circadian circuits together with general techniques for their optimization, we hope to establish a new framework for the systematic modelling of more complex clocks, as well as other circuits with different qualitative dynamics. In particular, we anticipate that the ability of logic models to provide a computationally efficient representation of system behaviour could greatly facilitate the reverse-engineering of large-scale biochemical networks

    HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

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    BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse
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