Introduction: Going Public

The period in which the public history movement has developed has been one of considerable change. This has been a result of the passing of post-war generations, the effects wrought by continuing internal and external conflicts, the globalisation of economies, the emergence of new media forms and the major impact of the digital revolution. This has seen significant shifts in the transmission, reception and practice of history

Drug treatments affecting ACE2 in COVID-19 infection: a systematic review protocol.

BACKGROUND: The SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. ACE2 expression may be associated with COVID-19 infection and mortality rates. Routinely prescribed drugs that up- or down-regulate ACE2 expression are, therefore, of critical research interest as agents that might promote or reduce risk of COVID-19 infection in a susceptible population. AIM: To collate evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2, and thus potentially affect COVID-19 infection. DESIGN & SETTING: Systematic review of studies published in MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Library, and Web of Science from inception to 1 April 2020. METHOD: A systematic review will be conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Inclusion criteria will be: (1) assesses the effect of drug exposure on ACE2 level of expression or activity; (2) the drug is included in the British National Formulary (BNF) and, therefore, available to prescribe in the UK; and (3) a control, placebo, or sham group is included as comparator. Exclusion criteria will be: (1) ACE2 measurement in utero; (2) ACE2 measurement in children aged <18 years; (3) drug not in the BNF; and (4) review article. Quality will be assessed using the Cochrane risk of bias tool for human studies, and the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool for animal studies. RESULTS: Data will be reported in summary tables and narrative synthesis. CONCLUSION: This systematic review will identify drug therapies that may increase or decrease ACE2 expression. This might identify medications increasing risk of COVID-19 transmission, or as targets for intervention in mitigating transmission

Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review.

Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265; Grant(s): MRC Epidemiology Unit programme: MC_UU_12015/4.OBJECTIVE: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. DESIGN: Systematic review. DATA SOURCE: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science. STUDY SELECTION: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. DATA EXTRACTION AND SYNTHESIS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies. RESULTS: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). CONCLUSIONS: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease

Concussion in the UK: a contemporary narrative review

Concussion has been receiving an increasing amount of media exposure following several high-profile professional sports controversies and multimillion-dollar lawsuits. The potential life-changing sequalae of concussion and the rare, but devastating, second impact syndrome have also gained much attention. Despite this, our knowledge of the pathological processes involved is limited and often extrapolated from research into more severe brain injuries. As there is no objective diagnostic test for concussion. Relying on history and examination only, the diagnosis of concussion has become the rate-limiting step in widening research into the disease. Clinical study protocols therefore frequently exclude the most vulnerable groups of patients such as those with existing cognitive impairment, concurrent intoxication, mental health issues or learning difficulties. This up-to-date narrative review aims to summarize our current concussion knowledge and provides an insight into promising avenues for future research

Refugee Integration Outcomes cohort study: Evidence for policy and planning

Evidence on refugee integration outcomes in the UK is lacking, partly due to an absence of datasets which permit refugees to be identified. The RIO longitudinal cohort study designed in collaboration with the Home Office aims to address this by linking administrative data longitudinally. RIO covers cohorts granted asylum and refugees resettled in England & Wales via the Vulnerable Persons and Vulnerable Children’s resettlement Schemes between 2015 and 2020. Linked data include the Personal Demographics Service from the NHS and Exit Checks from the Home Office. Census 2021 data have also been linked to the study. Deterministic linkage algorithms addressed different naming conventions across a wide set of cultures and administrative data quality. Associative linkage methods were developed to match residuals from the deterministic stage to their corresponding household if present. We conducted our own internal quality analysis to assess the quality of our linkage algorithms to improve our methodology ahead of incorporating new administrative data such as HMRC and DWP data. Experimental analysis has looked at social and economic outcomes for these refugee cohorts. Linkage to NHS data helps us understand access to health services and time taken to access these services once resettled. Census 2021 data provide a rich understanding of integration outcomes up to 6 years after arrival or grant of asylum. We demonstrate the potential of linked census data to provide evidence on housing, education, health, access to the labour market, education, households and secondary migration but also how this varies for asylum and refugee cohorts but also by age, sex and geographical region. RIO is aligned to the ONS strategic objective of inclusivity and recommendations made by the UK National Statistician’s Inclusive Data Task Force. RIO will ultimately help inform local authorities, government, charities and other organisations with resource allocation for these vulnerable populations. We are planning to make this dataset available to Accredited Researchers via the ONS Secure Research Service and the Integrated Data Service (IDS)

Reconsidering frameworks of Alzheimer’s dementia when assessing psychosocial outcomes

The purpose of this introductory article to the special issue on psychosocial outcome measures in Alzheimer’s & Dementia: Translational Research & Clinical Interventions is to outline new frameworks to more effectively capture and measure the full range of how people living with Alzheimer’s dementia and their family caregivers experience the disease process. Specifically, we consider the strengths and weaknesses of alternative perspectives, including person‐centered, strength‐based, and resilience‐focused approaches that may complement and extend the dominant deficit paradigm to reflect the entirety of the dementia experience. Our aim is to encourage innovative methods to measure psychosocial aspects of Alzheimer’s dementia and caregiving that have not yet received sufficient attention, including resources (e.g., services and supports) and positive caregiver and care recipient outcomes (e.g., positive mood and adaptation).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152840/1/trc2jtrci201902008.pd

Why test study protocol: a UK-wide audit using the primary care academic collaborative to explore the reasons for primary care testing

This is the author accepted manuscript. The final version is available on open access from the Royal College of General Practitioners via the DOI in this recordBackground The number of blood tests done in primary care has been increasing over the last 20 years. Some estimates suggest that up to a quarter of these tests may not have been needed. This could lead to a cascade effect of further investigations, appointments, or referrals, as well as anxiety for patients, increased workload and costs to the health service. To better understand the impact and sequelae of blood tests on patients, we need to know why blood tests are requested and what is done with the results. Aims To explore who orders blood tests and why, and how test results are actioned in primary care. Design & Setting Retrospective audit of electronic health records in general practices across the UK. Method The Primary care Academic CollaboraTive (PACT), a UK-wide network of primary care health professionals, will be utilised to collect data from individual practices. PACT members will be asked to review the electronic health records of 50 patients who had recent blood tests in their practice, and manually extract anonymised data on who requested the test, the indication, the result, and subsequent actions. Data will also be collected from PACT members to assess the feasibility of the collaborative model. Conclusion PACT offers a unique opportunity to extract clinical data which cannot otherwise be obtained. Understanding the indications for tests will help identify priority areas for research to optimise testing and patient safety in primary care.Bristol, North Somerset and South Gloucestershire Clinical Commissioning Grou

Insulin promotes Rip11 accumulation at the plasma membrane by inhibiting a dynamin- and PI3-kinase-dependent, but Akt-independent, internalisation event

Rip11 is a Rab11 effector protein that has been shown to be important in controlling the trafficking of several intracellular cargoes, including the fatty acid transporter FAT/CD36, V-ATPase and the glucose transporter GLUT4. We have previously demonstrated that Rip11 translocates to the plasma membrane in response to insulin and here we examine the basis of this regulated phenomenon in more detail. We show that Rip11 rapidly recycles between the cell interior and surface, and that the ability of insulin to increase the appearance of Rip11 at the cell surface involves an inhibition of Rip11 internalisation from the plasma membrane. By contrast the hormone has no effect on the rate of Rip11 translocation towards the plasma membrane. The ability of insulin to inhibit Rip11 internalisation requires dynamin and class I PI3-kinases, but is independent of the activation of the protein kinase Akt; characteristics which are very similar to the mechanism by which insulin inhibits GLUT4 endocytosis