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Appetite drives essential oral nutritional intake. Its regulation is complex, influenced by physiology, hedonism (the reward of eating) and learning from external cues within a person's society and culture. Appetite loss is common in the older population and not always attributable to medical conditions or treatment. Although the physiological basis of the anorexia of ageing (loss of appetite due to the ageing process) has been established, the effect of ageing on hedonism and external cues, which may be equally important, is less well understood. The anorexia of ageing is associated with reductions in dietary diversity and oral intake, and increased risk of malnutrition, sarcopenia and frailty. Early identification of poor appetite could allow timely intervention before weight loss occurs. There is no standardised tool for assessing appetite in clinical settings at present but the 4-item Simplified Nutritional Appetite Questionnaire (SNAQ) has the potential to be used in this way. This review, designed for clinicians, will discuss the regulation of appetite and the pathogenesis of the anorexia of ageing. It will describe the current evidence for interventions to manage the anorexia of ageing, which is limited, with little benefit reported from individual studies of education, physical activity and medication. There is some positive evidence for flavour enhancement, fortified food and oral nutritional supplements but mainly within single studies. Looking ahead, the aim is to develop multicomponent approaches to the treatment of the anorexia of ageing based on growing understanding of the role of physiological signalling, hedonism and external cues. [ABSTRACT FROM AUTHOR]

Push notifications offer a promising strategy for enhancing engagement with smartphone-based health interventions. Intelligent sensor-driven machine learning models may improve the timeliness of notifications by adapting delivery to a user’s current context (e.g. location). This exploratory mixed-methods study examined the potential impact of timing and frequency on notification response and usage of Healthy Mind, a smartphone-based stress management intervention. 77 participants were randomised to use one of three versions of Healthy Mind that provided: intelligent notifications; daily notifications within pre-defined time frames; or occasional notifications within pre-defined time frames. Notification response and Healthy Mind usage were automatically recorded. Telephone interviews explored participants’ experiences of using Healthy Mind. Participants in the intelligent and daily conditions viewed (d = .47, .44 respectively) and actioned (d = .50, .43 respectively) more notifications compared to the occasional group. Notification group had no meaningful effects on percentage of notifications viewed or usage of Healthy Mind. No meaningful differences were indicated between the intelligent and non-intelligent groups. Our findings suggest that frequent notifications may encourage greater exposure to intervention content without deterring engagement, but adaptive tailoring of notification timing does not always enhance their use. Hypotheses generated from this study require testing in future work. Trial registration number: [ABSTRACT FROM AUTHOR]

N-of-1 study designs involve the collection and analysis of repeated measures data from an individual not using an intervention and using an intervention. This study explores the use of semi-parametric and parametric bootstrap tests in the analysis of N-of-1 studies under a single time series framework in the presence of autocorrelation. When the Type I error rates of bootstrap tests are compared to Wald tests, our results show that the bootstrap tests have more desirable properties. We compare the results for normally distributed errors with those for contaminated normally distributed errors and find that, except when there is relatively large autocorrelation, there is little difference between the power of the parametric and semi-parametric bootstrap tests. We also experiment with two intervention designs: ABAB and AB, and show the ABAB design has more power. The results provide guidelines for designing N-of-1 studies, in the sense of how many observations and how many intervention changes are needed to achieve a certain level of power and which test should be performed. [ABSTRACT FROM AUTHOR]

Objectives Internet-based health behaviour interventions have variable effects on health-related outcomes. Effectiveness may be improved by optimizing the design of interventions. This study examined the specific effect on engagement of providing two different design features - tailoring and self-assessment. Design Three versions of an Internet-delivered intervention to support the self-care of mild bowel problems were developed that provided (1) self-assessment without tailored feedback, (2) self-assessment with tailored feedback, and (3) generic information only. Methods A qualitative study explored participants' engagement with each version of the intervention ( N = 24). A larger quantitative study systematically compared participants' use of the intervention and self-reported engagement using a partial factorial design ( n = 178). Results Findings from the qualitative study suggested that self-assessment without tailored feedback appeared to be less acceptable to participants because it was viewed as offering no personal benefit in the absence of personalized advice. In the quantitative study, self-assessment without tailored feedback was associated with greater dropout than when provided in conjunction with tailored feedback. There were significant group differences in participants' engagement with the intervention and perceptions of the intervention. Self-assessment without tailored feedback was rated as marginally less engaging and was associated with fewer positive perceptions than the generic information condition. Conclusions The acceptability of self-assessment or monitoring components may be optimized by also providing tailored feedback. Without tailored feedback, these components do not appear to be any more engaging than generic information provision. [ABSTRACT FROM AUTHOR]

Appetite loss in later life is common and associated with malnutrition; however, there is limited knowledge on older individuals' perspectives of appetite. This study aimed to explore what 'appetite' means to older adults, how they experience its change and perceived influences on this experience. Semi-structured interviews were conducted with thirteen participants, aged ≥65 years, in their own home, following a recent arm fracture. Transcripts were analysed using reflexive thematic analysis with inductive coding resulting in three themes. 1. 'Appetite as an emotional experience' encompassed positive or negative thoughts and feelings driving or undermining desire to eat. Mood, the appeal of food, cooking and effects of interaction and experiences with other people were factors in this narrative. 2. 'Appetite reflects a physical need' comprised physical bodily sensations or requirements as a driver for appetite with poor appetite resulting from early or over fullness. Declines with age, illness and less activity, were factors in this narrative. 3. 'Adaption to poor appetite aligns with perception of appetite and wider physical health' accounts for how experiential strategies, or practical strategies were used to mitigate poor appetite depending on the narrative of appetite loss, alongside perceptions of physical health and unplanned weight loss. Most individuals used one narrative in their discussions and reflections but for some, perceptions of appetite and its change were more complex. Understanding relationships between these perceptions of appetite and influential factors could facilitate development of multi-component, person-centred, strategies that are optimally meaningful and relevant to address appetite loss in later life. [ABSTRACT FROM AUTHOR]

Background: Malignant mesothelioma is an aggressive tumour of serosal surfaces most commonly pleura. Characterised cell lines represent a valuable tool to study the biology of mesothelioma. The aim of this study was to develop and biologically characterise six malignant mesothelioma cell lines to evaluate their potential as models of human malignant mesothelioma. Methods: Five lines were initiated from pleural biopsies, and one from pleural effusion of patients with histologically proven malignant mesothelioma. Mesothelial origin was assessed by standard morphology, Transmission Electron Microscopy (TEM) and immunocytochemistry. Growth characteristics were assayed using population doubling times. Spectral karyotyping was performed to assess chromosomal abnormalities. Authentication of donor specific derivation was undertaken by DNA fingerprinting using a panel of SNPs. Results: Most of cell lines exhibited spindle cell shape, with some retaining stellate shapes. At passage 2 to 6 all lines stained positively for calretinin and cytokeratin 19, and demonstrated capacity for anchorage-independent growth. At passage 4 to 16, doubling times ranged from 30–72 hours, and on spectral karyotyping all lines exhibited numerical chromosomal abnormalities ranging from 41 to 113. Monosomy of chromosomes 8, 14, 22 or 17 was observed in three lines. One line displayed four different karyotypes at passage 8, but only one karyotype at passage 42, and another displayed polyploidy at passage 40 which was not present at early passages. At passages 5–17, TEM showed characteristic features of mesothelioma ultrastructure in all lines including microvilli and tight intercellular junctions. Conclusion: These six cell lines exhibit varying cell morphology, a range of doubling times, and show diverse passage-dependent structural chromosomal changes observed in malignant tumours. However they retain characteristic immunocytochemical protein expression profiles of mesothelioma during maintenance in artificial culture systems. These characteristics support their potential as in vitro model systems for studying cellular, molecular and genetic aspects of mesothelioma. [ABSTRACT FROM AUTHOR]

The effectiveness of e-health interventions varies greatly. Despite this, there has been relatively little formal consideration of how differences in the design of an intervention (i.e., how the content is delivered) may explain why some interventions are more effective than others. This review primarily examines the use of the Internet to provide educational and self-management interventions to promote health. The article develops hypotheses about how the design of these interventions may be associated with outcomes. In total, 52 published reports from both a diversity sample and a representative sample were reviewed using techniques from Critical Interpretive Synthesis. Four core interactive design features were identified that may mediate the effects of intervention design on outcomes: Social context and support, contacts with intervention, tailoring, and self-management. A conceptual framework to summarize the design of e-health interventions delivered using the Internet is proposed. The framework provides a guide for systematic research to identify the effects of specific design features on intervention outcomes and to identify the mechanisms underlying any effects. To optimize the design of e-health interventions more work is needed to understand how and why these design features may affect intervention outcomes and to investigate the optimal implementation and dosage of each design feature. [ABSTRACT FROM AUTHOR]

Background: It is recognised as good practice to use qualitative methods to elicit users' views of internet-delivered health-care interventions during their development. This paper seeks to illustrate the advantages of combining usability testing with 'theoretical modelling', i.e. analyses that relate the findings of qualitative studies during intervention development to social science theory, in order to gain deeper insights into the reasons and context for how people respond to the intervention. This paper illustrates how usability testing may be enriched by theoretical modelling by means of two qualitative studies of users' views of the delivery of information in an internet-delivered intervention to help users decide whether they needed to seek medical care for their cold or flu symptoms. Methods: In Study 1, 21 participants recruited from a city in southern England were asked to 'think aloud' while viewing draft web-pages presented in paper format. In Study 2, views of our prototype website were elicited, again using think aloud methods, in a sample of 26 participants purposively sampled for diversity in education levels. Both data-sets were analysed by thematic analysis. Results: Study 1 revealed that although the information provided by the draft web-pages had many of the intended empowering benefits, users often felt overwhelmed by the quantity of information. Relating these findings to theory and research on factors influencing preferences for information-seeking we hypothesised that to meet the needs of different users (especially those with lower literacy levels) our website should be designed to provide only essential personalised advice, but with options to access further information. Study 2 showed that our website design did prove accessible to users with different literacy levels. However, some users seemed to want still greater control over how information was accessed. Conclusions: Educational level need not be an insuperable barrier to appreciating web-based access to detailed health-related information, provided that users feel they can quickly gain access to the specific information they seek. [ABSTRACT FROM AUTHOR]

Background: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. Methods: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). Results: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. Conclusion: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours. [ABSTRACT FROM AUTHOR]

CD8+ T lymphocytes are key effectors in the control of viral diseases and some tumours. In general, the majority of CD8+ T cells recognize a few immunodominant epitopes, but in some circumstances, subdominant specificities may be more relevant as targets for vaccines or immunotherapy. Epstein–Barr virus (EBV)-associated cancers are an example where knowledge of subdominant-specific CD8+ T cells is important because the immunodominant EBV proteins are not expressed in these cancers. We have developed a live-cell sorting method based on CD107 detection to remove CD8+ T cells recognising dominant EBV epitopes and show that this allows enrichment of subdominant-specific CD8+ T cells in subsequent cultures. This work shows that immunodomination in vitro suppresses the outgrowth of subdominant-specific CD8+ T cells in culture. The method may have broad applications for finding subdominant targets for immunotherapy and vaccines, and the principle suggests a means of improving subdominant CD8+ T-cell cultures grown for immunotherapy.Immunology and Cell Biology (2007) 85, 546–550; doi:10.1038/sj.icb.7100083; published online 12 June 2007 [ABSTRACT FROM AUTHOR]

Background The anorexia of ageing is important in the development of malnutrition, frailty and sarcopenia amongst the older population and is a particular problem for hospital inpatients. This study assessed appetite-related factors in a group of hospitalised older adults, to identify potential preventive strategies. Design Cross sectional observational study. Setting Eleven wards in one large hospital in England. Subjects Older inpatients aged ≥70 years, admitted non-electively. Methods Appetite was assessed using the four-item Simplified Nutritional Appetite Questionnaire (SNAQ). Associations between SNAQ score and appetite-related factors present in the dataset were assessed in continuous analyses, including habitual physical activity, mood, medication, cognition and living circumstances. Results 200 participants, mean age of 80.7 years (SD 6.9); 40% were women. Prevalence of poor appetite was 43%. In univariate analyses, lower medication count, higher habitual physical activity and better mood were associated with higher SNAQ scores during admission. In a multivariate analysis, independent associations of higher habitual physical activity and better mood with higher SNAQ scores during hospital admission remained. Conclusion In this group of older adults, better mood and higher habitual physical activity were independently associated with better appetite during hospital admission. These are potentially modifiable factors and could be targets for future research into interventions for the anorexia of ageing in the hospitalised older population. [ABSTRACT FROM AUTHOR]

Objective: To explore primary care practitioners' (PCPs) and patients' priorities and concerns for healthcare interactions for osteoarthritis (OA) in primary care.Methods: We searched Embase, CINAHL, Medline, PsychInfo (1990 to present) for primary qualitative and mixed methods studies with findings concerning healthcare interactions for OA symptoms. Patient and PCP perceptions were analysed separately then inter-related using a 'line of argument' synthesis.Results: Twenty-six studies reporting qualitative data from 557 patients and 199 PCPs were synthesised. Our findings suggest that therapeutic interactions for OA can be based on discordant priorities and concerns; some patients perceive that PCPs hold negative attitudes about OA and feel their concerns about impact are not appreciated; some PCPs feel patients have misconceptions about prognosis, and hold pessimistic views about outcomes; and both tend to de-prioritise OA within consultations.Conclusion: Greater working in partnership could build mutual trust, facilitate tailored provision of information, and foster a shared understanding of OA upon which to build realistic goals for management.Practice Implications: Developing a better shared understanding of OA has the potential to improve the quality of healthcare interactions for both patients and PCPs. The significant impact of OA on everyday life means it should be given higher priority in primary care consultations. [ABSTRACT FROM AUTHOR]

Objectives: Adolescent health behaviours do not support optimal development. Adolescents are reportedly difficult to engage in health behaviour improvement initiatives. Little is known about what adolescents value in relation to diet and physical activity or how best to target these in health interventions. This study explored adolescents' values in relation to diet and physical activity and how these values can inform health intervention design. Design: Qualitative semi‐structured interviews explored adolescents' lives, what they thought about diet and physical activity and what might support them to improve their health behaviours. Methods: A total of 13 group interviews were conducted with 54 adolescents aged 13–14 years, of whom 49% were girls and 95% identified as White British. Participants were recruited from a non‐selective secondary school in a large southern UK city. Inductive thematic analysis was used to identify key adolescent values. Results: Adolescents valued being with their friends, doing what they enjoyed and were good at; being healthy was important to them but only if achievable without compromising other things that are important to them. The need to be healthy was not aligned with adolescents' basic psychological needs, nor their strongly held priorities and values. Conclusions: Health is not a motivating factor for adolescents; therefore, interventions designed solely to improve health are unlikely to engage them. Instead, interventions that align with the values and priorities specified by adolescents are more likely to be effective in supporting them to eat well and be more active. [ABSTRACT FROM AUTHOR]

Objective: To identify the ways in which parental involvement can be incorporated into interventions to support adolescent health behaviour change.Design: Data from semi-structured interviews were analysed using inductive thematic analysis.Setting: Southampton, Hampshire, UK.Participants: A convenience sample of twenty-four parents of adolescents.Results: Parents consider themselves to play an important role in supporting their adolescents to make healthy choices. Parents saw themselves as gatekeepers of the household and as role models to their adolescents but recognised this could be both positive and negative in terms of health behaviours. Parents described the changing dynamics of the relationships they have with their adolescents because of increased adolescent autonomy. Parents stated that these changes altered their level of influence over adolescents' health behaviours. Parents considered it important to promote independence in their adolescents; however, many described this as challenging because they believed their adolescents were likely to make unhealthy decisions if not given guidance. Parents reported difficulty in supporting adolescents in a way that was not viewed as forceful or pressuring.Conclusions: When designing adolescent health interventions that include parental components, researchers need to be aware of the disconnect between public health recommendations and the everyday reality for adolescents and their parents. Parental involvement in adolescent interventions could be helpful but needs to be done in a manner that is acceptable to both adolescents and parents. The findings of this study may be useful to inform interventions which need to consider the transitions and negotiations which are common in homes containing adolescents. [ABSTRACT FROM AUTHOR]

Teenage pregnancy has a high risk of poor outcomes for both mother and baby. Teenage girls have the poorest diets of any population group in the UK, which compounds the risk of poor pregnancy outcomes. Pregnant teenagers trust advice from their midwives, but midwives feel they do not have time, confidence, or knowledge to discuss nutrition. This study examined how the relationship between pregnant teenagers and their midwives could be utilised to deliver support to improve diet quality. Qualitative interviews were conducted across three urban sites in the UK: Manchester, Doncaster, and Southampton with adolescent mothers and their midwives regarding diet and lifestyle, and what form of support would be helpful. In total, 106 young women and 20 midwives were interviewed. Most of the young mothers were 19 or younger (67%). Half had had their first child in the past year (52%) and 21% were pregnant during the study. Thematic analysis was used to identify ways to better support young mothers to eat well. Young women found it difficult to prioritise healthy eating; they often felt isolated and not in control of their own lives and wanted support from their midwife. Midwives felt that it was their role to support young mothers with diet in pregnancy but were anxious about initiating conversations and felt they lacked clear guidance. Pregnant teenagers and their midwives lack reliable resources and strategies for healthy eating support. An effective intervention to improve pregnant teenagers' diet quality must empower, inform, and motivate young mothers and their midwives, and enable connections between young mothers. • A uniquely large sample of pregnant teenagers and midwives was interviewed. • Young mothers want to eat well for the sake of their babies but find it difficult. • Young mothers need to feel heard, capable, and connect with other young mothers. • Dietary interventions should meet these needs. • Communication skills training for midwives and digital support are promising. [ABSTRACT FROM AUTHOR]

A recent systematic review of randomised trials suggested that empathic communication improves patient health outcomes. However, the methods for training healthcare practitioners (medical professionals; HCPs) in empathy and the empathic behaviours demonstrated within the trials were heterogeneous, making the evidence difficult to implement in routine clinical practice. In this secondary analysis of seven trials in the review, we aimed to identify (1) the methods used to train HCPs, (2) the empathy behaviours they were trained to perform and (3) behaviour change techniques (BCTs) used to encourage the adoption of those behaviours. This detailed understanding of interventions is necessary to inform implementation in clinical practice. We conducted a content analysis of intervention descriptions, using an inductive approach to identify training methods and empathy behaviours and a deductive approach to describe the BCTs used. The most commonly used methods to train HCPs to enhance empathy were face-to-face training (n = 5), role-playing (n = 3) and videos (self or model; n = 3). Duration of training was varied, with both long and short training having high effect sizes. The most frequently targeted empathy behaviours were providing explanations of treatment (n = 5), providing non-specific empathic responses (e.g. expressing understanding) and displaying a friendly manner and using non-verbal behaviours (e.g. nodding, leaning forward, n = 4). The BCT most used to encourage HCPs to adopt empathy behaviours was "Instruction on how to perform behaviour" (e.g. a video demonstration, n = 5), followed by "Credible source" (e.g. delivered by a psychologist, n = 4) and "Behavioural practice" (n = 3 e.g. role-playing). We compared the effect sizes of studies but could not extrapolate meaningful conclusions due to high levels of variation in training methods, empathy skills and BCTs. Moreover, the methods used to train HCPs were often poorly described which limits study replication and clinical implementation. This analysis of empathy training can inform future research, intervention reporting standards and clinical practice. [ABSTRACT FROM AUTHOR]

Clinical empathy can enhance patient outcomes. This study examined patients' perceptions of empathy in primary care consultations delivered by telephone. A mixed methods study was nested in a larger feasibility study conducted May-October 2020. Adults reporting a UK primary care consultation in the previous 2 weeks completed an online survey. A sample of survey respondents participated in a semi-structured qualitative interview. Interviews were analysed thematically. Survey respondents (n = 359) rated practitioners as between 'good' and 'very good' at established patient-reported indicators of clinical empathy. Telephone consultations were rated slightly lower than face-to-face or other consultations. 30 survey respondents were interviewed. Three qualitative themes identified how telephone consultations can shape clinical empathy: setting for an empathic encounter; feeling connected; being acknowledged. Primary care patients typically perceive good levels of clinical empathy in telephone consultations; specific features of telephone consultations may facilitate and/or hinder clinical empathy. To ensure patients feel listened to, acknowledged and understood, practitioners may need to increase their empathic verbalisations in telephone consultations. By using verbal responses to demonstrate active listening and by clearly describing and/or implementing next steps in management, practitioners may be able to enhance clinical empathy in telephone consultations. • Clinical empathy can improve patient outcomes. • Patients reported good clinical empathy in primary care telephone consultations. • Patients rated telephone consultations slightly less empathic than other types. • We show how telephone consultations may facilitate and/or hinder clinical empathy. • Verbal signs of listening may enhance empathy in telephone consultations. [ABSTRACT FROM AUTHOR]

Background: Malnutrition (specifically undernutrition) in older, community-dwelling adults reduces well-being and predisposes to disease. Implementation of screen-and-treat policies could help to systematically detect and treat at-risk and malnourished patients. We aimed to identify barriers and facilitators to implementing malnutrition screen and treat policies in primary/community care, which barriers have been addressed and which facilitators have been successfully incorporated in existing interventions. Method: A data-base search was conducted using MEDLINE, Embase, PsycINFO, DARE, CINAHL, Cochrane Central and Cochrane Database of Systematic Reviews from 2012 to June 2016 to identify relevant qualitative and quantitative literature from primary/community care. Studies were included if participants were older, community-dwelling adults (65+) or healthcare professionals who would screen and treat such patients. Barriers and facilitators were extracted and mapped onto intervention features to determine whether these had addressed barriers. Results: Of a total of 2182 studies identified, 21 were included (6 qualitative, 12 quantitative and 3 mixed; 14 studies targeting patients and 7 targeting healthcare professionals). Facilitators addressing a wide range of barriers were identified, yet few interventions addressed psychosocial barriers to screen-and-treat policies for patients, such as loneliness and reluctance to be screened, or healthcare professionals' reservations about prescribing oral nutritional supplements. Conclusion: The studies reviewed identified several barriers and facilitators and addressed some of these in intervention design, although a prominent gap appeared to be psychosocial barriers. No single included study addressed all barriers or made use of all facilitators, although this appears to be possible. Interventions aiming to implement screen-and-treat approaches to malnutrition in primary care should consider barriers that both patients and healthcare professionals may face. Review registrations: PROSPERO: CRD42017071398. The review protocol was registered retrospectively. [ABSTRACT FROM AUTHOR]

This paper is one in a series developed through a process of expert consensus to provide an overview of questions of current importance in research into engagement with digital behavior change interventions, identifying guidance based on research to date and priority topics for future research. The first part of this paper critically reflects on current approaches to conceptualizing and measuring engagement. Next, issues relevant to promoting effective engagement are discussed, including how best to tailor to individual needs and combine digital and human support. A key conclusion with regard to conceptualizing engagement is that it is important to understand the relationship between engagement with the digital intervention and the desired behavior change. This paper argues that it may be more valuable to establish and promote "effective engagement," rather than simply more engagement, with "effective engagement" defined empirically as sufficient engagement with the intervention to achieve intended outcomes. Appraisal of the value and limitations of methods of assessing different aspects of engagement highlights the need to identify valid and efficient combinations of measures to develop and test multidimensional models of engagement. The final section of the paper reflects on how interventions can be designed to fit the user and their specific needs and context. Despite many unresolved questions posed by novel and rapidly changing technologies, there is widespread consensus that successful intervention design demands a user-centered and iterative approach to development, using mixed methods and in-depth qualitative research to progressively refine the intervention to meet user requirements. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is Epstein–Barr virus (EBV) positive in all undifferentiated cases, expressing the latency II phenotype of latent membrane proteins (LMPs) 1 and 2, in addition to EBV nuclear antigen (EBNA) 1. Several studies have attempted to treat NPC with EBV-specific cytotoxic T lymphocyte (CTL) with a partial response. To improve this therapy, there is a need to expand CTL targeted to the latency II antigens of EBV, rather than the immunodominant EBV nuclear antigens 3–6 peptides typically expanded by lymphoblastoid cells. In order to maximize the expansion of LMP-specific CTL in vitro for use in adoptive immunotherapy of nasopharyngeal carcinoma patients, we used lymphoblastoid cell lines coated with synthetic peptides corresponding to CTL determinants from the LMP proteins. We investigated several issues pertaining to the expansion of an immunologically weak CTL response, including peptide and interleukin-2 concentration, and screening assays for selecting the optimal peptide for use in expansion of LMP-specific CTL. Although screening of ex vivo peripheral blood mononuclear cells did not prove to be useful in the selection of an LMP peptide for use in CTL cultures, the peptide and interleukin-2 concentrations were critical for the maximum expansion of CTL. Therefore, it is imperative that stimulation protocols are optimized for the expansion of LMP-specific CTL.Immunology and Cell Biology (2009) 87, 481–488; doi:10.1038/icb.2009.25; published online 26 May 2009 [ABSTRACT FROM AUTHOR]

Background: Poor diet and lack of physical activity are strongly linked to non-communicable disease risk, but modifying them is challenging. There is increasing recognition that adolescence is an important time to intervene; habits formed during this period tend to last, and physical and psychological changes during adolescence make it an important time to help individuals form healthier habits. Improving adolescents' health behaviours is important not only for their own health now and in adulthood, but also for the health of any future children. Building on LifeLab-an existing, purpose-built educational facility at the University of Southampton-we have developed a multi-component intervention for secondary school students called Engaging Adolescents in Changing Behaviour (EACH-B) that aims to motivate and support adolescents to eat better and be more physically active.Methods: A cluster randomised controlled trial is being conducted to evaluate the effectiveness of the EACH-B intervention. The primary outcomes of the intervention are self-reported dietary quality and objectively measured physical activity (PA) levels, both assessed at baseline and at 12-month follow-up. The EACH-B intervention consists of three linked elements: professional development for teachers including training in communication skills to support health behaviour change; the LifeLab educational module comprising in-school teaching of nine science lessons linked to the English National Curriculum and a practical day visit to the LifeLab facility; and a personalised digital intervention that involves social support and game features that promote eating better and being more active. Both the taught module and the LifeLab day are designed with a focus on the science behind the messages about positive health behaviours, such as diet and PA, for the adolescents now, in adulthood and their future offspring, with the aim of promoting personal plans for change. The EACH-B research trial aims to recruit approximately 2300 secondary school students aged 12-13 years from 50 schools (the clusters) from Hampshire and neighbouring counties. Participating schools will be randomised to either the control or intervention arm. The intervention will be run during two academic years, with continual recruitment of schools throughout the school year until the sample size is reached. The schools allocated to the control arm will receive normal schooling but will be offered the intervention after data collection for the trial is complete. An economic model will be developed to assess the cost-effectiveness of the EACH-B intervention compared with usual schooling.Discussion: Adolescents' health needs are often ignored and they can be difficult to engage in behaviour change. Building a cheap, sustainable way of engaging them in making healthier choices will benefit their long-term health and that of their future children.Trial Registration: ISRCTN 74109264 . Registered on 30 August 2019. EACH-B is a cluster randomised controlled trial, funded by the National Institute for Health Research (RP-PG-0216-20004). [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs. [ABSTRACT FROM AUTHOR]