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Introduction: Tracheoesophageal fistulas (TEF) are a rare complication that can occur in patients with radioactive iodine refractory metastatic follicular thyroid carcinoma (FTC) following treatment with radiotherapy (RT) and tyrosine kinase inhibitors (TKI)., Methods: We describe the case of a TEF development in a 69-year-old male who underwent targeted therapy TKIs and adjuvant RT for radioactive iodine refractory FTC., Results: In the case, staging investigations revealed a metastatic, poorly differentiated FTC refractory to radioactive iodine. After 2 years of disease control on Lenvatinib, the patient's condition progressed, necessitating a switch to Cabozantinib. Soon after, they presented with haemoptysis secondary to invasion of the primary thyroid tumour into the trachea. Radical radiotherapy (45 Gy/30 fractions) was also administered to the thyroid gland, ultimately complicated by radiation necrosis. Four months post-completion of RT and recommencing TKI, the patient presented with haemoptysis and hoarseness secondary to recurrent laryngeal nerve compression and tracheal invasion, as well as dysphagia secondary to oesophageal compression. Following an acute presentation with intractable throat pain, investigations revealed a TEF. Surgical and endoscopic management was deemed inappropriate given the patient's rapid deterioration and anatomical position of the TEF, and therefore a palliative approach was taken., Conclusion: This case report highlights a rare cause of TEF development in a patient having TKI therapy post-RT for advanced FTC. It highlights the importance of monitoring TEF development in this cohort of patients. It demonstrates the importance of patient counselling and education regarding treatment options and the rare side effects of treatments., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background/objective: To explore acceptability by patients and health care professionals of a new surveillance pathway for people with previously treated and stable diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR)., Subject/methods: Structured discussions in 10 focus groups with patients; two with ophthalmic photographers/graders, and one with ophthalmologists, held across the UK as part of a large diagnostic accuracy study (EMERALD)., Results: The most prominent issues raised by patients concerned (i) expertise of the various professionals within clinic, (ii) quality of interactions with clinic professionals, especially the flow of information from professionals to patients, and (iii) wish to be treated holistically. Ophthalmologists suggested such issues could be best dealt with via a programme of patient education and tended to overlook deeper implications of patient concerns for the organisation of services., Conclusion: For patients, the clinical service should not only include the identification and treatment of disease but also exchange of information, reassurance, and mitigation of anxiety. Alterations in the standard care pathway need to take account of such concerns and their implications, in addition to any assessments of 'efficiency' that may flow from changes in diagnostic technology, or the division of professional labour., (© 2022. Crown.)

Single-use plastics are a matter of convenience in everyday life, with the majority allocated to packaging production. However, it comes with a high environmental price as its mass recycling is challenging due to the heterogeneity of composition, contaminations of different kinds, and degradation caused by service and processing. This study aims to ascertain the impact of removing contaminants from post-consumer recycled polypropylene (rPP) on its degradation and properties by implementing a systematic approach for decontamination by washing. Four lots of recycled plastics with different degrees of contamination were evaluated via Fourier transform infrared, melt flow indexer, and differential scanning calorimetry and tested for tensile strength. Degradation of the rPP was manifested by the deterioration in ductility, resulting in 14.58% elongation at break (unwashed rPP) compared with 191.41% (virgin PP)) and a significant reduction in oxidation induction time. In the unwashed rPP sample, a wave intensity peak at 1730 cm -1 , assigned to the saturated C = 0 stretch of the carbonyl functional group, was detected. This peak was gradually disappearing with an increase in the cleaning efficiency of rPP, highlighting the role of contaminants as degradation catalysts. The cold-washing method showed similar processing and mechanical performance improvement results compared with the other washing methods, while being more environmentally friendly and energy efficient.

Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Evidence for the health benefits of urban green space tends to stem from small, short-term quasi-experimental or cross-sectional observational research, whilst evidence from intervention studies is sparse. The development of an urban greenway (9 km running along 3 rivers) in Northern Ireland provided the opportunity to conduct a natural experiment. This study investigated the public health impact of the urban greenway on a range of physical activity, health, wellbeing, social, and perceptions of the environment outcomes., Methods: A repeated cross-sectional household survey of adult residents (aged ≥16 years) who lived ≤1-mile radius of the greenway (intervention sample) and > 1-mile radius of the greenway (control sample) was conducted pre (2010/2011) and 6-months post implementation (2016/2017). We assessed changes in outcomes pre- and post-intervention follow-up including physical activity behaviour (primary outcome measure: Global Physical Activity Questionnaire), quality of life, mental wellbeing, social capital and perceptions of the built environment. Linear regression was used to calculate the mean difference between post-intervention and baseline measures adjusting for age, season, education, car ownership and deprivation. Multi-level models were fitted using a random intercept at the super output area (smallest geographical unit) to account for clustering within areas. The analyses were stratified by distance from the greenway and deprivation. We assessed change in the social patterning of outcomes over time using an ordered logit to make model-based outcome predictions across strata., Results: The mean ages of intervention samples were 50.3 (SD 18.9) years at baseline (n = 1037) and 51.7 (SD 19.1) years at follow-up (n = 968). Post-intervention, 65% (adjusted OR 0.60, 95% CI 0.35 to 1.00) of residents who lived closest to the greenway (i.e., ≤400 m) and 60% (adjusted OR, 0.64 95% CI 0.41 to 0.99) who lived furthest from the greenway (i.e.,≥1200 m) met the physical activity guidelines - 68% of the intervention sample met the physical activity guidelines before the intervention. Residents in the most deprived quintiles had a similar reduction in physical activity behaviour as residents in less deprived quintiles. Quality of life at follow-up compared to baseline declined and this decline was significantly less than in the control area (adjusted differences in mean EQ5D: -11.0 (95% CI - 14.5 to - 7.4); - 30.5 (95% CI - 37.9 to - 23.2). Significant change in mental wellbeing was not observed despite improvements in some indicators of social capital. Positive perceptions of the local environment in relation to its attractiveness, traffic and safety increased., Conclusions: Our findings illustrate the major challenge of evaluating complex urban interventions and the difficulty of capturing and measuring the network of potential variables that influence or hinder meaningful outcomes. The results indicate at this stage no intervention effect for improvements in population-level physical activity behaviour or mental wellbeing. However, they show some modest improvements for secondary outcomes including positive perceptions of the environment and social capital constructs. The public health impact of urban greenways may take a longer period of time to be realised and there is a need to improve evaluation methodology that captures the complex systems nature of urban regeneration., (© 2021. The Author(s).)

School performance measures are published annually in England to hold schools to account and to support parental school choice. This article reviews and evaluates the 'Progress 8' secondary school accountability system for state-funded schools. We assess the statistical strengths and weaknesses of Progress 8 relating to: choice of pupil outcome attainment measure; potential adjustments for pupil input attainment and background characteristics; decisions around which schools and pupils are excluded from the measure; presentation of Progress 8 to users, choice of statistical model, and calculation of statistical uncertainty; and issues related to the volatility of school performance over time, including scope for reporting multi-year averages. We then discuss challenges for Progress 8 raised by the COVID-19 pandemic. Six simple recommendations follow to improve Progress 8 and school accountability in England., Competing Interests: The authors have no conflict of interest to declare., (© 2021 The Authors. Review of Education published by John Wiley & Sons Ltd on behalf of British Educational Research Association.)

We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge., (© 2021. The Author(s).)

Purpose: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes., Methods: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses., Results: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications., Conclusion: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The stress pathway posits that those in disadvantaged circumstances are exposed to a higher degree of stressful experiences over time resulting in an accumulated biological burden which subsequently relates to poorer health. Trajectories of disadvantage, in the form of neighbourhood deprivation and structural social capital, are evaluated in their relation to allostatic load representing the cumulative "wear and tear" of chronic stress. This paper uses data from the British Household Panel Survey and Understanding Society in a latent class growth analysis. We identify groups of exposure trajectories over time using these classes to predict allostatic load at the final wave. The results show that persistent exposure to higher deprivation is related to worse allostatic load. High structural social capital over time relates to lower allostatic load, in line with a stress buffering effect, though this relationship is not robust to controlling for individual sociodemographic characteristics. By demonstrating a gradient in allostatic load by histories of deprivation, this analysis supports a biological embedding of disadvantage through chronic exposure to stressful environments as an explanation for social health inequalities.

Background: Owing to the increasing prevalence of diabetes, the workload related to diabetic macular oedema and proliferative diabetic retinopathy is rising, making it difficult for hospital eye services to meet demands., Objective: The objective was to evaluate the diagnostic performance, cost-effectiveness and acceptability of a new pathway using multimodal imaging interpreted by ophthalmic graders to detect reactivation of diabetic macular oedema/proliferative diabetic retinopathy in previously treated patients., Design: This was a prospective, case-referent, cross-sectional diagnostic study., Setting: The setting was ophthalmic clinics in 13 NHS hospitals., Participants: Adults with type 1 or type 2 diabetes with previously successfully treated diabetic macular oedema/proliferative diabetic retinopathy in one/both eyes in whom, at the time of enrolment, diabetic macular oedema/proliferative diabetic retinopathy could be active or inactive., Methods: For the ophthalmic grader pathway, review of the spectral domain optical coherence tomography scans to detect diabetic macular oedema, and seven-field Early Treatment Diabetic Retinopathy Study/ultra-wide field fundus images to detect proliferative diabetic retinopathy, by trained ophthalmic graders. For the current standard care pathway (reference standard), ophthalmologists examined patients face to face by slit-lamp biomicroscopy for proliferative diabetic retinopathy and, in addition, spectral domain optical coherence tomography imaging for diabetic macular oedema., Outcome Measures: The primary outcome measure was sensitivity of the ophthalmic grader pathway to detect active diabetic macular oedema/proliferative diabetic retinopathy. The secondary outcomes were specificity, agreement between pathways, cost-consequences, acceptability and the proportion of patients requiring subsequent ophthalmologist assessment, unable to undergo imaging and with inadequate quality images/indeterminate findings. It was assumed for the main analysis that all patients in whom graders diagnosed active disease or were 'unsure' or images were 'ungradable' required examination by an ophthalmologist., Results: Eligible participants with active and inactive diabetic macular oedema (152 and 120 participants, respectively) and active and inactive proliferative diabetic retinopathy (111 and 170 participants, respectively) were recruited. Under the main analysis, graders had a sensitivity of 97% (142/147) (95% confidence interval 92% to 99%) and specificity of 31% (35/113) (95% confidence interval 23% to 40%) to detect diabetic macular oedema. For proliferative diabetic retinopathy, graders had a similar sensitivity and specificity using seven-field Early Treatment Diabetic Retinopathy Study [sensitivity 85% (87/102), 95% confidence interval 77% to 91%; specificity 48% (77/160), 95% confidence interval 41% to 56%] or ultra-wide field imaging [sensitivity 83% (87/105), 95% confidence interval 75% to 89%; specificity 54% (86/160), 95% confidence interval 46% to 61%]. Participants attending focus groups expressed preference for face-to-face evaluations by ophthalmologists. In the ophthalmologists' absence, patients voiced the need for immediate feedback following grader's assessments, maintaining periodic evaluations by ophthalmologists. Graders and ophthalmologists were supportive of the new pathway. When compared with the reference standard (current standard pathway), the new grader pathway could save £1390 per 100 patients in the review of people with diabetic macular oedema and, depending on the imaging modality used, between £461 and £1189 per 100 patients in the review of people with proliferative diabetic retinopathy., Conclusions: For people with diabetic macular oedema, the ophthalmic grader pathway appears safe and cost saving. The sensitivity of the new pathway to detect active proliferative diabetic retinopathy was lower, but may still be considered acceptable for patients with proliferative diabetic retinopathy previously treated with laser. Suggestions from focus group discussions should be taken into consideration if the new pathway is introduced to ensure its acceptability to users., Limitations: Lack of fundus fluorescein angiography to confirm diagnosis of active proliferative diabetic retinopathy., Future Work: Could refinement of the new pathway increase its sensitivity to detect proliferative diabetic retinopathy? Could artificial intelligence be used for automated reading of images in this previously treated population?, Trial Registration: Current Controlled Trials ISRCTN10856638 and ClinicalTrials.gov NCT03490318., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 32. See the NIHR Journals Library website for further project information.

Purpose: The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR., Design: Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom., Participants: Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease., Methods: A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists)., Main Outcome Measures: Primary outcome: sensitivity of the new pathway., Secondary Outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings., Results: The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%-99%) and specificity of 31% (95% CI, 23%-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%-91%] and 48% [95% CI, 41%-56%], respectively) or UWF images (83% [95% CI, 75%-89%] and 54% [95% CI, 46%-61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%-93%] and 49% [95% CI, 42%-56%], respectively, for UWF versus 80% [95% CI, 69-88%] and 40% [95% CI, 34%-47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists' assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits., Conclusions: The new pathway has acceptable sensitivity and would release resources. Users' suggestions should guide implementation., (Copyright © 2020 American Academy of Ophthalmology. All rights reserved.)

Purpose: The purpose is to explore triggers for moral distress, constraints preventing physicians from doing the right thing and ensuing consequences in making decisions for patients approaching end of life in intensive care., Materials and Methods: The qualitative study was undertaken in a tertiary referral intensive care unit in Northern Ireland in the United Kingdom. Drawing upon patient case studies of decisions about non escalation and/or withdrawal of life support, we undertook indepth interviews with senior and junior physicians. Interviews were transcribed verbatim and narratively analysed., Results: Eighteen senior and junior physicians involved in 21 patient case studies were interviewed. Analysis determined two predominant themes: key moral distress triggers; and strategies and consequences. Junior residents reported most instances of moral distress, triggered by perceived futility, lack of continuity, protracted decisions and failure to ensure 'good death'. Senior physicians' triggers included constraint of clinical autonomy. Moral distress was far reaching, affecting personal life, working relationships and career choice., Conclusion: This study is the first to explore physicians' moral distress in end-of-life decisions in intensive care via a narrative inquiry approach using case studies. Results have implications for the education, recruitment and retention of physicians, relevant in the Covid 19 pandemic., Competing Interests: Declaration of Competing Interest The authors declare they have no competing interests., (Copyright © 2019. Published by Elsevier Inc.)

Background: Due to advances in care, most women diagnosed with breast cancer do not die from the disease itself. Instead, cardiovascular disease (CVD) remains the most frequent cause of death. Many breast cancer patients are older and have established CVD risk factors. They are at further risk due to exposure to anthracyclines, HER2 targeted agents, endocrine therapy and radiotherapy. In this study, we compared the 10-year predicted risk of breast cancer mortality versus that of cardiovascular (CV) morbidity/mortality in breast cancer patients receiving adjuvant chemotherapy using online predictive risk calculators. Furthermore, we evaluated the predicted outcome of CV risk factor optimisation on their overall CV risk., Methods: This was a cross sectional study. All patients with resected Stage I-III breast cancer who received adjuvant chemotherapy at our centre from September 2015 to November 2016 were identified. Data recorded included demographics, tumor characteristics, treatments and CV risk factors. To calculate predicted 10-year risk of CVD and impact of lifestyle changes, we used the JBS3 (Joint British Society) online risk calculator. To calculate the predicted 10-year risk of breast cancer mortality, we used the PREDICT calculator. Biostatistical methods included Wilcoxon signed rank test for predicted CVD risk pre and post cardiovascular risk optimization., Results: We identified 102 patients. Of this cohort, 76 patients were ≥ 50 years & 26 were < 50 years of age. The group had significant baseline cardiovascular risk factors: increased BMI (68 %, n = 70), ex-smoking (34 %, n = 35), current smoking (13 %, n = 13), hypertension (47 %, n = 47) and dyslipidemia (57 %). Of the total group, 48 % had a high (> 20 %) and 37 % had a moderate (10-20 %) 10-year predicted breast cancer mortality risk. Regarding 10-year predicted risk of CVD, 11 % and 22 % fell into the high (> 20 %) and moderate (10-20 %) risk categories, respectively. Assuming CV risk factor optimisation, there was a predicted improvement in median 10-year CV risk from 26.5 to 9.9 % (p = .005) in the high CVD risk group and from 14.0 to 6.6 % (p < .001) in the moderate CVD risk group., Conclusions: Benefits predicted with a CVD risk intervention model indicates that this should be incorporated into routine breast oncology care.

Primary Care Physicians (PCPs) are integral to the health of all people in the U.S. Many PCPs experience burnout, and declines in well-being. We conducted a randomized controlled trial of a six-session positive psychology-based coaching intervention to improve PCP personal and work-related well-being and decrease stress and burnout. Fifty-nine U.S.-based PCPs were randomized into a primary ( n = 29) or a waitlisted control group ( n = 30). Outcome measures were assessed preintervention, postintervention, and at three and six months post-intervention. Hypotheses 1a-1h were for a randomized controlled trial test of coaching on PCP burnout (a), stress (b), turnover intentions (c), work engagement (d), psychological capital (e), compassion (f), job self-efficacy (g), and job satisfaction (h). Results from 50 PCPs who completed coaching and follow-up assessments indicated significantly decreased burnout (H1a) and increased work engagement (H1d), psychological capital (H1e), and job satisfaction (H1h) for the primary group from pre- to postcoaching, compared to changes between comparable time points for the waitlisted group. Hypotheses 2a-2h were for stability of positive effects and were tested using follow-up data from participants in the primary and waitlisted groups combined. Results from 39 PCPs who completed the intervention and the six-month follow-up indicated that positive changes observed for H1a, H1d, H1e, and H1h were sustained during a six-month follow-up (supporting H2a, H2d, H2e, and H2h). Results indicate that coaching is a viable and effective intervention for PCPs in alleviating burnout and improving well-being. We recommend that employers implement coaching for PCPs alongside systemic changes to work factors driving PCP burnout. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Analyses of health over time must consider the potential impacts of ageing as well as any effects relating to cohort differences. The British Household Panel Survey (BHPS) and Understanding Society longitudinal studies are employed to assess trends in mental ill-health over a 26-year period. This analysis uses cross-classified multilevel models in an exploratory, non-parametric approach to evaluate age and cohort effects net of each other. Mental ill-health evidences an initial worsening trend as people age which then reverses and exhibits improvement in late-middle-age, before declining again in the latter stages of life. There were less defined cohort trends. The modelling technique also reveals the relative importance of the temporal contexts in relation to inter- and intra-individual effects on mental ill-health, demonstrating that the ageing and cohort dimensions explain little variation compared to these more dominant within and between influences. Ultimately, we suggest that researchers would benefit from wider use of this exploratory modelling strategy when evaluating underlying health trends and more research is now needed to explore potential explanations of these baseline trajectories., Competing Interests: The authors have declared that no competing interests exist.

The treatment landscape for metastatic melanoma has been revolutionised by the introduction of immunotherapy and targeted therapies. Despite these advances, some patients exhibit primary or acquired resistance to treatment. We present the case of a resected mucosal melanoma that on relapse underwent transformation to a dedifferentiated state. The relapsed tumour was phenotypically disparate and demonstrated loss of all typical melanoma-associated immunohistochemical markers. Furthermore, it demonstrated aggressive biological behaviour and immunotherapy resistance. We performed genomic profiling of the original and relapsed tumour to further elucidate the mechanisms underlying this rare phenomenon. Mass spectrometry-based single-nucleotide polymorphism genotyping technology was used to screen for mutations in the original and recurrent tumour. Whole-exome sequencing was performed on the original tumour, recurrent tumour and blood. Both the original and recurrent tumour shared a NRAS mutation, a similar aneuploidy profile and proportion of somatic single-nucleotide variants. However, in contrast to the original tumour, the recurrent tumour demonstrated a lower mutational burden and deletions in the CDKN2A/CDKN2B and CHEK2 genes. The genomic similarity between the original and recurrent tumour attests to a common ancestry and the possible existence of nongenomic drivers inciting phenotype plasticity. In contrast, the low mutational load and potential inactivation of tumour suppressor genes in the recurrent tumour may underlie its rapid proliferative rate and immunoresistance. Dynamic treatment models are desired in the future to track the genomic and epigenetic evolution of a tumour to guide optimal therapy choice and sequencing.

Following a presentation with abdominal pain, a 22-year-old female was diagnosed with a massive primary liver immature teratoma with evidence of omental and pelvic metastases. Despite chemotherapy, the teratoma continued to rapidly increase in size. Significant treatment-associated myelosuppression was challenging as the patient did not want to receive any blood products (religious objections). The only feasible approach was surgical resection. Surgical resection of the primary tumor and abdominal metastases was undertaken despite unappealing perioperative risk with histological specimens demonstrating only mature teratoma. We report the first case of a liver teratoma suggestive of growing teratoma syndrome treated with myelosuppressive chemotherapy and major hepatectomy without the use of any blood products.

This article reports on an ethnography of architectural projects for later life social care in the UK. Informed by recent debates in material studies and "materialities of care" we offer an analysis of a care home project that is sensitive to architectural materials that are not normally associated with care and well-being. Although the care home design project we focus on in this article was never built, we found that design discussions relating to a curved brick wall and bricks more generally were significant to its architectural "making". The curved wall and the bricks were used by the architects to encode quality and values of care into their design. This was explicit in the design narrative that was core to a successful tender submitted by a consortium comprising architects, developers, contractors, and a care provider to a local authority who commissioned the care home. However, as the project developed, initial consensus for the design features fractured. Using a materialized analysis, we document the tussles generated by the curved wall and the bricks and argue that mundane building materials can be important to, and yet marginalized within, the relations inherent to an "architectural care assemblage." During the design process we saw how decisions about materials are contentious and they act as a catalyst of negotiations that compromise "materialities of care.", (© 2019 The Authors. The British Journal of Sociology published by John Wiley & Sons Ltd on behalf of London School of Economics and Political Science.)

Introduction: The burden of obesity and risk of cardiovascular (CV) disease amongst an oncology population receiving active treatment is ill-defined. We performed a retrospective analysis assessing the incidence of obesity and cardiovascular (CV) risk factors in this group (grp) of patients as well as the predicted 10-year risk of a CV event., Methods: Data from all patients (pts) receiving intravenous chemotherapy in an Irish oncology satellite unit over an 18-month period was extracted from chemotherapy prescriptions and electronic patient records. To calculate patients' 10-year risk of developing CV disease, we used QRISK, a predictive risk calculator., Results: The prevalence of obesity (BMI > 30) amongst the total population was 19% (n = 21), with 26% (n = 28) overweight (BMI, 25-< 30). Information on CV risk factors was available in 93 pts. with the following rates being observed: hypertension 34%, dyslipidaemia 19%, current smoker 18% and diabetes 11%. The average 10-year risk of a CV event (stroke/MI) in this cohort was 19.2% (± 16.6), with a relative risk of 1.4 compared to their age-matched controls without CV risk factors., Conclusions: We observed similar or lower rates of obesity and CV risk factors in this cohort compared to the general adult Irish population. The average predicted risk of developing CV disease in this grp was moderate to high. This can have significant future implications with regard to cancer survivorship, disease recurrence and suitability for further oncological treatments.

Introduction: Diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) are the major causes of sight loss in people with diabetes. Due to the increased prevalence of diabetes, the workload related to these complications is increasing making it difficult for Hospital Eye Services (HSE) to meet demands., Methods and Analysis: Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy (EMERALD) is a prospective, case-referent, cross-sectional diagnostic study. It aims at determining the diagnostic performance, cost-effectiveness and acceptability of a new form of surveillance for people with stable DMO and/or PDR, which entails multimodal imaging and image review by an ophthalmic grader, using the current standard of care (evaluation of patients in clinic by an ophthalmologist) as the reference standard. If safe, cost-effective and acceptable, this pathway could help HES by freeing ophthalmologist time. The primary outcome of EMERALD is sensitivity of the new surveillance pathway in detecting active DMO/PDR. Secondary outcomes include specificity, agreement between new and the standard care pathway, positive and negative likelihood ratios, cost-effectiveness, acceptability, proportion of patients requiring subsequent full clinical assessment, unable to undergo imaging, with inadequate quality images or indeterminate findings., Ethics and Dissemination: Ethical approval was obtained for this study from the Office for Research Ethics Committees Northern Ireland (reference 17/NI/0124). Study results will be published as a Health Technology Assessment monograph, in peer-reviewed national and international journals and presented at national/international conferences and to patient groups., Trial Registration Number: NCT03490318 and ISRCTN:10856638., Competing Interests: Competing interests: NL, NW, AA-B, HM, DMcA, TA: none; CB: has been ad hoc advisor for Alcon, Bayer, Novartis, Alimera Sciences and Allergan; VC is a part-time employee of Boehringer Ingelheim International GmBH (BII), Germany; this study, however, is not being undertaken as part of the employment with BII and, thus, the content of this manuscript is not endorsed by BII. VC has also received speaker fees from Quantel Medical, France; SS has received research grants, travel feeds and attended advisory board meetings of Novartis, Bayer, Roche, Allergan, Heidelberg Engineering, Optos and Boehringer Ingelheim; DS acted as consultant to Alcon, attended advisory boards for Novartis and Bayer and received research funding from Bayer and Alcon. PS has attended Advisory Boards for Allergan, Roche, Boehringer and Bayer; his department has received Educational, Research or Audit Grants from Allergan, Novartis and Bayer., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Mediterranean diet (MD) interventions are demonstrated to significantly reduce cardiovascular disease (CVD) risk but are typically resource intensive and delivered by health professionals. There is considerable interest to develop interventions that target sustained dietary behaviour change and that are feasible to scale-up for wider public health benefit. The aim of this paper is to describe the process used to develop a peer support intervention to encourage dietary behaviour change towards a MD in non-Mediterranean adults at high CVD risk., Methods: The Medical Research Council (MRC) and Behaviour Change Wheel (BCW) frameworks and the COM-B (Capability, Opportunity, Motivation, Behaviour) theoretical model were used to guide the intervention development process. We used a combination of evidence synthesis and qualitative research with the target population, health professionals, and community health personnel to develop the intervention over three main stages: (1) we identified the evidence base and selected dietary behaviours that needed to change, (2) we developed a theoretical basis for how the intervention might encourage behaviour change towards a MD and selected intervention functions that could drive the desired MD behaviour change, and (3) we defined the intervention content and modelled outcomes., Results: A theory-based, culturally tailored, peer support intervention was developed to specifically target behaviour change towards a MD in the target population. The intervention was a group-based program delivered by trained peer volunteers over 12-months, and incorporated strategies to enhance social support, self-efficacy, problem-solving, knowledge, and attitudes to address identified barriers to adopting a MD from the COM-B analysis., Conclusions: The MRC and BCW frameworks provided a systematic and complementary process for development of a theory-based peer support intervention to encourage dietary behaviour change towards a MD in non-Mediterranean adults at high CVD risk. The next step is to evaluate feasibility, acceptability, and diet behaviour change outcomes in response to the peer support intervention (change towards a MD and nutrient biomarkers) using a randomized controlled trial design.

Background: Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non-Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non-Mediterranean high-risk populations., Methods: Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis., Results: Sixty-seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences., Conclusions: Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non-Mediterranean populations., (© 2017 The British Dietetic Association Ltd.)

Deprived neighbourhoods have long been associated with poorer health outcomes. However, many quantitative studies have not evidenced the mechanisms through which place 'gets under the skin' to influence health. The increasing prevalence of biosocial data provides new opportunities to explore these mechanisms and incorporate them into models of contextual effects. The stress pathway is a key biosocial mechanism; however, few studies have explicitly tested it in neighbourhood associations. This paper addresses this gap by investigating whether allostatic load, a biological response to chronic stress, mediates relationships of neighbourhood deprivation to physical and mental health. Data from UK Understanding Society is used to undertaken a multilevel mediation analysis. Allostatic load is found to mediate the association between neighbourhood deprivation and health, substantiating the biological mechanism of the stress pathway. More deprived areas are associated with higher allostatic load, and in turn worse allostatic load relates to poorer physical and mental health. Allostatic load is a stronger mediator of physical health than mental health, suggesting the stress pathway is more pertinent to explaining physical health gradients. Heterogeneity in the results between physical and mental health suggests more research is needed to disentangle the biosocial processes that could be important to health and place relationships., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Epidemiological and randomised controlled trial evidence demonstrates that adherence to a Mediterranean diet (MD) can reduce cardiovascular disease (CVD) risk. However, methods used to support dietary change have been intensive and expensive. Peer support has been suggested as a possible cost-effective method to encourage adherence to a MD in at risk populations, although development of such a programme has not been explored. The purpose of this study was to use mixed-methods to determine the preferred peer support approach to encourage adherence to a MD., Methods: Qualitative (focus groups) and quantitative methods (questionnaire and preference scoring sheet) were used to determine preferred methods of peer support. Sixty-seven high CVD risk participants took part in 12 focus groups (60% female, mean age 64 years) and completed a questionnaire and preference scoring sheet. Focus group data were transcribed and thematically analysed., Results: The mean preference score (1 being most preferred and 5 being least preferred) for group support was 1.5, compared to 3.4 for peer mentorship, 4.0 for telephone peer support and 4.0 for internet peer support. Three key themes were identified from the transcripts: 1. Components of an effective peer support group: discussions around group peer support were predominantly positive. It was suggested that an effective group develops from people who consider themselves similar to each other meeting face-to-face, leading to the development of a group identity that embraces trust and honesty. 2. Catalysing Motivation: participants discussed that a group peer support model could facilitate interpersonal motivations including encouragement, competitiveness and accountability. 3. Stepping Stones of Change: participants conceptualised change as a process, and discussed that, throughout the process, different models of peer support might be more or less useful., Conclusion: A group-based approach was the preferred method of peer support to encourage a population at high risk of CVD to adhere to a MD. This finding should be recognised in the development of interventions to encourage adoption of a MD in a Northern European population.

Background: Novice drivers are at relatively high risk of road traffic injury. There is good evidence that Graduated Driving Licensing (GDL) schemes reduce collisions rates, by reducing exposure to risk and by extending learning periods. Legislation for a proposed scheme in Northern Ireland was passed in 2016, providing an opportunity for future evaluation of the full public health impacts of a scheme in a European context within a natural experiment. This qualitative study was designed to inform the logic model for such an evaluation, and provide baseline qualitative data on the role of private cars in health and wellbeing., Methods: Nine group interviews with young people aged 16-23 (N = 43) and two group interviews with parents of young people (N = 8) were conducted in a range of settings in Northern Ireland in 2015. Data were analysed using thematic content analysis., Results: Informal car-pooling within and beyond households led to routine expectations of lift provision and uptake. Experiences of risky driving situations were widespread. In rural areas, extensive use of farm vehicles for transport needs meant many learner drivers had both early driving experience and expectations that legislation may have to be locally adapted to meet social needs. Cars were used as a site for socialising, as well as essential means of transport. Alternative modes (public transport, walking and cycling) were held in low esteem, even where available. Recall of other transport-related public health messages and parents' existing use of GDL-type restrictions suggested GDL schemes were acceptable in principle. There was growing awareness and use of in-car technologies (telematics) used by insurance companies to reward good driving., Conclusions: Key issues to consider in evaluating the broader public health impact of GDL will include: changes in injury rates for licensed car occupants and other populations and modes; changes in exposure to risk in the licensed and general population; and impact on transport exclusion. We suggest an important pathway will be change in social norms around offering and accepting lifts and to risk-taking. The growing adoption of in-car telematics will have implications for future GDL programmes and for evaluation.

Background: Increasing physical activity in the workplace can provide employee physical and mental health benefits, and employer economic benefits through reduced absenteeism and increased productivity. The workplace is an opportune setting to encourage habitual activity. However, there is limited evidence on effective behaviour change interventions that lead to maintained physical activity. This study aims to address this gap and help build the necessary evidence base for effective, and cost-effective, workplace interventions., Methods/design: This cluster randomised control trial will recruit 776 office-based employees from public sector organisations in Belfast and Lisburn city centres, Northern Ireland. Participants will be randomly allocated by cluster to either the Intervention Group or Control Group (waiting list control). The 6-month intervention consists of rewards (retail vouchers, based on similar principles to high street loyalty cards), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of participating workplaces will promote and monitor minutes of physical activity undertaken by participants. Both groups will complete all outcome measures. The primary outcome is steps per day recorded using a pedometer (Yamax Digiwalker CW-701) for 7 consecutive days at baseline, 6, 12 and 18 months. Secondary outcomes include health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Process measures will assess intervention "dose", website usage, and intervention fidelity. An economic evaluation will be conducted from the National Health Service, employer and retailer perspective using both a cost-utility and cost-effectiveness framework. The inclusion of a discrete choice experiment will further generate values for a cost-benefit analysis. Participant focus groups will explore who the intervention worked for and why, and interviews with retailers will elucidate their views on the sustainability of a public health focused loyalty card scheme., Discussion: The study is designed to maximise the potential for roll-out in similar settings, by engaging the public sector and business community in designing and delivering the intervention. We have developed a sustainable business model using a 'points' based loyalty platform, whereby local businesses 'sponsor' the incentive (retail vouchers) in return for increased footfall to their business., Trial Registration: ISRCTN17975376 (Registered 19/09/2014).

Sociologists of health and illness have tended to overlook the architecture and buildings used in health care. This contrasts with medical geographers who have yielded a body of work on the significance of places and spaces in the experience of health and illness. A review of sociological studies of the role of the built environment in the performance of medical practice uncovers an important vein of work, worthy of further study. Through the historically situated example of hospital architecture, this article seeks to tease out substantive and methodological issues that can inform a distinctive sociology of healthcare architecture. Contemporary healthcare buildings manifest design models developed for hotels, shopping malls and homes. These design features are congruent with neoliberal forms of subjectivity in which patients are constituted as consumers and responsibilised citizens. We conclude that an adequate sociology of healthcare architecture necessitates an appreciation of both the construction and experience of buildings, exploring the briefs and plans of their designers, and observing their everyday uses. Combining approaches and methods from the sociology of health and illness and science and technology studies offers potential for a novel research agenda that takes healthcare buildings as its substantive focus., (© 2015 Foundation for the Sociology of Health & Illness.)

Parents caring for a child with a life threatening or life limiting illness experience a protracted and largely unknown journey, as they and their child oscillate somewhere between life and death. Using an interpretive qualitative approach, interviews were conducted with parents (n = 25) of children who had died. Findings reveal parents' experiences to be characterised by personal disorder and transformation as well as social marginalisation and disconnection. As such they confirm the validity of understanding these experiences as, fundamentally, one of liminality, in terms of both individual and collective response. In dissecting two inter-related dimensions of liminality, an underlying tension between how transition is subjectively experienced and how it is socially regulated is exposed. In particular, a structural failure to recognise the chronic nature of felt liminality can impede parents' effective transition., (© 2015 Foundation for the Sociology of Health & Illness.)

It is now recognised that inactive lifestyles underpin much of the disease burden evident in the richer nations of the world. Indeed, the WHO has identified physical inactivity as a 'global public health problem' and has established minimum physical activity (PA) targets for people at different stages of the life-course. Yet, according to WHO, just under 1/3 of working age adults across the globe meet those targets and it is not at all clear how the disjunction between the recommendations of policy makers and the behaviour of ordinary people might be surmounted. Using an opportunity to examine the impact of an urban regeneration project on community residents in East Belfast (Northern Ireland) this paper examines the views of some 113 people on how to increase rates of PA in an area of multiple deprivation. The results of the analysis suggest that lay people rarely consider PA as a discrete issue, or one that centres on individuals and their motivation, but rather as one component in a complex web of concerns, processes and events that include such things as the actions of neighbours and relatives, material and political environments, vandalism, violence, and the weather. We explore and unravel the nature of those concerns using novel methods of content analysis that generate 'issue webs'. Particular attention is paid to the ways in which lay people conceptualize 'activity' and to the manner in which they point to ways of encouraging activity that are rooted in everyday life rather than in the corpocentric, agent-centred and often sport dominated strategies favoured by local policy makers. Our results support those who argue that interventions to increase rates of PA need to move beyond behavioural approaches that focus on individuals and consider the social, political and material contexts in which 'activity' occurs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: There is an urgent need to increase population levels of physical activity, particularly amongst those who are socio-economically disadvantaged. Multiple factors influence physical activity behaviour but the generalisability of current evidence to such 'hard-to-reach' population subgroups is limited by difficulties in recruiting them into studies. Also, rigorous qualitative studies of lay perceptions and perceptions of community leaders about public health efforts to increase physical activity are sparse. We sought to explore, within a socio-economically disadvantaged community, residents' and community leaders' perceptions of physical activity (PA) interventions and issues regarding their implementation, in order to improve understanding of needs, expectations, and social/environmental factors relevant to future interventions., Methods: Within an ongoing regeneration project (Connswater Community Greenway), in a socio-economically disadvantaged community in Belfast, we collaborated with a Community Development Agency to purposively sample leaders from public- and voluntary-sector community groups and residents. Individual semi-structured interviews were conducted with 12 leaders. Residents (n = 113), of both genders and a range of ages (14 to 86 years) participated in focus groups (n = 14) in local facilities. Interviews and focus groups were recorded, transcribed verbatim and analysed using a thematic framework., Results: Three main themes were identified: awareness of PA interventions; factors contributing to intervention effectiveness; and barriers to participation in PA interventions. Participants reported awareness only of interventions in which they were involved directly, highlighting a need for better communications, both inter- and intra-sectoral, and with residents. Meaningful engagement of residents in planning/organisation, tailoring to local context, supporting volunteers, providing relevant resources and an 'exit strategy' were perceived as important factors related to intervention effectiveness. Negative attitudes such as apathy, disappointing experiences, information with no perceived personal relevance and limited access to facilities were barriers to people participating in interventions., Conclusions: These findings illustrate the complexity of influences on a community's participation in PA interventions and support a social-ecological approach to promoting PA. They highlight the need for cross-sector working, effective information exchange, involving residents in bottom-up planning and providing adequate financial and social support. An in-depth understanding of a target population's perspectives is of key importance in translating PA behaviour change theories into practice.

Background: This paper focuses on the relationships between health 'policy' as it is embodied in official documentation, and health 'practice' as reported and reflected on in the talk of policy-makers, health professionals and patients. The specific context for the study involves a comparison of policies relating to the secondary prevention of coronary heart disease (CHD) in the two jurisdictions of Ireland - involving as they do a predominantly state funded (National Health Service) system in the north and a mixed health-care economy in the south. The key question is to determine how the detail of health policy as contained in policy documents connects to and gets translated into practice and action., Methods: The data sources for the study include relevant health-care policy documents (N=5) and progress reports (N=6) in the two Irish jurisdictions, and semi-structured interviews with a range of policy-makers (N=28), practice nurses (14), general practitioners (12) and patients (13) to explore their awareness of the documents' contents and how they saw the impact of 'policy' on primary care practice., Results: The findings suggest that although strategic policy documents can be useful for highlighting and channelling attention to health issues that require concerted action, they have little impact on what either professionals or lay people do., Conclusion: To influence the latter and to encourage a systematic approach to the delivery of health care it seems likely that contractual arrangements - specifying tasks to be undertaken and methods for monitoring and reporting on activity - are required., (© 2011 John Wiley & Sons Ltd.)

Background: There is a dearth of evidence regarding the impact of urban regeneration projects on public health, particularly the nature and degree to which urban regeneration impacts upon health-related behaviour change. Natural experiment methodology enables comprehensive large-scale evaluations of such interventions. The Connswater Community Greenway in Belfast is a major urban regeneration project involving the development of a 9 km linear park, including the provision of new cycle paths and walkways. In addition to the environmental improvements, this complex intervention involves a number of programmes to promote physical activity in the regenerated area. The project affords a unique opportunity to investigate the public health impact of urban regeneration., Methods/design: The evaluation framework was informed by the socio-ecological model and guided by the RE-AIM Framework. Key components include: (1) a quasi-experimental before-and-after survey of the Greenway population (repeated cross-sectional design), in tandem with data from a parallel Northern Ireland-wide survey for comparison; (2) an assessment of changes in the local built environment and of walkability using geographic information systems; (3) semi-structured interviews with a purposive sample of survey respondents, and a range of community stakeholders, before and after the regeneration project; and (4) a cost-effectiveness analysis. The primary outcome is change in proportion of individuals identified as being regularly physically active, according to the current UK recommendations. The RE-AIM Framework will be used to make an overall assessment of the impact of the Greenway on the physical activity behaviour of local residents., Discussion: The Connswater Community Greenway provides a significant opportunity to achieve long-term, population level behaviour change. We argue that urban regeneration may be conceptualised meaningfully as a complex intervention comprising multiple components with the potential, individually and interactively, to affect the behaviour of a diverse population. The development and implementation of our comprehensive evaluation framework reflects this complexity and illuminates an approach to the empirical, rigorous evaluation of urban regeneration. More specifically, this study will add to the much needed evidence-base about the impact of urban regeneration on public health as well as having important implications for the development of natural experiment methodology.

Aim: To explore moral distress in relatives doctors and nurses, in end-of-life care decision-making, in the adult intensive care unit., Background: Many deaths in intensive care involve decisions about withholding and withdrawing therapy, potentially triggering moral distress. Moral distress occurs when individuals feel constrained from acting in accordance with moral choice, or act against moral judgement, generating painful, unresolved emotions, and problems that continue long after an event. Prior research has focused mainly on nurses; less is known about doctors' experiences and occurrence and impact on relatives is unknown., Design: A narrative inquiry case study approach, funded by a Northern Ireland Health and Social Care Doctorate Fellowship Award (April 2011)., Methods: In-depth digitally recorded interviews will be conducted with relatives, doctors, and nurses involved in end-of-life cases comprising: (1) withdrawal of therapy, including circulatory death organ donation; (2) non-escalation of therapy; and (3) brain stem death with a request for organ donation. Relatives will be offered the opportunity to share their experiences on 'Healthtalkonline' by copyrighting audio-visual interviews to the Health Experiences Research Group, Oxford University. Research Ethics Committee approval was obtained (April 2012)., Discussion: This is the first time that moral distress is explored, in a case approach, among relatives, doctors, and nurses intimately involved in end-of-life decisions in intensive care. Dissemination of findings will make a large contribution to international knowledge and understanding in this area and alert healthcare professionals and relatives to an otherwise under-recognized, but potentially detrimental, experience. Findings will inform education, practice, and policy., (© 2012 Blackwell Publishing Ltd.)

The objective of this study was to investigate health and social care professionals' perspectives on developing services for children with life limiting conditions at the end-of-life using issues identified by bereaved parents as priorities. The study adopted qualitative methodology using nominal group technique in focus groups (n = 5) to collect data from 35 health and social care professionals. Six issues were identified across professional groupings as particularly challenging within the context of caring for children at the end-of-life: truth telling; symptom management; communication with, and relationships between families and professionals; emotional impact, the withdrawal of feeding or treatment and sibling support. Strong resonance was noted between professionals and parents in the emphasis placed on issues related to talking about death (to child and siblings) and decision-making about the withdrawal of treatment. Conversely, late referral to hospice care and lack of services in the community dominated accounts of parents whose children had non malignant conditions, but were not prioritized by professionals. Although the latter focused on the need for and challenges associated with optimizing symptom management, most parents viewed symptom control as highly effective. Caring for a dying child is a multidimensional experience for both parents and professionals. Convergence of thinking carries three main implications for service development. Firstly, the need for "joined up" palliative care services, particularly concerning timely referral to the range of support services. Secondly, more structured bereavement services. Third, within an ethos of family centered care, needs of siblings should be addressed effectively.

Objective: To examine the experiences of bereaved parents concerning the care provided to children who died from cancer compared to those who died from a non-malignant condition., Design: An in-depth qualitative study with bereaved parents of children who died as a result of a life-limiting diagnosis, recruited through two regional centres., Results: Although parents' accounts displayed commonalities, key differences were discernible. Typically, parents of children with cancer considered care at the end of life as well resourced and responsive to their and their child's needs. In contrast, parents of children with non-malignant conditions reported under-resourced and inadequately responsive services. Although both groups of parents called extensively on military metaphors such as 'battle', 'fight' and 'struggle', the focus of their respective energies was different. In the one case the adversary was disease and illness; in the other it was service providers and service provision., Conclusions: Community-based services for children and young people with cancer at the end of life were perceived by parents as responsive to parent and child needs. Conversely, community services for children and young people with non-malignant conditions were experienced as ad hoc and under-resourced. Community services for children with non-malignant conditions may require further development if they are to meet the levels of support offered to parents of children with cancer. If improvement is to be achieved, the need to raise awareness regarding hospice services, hospice referral and eligibility criteria across the entire gamut of service providers is essential.

Design: Cross-sectional qualitative study., Data Sources: Interviews with purposeful sample of 25 recently bereaved parents., Methods: Semi-structured in-depth interviews., Results: Four analytically distinct processes were identified in the responses of parents to the death of a child. These are referred to as 'piloting', 'providing', 'protecting' and 'preserving'. Regardless of individual circumstances, these processes were integral to all parents' coping, enabling an active 'doing' for their child and family throughout the trajectory of their child's illness and into bereavement., Conclusions: Facilitating the capacity of parents to 'do' is central to coping with the stress and uncertainty of living through the death of a child. The provision of informational, instrumental and emotional support by health care professionals in the context of 'doing' is core to quality palliative care., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This paper reports on a study of the ways in which 54 older people in South Wales (UK) talk about the symptoms and causes of cold and influenza (flu). The study was designed to understand why older people might reject or accept the offer of seasonal flu vaccine, and in the course of the interviews respondents were also asked to express their views about the nature and causes of the two key illnesses. The latter are among the most common infections in human beings. In terms of the biomedical paradigm the common cold is caused by numerous respiratory viruses, whilst flu is caused by the influenza virus. Medical diagnosis is usually made on clinical grounds without laboratory confirmation. Symptoms of flu include sudden onset of fever and cough, and colds are characterized by sneezing, sore throat, and runny nose, but in practice the symptoms often overlap. In this study we examine the degree by which the views of lay people with respect to both diagnosis and epidemiology diverge with that which is evident in biomedical discourse. Our results indicate that whilst most of the identified symptoms are common to lay and professional people, the former integrate symptoms into a markedly different observational frame from the latter. And as far as causation is concerned it is clear that lay people emphasize the role of 'resistance' and 'immunity' at least as much as 'infection' in accounting for the onset of colds and flu. The data are analyzed using novel methods that focus on the co-occurrence of concepts and are displayed as semantic networks. As well as reporting on its findings the authors draw out some implications of the study for social scientific and policy discussions concerning lay diagnosis, lay expertise and the concept of an expert patient., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is upregulated in a variety of tissues in obesity. It is still unclear as to whether NADPH oxidase upregulation in a specific tissue is part of a systemic response. Here we analyzed the expression pattern of NADPH oxidase in vascular, adipose, and kidney tissues in a rat model of diet-induced obesity. After weaning, rats were fed either a normal or high-fat diet for 12 weeks. The high-fat diet resulted in 20% increased body weight. In the aorta, Nox4 expression was increased by three-fold in obese rats. Upregulations of p22phox and p47phox in adipose, and Nox4, p22phox, and p47phox in kidney were observed in obesity. Marked increases in plasma leptin and insulin were observed, with more modest changes in adiponectin in obese rats. The average systolic blood pressure in the obese group was 11 mmHg higher than that of lean rats (P < 0.005). There was a significant correlation between blood pressure and aortic Nox4 expression (P < 0.01). In cultured vascular smooth muscle cells, adiponectin reduced the expression of Nox4 in a protein kinase A-dependent manner. Our results suggest that upregulation of NADPH oxidase in multiple tissues during obesity appears to be a systemic response. At least in vitro, adiponectin may have a protective antioxidant role by suppressing vascular NADPH oxidase expression. The association between NADPH oxidase Nox4 expression in the vasculature and the elevated blood pressure in obesity requires further investigation.

Translational and transdisciplinary research is needed to tackle complex public health problems. This article has three aims. Firstly, to determine how academics and non-academics (practitioners, policy makers and community workers) identified with the goals of the UKCRC Centre of Excellence for Public Health in Northern Ireland and how their attitudes varied in terms of knowledge brokerage and translation. Secondly, to map and analyse the network structure of the public health sector and the placement of the Centre within this. Thirdly, to aggregate responses from members of the network by work setting to construct the trans-sectoral network and devise the Root Mean Sum of Squares to determine the quality and potential value of connections across this network. The analysis was based on data collected from 98 individuals who attended the launch of the Centre in June 2008. Analysis of participant expectations and personal goals suggests that the academic members of the network were more likely to expect the work of the Centre to produce new knowledge than non-academics, but less likely to expect the Centre to generate health interventions and influence health policy. Academics were also less strongly oriented than non-academics to knowledge transfer as a personal goal, though more confident that research findings would be diffused beyond the immediate network. A central core of five nodes is crucial to the overall configuration of the regional public health network in Northern Ireland, with the Centre being well placed to exert influence within this. Though the overall network structure is fairly robust, the connections between some component parts of the network--such as academics and the third sector--are unidirectional. Identifying these differences and core network structure is key to translational and transdisciplinary research. Though exemplified in a regional study, these techniques are generalisable and applicable to many networks of interest: public health, interdisciplinary research or organisational involvement and stakeholder linkage., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

The purpose of this study was to test the effect of a motivational message on the intention of laypersons to learn cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use. A pretest-posttest, double-blind, randomized design was used with 220 community-dwelling adults. Participants were randomly assigned to the treatment group reading the CPR and AED pamphlet emphasizing learning CPR and AED use to save someone they love and the 3-minute window for response time; or to the comparison group reading the identical pamphlet without the 2 motivational statements. Intention to learn CPR and AED use and to look for AEDs in public areas was measured before and after reading the respective pamphlet. No significant difference emerged between the groups for the number of participants planning to learn CPR and AED use. A significant number of participants in both groups increased intention to learn CPR and AED use. Significantly more treatment participants than comparison participants planned to routinely look for AEDs in public areas after reading the pamphlet, however. Teaching critical facts such as the low survival rate for out-of-hospital cardiac arrest might encourage laypersons to learn CPR and AED use. Routinely teaching family members of people at risk for a cardiac arrest about the short window of time in which CPR and AED use must begin and encouraging them to learn about CPR and AEDs to save someone they love may encourage family members to identify the location of AEDs in public places.

Intrauterine growth restriction and accelerated postnatal growth predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal growth but also impairs mammary development and postnatal growth. We used cross fostering to compare the influence of prenatal and postnatal nutritional restraint on adult glucose tolerance, insulin secretion, insulin sensitivity, and hypothalamic neuropeptide Y content in Wistar Kyoto rats at 6 months of age. Bilateral uterine vessel ligation (restricted) to induce uteroplacental insufficiency or sham surgery (control) was performed on d-18 gestation. Control, restricted, and reduced (reducing litter size of controls to match restricted) pups were cross fostered onto a control or restricted mother 1 d after birth. Restricted pups were born small compared with controls. Restricted males, but not females, remained lighter up to 6 months, regardless of postnatal environment. By 10 wk, restricted-on-restricted males ate more than controls. At 6 months restricted-on-restricted males had increased hypothalamic neuropeptide Y content compared with other groups, and together with reduced-on-restricted males had increased retroperitoneal fat weight (percent body weight) compared with control-on-controls. Restricted-on-restricted males had impaired glucose tolerance, reduced first-phase insulin secretion, but unaltered insulin sensitivity, compared with control-on-controls. In males, being born small and exposed to an impaired lactational environment adversely affects adult glucose tolerance and first-phase insulin secretion, but improving lactation partially ameliorates this condition. This study identifies early life as a target for intervention to prevent later diabetes after prenatal restraint.

We quantitatively analyzed the developing prospective neural and non-neural ectoderm during chicken gastrulation on semithin transverse sections. At stage PS8 (primitive streak stage 8 of Lopez-Sanchez et al. [C. Lopez-Sanchez, L. Puelles, V. Garcia-Martinez, L. Rodriguez-Gallardo, Morphological and molecular analysis of the early developing chick requires an expanded series of primitive streak stages, J. Morphol. 264 (2005) 105-116.], equivalent to stage HH4), the thickest area of the ectoderm agrees in extent with the fate-mapped neural plate we had reported previously. The thickness of the median ectoderm is constantly higher up to a distance of 250mum from Hensen's node, and thickness decreases along a mediolateral gradient with a further drop at the prospective lateral border of the neural plate. A higher cell density of the developing ectoderm also coincided with the prospective neural plate. We observed that cell death does not play an important role in the spatial definition of the neural plate.

Background: Dementia is common among adults with Down's syndrome (DS); yet the diagnosis of dementia, particularly in its early stage, can be difficult in this population. One possible reason for this may be the different clinical manifestation of dementia among people with intellectual disabilities., Aims: The aim of this study was to map out the carers' perspective of symptoms of dementia among adults with DS in order to inform the development of an informant-rated screening questionnaire., Method: Unconstrained information from carers of people with DS and dementia regarding the symptoms, particularly the early symptoms of dementia, was gathered using a qualitative methodology. Carers of 24 adults with DS and dementia were interviewed. The interviews were recorded and fully transcribed. The transcripts were then analysed using qualitative software., Results: There appeared to be many similarities in the clinical presentation of dementia in adults with DS and the non-intellectually disabled general population. Like in the non-intellectually disabled general population, forgetfulness especially, impairment of recent memory combined with a relatively intact distant memory and confusion were common, and presented early in dementia among adults with DS. However, many 'frontal lobe'-related symptoms that are usually manifested later in the process of dementia among the general population were common at an early stage of dementia among adults with DS. A general slowness including slowness in activities and speech, other language problems, loss of interest in activities, social withdrawal, balance problems, sleep problems, loss of pre-existing skills along with the emergence of emotional and behaviour problems were common among adults with DS in our study., Conclusions: This study highlights the similarities in the clinical presentation of dementia among the general population and people with DS with a particular emphasis on the earlier appearance of symptoms associated with the frontal lobe dysfunction among adults with DS.

Objective: To develop a measure to assess post-acute outcome following from traumatic brain injury (TBI) with particular emphasis on the emotional and the behavioral outcome. The second objective was to assess the test-retest reliability, internal consistency, and factor structure of the newly developed patient version of the Head Injury Participation Scale (P-HIPS) and Patient-Head Injury Neurobehavioral Scale (P-HINAS)., Method: Thirty-two TBI individuals and 27 carers took part in in-depth qualitative interviews exploring the consequences of the TBI. Interview transcripts were analyzed and key themes and concepts were used to construct the 49-item P-HIPS. A postal survey was then conducted on a cohort of 113 TBI patients to 'field test' the P-HIPS and the P-HINAS., Results: All individual 49 items of the P-HIPS and their total score showed good test-retest reliability (0.93) and internal consistency (0.95). The P-HIPS showed a very good correlations with the Mayo Portland Adaptability Inventory-3 (MPAI-3) (0.87) and a moderate negative correlation with the Glasgow Outcome Scale-Extended (GOSE) (-0.51). Factor analysis extracted the following domains: 'Emotion/Behavior,' 'Independence/Community Living,' 'Cognition' and 'Physical'. The 'Emotion/Behavior' factor constituted the P-HINAS, which showed good internal consistency (0.93), test-retest reliability (0.91) and concurrent validity with MPAI subscale (0.82)., Conclusions: Both the P-HIPS and the P-HINAS show strong psychometric properties. The qualitative methodology employed in the construction stage of the questionnaires provided good evidence of face and content validity.

Objective: Develop and assess the psychometric properties of the Carer - Head Injury Participation Scale (C-HIPS) and its biggest factor the Carer - Head Injury Neurobehavioral Assessment Scale (C-HINAS). Furthermore, the aim was to examine the inter-informant reliability by comparing the self reports of individuals with traumatic brain injury (TBI) with the carer reports on the C-HIPS and the C-HINAS., Method: Thirty-two TBI individuals and 27 carers took part in in-depth qualitative interviews exploring the consequences of the TBI. Interview transcripts were analysed and key themes and concepts were used to construct a 49-item and 58-item patient (Patient - Head Injury Participation Scale [P-HIPS]) and carer outcome measure (C-HIPS) respectively, of which 49 were parallel items and nine additional items were used to assess carer burden. Postal versions of the P-HIPS, C-HIPS, Mayo Portland Adaptability Inventory-3 (MPAI-3), and the Glasgow Outcome Scale-Extended (GOSE) were completed by a cohort of 113 TBI individuals and 80 carers. Data from a sub-group of 66 patient/carer pairs were used to compare inter-informant reliability between the P-HIPS and the C-HIPS, and the P-HINAS and the C-HINAS respectively., Results: All individual 49 items of the C-HIPS and their total score showed good test-retest reliability (0.95) and internal consistency (0.95). Comparisons with the MPAI-3 and GOSE found a good correlation with the MPAI-3 (0.7) and a moderate negative correlation with the GOSE (-0.6). Factor analysis of these items extracted a 4-factor structure which represented the domains 'Emotion/Behavior' (C-HINAS), 'Independence/Community Living', 'Cognition', and 'Physical'. The C-HINAS showed good internal consistency (0.92), test-retest reliability (0.93), and concurrent validity with one MPAI subscale (0.7). Assessment of inter-informant reliability revealed good correspondence between the reports of the patients and the carers for both the C-HIPS (0.83) and the C-HINAS (0.82)., Conclusion: Both the C-HINAS and the C-HIPS show strong psychometric properties. The qualitative methodology employed in the construction stage of the questionnaires provided good evidence of face and content validity. Comparisons between the P-HIPS and the C-HIPS, and the P-HINAS and the C-HINAS indicated high levels of agreement suggesting that in situations where the patient is unable to provide self-reports, information provided by the carer could be used.