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Background: Patient reported outcome measures (PROMs) are used to understand the impact of lower limb reconstruction surgery on patients' quality of life (QOL). Existing measures have not been developed to specifically capture patient experiences amongst adults with lower limb conditions that require reconstruction surgery. This review aimed to synthesise qualitative evidence to identify what is important to patients requiring, undergoing, or following reconstructive surgery for lower limb conditions.Methods: MEDLINE, Embase, PsychINFO and Cinahl were searched from inception until November 2020. Studies were included if they employed qualitative research methods, involved patients requiring, undergoing or following lower limb reconstruction and explored patients' experiences of care, treatment, recovery and QOL. Mixed methods studies that did not separately report qualitative findings, mixed population studies that were not separately reported and studies in languages other than English were excluded. Included studies were analysed using thematic synthesis. The Critical Appraisal Skills Programme qualitative studies checklist was used to undertake quality assessment.Results: Nine studies met the inclusion criteria. The thematic synthesis identified two overarching themes: (1) areas of living key to QOL for lower limb reconstruction patients and (2) moving towards a new normal. The way in which lower limb reconstruction affects an individual's QOL and their recovery is complex and is influenced by a range of inter-related factors, which will affect patients to varying degrees depending on their individual circumstances. We identified these factors as: pain, daily functioning and lifestyle, identity, income, emotional wellbeing, support, the ability to adapt and adjust and the ability to move forwards.Conclusions: The way patients' QOL is affected after a lower limb reconstruction is complex, may change over time and is strongly linked to their recovery. These findings will aid us in developing a conceptual framework which identifies the outcomes important to patients and those that should be included in a PROM. Further research is then required to establish whether the range of factors we identified are captured by existing PROMs. Depending on the outcome of this work, a new PROM for patients following lower limb reconstruction may be required. [ABSTRACT FROM AUTHOR]

Background: Older patients with lower limb amputation, categorised as having "limited community mobility", are under-researched. Understanding their experience with a new prosthetic ankle-foot is important when designing clinical trials. The aim of this qualitative study was to explore the adjustments they made after amputation and the acceptability of a self-aligning ankle-foot (SA-AF) to older adults., Methods: Fourteen participants, who took part in the STEPFORWARD randomised controlled feasibility trial (ISRCTN15043643), were purposively recruited; nine were intervention participants and five were standard care participants. They were asked to reflect on their life prior to and consider the adjustments they made following their amputation. Participants in the intervention group were also asked about their views of the new SA-AF compared to their standard non-SA-AF. A thematic analysis was undertaken., Results: Three broad themes were identified: The impact of the amputation; Role of clinical support; and Experiences of the SA-AF. The findings tell a narrative of the long-term impact that amputation has on these individuals' lives. Participants randomised to receive the SA-AF were very positive about it, reporting less pain, greater mobility and being able to do more., Conclusion: Participants who used the SA-AF found it an acceptable intervention. These findings suggest that a full-scale RCT is warranted.

Background: The Covid-19 pandemic had a profound effect on the delivery of healthcare research. Covid-19 research was prioritised and many non-essential trials were paused. This study explores the engagement experiences of trial participants', PPIE contributors' and trial staff during the Covid-19 pandemic and towards recovery and restoring a diverse and balanced UK clinical trials portfolio., Methods: Interviews and focus groups were undertaken with PPIE contributors, trial participants and trial staff members from NIHR research trials across the UK (November 2020-June 2021) across portfolio specialities: Cancer, Oral and Dental Health, Musculoskeletal Disorders, Cardiovascular Disease, Neurological Disorders, Primary Care, and Conditions associated with susceptibility to Covid-19 (Diabetes, Stroke, Respiratory Disorders). Topic guides were developed for each participant group and interviews were conducted over Zoom. The transcripts were analysed using codebook thematic analysis in NVivo (V.12)., Results: 106 participants comprising, 45 PPIE contributors, 27 trial participants and 34 trial staff members were recruited. Three themes to engagement with trials during Covid-19 were developed. 1) Ensuring continued contact. Continued and tailored communication, having a trial point of contact and regular updates all enhanced trial engagement and retention. Patients' unfamiliarity with materials being sent electronically reduced engagement and trust. 2) A balanced move to remote consultations. Remote follow-up and monitoring were convenient and allowed for wider recruitment across the UK. Participants were more likely to discuss personal subjects in their own homes. Remote visits lacked a personal touch, some concerns over missed diagnoses or being unable to appreciate the situation, technical abilities or equipment failures were seen as barriers, especially for disadvantaged or older people. 3) The importance of feeling fully informed. Factors that supported attendance were knowledge about trial conduct adherence to Covid-19 regulations, social distancing, clear signage at the site and opportunities to ask questions. Barriers included not knowing what to expect and not feeling safe with rules and regulations., Conclusions: Our findings highlight a number of ways to future proof trial delivery against future pandemics or disruptions such as offering online options to participate in research, ensuring consistent communication between participants and the research team, making sure participants feel fully informed and the continued reassurance of safety in the clinical setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Leggett 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.)

Objectives: To develop a patient's attitude questionnaire regarding prevention in oral health for use internationally., Methods: Using a mixed methods approach, a questionnaire was developed and refined as part of ADVOCATE (Added Value for Oral Care) study, involving partners in six countries: Netherlands, Hungary, Denmark, Ireland, Germany, and the UK. A literature review explored the history of oral healthcare delivery systems to develop a template for each of the six ADVOCATE countries. A systematic review identified the perceived barriers and facilitators to preventive oral healthcare and underpinned a topic guide and established the patient questionnaire domains. Focus groups in each ADVOCATE country developed the first version of the questionnaire. Patient and Public Involvement and Engagement (PPIE) in each ADVOCATE country tested the questionnaire and led to further refinement. The questionnaire was produced in five languages. Content validity and reproducibility used principal component analysis (PCA) and exploratory factor analysis (EFA) refined the questionnaire., Results: The literature review aided an understanding of each country's oral healthcare system, and the findings from the 25 studies identified in the systematic review found the main barriers/facilitators to preventive oral healthcare were cost, knowledge (preventive treatments and advice), and a patient awareness and adherence to preventive advice/treatments. Interviews and focus groups with 148 participants in the ADVOCATE study identified receiving the appropriate level of care/feeling valued, cost, level of motivation/priority, not feeling informed, knowledge, and skill mix as the main barriers/facilitators. Fifty-three PPIE members refined the questionnaire. The pilot questionnaire was tested with 160 participants. Non-essential or highly correlated variables were then removed, leaving 38 items, covering 6 domains (cost, advice received, advice wanted, message delivery, motivation, knowledge, and responsibility) within the questionnaire. A second pilot test-run was undertaken with 185 participants. The test-re-test reliability demonstrated strong consistency of responses between the two time points (kappa range 0.3-0.7, most p < .0011), which culminated with a final version of the Patient Attitudes to Prevention in Oral Health Questionnaire (PAPOH) questionnaire., Conclusions: This mixed-methods approach enabled the development of a multi-language attitudinal questionnaire for use with patients (PAPOH) to compare attitudes to oral disease prevention internationally., (© 2022 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Purpose: Patient-reported outcome measures (PROMs) are used to understand the impact of lower limb reconstruction on patient's Health-Related Quality of Life (HRQL). Existing measures have not involved this group of patients and their experiences during development. This study aimed to develop a conceptual framework to reflect what is important to patients requiring, undergoing or after undergoing reconstructive surgery., Methods: Our population of interest was people requiring, undergoing or after undergoing reconstructive surgery due to trauma, malunion, nonunion, infection or congenital issues treated by internal or external fixation. We undertook semi-structured interviews with patients and orthopaedic healthcare professionals (surgeons, methodologists and patient contributors) in England., Results: Thirty-two patients and 22 orthopaedic healthcare professionals (surgeons, methodologists and patient contributors) were interviewed between November 2020 and June 2021. Eight domains from a previously developed preliminary conceptual framework were used as a framework around which to code the interviews using thematic analysis. Six domains important to patients (from the perspective of patients and orthopaedic healthcare professionals) were included in the final conceptual framework: pain, perception-of-self, work and finances, daily lifestyle and functioning, emotional well-being, and support. These findings, plus meetings with our advisory panel led to the refinement of the conceptual framework., Conclusion: The first five domains relate to important outcomes for patients; they are all inter-related and their importance to patients changed throughout recovery. The final domain-support (from work, the hospital, physiotherapists and family/friends)-was vital to patients and lessened the negative impact of the other domains on their HRQL. These new data strengthen our original findings and our understanding of the domains we identified in the QES. The next step in this research is to ascertain whether current PROMs used with this group of patients adequately capture these areas of importance., (© 2023. The Author(s).)

Background: Despite significant progress in the control of oral diseases since the discovery of fluoride in the 1940s, dental caries and periodontal diseases continue to affect a significant proportion of the population, particularly socially disadvantaged and lower socioeconomic groups. The National Health Service in England provides preventive advice and treatments as part of an oral health assessment, and evidence-based guidance recommends the use of fissure sealants and topical fluorides in addition to dietary and oral hygiene advice. Although oral health promotion and education have become expected parts of dental care, the need for restorative treatments remains relatively high. We aimed to explore how barriers to preventive advice and treatment for NHS patients may be hindering the provision of prevention in oral health to patients from the perspectives of multiple key stakeholders., Methods: Semi-structured interviews and focus groups were undertaken between March 2016-February 2017 with four groups of stakeholders: dentists, insurers, policy makers and patient participants. The interviews were analysed using deductive, reflexive thematic analysis., Results: Thirty-two stakeholders participated: 6 dentists, 5 insurers, 10 policy makers, and 11 patient participants. Four themes were developed: Perspectives on the clarity of oral health messaging and patient's knowledge, The variability of prioritising prevention, Influences of the dentist-patient relationship on effective communication and Motivation to enact positive oral health behaviours., Conclusions: The findings from this research indicate that patients' knowledge of and priority placed on prevention is variable. Participants believed that more targeted education could be valuable in enhancing these. A patient's relationship with their dentist could also influence their level of knowledge through the information shared with them, their receptivity to the preventive messages and the value they place on it. However, even with knowledge, prioritising prevention and a good patient-dentist relationship, without motivation to engage in preventive behaviour the impact of these is reduced. Our findings are discussed in relation to the COM-B model of behaviour change., (© 2023. The Author(s).)

Objectives: To examine the effect of general practitioners (GPs) working in or alongside the emergency department (GPED) on patient outcomes and experience, and the associated impacts of implementation on the workforce., Design: Mixed-methods study: interviews with service leaders and NHS managers; in-depth case studies (n=10) and retrospective observational analysis of routinely collected national data. We used normalisation process theory to map our findings to the theory's four main constructs of coherence, cognitive participation, collective action and reflexive monitoring., Setting and Participants: Data were collected from 64 EDs in England. Case site data included: non-participant observation of 142 clinical encounters; 467 semistructured interviews with policy-makers, service leaders, clinical staff, patients and carers. Retrospective observational analysis used routinely collected Hospital Episode Statistics alongside information on GPED service hours from 40 hospitals for which complete data were available., Results: There was disagreement at individual, stakeholder and organisational levels regarding the purpose and potential impact of GPED (coherence). Participants criticised policy development and implementation, and staff engagement was hindered by tensions between ED and GP staff (cognitive participation). Patient 'streaming' processes, staffing and resource constraints influenced whether GPED became embedded in routine practice. Concerns that GPED may increase ED attendance influenced staff views. Our quantitative analysis showed no detectable impact on attendance (collective action). Stakeholders disagreed whether GPED was successful, due to variations in GPED model, site-specific patient mix and governance arrangements. Following statistical adjustment for multiple testing, we found no impact on: ED reattendances within 7 days, patients discharged within 4 hours of arrival, patients leaving the ED without being seen; inpatient admissions; non-urgent ED attendances and 30-day mortality (reflexive monitoring)., Conclusions: We found a high degree of variability between hospital sites, but no overall evidence that GPED increases the efficient operation of EDs or improves clinical outcomes, patient or staff experience., Trial Registration Number: ISCRTN5178022., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Around 43% of emergency department (ED) attendances can be managed in general practice. Strategies to address this include directing appropriate patients to GPs working in or alongside EDs (GPED). Views of GPs choosing to work in GPED roles may inform planning and implementation of GPED services as well as wider general practice provision., Aim: To explore the experiences and motivations of GPs choosing to work in GPED services in England, and to identify factors that may support or hinder GPs working in GPED roles., Design and Setting: Thematic analysis of 42 semi-structured interviews of GPs working in 10 GPED case sites across England., Method: Qualitative GP interviews from a mixed-methods study of GPs in GPED roles were thematically analysed in relation to research aims., Results: Four themes were generated: the 'pull' of a portfolio career; the 'push' of disillusionment with general practice; professional reciprocity; sustainability of GPED services and core general practice. Flexible, favourable working conditions, collaboration, and professional development made GPED an attractive workplace, often as part of a portfolio career or after retiring from core general practice. Working in GPED services was largely driven by disillusionment with core general practice. Both GPED and core general practice were thought to benefit from GPED GPs' skills. There were concerns about GPED sustainability and destabilisation of core general practice., Conclusion: GPED may extend the clinical careers of experienced GPs and support recruitment and retention of more recently qualified GPs. Despite some benefits, GPED may destabilise core general practice and increase pressure on both environments., (© The Authors.)

Background: The Brushing RemInder 4 Good oral HealTh (BRIGHT) trial is investigating the clinical and cost-effectiveness of a multi-component behaviour change intervention to reduce the prevalence of dental caries in young people from deprived areas aged 11-13 years. Mobile health has gained popularity in delivering behaviour change interventions for improving oral health. The intervention, based on behaviour change theory, consists of two components; a single classroom-based session embedded in the school curriculum and a series of follow-up text messages (SMS) delivered twice daily to participants. This element of the process evaluation aimed to explore the acceptability of the BRIGHT intervention for pupils and school staff., Methods: Qualitative study, based on the concept of acceptability. Focus groups were conducted with 50 pupils, from six secondary schools across the UK, who had received the intervention. Semi-structured interviews were conducted with 12 members of staff. Purposive maximum variation sampling was used. Interviews were transcribed verbatim and analysed using a framework approach., Results: In line with the theoretical framework of acceptability, affective attitude, perceived effectiveness, ethicality, burden and self-efficacy were identified as factors that affect the acceptability of the BRIGHT intervention. Pupil participants appreciated learning about the consequences of inadequate brushing particularly the photographs of carious teeth during the classroom-based session. More detailed information on brushing techniques and follow-up lessons on oral health were recommended by pupils. In terms of the SMS, the data suggest that pupil participants found them to be helpful reminders for brushing their teeth. To further improve acceptability, more choice over the timing of the messages and greater interactivity to reduce tedium were suggested. Staff participants recognised the value of the lesson and reported that in general the content was suitable for their pupils. Having the lesson material prepared for them, having the necessary support and whether it was included in the curriculum, were factors that improved acceptability., Conclusion: Overall, pupils and staff found the BRIGHT intervention acceptable and made some suggestions which could be adopted in any subsequent implementation of the intervention., (© 2022. The Author(s).)

Background: Emergency Department attendance is increasing internationally, of which a significant proportion could be managed in general practice. In England, policies backed by substantial capital funding require such patients attending Emergency Departments be directed or 'streamed' to General Practitioners working in or parallel to Emergency Departments. However, evidence for streaming is limited and the processes of streaming patients attending Emergency Departments to General Practitioners lacks exploration., Objectives: This paper explores streaming to General Practitioners in and alongside Emergency Departments at ten sites across England. It highlights positive streaming practice, as well as issues that may contribute to poor streaming practice, in order to inform future service improvement., Methods: A longitudinal qualitative study was conducted with data collected between October 2017 and December 2019 across 10 case study sites throughout England as part of a broader mixed methods study. 186 non-participant observations and 226 semi-structured interviews with 191 health professionals working in Emergency Departments or related General Practitioner Services were thematically analysed in relation to streaming processes and experiences., Results: Six interconnected themes influencing streaming were identified: implementing and maintaining structural support; developing and supporting streaming personnel; implementing workable and responsive streaming protocols; negotiating primary/secondary care boundaries; developing and maintaining interprofessional relationships and concerns for patient safety. Streaming was considered central to the success of General Practitioners in/parallel to Emergency Departments. The importance of the skills of streaming nurses in delivering an optimal and safety critical service was highlighted, as was the skillset of General Practitioners and interprofessional relationships between streamers and General Practitioners. There was no distinct streaming model or method associated with good streaming practice to General Practitioners in/alongside Emergency Departments, instead factors for success were identified and key recommendations suggested. 'Inappropriate' streaming was identified as a problem, where patients streamed to General Practitioners in or parallel to Emergency Departments required Emergency Department management, or patients suitable for General Practitioner care were kept in the Emergency Department., Conclusion: Despite adopting differing methods, commonalities across case sites in the delivery of good streaming practice were identified, leading to identification of key recommendations which may inform development of streaming services., Study Registration: ISRCTN51780222. Tweetable abstract: Workplace culture and the skillset of streamers and General Practitioners is crucial to streaming of patients to General Practitioners in Emergency Departments., Competing Interests: Conflict of Interest One author (JB) is seconded part-time to the post of interim Chief Medical Officer at NHS Digital. All other authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore the potential impacts of introducing General Practitioners into Emergency Departments (GPED) from the perspectives of service leaders, health professionals and patients. These 'expectations of impact' can be used to generate hypotheses that will inform future implementations and evaluations of GPED., Design: Qualitative study consisting of 228 semistructured interviews., Setting: 10 acute National Health Service (NHS) hospitals and the wider healthcare system in England. Interviews were undertaken face to face or via telephone. Data were analysed thematically., Participants: 124 health professionals and 94 patients and carers. 10 service leaders representing a range of national organisations and government departments across England (eg, NHS England and Department of Health) were also interviewed., Results: A range of GPED models are being implemented across the NHS due to different interpretations of national policy and variation in local context. This has resulted in stakeholders and organisations interpreting the aims of GPED differently and anticipating a range of potential impacts. Participants expected GPED to affect the following areas: ED performance indicators; patient outcome and experience; service access; staffing and workforce experience; and resources. Across these 'domains of influence', arguments for positive, negative and no effect of GPED were proposed., Conclusions: Evaluating whether GPED has been successful will be challenging. However, despite uncertainty surrounding the direction of effect, there was agreement across all stakeholder groups on the areas that GPED would influence. As a result, we propose eight domains of influence that will inform our subsequent mixed-methods evaluation of GPED., Trial Registration Number: ISRCTN51780222., Competing Interests: Competing interests: JB is seconded part-time to the post of interim Chief Medical Officer at NHS Digital. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Lower limb conditions requiring reconstructive surgery can be either congenital or acquired from trauma, infection or other medical conditions. Patient-reported outcome measures (PROMs) are often used by healthcare professionals to assess the impact of a patient's condition (and treatment) on quality of life. However, we are not aware of any measures developed specifically for people requiring lower limb reconstructive surgery. Consequently, it is not clear the extent to which current PROMs accurately and specifically measure the outcomes that are important to these patients., Methods and Analysis: The 'PROLLIT' (Patient-Reported Outcome Measure for Lower Limb Reconstruction) involves three phases: to explore what is important to patients with regard to quality of life (phase 1), ascertain whether current measures adequately capture these experiences (phase 2) and if not begin, the development of a new PROM (phase 3). The population of interest is people requiring, undergoing or after undergoing reconstructive surgery for a lower limb condition. In this paper, we describe phase 1, which aims to develop a conceptual framework to identify and map what is important to this group with regard to social interactions, employment, perceived health and quality of life after condition onset/injury and throughout recovery. The conceptual framework will be developed through three steps: (step A) a qualitative evidence synthesis, (step B) a qualitative study with patients and staff to explore patient's views and experiences of lower limb reconstructive surgery and (step C) a round table discussion with key stakeholders where findings from step A and step B will be brought together and used to finalise the conceptual framework., Ethics Consideration and Dissemination: Ethical approval has been granted for the qualitative data collection (step B) from South Central Berkshire Research Ethics committee (REF:20/SC/0114). Findings from steps A and B will be submitted for peer-reviewed publication in academic journals, and presented at academic conferences., Prospero Registration Number: CRD42019139587., Isrctn Registration Number: ISRCTN75201623., Competing Interests: Competing interests: CM reports grants from Hull University Teaching Hospitals NHS Trust, during the conduct of the study; grants from British Orthopaedic Association, outside the submitted work. HS reports grants from Health & Technology Assessment, during the conduct of the study; grants from B.Braun, personal fees from Biocomposites and personal fees from Orthofix, outside the submitted work. MH, HL, AS and CH have nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Aim: To compare the provision and costs at the point of delivery of dental treatments in a sample of European Union (EU) Member States., Materials and Methods: A questionnaire with open-ended questions was sent to oral health policy-makers in Denmark, England, France, Germany, Hungary, Ireland, Italy, the Netherlands, Poland, Romania, Scotland and Spain. They were asked to answer questions on the probable costs and provision of treatment in their country for a vignette presented as a pre-defined case., Results: All respondents returned answers to all questions. Wide variations were reported in: who would deliver care, cost of items of care and total cost. For example, in France, only a dentist would provide the treatment. In Denmark, England, Germany, Ireland, Italy, the Netherlands and Scotland, it was likely that the treatment would be provided by a combination of dentist, dental hygienist and dental nurse. Fees ranged from €72 in England (if treated within the NHS) to €603 in Denmark. In Italy, Spain and for most patients in Romania, all treatment costs were paid by the patient. In the other nine countries, some subsidy from public funds was available. In terms of percentage of per capita Gross National Income, the cost to the patient ranged from 0.12% in France to 1.57% in Spain., Conclusions: It was apparent that there are wide variations between EU Member States in the manner in which oral healthcare is delivered, its cost and the extent to which the cost of treatment is subsidised from state funds or through private insurance., (© 2018 The Authors. International Dental Journal published by John Wiley & Sons Ltd on behalf of World Dental Federation.)

The provision of self-regulated learning (SRL) enhanced feedback on performing clinical skills and making a clinical diagnosis recognizes the importance of feedback on the use of key SRL processes. In contrast to the broader concept of self-directed learning, SRL has a specific focus on the individual learner's approach to achieve a task, including their planning, self-monitoring, and future adaptations. The key SRL processes can be identified using structured microanalysis during the clinical task and feedback to the learner using the tips outlined in this article. It is essential that SRL enhanced feedback is integrated with best practice on providing feedback to ensure that its potential is achieved.

Objectives: Remediation is usually offered to medical students and doctors in training who underperform on written or clinical examinations. However, there is uncertainty and conflicting evidence about the effectiveness of remediation. The aim of this systematic review was to synthesise the available evidence to clarify how and why remediation interventions may have worked in order to progress knowledge on this topic., Methods: The MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ERIC (Educational Resources Information Centre), Web of Science and Scopus databases were searched for papers published from 1984 to April 2012, using the search terms 'remedial teaching', 'education', 'medical', 'undergraduate'/or 'clinical clerkship'/or 'internship and residency', 'at risk' and 'struggling'. Only studies that included an intervention, then provided retest data, and reported at least one outcome measure of satisfaction, knowledge, skills or effects on patients were eligible for inclusion. Studies of practising doctors were excluded. Data were abstracted independently in duplicate for all items. Coding differences were resolved through discussion., Results: Thirty-one of 2113 studies met the review criteria. Most studies were published after 2000 (n=24, of which 12 were published from 2009 onwards), targeted medical students (n=22) and were designed to improve performance on an immediately subsequent examination (n=22). Control or comparison groups, conceptual frameworks, adequate sample sizes and long-term follow-up measures were rare. In studies that included long-term follow-up, improvements were not sustained. Intervention designs tended to be highly complex, but their design or reporting did not enable the identification of the active components of the remedial process., Conclusions: Most remediation interventions in medical education focus on improving performance to pass a re-sit of an examination or assessment and provide no insight into what types of extra support work, or how much extra teaching is critical, in terms of developing learning. More recent studies are generally of better quality. Rigorous approaches to developing and evaluating remediation interventions are required., (© Blackwell Publishing Ltd 2013.)

SecA2 is an ATPase present in some pathogenic Gram-positive bacteria, is required for translocation of a limited set of proteins across the cytosolic membrane, and plays an important role in virulence in several bacteria, including mycobacteria that cause diseases such as tuberculosis and leprosy. However, the mechanisms by which SecA2 affects virulence are incompletely understood. To investigate whether SecA2 modulates host immune responses in vivo, we studied Mycobacterium marinum infection in two different hosts: an established zebrafish model and a recently described mouse model. Here we show that M. marinum ΔsecA2 was attenuated for virulence in both host species and SecA2 was needed for normal granuloma numbers and for optimal tumor necrosis factor alpha response in both zebrafish and mice. M. marinum ΔsecA2 was more sensitive to SDS and had unique protrusions from its cell envelope when examined by cryo-electron tomography, suggesting that SecA2 is important for bacterial cell wall integrity. These results provide evidence that SecA2 induces granulomas and is required for bacterial modulation of the host response because it affects the mycobacterial cell envelope.