Search

The approach to stabilizing a quantum state by coupling to engineered reservoirs is limited by a trade-off between state fidelity and stabilization rate. Here the authors implement a protocol based on parametric system-bath coupling to achieve fast and high-fidelity Bell state stabilization in a qutrit-qubit system.

Poor adolescent mental health calls for universal prevention. The Mental Health Foundation's 'Peer Education Project' equips older students ('peer educators') to teach younger students ('peer learners') about mental health. The peer-led lessons cover defining good and bad mental health, risk and protective factors, self-care, help-seeking and looking after one another. While previous pre-post evaluations have suggested effectiveness, the mechanisms through which the intervention improves mental health literacy remain unclear. We purposively recruited seven secondary schools across England from 2020 to 2022 and collected data through five observations, 12 staff interviews and 15 student focus groups (totalling 134 students; 46 peer educators aged 14-18 years and 88 peer learners aged 11-13 years). Our realist analysis adopted retroductive logic, intertwining deductive and inductive approaches to test the initial programme theory against insights arising from the data. We developed Context - Mechanisms - Outcome configurations related to four themes: (i) modelling behaviours and forming supportive relationships, (ii) relevant and appropriate content, (iii) peer educators feeling empowered and (iV) a school culture that prioritises mental health support. Our refined programme theory highlights key mechanisms, contexts conducive to achieving the outcomes and ways to improve training, recruitment and delivery to maximise effectiveness for similar peer-led initiatives.

The Radiation Protection Division of the Health Protection Agency (HPA-RPD), formerly the National Radiological Protection Board, has periodically reported the doses to members of the public and workers in the UK from all sources of radiation. This paper is a review of the doses reported in these publications from the 1970s to 2000 or later. The paper aims to present how the estimated doses received by the UK population have changed over this time period, and where possible from earlier years as well, from all sources of radiation. It was not possible to directly compare the doses reported in the earlier reports. There have been changes in the type of doses estimated, the dosimetry (in particular the definition of effective dose) and improvements made in the measurement of natural background doses. In these cases the earlier reported doses have been recalculated using modern dosimetry so that the doses can be compared. The occupational doses reported in this paper are for those workers involved in the civil nuclear power production industry, industrial radiography or from the medical use of radiation sources. For workers it was found that the individual and collective dose has decreased significantly over this time through the introduction of legislation, the improvement in technology and better working practices. Members of the public are exposed to radiation following the atmospheric testing of nuclear weapons, discharges from UK civil nuclear sites and from diagnostic radiology as well as from natural sources. Exposure to anthropogenic sources has decreased over the period considered in this paper. However, the dose to the UK population as a whole, presented as a per caput dose to a population of 55 million, has not changed significantly as it is dominated by the constant level of exposure to natural sources of radiation. [ABSTRACT FROM AUTHOR]

A localized Zeeman field, intensified at heterostructure interfaces, could play a crucial role in a broad area including spintronics and unconventional superconductors. Conventionally, the generation of a local Zeeman field is achieved through magnetic exchange coupling with a magnetic material. However, magnetic elements often introduce defects, which could weaken or destroy superconductivity. Alternatively, the coupling between a superconductor with strong spin-orbit coupling and a nonmagnetic chiral material could serve as a promising approach to generate a spin-active interface. Here, we leverage an interface superconductor, namely, induced superconductivity in noble metal surface states, to probe the spin-active interface. Our results unveil an enhanced interface Zeeman field, which selectively closes the surface superconducting gap while preserving the bulk superconducting pairing. The chiral material, i.e., trigonal tellurium, also induces Andreev bound states (ABS) exhibiting spin polarization. The field dependence of ABS manifests a substantially enhanced interface Landé g -factor ( g eff ~ 12), thereby corroborating the enhanced interface Zeeman energy.

Introduction: Peer education interventions are widely used in secondary schools with an aim to improve students' health literacy and/or health behaviours. Although peer education is a popular intervention technique with some evidence of effectiveness, we know relatively little about the key components that lead to health improvements among young people, or components that may be less helpful. This review aims to identify the main mechanisms involved in school-based peer education health interventions for 11-18-year-olds., Methods: Five electronic databases were searched for eligible studies during October 2020, an updated search was then conducted in January 2023 to incorporate any new studies published between November 2020 and January 2023. To be included in the review, studies must have evaluated a school-based peer education intervention designed to address aspects of the health of students aged 11-18 years old and contain data relevant to mechanisms of effect of these interventions. No restrictions were placed on publication date, or country but only manuscripts available in English language were included., Results: Forty papers were identified for inclusion with a total of 116 references to intervention mechanisms which were subsequently grouped thematically into 10 key mechanisms. The four most common mechanisms discussed were: 1) Peerness; similar, relatable and credible 2) A balance between autonomy and support, 3) School values and broader change in school culture; and 4) Informal, innovative and personalised delivery methods. Mechanisms were identified in quantitative, qualitative and mixed methods intervention evaluations., Discussion: This study highlights a number of key mechanisms that can be used to inform development of future school-based peer education health interventions to maximise effectiveness. Future studies should aim to create theories of change or logic models, and then test the key mechanisms, rather than relying on untested theoretical assumptions. Future work should also examine whether particular mechanisms may lead to harm, and also whether certain mechanisms are more or less important to address different health issues, or whether a set of generic mechanisms always need to be activated for success., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Widnall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Poor adolescent mental health calls for universal prevention. The Mental Health Foundation's 'Peer Education Project' equips older students ('peer educators') to teach younger students ('peer learners') about mental health. The peer-led lessons cover defining good and bad mental health, risk and protective factors, self-care, help-seeking and looking after one another. While previous pre-post evaluations have suggested effectiveness, the mechanisms through which the intervention improves mental health literacy remain unclear. We purposively recruited seven secondary schools across England from 2020 to 2022 and collected data through five observations, 12 staff interviews and 15 student focus groups (totalling 134 students; 46 peer educators aged 14-18 years and 88 peer learners aged 11-13 years). Our realist analysis adopted retroductive logic, intertwining deductive and inductive approaches to test the initial programme theory against insights arising from the data. We developed Context-Mechanisms-Outcome configurations related to four themes: (i) modelling behaviours and forming supportive relationships, (ii) relevant and appropriate content, (iii) peer educators feeling empowered and (iV) a school culture that prioritises mental health support. Our refined programme theory highlights key mechanisms, contexts conducive to achieving the outcomes and ways to improve training, recruitment and delivery to maximise effectiveness for similar peer-led initiatives., (© The Author(s) 2023. Published by Oxford University Press.)

Many mental health problems begin in adolescence and occur on a spectrum of severity: early recognition and intervention is important. This study is a quantitative feasibility study of the Mental Health Foundation's Peer Education Project (PEP). Attrition, psychometric properties of questionnaires, indications of improvement on a range of outcomes, and sample size required for a powered trial of effectiveness were assessed. 203 students completed the survey both pre and post-intervention. It was found that existing previously-validated measures had good psychometric properties, with two new questionnaires demonstrating reasonable reliability (self-help confidence alpha = 0.78, mental health knowledge alpha = 0.59). There were indications of improvement in help-seeking intentions, the number of sources likely to seek help from, and mental health knowledge from pre- to post-intervention. A future trial of PEP with a sample of approximately 36 schools, researcher-led data collections, and help-seeking intentions or sources as a primary outcome appears to be feasible., (© 2023. The Author(s).)

Equine viral arteritis is an infectious disease of equids caused by equine arteritis virus (EAV), an RNA virus of the family Arteriviridae. Dendritic cells (DC) are important modulators of the immune response with the ability to present antigen to naïve T cells and can be generated in vitro from monocytes (MoDC). DC are important targets for many viruses and this interaction is crucial for the establishment-or rather not-of an anti-viral immunity. Little is known of the effect EAV has on host immune cells, particularly DC. To study the interaction of eqDC with EAV in vitro, an optimized eqMoDC system was used, which was established in a previous study. MoDC were infected with strains of different genotypes and pathogenicity. Virus replication was determined through titration and qPCR. The effect of the virus on morphology, phenotype and function of cells was assessed using light microscopy, flow cytometry and in vitro assays. This study confirms that EAV replicates in monocytes and MoDC. The replication was most efficient in mature MoDC, but variable between strains. Only the virulent strain caused a significant down-regulation of certain proteins such as CD14 and CD163 on monocytes and of CD83 on mature MoDC. Functional studies conducted after infection showed that EAV inhibited the endocytic and phagocytic capacity of Mo and mature MoDC with minimal effect on immature MoDC. Infected MoDC showed a reduced ability to stimulate T cells. Ultimately, EAV replication resulted in an apoptosis-mediated cell death. Thus, EAV evades the host anti-viral immunity both by inhibition of antigen presentation early after infection and through killing infected DC during replication.

Introduction: Peer education, whereby peers ('peer educators') teach their other peers ('peer learners') about aspects of health is an approach growing in popularity across school contexts, possibly due to adolescents preferring to seek help for health-related concerns from their peers rather than adults or professionals. Peer education interventions cover a wide range of health areas but their overall effectiveness remains unclear. This review aims to summarise the effectiveness of existing peer-led health interventions implemented in schools worldwide., Methods: Five electronic databases were searched for eligible studies in October 2020. To be included, studies must have evaluated a school-based peer education intervention designed to address the health of students aged 11-18-years-old and include quantitative outcome data to examine effectiveness. The number of interventions were summarised and the impact on improved health knowledge and reductions in health problems or risk-taking behaviours were investigated for each health area separately, the Mixed Methods Appraisal Tool was used to assess quality., Results: A total of 2125 studies were identified after the initial search and 73 articles were included in the review. The majority of papers evaluated interventions focused on sex education/HIV prevention (n = 23), promoting healthy lifestyles (n = 17) and alcohol, smoking and substance use (n = 16). Papers mainly reported peer learner outcomes (67/73, 91.8%), with only six papers (8.2%) focussing solely on peer educator outcomes and five papers (6.8%) examining both peer learner and peer educator outcomes. Of the 67 papers reporting peer learner outcomes, 35/67 (52.2%) showed evidence of effectiveness, 8/67 (11.9%) showed mixed findings and 24/67 (35.8%) found limited or no evidence of effectiveness. Of the 11 papers reporting peer educator outcomes, 4/11 (36.4%) showed evidence of effectiveness, 2/11 (18.2%) showed mixed findings and 5/11 (45.5%) showed limited or no evidence of effectiveness. Study quality varied greatly with many studies rated as poor quality, mainly due to unrepresentative samples and incomplete data., Discussion: School-based peer education interventions are implemented worldwide and span a wide range of health areas. A number of interventions appear to demonstrate evidence for effectiveness, suggesting peer education may be a promising strategy for health improvement in schools. Improvement in health-related knowledge was most common with less evidence for positive health behaviour change. In order to quantitatively synthesise the evidence and make more confident conclusions, there is a need for more robust, high-quality evaluations of peer-led interventions using standardised health knowledge and behaviour measures., (© 2022. The Author(s).)

Background: Worsening of adolescent mental health and exacerbated health inequalities after the COVID-19 pandemic calls for universal preventative strategies. The Mental Health Foundation's school-based Peer Education Project seeks to improve students' mental health literacy through peer educators (aged 14-18 years) teaching peer learners (aged 11-13 years) to recognise good and bad mental health, identify risk and protective factors, and seek help accordingly. Although previous before and after quantitative assessments have found the intervention to be effective, this realist evaluation aimed to qualitatively develop the theory of change, exploring how the mechanisms played out in different contexts to achieve the desired outcomes., Methods: Our initial programme theory was developed following expert stakeholder consultation and reviewing the literature. We divided mechanisms into resources and reasoning to explain how the intervention components (ie, resources), experienced within specific contexts, engendered responses in the participants (ie, reasoning), to produce observable outcomes. Data collected from six purposively recruited schools in England comprised staff interviews (n=11), student focus groups (n=15), and observations (n=5). Deductive and inductive analysis was undertaken, using NVivo-informed multiple causal statements represented as context-mechanism-outcome configurations (CMOcs), to test and refine the programme theory., Findings: We created several distinct CMOcs. For example, in learners accustomed to didactic teaching methods (context), conversing with educators having similar life experience (mechanism resource) endorsed and destigmatised help-seeking behaviour (mechanism reasoning) and facilitated a realisation that seeking help was appropriate and acceptable (outcome). Other mechanisms included the following: learners perceiving the information as tailored and relevant, educators feeling empowered, and a cultural shift percolating across the school., Interpretation: Our findings show how peer education can work to improve mental health literacy, which will inform changes to the intervention to maximise its effectiveness in different operational contexts. Future research could test our theory of change in a randomised controlled trial, and examine impacts on inequalities in a more diverse sample., Funding: National Institute for Health and Care Research School for Public Health Research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Quantum reservoir engineering is a powerful framework for autonomous quantum state preparation and error correction. However, traditional approaches to reservoir engineering are hindered by unavoidable coherent leakage out of the target state, which imposes an inherent trade off between achievable steady-state state fidelity and stabilization rate. In this work we demonstrate a protocol that achieves trade off-free Bell state stabilization in a qutrit-qubit system realized on a circuit-QED platform. We accomplish this by creating a purely dissipative channel for population transfer into the target state, mediated by strong parametric interactions coupling the second-excited state of a superconducting transmon and the engineered bath resonator. Our scheme achieves a state preparation fidelity of 84% with a stabilization time constant of 339 ns, leading to a 54 ns error-time product in a solid-state quantum information platform., (© 2022. The Author(s).)

Introduction: Clinical use of mobile phones have increased exponentially. Whilst evidence of contamination is documented, a key factor when determining potential risks of contamination, is establishing the duration the organism remains viable on the device. If pathogens are found to persist for extended duration, healthcare mobile phones may become fomites for cross departmental transmission., Aim: Determine the duration pathogenic bacteria, Acinetobacter baumannii, Escherichia coli, two Pseudomonas sp. Bacillus cereus, Enterococcus faecalis susceptible and resistant to vancomycin (VSE and VRE) Staphylococcus aureus susceptible and resistant to methicillin (MSSA and MRSA), and a coagulase negative Staphylococcus (CoNs) can remain viable on a mobile phone under controlled conditions., Method: Phones were inoculated with 10 6 - 10 7 of each bacterium. The duration of viability was measured from the point the inoculum had dried and CFUs retrieved at timed intervals over 28 days., Results: The mean percentage of bacteria viable at each time point was significantly different (20mins, P = .004, 1 hour P = .014, 6 hours P = .006, 24 hours P = .004, 7 days P = .007, 14 days P = .003, 21 days P = .002- and 28 days P = .004). Gram-positive bacteria remained viable longer than gram-negative bacteria (P = .010). MSSA declined faster than MRSA within the first 6 hours (P = .036)., Conclusions: The extended duration of bacterial viability indicates the ability for pathogens to persist on a device and remain viable long enough to be transmitted to new areas both within the hospital and out to the community. Mobile phone decontamination should occur in combination of hand hygiene., (Copyright © 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: During the decades representing working-age adulthood, most people will experience one or several significant life events or transitions. These may present a challenge to mental health., Aim: The primary aim of this rapid systematic review of systematic reviews was to summarise available evidence on the effectiveness of interventions to promote and protect mental health relating to four key life events and transitions: pregnancy and early parenthood, bereavement, unemployment, and housing problems. This review was conducted to inform UK national policy on mental health support., Methods: We searched key databases for systematic reviews of interventions for working-age adults (19 to 64 years old) who had experienced or were at risk of experiencing one of four key life events. Titles and abstracts were screened by two reviewers in duplicate, as were full-text manuscripts of relevant records. We assessed the quality of included reviews and extracted data on the characteristics of each literature review. We prioritised high quality, recent systematic reviews for more detailed data extraction and synthesis., Results: The search and screening of 3997 titles/abstracts and 239 full-text papers resulted in 134 relevant studies, 68 of which were included in a narrative synthesis. Evidence was strongest and of the highest quality for interventions to support women during pregnancy and after childbirth. For example, we found benefits of physical activity and psychological therapy for outcomes relating to mental health after birth. There was high quality evidence of positive effects of online bereavement interventions and psychological interventions on symptoms of grief, post-traumatic stress, and depression. Evidence was inconclusive and of lower quality for a range of other bereavement interventions, unemployment support interventions, and housing interventions., Conclusions: Whilst evidence based mental health prevention and promotion is available during pregnancy and early parenthood and for bereavement, it is unclear how best to support adults experiencing job loss, unemployment, and housing problems.

There has been much discussion recently that better healthcare systems lead to increased service access and utilisation. However, there are still concerns raised among the refugee and immigrant communities about barriers to access and utilisation of primary healthcare services in the UK. This study aimed to explore with refugee and immigrant community health champions (CHCs) their perceptions about such barriers based on feedback in their own discussions with fellow refugees, asylum-seekers and immigrants in the West Midlands, UK. A total of 42 refugees and immigrants were recruited. Qualitative design-focused group discussions were conducted among purposively selected participants. These discussions were conducted between May and September 2019, and data were analysed using thematic analysis. The barriers to service access and utilisation are categorised into four themes: (i) knowledge about health issues that most affected refugees and immigrants; (ii) community indications of factors that obstructed service access; (iii) challenges in identifying local teams involved in service provision; and (iv) accurate knowledge about the different teams and their roles in facilitating access. This study higlighted that the levels of service access and utilisation would depend on the competence and effectiveness of the health system. Urgency and seriousness of individuals' healthcare needs were the factors that were perceived to strongly influence refugees and immigrants to seek and utilise local services. We identified a number of potential barriers and challenges to service access and utilisation that should be overcome if primary healthcare service is to be planned and delivered effectively, efficiently and equitably in the West Midlands., (© 2021. The Author(s).)

Abstract We investigated the effects of taurine supplementation on cycling time to exhaustion in cold conditions. Eleven males cycled to exhaustion at a power output equivalent to the mid-point between ventilatory threshold and maximum aerobic power following 15-min rest in the cold (apparent temperature of ∼ 4°C; air flow of 4.17 m s -1 ). Two hours before, participants ingested taurine (50 mg·kg -1 ) or placebo beverage. Pulmonary gases, carbohydrate (CHO) and fat oxidation, body temperatures, mean local sweat rate, heart rate, rate of perceived exertion (RPE) and thermal comfort were recorded. Time to exhaustion was not different between trials (taurine = 14.6 ± 4.7 min; placebo = 13.4 ± 5.6 min, P  = 0.061, d  = 0.27). There were no effects ( P  > 0.05) of taurine on core temperature, mean skin temperature or local sweat rates. However, the placebo condition showed greater ( P  < 0.05) reductions in arm-to-finger temperature gradient (i.e. vasodilation) across pre-exercise passive cold exposure and increased CHO oxidation ( P  < 0.05). Participants also reached a thermally 'comfortable' level quicker in the taurine condition ( P  < 0.05). A 50 mg·kg -1 dose of taurine did not statistically benefit endurance exercise after moderate cold exposure but conferred some potential vascular and metabolic effects.

Background: Emotional disorders in young people are increasing but studies have found that this age group do not always recognise the signs and symptoms of mental health problems in themselves or others. The Mental Health Foundation's school-based Peer Education Project (PEP) has the potential to improve young people's understanding of their own mental health at a critical developmental stage (early adolescence) using a peer teaching method. This study is a process evaluation to understand: the mechanisms through which PEP might improve young people's mental health literacy, any challenges with delivery, how the project can be embedded within wider school life and how it can be improved to be of most benefit to the widest number of young people. We will also validate a bespoke mental health literacy questionnaire, and test the feasibility of using it to measure outcomes in preparation for a future study evaluating effectiveness., Methods: All schools recruited to the study will receive the PEP intervention. The process evaluation will be informed by realist evaluation approaches to build understanding regarding key mechanisms of change and the impact of different school contexts. The evaluation will test and revise an existing intervention logic model which has been developed in partnership with the Mental Health Foundation. Process evaluation data will be collected from newly recruited schools (n = 4) as well as current PEP user schools (n = 2) including training and lesson delivery observations, staff interviews and student focus groups. Baseline and follow-up data will be collected in all newly recruited intervention schools (n = 4) from all students in Year 7/8 (who receive the PEP) and recruited peer educators in Year 12 via a self-report survey., Discussion: This study will enable us to refine the logic model underpinning the peer education project and identify areas of the intervention that can be improved. Findings will also inform the design of a future effectiveness study which will test out the extent to which PEP improves mental health literacy., (© 2021. The Author(s).)

Background: The WHO and National Institute for Health and Care Excellence recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to compare the accuracy of triage tools for predicting severe illness in adults presenting to the ED with suspected COVID-19., Methods: We undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the UK. We collected data from people attending with suspected COVID-19 and used presenting data to determine the results of assessment with the WHO algorithm, National Early Warning Score version 2 (NEWS2), CURB-65, CRB-65, Pandemic Modified Early Warning Score (PMEWS) and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome., Results: We analysed data from 20 891 adults, of whom 4611 (22.1%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2553 (12.2%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point rule) 0.70; SFAHP (7-point rule) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.97 and 0.95, respectively) at the expense of specificity (0.30 and 0.27, respectively). The NEWS2 score showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used., Conclusion: CURB-65, PMEWS and the NEWS2 score provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity., Trial Registration Number: ISRCTN56149622., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Measurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19., Methods: We undertook a substudy of an observational cohort study across 70 emergency departments during the first wave of the COVID-19 pandemic in the UK. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. We constructed receiver-operating characteristic curves, calculated diagnostic parameters, and developed a multivariable model for predicting adverse outcome., Results: We analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% CI 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were, respectively, 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019)., Conclusions: Post-exertion oxygen saturation provides modest prognostic information in the assessment of selected patients attending the emergency department with suspected COVID-19., Trial Registration Number: ISRCTN Registry (ISRCTN56149622) http://www.isrctn.com/ISRCTN28342533., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

During the UK's COVID-19 pandemic lockdown there was national guidance to suspend routine dermatology work. As a consequence, over 800 patient appointments in a district general dermatology department were temporarily suspended. Remote consultations were carried out to triage and manage referrals, via telephone or video consultations. Data were prospectively recorded on 488 patient interactions. Outcomes included advice/treatment, discharge, surgery or clinic review; 25% of patients were either uncontactable or their problem had resolved. Over a third of referrals were discharged with advice/treatment initiated remotely; 56% of referred dermatoses required further clinical review; 25% of lesion referrals were booked directly to surgery. This process was time-intensive for the clinicians involved, and triage mechanisms could be improved. Sufficient referral information allows remote diagnosis; implementation of management plans and appropriate discharge of patients. This process has been shown to be feasible, and may be a temporary solution for other COVID-19 impacted dermatology departments., (© 2020 British Association of Dermatologists.)

Background: Hospital emergency departments play a crucial role in the initial assessment and management of suspected COVID-19 infection. This needs to be guided by studies of people presenting with suspected COVID-19, including those admitted and discharged, and those who do not ultimately have COVID-19 confirmed. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results., Methods and Findings: We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Mean age was 58.4 years, 11200 (50.4%) were female and 11034 (49.6%) male. Adults (age >16 years) were acutely unwell (median NEWS2 score of 4), frequently had limited performance status (46.9%) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.5%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Similar numbers of men and women presented to the ED, but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.2% v 13.0%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to have impaired performance status (43.1%, 26.8% and 51.6%), be admitted to hospital (60.8%, 57.3%, 69.6%) or die (11.6%, 11.2%, 16.4%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with suspected and confirmed COVID-19 had similar age, performance status and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.1% v 15.5%)., Conclusions: Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. Adults and children differ markedly and require different approaches to emergency triage. Admission and adverse outcome rates among adults suggest that policies to avoid unnecessary ED attendance achieved their aim. Subsequent COVID-19 confirmation confers a worse prognosis and greater need for organ support., Registration: ISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533., Competing Interests: All authors declare grant funding to their employing institutions from the National Institute for Health Research (NIHR), as outlined under financial disclosure information. SG is Deputy Director of the NIHR Health Technology Assessment (HTA) Programme, which funded the study, and chairs the NIHR HTA commissioning committee. These competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Smartphones used in clinical settings harbour potentially pathogenic bacteria, and this may pose an infection risk. Previous studies have relied on culture-based methods., Aim: To characterize the quantity and diversity of microbial contamination of hospital staff smartphones using culture-dependent and culture-independent methods; to determine the prevalence of antibiotic-resistant potential pathogens; to compare microbial communities of hospital staff and control group phones., Methods: Smartphones of 250 hospital staff and 191 control group participants were swabbed. The antibiotic resistance profile of Staphylococcus aureus and Enterococcus isolates was determined. Swabs were pooled into groups according to the hospital area staff worked in, and DNA was extracted. The microbial community of the phone was characterized using an Illumina MiSeq metabarcoding pipeline., Findings: Almost all (99.2%) of hospital staff smartphones were contaminated with potential pathogens, and bacterial colony forming units (CFUs) were significantly higher on hospital phones than in the control group. Meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) were only detected on hospital mobile phones. Metabarcoding revealed a far greater abundance of Gram-negative contaminants, and much greater diversity, than culture-based methods. Bacillus spp. were significantly more abundant in the hospital group., Conclusion: This study reinforces the need to consider infection-control policies to mitigate the potential risks associated with the increased use of smartphones in clinical environments, and highlights the limitations of culture-based methods for environmental swabbing., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Rationale: There is a need to develop imaging protocols which assess neutrophilic inflammation in the lung., Aim: To quantify whole lung neutrophil accumulation in (1) healthy volunteers (HV) following inhaled lipopolysaccharide (LPS) or saline and (2) patients with COPD using radiolabelled autologous neutrophils and single-photon emission computed tomography/CT (SPECT/CT)., Methods: 20 patients with COPD (Global initiative for chronic obstructive lung disease (GOLD) stages 2-3) and 18 HVs were studied. HVs received inhaled saline (n=6) or LPS (50 µg, n=12) prior to the injection of radiolabelled cells. Neutrophils were isolated using dextran sedimentation and Percoll plasma gradients and labelled with 99m Technetium (Tc)-hexamethylpropyleneamine oxime. SPECT was performed over the thorax/upper abdomen at 45 min, 2 hours, 4 hours and 6 hours. Circulating biomarkers were measured prechallenge and post challenge. Blood neutrophil clearance in the lung was determined using Patlak-Rutland graphical analysis., Results: There was increased accumulation of 99m Tc-neutrophils in the lungs of patients with COPD and LPS-challenged subjects compared with saline-challenged subjects (saline: 0.0006±0.0003 mL/min/mL lung blood distribution volume [mean ±1 SD]; COPD: 0.0022±0.0010 mL/min/mL [p<0.001]; LPS: 0.0025±0.0008 mL/min/mL [p<0.001]). The accumulation of labelled neutrophils in 10 patients with COPD who underwent repeat radiolabelling/imaging 7-10 days later was highly reproducible (0.0022±0.0010 mL/min/mL vs 0.0023±0.0009 mL/min/mL). Baseline interleukin (IL)-6 levels in patients with COPD were elevated compared with HVs (1.5±1.06 pg/mL [mean ±1 SD] vs 0.4±0.24 pg/mL). LPS challenge increased the circulating IL-6 levels (7.5±2.72 pg/mL) 9 hours post challenge., Conclusions: This study shows the ability to quantify 'whole lung' neutrophil accumulation in HVs following LPS inhalation and in subjects with COPD using autologous radiolabelled neutrophils and SPECT/CT imaging. Moreover, the reproducibility observed supports the feasibility of using this approach to determine the efficacy of therapeutic agents aimed at altering neutrophil migration to the lungs., Competing Interests: Competing interests: MB, AC, KP, SM, JM, ML, GB, EJ, MdG, FW and EMH are employees of GSK. NT, NF, RS, DG, CS, AW, JB, AMP and ERC have no competing interests to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

GM-CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM-CSF receptor (GM-CSFRα) complex, a process essential for signaling. Whereas GM-CSF controls many aspects of neutrophil biology, regulation of GM-CSFRα expression is poorly understood, particularly the role of GM-CSFRα in ligand clearance and whether signaling is sustained despite major down-regulation of GM-CSFRα surface expression. We established a quantitative assay of GM-CSFRα surface expression and used this, together with selective anti-GM-CSFR antibodies, to define GM-CSFRα kinetics in human neutrophils, and in murine blood and alveolar neutrophils in a lung injury model. Despite rapid sustained ligand-induced GM-CSFRα loss from the neutrophil surface, which persisted even following ligand removal, pro-survival effects of GM-CSF required ongoing ligand-receptor interaction. Neutrophils recruited to the lungs following LPS challenge showed initially high mGM-CSFRα expression, which along with mGM-CSFRβ declined over 24 hr; this was associated with a transient increase in bronchoalveolar lavage fluid (BALF) mGM-CSF concentration. Treating mice in an LPS challenge model with CAM-3003, an anti-mGM-CSFRα mAb, inhibited inflammatory cell influx into the lung and maintained the level of BALF mGM-CSF. Consistent with neutrophil consumption of GM-CSF, human neutrophils depleted exogenous GM-CSF, independent of protease activity. These data show that loss of membrane GM-CSFRα following GM-CSF exposure does not preclude sustained GM-CSF/GM-CSFRα signaling and that this receptor plays a key role in ligand clearance. Hence neutrophilic activation via GM-CSFR may play an important role in neutrophilic lung inflammation even in the absence of high GM-CSF levels or GM-CSFRα expression., (©2018 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc.)

Ipomoeassin F is a potent natural cytotoxin that inhibits growth of many tumor cell lines with single-digit nanomolar potency. However, its biological and pharmacological properties have remained largely unexplored. Building upon our earlier achievements in total synthesis and medicinal chemistry, we used chemical proteomics to identify Sec61α (protein transport protein Sec61 subunit alpha isoform 1), the pore-forming subunit of the Sec61 protein translocon, as a direct binding partner of ipomoeassin F in living cells. The interaction is specific and strong enough to survive lysis conditions, enabling a biotin analogue of ipomoeassin F to pull down Sec61α from live cells, yet it is also reversible, as judged by several experiments including fluorescent streptavidin staining, delayed competition in affinity pulldown, and inhibition of TNF biogenesis after washout. Sec61α forms the central subunit of the ER protein translocation complex, and the binding of ipomoeassin F results in a substantial, yet selective, inhibition of protein translocation in vitro and a broad ranging inhibition of protein secretion in live cells. Lastly, the unique resistance profile demonstrated by specific amino acid single-point mutations in Sec61α provides compelling evidence that Sec61α is the primary molecular target of ipomoeassin F and strongly suggests that the binding of this natural product to Sec61α is distinctive. Therefore, ipomoeassin F represents the first plant-derived, carbohydrate-based member of a novel structural class that offers new opportunities to explore Sec61α function and to further investigate its potential as a therapeutic target for drug discovery.

Objectives: Since 2006, general practitioners (GPs) in England, UK, have been incentivised to keep a register and monitor patients with chronic kidney disease (CKD) stages 3-5. Despite tensions and debate around the merit of this activity, there has been little qualitative research exploring clinician perspectives on monitoring early-stage CKD in primary care. This study aimed to examine and understand a range of different healthcare professional views and experiences of identification and monitoring in primary care of early-stage CKD, in particular stage 3., Design: Qualitative design using semistructured interviews., Setting: National Health Service (NHS) settings across primary and secondary care in South West England, UK., Participants: 25 clinicians: 16 GPs, 3 practice nurses, 4 renal consultants and 2 public health physicians., Results: We identified two related overarching themes of dissonance and consonance in clinician perspectives on early-stage CKD monitoring in primary care. Clinician dissonance around clinical guidelines for CKD monitoring emanated from different interpretations of CKD and different philosophies of healthcare and moral decision-making. Clinician consonance centred on the need for greater understanding of renal decline and increasing proteinuria testing to reduce overdiagnosis and identify those patients who were at risk of progression and further morbidity and who would benefit from early intervention. Clinicians recommended adopting a holistic approach for patients with CKD representing a barometer of overall health., Conclusions: The introduction of new National Institute for Health and Care Excellence (NICE) CKD guidelines in 2014, which focus the meaning and purpose of CKD monitoring by increased proteinuria testing and assessment of risk, may help to resolve some of the ethical and moral tensions clinicians expressed regarding the overmedicalisation of patients with a CKD diagnosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Although heart failure has a worse prognosis than some cancers, patients often have restricted access to well-developed end of life (EoL) models of care. Studies show that patients with advanced heart failure may have a poor understanding of their condition and its outcome and, therefore, miss opportunities to discuss their wishes for EoL care and preferred place of death. We aimed to explore the perceptions and experiences of health care professionals (HCPs) working with patients with heart failure around EoL care., Methods: A qualitative in-depth interview study nested in a wider ethnographic study of unplanned admissions in patients with heart failure (HoldFAST). We interviewed 24 HCPs across primary, secondary and community care in three locations in England, UK - the Midlands, South Central and South West., Results: The study revealed three issues impacting on EoL care for heart failure patients. Firstly, HCPs discussed approaches to communicating with patients about death and highlighted the challenges involved. HCPs would like to have conversations with patients and families about death and dying but are aware that patient preferences are not easy to predict. Secondly, professionals acknowledged difficulties recognising when patients have reached the end of their life. Lack of communication between patients and professionals can result in situations where inappropriate treatment takes place at the end of patients' lives. Thirdly, HCPs discussed the struggle to find alternatives to hospital admission for patients at the end of their life. Patients may be hospitalised because of a lack of planning which would enable them to die at home, if they so wished., Conclusions: The HCPs regarded opportunities for patients with heart failure to have ongoing discussions about their EoL care with clinicians they know as essential. These key professionals can help co-ordinate care and support in the terminal phase of the condition. Links between heart failure teams and specialist palliative care services appear to benefit patients, and further sharing of expertise between teams is recommended. Further research is needed to develop prognostic models to indicate when a transition to palliation is required and to evaluate specialist palliative care services where heart failure patients are included.

Objectives: Heart failure is a common cause of unplanned hospital admissions but there is little evidence on why, despite evidence-based interventions, admissions occur. This study aimed to identify critical points on patient pathways where risk of admission is increased and identify barriers to the implementation of evidence-based interventions., Design: Multicentre, longitudinal, patient-led ethnography., Setting: National Health Service settings across primary, community and secondary care in three geographical locations in England, UK., Participants: 31 patients with severe or difficult to manage heart failure followed for up to 11 months; 9 carers; 55 healthcare professionals., Results: Fragmentation of healthcare, inequitable provision of services and poor continuity of care presented barriers to interventions for heart failure. Critical points where a reduction in the risk of current or future admission occurred throughout the pathway. At the beginning some patients did not receive a formal clinical diagnosis, in addition patients lacked information about heart failure, self-care and knowing when to seek help. Some clinicians lacked knowledge about diagnosis and management. Misdiagnoses of symptoms and discontinuity of care resulted in unplanned admissions. Approaching end of life, patients were admitted to hospital when other options including palliative care could have been appropriate., Conclusions: Findings illustrate the complexity involved in caring for people with heart failure. Fragmented healthcare and discontinuity of care added complexity and increased the likelihood of suboptimal management and unplanned admissions. Diagnosis and disclosure is a vital first step for the patient in a journey of acceptance and learning to self-care/monitor. The need for clinician education about heart failure and specialist services was acknowledged. Patient education should be seen as an ongoing 'conversation' with trusted clinicians and end-of-life planning should be broached within this context., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: The purpose of this study was to explore the perceptions and experiences of health care clinicians working in multidisciplinary teams that include specialist heart failure nurses when caring for the management of heart failure patients., Methods: We used a qualitative in-depth interview study nested in a broader ethnographic study of unplanned admissions in heart failure patients (HoldFAST). We interviewed 24 clinicians across primary, secondary, and community care in 3 locations in the Midlands, South Central, and South West of England., Results: Within a framework of the role and contribution of the heart failure specialist nurse, our study identified 2 thematic areas that the clinicians agreed still represent particular challenges when working with heart failure patients. The first was communication with patients, in particular explaining the diagnosis and helping patients to understand the condition. The participants recognized that such communication was most effective when they had a long-term relationship with patients and families and that the specialist nurse played an important part in achieving this relationship. The second was communication within the team. Multidisciplinary input was especially needed because of the complexity of many patients and issues around medications, and the participants believed the specialist nurse may facilitate team communication., Conclusions: The study highlights the role of specialist heart failure nurses in delivering education tailored to patients and facilitating better liaison among all clinicians, particularly when dealing with the management of comorbidities and drug regimens. The way in which specialist nurses were able to be caseworkers for their patients was perceived as a method of ensuring coordination and continuity of care., (© 2015 Annals of Family Medicine, Inc.)

Patient selection and training is arguably the most important step toward building a successful home hemodialysis (HD) program. We present a step-by-step account of home HD training to guide providers who are developing home HD programs. Although home HD training is an important step in allowing patients to undergo dialysis in the home, there is a surprising lack of systematic research in this field. Innovations and research in this area will be pivotal in further promoting a higher acceptance rate of home HD as the renal replacement therapy of choice., (© 2015 International Society for Hemodialysis.)

Mycolactone is a polyketide macrolide lipid-like secondary metabolite synthesized by Mycobacterium ulcerans, the causative agent of BU (Buruli ulcer), and is the only virulence factor for this pathogen identified to date. Prolonged exposure to high concentrations of mycolactone is cytotoxic to diverse mammalian cells (albeit with varying efficiency), whereas at lower doses it has a spectrum of immunosuppressive activities. Combined, these pleiotropic properties have a powerful influence on local and systemic cellular function that should explain the pathophysiology of BU disease. The last decade has seen significant advances in our understanding of the molecular mechanisms underlying these effects in a range of different cell types. The present review focuses on the current state of our knowledge of mycolactone function, and its molecular and cellular targets, and seeks to identify commonalities between the different functional and cellular systems. Since mycolactone influences fundamental cellular processes (cell division, cell death and inflammation), getting to the root of how mycolactone achieves this could have a profound impact on our understanding of eukaryotic cell biology.

Background: Longer, more frequent dialysis at home can improve life expectancy for patients with chronic kidney disease. Increased use of home dialysis therapies also benefits the hospital system, allowing for more efficient allocation of clinic resources. However, the Australian and New Zealand Data Registry statistics highlight the low uptake of home haemodialysis and peritoneal dialysis across Australia., Objective: In August 2009, the Australia's HOME Network was established as a national initiative to engage and empower healthcare professionals working in the home dialysis specialty. The aim was to develop solutions to advocate for and ultimately increase the use of home therapies. This paper describes the development, achievement and future plan of the Australian HOME Network., Achievements: Achievements to date include: a survey of HOME Network members to assess the current state of patient and healthcare professional-targeted education resources; development of two patient case studies and activities addressing how to overcome the financial burden experienced by patients on home dialysis. Future projects aim to improve patient and healthcare professional education, and advocacy for home dialysis therapies., Conclusion: The HOME Network is supporting healthcare professionals working in the home dialysis specialty to develop solutions and tools that will help to facilitate greater utilisation of home dialysis therapies., (© 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Background: Depression is common in coronary heart disease (CHD) and increases the incidence of coronary symptoms and death in CHD patients. Interventions feasible for use in primary care are needed to improve both mood and cardiac outcomes. The UPBEAT-UK programme of research has been funded by the NHS National Institute for Health Research (NIHR) to explore the relationship between CHD and depression and to develop a new intervention for use in primary care., Methods: Using the Medical Research Council (MRC) guidelines for developing and evaluating complex interventions, we conducted a systematic review and qualitative research to develop a primary care-based nurse-led intervention to improve mood and cardiac outcomes in patients with CHD and depression. Iterative literature review was used to synthesise our empirical work and to identify evidence and theory to inform the intervention., Results: We developed a primary care-based nurse-led personalised care intervention which utilises elements of case management to promote self management. Following biopsychosocial assessment, a personalised care plan is devised. Nurses trained in behaviour change techniques facilitate patients to address the problems important to them. Identification and utilisation of existing resources is promoted. Nurse time is conserved through telephone follow up., Conclusions: Application of the MRC framework for complex interventions has allowed us to develop an evidence based intervention informed by patient and clinician preferences and established theory. The feasibility and acceptability of this intervention is now being tested further in an exploratory trial.

Background: Many patients unnecessarily receive proton-pump inhibitor (PPI) drugs long term with significant financial and safety implications. Educating, empowering and supporting patients to self-manage their symptoms can lead to significant and sustained reductions in PPI prescribing. We aimed to implement a programme to reduce inappropriate PPI prescribing., Method: Eligible patients in one general medical practice in rural Scotland were invited for participation between November 2008 and February 2010. Patients attended special nurse advisor clinics, completed dyspepsia questionnaires, received information, formulated self-management plans and were offered flexible support., Results: Of the study population, 437/2883 (15%) were prescribed PPIs. Of these, 166 (38%) were judged eligible for participation. After 12 months, 138/157 (83%) had reduced or stopped their PPIs, while 19/157 (11%) had reverted. The estimated annual net saving in the prescribing budget was ?3180.67. Self-reported understanding of symptom self-management increased from 6/20 (30%) to 18/20 (90%) patients after participation in the programme., Conclusion: A patient-centred programme delivered by a specialist nurse significantly reduced PPI prescribing with financial and potential therapeutic benefits. The vast majority of eligible patients were able to 'step down and off' or 'step off' PPI use after 12 months without any complications or deteriorating symptom control. Further research with larger cohorts of practices and patients is needed to develop a feasible, acceptable and effective programme if similar benefits are to be achieved for primary care in general.

Usnic acid, a highly functionalized dibenzofuran, is a polyketide secondary metabolite produced by several species of lichens. Synthesis of usnic acid from commercially available starting material was accomplished in two steps. The synthesis involves the methylation of phloracetophenone followed by oxidation with horseradish peroxidase. This work will lay the foundation for further biosynthetic studies on usnic acid.