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Purpose Workforce development is crucial to the offender personality disorder (OPD) service to provide contemporary, evidenced care and treatment. This study aims to provide an overview and the research evaluation results of a regional higher education programme delivered to a range of criminal justice workers used on the OPD pathway. Design/methodology/approach Three modules were developed and delivered; these are (1) enhancing understanding (20 students), (2) formulation and therapeutic intervention (20 students) and (3) relationships, teams and environments (17 students). A mixed-methods study evaluated participant confidence and compassion. Pre, post and six-month follow-up questionnaires were completed. Additionally, a series of focus groups were conducted to gain in-depth qualitative feedback with a cross-section of students across the modules (N = 7). Quantitative data was collected and analysed separately due to the three modules all having different content. Qualitative data was analysed, and a synthesis of qualitative findings was reported from data taken across the three modules. Findings A total of 52 students participated, drawn from three modules: Module 1 (N = 19); Module 2 (N = 18); Module 3 (N = 15). Confidence in working with people with a personality disorder or associated difficulties improved significantly following completion of any of the modules, whereas compassion did not. Results have been synthesised and have assisted in the future shaping of modules to meet the learning needs of students. Research limitations/implications Further evaluation of the effectiveness of educational programmes requires attention, as does the longer-term durability of effect. Further research is required to explore the post-training impact upon practice, and further exploration is required and larger sample sizes to draw definitive conclusions related to compassion. Practical implications This unique model of co-production that draws upon the expertise of people with lived experience, occupational frontline and academics is achievable and well received by students and can be reproduced elsewhere. Social implications The positive uptake and results of this study indicate a need for expansion of accessible OPD workforce training opportunities across the UK. Further research is required to explore student feedback and comparisons of effectiveness comparing different modes of training delivery, especially in light of the pandemic, which has forced organisations and higher education institutions to develop more digital and distance learning approaches to their portfolios. Originality/value This novel research provides an evaluation of the only higher education credit-bearing modules in the UK focussed solely upon the OPD workforce and aligned with the national drive for non-credit bearing awareness level training “knowledge and understanding framework” (KUF).

Substantial global population declines in pelagic sharks have led to the introduction of management and conservation measures, including gear restrictions and no-retention policies, to curb declines and encourage stock recovery. As the rate of discarding sharks increases, there is a growing need to understand prognostic factors that influence their post-release survival (PRS) outcomes. PRS was measured with survival pop-up satellite archival tags attached to shortfin mako (Isurus oxyrinchus) and silky sharks (Carcharhinus falciformis) released or discarded from pelagic tuna longline fishing vessels operating in the Western and Central Pacific Fisheries Commission Convention Area. In total, 117 tags were deployed on 60 mako and 57 silky sharks captured as bycatch during commercial pelagic longline fishing trips in New Zealand (n = 35), Fiji (n = 58), New Caledonia (n = 10) and the Republic of the Marshall Islands (n = 14). Mako engaged in long-distance movements between New Zealand, Australia, Fiji and New Caledonia, while silky sharks tagged in the Marshall Islands showed evidence of seasonal movements eastward. PRS was determined for 110 sharks (57 mako, 53 silky sharks). Most tagged sharks of both species were uninjured (89%) at capture and most sharks (88%) survived post-release until tag loss or the programmed pop-up date (60 days). However, when considering a complete fishing interaction (haulback, handling, release), PRS estimates were markedly reduced to 48.6% and 52.3% for mako and silky sharks, respectively. For both species, survivorship was greater in large (>150 cm fork length) uninjured sharks and sharks released with low shark length to trailing branchline ratios. While these findings suggest that retention bans offer sharks an increased chance of survival, continued efforts should be made to improve handling and release practices, reduce trailing gear and minimize pelagic shark bycatch.

Following the central dogma of molecular biology, gene expression variability can aid in predicting and explaining the wide variety of protein products, functions, and, ultimately, variability in phenotypes. There is currently overlapping terminology used to describe the types of variability in gene expression profiles, and overlooking these nuances can misrepresent important biological information. Here, we describe transcriptional diversity as quantifying transcriptional changes as a measure of the variability in 1) the total expression of all genes or a gene across samples (transcriptome diversity) or 2) the isoform-specific expression of a given gene (isoform diversity). We first overview modulators and quantification of gene expression variability. Then, we discuss the role alternative splicing plays in driving transcript isoform expression variability and how isoform diversity can be quantified. Additionally, we overview computational resources for calculating transcriptome and isoform diversity for short- and long-read sequencing data. Finally, we discuss future applications of transcriptional diversity. This review provides a comprehensive overview of how gene expression variability arises, and how measuring it determines a more complete picture of heterogeneity across proteins, cells, tissues, organisms, and species

This page explains the ethical approval we had to get in order to conduct this study

This is a replication study of how the perception of anger effects the perception of guilt, and if gender plays a part.

We made a video explaining our procedure in the development of our survey.

The aim of in-trawl catch monitoring for use in fishing operations is to detect, track and classify fish targets in real-time from video footage. Information gathered could be used to release unwanted bycatch in real-time. However, traditional multi-object tracking (MOT) methods have limitations, as they are developed for tracking vehicles or pedestrians with linear motions and diverse appearances, which are different from the scenarios such as livestock monitoring. Therefore, we propose a novel MOT method, built upon an existing observation-centric tracking algorithm, by adopting a new iterative association step to significantly boost the performance of tracking targets with a uniform appearance. The iterative association module is designed as an extendable component that can be merged into most existing tracking methods. Our method offers improved performance in tracking targets with uniform appearance and outperforms state-of-the-art techniques on our underwater fish datasets as well as the MOT17 dataset, without increasing latency nor sacrificing accuracy as measured by HOTA, MOTA, and IDF1 performance metrics.

We are collecting data with a survey and using the results in Jasp to identify variables.

This protocol describes a mixed-methods longitudinal study which aims to build a detailed understanding of how people experience and respond to the COVID-19 pandemic and government policy during the first 12-months since the start of the UK outbreak. The study will comprise of three work packages: a longitudinal prospective online survey, data linkage, and qualitative interviews.

Qualitative analysis of UNICEF's work to build government commitment to CMAM in northern Nigeria

Purpose This paper aims to explain how and why the philosophical changes to the pre-registration nursing standards by the UK’s Nursing and Midwifery Council (NMC) have resulted in a paradigm shift for mental health nursing. Design/methodology/approach This paper critically examines the changes to nursing education standards and offers an analysis of the problems associated with the shift towards a generic nursing syllabus. Findings The said shift prioritises physical health intervention, skills, procedures and tasks over the uniqueness of mental health nursing. Practical implications This paper argues that mental health nursing skills and qualities such as connection, genuine advocacy and therapeutic-use-of-self have been undervalued and under-represented by the new education standards. Originality/value This paper calls on the profession and service users to join the discourse and inform future mental health nursing identity. Ultimately, this paper calls on the NMC to reconsider the underpinning principles of the education standards and allot due consideration to the specific needs of the mental health nursing profession.

The wellbeing of students in higher education generally, and law students, in particular, has become an area of increasing concern in recent years. Despite the growing interest in the area, empirical work on the wellbeing of distance learning law students remains sparse. This paper builds on previous studies around wellbeing in higher education, especially in relation to law schools, by reporting on the findings of a series of focus groups conducted with distance learning law students at The Open University. Its aim was to explore participants’ perceptions of how studying law had impacted their wellbeing. Its findings indicate that participants viewed the online distance-learning nature of their studies as having the most significant impact on their wellbeing, generating a range of practical and psycho-social implications. Although issues specific to the law as a discipline were raised, it appeared to be the mode of delivery, not the subject content, that was of primary relevance. This exploratory study is particularly salient at this time when law schools across the globe have been forced to perform an ‘online pivot’, with many now also considering expanding their long-term online offerings. The paper concludes by considering the ways in which the results of this study could usefully inform future wellbeing initiatives within online legal education.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era., A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Background Blood biomarkers have the potential to help identify COVID-19 patients with bacterial coinfection in whom antibiotics are indicated. During the COVID-19 pandemic, procalcitonin testing was widely introduced at hospitals in the UK to guide antibiotic prescribing. We have determined the impact of this on hospital-level antibiotic consumption. Methods We conducted a retrospective, controlled interrupted time series analysis of organization-level data describing antibiotic dispensing, hospital activity and procalcitonin testing for acute hospitals/hospital trusts in England and Wales during the first wave of COVID-19 (24 February to 5 July 2020). Results In the main analysis of 105 hospitals in England, introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in total antibiotic use of −1.08 (95% CI: −1.81 to −0.36) DDDs of antibiotic per admission per week per trust. This effect was then lost at a rate of 0.05 (95% CI: 0.02–0.08) DDDs per admission per week. Similar results were found specifically for first-line antibiotics for community-acquired pneumonia and for COVID-19 admissions rather than all admissions. Introduction of procalcitonin in the ICU setting was not associated with any significant change in antibiotic use. Conclusions At hospitals where procalcitonin testing was introduced in emergency departments/acute medical units this was associated with an initial, but unsustained, reduction in antibiotic use. Further research should establish the patient-level impact of procalcitonin testing in this population and understand its potential for clinical effectiveness.

Additional file 5. Summary of paediatric early warning system improvement initiatives across all case studies.

Additional file 3. Summary of exploratory and sensitivity analyses.

Additional file 1: Table 1. Summary of theories that inform OUTCOME.

This protocol describes a mixed-methods longitudinal study which aims to build a detailed understanding of how people experience and respond to the COVID-19 pandemic and government policy during the first 12-months since the start of the UK outbreak. The study will comprise of three work packages: a longitudinal prospective online survey, data linkage, and qualitative interviews.

University student wellbeing is increasingly seen as a concern, and as demands on university staff time for research, teaching, leadership and pastoral support also increase, this is mirrored in concerns about staff wellbeing. Dominant sectoral narratives frame student and staff wellbeing as oppositional, with initiatives to support student wellbeing positioned as creating additional practical and emotional demands on staff time and resources. \ud \ud Using a large qualitative dataset collected in the UK, including staff and students, this paper argues that this does not have to be the case. Instead, there is a need to look beyond the provision of reactive services or isolated individual interventions, to proactively and cohesively embed cultural and structural change across the whole institution to support positive wellbeing outcomes for the whole university community. \ud \ud We report on the intrinsic interconnection between staff and student wellbeing; the importance of formal institutional policies in supporting or impeding staff and student wellbeing; access to training interventions to support staff and student wellbeing as a practical manifestation of these policies; and the impact of workplace culture and the centrality of compassion and community. The paper finds that it is important that institutions within higher education acknowledge and respond proactively to both staff and student wellbeing issues. To do so, institutions should seek to foster a sustainable and effective academic environment with a whole university approach.

Background: Lower urinary tract symptoms (LUTS) are common in older men and impact considerably on their quality of life. Management can be complex, and although most LUTS could be treated effectively in primary care, referrals to urology outpatients are increasing. The experiences of General Practitioners (GPs) and patients relating to the management of LUTS have not yet been fully explored. Aim: To explore GPs’ experiences of managing LUTS, together with patients’ experiences of and preferences for treatment in primary care. Design and setting: Qualitative telephone interviews with GPs and male patients presenting to primary care with bothersome LUTS. Method: Eleven GPs and 25 male patients were purposively sampled from 20 GP practices in 3 UK regions. Interviews were conducted between May 2018 and January 2019 and analysed using a framework approach. Results: Difficulty establishing causes and differentiating between prostate and bladder symptoms were key challenges to the diagnosis of LUTS in primary care, making treatment often a process of trial and error. Pharmacological treatments were commonly ineffective and often caused side-effects. Despite this, patients were generally satisfied with GP consultations and expressed a preference for treatment in primary care. Conclusion: Managing LUTS in primary care is a more accessible option for patients. Given the challenges of LUTS diagnosis, an effective diagnostic tool for use by GPs would be beneficial. Ensuring bothersome LUTS are not dismissed as a normal part of ageing is essential in improving patients’ quality of life. Greater exploration of the role of non-pharmacological treatments is needed.

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

Purpose The purpose of this paper is to consider the influence of the Emergency Department (ED) target wait time upon the discharge decision in ED, specifically for patients who have self-harmed. Pressures to discharge patients to avoid breaching the 4-h target wait time, potentially increase the risk of adverse responses from clinicians. For the patient who has self-harmed, such interactions may be experienced as invalidating and may result in adverse outcomes. Design/methodology/approach Secondary data analysis was applied to the retrospective referral data of a Mental Health Liaison Team (MHLT), collected over a period of 11 months from a single hospital in the North of England. In total, 734 episodes of care were referred to the team from ED, where the primary presentation was recorded as self-harm. Findings Over half of patients referred to the MHLT from ED having self-harmed were seen after already breaching the target and the potential for a more restrictive outcome reduced. Of those patients seen within 4 h, the potential for a more restrictive treatment option was increased. Practical implications Recommendations to improve the patient journey for those who have self-harmed include mental health triage and treatment in clinical areas outside of the target. Social implications This study challenges the concept of the target as being realistic and attainable for patients who have self-harmed. Originality/value This exploratory study provides a starting point from which to explore the impact of the target time upon discharge decisions and clinical outcomes specifically for those who have self-harmed.

After his election as Doge of Venice in June 1554, Francesco Venier (1489-1556) changed his modest sepulchral plans to something more in keeping with his new position as head of state. Instead of a simple burial of “little pomp” in the far-flung church of San Francesco della Vigna, Venier secured a prominent, well-located site within the prestigious and centrally located church of San Salvador, stipulating that no less than 1,000 ducats be spent on his funerary monument. The posthumous sepulchral commission – overseen by Venier’s beloved brother Piero – resulted in the enormous gilded, polychrome marble and stone monument still in situ today (fig. 1), adorned with sculptures by two of Venice’s greatest cinquecento sculptors, Jacopo Sansovino (ca. 1486-1570), and his erstwhile assistant, Alessandro Vittoria (ca. 1524/25- 1608). This article reconsiders the monument’s commissioning history, through a re-examination of published archival documents and printed primary sources, followed by an analysis of previously unpublished litigation records. These fascinating new documents not only reveal the legal proceedings that Francesco Sansovino (1521-1586) set in motion in March 1571, four months after his father’s death, but also clarify, for the first time, the extent of Jacopo Sansovino’s involvement in the project and confirm the iconography of the two niche statues., None

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255, Funder: University College London, Birkbeck MRC Doctoral Training Programme, Funder: The Jikei University School of Medicine, Funder: Action Medical Research (GN2779), Funder: NIHR Clinical Lectureship (CL-2017-01-004), Funder: NIHR (ACF-2018-01-004) and the BMA Foundation, Funder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194), Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944), Funder: Barbour Foundation, Funder: ERC Consolidator and EU MRG-Grammar awards, Funder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002), Funder: European Molecular Biology Laboratory (EMBL), Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Studies investigating the spatial distribution of environmental hazards have repeatedly demonstrated the existence of environmental racism -- the disproportionate impact of environmental hazards on communities of color. We aim to contribute to research on environmental racism by asking how relationships between race and hazard exposure change over time. Our study area, Salt Lake City (SLC), UT, USA is one of the largest cities in the intermountain west and is expected to see continued population growth. SLC was 99% white from 1860-1950. 2019 census estimates indicate that SLC is becoming more racially diverse with 35.6% of the population identifying as racial categories other than “white alone.” Latinx people represent the largest proportion of SLC’s growing racial diversity (21.2%). We analyze American Community Survey (ACS) demographic data comparing 2 years spanning a ~10 year period (2010 and 2019) to determine whether census tracts with high densities of environmental hazard sites have a growing, shrinking, or unchanging proportion of Latinx residents. We connect this analysis to mortgage redlining practices that promoted urban segregation along race and class lines and ask whether these practices and the resulting geographies of housing inequality have created conditions restricting the growth of communities of color to polluted areas. We argue that racist planning practices effectively weave environmental racism into the fabric of cities and that cities with growing communities of color must consider how existing spatial patterns of segregation may perpetuate exposure to environmental harms.

Major Lower Limb Amputation (MLLA) is a life changing event with significant morbidity and mortality. Inaccurate risk prediction can lead to poor decision making, resulting in delay to definitive surgery, or undertaking amputation when not in the patient’s best interest. We aim to answer: In adult patients undergoing MLLA for chronic limb threatening ischaemia or diabetes, how accurately do health care professionals prospectively predict outcomes after MLLA, and how does this compare to existing prediction tools?\ud Methods\ud \ud A multicentre prospective observational cohort study is being delivered through the Vascular and Endovascular Research Network. Dissemination was via an existing network of contacts and social media.\ud \ud Consecutive data will be collected for seven months from site launch date, including demographic data and pre-operative outcome predictions from surgeons, anaesthetists, and allied healthcare professionals. Follow-up data will comprise 30-day (mortality, morbidity, MLLA revision, surgical site infection, and blood transfusion) and 1-year (mortality, MLLA revision and ambulation). The accuracy of surgeons’ predictions will be evaluated and compared to pre-existing risk prediction scoring tools.\ud Results\ud \ud PERCEIVE launched on 01/10/2020 with 23 centres (16 UK, 7 international) registered to collect data. 50 other centres (27 UK, 23 international) have expressed interest/are pursuing local audit/ethical approval. We aim to collect data on clinicians estimate of outcomes for over 500 patients.\ud Discussion\ud \ud This study will utilise a trainee research network to provide data on the accuracy of healthcare professionals’ predictions of outcomes following MLLA and compare this to the utility of existing prediction tools in this patient cohort.

Background C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible.Aim To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care.Design and setting Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial).Method Clinicians collected participants’ demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP Results A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85).Conclusion Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions.

We aim to contribute to research on environmental racism by asking how relationships between race and hazard exposure change over time. We analyze American Community Survey (ACS) demographic data from 2010 and 2019 to determine whether census tracts with high densities of EPA environmental hazard sites have a growing, shrinking, or unchanging proportion of Latinx residents. We argue that racist planning practices effectively weave environmental racism into the fabric of cities and that cities with growing communities of color must consider how existing spatial patterns of segregation may perpetuate exposure to environmental harms.

IntroductionSepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality.Methods and analysisPRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation.Ethics and disseminationThe trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.Trial registration numberISRCTN54006056.

OBJECTIVES: Quality improvement (QI) may help to avert or mitigate the risks of suboptimal care, but it is often poorly reported in the healthcare literature. We aimed to identify the influences on reporting QI in the area of perioperative care, with a view to informing improvements in reporting QI across healthcare. DESIGN: Qualitative interview study. SETTING: Healthcare and academic organisations in Australia, Europe and North America. PARTICIPANTS: Stakeholders involved in or influencing the publication, writing or consumption of reports of QI studies in perioperative care. RESULTS: Forty-two participants from six countries took part in the study. Participants included 15 authors (those who write QI reports), 12 consumers of QI reports (practitioners who apply QI research in practice), 11 journal editors and 4 authors of reporting guidelines. Participants identified three principal challenges in achieving high-quality QI reporting. First, the broad scope of QI reporting-ranging from small local projects to multisite research across different disciplines-causes uncertainty about where QI work should be published. Second, context is fundamental to the success of a QI intervention but is difficult to report in ways that support replication and development. Third, reporting is adversely affected by both proximal influences (such as lack of time to write up QI) and more distal, structural influences (such as norms about the format and content of biomedical research reporting), leading to incomplete reporting of QI findings. CONCLUSIONS: Divergent terminology and understandings of QI, along with existing reporting norms and the challenges of capturing context adequately yet succinctly, make for challenges in reporting QI. We offer suggestions for improvement.

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.

Additional file 1. CMAM Interview and verification instruments. Facility-level data collection tools; LGA-level data collection tools; State-level data collection tools; Federal-level data collection tools; Protocol for verification of CMAM admission and discharge data; OTP data verification collection forms, and RUTF data verification collection forms.

Objectives Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort. Methods The COPE study cohort (n=11,113) were recruited via and online survey at enrolment March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6,942 people at 3-months (June/July 2020) and 5,037 at 12-months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, self-efficacy, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3- and 12-months to assess the association between motivational factors and vaccine hesitancy. Longitudinal change in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect ANOVA models. Results Fear of COVID-19, perceived susceptibility to COVID-19 and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12-months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19 related restrictions as the vaccination program progressed. Conclusions Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact on future COVID-19 vaccination uptake.

This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.

This article, based on a qualitative study conducted in June–July 2019, assesses how barristers at the Bar of Northern Ireland perceive wellbeing and mental ill-health within their profession. It will argue that the Bar can be a competitive and potentially hostile workplace environment, leading to detrimental impacts on wellbeing. It will also contend that being a barrister in Northern Ireland provides its own unique challenges for practitioners due to the self-employed independent nature of the role, where practitioners do not work in chambers or stables like their counterparts in England & Wales and Scotland. At the same time, barristers spoke positively about the flexibility of their roles and beneficial forms of collegiality, as well as an evolving culture which places greater emphasis on wellbeing. This article will argue, using the ‘job demands and resources’ model, that efforts should be made to decrease job demands and increase the job resources of barristers of the Bar of Northern Ireland to improve levels of wellbeing. This model could also be applied to the Bar in other jurisdictions to assess the impact of both shared and unique challenges and opportunities.

Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.

COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a mucosal surface, mainly the lungs or the intestine, where epithelial cells can be infected with virus. Although it is clear that virus within the lungs can cause severe pathology, driven by an exaggerated immune response, infection within the intestine generally seems to cause minor or no symptoms. In this review, we compare the disease processes between the lungs and gastrointestinal tract, and what might drive these different responses. As the microbiome is a key part of mucosal barrier sites, we also consider the effect that microbial species may play on infection and the subsequent immune responses. Because of difficulties obtaining tissue samples, there are currently few studies focused on the local mucosal response rather than the systemic response, but understanding the local immune response will become increasingly important for understanding the mechanisms of disease in order to develop better treatments.

This thesis offers, for the first time, an in-depth study of the principal aspects of the business of sculpture in Venice from 1525 to 1625. Based on systematic examination, analysis and interpretation of myriad archival sources (unpublished and published), primary texts and key objects, it answers fundamental questions such as: how was sculpture commissioned in Renaissance and Early Modern Venice? Why were some contracts verbal, yet others written? How was quality assured? What meanings did materials have? How did sculptors’ workshops operate? The first two chapters examine the various stages of the commissioning process, from a patron’s initial motivations, to choosing a sculptor, drawing up a contract and agreeing a price. Chapter 1 examines who commissioned sculpture and why, the genres favoured, and how locations were chosen and secured. Chapter 2 analyses the documentary evidence for the format and content of contracts, the use of drawings and models, and the involvement of third parties. It also considers how patrons sought to ensure the quality of the finished work. Chapter 3, ‘Materials: Sourcing, Supply, Significance’, concentrates on the media most commonly employed: marble, stone, bronze, stucco and clay in the form of terracotta. It assesses the practicalities of sourcing, supply, cost and transportation, and then considers the aesthetic and pragmatic reasons for material choices and what these choices would have signified to the patron, sculptor and Venetian society more widely. The final chapter, ‘Workshops, Authorship, Networks, Problem-solving’, explores how sculptors’ workshops were organised and the division and delegation of labour. It discusses the concept of authorship and the nature and meaning of signatures, given that sculptural production was an inherently collaborative process. An analysis of the importance of the sculptor’s network follows, focusing on the life and career of Girolamo Campagna. The chapter concludes with a discussion of how sculptors and patrons could resolve any problems that arose during the production process. This thesis is underpinned by a catalogue of select commissions, with new transcriptions of pertinent archival sources where possible. The chosen case-studies span the century under examination and represent a diverse range of commissions (in terms of patron, sculptor, genre, material, location etc.) and documentary evidence (such as wills, contracts, account-books, letters, notarial acts, ballot records).

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.

Organic vegetable production can be profitable for growers in Utah looking to supply local markets. Much of Utah has short growing seasons (

This report sets out a review of existing approaches to the segmentation of energy consumers in Great Britain in order to understand the extent to which these are useful in the Scottish context

The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. S exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor binding site, and subsequently from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S which allow production of thermostable, crosslinked, S protein trimers that are trapped in the closed, pre-fusion, state. We have determined the structures of crosslinked and non-crosslinked proteins, identifying two distinct closed conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.

En likvärdig undervisning är något som varje individ oavsett bakgrund, behov och förutsättningar ska ges (Skolverket, 2011a). I den gymnasiala samtida undervisningen i ämnet idrott och hälsa, brister lärare i att anpassa sin undervisning utefter eleverna (Skolinspektionen, 2010b). Detta resulterar i ett exkluderande klimat där eleverna inte ges förutsättningar att utvecklas utefter sina egna förutsättningar (Skolinspektionen, 2018). Syftet med studien var således att undersöka hur lärare, verksamma i gymnasiet, tolkar begreppet likvärdighet samt hur de väljer att arbeta för att uppnå detta i sin undervisning. Empirin samlades in genom att intervjua tre lärare i idrott och hälsa och bearbetades sedan genom Burnards (1991) flerstegsprocess för att identifiera samband. Resultatet analyserades utifrån läroplansteori och ramfaktorteori (Linde, 2009). Resultatet visar på att lärare arbetar med skilda undervisningsmetoder för att anpassa undervisningen utefter eleverna med ökad inkludering och likvärdighet som mål. Respondenterna synliggjorde även att läroplanen lämnar stort tolkningsutrymme samt att hur lärare ser på ämnet skiljer sig åt. Studiens slutsats är att det finns många faktorer, som till exempel lärares kompetens, synsätt samt elevgrupp, som påverkar hur lärare väljer att forma sin undervisning. Konsekvensen av dessa faktorers påverkan är att den utbildning som elever ges inte alltid följer de riktlinjer som råder för likvärdigheten i skolans verksamhet.