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PRISM 2006 Home Programme Abstracts

PRISM 2006 Talk Abstracts

(in alphabetical order)

1. (Group 2, Public Health, AXB 013)
   VARIATION OF MUSCULOSKELETAL CONSULTATION PREVALENCE, BY PRACTICE AND SOCIAL DEPRIVATION CATEGORY: DATA FROM THE GENERAL PRACTICE RESEARCH DATABASE (GPRD)
   Alexandra M Clarke, MSc, Kelvin Jordan, PhD, Peter R Croft, MD and Deborah PM Symmons, MD FRCP
   The University of Manchester
   
   Background: The last national data on the morbidity of musculoskeletal conditions presenting to primary care came from the Morbidity Statistics from General Practice Survey in 1991. There are no plans to produce a further morbidity survey. The GPRD is a computerised database of anonymised patient data from general practices. It currently has information on approximately 5% of the UK population. Objectives: To determine if variations in recorded morbidity of musculoskeletal conditions exist between practice and deprivation category.
   Methods: Data were available for all patients consulting with a musculoskeletal condition to a GPRD practice in 2001. Standardised prevalence rates for musculoskeletal conditions were compared by practice. Index of Multiple Deprivation quartiles (based on practice location) were used to determine the risk of consultation for musculoskeletal disease across deprivation category.
   Results: The overall prevalence of musculoskeletal consultation was 13%. Adjusted consultation rates ranged from 11-236 per 1000. The risk of consultation was higher in practices that were based in areas of greater deprivation. Conclusions: The consultation prevalence for musculoskeletal diseases varies greatly between practices, and differences were found between deprivation quartiles. These differences may reflect actual differences in prevalence but are more likely to represent differences in consultation behaviour amongst GPs.
   
   
2. (Group 3, Approaches to Research, AXB 014)
   Paradigm Changes and The (My) PhD
   Tim Donovan
   St Martin's / Lancaster University
   
   In the book 'How to get a PhD' (Phillips E., Pugh DS, 2005), the authors suggest that worrying about paradigm shifts is a very good way of not getting a PhD by overestimating what is required. It is however important to put my research into context and maybe one should have an awareness of how research is affected by changes in the explanatory schemes of the science. My research is looking at the effect of perceptual feedback in medical image interpretation, a subject that draws on many disciplines that seem to be having paradigm changes. Radiology now has a new imaging paradigm of functional imaging that has its foundations in molecular medicine with their emphasis on biochemistry and molecular pathways. In psychology and neuroscience our understanding of the brain is changing and there is a move towards explaining how the brain works as a whole. In vision research there is a rejection of the view that vision is simply a process of passive image interpretation. These are important issues and will affect the way I intend to write up my PhD.
   
   
3. (Group 3, Approaches to Research, AXB 014)
   Bias in Meta-Analysis as part of a Systematic Review
   Kerry Dwan, Paula Williamson, Carrol Gamble
   University of Liverpool
   
   Abstract: Important new findings in medical research have become evident due to the extensive use of meta-analysis in systematic reviews. An example of this is the increased risk of death following administration of human albumin solution, which was once standard practice. Several types of bias have been recognised as a potential threat to the validity of meta-analysis. Publication bias, were by a study is published or not depending on its results, has been shown to exist. Evidence is also gathering for the existence of outcome selection bias. This occurs when several outcomes are recorded in a trial but only the most significant included for publication. Different methods of meta-analysis are compared and different approaches in assessing the existence of bias are investigated.
   
   
4. (Group 3, Approaches to Research, AXB 014)
   Don't Let Degree Protocol Starve Your Research - How a Dieting Project Happily Gained Weight
   Malcolm Evans
   Manchester Metropolitan University
   
   The presenter, who has a long standing interest in obsessive dieting behaviour, discusses both the frustrations he has found within a formal research degree process and also how novelty and value has developed within the research itself. He contends that the potential for investigative dynamism in a research degree project risks being limited by the need to produce both a detailed proposal and the finite results of a thesis. He further argues that there are deep seated issues within the ethics of social health research which prioritise more the academic world of degree approval over an awareness of the creation of widespread value. Weight and dieting stand out as amongst the most politically charged health research areas of the day and he outlines these contentious issues and his own developing insights within his critique of what he sees as the contentious structures of the academic process. Negotiating these concerns, he summarises his research and some of the provisional findings.
   
   
5. (Group 2, Public Health, AXB 013)
   Increased Risk of Lymphoma Observed In A 10 Year Prospective Study Of A Large Primary-Care Based Inception Cohort Of Patients With Inflammatory Polyarthritis
   J.Franklin, M.Lunt, D.Symmons, A.Silman
   The University of Manchester
   
   It is widely accepted that patients with rheumatoid arthritis (RA) are at an increased risk of lymphoma. We have investigated if this increase is also apparent in a large cohort of patients with incident inflammatory polyarthritis (IP) and also investigated the role of disease severity factors on risk.
   We recruited 2,105 patients with IP to a large population-based primary-care register. Cases of lymphoma were ascertained with hospital records. Lymphoma rates, both overall and in the disease subgroups, were compared with those expected for the NOAR region population adjusting for age, sex and calendar year.
   The risk of lymphoma was more than doubled in the IP cohort when compared to the general population (SIR=2.4, 95%CI 1.2-4.2). All the severity markers examined were associated with increases in risk whereas, in those subjects without the severity markers, there were no statistically significant increases.
   Conclusions: This study confirms findings from studies of lymphoma risk in RA, and shows that the risk is even greater in those with markers of severe disease.
   
   
6. (Group 1, Science and Technology, AXB 006)
   Negative regulation of HIF-1during prolonged hypoxia induction, with emphasis on the interaction with p53
   Lina Franzén, Kaye Williams, Ian Stratford
   The University of Manchester
   
   Hypoxia inducible factor 1 (HIF-1) is a transcription factor activated by low levels of oxygen; hypoxia. HIF-1 is a popular target for cancer therapy since it transcribes genes involved in angiogenetic and metastatic activity. It has been observed that the activity of HIF-1 declines after prolonged exposure to hypoxia. One might speculate that HIF-1 is regulated via negative feedback and one of the proposed inhibitors is p53. The aim of this study is to investigate how p53 and HIF-1 interact during hypoxia. Using promoter analysis, two HIF-1 binding sites were found in the p53 gene. This makes p53 a potential negative feedback regulator of HIF-1. We were able to demonstrate that p53-/- tumour cells seem to undergo p53-independent apoptosis when exposed to hypoxia. A potential alternative pro-apoptotic protein activated by hypoxia is nix. We found two potential HIF-1 binding sites in the promoter region of the nix-gene using promoter-analysis.
   
   
7. (Group 2, Public Health, AXB 013)
   An evaluation of two health utility measures in patients with rheumatoid arthritis (RA).
   Mark Harrison, Nick Bansback, Linda Davies & Deborah Symmons
   The University of Manchester
   
   Background: Utility measures provide weights in order to estimate quality-adjusted life years, used in economic analysis of health interventions. The EQ5D and SF6D utility measures are commonly used in RA, however their relative sensitivity to change and properties compared to RA specific measures has rarely been studied. Methods: A 3-year longitudinal study of RA collected the EQ5D, SF6D and a full range of disease specific measures. Validity was assessed by correlating (Spearman's rank) the utility measures with measures of different aspects of RA. The minimum important difference (MID) and relative sensitivity to change (effect size ratio [ESR]) was compared in groups defined by self reported change. Results: The EQ5D and SF6D correlate with RA damage and activity measures. The EQ5D MID was larger in deteriorating (0.10) than improving patients (0.04), whereas those of the SF6D were constant (0.04). The EQ5D was more sensitive than the SF6D (ESR 1.14:1) in deteriorating and less sensitive (ESR 0.78:1) in improving patients. Conclusions: The EQ5D and SF6D have construct validity and detect important change in RA. However, the two measures assess slightly different aspects of health. The relative sensitivity to change depends on the direction of change.
   
   
8. (Group 4, Health Care:Treatment and Systems, AXB 030)
   Meeting information needs of emergency medicine
   N. Harrop, Prof. A Gillies
   UCLan
   
   The National Programme for IT is intended to integrate and improve the efficiency of the NHS. It is a centrally-specified, technically-led project, focused around national procurement and "ruthless standardisation". The information environment within the NHS is locally-situated and diverse in character. These issues will be illustrated in a case study. Implications for the design and assimilation of information systems within the NHS will be discussed
   
   
9. (Group 2, Public Health, AXB 013)
   The Needs of Older Adults in Prison
   Adrian Hayes, Professor Jenny Shaw, Professor Alistair Burns, Dr Friederike Yarwood, Dr Arunraj Kaimal, Dr Anne Byrne & Dr Vineel Reddy
   The University of Manchester
   
   Introduction: There is currently no national strategy for the care and management of older adults in prison, despite this group having very different needs to younger prisoners. Both mental and physical health problems are more prevalent than amongst younger prisoners, or community-based groups of a similar age. Furthermore, custodial services such as resettlement have been severely criticised for older prisoners. No UK research has considered social care needs, quality of life or security needs for this group.
   Objectives: This project aims to establish the health, social and environmental needs of older adults in prison, to determine a useful age cut-off for this group, and to translate identified needs into service requirements.
   Methods: All prisoners in the North West region aged over 60 (200 prisoners) will be approached for interview. Half of prisoners aged between 50 and 59 at three establishments will also be approached (100 prisoners). Prisoners' mental and physical health, social care and security needs as well as quality of life will be assessed through interviews and audit of health/discipline records. A panel will also assess what services would be provided to adults in the community with similar needs.
   Results: Preliminary results from one prison showed that the younger group had significantly poorer quality of life and significantly more unmet health and social needs than the older.
   
   
10. (Group 4, Health Care:Treatment and Systems, AXB 030)
    Refractive error in Diabetes Mellitus.
    Byki Huntjens and Clare O'Donnell
    The University of Manchester
    
    Aims: Refractive error shifts are common in patients with diabetes mellitus. The aim of this study was to investigate diurnal variations in refractive error and blood glucose levels in diabetic subjects and healthy volunteers.
    Methods: Refractive error (RE), central corneal thickness, anterior chamber depth (ACD), lens thickness (LT), axial length (AL), intra-ocular pressure, and blood glucose levels (BGLs) were measured between 8AM and 8PM at approximately two hourly intervals, in 21 type 2 diabetic subjects, 20 type 1 diabetic subjects, and 20 non-diabetic controls.
    Results: The RE was found to vary significantly with time (ANOVA, P=0.03). The RE correlated positively with age (p=0.008), and negatively with ACD (p=0.001) and AL (p<0.0005). BGLs showed correlations with CCT, ACD, and LT, however these were not constant during the day.
    Conclusions: Fluctuating BGLs do not appear to influence refractive error in a predictable way in diabetic or control subjects.
    
    
11. (Group 4, Health Care:Treatment and Systems, AXB 030)
    Characterisation and Osteogenic Differentiation of Fat Pad Derived Stem Cells and their Potential Clinical Applications
    Khan WS, Adesida AB, Andrew JG, Hardingham TE
    The University of Manchester
    
    Human bone marrow derived stem cells exhibit an age-related decline in osteogenic potential. Tissue engineering approaches for the repair of bone could be optimised by the identification of a stem cell source that does not show age-related changes. Fat pad derived cells were isolated from two groups of patients with a mean age of 57 and 86. The cells were compared with respect to their cell surface characterisation and ability to undergo osteogenic differentiation. Cells isolated from both groups exhibited a profile of cell surface molecules similar but not identical to that of bone marrow derived stem cells. The cells from both groups cultured in osteogenic medium exhibited significant upregulation of alkaline phosphatase and osteocalcin genes, and significantly greater alkaline phosphatase enzyme activity compared to the control medium. The cells also showed greater calcium phosphate deposition on alizarin red staining. There was no significant difference between the osteogenic potential of the two age groups. The fat pad appears to be a source of stem cells that does not show age-related changes in later life. This has many potential tissue engineering applications for the repair of bone defects in an increasingly aging population.
    
    
12. (Group 1, Science and Technology, AXB 006)
    Improving the Intracellular Delivery of Aminoglycosides using Anionic PAMAM Dendrimers
    E.Lepp, H. Aojula, D.Attwood and A. D'Emanuele
    The University of Manchester
    
    The treatment of intracellular infection poses an ever-increasing challenge. With the incidence of diseases such as tuberculosis and malaria escalating, the demand for antibiotics that can target the site of infection is greater than ever. Aminoglycosides are broad spectrum antibiotics but they have disadvantages such as their potential nephrotoxicity and poor physicochemical properties. Dendrimers are taken efficiently into cells by endocytosis. This work investigates (i) the potential of anionic PAMAM dendrimers to bind with an aminoglycoside and (ii) the release of the antibiotic and its subsequent activity. The antimicrobial activity of the antibiotics and the antibiotic complexes was evaluated. Two methods of associating aminoglycosides with anionic G3.5 PAMAM dendrimers were employed: electrostatic interaction and covalent conjugation via an acid-labile hydrazone linker. Interaction between the dendrimer and aminoglycosides was confirmed by 1H-NMR a fluorescamine assay and the Sackaguchi Method. The activity of the antibiotic was measured using a standard microbial agar assay against Salmonella ACTC 23564. The movement of FITC-labelled antibiotic-dendrimer into cells was followed by fluorescent microscopy. These systems have the potential to enhance delivery of antibiotics to sites of infection traditionally difficult to treat.
    
    
13. (Group 3 Approaches to research, AXB 014)
    Nurse Role Formation and E-Learning
    Jill McCarthy
    Manchester Metropolitan University
    
    The presentation will discuss part of my doctoral thesis which is concerned with professional role formation in student nurses. The discussion will demonstrate how role adoption takes place in both the theoretical and practical components of adult nursing courses and will unpick why adoption of the professional role is imperative for good nursing care to take place. After placing the professional role in context, the presentation will proceed to discuss how nurse educators are being encouraged to replace traditionally taught units of study by e-learning units and the ethical implications this may have for the nursing profession. The drivers behind the e-learning initiative in student nurse education will also be unpicked alongside the possible underlying rationale.
    
    
14. (Group 2, Public Health, AXB 013)
    Researching community health in rural Hyrgyzstan
    O'Brien, V. Djusipov, K
    Liverpool University
    
    The Visible Voice project made use of participatory video techniques to help villagers in the remote mountain villages of Tolok and Kokjar, Kyrgyzstan, explore and prioritise local community health needs. Methods: Following on from an initial training workshop the villagers devised, filmed and edited four short films depicting their everyday lives and health concerns. Results: The qualititaive data gathered through discussions in workshops, interviews with villagers, photographic observation of village life and collaborative analysis of video and photographic materials provided a deep source of data on lifestyle, culture and health which complements medical and epidemiological data already available for communities in remote mountain villlages of Kyrgyzstan. In more general terms the experiences of the researcher provide an insight into how visual research methods can be used to aid communication between researchers and participants across cultural and language boundaries. We believe that participatory video and photography can also be useful in health research with culturally diverse communities in the UK.
    
    
15. (Group 1, Science and Technology, AXB 006)
    Yeast as a Delivery System for Oral Vaccines
    Walid Omara, Lubomira Stativa, Steve Oliver
    The University of Manchester
    
    Saccharomyces cerevisae is a popular unicellular eukaryotic system for molecular biology and as a result it has become one of the most commonly used host cell systems for the production of foreign proteins for research and industrial or medical use. In this study, we are aiming to use S. cerevisae as a vehicle for the release of heterologous proteins. To approach this, we used HPV16 L1 gene, (regulated by GAL1, HXT5, PGK1, SML1 or SSA3) as an example of protein that forms virus like particles (VLPs) in yeast and can be used as a prophylactic vaccine against cervical cancer, the second leading cause of cancer mortality after breast cancer The host strain used is the fragile mutant of S. cerevisiae in which the promoter of the genes SRB1, PKC1 and CHS3 (shown to be involved in cell wall biogenesis) is replaced by the regulated promoter, pMET3. In this conditional mutant cell lysis is triggered upon down-regulation of these genes by addition of methionine. Since one of the project aims was to demonstrate production and release of the heterologous protein from the conditional lysis mutant yeast cells, GFP was chosen as a good candidate for this purpose.
    
    
16. (Group 1, Science and Technology, AXB 006)
    The over-expression of Gelsolin Family Capping Proteins in Pancreatic Cancer Cells and their role in motility
    S. I. Patel, F. J. Ashcroft, C. C. Thompson, W. Prime, F. Campbell, A. Dodson and E. Costello.
    University of Liverpool
    
    Pancreatic cancer is an aggressive disease characterised by rapid invasion within the pancreas and to distal sites. Here, we report that CapG and gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer. We describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. Immunohistochemical analysis of benign (n=44 patients) and malignant (n=69) pancreatic ductal cells demonstrated significantly higher CapG staining in nuclear (P < 0.0001) and cytoplasmic (P < 0.0001) compartments of malignant cells. Gelsolin immunostaining of benign (n=24 patients) and malignant (n=68 patients) pancreatic ductal cells revealed higher expression in both compartments (P < 0.0001). High nuclear CapG was associated with increased tumour size (P = 0.001). High nuclear gelsolin correlated with reduced survival (P = 0.01). CapG and gelsolin levels were reduced using RNA interference in Suit-2, MiaPaCa-2 and Panc-1 cells. The effect of this on cell motility was assessed using wound healing assays and Boyden chambers. Reduction of CapG or gelsolin expression in cell lines significantly impaired thier motility. In conclusion, we have shown the overexpression of CapG and gelsolin in pancreatic cancer and have demonstrated a role for them in the modulation of cell motility in vitro. This suggests a potentially important role for these in pancreatic cancer cell motility and consequently dissemination.
    
    
17. (Group 1, Science and Technology, AXB 006)
    Usefulness of a gravity stress view in detecting the unstable Weber B fractures of the ankle
    A Puttaraju, B Sankar, H Nalwad, BN Muddu
    Tameside General Hospital
    
    The aim is to determine the usefulness of a gravity stress view in detecting the unstable Weber B fractures of the fibula with no evidence of a medical side injury on clinical examination or standard radiographs.
    Materials and Methods: We used a standard protocol for patient selection, exclusion, surgery/conservative management and follow up. Fracture dislocations, those with medial/posterior malleolus fractures and those with preliminary X-rays showing a talar shift/tilt were excluded. If the medial clear space increased beyond 4mm on stress radiographs, surgical fixation of the lateral malleolus was performed. If this remained 4mm or less conservative treatment was undertaken.
    Results: We recruited 18 patients with isolated Weber B fractures. In 7 patients the medial clear space increased from 4mm to an average of 6.29 mm . 6 of these 7 patients were operated. The medial clear space remained 4mm or less in the remaining 11 patients and were therefore managed conservatively. No complications were noted in either the surgical or the non surgical group. All the 17 patients who were followed up in our hospital had excellent final AOFAS Scores.
    Conclusion: We conclude that gravity stress views can accurately detect instability in Weber B fractures of the ankle and we recommend its routine use in these.
    
    
18. (Group 1, Science and Technology, AXB 006)
    Polarus Nailing for Non unions of 2 part surgical Neck of Humerus fractures
    A Puttaraju, B Sankar, H Nalwad, BN Muddu
    Tameside General Hospital
    
    Aim: We describe our experience of treating non unions of two part surgical neck of humerus fractures using the Polarus Nail and bonegrafting.
    Methodology: Over a period of 8 years, 10 patients underwent the above procedure in our hospital. The records and radiographs of these patients were reviewed and the patients were finally assessed using the Constant and Oxford Shoulder Scoring System.
    Results: 7 non-unions occurred in patients treated conservatively and 3 non unions resulted following attempted osteosynthesis using rush pins. The average age of our patients was 69.1 years and the average duration of non union was 14.3 months. The time to radiological union in the remaining 7 patients was 13.2 (12-16) weeks. The mean Constant score was 68.2. The mean Oxford shoulder score was 20.2. Adjusting for age and sex in the Constant scoring system, the shoulder function was excellent in 3, good in 1 and moderate in 2. On the Oxford scoring system, the shoulder function was excellent in 3, good in 2 and moderate in 1 Conclusions Internal fixation with Polarus nail and bone grafting gives good and predictable results and should be considered while dealing with 2 part surgical neck of humerus non unions.
    
    
19. (Group 2, Public Health, AXB 013)
    Longitudinal Effects of a Playground Redesign Intervention on Children's Physical Activity Levels during Playtime
    Nicola D. Ridgers, Gareth Stratton, Stuart J. Fairclough & David J. Richardson.
    Liverpool John Moores University
    
    Few studies have investigated the physical activity levels of children with different body mass index (BMI) values in settings where they have daily opportunities to be physically active. The aim of the study was to evaluate the longer-term effects of a playground redesign intervention on children's playtime physical activity levels. One hundred and fifty-nine children (intervention = 81, control = 78) from 21 schools had their physical activity levels quantified using accelerometry at baseline, 6-weeks and 6-months following the intervention. Children were divided into quartile groups based on baseline BMI. Data were analysed using repeated measures ANOVA's. Results revealed no significant differences between the quartile groups playtime physical activity across time. The group x time interaction was significant, with the intervention group engaging in significantly more physical activity at 6 weeks and 6 months following the playground markings compared to the control group. In conclusion, the intervention had a positive effect on playtime physical activity, with similar increases observed and maintained across the quartile range.
    
    
20. (Group 4, Health Care: Treatment and Systems, AXB 030)
    An evaluation of corneal nerve morphology and function in moderate keratoconus
    Luisa Simo Mannion, Cindy Tromans, Clare O'Donnell
    The University of Manchester
    
    PURPOSE: To evaluate the corneal nerve morphology and function in moderate keratoconus.
    METHODS: The central corneal nerve fibres of 13 subjects with moderate keratoconus and 13 age, gender and iris colour matched control subjects were imaged using a confocal microscope (ConfoScan3, Nidek Technologies, Italy) and analysed using image processing software (Scion image, Scion Corporation, Frederick, MD). The corneal nerve sensitivity was measured using a Cochet-Bonnet aesthesiometer (Luneau Ophthalomogie, Chartres, France)
    RESULTS: The density of the nerve fibres at the stroma was similar for both groups (445.6± 107.4µm/mm2 449.1± 124.5µm/mm2; p= 0.94) but decreased in the keratoconics at the sub-basal plexus (1018.3± 489.6µm/mm2 vs. 1820.7±789.5µm/mm2; p=0.007). The diameter of the nerve fibres was seen to be greater for the stromal nerves of the control group (keratoconus 10.2±4.6µm vs. control 5.5±1.9µm; p=0.006). A reduction on corneal nerve sensitivity was seen only in the keratoconus sub-group that did not wear contact lenses (Keratoconus with contact lenses (n=8) vs. controls with contact lenses (n=6): 1.18±0.19g/mm2 vs. 0.98±0.05g/mm2)
    CONCLUSION: The corneal nerve morphology in moderate keratoconus is affected. The increased diameter of the nerve fibres in the stroma might explain why they appear to be more visible when viewing these corneas under a slit-lam biomicroscope.
    
    
21. (Group 4, Health Care: Treatment and Systems, AXB 030)
    Meta-analyses of the management of locally advanced and metastatic pancreatic cancer
    Sultana A, Tudur Smith C, Ghaneh P
    University of Liverpool
    
    BACKGROUND: There is a lack of consensus on management of advanced pancreatic cancer.
    AIMS: To examine the different approaches to pancreas cancer treatment.
    METHODS: Relevant randomised controlled trials (RCTs) were identified and the primary end point of overall survival (OS), summarised using hazard ratio (HR), was extracted
    RESULTS: Survival was improved with chemotherapy compared to best supportive care (BSC) (HR 0.64; 95% CI 0.42 to 0.98). 5FU combination chemotherapy did not result in better OS compared to 5FU (HR 0.94; 95% CI= 0.82 to 1.08). Survival was improved following gemcitabine combination chemotherapy compared to gemcitabine (HR 0.89; 95% CI 0.83 to 0.96). ChemoRT improved survival over RT (HR 0.70; 95% CI 0.52 to 0.94). ChemoRT followed by chemotherapy did not lead to a survival advantage over chemotherapy (HR 0.79; CI 0.32 to 1.95).
    CONCLUSIONS: There was a significant survival benefit for chemotherapy over BSC, gemcitabine combinations over gemcitabine and chemoRT over radiation.
    
    
22. (Group 4, Health Care: Treatment and Systems, AXB 030)
    NEW PUBLIC MANAGEMENT (NPM) AND PERFORMANCE MEASUREMENT: A CASE STUDY IN NATIONAL HEALTH SERVICE (UK)
    Paresh Wankhade
    Liverpool Hope University
    
    One remarkable feature of NPM reforms is the importance of performance measurement despite the variation in the theme. Problem of measuring performance in nonprofits/public sector is more acute due to various contradictions. As a tax financed public service, the NHS in UK makes no profit and declares no dividend. There is no simple way to sum up the myriad activities in the NHS. My research aims to the evaluate and analyse the evidence gathered in my case study (North West Ambulance Trust) as to whether the 'star rating system' and targets improve performance in the NHS and if most of the indicators of healthcare performance are "tin openers rather than dials". The method used will be semi-structured interviews with the senior management and staff and through participation observation. My research will also look at the proposed merger (w.e.f.1st July 2006) of four ambulance trust in the region with different performance levels and how it will help to sustain performance. The use of targets in 'gaming' will also be examined in the case study. The findings of the research will be significant for a number of different audiences including policy makers, practitioners and the research community.
    
    
23. (Group 3, Approaches to Research, AXB 014)
    Developing Measures of Symptoms of Traumatic Life Events for the Intellectual Disability Population.
    Sarah Wigham
    Lancaster University
    
    Objectives: The link between mental ill health and traumatic life events is well established in the general population literature on post-traumatic stress disorder (PTSD). The objective of this study is to develop screening measures of symptoms of traumatic life events, which are accessible to the intellectual disability (ID) population.
    Design: A pilot to draft the measures.
    Method: Using interviews, questionnaires and focus groups, 6 service users, 2 advocates, 2 carers, plus 16 staff from mental health and forensic ID services in Northumberland, were consulted regarding the symptoms of traumatic life events in the ID population.
    Results: Data has been analysed via content analysis. The majority of the symptom themes derived are consistent with general population studies, though some differences were loss of skills, and challenging behaviours.
    Conclusions: The reliability and validity of the measures will be examined next.
    
    
24. (Group 3, Approaches to Research, AXB 014)
    Are the needs of the ethnic population being served by the present NHS
    Surita Bhat, SpR General/Geriatric Medicine, Alka Gupta, Medical Student
    Romesh Gupta, Consultant Physician, Lancashire Teaching Hospitals NHS Foundation Trust
    
    The ethnic minority population from south east Asia are more prone to suffer increasingly with hypertension, coronary artery disease, stroke, renal failure and Diabetes Mellitus. Unfortunately their access to the health care services both primary and secondary is poor. There have been several initiatives by the department of health and healthcare commission to try and address this issue and to put an increased emphasis on achieving equity. Locally the Lancashire Gujarat Health Users Forum was established five years ago and works in partnership with the primary care trust and acute hospital as well as other voluntary organisations to improve the health of the ethnic minority population. To be able to address the issues in a constructive manner a survey was undertaken of nearly 200 people for the local ethnic minority community. 100 male and 85 female from various religious backgrounds responded on issues including physical and mental needs, views about residential care and end of life issues. This paper will present the findings of this survey and the way forward to address the issues of inequality in the healthcare of ethnic minorities.
    
    

PRISM 2006 Poster Abstracts

1. Protein Kinase CII is overexpressed and influences B-Cell Receptor signalling in Chronic Lymphocytic Leukaemia cells.
   Simon T. Abrams, Tasneem Lakum, Gemma M. Jones, Ke Lin, Andrew T. Treweeke, Mosavar Farahani, Mirko Zuzel, and Joseph R. Slupsky
   University of Liverpool
   
   Chronic Lymphocytic leukaemia (CLL) is an incurable disease of mature malignant B cells characterised by prolonged cell survival. B cell receptor (BCR) signals are important for the survival of CLL cells. Therefore, factors mediating these signals will have an important pathophysiological role. Protein Kinase C; (PKC;) is known to be an important mediator of BCR signals in B cells. Here, we show that PKCII is overexpressed in CLL cells compared to normal B cells. Analysis of membrane associated PKCII showed a variation in the levels of PKCII activity between different CLL cases, which correlates with the ability of CLL cells to respond to B cell receptor (BCR) mediated signals and survival. Thus, the magnitude of BCR-induced Ca2+ fluxes and increases in cell survival were markedly greater in CLL cases with low PKCII activity compared to CLL cases with high PKCII activity. These results suggest that overexpressed PKCII plays an important role in mediating BCR signals in CLL cells. As chronic antigenic stimulation is important for in vivo survival of CLL cells, these results elucidate a pathophysiological role of PKCII in the regulation of this stimulation. Thus, PKCbII activity levels may be an important contributing factor to CLL disease progression.
   
   
2. Public Engagement with Science
   M.Alami
   MMU
   
   The uncertainty of hazards resulting from consuming GM foods over the course of the last decade has been unique. During this time, the risk scene has observed continuous debate, change and public health concerns, in particular those that concern food 'scares' or 'panics'. In response, there is now a growing trend in adopting deliberative democratic methods to gather public views in an attempt to pacify public concerns. One main effect of the schism in US and EU approaches to risk has been the call for a reversal of the burden of proof. This poster explores two main schools of thought. First, it delves into the 'world' of science. Second, it explores precautionary approaches to GM food consumption 'hazards' or 'risks'. According to Wynne, 'risk' may be seen as "intellectually-constructed." I explore that through a close analysis of two main risk management strategies. By careful analysis of the two main pillars of management: precautionary and discursive doctrines show that these two doctrines may be applied simultaneously when addressing technological risks.
   
   
3. Functional assays for Hsp70 using Surface plasmon Resonance
   Ola M.B. Altaie, Claire Hunter-Lavin & John H.H.Williams.
   University of Chester
   
   Abstract: Heat shock proteins (HSP) were first characterized as intracellular proteins, which have vital cellular function under normal growth conditions. Recently, it has been recognized that Hsp70 and anti-Hsp70 are both present in serum, but it is not known whether they interact in vivo. We have investigated the binding of Hsp70 and anti-Hsp70 using Surface Plasmon Resonance (BIAcore Q) which measures the interactions in real time. The interactions were studied in two ways: by immobilising either the protein or the antibody on the CM5 chip. The results showed significant binding of Hsp70 with its antibody. Hsp70 does not compete for binding of the free anti-Hsp70 to immobilized protein. Passing Hsp70 over immobilized antibody also showed binding. Furthermore, denatured protein from cell extracts binds to immobilized Hsp70. These data provide a basis for further study investigating the biological form of Hsp70 in vivo.
   
   
4. A Receptor for TRAIL
   Nina C. Dempsey, Robert C. Coleman, Claire Hunter-Lavin, Michael J. Marshall & John H.H. Williams
   University of Chester
   
   The role of OPG in bone turnover is well established, however this protein has now been shown to have anti-apoptotic properties which may contribute to the survival of cancer cells. OPG has been found to be a fifth receptor for TRAIL, an apoptosis-inducing protein produced in tumours by invading monocytes. The binding of OPG with TRAIL prevents ligation of TRAIL with its cell surface receptors, thereby inhibiting apoptosis. Here, using surface plasmon resonance, we demonstrate the binding of OPG-Fc with TRAIL and compare this binding with that of OPG-Fc and RANKL. Using BIAevaluation software, we quantify the binding of TRAIL and OPG-Fc and show that it is stronger than the binding affinity of OPG and RANKL. Using ELISA we also demonstrate that TRAIL can effectively compete with anti-OPG for OPG binding.
   
   
5. Molecular characterization of VP4, VP7, and NSP4 genes of Novel P[8]G12 rotavirus genotype strains detected in Maddina, Saudi Arabia.
   Kheyami A, Nakagomi O, Dove W, Cunliffe NA, Hart CA
   University of Liverpool
   
   Annually, rotavirus mortality ranges from 418000 to 870000 deaths. G1-G4 and G9 and P[4], P[6] and P[8] are the major rotavirus types found in global collections of strains. However, some rare types (G5, G8, and G12) and rare combinations of G and P types from different countries have also been reported. In a recently completed one year study of viral gastroenteritis in children in Maddina, Saudi Arabia, we identified G12 as an emerging serotype accounting for 4% of circulating rotavirus strains. We here sequenced the genes encoding the neutralization proteins VP7 (G12) and VP4 (P[8]), and the non-structural protein NSP4, of a representative of the novel genotype strains (designated MD844). G12P[8] strain was detected from a total of seven samples (4%). The samples were obtained from patients aged between 5 to 12 months old. The VP7 sequence of MD844 was most closely related to human and animal serotype G12 rotaviruses whereas VP4 sequence of the strain showed closest homology to rotaviruses of P[8]. The NSP4 gene sequence was classified in NSP4 genetic group B (Wa-like) viruses. These results suggest that Saudi G12 strains detected in this study are reassortment between G1P[8] and the globally circulating G12 strains The detection of G12 strains in several countries implies the recent expansion of the distribution area of the G12 rotavirus.
   
   
6. Heat Shock Proteins protect against both apoptosis and necrosis in Jurkat cells
   Francesca M.G. Leoni, Helen Williams, Rachel Nelson, Claire Hunter-Lavin, & John H. H. Williams
   University of Chester
   
   Previous studies have shown, that over-expression of Hsps provides protection against apoptosis by preventing the cleavage of caspase-3. Our studies focused on the effect of Hsps on viability, apoptosis and necrosis in Jurkat cells. We identified a critical time (2.5 h) and temperature point (42ºC) at which apoptosis reached a peak, and after this, an elevation in temperature resulted in an increase in necrosis, alongside a decrease in viability. We also showed an induction of hsp70, hsp90, and hsp27 genes at this time and temperature. We then hypothesised that as soon the cell synthesised Hsps, they provided protection of the cell and the rate of apoptosis decreased. Using several known inhibitors and inducers of Hsps we showed that reducing Hsp expression makes cells more susceptible to heat-induced apoptosis and necrosis. These data support a role for Hsp70 and Hsp90 in protection against heat-induced cell death.
   
   
7. Re-forming brain connections in Parkinson's disease
   Y.Liu and M.A.Gates
   Institute of Science and Technology in Medicine, Keele University
   
   Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The main symptom is abnormal motor movement (e.g. slowness of movement).It could eventually kill the patients by complications related to muscle movement problems. It is known that the damage of dopamine-producing neurons in substantial nigra pars compacta (SNc) causes the decrease of dopamine in the striatum (STr). The lack of dopamine in STr leads to a failure to elicit the muscle movement by the neural system. So the destruction of the link between SNc and STr is the key point in Parkinson's disease. In order re-form the circuit back into the brain, the current proposal aims to pre-construct the nigro-striatal projection in a biodegradable scaffold that could be used to replace the circuit in an animal model of Parkinson's disease. Once the circuitry been replaced successfully, hopefully we will see satisfying results on PD patients after transplantation.
   
   
8. Production of hydrogen peroxide from the amylin peptide implicated in type 2 diabetes mellitus
   Atef Masad, Lee Hayes, Brian Tabner, Leanne Cooper, Matt German, Nigel Fullwood and David Allsop
   Lancaster University
   
   The formation of amyloid fibrils from a variety of different proteins is a common link between many diseases, including type 2 diabetes mellitus (T2DM). The presence of amyloid deposits is often associated with considerable damage to tissues, and there is increasing evidence that this could be due to the generation of hydrogen peroxide by the amyloid proteins, via a mechanism involving redox-active metal ions. The Fenton reaction converts hydrogen peroxide into hydroxyl radicals, which can inflict severe oxidative damage to cells. Amyloid deposits derived from the peptide 'amylin' are found in the pancreas in T2DM. We have used the Amplex red dye method to detect any hydrogen peroxide generated during the incubation of amylin, and have correlated these data with peptide aggregation. We found that human amylin generated hydrogen peroxide during its aggregation into amyloid fibrils, and that this process was greatly stimulated by Cu(II) ions. Furthermore, we also found that human amylin was selectively bound to a copper-loaded immobilised metal-affinity chromatography (IMAC) column. We conclude that the direct formation of reactive oxygen species from the amylin peptide could be responsible for its toxicity towards islet cells in T2DM.
   
   
9. Electronic Shunt System for Hydrocephalus
   Lina Momani and Waleed Al-Nuaimy
   University of Liverpool
   
   Hydrocephalus is the accumulation of CSF in the brain due to the malfunction of the natural drainage system by a serious infection, fever, accident, premature born babies, etc. The percentage of people having hydrocephalus is increasing rapidly, that urges the need for effective treatment. Nowadays, a passive, differential pressure operated, mechanical shunt is used to treat hydrocephalus patients, that satisfies 50% of its patients but with serious drawbacks e.g. overdrainage, underdrainage, long-term drift, low durability. The current treatment for hydrocephalus involves the use of shunt that consist of a valve and catheters that drains CSF from the brain to the abdominal areas. Most of these valves-if not all- operate depending on the differential pressure across the valve not the value of ICP. This project aims to develop electronic shunt system that would correspond instantaneously and continuously to the change in the ICP value not to the change in the differential pressure across the valve, which involves monitoring and controlling the ICP. At the same time, the system would save the ICP readings for future need of ICP history. The electronic shunt system would consist of pressure sensor, mechatronic valve, microcontroller, RF transceiver, proximal and distal catheters, and internal rechargeable battery. Implementing such system would reduce the drawbacks of the available shunts significantly , if not eliminate them.
   
   
10. Weight Gain & Obesity in a High Secure Hospital
    Morgan, P., Pinkney, J., MacFarlane, I.
    University of Liverpool
    
    A cross-sectional survey was carried out with retrospective analysis of body mass index (BMI) and presence of diabetes mellitus in a sample of 420 patients (12% female) resident in a high secure psychiatric hospital in mid 2002. Obesity (BMI>30kg.m-2) was present in 27% of patients (morbid obesity (BMI >40) 14%), a mean 8.3 years earlier obesity was present in only 12% of this sample. 8% of patients were known to have diabetes (all Type 2). Current obesity was strongly associated with non-obesity at the time of original admission (p<0.0001), female sex (p<0.001), and age 31-40 years (p=0.001). Measures to prevent obesity (lifestyle advice / anti-obesity drugs) should be a high priority.
    
    
11. Tetracycline-inducible pancreatic cancer cell lines
    Sabina Patel, Melanie Bier and Eithne Costello
    University of Liverpool
    
    Precise control of the level of protein expression in cells can yield quantitative and temporal information on the role of a given gene. The most promising and widely used technique for regulating heterologous gene expression has been the tetracycline-regulated gene expression system. The technique consists of consecutive transfections of the target cells with two transgenes, the first of which encodes a tetracycline-controlled transactivator protein (tTA) and the second of which is the modified gene of interest, with a tetracycline response element (TRE) in its 5' regulatory sequence. Although a second-generation tet-on transactivator was recently described, it has not been widely investigated for its potential as a tool for regulating genes in cells and particularly in cells previously recalcitrant to the first-generation tet-on approach, such as pancreatic cancer cells.Four pancreatic cancer cell clones (derived from the pancreatic cancer cell line Suit-2) incorporating a second-generation doxycycline-inducible gene expression system have been generated. These four clones were tested for transient inducible expression of the luciferase gene and for stable inducible expression of the actin capping protein CapG. High levels of expression were obtained in a time- and dose-dependent manner. In conclusion, we have generated pancreatic cancer-derived cell clones in which expression of genes is controllable.
    
    
12. Your postcode could seriously affect your health - the demographics of haemophilus influenzae around Morecambe Bay
    Dawn V Smith David Telford Keith Jones
    Lancaster University
    
    The microorganism Haemophilus influenzae inhabits the mucous membranes of humans, usually the upper respiratory tract. Non-capsulate strains are associated with adult bronchitis, pneumonia and infant eye and ear infections.Patients with chronic chest disease such as chronic obstructive pulmonary disease (COPD) are most at risk. COPD is a progressive respiratory disease that destroys the lungs, inflicting damage on the rest of the body. It is assuming epidemic proportions and incidence has overtaken media heavyweights, breast and prostate cancer. To study the epidemiology of H.influenzae in the Morecambe Bay area, 967 isolates were collected from the 3 Trust hospitals over 2 years. Several aspects were studied including: Comparison of infection rates in rural and urban areas Whether different housing types influenced H.influenzae infections We concluded that: Where you live does make a difference COPD patients with H.influenzae infections are most prevalent in the elderly population, particularly those living in poorer housing.
    
    
13. Expression of HIF 1 alpha,p21 and p53 in Resected Neurofibromas
    M.H.Sulaiman,K.Vishwanathan,M.M.Roebuck, T.R.Helliwell and S.P.Frostick
    University of Liverpool
    
    Neurofibromatosis type 1(NF1)is a common autosomal dominant disoder affecting approximately 1 in 3000 individuals.Approximately two-thirds of patients with NF1 are predisposed to develop multiple neurofibromas and are at the risk of transformation of NF1 to malignant peripheral nerve sheath tumour(MPNST).The molecular alterations contributing to the transformation of NF1 to MPNST is not fully understood.Additionally, it is not known whether the neurofibromas as benign tumours, are held in premature senescence and the possible role played by hypoxia.Thus we examined the expression of hypoxia inducing factor 1 alpha (HIF-1), and cell cycle arrest components such as p27, and p53. Immunochemical analysis revealed positive expression of p21,p53 and HIF-1 alpha in all the resected samples.In conclusion, this study suggest that the NF1 cells are held in a state of genotoxic arrest and emphasise the possible role of HIF-1, p21,and p53 in the development of both sporadic and NF1-associated MPNST tumours.Studies will be needed to show if these cells also express senescence associated beta - galactosidase.
    
    
14. Lymphocyte-Specific Tyrosine Kinase (Lck) in Chronic Lymphocytic Leukaemia Cells and its Potential Role in Cell Survival.
    Victoria Thompson
    University of Liverpool
    
    Chronic Lymphocytic Leukaemia (CLL) is a heterogeneous disease which originates from antigen- experienced B cells. It is thought that interaction of the malignant cells with antigen stimulates their survival and contributes to the pathogenesis of CLL. Lymphocyte-Specific Tyrosine Kinase (Lck) expression in B cells can be induced by B-cell receptor (BCR) engagement, and may therefore be a marker of similar stimulation in B lymphoid malignancies. The aim of this project was to investigate the expression and function of Lck in CLL. I found that CLL cells express high levels of Lck and that there was little variation in the levels of expression between individual cases. The levels of Lck protein present in CLL cells decreased over 120 hour culture suggesting that in vivo stimuli such as BCR crosslinking by antigen may be inducing the expression of this protein. Recent work using specific inhibitors of Lck activity suggest that Lck plays a role in protecting CLL cells from spontaneous apoptosis. However, Lck does not seem to play a direct role in CLL-cell response to BCR engagement. I conclude that Lck expression in CLL cells contributes to disease pathogenesis by contributing to cell cytoprotection.
    
    
15. Is Duffy Antigen Expressed on Endothelial Cells Undergoing Angiogenesis in Rheumatoid Arthritis?
    Catherine Wilson, Lucy gardner, Brian Ashton, Jim Middleton
    Institute of Orthopaedics
    
    Rheumatoid Arthritis (RA) is a chronic, destructive inflammatory disease that primarily affects the small diarthrodial joints of the hands and feet. The main focus of inflammation occurs in the synovial tissue that lines the joint cavity. Early RA synovial tissue has an increase in angiogenesis and the infiltration of inflammatory cells is usually quite mild. In more chronic cases, there is increased infiltration and the number of blood vessels is significantly increased. Chemokines are known to have angiogenic properties. In this study, we looked at whether the chemokine binding molecule Duffy antigen occurred on blood vessels undergoing angiogenesis. Double label immunofluorescence was performed using alpha v beta 3, an integrin that is widely used as a marker for angiogenesis, and an antibody for Duffy antigen. Previous studies have shown Duffy antigen expression in the endothelial cells of post-capillary venules in all RA and non-RA synovia. Duffy antigen expression is up-regulated in the early stages of RA then down-regulated with disease duration. In early RA the proportion of alpha v beta 3 co-localisation with Duffy was relatively low and did not show variation with disease duration suggesting that there is little expression of Duffy in newly angiogenic blood vessels.
    
    
16. Interventions working to address the needs of children and young people who have drug using parents or carers.
    Kerry Woolfall
    Liverpool John Moores University
    
    Interventions working to address the needs of children and young people who have drug using parents or carers. Kerry Woolfall, researcher within the National Collaborative Centre for Drug Prevention (NCCDP) Liverpool John Moores University, is launching a postdoctoral study investigating interventions working with children of drug using parents. The research aims to document and evaluate the effectiveness of interventions working to meet the needs of these vulnerable children in the Northwest of England. The main aims of this study will be to:
    • Provide an indepth insight into the impact of parental drug use on the child/ren and the family as a whole over a five-year period;
    • Review the support received by the young people and the perceived impact each method of support has for each child and family;
    • Compare and contrast the impact of each Initiative in order to identify the most and least appropriate model of support for children and families to address their needs;
    • Monitor views on drug use and levels of drug use over the five-year period;
    • Explore whether any particular form of intervention are better suited than others to meet the needs of particular groups of children such as older children, or those where the child is in the care of the Local Authority.

 

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