Inhibition of Poly(ADP-Ribose) polymerase enhances the toxicity of 131I-Metaiodobenzylguanidine/Topotecan combination therapy to cells and xenografts that express the noradrenaline transporter

Targeted radiotherapy using [131I]meta-iodobenzylguanidine ([131I]MIBG) has produced remissions in some neuroblastoma patients. We previously reported that combining [131I]MIBG with the topoisomerase I (Topo-I) inhibitor topotecan induced long-term DNA damage and supra-additive toxicity to NAT-expressing cells and xenografts. This combination treatment is undergoing clinical evaluation. This present study investigated the potential of PARP-1 inhibition, in vitro and in vivo, to further enhance [131I]MIBG/topotecan efficacy

Family Medicine needs assessment: Studying the clinical work of general practitioners in Ethiopia

Background and Objective: Some universities in sub-Saharan Africa have initiated Family Medicine (FM) residency programs. This study was conducted by FM colleagues at Addis Ababa University (AAU) in Ethiopia and the University of Toronto, Canada to inform the FM residency curriculum at AAU. It was designed to determine the clinical problems that family physicians in Ethiopia may encounter.Methods: We used a mixed methods approach: Modified time-motion study and brief interviews. We observed 46 general practitioners (GPs) across ten sites in Ethiopia. Trained observers recorded time-motion data while GPs conducted their daily work. This data was supplemented by brief interviews with the GPs.Findings: Clinical encounters occupied 82% of GP work. The common symptoms were digestive-abdominal pain (21% visits), respiratory-cough (16%), and general-fever and chills (16%). The common diagnoses were infectious (22% visits), genitourinary (12%), circulatory (10%), and endocrine (10%). Challenges identified were lack of clinical resources (57% of GPs), difficulties in communication (48%) and excessive workload (33%). Most common requests were for information technology (78%) and HIV (46%) training.Conclusion: The profile of common symptoms and diagnoses indicated the competencies family physicians in the regions should have. This information will be used to develop an appropriate FM curriculum at AAU

The politics of aspiration: neo-liberal education policy, 'low' parental aspirations, and primary school Extended Services in disadvantaged communities

Geographical research on education has grown rapidly in both volume and scope during the first decade of the twenty-first century, and one relatively new theme to emerge from this growing literature is that of education and aspiration. Much of the nascent interest in aspiration concerns access to quality schooling and University education. In this paper by contrast we highlight the importance of studying the ways aspirations are (re)produced within the school community. Our empirical focus is on low-income England under New Labour. Here we pursue a two-fold approach: firstly examining how education professionals define parental aspirations for primary-aged children as low; before secondly considering their alternative understandings of appropriate aspirations and the practices through which they seek to promote these, both in school and through the use of Extended Services for parents and children. In conclusion we highlight the importance of inward and outward geographies of education which ‘recouple’ schools with their social context, and discuss the moral and political ambiguities involved in practices designed to raise aspirations

Physicians’ Perspectives on Prescribing Benzodiazepines for Older Adults: A Qualitative Study

BACKGROUND: There is a continued high prevalence of benzodiazepine use by older community-residing adults and of their continued prescription by practitioners, despite well known adverse effects and the availability of safer, effective alternatives. OBJECTIVES: To understand factors influencing chronic use of benzodiazepines in older adults. DESIGN: Qualitative study, semistructured interviews with physicians. PARTICIPANTS: Thirty-three practicing primary care physicians around Philadelphia. APPROACH: Qualitative interviews were audiotaped, transcribed, and entered into a qualitative software program. A multidisciplinary team coded transcripts and developed themes. RESULTS: Physicians generally endorsed benzodiazepines as effective treatment for anxiety, citing quick action and strong patient satisfaction. The use of benzodiazepines in older adults was not seen to be problematic because they did not show drug-seeking or escalating dose behavior suggesting addiction. Physicians minimized other risks of benzodiazepines and did not view monitoring or restricting renewal of prescriptions as an important clinical focus relative to higher-priority medical issues. Many physicians expressed skepticism about risks of continued use and considerable pessimism in the successful taper/discontinuation in older patients with long-term use and prior failed attempts. Physicians also anticipated patient resistance to any such efforts, including switching physicians. CONCLUSIONS: Primary care physicians are averse to addressing the public health problem of benzodiazepine overuse in the elderly. Their attitudes generally conflict with practice guidelines and they complain of a lack of training in constructive strategies to address this problem. A 2-pronged effort should focus on increasing skill level and preventing new cases of benzodiazepine dependency through improved patient education and vigilant monitoring of prescription renewal

Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

<p>Abstract</p> <p>Background</p> <p>Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT) and the resulting need to build capacity in both the science and practice of KT.</p> <p>Findings</p> <p>We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date.</p> <p>Conclusions</p> <p>We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.</p

The food superstore revolution: changing times, changing research agendas in the UK

This paper considers the changing scope of research into UK food superstores over a 30-year period. Rather than catalogue changing market shares by format, we seek instead to show how change links to national policy agendas. Academic research has evolved to address the growing complexities of the social, technological, economic and political impacts of the superstore format. We exemplify this by tracing the progression of retail change in Portsmouth, Hampshire, over 30 years. We discover that academic research can conflict with the preconceptions of some public policymakers. The position is exacerbated by a progressive decline in public information – and a commensurate rise in factual data held by commercial data companies – that leaves policymakers with a choice of which data to believe. This casts a shadow over the objectivity of macro-policy as currently formulated. Concerns currently arise because the UK Competition Commission (2008 but ongoing) starts each inquiry afresh with a search for recent data. Furthermore, it has recently called for changes to retail planning – the very arena in which UK superstore research commenced

Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases

Neuroinflammation is a process characterised by drastic changes in microglial morphology and by marked upregulation of the 18-kDa translocator protein (TSPO) on the mitochondria. The continual increase in incidence of neuroinflammation and neurodegenerative diseases poses a major health issue in many countries, requiring more innovative diagnostic and monitoring tools. TSPO expression may constitute a biomarker for brain inflammation that could be monitored by using TSPO tracers as neuroimaging agents. From medical imaging perspectives, this review focuses on the current concepts related to the TSPO, and discusses briefly on the status of its PET imaging related to neuroinflammation and neurodegenerative diseases in humans

Reassessing Britain’s ‘post-war consensus’: the politics of reason 1945–1979

Since the late-1970s, scholars have been engaged in a vibrant debate about the nature of post-war British politics. While some writers have suggested that the three decades that succeeded the Second World War witnessed a bi-partisan consensus on key policy questions, others have argued that it was conflict, not agreement, that marked the period. This article offers a novel contribution to this controversy by drawing attention to the epistemological beliefs of the Labour and Conservative parties. It argues that once these beliefs are considered, it becomes possible to reconcile some of the competing claims made by proponents and critics of the ‘post-war consensus’ thesis. Labour and Conservative leaders may have been wedded to different beliefs, but they also shared a common enthusiasm for empiricist reasoning and were both reluctant to identify fixed political ‘ends’ that they sought to realise. Consequently, they were both committed to evolutionary forms of change, and they eschewed the notion that any social or political arrangement was of universal value

Back the bid: the 2012 summer games and the governance of London

The Olympic Park being developed in east London for the 2012 Games is one large urban renewal project among many in the city. The impact of the Games on urban development may be of less significance than the impact on city politics. Bidding for and delivering the Games has contributed to a reassessment of the recent experiment with mayoral government. The paper examines these changing representations of the structures of London government that are now seen as a success. Much of the literature on Olympic cities is highly critical of the impact of the games, but the (current) substantial support for London2012 also needs to be explained. We examine how London has created opportunities for support, and moments and spaces for celebration when political leaders and Londoners can come together around particular representations of themselves and the city

Do physician outcome judgments and judgment biases contribute to inappropriate use of treatments? Study protocol

<p>Abstract</p> <p>Background</p> <p>There are many examples of physicians using treatments inappropriately, despite clear evidence about the circumstances under which the benefits of such treatments outweigh their harms. When such over- or under- use of treatments occurs for common diseases, the burden to the healthcare system and risks to patients can be substantial. We propose that a major contributor to inappropriate treatment may be how clinicians judge the likelihood of important treatment outcomes, and how these judgments influence their treatment decisions. The current study will examine the role of judged outcome probabilities and other cognitive factors in the context of two clinical treatment decisions: 1) prescription of antibiotics for sore throat, where we hypothesize overestimation of benefit and underestimation of harm leads to over-prescription of antibiotics; and 2) initiation of anticoagulation for patients with atrial fibrillation (AF), where we hypothesize that underestimation of benefit and overestimation of harm leads to under-prescription of warfarin.</p> <p>Methods</p> <p>For each of the two conditions, we will administer surveys of two types (Type 1 and Type 2) to different samples of Canadian physicians. The primary goal of the Type 1 survey is to assess physicians' perceived outcome probabilities (both good and bad outcomes) for the target treatment. Type 1 surveys will assess judged outcome probabilities in the context of a representative patient, and include questions about how physicians currently treat such cases, the recollection of rare or vivid outcomes, as well as practice and demographic details. The primary goal of the Type 2 surveys is to measure the specific factors that drive individual clinical judgments and treatment decisions, using a 'clinical judgment analysis' or 'lens modeling' approach. This survey will manipulate eight clinical variables across a series of sixteen realistic case vignettes. Based on the survey responses, we will be able to identify which variables have the greatest effect on physician judgments, and whether judgments are affected by inappropriate cues or incorrect weighting of appropriate cues. We will send antibiotics surveys to family physicians (300 per survey), and warfarin surveys to both family physicians and internal medicine specialists (300 per group per survey), for a total of 1,800 physicians. Each Type 1 survey will be two to four pages in length and take about fifteen minutes to complete, while each Type 2 survey will be eight to ten pages in length and take about thirty minutes to complete.</p> <p>Discussion</p> <p>This work will provide insight into the extent to which clinicians' judgments about the likelihood of important treatment outcomes explain inappropriate treatment decisions. This work will also provide information necessary for the development of an individualized feedback tool designed to improve treatment decisions. The techniques developed here have the potential to be applicable to a wide range of clinical areas where inappropriate utilization stems from biased judgments.</p