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  • Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation

    Hulme, Charlotte H.; Wilson, Emma L.; Fuller, Heidi R.; Roberts, Sally; Richardson, James B.; Gallacher, Pete; Peffers, Mandy J.; Shirran, Sally L.; Botting, Catherine H.; Wright, Karina T.; Keele University; Robert Jones and Agnes Hunt Orthopaedic Hospital; University of Chester; University of Liverpool; University of St Andrews (BioMed Central, 2018-05-02)
    Background: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. Results: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.
  • The impact of severe haemophilia and the presence of target joints on health-related quality-of-life

    O’Hara, Jamie; Walsh, Shaun; Camp, Charlotte; Mazza, Giuseppe; Carroll, Liz; Hoxer, Christina; Wilkinson, Lars; University of Chester; HCD Economics; University College London; The Haemophilia Society; Novo Nordisk (BioMed Central, 2018-05-02)
    Background: Joint damage remains a major complication associated with haemophilia and is widely accepted as one of the most debilitating symptoms for persons with severe haemophilia. The aim of this study is to describe how complications of haemophilia such as target joints influence health-related quality of life (HRQOL). Methods: Data on hemophilia patients without inhibitors were drawn from the ‘Cost of Haemophilia across Europe – a Socioeconomic Survey’ (CHESS) study, a cost-of-illness assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the UK). Physicians provided clinical and sociodemographic information for 1285 adult patients, 551 of whom completed corresponding questionnaires, including EQ-5D. A generalised linear model was developed to investigate the relationship between EQ-5D index score and target joint status (defined in the CHESS study as areas of chronic synovitis), adjusted for patient covariates including socio-demographic characteristics and comorbidities. Results: Five hundred and fifteen patients (42% of the sample) provided an EQ-5D response; a total of 692 target joints were recorded across the sample. Mean EQ-5D index score for patients with no target joints was 0.875 (standard deviation [SD] 0.179); for patients with one or more target joints, mean index score was 0.731 (SD 0.285). Compared to having no target joints, having one or more target joints was associated with lower index scores (average marginal effect (AME) -0.120; SD 0.0262; p < 0.000). Conclusions: This study found that the presence of chronic synovitis has a significant negative impact on HRQOL for adults with severe haemophilia. Prevention, early diagnosis and treatment of target joints should be an important consideration for clinicians and patients when managing haemophilia.
  • Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors

    Shatwan, Israa M.; Winther, Kristian H.; Ellahi, Basma; Elwood, Peter; Ben-Shlomo, Yoav; Givens, Ian; Rayman, Margaret P.; Lovegrove, Julie A.; Vimaleswaran, Karani S.; University of Reading; King Abdulaziz University; University Hospital Denmark; University of Chester; University Hospital of Wales; University of Bristol; University of Surrey (BioMed Central, 2018-04-30)
    Background: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. Results: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10− 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10− 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10− 6 and P = 3 × 10− 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10− 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. Conclusion: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts.
  • The relationship between target joints and direct resource use in severe haemophilia

    O’Hara, Jamie; Walsh, Shaun; Camp, Charlotte; Mazza, Giuseppe; Carroll, Liz; Hoxer, Christina; Wilkinson, Lars; University of Chester; HCD Economics, The Innovation Centre, Daresbury; University College London; The Haemophilia Society; Novo Nordisk A/S (SpringerOpen, 2018-01-16)
    Objectives Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related direct costs (NDDCs) has not been studied. Methods Data on haemophilia patients without inhibitors was drawn from the ‘Cost of Haemophilia across Europe – a Socioeconomic Survey’ (CHESS) study, a cost assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the United Kingdom) in which 139 haemophilia specialists provided demographic and clinical information for 1285 adult patients. NDDCs were calculated using publicly available cost data, including 12-month ambulatory and secondary care activity: haematologist and other specialist consultant consultations, medical tests and examinations, bleed-related hospital admissions, and payments to professional care providers. A generalized linear model was developed to investigate the relationship between NDDCs and target joints (areas of chronic synovitis), adjusted for patient covariates. Results Five hundred and thirteen patients (42% of the sample) had no diagnosed target joints; a total of 1376 target joints (range 1–10) were recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average mean effect EUR 779; p < 0.001). Conclusions Our analysis suggests that the presence of one or more target joints has a significant impact on NDDCs for patients with severe haemophilia, ceteris paribus. Prevention and management of target joints should be an important consideration of managing haemophilia patients.
  • The ReSiT study (reducing sitting time): rationale and protocol for an exploratory pilot study of an intervention to reduce sitting time among office workers

    Gardner, Benjamin; Dewitt, Stephen; Smith, Lee; Buckley, John P.; Biddle, Stuart J. H.; Mansfield, Louise; King's College London; Anglia Ruskin University; University of Chester; University of Southern Queensland; Brunel University (BioMed Central, 2017-11-28)
    Background Desk-based workers engage in long periods of uninterrupted sitting time, which has been associated with morbidity and premature mortality. Previous workplace intervention trials have demonstrated the potential of providing sit-stand workstations, and of administering motivational behaviour change techniques, for reducing sitting time. Yet, few studies have combined these approaches or explored the acceptability of discrete sitting-reduction behaviour change strategies. This paper describes the rationale for a sitting-reduction intervention that combines sit-stand workstations with motivational techniques, and procedures for a pilot study to explore the acceptability of core intervention components among university office workers. Methods The intervention is based on a theory and evidence-based analysis of why office workers sit, and how best to reduce sitting time. It seeks to enhance motivation and capability, as well as identify opportunities, required to reduce sitting time. Thirty office workers will participate in the pilot study. They will complete an initial awareness-raising monitoring and feedback task and subsequently receive a sit-stand workstation for a 12-week period. They will also select from a ‘menu’ of behaviour change techniques tailored to self-declared barriers to sitting reduction, effectively co-producing and personally tailoring their intervention. Interviews at 1, 6, and 12 weeks post-intervention will explore intervention acceptability. Discussion To our knowledge, this will be the first study to explore direct feedback from office workers on the acceptability of discrete tailored sitting-reduction intervention components that they have received. Participants’ choice of and reflections on intervention techniques will aid identification of strategies suitable for inclusion in the next iteration of the intervention, which will be delivered in a self-administered format to minimise resource burden. Trial registration ISRCTN29395780 (registered 21 November 2016)
  • Modelling low velocity impact induced damage in composite laminates

    Shi, Yu; Soutis, Constantinos; University of Chester; University of Manchester (SpringerOpen, 2017-07-26)
    The paper presents recent progress on modelling low velocity impact induced damage in fibre reinforced composite laminates. It is important to understand the mechanisms of barely visible impact damage (BVID) and how it affects structural performance. To reduce labour intensive testing, the development of finite element (FE) techniques for simulating impact damage becomes essential and recent effort by the composites research community is reviewed in this work. The FE predicted damage initiation and propagation can be validated by Non Destructive Techniques (NDT) that gives confidence to the developed numerical damage models. A reliable damage simulation can assist the design process to optimise laminate configurations, reduce weight and improve performance of components and structures used in aircraft construction.
  • Autologous chondrocyte implantation-derived synovial fluids display distinct responder and non-responder proteomic profiles

    Hulme, Charlotte H.; Wilson, Emma L.; Peffers, Mandy J.; Roberts, Sally; Simpson, Deborah M.; Richardson, James B.; Gallacher, Pete; Wright, Karina T.; Keele University; Robert Jones and Agnes Hunt Orthopaedic Hospital; University of Chester; University of Liverpool (BioMed Central, 2017-06-30)
    Background Autologous chondrocyte implantation (ACI) can be used in the treatment of focal cartilage injuries to prevent the onset of osteoarthritis (OA). However, we are yet to understand fully why some individuals do not respond well to this intervention. Identification of a reliable and accurate biomarker panel that can predict which patients are likely to respond well to ACI is needed in order to assign the patient to the most appropriate therapy. This study aimed to compare the baseline and mid-treatment proteomic profiles of synovial fluids (SFs) obtained from responders and non-responders to ACI. Methods SFs were derived from 14 ACI responders (mean Lysholm improvement of 33 (17–54)) and 13 non-responders (mean Lysholm decrease of 14 (4–46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Label-free proteome profiling of dynamically compressed SFs was used to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI. Results Only 1 protein displayed a ≥2.0-fold differential abundance in the preclinical SF of ACI responders versus non-responders. However, there is a marked difference between these two groups with regard to their proteome shift in response to cartilage harvest, with 24 and 92 proteins showing ≥2.0-fold differential abundance between Stages I and II in responders and non-responders, respectively. Proteomic data has been uploaded to ProteomeXchange (identifier: PXD005220). We have validated two biologically relevant protein changes associated with this response, demonstrating that matrix metalloproteinase 1 was prominently elevated and S100 calcium binding protein A13 was reduced in response to cartilage harvest in non-responders. Conclusions The differential proteomic response to cartilage harvest noted in responders versus non-responders is completely novel. Our analyses suggest several pathways which appear to be altered in non-responders that are worthy of further investigation to elucidate the mechanisms of ACI failure. These protein changes highlight many putative biomarkers that may have potential for prediction of ACI treatment success.
  • Transposing tirtha: Understanding religious reforms and locative piety in early modern Hinduism

    Thakkar, Chirayu; University of Chester (SpringerOpen, 2017-06-17)
    The paper deals with a historical and hitherto obscure case of de-commercialisation of sacred geography of India. Sahajanand Swami, an eighteenth century religious leader from Gujarat who became popular as Bhagwan Swaminarayan took an initiative to eliminate corruption in Dwarka, one of the most sacred destination in Hindu imagination. He also attempted to transpose the piety of Dwarka and recreate a parallel religious experience at Vadtal, an important site in Swaminarayan Hinduism. This process of making sacred sites more egalitarian is classified here as a 'religious reform'. The paper assesses this bivalent pursuit as an institutional reform within religion as well as a religious process in the context of piety, authority and orthodoxy. Through the example of Sahajanand Swami, it is argued to calibrate the colonial paradigm of reform that was largely contextual to social issues and western thought and failed to appreciate the religious reforms of that era. By constructing a nuanced typology of 'religious reform' distinct from 'social reforms', the paper eventually calls for a reassessment of religious figures who have significantly contributed in reforming the Hindu tradition in the medieval and modern era.
  • The cost of severe haemophilia in Europe: the CHESS study

    O’Hara, Jamie; Hughes, David; Camp, Charlotte; Burke, Tom; Carroll, Liz; Diego, Daniel-Anibal G; University of Chester; HCD Economics, Daresbury; The Haeomophelia Society, London; FedHemo, Madrid (BioMed Central, 2017-05-31)
    Background Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level. Results Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss. Conclusions The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost burden in severe haemophilia. However, the importance of the indirect impact of haemophilia on the patient and family should not be overlooked. The CHESS study highlights the benefits of observational study methodologies in capturing a ‘snapshot’ of information for patients with rare diseases.
  • Neuropsychiatric symptoms following metal-on-metal implant failure with cobalt and chromium toxicity

    Green, Ben; Griffiths, Emily; Almond, Solomon; University of Chester; Public Health England (BioMed Central, 2016-01-24)
    Background: There were at least 31,171 metal-on-metal (MoM) hip implants in the UK between 2003 and 2011. Some of these were subject to failure and widescale recalls and revisions followed. Method This is a presentation of ten cases (mean age 60 years) where we evaluated neuropsychiatric morbidity following metal-on-metal hip implant failure and revision. Implants were ASR total hip replacement (acetabular implant, taper sleeve adaptor and unipolar femoral implants) performed between 2005 and 2009. This case series describes, for the first time, neuropsychiatric complications after revision where there has been cobalt and chromium toxicity. Results Pre-revision surgery, nine patients had toxic levels of chromium and cobalt (mean level chromium 338 nmol/l, mean cobalt 669.4 nmol/l). Depression assessment showed 9 of 9 respondents fulfilled the BDI criteria for depression and 3 of these were being treated. 7 of 9 patients showing short term memory deficit with mean mini mental state examination score of 24.2. The normal population mean MMSE for this group would be expected to be 28 with <25 indicating possible dementia. Conclusions We found neurocognitive and depressive deficits after cobalt and chromium metallosis following MoM implant failure. Larger studies of neurocognitive effects are indicated in this group. There may be implications for public health.
  • Development and feasibility of a Swallowing intervention Package (SiP) for patients receiving radiotherapy treatment for head and neck cancer—the SiP study protocol

    Wells, Mary; King, Emma; Toft, Kate; MacAulay, Fiona; Patterson, Joanne; Dougall, Nadine; Hulbert-Williams, Nicholas J.; Boa, Sally; Slaven, Eleanor; Cowie, Julie; McGarva, John; Niblock, Patricia G.; Philp, Julie; Roe, Justin; University of Stirling; NHS Lothian; NHS Tayside; City Hospitals Sunderland NHS Foundation Trust; University of Chester; Srathcarron Hospice; NHS Greate Glasgow and Clyde; NHS Forth Valley; NHS Fife; The Royal Marsden NHS Foundation Trust (BioMed Central, 2016-08-04)
    Background Head and neck cancer (HNC) is the sixth most common cancer worldwide, and the functional, psychological and social consequences of HNC cancer and its treatment can be severe and chronic. Dysphagia (swallowing problems) affects up to two thirds of patients undergoing combined chemoradiotherapy. Recent reviews suggest that prophylactic swallowing exercises may improve a range of short- and long-term outcomes; however, the importance of psychological and behavioural factors on adherence to swallowing exercises has not been adequately studied. This study aims to develop and test the feasibility of a Swallowing intervention Package (SiP) designed in partnership with patients, speech and language therapists (SLTs) and other members of the head and neck multi-disciplinary team (MDT), for patients undergoing chemoradiotherapy (CRT) or radiotherapy (RT) for head and neck cancer. Methods/design This feasibility study uses quantitative and qualitative research methods, within a quasi-experimental design, to assess whether patients will tolerate and adhere to the SiP intervention, which aspects of the intervention can be implemented and which cannot, whether treatment fidelity can be achieved across different contexts, whether study processes and outcome measures will be feasible and acceptable and to what extent the intervention is likely to have an impact on swallowing dysfunction and quality of life. Patients are being recruited from five sites in Scotland and England (three interventions and two usual care). The SLT based in the relevant intervention centre teaches the exercise programme and provides supporting materials. A combination of patient-reported outcome measures (PROMs), adherence measures and clinical swallowing assessments are used prior to intervention (baseline), at the end of treatment, 3 and 6 months post-treatment. Discussion This collaborative study has taken a unique approach to the development of a patient-centred and evidence-based swallowing intervention. The introduction of an e-SiP app provides an exploration of the use of technology in delivering this intervention. The study provides an opportunity to examine the feasibility of delivering and participating in a supported swallowing intervention across several different NHS sites and will provide the evidence needed to refine intervention and study processes for a future trial. Trial registration NCRI portfolio, 18192 & 20259
  • A qualitative study exploring midlife women’s stages of change from domestic violence towards freedom

    Keeling, June J.; Smith, Debra; Fisher, Colleen; University of Chester; University of Central Lancashire; The University of Western Australia (BioMed Central, 2016-03-08)
    Background Domestic Violence (DV) remains a significant global health problem for women in contemporary society. Existing literature on midlife women’s experiences of domestic violence is limited and focuses on health implications. Leaving a violent relationship is a dynamic process that often requires multiple attempts and separations prior to final termination. The aim of this study was to explore the process of leaving a violent relationship for midlife women. Methods This qualitative study involved fifteen women aged between 40–55 who had accessed residential and non-residential community support services for domestic violence within the UK. Community-based support agencies provided these women with access to letters of invitation and participant information sheet explaining the study. The women notified agency staff who contacted the research team to arrange a mutually convenient time to meet within a safe place for both the women and researchers. It was stressed to all potential participants that no identifiable information would be shared with the agency staff. Women were considered survivors of DV if they defined themselves as such. Data were gathered through semi structured interviews, transcribed verbatim and thematically analysed. Results Midlife women appear to differ from younger women by transitioning quickly though the stages of change, moving rapidly through the breaking free onto the maintenance stage. This rapid transition is the resultant effect of living with long-term violence causing a shift in the women’s perception towards the violent partner, with an associated reclamation of power from within the violent relationship. A realisation that rapid departure from the violence may be critical in terms of personal safety, and the realisation that there was something ‘wrong’ within the relationship, a ‘day of dawning’ that had not been apparent previously appears to positively affect the trajectory of leaving. Conclusions Midlife women appeared to navigate through the stages of change in a rapid linear process, forging ahead and exiting the relationship with certainty and without considering options. Whilst these findings appear to differ from younger women’s process of leaving, further research is needed to explore and understand the optimum time for intervention and support to maximise midlife women’s opportunities to escape an abusive partner, before being reflected appropriately in policy and practice.
  • Physical activity guidelines and cardiovascular risk in children: a cross sectional analysis to determine whether 60 minutes is enough

    Füssenich, Lotte M.; Boddy, Lynne M.; Green, Daniel J.; Graves, Lee E. F.; Foweather, Lawrence; Dagger, Rebecca M.; McWhannell, Nicola; Henaghan, Jayne; Ridgers, Nicola D.; Stratton, Gareth; Hopkins, Nicola D.; Radboud University Nijmegen Medical Centre; Liverpool John Moore’s University; University of Western Australia; Liverpool Hope University; University of Chester; Deakin University; Swansea University (BioMed Central, 2016-01-22)
    Background: Physical activity reduces cardiovascular mortality and morbidity. The World Health Organisation (WHO) recommends children engage in 60 min daily moderate-to-vigorous physical activity (MVPA). The effect of compliance with this recommendation on childhood cardiovascular risk has not been empirically tested. To evaluate whether achieving recommendations results in reduced composite-cardiovascular risk score (CCVR) in children, and to examine if vigorous PA (VPA) has independent risk-reduction effects. Methods PA was measured using accelerometry in 182 children (9–11 years). Subjects were grouped according to achievement of 60 min daily MVPA (active) or not (inactive). CCVR was calculated (sum of z-scores: DXA body fat %, blood pressure, VO2peak, flow mediated dilation, left ventricular diastolic function; CVR score ≥1SD indicated ‘higher risk’). The cohort was further split into quintiles for VPA and odds ratios (OR) calculated for each quintile. Results Active children (92 (53 boys)) undertook more MVPA (38 ± 11 min, P < 0.001), had greater VO2peak (4.5 ± 0.8 ml/kg/min P < 0.001), and lower fat % (3.9 ± 1.1 %, P < 0.001) than inactive. No difference were observed between active and inactive for CCVR or OR (P > 0.05). CCVR in the lowest VPA quintile was significantly greater than the highest quintile (3.9 ± 0.6, P < 0.05), and the OR was 4.7 times higher. Conclusion Achievement of current guidelines has positive effects on body composition and cardiorespiratory fitness, but not CCVR. Vigorous physical activity appears to have beneficial effects on CVD risk, independent of moderate PA, implying a more prescriptive approach may be needed for future VPA guidelines.
  • Health inequalities as a foundation for embodying knowledge within public health teaching: a qualitative study

    Mabhala, Mzwandile A.; University of Chester (BioMed Central, 2013-06-28)
    Introduction: Recent UK health policies identified nurses as key contributors to the social justice agenda of reducing health inequalities, on the assumption that all nurses understand and wish to contribute to public health. Following this policy shift, public health content within pre-registration nursing curricula increased. However, public health nurse educators (PHNEs) had various backgrounds, and some had limited formal public health training, or involvement in or understanding of policy required to contribute effectively to it. Their knowledge of this subject, their understanding and interpretation of how it could be taught, was not fully understood. Methodology This research aimed to understand how public health nurse educators’ professional knowledge could be conceptualised and to develop a substantive theory of their knowledge of teaching public health, using a qualitative data analysis approach. Qualitative in-depth semi-structured interviews (n=26) were conducted with eleven university-based PHNEs. Results Integrating public health into all aspects of life was seen as central to the knowing and teaching of public health; this was conceptualised as ‘embodying knowledge’. Participants identified the meaning of embodying knowledge for teaching public health as: (a) possessing a wider vision of health; (b) reflecting and learning from experience; and (c) engaging in appropriate pedagogical practices. Conclusion The concept of public health can mean different things to different people. The variations of meaning ascribed to public health reflect the various backgrounds from which the public health workforce is drawn. The analysis indicates that PHNEs are embodying knowledge for teaching through critical pedagogy, which involves them engaging in transformative, interpretive and integrative processes to refashion public health concepts; this requires PHNEs who possess a vision of what to teach, know how to teach, and are able to learn from experience. Their vision of public health is influenced by social justice principles in that health inequalities, socioeconomic determinants of health, epidemiology, and policy and politics are seen as essential areas of the public health curriculum. They believe in forms of teaching that achieve social transformation at individual, behavioural and societal levels, while also enabling learners to recognise their capacity to effect change.
  • Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

    Eccles, Suzanne A.; Aboagye, Eric O.; Ali, Simak; Anderson, Annie S.; Armes, Jo; Berditchevski, Fedor; Blaydes, Jeremy P.; Brennan, Keith; Brown, Nicola J.; Bryant, Helen E.; Bundred, Nigel J.; Burchell, Joy M.; Campbell, Anna M.; Carroll, Jason S.; Clarke, Robert B.; Coles, Charlotte E.; Cook, Gary J.; Cox, Angela; Curtin, Nicola J.; Dekker, Lodewijk V.; dos Santos Silva, Isabel; Duffy, Stephen W.; Easton, Douglas F.; Eccles, Diana M.; Edwards, Dylan R.; Edwards, Joanne; Evans, D. Gareth; Fenlon, Deborah F.; Flanagan, James M.; Foster, Claire; Gallagher, William M.; Garcia-Closas, Montserrat; Gee, Julia M. W.; Gescher, Andy J.; Goh, Vicky; Groves, Ashley M.; Harvey, Amanda J.; Harvie, Michelle N.; Hennessy, Bryan T.; Hiscox, Stephen; Holen, Ingunn; Howell, Sacha J.; Howell, Anthony; Hubbard, Gill; Hulbert-Williams, Nicholas J.; Hunter, Myra S.; Jasani, Bharat; Jones, Louise J.; Key, Timothy J.; Kirwan, Cliona C.; Kong, Anthony; Kunkler, Ian H.; Langdon, Simon P.; Leach, Martin O.; Mann, David J.; Marshall, John F.; Martin, Lesley A.; Martin, Stewart G.; Macdougall, Jennifer E.; Miles, David W.; Miller, William R.; Morris, Joanna R.; Moss, Sue M.; Mullan, Paul; Natrajan, Rachel; O’Connor, James P.; O’Connor, Rosemary; Palmieri, Carlo; Pharoah, Paul D. P.; Rakha, Emad A.; Reed, Elizabeth; Robinson, Simon P.; Sahai, Erik; Saxton, John M.; Schmid, Peter; Smalley, Matthew J.; Speirs, Valerie; Stein, Robert; Stingl, John; Streuli, Charles H.; Tutt, Andrew N. J.; Velikova, Galina; Walker, Rosemary A.; Watson, Christine J.; Williams, Kaye J.; Young, Leonie S.; Thompson, Alastair M.; Imperial College London ; University of Dundee ; University of Southampton ; University of Birmingham ; University of Manchester ; University of Sheffield ; Kings College London ; University College London ; Cancer Research UK/University of Cambridge ; Newcastle University ; University of Nottingham ; London School of Hygiene and Tropical Medicine ; Queen Mary University of London ; University of Glasgow ; University of East Anglia ; University College Dublin ; The Institute of Cancer Research ; University of Cardiff ; University of Leeds ; Royal College of Surgeons Ireland ; University of Chester ; University of Oxford ; University of Edinburgh ; National Cancer Research Institute ; Queen’s University Belfast ; University College Cork ; University of Leicester ; Princess Alice Hospice ; University of Sussex ; University of Liverpool ; London Research Institute ; Brunel University ; Cambridge University Hospitals NHS (BioMed Central, 2013-10-01)
    Introduction: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. Results The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. Conclusions With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.
  • Lower limb orthopaedic surgery results in changes to coagulation and non-specific inflammatory biomarkers, including selective clinical outcome measures

    Hughes, Stephen F.; Hendricks, Beverly D.; Edwards, David R.; Bastawrous, Salah S.; Middleton, Jim F.; University of Chester; Keele University; Glan Clwyd Hospital; Gwynedd Hospital; University of Bristol (BioMed Central, 2013-11-09)
    Background: With an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective). Methods Test subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever. Results THR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections. Conclusions The most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care.
  • Eating for 1, Healthy and Active for 2; feasibility of delivering novel, compact training for midwives to build knowledge and confidence in giving nutrition, physical activity and weight management advice during pregnancy

    Basu, Andrea J.; Kennedy, Lynne; Tocque, Karen; Jones, Sharn; University of Chester; Wrexham Maelor Hospital (BioMed Central, 2014-07-04)
    Background: Women in Wales are more likely to be obese in pregnancy than in any other United Kingdom (UK) country. Midwives are ideally placed to explore nutrition, physical activity and weight management concerns however qualitative studies indicate they lack confidence in raising the sensitive issue of weight. Acknowledging this and the reality of finite time and resources, this study aimed to deliver compact training on nutrition, physical activity and weight management during pregnancy to increase the knowledge and confidence of midwives in this subject. Methods A compact training package for midwives was developed comprising of evidence based nutrition, physical activity and weight management guidance for pregnancy. Training was promoted via midwifery leads and delivered within the Health Board. Questionnaires based on statements from national public health guidance were used to assess changes in self-reported knowledge and confidence pre and post training. Descriptive statistics were applied and 95% confidence intervals were calculated. Results 43 midwives registered for training, 32 (74%) attended and completed the questionnaires. Although, pre training knowledge and confidence varied between participants, statistically significant improvements in self-reported knowledge and confidence were observed post training. 97% indicated knowledge of pregnancy specific food and nutrition messages as ‘better’ (95% CI 85 to 100), as opposed to 3% stating ‘stayed the same’ – 60% stated ‘much better’. 83% indicated confidence to explain the risks of raised BMI in pregnancy was either ‘much’ or ‘somewhat better’ (95% CI 66 to 93), as opposed to 17% stating ‘stayed the same’. 89% indicated confidence to discuss eating habits and physical activity was ‘much’ or ‘somewhat better’ (95% CI 73 to 97) as opposed to 11% stating ‘stayed the same’. Emergent themes highlighted that training was positively received and relevant to midwifery practice. Conclusions This study provides early indications that a compact nutrition, physical activity and weight management training package improves midwives self-reported knowledge and confidence. Cascading training across the midwifery service in the Health Board and conducting further studies to elicit longer term impact on midwifery practice and patient outcomes are recommended.
  • Exploring the Development Needs of Postgraduate Taught Dissertation Supervisors

    Regan, Julie-Anne; Taylor, Kirsty; Simcock, Thomas; University of Chester (2014-10)
    The Graduate School, in collaboration with the Learning and Teaching Institute (LTI), undertook this project to explore the development needs of PGT dissertation supervisors. This information was vital to the effective planning of development opportunities, in order to enhance dissertation supervision on PGT programmes and ultimately improve the overall postgraduate student experience.
  • Welsh periodicals in the nineteenth century

    Peters, Lisa; University of Chester (2014-05-27)
    This presentation places the developing Welsh periodical press within the changing economic, political, and social nature of nineteenth century Wales.
  • Information literacy

    Fiander, Wendy; University of Chester (SAGE, 2011)
    This book chapter discusses the importance of developing information literacy skills in healthcare students.

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