Hypothesis:soluble Aβ oligomers in association with redox-active metal ions are the optimal generators of reactive oxygen species in Alzheimer's disease

Considerable evidence points to oxidative stress in the brain as an important event in the early stages of Alzheimer's disease (AD). The transition metal ions of Cu, Fe, and Zn are all enriched in the amyloid cores of senile plaques in AD. Those of Cu and Fe are redox active and bind to Aβ in vitro. When bound, they can facilitate the reduction of oxygen to hydrogen peroxide, and of the latter to the hydroxyl radical. This radical is very aggressive and can cause considerable oxidative damage. Recent research favours the involvement of small, soluble oligomers as the aggregating species responsible for Aβ neurotoxicity. We propose that the generation of reactive oxygen species (i.e., hydrogen peroxide and hydroxyl radicals) by these oligomers, in association with redox-active metal ions, is a key molecular mechanism underlying the pathogenesis of AD and some other neurodegenerative disorders

Idylls of socialism : the Sarajevo Documentary School and the problem of the Bosnian sub-proletariat

This historical overview of the Sarajevo Documentary School considers the films, in the light of their recent re-emergence, as indicative of both the legacy of socialist realism (even in the context of Yugoslav media) and attempted social engineering in the Bosnia of the 1960s and 1970s. The argument is made that the documentaries, despite their questionable aesthetic status (in respect of cinma-vrit and ethnography) and problematic ideological strategies and attempted interventions, document a history and offer insights that counter the prevailing revisionist trends in the presentation of Eastern and Central European history

Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice

We thank AstraZeneca for providing AZ-4217, Mark Smith (Imperial College, London) and Yuchio Yanagawa (Gunma University, Maebashi) for VGlut2-GFP and GAD67-GFP tissue, respectively. This work was funded by Medical Research Council (MR/K003291/1), Diabetes UK (12/0004458), British Heart Foundation (PG/15/44/31574) and Biotechnology and Biological Sciences Research Council CASE (with AstraZeneca) award (BB/I015663/1) to MLJA and by a grant to LKH from the Wellcome Trust (WT098012).Peer reviewe

Determining the extent to which simulation can be used to train RAF pilots to fly and fight the Eurofighter Typhoon

This research examines the extent to which simulation can be used to train pilots of the Royal Air Force to fly and fight the Eurofighter Typhoon, and is the culmination of a series of trials over a period of 4 years. The approach was threefold, firstly examining the performance of students trained entirely on the Operational Conversion Unit’s full syllabus in the simulator and then tested against their peers on each of the four phases in live flight, secondly investigating the cultural acceptance levels of the present Typhoon pilots and lastly using lessons learnt to generate and test a syllabus to train Typhoon pilots to Mult Role Combat Ready in 40% of the present time. It was found that increasing the proportion of synthetics from the lowest Live Synthetic Balance (LSB) of 75:25 used on the front-line meets a cultural and resource barrier at 50:50. This did not represent the maximum LSB achievable however with the heavily synthetic Multi-Role Syllabus reaching an LSB of 21:79 with successful completion of the end of course test. Cultural acceptance of the simulator had correlations with the squadron a pilot was assigned to, the manner in which the simulators were programmed for use and the experience level of the pilot. No evidence was found within the sample to suggest age had an effect. Recommendations on minimum proportions of live and synthetic training was mapped for each of the required tasks and comparisons of these were made across complexity levels. Resource savings found by the generating and testing a Multi Role Combat Ready syllabus that recognised and incorporated all the strengths, weaknesses and lessons identified in the previous trials generated a saving of approximately 9 months and 100 Typhoon live flying hours per student, equivalent to approximately 1300 man maintenance hours that could be reinvested into personnel in the form of leave, adventurous training or development

Flow impacts on estuarine finfish fisheries of the Gulf of Carpentaria

The estuaries of Australia s tropical rivers support commercial fisheries for finfish and shellfish valued at over $220 million per annum. There are also significant tourism-related and local recreational and indigenous fisheries for icon species such as barramundi. Development of water resources in Australia's Tropical Rivers region is being considered for the Flinders, Mitchell, McArthur, Roper, Daly and Victoria catchments. Greater knowledge of the freshwater requirements of tropical aquatic ecosystems, including estuaries is crucial, so that the communities of catchments where water resource development occurs can be assured that the downstream effects of such development are considered and managed based on the best available knowledge

Characteristics of individuals presenting to treatment for primary alcohol problems versus other drug problems in the Australian patient pathways study

Background: People seeking treatment for substance use disorders often have additional health and social issues. Although individuals presenting with alcohol as the primary drug of concern (PDOC) account for nearly half of all treatment episodes to the Australian alcohol and other drug (AOD) service system, previous treatment cohort studies have focused only on the profile of Australian heroin or methamphetamine users. While studies overseas indicate that clients seeking treatment primarily for their drinking are less likely to experience social and economic marginalisation than those seeking treatment primarily for illicit or pharmaceutical drug use, very little research has directly compared individuals presenting with alcohol as the PDOC to those primarily presenting with other drugs as their PDOC. Methods: Seven hundred and ninety-six participants were recruited at entry to specialist AOD treatment in Victoria and Western Australia, and completed measures of demographic and social factors, substance use, quality of life, service use, and criminal justice involvement. We compared those with alcohol as their PDOC to those with other drugs as their PDOC using Pearson chi-square and Mann–Whitney U tests. Results: Rates of social disadvantage, poor quality of life, high severity of substance dependence, and past-year AOD, mental health, acute health, and social service use were high in all groups. However, participants with alcohol as the PDOC were older; more likely to have an educational qualification; less likely to report criminal justice involvement, housing/homelessness service use, tobacco smoking, or problems with multiple substances; and reported better environmental quality of life; but were more likely to have used ambulance services, than those with other drugs as their PDOC. Conclusions: While those seeking treatment primarily for alcohol problems appear less likely to suffer some forms of social and economic disadvantage or to use multiple substances than those with a primary drug problem, they experience similarly high levels of substance dependence severity and mental health and AOD service use. These findings reinforce the need for AOD services to integrate or coordinate care with programs that address the many complexities clients frequently present with, while also acknowledging differences between those seeking treatment for alcohol versus other drug problems

Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation

© 2016 Royal Australasian College of Physicians Background: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. Aims: To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer. Methods: A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were ≥18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns. Results: There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial. Conclusion: Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed

Improving the management of pain from advanced cancer in the community: study protocol for a pragmatic multi-centre randomised controlled trial

Introduction: For patients with advanced cancer, research shows that pain is frequent, burdensome and undertreated. Evidence-based approaches to support cancer pain management have been developed but have not been implemented within the context of the UK National Health Service. This protocol is for a pragmatic multi-centre randomised controlled trial to assess feasibility, acceptability, effectiveness and cost effectiveness for a multi-component intervention for pain management in patients with advanced cancer. Methods and Analysis: This trial will assess the feasibility of implementation and uptake of evidence based interventions, developed and piloted as part of the IMPACCT Programme grant, into routine clinical practice and determine whether there are potential differences with respect to patient rated pain, patient pain knowledge and experience, healthcare use, quality of life, and cost effectiveness. 160 patients will receive either the intervention (usual care plus supported self-management) delivered within the oncology clinic and palliative care services by locally assigned community palliative care nurses, consisting of a self-management educational intervention and eHealth intervention for routine pain assessment and monitoring; or usual care. The primary outcomes are to assess implementation and uptake of the interventions, and differences in terms of pain severity. Secondary outcomes include pain interference, participant pain knowledge and experience, and cost effectiveness. Outcome assessment will be blinded and patient reported outcome measures collected via post at 6 and 12 weeks following randomisation. Ethics and Dissemination: This RCT has the potential to significantly influence NHS service delivery to community based patients with pain from advanced cancer. We aim to provide definitive evidence of whether two simple interventions delivered by community palliative care nurse in palliative care that support-self-management are clinically and cost effective additions to standard community palliative care

GP/GPN partner* perspectives on clinical placements for student nurses in general practice: can a community of practice help to change the prevailing culture within general practice?

Background: The UK Government document 5 year forward view describes the need to move chronic disease management from secondary to primary care, which will require a significant increase in the numbers of General Practice Nurses (GPNs). Until recently, there has been no specific recruitment strategy to address this increased need. In recent times, a number of solutions have been suggested to address this impending GPN recruitment crisis. For example, Health Education England (HEE) commission General Practitioners (GPs), who are members of the Advanced Training Practice Scheme (ATPS), to provide placements for student nurses within general practice. Methods: A descriptive qualitative study was undertaken, in which data were collected using semi-structured interviews with 16 GPs and 2 GPN partners∗. Qualitative analysis used a framework approach and themes were cross-checked within the team and member checking was undertaken with a convenience sample of GPs. The research had ethical approval and anonymity and confidentiality were maintained. Results: From the GP perspective, there were two key themes that emerged from the data. The first theme of 'fishing in the same small pond' included succession planning for the general practice workforce, the 'merry go round' of poaching staff from other practices, and the myths and misunderstandings that have grown up around general practice nursing. The second theme, 'growing your own', looked at the impact of the student nurse placements as a means to address the crisis in GPN recruitment. There was recognition of the need for cultural change in the way that GPNs are recruited, and that the ATPS was one way of helping to achieve that change. There were however a number of challenges to sustaining this cultural shift, such as the financial constrains placed upon the GP practice, and the need to function as a 'small business'. Conclusions: Despite all the challenges, the evidence is that, through the Community of Practice (CoP), the ATPS scheme is beginning to 'bear fruit', and there is a subtle but discernible move by GPs from a 'why would we?' to 'why wouldn't we?' invest in education and training for nurses in general practice. N.B. The term GPN partner∗denotes a GPN who is a 'full partner' in the practice business, holding the same NHS contracts and the same status as a GP. For the purposes of the paper itself, the term GP will be used to denote both types of partner

The Moral of the Tale: Stories, Trust, and Public Engagement with Clinical Ethics via Radio and Theatre.

Trust is frequently discussed with reference to the professional-patient relationship. However, trust is less explored in relation to the ways in which understanding of, and responses to, questions of ethics are discussed by both the "public" and "experts." Public engagement activity in healthcare ethics may invoke "trust" in analysing a moral question or problem but less frequently conceives of trust as integral to "public engagement" itself. This paper explores the relationship between trust and the ways in which questions of healthcare ethics are identified and negotiated by both "experts" and the public. Drawing on two examples from the author's "public engagement" work-a radio programme for the British Broadcasting Corporation and work with a playwright and theatre-the paper interrogates the ways in which "public engagement" is often characterized. The author argues that the common approach to public engagement in questions of ethics is unhelpfully constrained by a systemic disposition which continues to privilege the professional or expert voice at the expense of meaningful exchange and dialogue. By creating space for novel interactions between the "expert" and the "public," authentic engagement is achieved that enables not only the participants to flourish but also contributes to trust itself