"There's no place like home" A pilot study of perspectives of international health and social care professionals working in the UK

Background Many countries are reporting health workforce shortages across a range of professions at a time of relatively high workforce mobility. Utilising the global market to supply shortage health skills is now a common recruitment strategy in many developed countries. At the same time a number of countries report a 'brain drain' resulting from professional people leaving home to work overseas. Many health and social care professionals make their way to the UK from other countries. This pilot study utilises a novel 'e-survey' approach to explore the motives, experiences and perspectives of non-UK health and social care professionals who were working or had worked in the UK. The study aims to understand the contributions of international health and social care workers to the UK and their 'home' countries. The purpose of the pilot study is also in part to test the appropriateness of this methodology for undertaking a wider study. Results A 24-item questionnaire with open-ended and multiple choice questions was circulated via email to 10 contacts who were from a country outside the UK, had trained outside the UK and had email access. These contacts were requested to forward the email to other contacts who met these criteria (and so on). The email was circulated over a one month pilot period to 34 contacts. Responses were from physiotherapists (n = 11), speech therapists (n = 4), social workers (n = 10), an occupational therapist (n = 1), podiatrists (n = 5), and others (n = 3). Participants were from Australia (n = 20), South Africa (n = 10), New Zealand (n = 3) and the Republic of Ireland (n = 1). Motives for relocating to the UK included travel, money and career opportunities. Participants identified a number of advantages and disadvantages of working in the UK compared to working in their home country health system. Respondents generally reported that by working in the UK, they had accumulated skills and knowledge that would allow them to contribute more to their profession and health system on their return home. Conclusion This pilot study highlights a range of issues and future research questions for international learning and comparison for the health and social care professions as a result of international workforce mobility. The study also highlights the usefulness of an e-survey technique for capturing information from a geographically diverse and mobile group of professionals

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma

Extent: 15p.Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.Derek J. Nancarrow, Andrew D. Clouston, B. Mark Smithers, David C. Gotley, Paul A. Drew, David I. Watson, Sonika Tyagi, Nicholas K. Hayward, David C. Whiteman, for the Australian Cancer Study and the Study of Digestive Healt

'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

The role of attachment in body weight gain and weight loss in bariatric patients

Purpose: To explore the role of attachment styles in obesity. Material and methods: The present study explored differences in insecure attachment styles between an obese sample waiting for bariatric surgery (n=195) and an age, sex and height matched normal weight control group (n=195). It then explored the role of attachment styles in predicting change in BMI one year post bariatric surgery (n=143). Results: The bariatric group reported significantly higher levels of anxious attachment and lower levels of avoidant attachment than the control non obese group. Baseline attachment styles did not, however, predict change in BMI post-surgery. Conclusion: Attachment style is different in those that are already obese from those who are not. Attachment was not related to weight loss post-surgery

Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis

Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targetable RP2 pathway. In a prospective clinical trial of response-adapted RT for patients (n = 39) with locally advanced non-small cell lung cancer, we analyzed patients\u27 plasma, collected pre- and during RT, for microRNAs (miRNAs) and cytokines using array and multiplex enzyme linked immunosorbent assay (ELISA), respectively. Interactions between candidate biomarkers, radiobiological, and clinical parameters were analyzed using data-driven Bayesian network (DD-BN) analysis. We identified alterations in specific miRNAs (miR-532, -99b and -495, let-7c, -451 and -139-3p) correlating with lung toxicity. High levels of soluble tumor necrosis factor alpha receptor 1 (sTNFR1) were detected in a majority of lung cancer patients. However, among RP patients, within 2 weeks of RT initiation, we noted a trend of temporary decline in sTNFR1 (a physiological scavenger of TNFα) and ADAM17 (a shedding protease that cleaves both membrane-bound TNFα and TNFR1) levels. Cytokine signature identified activation of inflammatory pathway. Using DD-BN we combined miRNA and cytokine data along with generalized equivalent uniform dose (gEUD) to identify pathways with better accuracy of predicting RP2 as compared to either miRNA or cytokines alone. This signature suggests that activation of the TNFα-NFκB inflammatory pathway plays a key role in RP which could be specifically ameliorated by etanercept rather than current therapy of non-specific leukotoxic corticosteroids

Development and evaluation of a tool for the assessment of footwear characteristics

<p>Abstract</p> <p>Background</p> <p>Footwear characteristics have been linked to falls in older adults and children, and the development of many musculoskeletal conditions. Due to the relationship between footwear and pathology, health professionals have a responsibility to consider footwear characteristics in the etiology and treatment of various patient presentations. In order for health professionals and researchers to accurately and efficiently critique an individual's footwear, a valid and reliable footwear assessment tool is required. The aim of this study was to develop a simple, efficient, and reliable footwear assessment tool potentially suitable for use in a range of patient populations.</p> <p>Methods</p> <p>Consideration of previously published tools, other footwear related literature, and clinical considerations of three therapists were used to assist in the development of the tool. The tool was developed to cover fit, general features, general structure, motion control properties, cushioning, and wear patterns. A total of 15 participants (who provided two pairs of shoes each) were recruited, and assessment using the scale was completed on two separate occasions (separated by 1 – 3 weeks) by a physiotherapist and a podiatrist on each participant's dominant foot. Intra-rater and inter-rater reliability were evaluated using intra-class correlation coefficients (ICCs) (model 2, 1) and the 95% limits of agreement (95% LOAs) for continuous items, and percentage agreement and kappa (κ) statistics for categorical items.</p> <p>Results</p> <p>All categorical items demonstrated high percentage agreement statistic for intra-rater (83 – 100%) and inter-rater (83 – 100%) comparisons. With the exception of last shape and objective measures used to categorise the adequacy of length, excellent intra-rater (ICC = 0.91 – 1.00) and inter-rater reliability (ICC = 0.90 – 1.00) was indicated for continuous items in the tool, including the motion control properties scale (0.91 – 0.95).</p> <p>Conclusion</p> <p>A comprehensive footwear assessment tool with good face validity has been developed to assist future research and clinical footwear assessment. Generally good reliability amongst all items indicates that the tool can be used with confidence in research and clinical settings. Further research is now required to determine the clinical validity of each item in various patient populations.</p

FRA2A is a CGG repeat expansion associated with silencing of AFF3

Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship