Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. Wild-type (wt) or IL-1R1 KO mice were treated with a single session of XRT (20 or 14 gray [Gy]). Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson’s trichrome was used to assess myocardial fibrosis and pericardial thickening. After 20 Gy, the contractile reserve was impaired in wt mice at d 3, and the LV ejection fraction (EF) was reduced after 4 months when compared with sham-XRT. IL-1R1 KO mice had preserved contractile reserve at 3 d and 4 months and LVEF at 4 months after XRT. Anakinra treatment for 1 d before and 7 d after XRT prevented the impairment in contractile reserve. A significant increase in LV end-diastolic pressure, associated with increased myocardial interstitial fibrosis and pericardial thickening, was observed in wt mice, as well as in IL-1R1 KO–or anakinra-treated mice. In conclusion, induction of IL-1 by XRT mediates the development of some, such as the contractile impairment, but not all aspects of the XRT-induced cardiomyopathy, such as myocardial fibrosis or pericardial thickening

The abolition of the General Teaching Council for England and the future of teacher discipline

With the abolition of the General Teaching Council for England in the 2011 Education Act, this article considers the future of teacher discipline in England. It provides a critique of the changes to the regulation of teacher misconduct and incompetence that draws on a Foucauldian framework, especially concerning the issue of public displays of discipline and the concomitant movement to more hidden forms. In addition, the external context of accountability that accompanies the reforms to teacher discipline are considered including the perfection of the panoptic metaphor presented by the changes to Ofsted practices such as the introduction of zero-notice inspections. The article concludes that the reforms will further move teachers from being occupational professionals to being organisational professionals marking them apart from comparable professions in medicine and law

Crossing borders: new teachers co-constructing professional identity in performative times

This paper draws on a range of theoretical perspectives on the construction of new teachers’ professional identity. It focuses particularly on the impact of the development in many national education systems of a performative culture of the management and regulation of teachers’ work. Whilst the role of interactions with professional colleagues and school managers in the performative school has been extensively researched, less attention has been paid to new teachers’ interactions with students. This paper highlights the need for further research focusing on the process of identity co-construction with students. A key theoretical concept employed is that of liminality, the space within which identities are in transition as teachers adjust to the culture of a new professional workplace, and the nature of the engagement of new teachers, or teachers who change schools, with students. The authors argue that an investigation into the processes of this co-construction of identity offers scope for new insights into the extent to which teachers might construct either a teacher identity at odds with their personal and professional values, or a more ‘authentic’ identity that counters performative discourses. These insights will in turn add to our understanding of the complex range of factors impacting on teacher resilience and motivation

Creating citizen-consumers? Public service reform and (un)willing selves

About the book: Postmodern theories heralded the "death of the subject", and thereby deeply contested our intuition that we are free and willing selves. In recent times, the (free) will has come under attack yet again. Findings from the neuro- and cognitive sciences claim the concept of will to be scientifically untenable, specifying that it is our brain rather than our 'self' which decides what we want to do. In spite of these challenges however, the willing self has come to take centre stage in our society: juridical and moral practices ascribing guilt, or the organization of everyday life attributing responsibilities, for instance, can hardly be understood without taking recourse to the willing subject. In this vein, the authors address topics such as the genealogy of the concept of willing selves, the discourse on agency in neuroscience and sociology, the political debate on volition within neoliberal and neoconservative regimes, approaches toward novel forms of relational responsibility as well as moral evaluations in conceptualizing autonomy

Recognising Desire: A psychosocial approach to understanding education policy implementation and effect

It is argued that in order to understand the ways in which teachers experience their work - including the idiosyncratic ways in which they respond to and implement mandated education policy - it is necessary to take account both of sociological and of psychological issues. The paper draws on original research with practising and beginning teachers, and on theories of social and psychic induction, to illustrate the potential benefits of this bipartisan approach for both teachers and researchers. Recognising the significance of (but somewhat arbitrary distinction between) structure and agency in teachers’ practical and ideological positionings, it is suggested that teachers’ responses to local and central policy changes are governed by a mix of pragmatism, social determinism and often hidden desires. It is the often underacknowledged strength of desire that may tip teachers into accepting and implementing policies with which they are not ideologically comfortable

We are all teacher educators now: understanding school-based teacher educators in times of change in England

Within the context of the European Commission’s recent policy gaze on teacher education (European Commission, Improving teacher quality: The EU agenda – lifelong learning: policies and programme. Brussels, April 2010, EAC.B.2. D (2010) PSH, 2010; European Commission, Supporting teacher educators for better learning outcomes. European Commission, Brussels, 2013; European Commission, Strengthening teaching in Europe: new evidence from teachers compiled by Eurydice and CRELL, June 2015. Available from: http://ec.europa.eu/education/library/policy/teaching-profession-practices_en.pdf, 2015), this chapter contributes to an improved understanding of the hybrid, poly-contextualised identities of school-based teacher educators. At a time of systemic change in the education systems of many countries, teachers in schools are increasingly being asked to be responsible for the education and training of future teachers. Within the English backdrop of a rapidly changing landscape for teacher education, we present initial findings from a small-scale study exploring, through interview data, how the knowledge bases and identities of two groups of insiders, university and school-based teacher educators, were perceived by those hybrid teacher educators (Zeichner 2010) working in schools. Our findings reveal differences in school-based teacher educators’ views on their work and the work of university-based teacher educators, school-based teacher educators’ views on the role educational research has in the work they do and the ways in which different professional pathways (e.g. occupational/university; primary/secondary) influence views on what it means to be a teacher educator

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Innovation in technology-enhanced assessment in the UK and the USA: future scenarios and critical considerations

This paper uses methods derived from the field of futures studies to explore the future of technology-enhanced assessment. Drawing on interviews and consultation activities with experts, the paper aims to discuss the conditions that can impede or foster ‘innovation’ in assessment and education more broadly. Through a review of relevant research, the paper suggests an interpretive model of the factors sustaining the conservatism of educational assessment: the utilitarian view of education, dominant beliefs about academic excellence, and market or quasi-market dynamics. In the central section of the paper, three scenarios of innovation in assessment are described, developed through an iterative process involving researchers, representatives from the e-assessment industry, and experts from British awarding organisations. In the final section, a critical discussion draws attention to the implications that data pervasiveness and computer-generated predictive models may have for the future of education

Revealing the community within: valuing the role of local community structures within evidence-based school intervention programmes

Schools and the families they serve are sometimes perceived as deficient and in need of fixing. One response has been the implementation of evidence-based family intervention programmes, which may be highly regulated and prescriptive as a condition of their (often philanthropic) funding. This article seeks to explore and bring to the foreground the often hidden role of the pre-existing, informal community networks with a view to more authentic evaluation of these externally imposed programmes. The article draws on a range of qualitative data reflecting the lived experiences of participants—including parents and other community members—in a family and parenting programme at an English primary school. The analysis uses the work of Tönnies as a theoretical lens. It suggests that while there are tensions caused by the rigid requirements of external programmes, these are overcome in many cases by the highly effective, but often unacknowledged, contributions of the informal aspects of community. It is argued that these operate within and complement the formal programme. Far from subverting the more overt procedures, they actually enable it to function successfully, leading to additional, unanticipated transformations among participants. The article concludes that these organic, often invisible connections need to be identified, documented and nurtured if their full potential is to be recognised and realised when evaluating similar interventions

CP-31398, a putative p53-stabilizing molecule tested in mammalian cells and in yeast for its effects on p53 transcriptional activity

BACKGROUND: CP-31398 is a small molecule that has been reported to stabilize the DNA-binding core domain of the human tumor suppressor protein p53 in vitro. The compound was also reported to function as a potential anti-cancer drug by rescuing the DNA-binding activity and, consequently, the transcription activation function of mutant p53 protein in mammalian tissue culture cells and in mice. RESULTS: We performed a series of gene expression experiments to test the activity of CP-31398 in yeast and in human cell cultures. With these cell-based assays, we were unable to detect any specific stimulation of mutant p53 activity by this compound. Concentrations of CP-31398 that were reported to be active in the published work were highly toxic to the human H1299 lung carcinoma and Saos-2 cell lines in our experiments. CONCLUSION: In our experiments, the small molecule CP-31398 was unable to reactivate mutant p53 protein. The results of our in vivo experiments are in agreement with the recently published biochemical analysis of CP-31398 showing that this molecule does not bind p53 as previously claimed, but intercalates into DNA