Tumor associated macrophages as key contributors and targets in current and future therapies for melanoma.

INTRODUCTION: Despite the success of immunotherapies for melanoma in recent years, there remains a significant proportion of patients who do not yet derive benefit from available treatments. Immunotherapies currently licensed for clinical use target the adaptive immune system, focussing on Tcell interactions and functions. However, the most prevalent immune cells within the tumor microenvironment (TME) of melanoma are macrophages, a diverse immune cell subset displaying high plasticity, to which no current therapies are yet directly targeted. Macrophages have been shown not only to activate the adaptive immune response, and enhance cancer cell killing, but, when influenced by factors within the TME of melanoma, these cells also promote melanoma tumorigenesis and metastasis. AREAS COVERED: We present a review of the most up-to-date literatureavailable on PubMed, focussing on studies from within the last 10 years. We also include data from ongoing and recent clinical trials targeting macrophages in melanoma listed on clinicaltrials.gov. EXPERT OPINION: Understanding the multifaceted role of macrophages in melanoma, including their interactions with immune and cancer cells, the influence of current therapies on macrophage phenotype and functions and how macrophages could be targeted with novel treatment approaches, are all critical for improving outcomes for patients with melanoma.

Metabolic changes in response to varying whole-grain wheat and rye intake.

Epidemiological studies have shown associations between whole-grain intake and lowered disease risk. A sufficient level of whole-grain intake to reach the health benefits has not been established, and there is limited knowledge about the impact of whole-grain intake on metabolite levels. In this clinical intervention study, we aimed to identify plasma and urine metabolites associated with two different intake levels of whole-grain wheat and rye and to correlate them with clinical plasma biomarkers. Healthy volunteers (N = 68) were divided into two groups receiving either whole-grain wheat or whole-grain rye in two four-week interventions with 48 and 96 g/d of whole grains consumed. The metabolomics of the plasma samples was performed with UPLC-QTOF-MS. Plasma alkylresorcinols were quantified with GC-MS and plasma and urinary mammalian lignans with HPLC-ECD. The high-dose intervention impacted the metabolite profile, including microbial metabolites, more in the rye-enriched diet compared with wheat. Among the increased metabolites were alkylresorcinol glucuronides, sinapyl alcohol, and pipecolic acid betaine, while the decreased metabolites included acylcarnitines and ether lipids. Plasma alkylresorcinols, urinary enterolactone, and total mammalian lignans reflected the study diets in a dose-dependent manner. Several key metabolites linked with whole-grain consumption and gut microbial metabolism increased in a linear manner between the two interventions. The results reveal that an increase in whole-grain intake, particularly rye, is strongly reflected in the metabolite profile, is correlated with clinical variables, and suggests that a diet rich in whole grains promotes the growth and/or metabolism of microbes producing potentially beneficial microbial metabolites.

Healthy grocery delivery in the usual care for adults recovering from an acute coronary event: protocol for a three-arm randomised controlled trial.

INTRODUCTION: Coronary heart disease is a major contributor to the global burden of disease. Appropriate nutrition is a cornerstone of the prevention and treatment of coronary heart disease; however, barriers including cost and access to recommended foods limits long-term adherence for many. We are conducting, in adults with coronary heart disease, a randomised controlled trial comparing usual care with two dietary interventions in which usual care is augmented by 12 weeks free delivered groceries. METHODS AND ANALYSIS: Three hundred adults recovering from an acute coronary event will be recruited from outpatient cardiovascular services in three regions of Aotearoa New Zealand. Participants will be randomly allocated to three arms: usual care (control group), usual care and the free delivery of foods high in dietary fibre or usual care and the free delivery of foods high in unsaturated fats. Interventions duration is 12 weeks, with a further 12 months follow-up. The primary outcome measures are change in low-density lipoprotein (LDL) cholesterol concentration following the intervention, and a cost-effectiveness analysis of healthcare access and social costs in the year after the intervention. A broad range of secondary outcome measures include other blood lipids, anthropometry, glycaemia, inflammatory markers, gut microbiome, dietary biomarkers, food acceptability, dietary change and the facilitators and barriers to dietary change. The trial will determine whether the free provision of groceries known to reduce cardiovascular risk within usual care will be clinically beneficial and justify the cost of doing so. Results may also provide an indication of the relative benefit of foods rich in dietary fibre or unsaturated fats in coronary heart disease management. ETHICS AND DISSEMINATION: This trial, The Healthy Heart Study, has Health and Disability Ethics Committee approval (20/NTB/121), underwent Maori consultation, and has locality authority to be conducted in Canterbury, Otago and Southland. TRIAL REGISTRATION NUMBER: ACTRN12620000689976, U1111-1250-1499.

Worms and welfare: Behavioural and physiological changes associated with gastrointestinal nematode parasitism in lambs.

Parasitism with gastrointestinal nematodes (GIN) is a worldwide issue impacting negatively on animal production, health, and welfare. Therefore, early diagnostic signs of parasitism are required to allow for timely interventions. The objective of this study was to evaluate the behavioural and physiological changes in lambs associated with GIN infection. We used 30, 8-month-old Romney-cross wethers, that were administered anthelmintics until faecal egg counts (FEC) were zero and housed in an indoor facility. The study lasted 9 weeks, which comprised a 3-week pre-treatment, and a 6-week treatment phase. Lambs were randomly assigned to one of two treatments (n = 15/treatment) trickle-dosed with: 1) 1500 infective third stage larvae (L3) three days/week for 6 weeks (27,000 total L3; challenged), or 2) water 3 days/week for 6 weeks (control). Within each pen there were 5 pairs of lambs (balanced for liveweight), with each pair comprising a challenged and control lamb. Blood, faecal, and saliva samples were collected 1 week pre-treatment and weekly for 6 weeks of treatment. Behaviour was observed (e.g., feeding, lying, standing) from video-camera recordings using scan sampling every 5 min for 8 h, 1 day pre-treatment and on the day immediately prior to physiological sampling across the 6-week treatment phase (7 days in total). Accelerometers were attached to each lamb to continuously monitor behaviour from 3 weeks pre-treatment and for the remainder of the study. Liveweight, body condition, faecal soiling and faecal consistency scoring were performed weekly as was lipidomic analysis of plasma samples. From week 2 of treatment, challenged lambs spent less time feeding and more time lying than control lambs until week 5 of treatment (P ≤ 0.01). At week 3 of treatment, elevated lipids (mainly triglycerides and phospholipids), loose faeces and faecal soiling around the anus were observed in challenged lambs compared with controls (P ≤ 0.05). From week 4 of treatment, FEC were elevated in the challenged compared to control lambs (P ≤ 0.05). There was also lower liveweight gain at 4 and 5 weeks of treatment in the challenged lambs compared with control lambs (P ≤ 0.05). These results show a clear timeline of changes in behaviour (e.g., feeding and lying), lipids such as triglycerides, and digestive function (e.g., faecal soiling) suggestive of GIN subclinical disease, which show promise for use in future studies on early identification of subclinical GIN parasitism in lambs.

Metabolomic evolution of the postpartum dairy cow uterus.

High rates of early pregnancy loss are a critical issue in dairy herds, particularly in seasonal, grazing systems. Components of the uterine luminal fluid (ULF), on which the early embryo depends for sustenance and growth, partly determine early pregnancy losses. Here, changes in ULF from early to mid-postpartum in crossbred dairy cows were explored, linking them with divergent embryo development. For this, the uteri of 87 cows at Day 7 of pregnancy at first and third estrus postpartum were flushed to collect ULF. Eighteen metabolites (chiefly organic acids and sugars) significantly varied in abundance across postpartum, indicating a molecular signature of physiological recovery consistent of the upregulation of pyrimidine metabolism and glycerophospholipid metabolism, and downregulation of pentose phosphate and taurine metabolism pathways. Joint pathway analysis of metabolomics data and a previously generated proteomics data set on the same ULF samples suggests key links between postpartum recovery and subsequent successful embryo development. These include upregulation of VEGFA and downregulation of metabolism, NRF2, T-cell receptor, which appear to improve the ULF's capacity of sustaining normal embryo development, and a putative osmo-protectant role of beta-alanine. These relationships should be further investigated to develop tools to detect and reduce early pregnancy loss in dairy cows.

Quality Management in forensic science: A closer inspection.

An international survey was conducted on the benefits and limitations of accreditation to ISO17025 in forensic science, and how quality management could be improved to reflect the complexities of the end-to-end process. The survey was in response to growing concern within the forensic science community that the standard ISO17025 (and ISO17020), which is the backbone of forensic science accreditation, does not have sufficient depth and reach to properly address the quality of both the inputs (crime scene traces) and outputs (e.g., opinions in a report) of forensic science. The survey was developed around three themes: (1) fitness for purpose, (2) competences and (3) education & training. It targeted directors and senior managers, including quality managers, of forensic science laboratories/facilities. The survey was developed by the research team and disseminated with the cooperation of the International Forensic Strategic Alliance (IFSA) and six regional Networks: the American Society of Crime Laboratory Directors (ASCLD), the European Network of Forensic Science institutes (ENFSI), the Australian and New Zealand Forensic Executive Committee (ANZFEC) (formerly SMANZFL), Acadamia Iberoamericana de Criminalistica Estudios Forenses (AICEF), Asian Forensic Sciences Network (AFSN) and Southern Africa Regional Forensic Science Network (SARFS). What emerged for each of the three themes of the survey are areas of concern where the forensic science community should reconsider its approach to quality management if it is to have continuing value and relevance into the future. The results are evaluated and discussed. Briefly, the results include evidence of a lack of fitness for purpose of ISO17025 as a standard for the forensic science continuum, a lack of agreement on what forensic science is and poor levels of recognition of crime scene investigation, many competences, particularly cognitive competences, are not identified, monitored or assessed and the incentive to gain accreditation and maintain continuous improvement is intrinsic rather than customer driven.

Efficacy of Electrochemotherapy in Breast Cancer Patients of Different Receptor Status: The INSPECT Experience.

Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ (p = 0.0297) and HR+ (p = 0.0094), while overall survival was affected by time to local progression in all groups (p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions.

B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma.

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma.

European e-Delphi process to define expert consensus on electrochemotherapy treatment indications, procedural aspects, and quality indicators in melanoma.

BACKGROUND: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.

Electrochemotherapy is an effective locoregional therapy for skin metastases from melanoma, a problem faced by almost half of patients with metastatic disease. The lack of comparative studies and the heterogeneity of its clinical application among centres make it challenging to support consistent, evidence-based recommendations. To address this unmet need, a three-round online survey was conducted to establish a consensus on treatment indications, standard operating procedures, and quality indicators. In the survey, a panel of 100 European melanoma experts agreed on 56 statements that can be used to improve patient selection, homogenize treatment application, and monitor outcomes.

Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4.

Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma. CSPG4 IgE binds to human melanomas including metastases, mediates tumoricidal antibody-dependent cellular cytotoxicity and stimulates human IgE Fc-receptor-expressing monocytes towards pro-inflammatory phenotypes. IgE demonstrates anti-tumor activity in human melanoma xenograft models engrafted with human effector cells and is associated with enhanced macrophage infiltration, enriched monocyte and macrophage gene signatures and pro-inflammatory signaling pathways in the tumor microenvironment. IgE prolongs the survival of patient-derived xenograft-bearing mice reconstituted with autologous immune cells. No ex vivo activation of basophils in patient blood is measured in the presence of CSPG4 IgE. Our findings support a promising IgE-based immunotherapy for melanoma.

The Relationship between Whole-Grain Intake and Measures of Cognitive Decline, Mood, and Anxiety-A Systematic Review.

Greater intake of whole grains, compared to refined grains, is consistently associated with a reduced risk of cardiovascular disease and type 2 diabetes, both of which are associated with cognitive decline. To better understand the relationship between whole-grain intake, cognition, mood, and anxiety, a systematic review was conducted to synthesize available evidence linking whole grains to these outcomes. Four electronic databases were searched from inception to August 2021 for potentially relevant observational and interventional studies. Risk of bias (RoB) assessments were performed using the newly developed Nutrition Quality Evaluation Strengthening Tools, and the Grades of Recommendation, Assessment, Development, and Evaluation approach was used to determine the strength of evidence for each outcome. In total, 23 studies [4 randomized controlled trials (RCTs) and 19 observational studies] met the predefined eligibility criteria. Of these,12 studies included analysis of whole-grain intake and cognitive decline, 9 included mood outcomes, and 2 included both cognition and mood outcomes. The overall evidence for an association between whole-grain intake and cognition is inconclusive. With respect to mood outcomes, evidence from RCTs prospective cohort and case-control studies suggest that higher intake is linked to improved outcomes for mood and depression although the evidence is mixed for cross-sectional studies. Reporting of whole-grain intake fell short of suggested standards, and the strength of available evidence was low or very low for all outcomes. A high RoB toward studies reporting results was also noted, complicating both the interpretation of some studies and the combined evidence. Of note, few well-designed RCTs assessing the effect of whole-grain intake on measures of cognition, mood, and anxiety were identified, highlighting the need for more studies in this area. The available, although limited, evidence suggests that greater whole-grain intake is associated with better mood and anxiety-related scores and is inconclusive regarding cognitive outcomes. PROSPERO registration: CRD42021266355.

Evaluating childsmile, Scotland's National Oral Health Improvement Programme for children.

In the early 2000s, a Scottish Government Oral Health Action Plan identified the need for a national programme to improve child oral health and reduce inequalities. 'Childsmile' aimed to improve child oral health in Scotland, reduce inequalities in outcomes and access to dental services, and to shift the balance of care from treatment to prevention through targeted and universal components in dental practice, community and educational settings. This paper describes how an embedded, theory-based research and evaluation arm with multi-disciplinary input helps determine priorities and provides important strategic direction. Programme theory is articulated in dedicated, dynamic logic models, and evaluation themes are as follows: population-level data linkage; trials and economic evaluations; investigations drawing from behavioural and implementation science; evidence reviews and updates; and applications of systems science. There is also a growing knowledge sharing network internationally. Collaborative working from all stakeholders is necessary to maintain gains and to address areas that may not be working as well, and never more so with the major disruptions to the programme from the COVID-19 pandemic and response. Conclusions are that evaluation and research are synergistic with a complex, dynamic programme like Childsmile. The evidence obtained allows for appraisal of the relative strengths of component interventions and the reach and impact of Childsmile to feed into national policy.

Perspectives on the future of dissemination and implementation research in oral and craniofacial sciences.

Dissemination and implementation science is a field of research that promotes the adoption and maintenance of evidence-based interventions in healthcare delivery and community settings and seeks to understand the processes by which such adoption and maintenance occur. While dissemination and implementation science is an established field in health services research, it is relatively new and making inroads in dental, oral and craniofacial research. This article summarizes the proceedings from a scientific panel on 'Dissemination and Implementation Science for Oral and Craniofacial Health' that was held during the international Behavioral and Social Oral Health Sciences Summit. The panelists were four experts on dissemination and implementation science in dental and non-dental academic settings in the United States and Scotland, with affiliations ranging from schools of dentistry and public health to the National Institutes of Health and a healthcare system with integrated dental services. The panel discussion addressed how dissemination and implementation science can be used to further oral health research. The narrative report presented here aims to describe the panelists' reflections and insights on their current initiatives in dissemination and implementation research to inform future research endeavors within the oral and craniofacial sciences. Specifically, this article focuses on six discussion topics: (1) how organizational determinants can serve as facilitators or barriers to the implementation of evidence-based dental practice; (2) how dentistry can 'de-implement' practices that are not effective; (3) how implementation science can support the delivery of evidence-based dental practice using adaptation; (4) how to get started in implementation science; (5) how the broader environment can support large-scale implementation efforts; and (6) how oral and craniofacial science is well suited for advancing dissemination and implementation research.

Molecular insights into quality and authentication of sheep meat from proteomics and metabolomics.

Sheep meat (encompassing lamb, hogget and mutton) is an important source of animal protein in many countries, with a unique flavour and sensory profile compared to other red meats. Flavour, colour and texture are the key quality attributes contributing to consumer liking of sheep meat. Over the last decades, various factors from 'farm to fork', including production system (e.g., age, breed, feeding regimes, sex, pre-slaughter stress, and carcass suspension), post-mortem manipulation and processing (e.g., electrical stimulation, ageing, packaging types, and chilled and frozen storage) have been identified as influencing different aspects of sheep meat quality. However conventional meat-quality assessment tools are not able to elucidate the underlying mechanisms and pathways for quality variations. Advances in broad-based analytical techniques have offered opportunities to obtain deeper insights into the molecular changes of sheep meat which may become biomarkers for specific variations in quality traits and meat authenticity. This review provides an overview on how omics techniques, especially proteomics (including peptidomics) and metabolomics (including lipidomics and volatilomics) are applied to elucidate the variations in sheep meat quality, mainly in loin muscles, focusing on colour, texture and flavour, and as tools for authentication. SIGNIFICANCE: From this review, we observed that attempts have been made to utilise proteomics and metabolomics techniques on sheep meat products for elucidating pathways of quality variations due to various factors. For instance, the improvement of colour stability and tenderness could be associated with the changes to glycolysis, energy metabolism and endogenous antioxidant capacity. Several studies identify proteolysis as being important, but potentially conflicting for quality as the enhanced proteolysis improves tenderness and flavour, while reducing colour stability. The use of multiple analytical methods e.g., lipidomics, metabolomics, and volatilomics, detects a wider range of flavour precursors (including both water and lipid soluble compounds) that underlie the possible pathways for sheep meat flavour evolution. The technological advancement in omics (e.g., direct analysis-mass spectrometry) could make analysis of the proteins, lipids and metabolites in sheep meat routine, as well as enhance the confidence in quality determination and molecular-based assurance of meat authenticity.

Rapid Evaporative Ionisation Mass Spectrometry fingerprinting can discriminate lamb meat due to different ageing methods and levels of dehydration.

Dry-ageing is a technique for developing characteristic dry-aged flavour through the interplay of dehydration, lipid oxidation and microbial activities. In this study, we tested the hypothesis that the extent of drying influences the metabolite profile and the final flavour of lamb using an "Age-and-Dry" regime; and that Rapid Evaporative Ionisation Mass Spectrometry (REIMS) fingerprinting can be used to discriminate the metabolic fingerprints of lambs due to ageing methods and dehydration levels. Lamb loins (n = 60) were dehydrated with low (12%), medium (17%) and high (22%) weight losses and compared with the wet-aged equivalents using REIMS and evaluated by 12-member sensory panel. Orthogonal projection to latent structures-discriminant analysis (OPLS-DA) models based on 1400 tentatively identified m/z features were obtained for ageing methods (Q2 > 0.95) and dehydration levels (Q2 > 0.82) with high discrimination accuracy. Increased concentrations of dipeptides and metabolites associated with energy metabolism were observed in aged-and-dried lamb meat which supports the umami and savoury taste perceived by the sensory panel. A reduced concentration of polyunsaturated fatty acids with more aldehydes was observed in aged-and-dried lamb meat contributing to the nutty, roasted, and fatty flavour notes detected by the sensory panellists in these samples compared to the wet-aged. SIGNIFICANCE: Outcomes of this study demonstrated that REIMS can be used to accurately discriminate between different ageing methods and dehydration levels of meat, and the compounds that are associated with lamb flavour. The implications of this finding include: (1) the metabolite concentrating effect of dehydration and the associated effect on aged lamb flavour determined in this study could be used to tailor the processing of dry-aged lamb to deliver specific flavour outcomes in an industrial setting; (2) the ability of REIMS to rapidly detect differences in the aged lamb flavour due to dehydration effect would improve the quality of dry-aged meat and the efficiency with which it can be industrially produced. Thus, REIMS can be used as a rapid authentication and quality prediction tool for different ageing regimes and flavour for the meat industry.

Risk prediction models for head and neck cancer: A rapid review.

Background: Cancer risk assessment models are used to support prevention and early detection. However, few models have been developed for head and neck cancer (HNC). Methods: A rapid review of Embase and MEDLINE identified n = 3045 articles. Following dual screening, n = 14 studies were included. Quality appraisal using the PROBAST (risk of bias) instrument was conducted, and a narrative synthesis was performed to identify the best performing models in terms of risk factors and designs. Results: Six of the 14 models were assessed as "high" quality. Of these, three had high predictive performance achieving area under curve values over 0.8 (0.87-0.89). The common features of these models were their inclusion of predictors carefully tailored to the target population/anatomical subsite and development with external validation. Conclusions: Some existing models do possess the potential to identify and stratify those at risk of HNC but there is scope for improvement.

A qualitative study of organisational resilience in care homes in Scotland.

Providing care for the dependent older person is complex and there have been persistent concerns about care quality as well as a growing recognition of the need for systems approaches to improvement. The I-SCOPE (Improving Systems of Care for the Older person) project employed Resilient Healthcare (RHC) theory and the CARE (Concepts for Applying Resilience) Model to study how care organisations adapt to complexity in everyday work, with the aim of exploring how to support resilient performance. The project was an in-depth qualitative study across multiple sites over 24 months. There were: 68 hours of non-participant observation, shadowing care staff at work and starting broad before narrowing to observe care domains of interest; n = 33 recorded one-to-one interviews (32 care staff and one senior inspector); three focus groups (n = 19; two with inspectors and one multi-disciplinary group); and five round table discussions on emergent results at a final project workshop (n = 31). All interviews and discussion groups were recorded and transcribed verbatim. Resident and family interviews (n = 8) were facilitated through use of emotional touchpoints. Analysis using QSR NVivo 12.0 focused on a) capturing everyday work in terms of the interplay between demand and capacity, adaptations and intended and unintended outcomes and b) a higher-level thematic description (care planning and use of information; coordination of everyday care activity; providing person-centred care) which gives an overview of resilient performance and how it might be enhanced. This gives important new insight for improvement. Conclusions are that resilience can be supported through more efficient use of information, supporting flexible adaptation, coordination across care domains, design of the physical environment, and family involvement based on realistic conversations about quality of life.

Head and neck cancer in the UK: what was the stage before COVID-19? UK cancer registries analysis (2011-2018).

Introduction People who present with more advanced stage head and neck cancer (HNC) are associated with poorer outcomes and survival. The burden and trends of advanced stage HNC are not fully known at the population level. The UK national cancer registries routinely collect data on HNC diagnoses.Aims To describe trends in stage of diagnosis of HNCs across the UK before the COVID-19 pandemic.Methods Aggregated HNC incidence data were requested from the national cancer registries of the four UK countries for the ten most recent years of available data by subsite and American Joint Commission on Cancer stage at diagnosis classification. Additionally, data for Scotland were available by age group, sex and area-based socioeconomic deprivation category.Results Across the UK, rates of advanced stage HNC had increased, with 59% of patients having advanced disease at diagnosis from 2016-2018. England had a lower proportion of advanced disease (58%) than Scotland, Wales or Northern Ireland (65-69%) where stage data were available. The completeness of stage data had improved over recent years (87% by 2018).Conclusion Prior to the COVID-19 pandemic, diagnoses of HNC at an advanced stage comprised the majority of HNCs in the UK, representing the major challenge for the cancer healthcare system.