'The burden is very much on yourself': A qualitative study to understand the illness and treatment burden of hearing loss across the life course.

INTRODUCTION: Hearing loss is a chronic health condition that rises sharply with age. The way people respond to and cope with health conditions is influenced by their capacity to perform illness and treatment-related work. The aim was to explore the cumulative burdens of living with hearing loss and the resources mobilised to ease the burdens. METHODS: A qualitative design was used with semi-structured interviews (online or in-person) with participants recruited through audiology services and nonclinical services, such as lip-reading classes. Forty-six participants with hearing loss aged between 16 and 96 years were interviewed. An abductive approach, informed by May et al.'s burden of treatment theory, was used to analyse the data. RESULTS: The illness burden involved participants working to make sense of their hearing loss, engaging in emotional work in response to changes in sound, social interactions and identity and coping with the daily frustrations required to communicate with others. Abandonment and uncertainty characterised the treatment burden; participants engaged in emotional work to adjust to hearing technology and deal with the uncertainty of how their hearing might progress. To ameliorate the burdens, participants drew on internal resources (psychological, health literacy, cognitive) and external resources (social support, financial, information, technology). CONCLUSIONS: The workload of hearing loss appears largely devolved to the patient and is not always visible. Our work indicates the need to widen approaches in audiological care through the implementation of lifeworld-led care, family-centred care and peer support to build support for those with hearing loss. PATIENT OR PUBLIC CONTRIBUTION: We developed the project in consultation with members of the public who have lived experience of hearing loss recruited through Aston University and volunteer links to audiology services. We also consulted people more likely to be affected by hearing loss adults including adults with learning disabilities, older adults in residential care and people from South Asia (Bangladeshi, Indian and Pakistani communities). These individuals commented on the study aims, interview schedule and participant recruitment practices. One of our co-authors (expert by experience) contributed to the development and interpretation of themes and preparation of the final manuscript.

TLR2 on CD4+ and CD8+ T cells promotes control of Mycobacterium tuberculosis infection.

Although a role for TLR2 on T cells has been indicated in prior studies, in vivo stimulation of TLR2 on T cells by Mtb and its impact on Mtb infection has not been tested. Furthermore, it is not known if the enhanced susceptibility to Mtb of Tlr2 gene knockout mice is due to its role in macrophages, T cells, or both. To address TLR2 on T cells, we generated Tlr2fl/flxCd4cre/cre mice, which lack expression of TLR2 on both CD4 and CD8 T cells, to study the in vivo role of TLR2 on T cells after aerosol infection with virulent Mtb. Deletion of TLR2 in CD4+ and CD8+ T cells reduces their ability to be co-stimulated by TLR2 ligands for cytokine production. These include both pro- (IFN-γ, TNF-α) and anti-inflammatory cytokines (IL-10). Deletion of TLR2 in T cells affected control of Mtb in the lungs and spleens of infected mice. This suggests that T-cell co-stimulation by mycobacterial TLR2 ligands in vivo contributes to the control of Mtb infection in the lung and spleen.

Human alveolar macrophages display marked hypo-responsiveness to IFN-γ in both proteomic and gene expression analysis.

Alveolar macrophages (AM) perform a primary defense mechanism in the lung through phagocytosis of inhaled particles and microorganisms. AM are known to be relatively immunosuppressive consistent with the aim to limit alveolar inflammation and maintain effective gas exchange in the face of these constant challenges. How AM respond to T cell derived cytokine signals, which are critical to the defense against inhaled pathogens, is less well understood. For example, successful containment of Mycobacterium tuberculosis (Mtb) in lung macrophages is highly dependent on IFN-γ secreted by Th-1 lymphocytes, however, the proteomic IFN-γ response profile in AM remains mostly unknown. In this study, we measured IFN-γ induced protein abundance changes in human AM and autologous blood monocytes (MN). AM cells were activated by IFN-γ stimulation resulting in STAT1 phosphorylation and production of MIG/CXCL9 chemokine. However, the global proteomic response to IFN-γ in AM was dramatically limited in comparison to that of MN (9 AM vs 89 MN differentially abundant proteins). AM hypo-responsiveness was not explained by reduced JAK-STAT1 signaling nor increased SOCS1 expression. These findings suggest that AM have a tightly regulated response to IFN-γ which may prevent excessive pulmonary inflammation but may also provide a niche for the initial survival and growth of Mtb and other intracellular pathogens in the lung.

Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70-100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin's mechanism of anticancer activity in this context is unclear. METHODS: Metformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged ≥ 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI. DISCUSSION: Alongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis. TRIAL REGISTRATION: ISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.

Challenges to well-being in critical care.

BACKGROUND: Paediatric critical care (PCC) is a high-pressure working environment. Staff experience high levels of burnout, symptoms of post-traumatic stress, and moral distress. AIM: To understand challenges to workplace well-being in PCC to help inform the development of staff interventions to improve and maintain well-being. STUDY DESIGN: The Enhanced Critical Incident Technique (ECIT) was used. ECIT encompasses semi-structured interviews and thematic analysis. We identified 'critical incidents', challenges to well-being, categorized them in a meaningful way, and identified factors which helped and hindered in those moments. Fifty-three nurses and doctors from a large UK quaternary PCC unit were consented to take part. RESULTS: Themes generated are: Context of working in PCC, which examined staff's experiences of working in PCC generally and during COVID-19; Patient care and moral distress explored significant challenges to well-being faced by staff caring for increasingly complex and chronically ill patients; Teamwork and leadership demonstrated the importance of team-belonging and clear leadership; Changing workforce explored the impact of staffing shortages and the ageing workforce on well-being; and Satisfying basic human needs, which identified absences in basic requirements of food and rest. CONCLUSIONS: Staff's experiential accounts demonstrated a clear need for psychologically informed environments to enable the sharing of vulnerabilities, foster support, and maintain workplace well-being. Themes resonated with the self-determination theory and Maslow's hierarchy of needs, which outline requirements for fulfilment (self-actualization). RELEVANCE TO CLINICAL PRACTICE: Well-being interventions must be informed by psychological theory and evidence. Recommendations are flexible rostering, advanced communication training, psychologically-informed support, supervision/mentoring training, adequate accommodation and hot food. Investment is required to develop successful interventions to improve workplace well-being.

Care-giving experiences of parents of young people with PMLD and complex healthcare needs in the transition to adulthood years: a qualitative poetic synthesis.

OBJECTIVE: To synthesise qualitative research exploring the care-giving experiences of parents of young people with profound and multiple learning disabilities (PMLD) and complex healthcare needs, in the transition to adulthood years. METHOD: Four databases were systematically searched: Scopus, WoS Core Collection, Medline and SciELO. Included papers were assessed for quality and thematically synthesised. Findings are presented in the form of free-verse poems. RESULTS: Nineteen papers from eight countries were included. Analysis generated three themes: interdependency of parent and child, where parents retained responsibility for their child's care; apprehension regarding sharing and shifting responsibility between parents and professionals; an uncertain future in terms of care provision. CONCLUSIONS: Parents are concerned about the future care of their children. Training professionals in alternative and effective communication is fundamental to successful transition. Encouraging discussions about advanced care planning may also alleviate parental concerns and ensure good outcomes for young people with PMLD.

Protocol for the development and validation of a patient-reported experience measure (PREM) for people with hearing loss: the PREM-HeLP.

INTRODUCTION: Hearing loss is a common chronic health condition and adversely affects communication and social function resulting in loneliness, social isolation and depression. We know little about the patient experience of living with hearing loss and their views on the quality of the audiology service. In this study, we will develop and validate the first patient-reported experience measure (PREM) to understand patients' experiences of living with hearing loss and their healthcare interactions with audiology services. METHODS AND ANALYSIS: We will develop the PREM in three phases: (1) development of PREM prototype (items/statements) derived from previous qualitative work and narrative review, (2) cognitive interview testing of the PREM prototype using a 'think aloud' technique to examine the acceptability and comprehensibility of the tool and refine accordingly and (3) psychometric testing of the modified PREM with 300 participants to assess the reliability and validity of the tool using Rasch analyses with sequential item reduction. Eligible participants will be young people and adults aged 16 years and over who have hearing loss. Participants will be recruited from three clinical sites located in England (Bath, Bristol) and Scotland (Tayside) and non-clinical settings (eg, lip-reading classes, residential care settings, national charity links, social media). ETHICS AND DISSEMINATION: The study was approved by the West of Scotland Research Ethics Service (approval date: 6 May 2022; ref: 22/WS/0057) and the Health Research Authority and Health and Care Research Wales (HCRW) Approval (approval date: 14 June 2022; IRAS project ID: 308816). Findings will be shared with our patient and public involvement groups, academics, audiology communities and services and local commissioners via publications and presentations. The PREM will be made available to clinicians and researchers without charge.

'It wasn't the strategies on their own': Exploring caregivers' experiences of accessing services in the development of interventions for autistic people with intellectual disability.

LAY ABSTRACT: Many autistic individuals with intellectual disability experience anxiety, and for those who use few or no words, anxiety may present as behaviour that challenges, such as self-injury and avoiding anxiety-provoking situations. Families report difficulty accessing support from services for autistic individuals experiencing anxiety. Moreover, once receiving support, effective interventions for autistic people with intellectual disability are limited. We completed individual and group discussions with 16 caregivers of autistic people with intellectual disability, to (a) explore their experiences of accessing services for anxiety and/or behaviour that challenges for their child; and (b) understand what matters to caregivers when developing interventions that have been designed for them and the autistic individual with intellectual disability that they support. Caregivers reported that services, in their experience, did not deliver the support that they expected, and that they often needed to 'fight' for support. Caregivers considered services and families working together, the inclusion of peer support, and families being offered interventions that are flexible to individual circumstances to be important. These considerations are valuable for clinicians and researchers developing interventions and aiming to improve outcomes for autistic people with intellectual disability and their families.

Impact of Mycobacterium tuberculosis Glycolipids on the CD4+ T Cell-Macrophage Immunological Synapse.

Mycobacterium tuberculosis cell-wall glycolipids such as mannosylated lipoarabinomannan (ManLAM) can inhibit murine CD4+ T cells by blocking TCR signaling. This results in suppression of IL-2 production, reduced T cell proliferation, and induction of CD4+ T cell anergy. This study extended these findings to the interaction between primary human CD4+ T cells and macrophages infected by mycobacteria. Exposure of human CD4+ T cells to ManLAM before activation resulted in loss of polyfunctionality, as measured by IL-2, IFN-γ, and TNF-α expression, and reduced CD25 expression. This was not associated with upregulation of inhibitory receptors CTLA-4, PD-1, TIM-3, and Lag-3. By confocal microscopy and imaging flow cytometry, ManLAM exposure reduced conjugate formation between macrophages and CD4+ T cells. ManLAM colocalized to the immunological synapse (IS) and reduced translocation of lymphocyte-specific protein tyrosine kinase (LCK) to the IS. When CD4+ T cells and Mycobacterium bovis BCG-infected monocytes were cocultured, ManLAM colocalized to CD4+ T cells, which formed fewer conjugates with infected monocytes. These results demonstrate that mycobacterial cell-wall glycolipids such as ManLAM can traffic from infected macrophages to disrupt productive IS formation and inhibit CD4+ T cell activation, contributing to immune evasion by M. tuberculosis.

Compassionate communities interventions: a scoping review.

BACKGROUND: The compassionate communities (CC) movement is an emergent health promotion approach to palliative care that views illness, dying, death, and loss as universal experiences, and challenges the notion that disease precludes one from health care attention and interest. It seeks to normalise these phenomena and reorientate care to communities by activating naturally occurring networks and mobilising community resources. A surge of interventions aligned with the ethos of CC has been observed over the last decade. This scoping review seeks to synthesise what is currently known about the design, efficacy, and impact of CC interventions. METHODS: Cochrane, PubMed, Scopus, and Web of Science were systematically searched. Hand searching was performed on three key journals, reference lists and citation lists of included articles, and relevant review articles. Two levels of analysis were conducted. First, a numerical presentation of the characteristics of CC interventions. Second, a thematically orientated narrative analysis of intervention efficacy. RESULTS: A total of 1,882 records were screened; 62 papers were included. Most were implemented by palliative care organisations in Europe, North America, and Australia. Included studies were mapped against Clark et al.'s taxonomy of end-of-life interventions: educational (n=17); service (n=20); clinical (n=3); cultural (n=4); and multi-dimensional (n=18) interventions are discussed. While preliminary findings are positive, claims of efficacy are limited due to methodological paucity in the field. CONCLUSIONS: We argue that the field would benefit from more transparent and theoretically driven CC interventions in order to explicate the mechanism(s) for successful intervention implementation.

Protocol for a qualitative study exploring the lived experience of hearing loss and patient reported experience in the UK: the HeLP study.

INTRODUCTION: Worldwide, hearing loss is a significant public health issue and one of the most common chronic health conditions experienced by older adults. Hearing loss is associated with communication difficulties, social withdrawal, isolation and lower quality of life. Although hearing aid technology has improved significantly, the workload of managing hearing aids has increased. The aim of this qualitative study is to develop a novel theory of people's lived experience of hearing loss across the lifespan. METHODS: Eligible participants will be young people and adults aged 16 years and above who have a hearing loss and carers/family members of people with a hearing loss. This study will use individual, in-depth face-to-face or online interviews. With participants' permission, interviews will be audio-recorded and transcribed verbatim. A grounded theory approach to concurrent data gathering and analysis will develop grouped codes and categories and link these to provide a novel theory to describe the experience of hearing loss. ETHICS AND DISSEMINATION: The study was approved by the West of Scotland Research Ethics Service (approval date: 6 May 2022 ref: 22/WS/0057) and the Health Research Authority and Health and Care Research Wales Approval (approval date: 14 June 2022; IRAS project ID: 308816). The research will inform the development of a Patient Reported Experience Measure to improve the information and support given to patients. Findings will be disseminated through peer-reviewed articles and at academic conferences, as well as to our patient and public involvement groups, healthcare professionals, audiology services and local commissioners.

How the COVID-19 crisis affected the well-being of nurses working in paediatric critical care: A qualitative study.

OBJECTIVES: Evidence shows paediatric critical care (PCC) nurses display high rates of burnout, moral distress, symptoms associated with post-traumatic stress disorder (PTSD) and poor well-being. The COVID-19 pandemic magnified these pressures producing extremely challenging working conditions. The objective was to understand PCC nurses' lived experience of working during COVID-19 to determine the impact it had on their well-being. DESIGN: A qualitative design was used with individual, semi-structured online interviews analysed using thematic analysis. RESULTS: Ten nurses from six PCC units in England participated. Five themes were generated: (i) Challenges of working in Personal Protective Equipment (PPE), (ii) Adapting to redeployment to adult intensive care, (iii) Changes to staff working relationships, (iv) Being unable to attain work-life balance and (v) Unprocessed traumatic experiences of working in COVID-19. It was clear COVID-19 presented novel challenges to PCC nurses' well-being. With those came enforced changes in practice; some were temporary, for example use of PPE and redeployment, but others provided insight into the prerequisites for good staff well-being, for example strong professional relationships, work-life balance and managing one's psychological health. CONCLUSIONS: Findings show authentic connections between peers, verbal and non-verbal communication and a sense of belonging were crucial to nurses' well-being. A dent in PCC nurses' perceived competence significantly affected their well-being. Finally, staff need a psychologically safe space to process distress and trauma experienced during COVID-19. Future research needs to test evidence-based, theoretically-informed well-being interventions to improve and maintain PCC nurses' well-being.

Visual representations of coping with body dysmorphic disorder: a multimodal hermeneutic phenomenological approach.

BACKGROUND: Body dysmorphic disorder (BDD) is a mental health condition characterised by distress associated with perceived defects in one's physical appearance. Such defects are likely to be very slight or invisible to external observers, making it difficult for people with BDD to convey what they see. METHODS: Participants created artwork representing how they cope with BDD, then completed a follow-up interview to discuss their artwork. Framework for the Analysis of Drawings was used together with Interpretative Phenomenological Analysis. FINDINGS: Three overarching themes were generated from the analysis, centred around BDD's fusion with one's lifeworld, perceptual detachment, and fragmented selves. CONCLUSIONS: We suggest incorporating artwork creation in BDD research and clinical settings may elucidate understanding of "hidden" experiences. Clinicians may find it helpful to reflect on how the distinctive BDD "way of seeing" can infuse not just specific perceptions of the body, but also the person's wider relationship to the world.

Diarised Reflections on COVID-19 and Bereavement: Disruptions and Affordances.

COVID-19 lockdown and social distancing measures have restricted funerals and memorial events and have limited the face-to-face social networks that grieving people might normally be able to draw upon for emotional support. However, while there is considerable expert informed speculation about the impacts of grief and "COVID bereavement", detailed accounts of experiences of bereavement and bereavement support during the pandemic have the potential to enrich and provide nuance and subtlety to the evidence base. This paper draws on diary accounts of bereavement support volunteers in the UK, who have been providing support for the bereaved through these challenging times. These reveal layers of complexity to the experiences of loss, grief and bereavement during these extraordinary times. However, they also point to a number of additional themes that lend a more positive valence to the suspension of normal social expectations and memorial practices associated with the pandemic, which, we argue should be reflected upon for their potential to address the discontents of contemporary governance of end of life and bereavement.

Psychological Adjustment in Apert Syndrome: Parent and Young Person Perspectives.

To date, limited research has been carried out into the psychological impact of having a diagnosis of Apert syndrome (AS) and the life experiences of families living with this condition. The aim of the current study was to explore psychological adjustment to AS from the perspectives of young people, and their parents, with the broader goal of informing care, and support for this population.Four young people (2 male) aged 11 to 15 years and their mothers were interviewed in their homes using a semistructured interview guide and photo-elicitation methods. Transcripts were analyzed using Interpretive Phenomenological Analysis.Three superordinate themes were identified from the data: (1) Acceptance and Adjustment: A Cyclical Journey; (2) A Barrier to Adjustment: Navigating Treatment; and (3) Facilitating Adjustment: Social Support. Families described adjustment as a cyclical process, which was sensitive to change, particularly in the context of ongoing medical treatment. Families also utilized many resources, particularly in the form of social support, to adjust to the challenges of AS and build resilience.The findings of this study have important implications for the implementation of patient-centered care within designated craniofacial treatment centers, which should at a minimum include the provision of reliable information throughout the treatment pathway, additional support from health professionals at key times of transition, and the coordination of support across medical teams, and other key organizations in the child's life.

A phenomenological exploration of self-identified origins and experiences of body dysmorphic disorder.

Body dysmorphic disorder (BDD) is a debilitating mental health condition that presently affects ~2% of the general population. Individuals with BDD experience distressing preoccupations regarding one or more perceived defects in their physical appearance. These preoccupations and perceived distortions can have a profound impact on key areas of social functioning and psychological health. Individuals' BDD origins have not been explored in significant depth and have been, often unhelpfully, conflated with social media usage and exposure to idealistic imagery of the body. Such generalisations fail to acknowledge the complexity of BDD development and onset, highlighting the importance of moving towards an understanding of people's implicit theories regarding their own experience. It is therefore essential to gain insight into how individuals make sense of the experiences which they believe led to the development and onset of BDD. The aim of this exploratory study was to elicit and phenomenologically analyse the accounts of individuals with lived experience of BDD in order to examine their beliefs about its origins and understand how they navigate the world with a distorted sense of self. Participants provided written and verbal accounts regarding both their BDD onset and experiences of living with the disorder. Both components of the study were analysed using Interpretative Phenomenological Analysis. Four main themes were generated from the data: Exposure to bullying and external critique of appearance; Experiencing rejection, shame, and a sense of not being enough; Developing an awareness of the solidification of concerns, and Learning about and reflecting upon triggers. Participants attributed their BDD onset to adverse experiences such as childhood bullying, receiving appearance-focused criticism, rejection and being subjected to emotional and physical abuse. The findings from this study highlight the complexity of BDD development and onset in individuals, and the need for appropriate care and treatment for those affected by BDD.

Qualitative study exploring the well-being experiences of paediatric critical care consultants working in the UK during the COVID-19 pandemic.

OBJECTIVES: The aim of this study was to examine the well-being experiences of consultants working in paediatric critical care (PCC) settings in the UK during the COVID-19 pandemic. DESIGN: Qualitative design using individual interviews and thematic analysis. SETTING: PCC. PARTICIPANTS: Eleven medical consultants working in PCC in a range of PCC settings/transport teams in the UK from nine units participated. Participants ranged in years of experience as a consultant from four to 23 years. METHODS: A set of open semistructured questions were used to elicit information about participants' experiences of workplace well-being. Interviews were audiorecorded and transcribed. FINDINGS: Thematic analysis identified six themes and data saturation was reached. These were as follows: (1) positive and negative impact of working during COVID-19, (2) job satisfaction and public scrutiny in the unique environment of PCC, (3) supporting the workforce through modified shift work, (4) perceptions of support and recognition offered from the hospital management, (5) successful coping strategies are personal and adaptive, and (6) importance of civility and good teamwork CONCLUSION: Findings show that consultants' well-being is challenged in a number of ways and that the solutions to the problem of burn-out are multifaceted. Action is required from individual consultants, clinical teams, hospital management and national regulatory bodies. Our work corroborates the recent General Medical Council report highlighting doctors' core needs for well-being: autonomy, belonging, competence. Burn-out is a long-term problem, requiring sustainable solutions. Future research needs to develop and evaluate the effectiveness of evidence-based interventions to improve consultants' well-being. Trials of effectiveness need to present evidence that will persuade hospital management to invest in their consultants' well-being within the economic context of reduced budgets and limited PCC workforce.

Understanding what wellbeing means to medical and nursing staff working in paediatric intensive care: an exploratory qualitative study using appreciative inquiry.

AIMS AND OBJECTIVES: To explore what wellbeing means to medical and nursing staff working in a large paediatric intensive care (PIC). DESIGN: Exploratory qualitative design using an appreciative inquiry framework. SETTING: PIC unit; primary, secondary and tertiary. PARTICIPANTS: 46 nurses and doctors working on PIC. INTERVENTIONS: A set of images were used together with open-ended questions to prompt staff to discuss what wellbeing means to them. Interviews were audiorecorded and transcribed. Data were analysed thematically. RESULTS: Images depicting nature, children and groups of adults were selected most. Meanings of wellbeing for PIC staff can be understood through three themes: (1) Being nurtured and supported at work, (2) Importance of nature and (3) Social support independent of work. The first theme considered the importance of being listened to at work as well as staff highlighting the value of being in control at work. Within the second theme, being active in nature and outdoors as well as the importance of being in the present moment was illustrated. Within the final theme, staff expressed the value of having support independent of work and highlighted the importance of spending time with family. CONCLUSIONS: This study provides a unique insight into how individuals working in PIC experience wellbeing and what wellbeing means to them. Understanding how healthcare professionals in PIC settings experience wellbeing and what wellbeing means to them will enable researchers to develop interventions designed to enhance staff wellbeing based on lived experience.

When benefit eligibility and patient-led care intersect. Living in the UK with chronic illness: Experiences of the work capability assessment.

Individuals living with chronic physical health conditions are more likely to be out-of-work than other groups. Often framed as a 'response' to these statistics, many countries have introduced policy instruments for promoting the employment of individuals with chronic conditions. This qualitative study sought to explore the impact of welfare reforms on UK individuals. Employing a phenomenological approach, semi-structured interviews were conducted with five participants living with chronic conditions. Three themes were generated using Interpretative Phenomenological Analysis: 'intersubjective sense making of the condition'; 'battles for control' and 'the fluidity and strengthening of identity'. Implications for further, holistic, policy reform are explored.

Prediction of strain engineerings that amplify recombinant protein secretion through the machine learning approach MaLPHAS.

This article presents a discussion of the process of precision fermentation (PF), describing the history of the space, the expected 70% growth over the next 5 years, various applications of precision fermented products, and the markets available to be disrupted by the technology. A range of prokaryotic and eukaryotic host organisms used for PF are described, with the advantages, disadvantages and applications of each. The process of setting up PF and strain engineering is described, as well as various ways that computational analysis and design techniques can be employed to assist PF engineering. The article then describes the design and implementation of a machine learning method, machine learning predictions having amplified secretion (MaLPHAS) to predict strain engineerings, which optimise the secretion of a recombinant protein. This approach showed an in silico cross-validated R 2 accuracy on the training data of up to 46.6% and in an in vitro test on a Komagataella phaffii strain, identified one gene engineering out of five predicted, which was shown to double the secretion of a heterologous protein and outperform three of the best-known edits from the literature for improving secretion in K. phaffii.