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 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

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

Ethos and Politics in the Youth Hostels Association (YHA) in the 1930s

The Youth Hostels Association (YHA) was a formally non-political organization founded to provide cheap accommodation for walkers and cyclists. However, the YHA drew on, and was influenced by, values and ideas which both attracted a particular kind of member and informed its domestic political interventions. The article specifically examines the connections between the YHA and other organizations, aspects of the politics of membership relating to the concepts of respectability and class and the political interventions of the YHA in the areas of unemployment and the access movement

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

Crowning glory: public law, power and the monarchy

‘New public law’ has a keen interest in the deployment of power and the shifting nature of the public and private. In this article, we argue that the historical legacy of the Crown has hindered the ability of public lawyers to respond to changes in modes of governance in the UK. The constitutional law textbook tradition has played a key role in limiting critiques of the Crown because of the obfuscation that surrounds the legal and political status of the Monarch. However, instead of discounting the significance of the monarchy, we use it as a resource for exploring governing power, the blurring of boundaries and constitutional renewal. Our starting point is the life, death and, most importantly, the funeral of Diana, Princess of Wales. The latter event exposed the political relevance of the ‘personal’ in a most dramatic way, generating claims about the ‘feminisation of the government’ and ‘emotions augmenting democracy’. We follow through on these claims in order to focus on the effects of adopting private, intimate-sphere norms in the public sphere, in particular public-sphere decision making. While aware of the risks associated with this ‘transformation’ of democracy, we conclude that the increasing centrality of the intimate merits onsideration in new public law’s search for progressive tools of modern governance