Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics.

Rationale: Genetic studies suggest that SOX17 (SRY-related HMG-box 17) deficiency increases pulmonary arterial hypertension (PAH) risk. Objectives: On the basis of pathological roles of estrogen and HIF2α (hypoxia-inducible factor 2α) signaling in pulmonary artery endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF2α inhibition. Methods: We used metabolic (Seahorse) and promoter luciferase assays in PAECs together with the chronic hypoxia murine model to test the hypothesis. Measurements and Main Results: Sox17 expression was reduced in PAH tissues (rodent models and from patients). Chronic hypoxic pulmonary hypertension was exacerbated by mice with conditional Tie2-Sox17 (Sox17EC-/-) deletion and attenuated by transgenic Tie2-Sox17 overexpression (Sox17Tg). On the basis of untargeted proteomics, metabolism was the top pathway altered by SOX17 deficiency in PAECs. Mechanistically, we found that HIF2α concentrations were increased in the lungs of Sox17EC-/- and reduced in those from Sox17Tg mice. Increased SOX17 promoted oxidative phosphorylation and mitochondrial function in PAECs, which were partly attenuated by HIF2α overexpression. Rat lungs in males displayed higher Sox17 expression versus females, suggesting repression by estrogen signaling. Supporting 16α-hydroxyestrone (16αOHE; a pathologic estrogen metabolite)-mediated repression of SOX17 promoter activity, Sox17Tg mice attenuated 16αOHE-mediated exacerbations of chronic hypoxic pulmonary hypertension. Finally, in adjusted analyses in patients with PAH, we report novel associations between a SOX17 risk variant, rs10103692, and reduced plasma citrate concentrations (n = 1,326). Conclusions: Cumulatively, SOX17 promotes mitochondrial bioenergetics and attenuates PAH, in part, via inhibition of HIF2α. 16αOHE mediates PAH development via downregulation of SOX17, linking sexual dimorphism and SOX17 genetics in PAH.

Utility of the capabilities, opportunities, motivations model for understanding changes in behavior.

BACKGROUND: Wearing face coverings to prevent airborne viral transmission has at times been legally mandated, followed by periods when rules were relaxed. The present study tracks changes in face covering and the impacts on people's perceptions of their capabilities, opportunities and motivations. METHODS: Three-wave survey. At wave 1 (25 January-6 February 2022), 10 622 UK adults reported: (a) sociodemographic characteristics; (b) face covering in work, public transport and indoor leisure settings and (c) capabilities, opportunities and motivations. Measures were repeated 1-18 March 2022 and 20 May-6 June 2022. Data were analyzed descriptively, within-participants analysis of covariance (ANCOVA) and multiple linear regression. RESULTS: Face covering decreased over time as rules around the wearing of face coverings relaxed. Perceptions of capabilities, opportunities and motivations to wear face coverings were consistently associated with the actual wearing of face coverings, with marked decreases in motivations over time. CONCLUSIONS: Decreases in motivations seem to explain best the reasons for declining levels of face covering. Further work is required to develop interventions to change people's motivations and promote the wearing of face coverings, should they be required in the future.

A case series of live attenuated vaccine administration in dupilumab-treated children with atopic dermatitis.

BACKGROUND AND OBJECTIVE: Current regulatory labeling recommends avoiding live vaccine use in dupilumab-treated patients. Clinical data are not available to support more specific guidance for live or live attenuated vaccines administration in dupilumab-treated patients. METHODS: Children (6 months-5 years old) with moderate-to-severe atopic dermatitis (AD) enrolled in a phase 2/3 clinical trial of dupilumab (LIBERTY AD PRESCHOOL Part A/B; NCT03346434) and subsequently participated in the LIBERTY AD PED-OLE (NCT02612454). During these studies, protocol deviations occurred in nine children who received measles, mumps, rubella (MMR) vaccine with or without varicella vaccine; five with a ≤12-week gap between dupilumab administration and vaccination and four with a >12-week gap after discontinuing dupilumab. RESULTS: Nine children (1 female; 8 male) had severe AD at baseline (8-56 months old). Of the nine children, five had a ≤12-week gap ranged 1-7 weeks between dupilumab administration and vaccination who received MMR vaccine (n = 2) or MMR and varicella vaccines (n = 3); among these, one resumed dupilumab treatment as early as 2 days and four resumed treatment 18-43 days after vaccination. No treatment-emergent adverse events, including serious adverse events and infections, were reported within the 4-week post-vaccination period in any children. CONCLUSIONS: In this case series of dupilumab-treated children with severe AD who received MMR vaccine with or without varicella vaccine, no adverse effects (including vaccine-related infection) were reported within 4 weeks after vaccination. Further studies are warranted to evaluate the safety, tolerability, and immune response to live attenuated vaccines in dupilumab-treated patients.

Theory-based Trial to Promote Uptake and Sustained Use of Face Coverings During the COVID-19 Pandemic.

BACKGROUND: Transmission of airborne viruses can be mitigated by wearing face coverings but evidence suggests that face covering declines with the removal of relevant legislation, partly due to low automatic motivation. PURPOSE: Test whether an intervention based on implementation intentions could support people's automatic motivation and promote face covering during the COVID-19 pandemic. METHODS: Randomized controlled design. At baseline (May 20 to June 6, 2022), 7,835 UK adults reported how much time they spent wearing face coverings in work, public transport, and indoor leisure settings as well as their capabilities, opportunities, and motivations. 3,871 participants were randomized to form implementation intentions; 3,964 control participants completed questionnaires only. Measures were repeated 6 months postbaseline (November 1 to November 14, 2022). Data were analyzed using mixed measures ANOVAs and Bayes Factors to examine whether the observed data supported the experimental hypothesis. RESULTS: The proportion of time spend wearing face coverings declined substantially across the 6-month study period, from 15.28% to 9.87% in work settings, 38.31% to 24.55% on public transport, and 9.58% to 7.85% in leisure settings. Bayes Factors indicated moderate relative evidence of no effect of implementation intentions on behavior in work and leisure settings, and inconclusive evidence of a positive effect on public transport. CONCLUSIONS: In the context of declining COVID-19 rates and removal of legal mandates, implementation intentions were not effective in sustaining face covering. Further research is required to ensure that evidence-based interventions are prepared and deployed in the event of future pandemics.

The spread of viruses through the air can be reduced by people wearing face coverings. The evidence suggests that face covering reduces with the removal of relevant legislation, partly due to habits not being formed. The aim of the present study was to test whether an intervention designed to help people to form new habits could support people's face covering during the COVID-19 pandemic. We asked 7,835 UK adults how much time they spent wearing face coverings in work, public transport, and indoor leisure settings. We chose 3,871 participants at random to form new habits; 3,964 participants completed questionnaires only. Measures were repeated 6 months later. The proportion of time spend wearing face coverings declined sharply across the 6-month study period, from 15.28% to 9.87% in work settings, 38.31% to 24.55% on public transport, and 9.58% to 7.85% in leisure settings. Our analyses showed a small positive effect of forming new habits on wearing face coverings in public transport settings. In the context of declining COVID-19 rates and the removal of legal mandates, our intervention was not effective in sustaining face covering. Further research is required to ensure that evidence-based interventions are prepared and deployed in the event of future pandemics.

how these findings canPublic transport: lessons learned by the sector through the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic had a significant impact on the operations and functionality of the public transport sector in the UK. This paper reflects on the experience of this sector through the pandemic period, and considers recommendations for any future mitigations required for either new COVID-19 waves or a different public health emergency. METHODS: Semi-structured interviews were carried out with public transport experts, organisational leaders, workers and passengers in two phases: Phase 1 from January to May 2021, and Phase 2 from December 2021 to February 2022. Interviews were analysed thematically. RESULTS: Using the 'What? So What? Now What?' reflective model, ideas are drawn out to describe (a) what changes occurred, (b) what effects these changes had on service provision as well as perceptions of risk and mitigation and (c) what lessons have been learned and how these findings can feed into pandemic preparedness for the future. Respondent reflections focussed on the importance of communication, leadership, and maintaining compliance. CONCLUSIONS: The wealth of experience gained through the COVID-19 pandemic in the public transport sector is extremely valuable. Through reflection on this experience, specific recommendations are made relating to these factors, covering: maintaining links across industry, access to information and data, understanding of mitigation effectiveness, improving messaging, challenges of behavioural mitigations, and clear lines of accountability. The recommendations made on the basis of this reflective process will help to improve public health strategy within the public transport sector.

Areas of enduring COVID-19 prevalence: drivers of prevalence and mitigating strategies.

BACKGROUND: UK local authorities that experienced sustained high levels of COVID-19 between 1st March 2020 and 28th February 2021 were described by the UK Scientific Advisory Group for Emergencies as areas of enduring prevalence. This research was carried out in order to examine the views of local authority Directors of Public Health, who played a crucial role in the local response to COVID-19, on reasons for sustained high levels of prevalence in some areas, alongside an investigation of the mitigation strategies that they implemented during the course of the pandemic. METHODS: Interviews were conducted with Directors of Public Health in 19 local authority areas across England, between July and November 2021. This included nine areas identified as areas of enduring prevalence and ten 'comparison' areas. RESULTS: The outcomes of this study suggests that the geographical differences in prevalence rates are strongly influenced by health inequalities. Structural factors including deprivation, employment, and housing, due to their disproportionate impact on specific groups, converged with demographic factors, including ethnicity and age, and vaccination rates, and were identified as the main drivers of enduring prevalence. There are key differences in these drivers both within and, to a lesser extent, between local authorities. Other than these structural barriers, no major differences in facilitators or barriers to COVID-19 mitigation were identified between areas of varying prevalence. The main features of successful mitigation strategies were a locally tailored approach and partnership working involving local authority departments working with local health, community, voluntary and business organisations. CONCLUSIONS: This study is the first to add the voices of Directors of Public Health, who played a crucial role in the local COVID-19 response. Areas of enduring prevalence existed during the pandemic which were caused by a complex mix of structural factors related to inequalities. Participants advised that more research is needed on the effectiveness of mitigation strategies and other measures to reduce the impact of structural inequalities, to better understand the factors that drive prevalence. This would include an assessment of how these factors combine to predict transmission and how this varies between different areas.

Novel Mutations and Decreased Expression of the Epigenetic Regulator TET2 in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy. Hereditary cases are associated with germline mutations in BMPR2 and 16 other genes; however, these mutations occur in <25% of patients with idiopathic PAH and are rare in PAH associated with connective tissue diseases. Preclinical studies suggest epigenetic dysregulation, including altered DNA methylation, promotes PAH. Somatic mutations of Tet-methylcytosine-dioxygenase-2 (TET2), a key enzyme in DNA demethylation, occur in cardiovascular disease and are associated with clonal hematopoiesis, inflammation, and adverse vascular remodeling. The role of TET2 in PAH is unknown. METHODS: To test for a role of TET2, we used a cohort of 2572 cases from the PAH Biobank. Within this cohort, gene-specific rare variant association tests were performed using 1832 unrelated European patients with PAH and 7509 non-Finnish European subjects from the Genome Aggregation Database (gnomAD) as control subjects. In an independent cohort of 140 patients, we quantified TET2 expression in peripheral blood mononuclear cells. To assess causality, we investigated hemodynamic and histological evidence of PAH in hematopoietic Tet2-knockout mice. RESULTS: We observed an increased burden of rare, predicted deleterious germline variants in TET2 in PAH patients of European ancestry (9/1832) compared with control subjects (6/7509; relative risk=6; P=0.00067). Assessing the whole cohort, 0.39% of patients (10/2572) had 12 TET2 mutations (75% predicted germline and 25% somatic). These patients had no mutations in other PAH-related genes. Patients with TET2 mutations were older (71±7 years versus 48±19 years; P<0.0001), were more unresponsive to vasodilator challenge (0/7 versus 140/1055 [13.2%]), had lower pulmonary vascular resistance (5.2±3.1 versus 10.5±7.0 Wood units; P=0.02), and had increased inflammation (including elevation of interleukin-1ß). Circulating TET2 expression did not correlate with age and was decreased in >86% of PAH patients. Tet2-knockout mice spontaneously developed PAH, adverse pulmonary vascular remodeling, and inflammation, with elevated levels of cytokines, including interleukin-1ß. Long-term therapy with an antibody targeting interleukin-1ß blockade resulted in regression of PAH. CONCLUSIONS: PAH is the first human disease related to potential TET2 germline mutations. Inherited and acquired abnormalities of TET2 occur in 0.39% of PAH cases. Decreased TET2 expression is ubiquitous and has potential as a PAH biomarker.

Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension.

Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis.Measurements and Main Results: After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (n = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41-0.87]; P = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23-1.01]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50-0.84]; P = 0.001). An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15-0.93]; P = 0.034).Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.

Assembling the Healthopolis: Competitive city-regionalism and policy boosterism pushing Greater Manchester further, faster.

Health and care policy is increasingly promoted within visions of the competitive city-region. This paper examines the importance of policy boosterism within the political construction of city-regions in the context of English devolution. Based on a two-year case study of health and social care devolution in Greater Manchester, England, we trace the relational and territorial geographies of policy across and through new "devolved" city-regional arrangements. Contributing to geographical debates on policy assemblages and city-regionalism, we advance a conceptual framework linking crisis and opportunity, emulation and exceptionalism, and evidence and experimentation. The paper makes two key contributions. First, we argue health and care policy is increasingly drawn towards the logic of global competitiveness without being wholly defined by neoliberal political agendas. Fostering transnational policy networks helped embed global "best practice" policies while simultaneously hailing Greater Manchester as a place beyond compare. Second, we caution against positioning the city-region solely at the receiving end of devolutionary austerity. Rather, we illustrate how the urgency of devolution was conditioned by crisis, yet concomitantly framed as a unique opportunity by the local state harnessing policy to negotiate a more fluid politics of scale. In doing so, the paper demonstrates how attempts to resolve the "local problem" of governing health and care under austerity were rearticulated as a "global opportunity" to forge new connections between place, health, and economy. Consequently, we foreground the multiple tensions and contradictions accumulating through turning to health and care to push Greater Manchester further, faster. The paper concludes by asking what the present crisis might mean for city-regions in good health and turbulent times.

Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension.

The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort.IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models.Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08-1.38; p<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease.IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.

Regional assemblage and the spatial reorganisation of health and care: the case of devolution in Greater Manchester, England.

In this paper, we examine how space is integral to the practices and politics of restructuring health and care systems and services and specifically how ideas of assemblage can help understand the remaking of a region. We illustrate our arguments by focusing on health and social care devolution in Greater Manchester, England. Emphasising the open-ended political construction of the region, we consider the work of assembling different actors, organisations, policies and resources into a new territorial formation that provisionally holds together without becoming a fixed totality. We highlight how the governing of health and care is shaped through the interplay of local, regional and national actors and organisations coexisting, jostling and forging uneasy alliances. Our goal is to show that national agendas continued to be firmly embedded within the regional project, not least the politics of austerity. Yet through keeping the region together as if it was an integrated whole and by drawing upon new global policy networks, regional actors strategically reworked national agendas in attempts to leverage and compete for new resources and powers. We set out a research agenda that foregrounds how the political reorganisation of health and care is negotiated and contested across multiple spatial dimensions simultaneously.

Beyond the parish pump: what next for public health?

BACKGROUND: Public health has had a history characterised by uncertainty of purpose, locus of control, and workforce identity. In many health systems, the public health function is fragmented, isolated and under-resourced. We use the most recent major reforms to the English National Health Service and local government, the Health and Social Care Act 2012 (HSCA12), as a lens through which to explore the changing nature of public health professionalism. METHODS: This paper is based upon a 3-year longitudinal study into the impacts of the HSCA12 upon the commissioning system in England, in which we conducted 141 interviews with 118 commissioners and senior staff from a variety of health service commissioner and provider organisations, local government, and the third sector. For the present paper, we developed a subset of data relevant to public health, and analysed it using a framework derived from the literature on public health professionalism, exploring themes identified from relevant policy documents and research. RESULTS: The move of public health responsibilities into local government introduced an element of politicisation which challenged public health professional autonomy. There were mixed feelings about the status of public health as a specialist profession. The creation of a national public health organisation helped raise the profile of profession, but there were concerns about clarity of responsibilities, accountability, and upholding 'pure' public health professional values. There was confusion about the remit of other organisations in relation to public health. CONCLUSIONS: Where public health professionals sit in a health system in absolute terms is less important than their ability to develop relationships, negotiate their roles, and provide expert public health influence across that system. A conflation between 'population health' and 'public health' fosters unrealistic expectations of the profession. Public health may be best placed to provide leadership for other stakeholders and professional groups working towards improving health outcomes of their defined populations, but there remains a need to clarify the role(s) that public health as a specialist profession has to play in helping to fulfil population health goals.

Leadership for health commissioning in the new NHS.

PURPOSE: The purpose of this paper is to explore the early experiences of those involved with the development of Clinical Commissioning Groups (CCGs), examining how the aspiration towards a "clinically-led" system is being realised. The authors investigate emerging leadership approaches within CCGs in light of the criterion for authorisation that calls for "great leaders". DESIGN/METHODOLOGY/APPROACH: Qualitative research was carried out in eight case studies (CCGs) across England over a nine-month period (September 2011 to May 2012) when CCGs were in their early development. The authors conducted a mix of interviews (with GPs and managers), observations (at CCG meetings) and examined associated documentation. Data were thematically analysed. FINDINGS: The authors found evidence of two identified approaches to leadership - positive deviancy and responsible guardianship - being undertaken by GPs and managers in the developing CCGs. Historical experiences and past ways of working appeared to be influencing current developments and a commonly emerging theme was a desire for the CCG to "do things differently" to the previous commissioning bodies. The authors discuss how the current reorganisation threatens the guardianship approach to leadership and question if the new systems being implemented to monitor CCGs' performance may make it difficult for CCGs to retain creativity and innovation, and thus the ability to foster the positive deviant approach to leadership. ORIGINALITY/VALUE: This is a large scale piece of qualitative research carried out as CCGs were beginning to develop. It provides insight into how leadership is developing in CCGs highlighting the complexity involved in these roles.

Persistent social interactions beget more pronounced personalities in a desert-dwelling social spider.

The social niche specialization hypothesis predicts that repeated social interactions will generate social niches within groups, thereby promoting consistent individual differences in behaviour. Current support for this hypothesis is mixed, probably because the importance of social niches is dependent upon the ecology of the species. We test whether repeated interactions among group mates generate consistent individual differences in boldness in the social spider, Stegodyphus dumicola. In support of the social niche specialization hypothesis, we found that consistent individual differences in boldness increased with longer group tenure. Interestingly, these differences took longer to appear than in previous work suggesting this species needs more persistent social interactions to shape its behaviour. Recently disturbed colonies were shyer than older colonies, possibly reflecting differences in predation risk. Our study emphasizes the importance of the social environment in generating animal personalities, but also suggests that the pattern of personality development can depend on subtle differences in species' ecologies.

The limits of market-based reforms in the NHS: the case of alternative providers in primary care.

BACKGROUND: Historically, primary medical care in the UK has been delivered by general practitioners who are independent contractors, operating under a contract, which until 2004 was subject to little performance management. In keeping with the wider political impetus to introduce markets and competition into the NHS, reforms were introduced to allow new providers to bid for contracts to provide primary care services in England. These contracts known as 'Alternative Provider Medical Services', were encouraged by two centrally-driven rounds of procurement (2007/8 and 2008/9). This research investigated the commissioning and operation of such Alternative Providers of Primary Care (APPCs). METHODS: Two qualitative case studies were undertaken in purposively sampled English Primary Care Trusts (PCTs) and their associated APPCs over 14 months (2009-10). We observed 65 hours of meetings, conducted 23 interviews with PCT and practice staff, and gathered relevant associated documentation. RESULTS AND CONCLUSIONS: We found that the procurement and contracting process was costly and time-consuming. Extensive local consultation was undertaken, and there was considerable opposition in some areas. Many APPCs struggled to build up their patient list sizes, whilst over-performing on walk-in contracts. Contracting for APPCs was 'transactional', in marked contrast to the 'relational' contracting usually found in the NHS, with APPCs subject to tight performance management. These complicated and costly processes contrast to those experienced by traditionally owned GP partnerships. However, managers reported that the perception of competition had led existing practices to improve their services. The Coalition Government elected in 2010 is committed to 'Any Qualified Provider' of secondary care, and some commentators argue that this should also be applied to primary care. Our research suggests that, if this is to happen, a debate is needed about the operation of a market in primary care provision, including the trade-offs between transparent processes, fair procurement, performance assurance and cost.

Who do we think we are? Analysing the content and form of identity work in the English National Health Service.

PURPOSE: The language used by National Health Service (NHS) "commissioning" managers when discussing their roles and responsibilities can be seen as a manifestation of "identity work", defined as a process of identifying. This paper aims to offer a novel approach to analysing "identity work" by triangulation of multiple analytical methods, combining analysis of the content of text with analysis of its form. DESIGN/METHODOLOGY/APPROACH: Fairclough's discourse analytic methodology is used as a framework. Following Fairclough, the authors use analytical methods associated with Halliday's systemic functional linguistics. FINDINGS: While analysis of the content of interviews provides some information about NHS Commissioners' perceptions of their roles and responsibilities, analysis of the form of discourse that they use provides a more detailed and nuanced view. Overall, the authors found that commissioning managers have a higher level of certainty about what commissioning is not rather than what commissioning is; GP managers have a high level of certainty of their identity as a GP rather than as a manager; and both GP managers and non-GP managers oscillate between multiple identities depending on the different situations they are in. ORIGINALITY/VALUE: This paper offers a novel approach to triangulation, based not on the usual comparison of multiple data sources, but rather based on the application of multiple analytical methods to a single source of data. This paper also shows the latent uncertainty about the nature of commissioning enterprise in the English NHS.

Understanding the work done by NHS commissioning managers: an exploration of the microprocesses underlying day-to-day sensemaking in UK primary care organisations.

PURPOSE: The purpose of this paper is to explore the practical daily work undertaken by middle-level managers in Primary Care Trusts (PCTs), focusing upon the micro-processes by which these managers enact sensemaking in their organisations. DESIGN/METHODOLOGY/APPROACH: The research took a case study approach, undertaking detailed case studies in four PCTs in England. Data collection included shadowing managers, meeting observations and interviews. FINDINGS: The research elucidated two categories of enactment behaviour exhibited by PCT managers: presence/absence; and the production of artefacts. Being "present" in or "absent" from meetings enacted sensemaking over and above any concrete contribution to the meeting made by the actors involved. This paper explores the factors affecting these processes, and describes the situations in which enactment of sense is most likely to occur. Producing artefacts such as meeting minutes or PowerPoint slides also enacted sense in the study sites in addition to the content of the artefact. The factors affecting this are explored. PRACTICAL IMPLICATIONS: The study has practical implications for all managers seeking to maximise their influence in their organisations. It also provides specific evidence relevant to managers working in the new Clinical Commissioning Groups currently being formed in England. ORIGINALITY/VALUE: The study expands the understanding of sensemaking in organisations in two important ways. Firstly, it moves beyond discourse to explore the ways in which behaviours can enact sense. Secondly, it explores the distinction between active and unconscious sensemaking.

Experiences, Perceptions of Risk, and Lasting Impacts of COVID-19 for Employees in the Public Transport Sector.

BACKGROUND: Age-standardized mortality rates for taxi drivers, chauffeurs, bus and coach drivers show that public transport workers were at high risk at the beginning of the COVID-19 pandemic. Nevertheless, the public transport sector was required to continue services throughout the pandemic. OBJECTIVES: This paper aims to develop a better understanding of the experiences of organizational leaders and workers within the UK public transport sector (bus, rail, and tram). Specifically, it aims to explore the perceived balance of risk and mitigation of SARS-CoV-2 transmission, report on their perceptions of safety in public transport during the pandemic and in the future, and consider how these perceptions and changes impact on long-term worker health and wellbeing. METHODS: This study formed part of a larger stakeholder engagement with the public transport sector. Organizational leaders and workers were recruited (n = 18) and semi-structured interviews carried out between January and May 2021. Data were analysed thematically. RESULTS: Overarching and subthemes were identified. Themes relating to perceptions and impacts of risk of COVID-19 for employees included: acceptability of risk for workers, perceptions of risk mitigation effectiveness, changes to working practices and their impact on morale and wellbeing, issues with compliance to mitigations such as social distancing and face coverings in passenger and co-worker groups alongside a lack of power to challenge behaviour effectively, and the roles of leadership and messaging. Themes related to long-lasting impacts of COVID-19 on working practices and effects on health and wellbeing included: continuing mitigations, impact of increasing passenger numbers, impact of vaccination programme, and impact of changes to business structure. CONCLUSIONS: Most public transport employees reported feeling safe, related to the extent to which their role was public-facing. However, data were collected during a time of very low passenger numbers. Current mitigation measures were thought effective in reducing the risk of viral transmission, although measures may have a detrimental effect on worker morale and wellbeing. Issues relating to non-compliance with guidance and 'in-group' behaviour were identified. Impacts on wider business sustainability and individual wellbeing of staff should be considered when developing responses to any future pandemics. Recommendations are made for prioritizing employee engagement with colleagues, and the importance of strong leadership and clear messaging in promoting adherence to behavioural mitigations.