an experimental approach with a trauma film paradigm

Background Intrusive memories of traumatic events are a core feature of post- traumatic stress disorder but little is known about the neurobiological formation of intrusions. The aim of this study was to determine whether the activity of the noradrenergic system during an intrusion-inducing stressor would influence subsequent intrusive memories. Method We conducted an experimental, double-blind, placebo-controlled study in 118 healthy women. Participants received a single dose of either 10 mg yohimbine, stimulating noradrenergic activity, or 0.15 mg clonidine, inhibiting noradrenergic activity, or placebo. Subsequently, they watched an established trauma film which induced intrusions. The number of consecutive intrusions resulting from the trauma film, the vividness of the intrusions, and the degree of distress evoked by the intrusions were assessed during the following 4 days. Salivary cortisol and α-amylase were collected before and after the trauma film. Results A significant time × treatment interaction for the number of intrusions and the vividness of intrusions indicated a different time course of intrusions depending on treatment. Post-hoc tests revealed a delayed decrease of intrusions and a delayed decrease of intrusion vividness after the trauma film in the yohimbine group compared with the clonidine and placebo groups. Furthermore, after yohimbine administration, a significant increase in salivary cortisol levels was observed during the trauma film. Conclusions Our findings indicate that pharmacological activation of the noradrenergic system during an emotionally negative event makes an impact on consecutive intrusive memories and their vividness in healthy women. The noradrenergic system seems to be involved in the formation of intrusive memories

The organisational and human resource challenges facing primary care trusts : protocol of a multiple case study

BACKGROUND: The study is designed to assess the organisational and human resource challenges faced by Primary Care Trusts (PCTs). Its objectives are to: specify the organisational and human resources challenges faced by PCTs in fulfilling the roles envisaged in government and local policy; examine how PCTs are addressing these challenges, in particular, to describe the organisational forms they have adopted, and the OD/HR strategies and initiatives they have planned or in place; assess how effective these structures, strategies and initiatives have been in enabling the PCTs to meet the organisational and human resources challenges they face; identify the factors, both internal to the PCT and in the wider health community, which have contributed to the success or failure of different structures, strategies and initiatives. METHODS: The study will be undertaken in three stages. In Stage 1 the key literature on public sector and NHS organisational development and human resources management will be reviewed, and discussions will be held with key researchers and policy makers working in this area. Stage 2 will focus on detailed case studies in six PCTs designed to examine the organisational and human resources challenges they face. Data will be collected using semi-structured interviews, group discussion, site visits, observation of key meetings and examination of local documentation. The findings from the case study PCTs will be cross checked with a Reference Group of up to 20 other PCG/Ts, and key officers working in organisational development or primary care at local, regional and national level. In Stage 3 analysis of findings from the preparatory work, the case studies and the feedback from the Reference Group will be used to identify practical lessons for PCTs, key messages for policy makers, and contributions to further theoretical development

East Midlands Research into Ageing Network (EMRAN) Discussion Paper Series

Academic geriatric medicine in Leicester . There has never been a better time to consider joining us. We have recently appointed a Professor in Geriatric Medicine, alongside Tom Robinson in stroke and Victoria Haunton, who has just joined as a Senior Lecturer in Geriatric Medicine. We have fantastic opportunities to support students in their academic pursuits through a well-established intercalated BSc programme, and routes on through such as ACF posts, and a successful track-record in delivering higher degrees leading to ACL post. We collaborate strongly with Health Sciences, including academic primary care. See below for more detail on our existing academic set-up. Leicester Academy for the Study of Ageing We are also collaborating on a grander scale, through a joint academic venture focusing on ageing, the ‘Leicester Academy for the Study of Ageing’ (LASA), which involves the local health service providers (acute and community), De Montfort University; University of Leicester; Leicester City Council; Leicestershire County Council and Leicester Age UK. Professors Jayne Brown and Simon Conroy jointly Chair LASA and have recently been joined by two further Chairs, Professors Kay de Vries and Bertha Ochieng. Karen Harrison Dening has also recently been appointed an Honorary Chair. LASA aims to improve outcomes for older people and those that care for them that takes a person-centred, whole system perspective. Our research will take a global perspective, but will seek to maximise benefits for the people of Leicester, Leicestershire and Rutland, including building capacity. We are undertaking applied, translational, interdisciplinary research, focused on older people, which will deliver research outcomes that address domains from: physical/medical; functional ability, cognitive/psychological; social or environmental factors. LASA also seeks to support commissioners and providers alike for advice on how to improve care for older people, whether by research, education or service delivery. Examples of recent research projects include: ‘Local History Café’ project specifically undertaking an evaluation on loneliness and social isolation; ‘Better Visits’ project focused on improving visiting for family members of people with dementia resident in care homes; and a study on health issues for older LGBT people in Leicester. Clinical Geriatric Medicine in Leicester We have developed a service which recognises the complexity of managing frail older people at the interface (acute care, emergency care and links with community services). There are presently 17 consultant geriatricians supported by existing multidisciplinary teams, including the largest complement of Advance Nurse Practitioners in the country. Together we deliver Comprehensive Geriatric Assessment to frail older people with urgent care needs in acute and community settings. The acute and emergency frailty units – Leicester Royal Infirmary This development aims at delivering Comprehensive Geriatric Assessment to frail older people in the acute setting. Patients are screened for frailty in the Emergency Department and then undergo a multidisciplinary assessment including a consultant geriatrician, before being triaged to the most appropriate setting. This might include admission to in-patient care in the acute or community setting, intermediate care (residential or home based), or occasionally other specialist care (e.g. cardiorespiratory). Our new emergency department is the county’s first frail friendly build and includes fantastic facilities aimed at promoting early recovering and reducing the risk of hospital associated harms. There is also a daily liaison service jointly run with the psychogeriatricians (FOPAL); we have been examining geriatric outreach to oncology and surgery as part of an NIHR funded study. We are home to the Acute Frailty Network, and those interested in service developments at the national scale would be welcome to get involved. Orthogeriatrics There are now dedicated hip fracture wards and joint care with anaesthetists, orthopaedic surgeons and geriatricians. There are also consultants in metabolic bone disease that run clinics. Community work Community work will consist of reviewing patients in clinic who have been triaged to return to the community setting following an acute assessment described above. Additionally, primary care colleagues refer to outpatients for sub-acute reviews. You will work closely with local GPs with support from consultants to deliver post-acute, subacute, intermediate and rehabilitation care services. Stroke Medicine 24/7 thrombolysis and TIA services. The latter is considered one of the best in the UK and along with the high standard of vascular surgery locally means one of the best performances regarding carotid intervention

Emergency care for older people living with frailty: patient and carer perspectives

Background Little is known about how frailty impacts on older people’s experiences of emergency care, despite patient experience being essential to providing person-centred care. This qualitative study reports on the experiences of older people with frailty in the ED and their and their carers’ preferences for emergency care. Methods Older people (aged 75+ years) who were at least mildly frail and/or their carers, with current or recent experience of emergency care, were recruited from three EDs in England between January and June 2019. Data were collected via semi-structured in-depth interviews which explored participants’ views on their recent experience of emergency care and their priorities and preferred outcomes. Interviews were audio-recorded, transcribed verbatim and analysed following the principles of the Framework approach. Results Forty participants were interviewed: 24 patients and 16 carers who, between them, described ED attendances for 28 patients across the three sites. Often informed by previous negative experiences, there was a strong desire to avoid conveyance to EDs, and a sense of helplessness or acquiescence to attend. Although staff attitudes were on the whole seen as positive, the ED experience was dominated by negative experiences relating to very basic issues such as a lack of help with eating, drinking, toileting and discomfort from long waits on hard trolleys. Participants reported that communication and involvement in decision making could be improved, including involving next of kin, who were viewed as critical to supporting vulnerable older people during sometimes very protracted waits. Conclusion Frailty reflects a vulnerability and a need for support in basic activities of daily living, which EDs in this study, and perhaps more widely, are not set up to provide. Changes at the levels of clinical practice and service design are required to deliver even the most basic care for older people with frailty in the ED environment

What matters most in acute care: an interview study with older people living with frailty

Background Healthcare outcome goals are central to person-centred acute care, however evidence among older people is scarce. Older people who are living with frailty have distinct requirements for healthcare delivery and have distinct risk for adverse outcomes from healthcare. There is insufficient evidence for whether those living with frailty also have distinct healthcare outcome goals. This study explored the nature of acute care outcome goals in people living with frailty. Methods Healthcare outcome goals were explored using semi-structured patient interviews. Participants aged over 65 with Clinical Frailty Score 5-8 (mild to very severe frailty) were recruited during their first 72 hours in a UK hospital. Purposive, maximum variation sampling was guided by lay partners from a Patient and Public Involvement Forum specialising in ageing-related research. Qualitative analysis used a blended approach based on framework and constant comparative methodologies for the identification of themes. Findings were validated through triangulation with participant, lay partner, and technical expert review. Results The 22 participants were aged 71 to 98 and had mild to very severe frailty. One quarter were living with dementia. Most participants had reflected on their situation and considered their outcome goals. Theme categories (and corresponding sub-categories) were ‘Autonomy’ (information, control, and security) and ‘Functioning’ (physical, psychosocial, and relief). A novel ‘security’ theme was identified, whereby participants sought to feel safe in their usual living place and with their health problems. Those living with milder frailty were concerned to maintain ability to support loved ones, while those living with most severe frailty were concerned about burdening others. Conclusions Outcome goals for acute care among older participants living with frailty were influenced by the insecurity of their situation and fear of deterioration. Patients may be supported to feel safe and in control through appropriate information provision and functional support

Identifying models of care to improve outcomes for older people with urgent care needs: a mixed methods approach to develop a system dynamics model

Background We aimed to understand urgent and emergency care pathways for older people and develop a decision support tool using a mixed methods study design. Objective(s), study design, settings and participants Work package 1 identified best practice through a review of reviews, patient, carer and professional interviews. Work package 2 involved qualitative case studies of selected urgent and emergency care pathways in the Yorkshire and Humber region. Work package 3 analysed linked databases describing urgent and emergency care pathways identifying patient, provider and pathway factors that explain differences in outcomes and costs. Work package 4 developed a system dynamics tool to compare emergency interventions. Results A total of 18 reviews summarising 128 primary studies found that integrated social and medical care, screening and assessment, follow-up and monitoring of service outcomes were important. Forty patient/carer participants described emergency department attendances; most reported a reluctance to attend. Participants emphasised the importance of being treated with dignity, timely and accurate information provision and involvement in decision-making. Receiving care in a calm environment with attention to personal comfort and basic physical needs were key. Patient goals included diagnosis and resolution, well-planned discharge home and retaining physical function. Participants perceived many of these goals of care were not attained. A total of 21 professional participants were interviewed and 23 participated in focus groups, largely confirming the review evidence. Implementation challenges identified included the urgent and emergency care environment, organisational approaches to service development, staff skills and resources. Work package 2 involved 45 interviews and 30 hours of observation in four contrasting emergency departments. Key themes relating to implementation included: intervention-related staff: frailty mindset and behaviours resources: workforce, space, and physical environment operational influences: referral criteria, frailty assessment, operating hours, transport. context-related links with community, social and primary care organisation and management support COVID-19 pandemic. approaches to implementation service/quality improvement networks engaging staff and building relationships education about frailty evidence. The linked databases in work package 3 comprised 359,945 older people and 1,035,045 observations. The most powerful predictors of four-hour wait and transfer to hospital were age, previous attendance, out-of-hours attendance and call handler designation of urgency. Drawing upon the previous work packages and working closely with a wide range of patient and professional stakeholders, we developed an system dynamics tool that modelled five evidence-based urgent and emergency care interventions and their impact on the whole system in terms of reducing admissions, readmissions, and hospital related mortality. Limitations Across the reviews there was incomplete reporting of interventions. People living with severe frailty and from ethnic minorities were under-represented in the patient/carer interviews. The linked databases did not include patient reported outcomes. The system dynamics model was limited to evidence-based interventions, which could not be modelled conjointly. Conclusions We have reaffirmed the poor outcomes frequently experienced by many older people living with urgent care needs. We have identified interventions that could improve patient and service outcomes, as well as implementation tools and strategies to help including clinicians, service managers and commissioners improve emergency care for older people. Future work Future work will focus on refining the system dynamics model, specifically including patient-reported outcome measures and pre-hospital services for older people living with frailty who have urgent care needs. Study registrations This study is registered as PROSPERO CRD42018111461. WP 1.2: University of Leicester ethics: 17525-spc3-ls:healthsciences, WP 2: IRAS 262143, CAG 19/CAG/0194, WP 3: IRAS 215818, REC 17/YH/0024, CAG 17/CAG/0024. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme [project number 17/05/96 (Emergency Care for Older People)] and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 14. See the NIHR Journals Library website for further project information

Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis

Date of Acceptance: 27/08/2015 Funding was provided by the Wellcome Trust grant WT081633MA-NCE and Biological Sciences Research Council Grant BB/K001043/1. Prof Fragoso is the recipient of a Post Doctoral Science without Borders grant from the Brazilian National Council for Scientific and Technological Development (CNPq, 237450/2012-7).Peer reviewedPublisher PD

Identification and Characterization of the RLIP/RALBP1 Interacting Protein Xreps1 in Xenopus laevis Early Development

Background: The FGF/Ras/Ral/RLIP pathway is required for the gastrulation process during the early development of vertebrates. The Ral Interacting Protein (RLIP also known as RalBP1) interacts with GTP-bound Ral proteins. RLIP/RalBP1 is a modular protein capable of participating in many cellular functions. Methodology/Principal Findings: To investigate the role of RLIP in early development, a two-hybrid screening using a library of maternal cDNAs of the amphibian Xenopus laevis was performed. Xreps1 was isolated as a partner of RLIP/RalBP1 and its function was studied. The mutual interacting domains of Xreps1 and Xenopus RLIP (XRLIP) were identified. Xreps1 expressed in vivo, or synthesized in vitro, interacts with in vitro expressed XRLIP. Interestingly, targeting of Xreps1 or the Xreps1-binding domain of XRLIP (XRLIP(469–636)) to the plasma membrane through their fusion to the CAAX sequence induces a hyperpigmentation phenotype of the embryo. This hyperpigmented phenotype induced by XRLIP(469–636)-CAAX can be rescued by co-expression of a deletion mutant of Xreps1 restricted to the RLIP-binding domain (Xreps1(RLIP-BD)) but not by co-expression of a cDNA coding for a longer form of Xreps1. Conclusion/Significance: We demonstrate here that RLIP/RalBP1, an effector of Ral involved in receptor-mediated endocytosis and in the regulation of actin dynamics during embryonic development, also interacts with Reps1. Although these two proteins are present early during embryonic development, they are active only at the end of gastrulation. Ou