Tempered radicalism: A model for navigating academic practice and identity in the twenty-first-century neoliberal university?

This article explores Meyerson and Scully's concept of ‘tempered radicalism’ (1995) in the context of contemporary academic practice and identity. We report on a collaborative autoethnographic study which addressed the question: ‘What does the concept of tempered radicalism mean to us as academics in contemporary higher education?’. We explore how the concept of tempered radicalism allows us to consider our own actions and abilities to drive change within an increasingly challenging higher education environment moulded by the policies, values and practices of neoliberal economics. In this context, we share differing perspectives on what it means to bring a values-based criticality to our work. It is the breadth of Meyerson and Scully's concept which allows us to approach this exploration in a way which emphasises commonality rather than difference and facilitates collaboration. This article therefore showcases the utility of tempered radicalism to academics with a range of perspectives

The first consultation with a depressed patient: A qualitative study of GPs' approaches to diagnosis.

BackgroundThe first consultation with a depressed patient is important because many patients do not return for subsequent visits. Therefore, the first consultation provides a unique opportunity for diagnosis (if required) and treatment, but there are risks of both under and over-diagnosis.AimTo understand how general practitioners utilize diagnosis when patients present with a new episode of depression.MethodWe approached a random selection of twenty-one general practitioners (GPs) in Auckland, New Zealand and asked them to participate in a semi-structured telephone interview. The interviews explored "the first consultation for a depressed/distressed patient" were undertaken to theme saturation. Interviews were hand-written and later transcribed.ResultsWe identified three major themes in GPs' approach to diagnosis. The issue of diagnosis was underpinned by a complex understanding of depression and the GP role. GPs did not always make a formal diagnosis, but the experience of a patient's distress/depression was understood by drawing on a range of factors and resources. These included time, screening tools, clinician experience, and patient affect. GPs were careful about how they communicated a diagnosis, both in their documentation and in their conversations with patients.ConclusionAt an initial appointment, the distressed/depressed patient can present to their GP with various symptoms and differing degrees of distress. GPs draw upon a variety of skills and resources to negotiate these complexities. The value of a diagnosis was questioned and issues such as impairment may be more useful concepts for GPs. This is the first study to report the findings of the first visit

Annexin II Light Chain p11 Interacts With ENaC to Increase Functional Activity at the Membrane

The epithelial Na+ channel (ENaC) provides for Na+ absorption in various types of epithelia including the kidney, lung, and colon where ENaC is localized to the apical membrane to enable Na+ entry into the cell. The degree of Na+ entry via ENaC largely depends on the number of active channels localized to the cell membrane, and is tightly controlled by interactions with ubiquitin ligases, kinases, and G-proteins. While regulation of ENaC endocytosis has been well-studied, relatively little is understood of the proteins that govern ENaC exocytosis. We hypothesized that the annexin II light chain, p11, could participate in the transport of ENaC along the exocytic pathway. Our results demonstrate that all three ENaC channel subunits interacted with p11 in an in vitro binding assay. Furthermore, p11 was able to immunoprecipitate ENaC in epithelial cells. Quantitative mass spectrometry of affinity-purified ENaC-p11 complexes recovered several other trafficking proteins including HSP-90 and annexin A6. We also report that p11 exhibits a robust protein expression in cortical collecting duct epithelial cells. However, the expression of p11 in these cells was not influenced by either short-term or long-term exposure to aldosterone. To determine whether the p11 interaction affected ENaC function, we measured amiloride sensitive Na+ currents in Xenopus oocytes or mammalian epithelia co-expressing ENaC and p11 or a siRNA to p11. Results from these experiments showed that p11 significantly augmented ENaC current, whereas knockdown of p11 decreased current. Further, knockdown of p11 reduced ENaC cell surface population suggesting p11 promotes membrane insertion of ENaC. Overall, our findings reveal a novel protein interaction that controls the number of ENaC channels inserted at the membrane via the exocytic pathway

Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial

Background: Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis. Methods: People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants. Results: One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12–30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2–4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide. Conclusions: People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness. Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019

Strategic Design and Delivery of Integrated Catchment Restoration Monitoring: Emerging Lessons from a 12-Year Study in the UK

Despite growing interest in river and catchment restoration, including a focus on nature-based solutions, assessing effectiveness of restoration programmes continues to prove a challenge. The development of the Eddleston Water project, the Scottish Government’s empirical study of the impact of implementing natural flood management measures on flood risk and habitat restoration, provides the opportunity to review restoration monitoring at a strategic and operational level for this long-running catchment restoration programme. The project has implemented an extensive range of restoration measures along the river and across the 69 km2 catchment. This paper reviews the monitoring strategy and assesses both how the monitoring network developed meets its strategic aims and what subsequent changes were made in monitoring design and implementation. Covering hydrology, hydromorphology and ecology, we explore how all three are integrated to provide a comprehensive assessment of restoration success. Lessons to help inform other river rehabilitation monitoring programmes include the importance of a scoping study and capturing the full range of environmental variables pre-restoration; the limitations of BACI designs; and the need to focus integrated monitoring on a process-based framework and impact cascade, whilst also covering the full trajectory of recovery

Periscope Proteins are variable length regulators of bacterial cell surface interactions

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system

Holistic health and social care outreach for people experiencing homelessness with recent non-fatal overdose in Glasgow, Scotland: the Pharmacist and third sector Homeless charity worker Outreach Engagement Non-medical Independent prescriber Rx (PHOENIx) pilot randomised controlled trial

Objectives: To examine randomised controlled trial (RCT) progression criteria including emergency department (ED) attendance and non-fatal overdose, from a holistic, integrated health and social care outreach intervention (PHOENIx), for people experiencing homelessness with recent non-fatal street drug overdose. Design: Pilot RCT. 1:1 randomisation to PHOENIx plus usual care (UC) or UC. Setting: Glasgow, Scotland. Participants: 128 adults experiencing homelessness with at least one non-fatal street drug overdose in the preceding 6 months. Interventions: Pharmacists from the National Health Service and third sector homelessness workers offered weekly outreach. PHOENIx teams develop therapeutic relationships to address health (physical health, mental health and problem drug use) and social care (housing, welfare benefits and social prescribing) in addition to UC. UC comprised building-based primary and secondary health, social and third sector services. Outcomes: Primary: progression criteria: recruitment (≥100 participants in 4 months); ≥80% of participants with data collected at baseline, 6 and 9 months; ≥60% of participants retained in the trial at each follow-up period (6 and 9 months); ≥60% of participants receiving the intervention weekly; any reduction in the rate of presentation to ED and overdoses, at 6- or 9-month follow-up. Secondary: participants with, and time to: hospitalisations; health-related quality of life (QoL); treatment uptake for physical and mental health conditions, and problematic drug use. Results: Progression criteria were exceeded. In PHOENIx compared with UC, there appeared to be a delay in the median time to ED visit, overdose and hospitalisation but no improvement in number of participants with ED visits, overdoses or hospitalisations. QoL and treatment uptake appeared to be higher in PHOENIx versus UC at 6 and 9 months. Conclusions: A definitive RCT is merited, to assess the impact of PHOENIx on people with multiple, severe disadvantages

Regulation of Amyloid Precursor Protein Processing by the Beclin 1 Complex

Autophagy is an intracellular degradation pathway that functions in protein and organelle turnover in response to starvation and cellular stress. Autophagy is initiated by the formation of a complex containing Beclin 1 (BECN1) and its binding partner Phosphoinositide-3-kinase, class 3 (PIK3C3). Recently, BECN1 deficiency was shown to enhance the pathology of a mouse model of Alzheimer Disease (AD). However, the mechanism by which BECN1 or autophagy mediate these effects are unknown. Here, we report that the levels of Amyloid precursor protein (APP) and its metabolites can be reduced through autophagy activation, indicating that they are a substrate for autophagy. Furthermore, we find that knockdown of Becn1 in cell culture increases the levels of APP and its metabolites. Accumulation of APP and APP C-terminal fragments (APP-CTF) are accompanied by impaired autophagosomal clearance. Pharmacological inhibition of autophagosomal-lysosomal degradation causes a comparable accumulation of APP and APP-metabolites in autophagosomes. Becn1 reduction in cell culture leads to lower levels of its binding partner Pik3c3 and increased presence of Microtubule-associated protein 1, light chain 3 (LC3). Overexpression of Becn1, on the other hand, reduces cellular APP levels. In line with these observations, we detected less BECN1 and PIK3C3 but more LC3 protein in brains of AD patients. We conclude that BECN1 regulates APP processing and turnover. BECN1 is involved in autophagy initiation and autophagosome clearance. Accordingly, BECN1 deficiency disrupts cellular autophagy and autophagosomal-lysosomal degradation and alters APP metabolism. Together, our findings suggest that autophagy and the BECN1-PIK3C3 complex regulate APP processing and play an important role in AD pathology