Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer.

Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3. Tumors with a high density of CTLs showed enrichment for transcripts linked to tissue-resident memory cells (TRM cells), such as CD103, and CTLs from CD103hi tumors displayed features of enhanced cytotoxicity. A greater density of TRM cells in tumors was predictive of a better survival outcome in lung cancer, and this effect was independent of that conferred by CTL density. Here we define the 'molecular fingerprint' of tumor-infiltrating CTLs and identify potentially new targets for immunotherapy.

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

Evaluation of a mobile COVID-19 vaccination van outreach service in an outer South London borough.

BACKGROUND: This study aimed to explore differences in users of a COVID-19 mobile vaccine van service and users of a COVID-19 static vaccination hub, and the impact of changes in national COVID-19 vaccine policy on vaccine uptake. METHODS: The age distribution of male and female service users in each service was compared. The average number of vaccines administered per hour per week was analysed. RESULTS: Females aged 80-89 represented 51.9% (95% CI 49.5-54.3%) of female vaccine van users compared with 2.8% (95% CI 2.5-3.1%) of female static hub users. The static hub had significantly greater proportions of female service users in all other age brackets.For males, the greatest difference was in those aged 70-79 who represented 29.8% (95% CI 27-32.6%) of vaccine van users and 16.6% (95% CI 16-17.2%) static hub users.Fewer vaccines were administered 2-3 weeks before the COVID-19 autumn booster policy change compared with 2-3 weeks after; 1.92 versus 6.25 vaccines per hour, respectively (Mann-Whitney U = 7, n1 = 11, n2 = 8, P < 0.01 two-tailed). CONCLUSIONS: These findings suggest that a mobile vaccine van service is an effective model for increasing COVID-19 vaccination uptake in elderly residents, particularly after a national policy change.

Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

BACKGROUND: Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 23/29 statements in round 1 and 17/18 statements in round 2. There was a high level of concordance with treatment criteria in the adult setting. The limitations of applying assessment tools developed for use in adult patients to the paediatric setting were highlighted. Treatment targets in the paediatric setting should include objective metrics for disease severity and psychological impact on the patients and their family, and be based on validated, age-appropriate tools. CONCLUSION: While the assessment, classification and management of moderate to severe psoriasis in paediatric patients aligns with metrics established for adults, it is vital that nuances in the transition from childhood to adolescence be taken into account. Future research should focus on psoriasis severity assessment scales specific to the paediatric setting.

A decision methodology for site-level ecosystem accounting.

The United Nations System of Environmental-Economic Accounting Ecosystem Accounting (SEEA EA) framework is the international standard for ecosystem accounting. To date, application of SEEA EA has been predominantly at large scales, usually at landscape and national levels. However, many environmental management decisions are taken locally, in site-specific contexts. While the use of SEEA EA continues to develop at all scales, there is currently no widely endorsed methodology for employing SEEA EA at local scales, such as the site level. We present a methodology for developing site-level ecosystem accounts, describing the important decisions at each step of the process. We also provide two case studies that demonstrate the context-dependent nature of the decision-making process of ecosystem accounting at small scales. The two major challenges for site-level accounting are stakeholder engagement and data availability. As the use of SEEA EA continues to increase in policy and decision-making processes worldwide, there is a need for local-scale case studies that adapt this methodology across a broad range of contexts. Our case studies provide some of the first published examples of the application of SEEA EA at the site level and are intended to promote consistent implementation of ecosystem accounting across scales.

Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

INTRODUCTION: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC. OBJECTIVES: To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine. METHODS: A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine). RESULTS: Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented. CONCLUSION: The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.

Universal Cooling Dynamics toward a Quantum Critical Point.

We investigate the loss of adiabaticity when cooling a many-body quantum system from an initial thermal state toward a quantum critical point. The excitation density, which quantifies the degree of adiabaticity of the dynamics, is found to obey scaling laws in the cooling velocity as well as in the initial and final temperatures of the cooling protocol. The scaling laws are universal, governed by the critical exponents of the quantum phase transition. The validity of these statements is shown analytically for a Kitaev quantum wire coupled to Markovian baths and argued to be valid under rather general conditions. Our results establish that quantum critical properties can be probed dynamically at finite temperature, without even varying the control parameter of the quantum phase transition.

Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Dipeptidyl Peptidase-4 Inhibitor on the Risks of New-Onset Atrial Fibrillation, Stroke and Mortality in Diabetic Patients: A Propensity Score-Matched Study in Hong Kong.

OBJECTIVE: To compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on adverse outcomes in diabetic patients in Hong Kong. METHODS: This was a retrospective population-based cohort study of type 2 diabetes mellitus patients (n = 72,746) treated with SGLT2I or DPP4I between January 1, 2015, and December 31, 2020, in Hong Kong. Patients with exposure to both DPP4I and SGLT2I therapy, without complete demographics or mortality data, or who had prior atrial fibrillation (AF) were excluded. The study outcomes were new-onset AF, stroke/transient ischemic attack, cardiovascular mortality and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed. RESULTS: The unmatched study cohort included 21,713 SGLT2I users and 39,510 DPP4I users (total: n = 61,233 patients; 55.37% males, median age: 62.7 years [interquartile range (IQR): 54.6-71.9 years]). Over a median follow-up of 2030 (IQR: 1912-2117) days, 2496 patients (incidence rate [IR]: 4.07%) developed new-onset AF, 2179 patients (IR: 3.55%) developed stroke/transient ischemic attack, 1963 (IR: 3.20%) died from cardiovascular causes and 6607 patients (IR: 10.79%) suffered from all-cause mortality. After propensity score matching (SGLT2I: n = 21,713; DPP4I: n = 21,713), SGLT2I users showed lower incidence of new-onset AF (1.96% vs. 2.78%, standardized mean difference [SMD] = 0.05), stroke (1.80% vs. 3.52%, SMD = 0.11), cardiovascular mortality (0.47% vs. 1.56%, SMD = 0.11) and all-cause mortality (2.59% vs. 7.47%, SMD = 0.22) compared to DPP4I users. Cox regression found that SGLT2I users showed lower risk of new-onset AF (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: [0.56, 0.83], P = 0.0001), stroke (HR: 0.64, 95% CI: [0.53, 0.79], P < 0.0001), cardiovascular mortality (HR: 0.39, 95% CI: [0.27, 0.56], P < 0.0001) and all-cause mortality (HR: 0.44, 95% CI: [0.37, 0.51], P < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory tests. CONCLUSIONS: Based on real-world data of type 2 diabetic patients in Hong Kong, SGLT2I use was associated with lower risk of incident AF, stroke/transient ischemic attack, and cardiovascular and all-cause mortality outcomes compared to DPP4I use.

Engaging the agricultural community in the development of mental health interventions: a qualitative research study.

BACKGROUND: Farmers and those involved in the wider agricultural industry have a high suicide rate. They are also a 'hard to reach' group who make less than average use of mental health services. There is therefore a need to understand how best to develop interventions that meet their needs. The aims of this study were to develop a deeper understanding of the farming context and target population and to engage farmers in the shaping of two potential mental health interventions that could be incorporated in a pilot RCT. METHODS: The study was informed throughout by a reference group, who assisted in co-production of the research materials. A snowball approach was used to recruit interested individuals who had an association with farming. Twenty one telephone interviews were undertaken and analysed using the six phases of thematic analysis proposed by Braun and Clarke. RESULTS: Key themes (and sub-themes shown in brackets) related to the study aims were: everyday life (work-life balance; isolation and loneliness); farm management (technology and social media; production, people management, learning and teaching; external pressures; livestock and farm production; financial aspects); demographics (effects of aging); engagement (appropriate wording when talking about mental health; recognising need for help; religion; normalising mental health issues; approaching the conversation); training (mental health training for supporters of the farming community; health & safety and the inclusion of mental health training); and personal stories and experiences, which was an emerging theme. CONCLUSIONS: Recruiting farmers into research studies is best done by meeting farmers where they are found, for example, farmers marts. Accessibility of content, tailoring to the farming community, and guided support are key to effective recruitment and retention.

Secukinumab use in the treatment of Netherton's syndrome.

Netherton syndrome is a rare, severe genetic disorder of cornification without specific treatment. We describe two cases who demonstrated marked cutaneous improvement with secukinumab and suggest a role for IL-17 therapy in treating this condition.

Octreotide versus oral dietary modification for the treatment of chylous fistula following neck dissection: A systematic review and meta-analysis.

AIMS: Chylous fistula following neck surgery is a rare, but significant complication. Currently, there is no standardised treatment, which may comprise pressure dressings, oral dietary modification (ODM), surgery or a combination of such measures. Octreotide is a somatostatin analogue that has gained popularity in the management of cervical chyle leaks. The effectiveness of octreotide compared with ODM is unclear. We provide a comprehensive, systematic review of the literature pertaining to the management of chylous fistulae, comparing both treatment strategies. METHODS: The bibliographic databases MEDLINE, Cochrane, PubMed, EMBASE and Google Scholar were searched from inception to October 2019. Search terms included (chyle [title/abstract]) OR (chylous [title/abstract]) AND (fistula [title/abstract]) OR (fistulae [title/abstract]) OR (leak [title/abstract]) AND (neck [title/abstract]) OR (dissection [title/abstract]). The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Risk of bias was assessed using guidelines from the Joanna Briggs Institute. Outcome measures included the proportion of chylous fistulae that spontaneously resolved without the need for surgery and time taken until resolution, for both DM and octreotide, respectively. RESULTS: The primary search identified 20 articles for review, comprising 313 patients. Two studies were suitable for pooled analysis. There was no statistically significant difference in the time taken for chylous fistula to resolve between groups (octreotide 10.0 days; ODM 12.0 days; P = .38). The overall rate of resolution was 89.6% and 81.5%, respectively (P = .25). Surgery was highly effective in cases failing to resolve following intervention with either method (96% [53/55] patients). CONCLUSION: The use of octreotide for chylous fistula following neck dissection surgery is associated with a high rate of spontaneous resolution. However, significant heterogeneity, bias and concurrent use of ODM/TPN for patients in studies investigating octreotide precludes universal recommendation at this time. Further research in the form of randomised controlled trials is required to establish an independent treatment effect.

The ACE Index: mapping childhood adversity in England.

BACKGROUND: Studies of adults show that adverse childhood experiences (ACEs) are associated with health and social problems and are more common among people living in deprived areas. However, there is limited information about the geographical pattern of contemporary ACEs. METHODS: We used data from the police, social services, schools and vital statistics in England to calculate population rates of events that represent childhood adversity. We constructed an 'ACE Index' that summarizes the relative frequency of ACEs at local authority level, informed by the methods of the Index of Multiple Deprivation. We explored associations between the ACE Index and local characteristics in cross-sectional ecological analysis. RESULTS: The ACE Index was strongly associated with the proportion of children that live in income-deprived households (child poverty). In addition, the ACE Index was independently associated with higher population density and was higher in certain regions, particularly the north-east. CONCLUSIONS: The association between ACEs and child poverty provides evidence of a process in which deprivation increases the risk of adverse experiences in childhood. The ACE Index can inform allocation of resources for prevention and mitigation of ACEs.

Systematic review and meta-analysis on the use of probiotic supplementation in pregnant mother, breastfeeding mother and infant for the prevention of atopic dermatitis in children.

Probiotic supplementation may decrease the risk of allergic disease; however, there are differences between studies, such as the type of probiotic, the route or the duration of supplementation. Therefore, determining the most effective probiotic strain/s, route of administration and duration for clinical recommendation has been difficult. An electronic systematic literature search was undertaken between using Ovid MEDLINE, Embase, PubMed and Cochrane. Risk ratio (RR) and 95% confidence interval (CI) are presented for the studies. PEDro scale and Newcastle-Ottawa Scale were used to assess the quality of the included studies. A total of 21 studies met the inclusion criteria. Strain-specific sub-meta-analyses indicated that single strains are not as effective as probiotic mixtures and administration to a combination of pregnant mothers, breastfeeding mothers and infants had a reduced risk in the onset of atopic dermatitis in children. Our systematic review and meta-analysis showed that a mixture of probiotic supplementation given to the mother in pregnancy and continuing while breastfeeding and also to the infant in children classified as high-risk for atopic dermatitis and non-high-risk groups is the most efficacious in reducing the risk of incidence of atopic dermatitis in children.

Elective neck dissection for salvage total laryngectomy: A systematic review, meta-analysis and "decision-to-treat" approach.

INTRODUCTION: The authors provide an updated, systematic and comprehensive summary of the literature concerning management of the N0 neck in patients for whom primary irradiation for squamous cell carcinoma of the larynx has been unsuccessful and salvage surgery in the form of total laryngectomy (TL) advocated. METHODS: Bibliographic databases MEDLINE, Cochrane, PubMed and Embase were searched from inception to April 2019, with no language restrictions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Risk of bias was defined using the Joanna Briggs Institute guidelines. Outcome measures were defined as the impact of END on locoregional control, complication rate, disease-specific and overall survival (DSS and OS). RESULTS: The primary search identified 19 eligible articles, comprising 1353 patients, (1552 ENDs). The overall risk of occult metastases was 14% (9% of ENDs). The relative risk (RR) of developing complications was 1.29 when END was performed, compared to observation of the neck (CI 0.86-1.92). Contrariwise, patients in whom the neck was managed with neck dissection had a decreased risk of developing regional recurrence (RR 0.62, CI 0.35-1.08). There was no statistically significant variation between DSS and OS between END and neck observation groups, respectively. SUMMARY: END during salvage TL may reduce the rate of regional recurrence, but not at the expense of improving DSS or OS. Rates of occult metastases, regional recurrence and "cure" through salvage neck dissection are not equivalent. Significant bias in all collated manuscripts should encourage the reader to interpret conclusions with caution. Patients should be fully involved in the decision-making process and their performance status and co-morbidities taken carefully into account when deciding to increase the extent of surgery, which we believe should remain limited to TL in the majority of cases.

Interspecialty referral of oesophagogastric and pharyngolaryngeal cancers delays diagnosis and reduces patient survival: A matched case-control study.

OBJECTIVES: Pharyngolaryngeal and oesophagogastric cancers present with swallowing symptoms and as such, their clinical evaluation traverses boundaries between different specialties. We studied the incidence and significance of interspecialty cancer referrals (ICRs), that is, pharyngolaryngeal cancers first evaluated by gastroenterology and oesophagogastric cancers first evaluated by otolaryngology. DESIGN: A subset analysis of our Integrated Aerodigestive Partnership's audit dataset, of all ICR patients, and an equal number of controls matched for age, sex and cancer subsite. MAIN OUTCOME MEASURES: Information about patient age and presenting symptoms was recorded. The relationship between symptoms and ICR risk was examined with binary logistic regression. Referral-to-diagnosis latency was compared between ICR and control patients with unpaired Student's t test. Cox regression was used to identify independent predictors of overall survival. RESULTS: Of 1130 patients with pharyngolaryngeal and oesophagogastric cancers between 2008 and 2018, 60 diagnoses (5.3%) were preceded by an ICR. Referral-to-diagnosis latency increased from 43 ± 50 days for control patients to 115 ± 140 days for ICR patients (P < .0001). Dysphagia significantly increased the risk of an ICR (odds ratio 3.34; 95% CI 1.30-8.56), and presence of classic gastroesophageal reflux symptoms (heartburn or regurgitation; OR 0.25; 95% CI 0.08-0.83) and "distal" symptoms (nausea/vomiting, abdominal pain or dyspepsia; OR 0.23; 95% CI 0.08-068) significantly reduced the risk. Eleven pharyngolaryngeal cancers (of 26; 42%) were missed by gastroenterology, and eight (of 34; 24%) oesophageal cancers were missed by otolaryngology. An ICR was an independent adverse prognostic risk factor on multivariable analysis (hazard ratio 1.76; 95% CI 1.11-2.73; P < .02; log-rank test). Two systemic root causes were poor visualisation of pharynx and larynx by per-oral oesophago-gastro-duodenoscopy (OGD) for pharyngolaryngeal cancers, and poor sensitivity (62.5%) of barium swallow when it was used to 'evaluate' oesophageal mucosa. CONCLUSIONS: An interspecialty cancer referral occurs in a significant proportion of patients with foregut cancers. It almost triples the time to cancer diagnosis and is associated with a high incidence of missed cancers and diminished patient survival. It is a complex phenomenon, and its reduction requires an integrated approach between primary and secondary care, and within secondary care, to optimise referral pathways and ensure appropriate and expeditious specialist evaluation.

HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma.

BACKGROUND: Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a distinct clinical phenotype; metabolic differences between these HNSCC subtypes remain poorly understood. METHODS: We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPV-ve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPV-ve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays. RESULTS: Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was significantly increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity. CONCLUSION: HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications.

Barriers to Uptake of Postpartum Long-Acting Reversible Contraception: Qualitative Study of the Perspectives of Ugandan Health Workers and Potential Clients.

Health workers have received training on delivering postpartum long-acting reversible contraceptives (LARCs) through several projects in Uganda, yet uptake still remains poor. To understand the reasons, and to gather suggestions for improving uptake, we conducted individual semi-structured interviews with a total of 80 postpartum parents, antenatal parents, health workers, and village health teams in rural south-west Uganda. Interviews were recorded, transcribed, translated, and analyzed using qualitative thematic analysis. Specific barriers to uptake of immediate postpartum contraception for women included: the need to discuss this option with their husband, the belief that time is needed to recover before insertion of a LARC, and fear that the baby might not survive. Furthermore, social consequences of side-effects are more serious in low-income settings. Suggestions for improving uptake of postpartum contraception included health education by "expert users," couples counseling during antenatal care, and improved management of side-effects.

Feasibility and outcomes of fibreoptic endoscopic evaluation of swallowing following prophylactic swallowing rehabilitation in head and neck cancer.

OBJECTIVES: Investigate the feasibility and outcomes of fibreoptic endoscopic evaluation of swallowing (FEES) following a programme of prophylactic swallowing exercises in head and neck cancer (HNC) patients treated with radiotherapy. DESIGN: Prospective, single cohort, feasibility study. SETTING: Three head and neck cancer centres in Scotland. PARTICIPANTS: Pre-radiotherapy HNC patients who consented to participate in a prophylactic swallowing intervention. OUTCOME MEASURES: Fibreoptic endoscopic evaluation of swallowing recruitment and retention rates, assessment acceptability and compliance, qualitative process evaluation. RESULTS: Higher rates of recruitment and retention were achieved in centres where FEES equipment was available on-site. Travel and anticipated discomfort were barriers to recruitment. Data completion was high for all rating scales, with good reliability. Following radiotherapy, swallowing safety significantly deteriorated for liquid boluses (P = 0.005-0.03); pharyngeal residue increased for liquid and semi-solid boluses. Pharyngo-laryngeal oedema was present pre-treatment and significantly increased post-radiotherapy (P = 0.001). Patients generally reported positive experience of FEES for their own learning and establishing a baseline. CONCLUSIONS: Fibreoptic endoscopic evaluation of swallowing is an acceptable method of assessing patients for a prophylactic swallowing intervention and offers some additional information missing from VF. Barriers have been identified and should be taken into account in order to maximise recruitment for future trials.

Novel Approaches for Vaccination Against HPV-Induced Cancers.

To date, more than 5 % of all cancers are as a result of human papillomavirus (HPV) infection, and this incidence is increasing. Early recognition of disease is associated with good survival, but late presentation results in devastating consequences. Prevention is better than cure, and there are now successful prophylactic vaccination programmes in place. We discuss these and the prospect of therapeutic vaccinations in the near future to address a growing need for improved therapeutic options.

What's in a name: are cultured red blood cells 'natural'?

The case of cultured red blood cells (RBCs) currently being grown in a laboratory for future use in human transfusion raises questions about the ontological status of such products of modern biotechnology. This paper presents results from a six-year ethnographic study involving interviews, focus groups and other forms of engagement with the scientific research team and other stakeholders, including public groups, which sought to understand respondents' reactions to cultured RBCs. These cells, derived from stem cell technology, have the potential to address the global shortage of donated blood. How these blood cells are situated within the spectrum of 'natural' to 'synthetic' will shape expectations and acceptance of this product, both within the scientific community and by wider publics: these blood cells are both novel and yet, at the same time, very familiar. Drawing on discussions related to classification and 'anchoring', we examine the contrasting discourses offered by our respondents on whether these blood cells are 'natural' or not and consider the impact that naming might have on both their future regulation and the eventual uptake of cultured RBCs by society.