prism conference pack

30 October 2009 The University of Manchester

www.vitae.ac.uk/nwhub

Postgraduate Researchers in Science Medicine

conference 2009

Postgraduate Researchers in Science Medicine conference, 30/10/2009

09:00 Registration B000 Entrance Hall

09:20 Welcome address Prof Dame Nancy Rothwell, Deputy President & Deputy Vice-Chancellor, University of Manchester

C001 Great Hall

09:35 Keynote speech Prof Jane Worthington, Professor of Chronic Disease Genetics and Scientific Director and Deputy Director of the arc Epidemiology Unit, University of Manchester

C001 Great Hall

10.10 Concurrent student symposia 1: Session A: Chair: Dr John Griffiths 10:10 Motility of bacteria in microfluidic structures, M Binz 10:25 Substance abuse among University student in Karbala/Iraq in May 2005, A Al

Mousawi 10:40 Early stage pancreatic cancer serum protein biomarkers, S Murray 10:55 Using MRC framework for complex intervention for developing of a culturally

sensitive family intervention in Egypt, R Wahid

G13D

Session B: Chair: Dr Sarah Heathfield 10:10 UK Endodontists experience using ultrasonics for removal of intra-canal separated

instruments, A Madarati 10:25 Hypertension; from rhythm to reason, A Bradbury 10:40 Modelling organ function after radiotherapy, E Rutkowska 10:55 Clotting analysis of blood samples from intensive care unit patients, B Sempasa

C001

Session C Chair: Dr Amy Mason 10:10 Why should we listen to the stories told by people with epilepsy? D Snape 10:25 The challenge of embracing a wider epistemology, C Kennedy 10:40 Touch and the body in psychotherapy, K Dymoke 10:55 The relationship of well-being to intrinsic and extrinsic motivation among dental

students, A Montasem

B004

11:10 Coffee B000 Entrance Hall

11.40 Concurrent student symposia 2:

Session A: Chair: Dr John Griffiths 11:40 Use of Platelet Rich Plasma (PRP) as a biologic modulator, M Badr 11:55 Increased cortical surface area of left Brodmann area 44 in male orchestral

musicians correlated positively with years of musical performance, I Abdul-Kareem 12:10 Raised maternal body mass index (BMI) is associated with altered activity of

placental nutrient transporters, A Ditchfield 12:25 The relationship between muscle activity, stature recovery and clinical outcome in

chronic low back pain, S Lewis

G13D

Programme


Session B: Chair: Dr Sharon Sneddon 11:40 Physical characterization of multicellular tumour spheroids – toward composition and

growth characteristics, A Ur Rahman 11:55 Systemic sclerosis serum increases endothelial cell apoptosis and activation in

neutrophil-endothelial cell co-cultures: a role for interleukin 6, T Barnes 12:10 Investigating the effect of the immunosuppressant Mycophenolic acid on neutrophil

function, L Hopcroft 12:25 Development of topical anti cancer medication for post operative patients with head

and neck cancer, A Aslam

C001

Session C: Chair: Dr Karen Forbes 11:40 Development of an integrated miniaturised real time polymerase chain reactor, A

Markey 11:55 p53 induces cell motility and invasion by upregulation of MDM2 in renal cell

carcinoma, R Polanski 12:10 Characterisation of TMEM114, a protein associated with dominant congenital

cataract, G Maher 12:25 Phenotype-genotype correlations in Amelx and Enam murine models of

Amelogenesis imperfecta, T Coxon

B004

12:40 Lunch & poster presentation session B000 Entrance Hall

13.40 Workshop session A:

How to survive a viva Dr Judy Williams, Faculty Head of Skills Training and Development Team, University of Manchester & Vitae NW Hub Co-ordinator

J015

Constructive and creative thinking Dr Adrian West, Skills Trainer, University of Liverpool

B004

Boost your writing skills Dr Rachel Cowen, Research Staff Trainer, University of Manchester

G13D

Engaging others with your research Dr Ann Barlow, Faculty Head of Skills Training and Development Team, University of Manchester

H008

14.30 Workshop session B:

How to survive a viva Dr Judy Williams, Faculty Head of Skills Training and Development Team, University of Manchester & Vitae NW Hub Co-ordinator

J015

Enterprise for researchers Dr Rob Phillips, Lecturer, Manchester Enterprise Centre

B004

Publish or perish – navigating the peer review process Dr Rachel Cowen, Research Staff Trainer, University of Manchester

G13D

Programme

Programme


Using web 2.0 to enhance your research Dr Emma Gillaspy, Vitae North West Hub Manager, University of Manchester H008

15:20 Coffee B000 Entrance Hall

15.40 Workshop session C: Managing your PhD supervisor Dr Judy Williams, Faculty Head of Skills Training and Development Team, University of Manchester & Vitae NW Hub Co-ordinator Dr Richard Hinchcliffe, Director of Postgraduate Training, University of Liverpool

J015

Postdoctoral perspectives Dr Elizabeth Wilkinson, Head of Postgraduate Career Development, University of Manchester Panel: Dr Julian Breeze, Dr Rachel Oldershaw, Dr Sarah Withers, Dr Nerys Astbury, Dr Stephen Richardson

B004

Presentation skills: Feel the fear and do it anyway Ms Dee-Ann Johnson, Communications Officer, University of Manchester G13D

Engaging others with your research Dr Ann Barlow, Faculty Head of Skills Training and Development Team, University of Manchester

H008

16:30 Closing comments and prize giving Dr Emma Gillaspy, Vitae North West Hub Manager, University of Manchester

C001 Great Hall

16:45 Networking reception B000 Entrance Hall

17:30 Close

Programme


Workshop session A (13.40-14.25):

How to survive a viva Room J015 Judy Williams (University of Manchester) Using interactive discussion, participants will gain an insight into the viva process. The workshop will cover typical scenarios, how to prepare effectively, what to do during the viva itself and how to deal with the possible outcomes.

Constructive and creative thinking Room B004 Adrian West (University of Liverpool) For research, human thinking is the most important resource we have. Like literacy and numeracy, it is a skill that can be learned and practiced. In research especially we aim to engage in fresh thinking and to hone the quality of our thinking skills. In this session we will explore some of the tools for Practical Thinking devised by Dr Edward de Bono. The techniques can make innovative thinking part of your everyday work style.

Boost your writing skills Room G13D Rachel Cowen (University of Manchester) This workshop will explore how to maximise your writing output and how to overcome common obstacles that reduce the effectiveness and productivity of your research writing.

Engaging others with your research Room H008 Ann Barlow (University of Manchester) It is increasingly necessary for researchers to contribute to promoting the public understanding of one’s own research field. This workshop is designed to encourage researchers to showcase their research to the wider public.

The workshop is designed to encourage researchers to think critically about the process of communicating research outcomes to a wide audience and a variety of stakeholders.

Workshop outlines


Workshop session B (14.30-15.15):

How to survive a viva Room J015 Judy Williams (University of Manchester) Using interactive discussion, participants will gain an insight into the viva process. The workshop will cover typical scenarios, how to prepare effectively, what to do during the viva itself and how to deal with the possible outcomes.

Enterprise for researchers Room B004 Rob Phillips (University of Manchester) Postgraduate and postdoctoral researchers are increasingly finding the need for a more diverse range of skills in the workplace. Whether in academia or the commercial world, innovation, networking and business skills are invaluable. This workshop will stimulate your interest in enterprise and provide advice on developing your entrepreneurial skills as a researcher.

Publish or perish – navigating the peer review process Room G13D Rachel Cowen (University of Manchester) There is increasing pressure on many postgraduate and post-doctoral students wishing to pursue an academic career to publish the results of their research as soon as possible. With so many journals to choose from, and so many people seeking to publish, actually getting to the stage of submission can be daunting enough. When this is combined with the possibility of rejection, coping with reviewers comments, and inevitably revising and at times substantially rewriting your work, many people would prefer to bypass this aspect of their work entirely. This workshop provides some basic, practical advice about how to go about getting your work submitted, reviewed and published in academic journals, and start you thinking strategically about how to get your work out there!

Using web 2.0 to enhance your research Room H008 Emma Gillaspy (University of Manchester) Information and Communications Technologies are changing the way in which people work, communicate and collaborate. Powerful new technologies such as blogging and web 2.0 now make it possible for anyone to communicate on global scale. In this session you will explore how you can use some of these technologies in your role as a researcher. In particular it will highlight how communications technologies are currently being used by the academic community and how you can raise your research profile.

Workshop outlines


Workshop session C (15.40-16.25):

Managing your PhD supervisor Room J015 Judy Williams (University of Manchester) Richard Hinchcliffe (University of Liverpool) Many research students believe that all of their problems could be solved if they had the dream supervisor. While this is probably untrue, it does highlight just how important the student-supervisor relationship is! This workshop will explore what is expected from both parties and how to build a good working relationship with your supervisor.

Postdoctoral perspectives Room B004 Elizabeth Wilkinson (University of Manchester) Panel: Dr Julian Breeze, Dr Rachel Oldershaw, Dr Sarah Withers, Dr Nerys Astbury, Dr Stephen Richardson Drawing on a range of experiences the panel of postdoctoral researchers will discuss how they got to where they are today and what life in research is really like. Participants are encouraged to participate in the session by asking the panel relevant questions about their experiences and background. If you are considering a career in research this is your opportunity to find out the gritty details.

Presentation skills: Feel the fear and do it anyway Room G13D Dee-Ann Johnson (University of Manchester) How do you best convince someone that your research is both interesting and important? Presenting your research findings skilfully is critical to getting a job, finding funding and building a career. This workshop will take a new look at ways to project yourself and your research to engage and influence your audience that will help you throughout your future career.

Engaging others with your research Room H008 Ann Barlow (University of Manchester) It is increasingly necessary for researchers to contribute to promoting the public understanding of one’s own research field. This workshop is designed to encourage researchers to showcase their research to the wider public.

The workshop is designed to encourage researchers to think critically about the process of communicating research outcomes to a wide audience and a variety of stakeholders.

Workshop outlines


Prof Dame Nancy Rothwell

Nancy Rothwell obtained a first class degree in Physiology in 1976, a PhD in 1978 and a DSc in 1987 from the University of London. Her early research identified mechanisms of energy balance regulation, obesity and cachexia. In 1984 she was awarded a Royal Society Research Fellowship and relocated to Manchester in 1987. Nancy was awarded a Chair in physiology in 1994, then a prestigious Medical Research Council, Research Chair in 1998.

Her current research focuses on the role of inflammation in brain disease and has identified the role of the cytokine interleukin-1 (IL-1) in diverse forms of brain injury. Her recent studies have begun to elucidate the mechanisms regulating IL-1 release and its action, and her group has conducted the first early clinical trial of an IL-1 inhibitor in stroke. She has recently served as president of the British Neuroscience Association, a council member of MRC, BBSRC, NESTA, The Academy of Medical Sciences and Cancer Research UK.

Nancy currently oversees a research group of about 20 scientists, with significant external funding, and is Deputy President and Deputy Vice-Chancellor at the University of Manchester. She is a member of the Royal Society Council, Vice President of the Royal Society, Chair of the Royal Society Education Committee, President of the Biosciences Federation, and a non-executive director of AstraZeneca. In 2003 she won the prestigious Pfizer Research Prize, in 2004 was elected a Fellow of the Royal Society and in 2005 was honoured with a DBE.

Nancy takes a strong and active interest in public communication of science and regularly gives talks to schools and the public and contributes to television, radio and press, particularly on sensitive issues in science. In 1998 she delivered the Royal Institution Christmas Lectures, televised by the BBC.

Speaker biographies


Prof Jane Worthington

Professor Jane Worthington completed her own PhD studies at The University of London in 1987. Since that time she has pursued a university based research career, initially at The University of Leicester and since 1990 at The University of Manchester. For the last 15 years she has researched complex disease genetics with the main focus being on the identification of genetic risk factors for rheumatoid arthritis. Publication of over 150 peer-reviewed papers is largely a reflection of the activities of her highly successful research team which has always had included multiple post-graduate students. Recognition of the importance of providing good quality training to research students led to her taking an active role in graduate education within The University of Manchester. Following many years as a post-graduate tutor, three years ago she became Postgraduate Director for The School of Translational Medicine in The Faculty of Medical and Human Sciences, with responsibility for over 250 PGR and PGT students. In a demanding senior academic position, the opportunity to interact with and supervise students undertaking research degrees, continues to be the most inspiring and enjoyable aspect of the role.

Dr Judy Williams

Judy Williams works in the University of Manchester as Research Training Manager within the Faculty of Medical and Human Sciences. The training team looks after the research and generic skills training, and career development needs of postgraduate students, early career researchers and academics. This involves delivering bespoke training programmes to meet the needs of a diverse cohort ranging from physicians to dentists to molecular biologists and health service researchers.

With the launch of the Vitae programme Judy has taken on the role as North West Hub coordinator. Judy coordinates and chairs the hub steering group, comprising members from each key Higher Education Institution in the North West. Vitae delivers a range of regional and national events to nurture and support students, staff and trainers. Judy is also employed as a Teaching fellow, and as such she is based in the Manchester Medical School within the Medical Education Research group

Speaker biographies


Dr Adrian West

Dr Adrian West is a skills trainer at the University of Liverpool. He has held UK and European research grants in the field of shared virtual realities, and is Research Director for the Edward de Bono Foundation U.K.

Dr Rachel Cowen

Rachel Cowen graduated in 1992 with an Honours degree in Biochemistry from the University of Leeds followed by a Masters degree in Information Technology from the University of Nottingham. She embarked on a research career in the field of oncology as a Research Assistant for Cancer Research UK and then in private R&D at Pfizer Central Research, UK. She returned to academia in 1997 and was awarded her doctorate in cancer gene therapy in 2001 from the University of Manchester. For the last 7 years she has worked as an MRC funded Research Fellow in the School of Pharmacy at the University of Manchester. In June 2007 Rachel took up her current position as Research Staff trainer in the Faculty of Medical and Human Sciences Training Team. Her role is to develop the research and generic skills of research staff and new academics in the Faculty, to support them in their careers and to promote their continued professional development. She is a member of the Vitae North West Hub Steering Group. She also retains a small research team funded by the Breast Cancer Campaign to investigate the potential use of a novel protein (opticin) for the treatment of metastatic breast cancer.

Dr Ann Barlow

Ann Barlow is Head of Skills Training and Development in the Faculty of Humanities at The University of Manchester. Although she is currently engaged with developing programmes for post-graduate and early-career researchers, Ann’s career in education has spanned all age groups and educational levels from infant special-needs to octogenarians learning in retirement. Prior to joining the Skills Training and Development Team in January 2009, Ann managed Courses for the Public at the University of Manchester where she was responsible for the design, development and delivery of courses for engaging the wider community with the research and scholarship of the University.

Speaker biographies


Dr Rob Phillips

Rob joined MEC as an Enterprise Fellow in 2004 before taking up the post of Enterprise Academic in 2006. Rob has a background in Biochemistry having done an MSc at UCL and a PhD at Southampton. He then worked for the National Institute for Medical Research in London and has a number of years experience working with patented scientific inventions. He is currently an Enterprise Academic at MEC and also works on technology transfer projects at the University of Manchester Incubator Company.

Dr Emma Gillaspy

Emma is the Vitae North West Hub manager. Based at the University of Manchester, Emma is responsible for delivering the Vitae programme across the Higher Education Institutions in the North West. Vitae provides career and professional development support for postgraduate researchers and research staff. Emma has a particular interest in the use of technology in researcher training.

Before taking on this role in July 2008, Emma previously managed the UK and Ireland contributions to Orphanet, a Europe-wide initiative to raise awareness and improve the diagnosis and treatment of rare diseases. Emma originally trained as a clinical molecular geneticist at the National Genetics Reference Laboratory (NGRL) Manchester following graduation from a PhD studying the genetics of Osteoarthritis.

Dr Richard Hinchcliffe

Richard was the national postgraduate representative for the British Association of American Studies 1998 –2000 during which time he completed his PhD. He lectured at Edge Hill University College and University of Central Lancashire from 1995 to 2001 when he became the Director of Postgraduate Training for the University of Liverpool. He is lead editor of Skills Training in Research Degree Programmes: Politics and Practice for the Open University Press.

Richard enjoyed a down and out pre university existence enjoying many temporary but interesting jobs including theatre stagehand, Narrow Gauge Engine Driver, Toyshop sales assistant and nightclub impresario. In 1980 he started working at Steamtown Railway Museum Lancashire as site engineer and then as manager. Married with two children he enjoys re-roofing houses, digging the garden and tidying the garage.

Speaker biographies


Dr Elizabeth Wilkinson

Elizabeth's career has spanned chemistry, software engineering, HR and manufacturing management and for the last 11 years, careers consultancy, currently as Head of Postgraduate Career Development at The University of Manchester. In addition to advising undergraduates, postgraduates and research staff, she has helped develop national careers resources for postgraduates, and was one of the founding members of the UK GRAD programme, (forerunner of Vitae), helping set up the North West Hub. She was one of the team who created the Manchester Leadership Programme, introducing undergraduates to leadership challenges involved in economic, environmental and social sustainability. This year, a similar programme for researchers is being piloted. She writes a regular careers blog for Manchester postgraduates at http://manchesterpgcareers.wordpress.com and is currently working on a website to support academic careers.

Ms Dee-ann Johnson

Dee-Ann is responsible for managing and delivering the communication activities associated with Graduate and Researcher Development in the Faculty of Engineering & Physical Sciences at the University of Manchester. Her role includes event management, developing training materials, workshop facilitation, and supporting researchers involved in public engagement. Following a career as a technical author, usability specialist, and communications project manager she moved to the UK to pursue a career in research and professional development.

Speaker biographies


SS1A1 (10:10, Room G13D) Motility of bacteria in microfluidic structures M Binz, C Edwards and DV Nicolau Keywords: bacterial motility, microfluidics, Serratia marcescens Bacteria, microorganisms that are critical to so many areas of human life and activities with both beneficial and deleterious effects, live in a wide range of environments presenting complex surfaces. Traditionally bacteria are cultivated on the surface of agar, an environment that is experimentally convenient, but it does not resemble the diverse micro-geometries of their natural habitat, such as abiotic (e.g., soil) and biotic (e.g., plant and other organisms) surfaces. In this work, microstructured environments were manufactured from a biocompatible polymer, polydimethylsiloxane, to test the motility behaviour of bacteria moving into complex, channel-like, closed geometries with different shapes and dimensions. The motile bacteria were imaged by light microscopy and observed in replicate trials. It was found that bacteria were capable of swimming through even narrow microchannels and that their swimming paths, velocity and modes were influenced by a combined effect of channel width and its complexity. These results show that the structured microfluidics environment can be used as a simple means to observe and quantify the movement and navigation behaviour of bacteria through geometrically heterogeneous environments. The motion of motile bacteria close to surface is relevant to understanding the early stage of biofilm formation or pathogenic infection. SS1A2 (10:25, Room G13D) Substance abuse among University students in Karbala/Iraq in May 2005 AM Al Mousawi Keywords: substance abuse, University student, Karbala/Iraq, smoking The World Health Organization (WHO) estimates that these three contributed together 12.4% of all deaths worldwide in the year 2000 as there are two billion alcohol users with 76.3 million persons with alcohol use disorders and 1.3 billion smokers and 185 million illicit drug users with 19 million persons with drug use disorders. The importance of youth population is clear from the fact that they represent a high percentage, under 15 years of age population approaching 50%, of the population in Africa and Asia and also they represent the working ages of the community A cross-sectional survey study performed in in University student in Karbala/Iraq in May 2005 about substance abuse prevalence. The study include whole University student of 2289 student and done through self answered questionnaire and shows the prevalence rates of tobacco smoking alcohol use and illicit substance use and some licit substance abuse. The study correlates these uses with demographic characteristics and other student’s characteristics, and explores student’s knowledge about substance abuse and causes for abuse in abusers and problems experienced by them. It may be the first wide scale substance abuse study done in Iraq.

SS1A3 (10:40, Room G13D) Early stage pancreatic cancer serum protein biomarkers S Murray, B Greenhalf, E Costello and J Neoptolemos Keywords: cancer, biomarkers, proteomics, early detection Introduction Pancreatic cancer has a poor prognosis. A reason for this is that it is often detected at an advanced stage when it is difficult to treat. If we could detect it earlier, we would have a better chance of treating it successfully. To try and detect pancreatic cancer earlier, we are looking for protein biomarkers in the patient’s blood that indicate the presence or development of the disease. Methods Blood serum was taken from patients with early stage pancreatic cancer, late stage pancreatic cancer, chronic pancreatitis, and healthy individuals. To identify which proteins were present in the blood serum, and to quantify the amount of each protein in each patient group we used iTRAQ (Isobaric Tags for Relative and Absolute Quantification). Results We identified 254 proteins and quantified 234 proteins with greater than 95% confidence. Of these proteins, 19 were up-regulated (≥3 -fold), and 21 were down-regulated (≥3 -fold) in the early stage cancer group compared to the control groups (chronic pancreatitis and healthy individuals). Conclusions We have found many potential serum protein biomarkers for early stage pancreatic cancer. These markers are now being validated with ELISA (Enzyme-linked immunosorbent assay) and Western Blotting

Abstracts Spoken presentations


SS1A4 (10:55, Room G13D) Using MRC framework for complex intervention for developing a culturally sensitive family intervention in Egypt. R Wahid Keywords: complex intervention, family intervention, schizophrenia, culture adaptation Background: Schizophrenia is a severe enduring mental illness that has a disruptive and distressing effect on the sufferers and family members who care for them. Family intervention is widely advocated as a standard model for the management of schizophrenia and for meeting the relatives’ needs for support and information. Despite the high proportion of Egyptian family members providing care to a relative with schizophrenia and the high rates of burden they report, no work has been done in terms of developing and assessing the effectiveness of such intervention in Egyptian context. Aims: To develop a culturally sensitive, acceptable and feasible family intervention for carers of people with a diagnosis of schizophrenia in Egypt. Methodology: Guided by the Medical Research Councils framework for the evaluation of complex health care interventions. A preliminary investigation was conducted using single group pre-test post-test design. Data regarding the effect of the intervention on the Carers’ knowledge about schizophrenia and data regarding the acceptability were collected. Results: 15 participants were offered the intervention. Knowledge level was compared pre and post intervention to assess change in level of knowledge following participation in the intervention. Post intervention showed a significant increase in the carers’ knowledge. Although, the feasibility of the intervention was challenging, the results indicated that the family intervention was highly acceptable. Conclusion: This study provides initial evidence of the efficiency of culturally sensitive family intervention for carers with ill relative suffering from schizophrenia in Egypt. Due to the methodological limitations, more rigorous investigation of the efficiency of the intervention in a larger scale RCT is recommended.

SS1B1 (10:10, Room C001) UK endodontists experience using ultrasonics for removal of intra-canal separated instruments A Madarati, A Qualtrough and D Watts Keywords: endodontic fractured instruments, ultrasonics, questionnaire Introduction When ultrasonics devices are used for removal of fractured instruments, there are some commonly used steps and procedures. Aims This questionnaire aimed to investigate the experience of UK endodontists with aspects of ultrasonic use for removal of intra-canal fractured instruments. Methods and Materials A questionnaire form comprised both close-ended and partially close-ended questions with a covering letter, explaining aims of the study and indicating that all information would remain confidential and anonymous, were sent to the 180 UK’s endodontists. Non-respondents were sent a reminder. After collecting the responses, data were analysed using frequencies and the chi-square test (p<0.05). Results 96.7% of endodontists use ultrasonics for removal of separated instruments. Only 22.2% never use coolant while ultrasonic tips are activated. Significantly, the highest proportion of ultrasonics users (53.1%) activate tips at a low or the lowest power-settings. Also, the highest proportion (52.6%) activate the tips for about 10s. Conclusion Endodontists showed different preferences in using ultrasonics for removal of separated instruments. Overall, they do not consider recommended procedures and steps. This may reflect the conservative attitude of these endodontists towards management of separated instruments using ultrasonics. Moreover, this suggests the importance of bringing up-to-date research findings into practice.



SS1B2 (10:25, Room C001) Hypertension; from rhythm to reason A Bradbury Keywords: hypertension, endothelial dysfunction, wavelet analysis Endothelial dysfunction is a common feature of essential hypertension but the exact nature of this dysfunction is not fully understood. Previous studies have observed a muted response to the vasodilator acetycholine in hypertensive subjects. Here, by applying the techniques of dynamic analysis, we show that endothelial dysfunction in patients being treated for essential hypertension is associated with poor or lacking response of endothelial cells to mechanisms that have been linked to pulsatile shear stress forces. Our analysis characterises the dynamics of fluctuations in acetylcholine stimulated blood perfusion measurements in hypertensive and normotensive subjects. It shows a statisitically significant difference in low frequency oscillations (0.005-0.0095Hz) between the two groups. Activity in this frequency interval has previously been associated with endothelial derived hyperpolarisation factor which has been associated with endothelial response to pulsatile shear stress. Our analysis shows no improvement in this aspect of endothelial functionality across the wide range of medications taken by our subjects. SS1B3 (10:40, Room C001) Modelling organ function after radiotherapy E Rutkowska, C Baker, A Nahum Keywords: radiotherapy, complications, modelling During external beam radiotherapy radiation dose is deposited in normal tissues situated in the beam paths, sometimes resulting in complications. The risk of causing complications could be reduced with a greater understanding of organ response to irradiation. However, studies of dose-volume effects in normal tissues during radiotherapy are generally limited by small patient numbers and the influence of confounding factors. A computer model has been developed which can simulate the 3D distribution of radiation-induced tissue damage and the resulting organ response. Studies on pseudo-clinical data generated by this model give insight into the methodology of studying dose-volume effects and translating such clinical experience into optimising future radiotherapy treatment planning. The literature has been studied to find suitable parameter values for the developed 3D model. Radiobiological experiments on animals and cells and analyses in some clinical studies provide information on local tissue dose effects, while there is only sparse information about how different patterns of tissue damage influence the overall organ response. A discussion around how the function of an organ depends on the organisation of its subunits is invited.

SS1B4 (10:55, Room C001) Clotting analysis of blood samples from intensive care unit patients B Sempasa Keywords: clot stability in plama, whole blood Introduction: Patients in the intensives care unit have complex haemostatic changes, which may be either procagulant or anticoagulant. Global assays may reflect a patient’s net haemostatic balance and can contribute to pro- or anti-coagulant assessment. In this project, global assays were used to investigate both coagulation and fibrinolysis in samples taken from ICU patients. Materials and Methods: Whole blood samples were taken from 11 patients from the ICU, 9 haemophiliacs and 10 healthy individuals. These samples were analysed using coagulation screens, individual factor assays and global assays [calibrated automated thrombography (CAT), whole blood and plasma low- dose tissue factor activated ROTEM and the clot formation and lysis (CLoFAL) assay]. Results: Factor levels were decreased in ICU samples compared to healthy individuals (PT, p=0.0002; APTT, p=0.0004; FII, p=0.0001; FVII, p=0.0044; FVIII, =0.0001; FX, p=0.0005). CAT showed that the initiation of thrombin generation (11.68 + 1.827), the ttPeak (42.83 + 17.15) and the start tail (39.60 + 4.594) were markedly reduced in ICU samples The average ETP (1034 + 152.2) in these samples was also reduced. The ROTEM assay showed a prolonged clotting time and the rate of clot formation in the ICU sample group. The CLoFAL assay showed reduced clot stability (p<0.01) ICU sample groups. Conclusion: ICU sample coagulation was abnormal compared to that of healthy volunteers. Several factors such as the fibrinogen and procoagulant factors influenced coagulation and the rate of thrombin generation. The clot stability in ICU samples was also found to be abnormal compared to the recorded in the healthy volunteer group. Global assays showed that even though there is a deficiency in factor levels and the initiation of coagulation is delayed, once started, clot formation was normal and in some patients enhanced.



SS1C1 (10:10, Room B004) Why should we listen to the stories told by people with epilepsy? D Snape Keywords: narrative research, epilepsy, lived experience Narrative inquiry is one of many kinds of research gathered under the umbrella of qualitative research approaches. Interest in narrative has risen with the emergence of postmodernism and its scepticism towards the ‘meta-narratives’ underpinning scientific theory and knowledge . Central to all narrative inquiry is attention to the potential of stories to give meaning to people's lives, and the treatment of data as stories. However, as a research approach it does not have any single heritage or methodology and those who practice it draw upon diverse sources of influence; often using an amalgam of methods. Firstly, this paper will discuss the theoretical influences on my own thinking about what narrative inquiry as a methodology might be and how these influences guided my own narrative practice. Next, I draw on examples of work published by others in the field of illness narratives and from stories told by my own participants to demonstrate why narrative may be of benefit to the field of epilepsy research. SS1C2 (10:25, Room B004) The challenge of embracing a wider epistemology C Kennedy Keywords: participation, mothers, experience, empowerement, food This project is a participatory (cooperative) inquiry initiated with a group of 13 mothers from a disadvantaged community to explore their experiences of bringing up and feeding young children. Unanticipated challenges served to derail my preconceived notions of how the research would proceed and the nature of the knowledge it would generate. As a former biologist, nurse, health visitor and children’s centre manager I operated from a standpoint in which rational theory directs practice. In contrast within the participatory paradigm I had selected for my research project theory arises from practice. As a professional I am responsible for decision making and giving directive advice but as a researcher I espouse a radical participative standpoint based upon human flourishing and use of democratic process at all stages of the research. The challenges and experience of reconciling the dialectical perspectives of my educational and professional formation as a positivist and my experiences as a participatory researcher have enabled me to embrace a wider epistemology of different kinds of knowledge. My values as a health professional remain unchanged but my research now leads me to recommend a more holistic empowerment model of health promotion for mothers in disadvantaged communities.

SS1C3 (10:40, Room B004) Touch and the body in psychotherapy K Dymoke Keywords: touch, psychotherapy, relationship, communication, embodiment The use of touch in therapy requires specialist skills as touch can be powerful for both the therapist and client. The therapist needs to know not only HOW to administer touch in the therapeutic process but also to be informaed and to consider the social cultural and subjective preconceptions that influence it's function and efficacy. The key aspects of a case study research project will be presented, the aims and objectives and methods used, to analyse the impact of touch in movement psychotherapy for Learning Disabled Adults. With reference to literature and experience, the presentation will question contemporary discourses and illustrate counter arguments to non-touch policies causing fear and censorship of touch. This is a practice based study and so the presentation will involve some audience participation to aid reflection and embodied response.



SS1C4 (10:55, Room B004) The relationship of well-being to intrinsic and extrinsic motivation among dental students A Montasem Keywords: dental students, intrinsic/extrinsic goals, well-being, need satisfaction, self-determination theory Aims: Dental study is known to be stressful and dental students often experience poor psychological well-being (Gorter et al., 2008). Previous research has shown that successful goal striving is linked to improved subjective well-being (e.g. Koestner et al., 2002). The present research seeks to analyse the personal goal system of dental students’ using the self-concordance model (Sheldon & Elliot, 1999). Self-concordance describes the extent to which goals are perceived to be congruent with a person’s core, intrinsic, motives and values. Self-concordance is hypothesised to improve the likelihood of goal attainment and, thus, positive well-being; self-disconcordant goals are expected to have the opposite effect. Materials and Methods: 187 students from Liverpool Dental School completed a questionnaire (time1) that contained measures of personal goals (Little, 1993), the extent to which those goals are self-concordant (Sheldon & Elliot, 1999) and goal difficulty/importance. Goal attainment and subjective well-being (negative/positive affect, life satisfaction) was measured two months later (time 2). Results: Structural equation modelling showed that intrinsic goal motives positively predicted emotional well-being (beta = .25, p <.001). Extrinsic goal motives predicted negative emotional well-being, but only, if mediated by goal difficulty (beta= .33, p < .001; beta= .19, p < .001). Goal accomplishment was unrelated to other study variables. Conclusions: Findings support the link between goal concordance and affect, but not the role of goal attainment. Causal relationships cannot be demonstrated by the methods used in this study, and further research could examine whether interventions that promote self-concordant goal setting will improve subjective well-being in Dental students. Methods of encouraging dental students to set concordant goals are discussed.

SS2A1 (11:40, Room G13D) Use of Platelet Rich Plasma (PRP) as a biologic modulator M Badr, P Coulthard and R Oliver Keywords: bone, graft, enhancment, biologic, modulators Introduction: Platelet Rich Plasma (PRP) is believed to be of a potential enhancing effect on hard and soft tissue healing. Conflicting results from a wide range of study designs suggests that further controlled clinical trials are needed to consider the PRP definitive reconstructive role. Aim: The aim of this project was to evaluate the PRP as a biologic modulator for graft and soft tissue healing. Materials and Methods: in a randomised controlled trial, patients were randomized to test and control groups, both received iliac crest bone graft to the maxilla. PRP was mixed with the test group bone grafts. Implant stability measurements were recorded at placement and exposure time. Analysis: Multiple linear regression analysis was used taking the patient as the unit of measurements. Results: posterior implants in the test group showed higher stability values. Conclusion: PRP could be of valuable clinical effect on implant stability.



SS2A2 (11:55, Room G13D) Increased cortical surface area of left Brodmann area 44 in male orchestral musicians correlated positively with years of musical performance I Abdul-Kareem and V Sluming Keywords: musicians, Broca's region, surface area Background and purpose Environmental challenges may result in adaptive changes in the brain. Musicians’ brains have long been studied for possible structural brain differences in response to skill acquisition. In addition to language, Broca’s region (comprising Brodmann areas 44 and 45) is crucial for several musically relevant abilities, notably audiomotor integration. Measuring cerebral cortical surface area is of considerable theoretical interest as it was hypothesized that the number of neurons in a brain region is proportional to its surface area. Materials and methods Twenty six right handed male orchestral musicians were compared to 26 musically naive age-, sex- and handedness-matched subjects. T1-Weighted MRI images were obtained at 1.5T scanner. Cortical surface area for Brodmann areas 44/45 of both hemispheres was measured using automatic user independent method. Result Multivariate analysis of variance shows that musicians have significantly increased cortical surface area of left BA44 (F1,49 =4.13, p=0.02) with no significant results in left BA45, right BA44/45. Results were positively correlated with years of musical performance (r=0.5, p=0.01). Conclusion We hypothesize that prolonged skill acquisition in the form orchestral musical performance is an environmentally enriching activity resulting in structural reorganization through increased cortical area of a brain region essential for that performance.

SS2A3 (12:10, Room G13D) Raised maternal body mass index (BMI) is associated with altered activity of placental nutrient transporters A Ditchfield, S Greenwood, T Mills, M Wareing and C Sibley Keywords: obesity, pregnancy, placenta, nutrient, fetus Background: Maternal obesity is associated with increased risk of pregnancy complications including stillbirth, fetal developmental anomalies and delivery of a baby significantly larger, or smaller, than expected for gestational age. Normal fetal growth and development depends on an appropriate supply of maternal nutrients by transport across the placenta. Here we test the hypothesis that placental nutrient transport is altered in women with raised BMI compared to women of normal weight. Method: Maternal BMI was recorded at the first antenatal visit. Placentas were collected at term and the activity of the System A and System β amino acid transporters measured as the sodium-dependent uptake of specific substrates 14C methylaminoisobutyric acid and 3H taurine respectively. Results: Placental System A activity was significantly higher in overweight (BMI 25-29.9; n=6) compared to normal weight (BMI 18.5-24.9; n=7) women (p<0.005). In contrast, System β activity was markedly lower in placentas of obese (BMI ≥30; n=7) compared to normal weight women (p<0.004), and negatively correlated to maternal BMI (p<0.05; n=20). Conclusions: The differential effect of raised BMI on System A (increased) and System β (reduced) activity supports the possibility that inappropriate placental nutrient delivery underpins disorders of fetal growth and development associated with maternal obesity.



SS2A4 (12:25, Room G13D) The relationship between muscle activity, stature recovery and clinical outcome in chronic low back pain S Lewis, N Fowler, P Holmes, S Woby and J Hindle Keywords: back pain, stature recovery, muscle activity Intervertebral discs have a high fluid content and lose height when the spine is loaded, which impacts on overall body height. Previous research has shown that individuals with chronic low back pain (CLBP) recover this height more slowly and this is thought to be linked to the increased back muscle activity which tends to be exhibited by CLBP patients. The aim of this study was therefore to investigate the relationship between stature recovery and muscle activity in CLBP patients. The links with a number of psychological factors were also investigated since they are acknowledged to be important in the development of the condition, possibly via their effect on muscle activity. Muscle activity while in a relaxed standing position was assessed via electromyography (EMG) and stadiometry was used to measure the amount of stature recovery during a 40-minute unloading period. Questionnaires assessed a number of psychological factors. Preliminary results involving sixteen patients support the hypothesis of a correlation between stature recovery and muscle activity. Significant relationships were also found between stature recovery and pain, disability and anxiety. SS2B1 (11:40, Room C001) Physical characterization of multicellular tumour spheroids - toward composition and growth characteristics A Ur Rahman, DA Berk and A Pluen Keywords: multicellular tumour spheroids, viability, extracellular volume, composition and growth characteristics Tumour tissues offer resistance to penetration of therapeutic molecules. Multicellular tumour spheroids (MCTS) have been proposed as model of in-vivo tumour tissue. The aim of study was to explore the composition and growth characteristics of MCTS along with the age of spheroids through confocal microscopy and haemocytometry. Our results show that growth of spheroids was linear over the first week and after 9th day the growth rate decreased. Extracellular volume per cell also show a complex dependence on spheroid age (P<0.003). Viable fraction of cells varied as a function of spheroid age (P<0.0004). The data obtained was applied to a simple model of spheroid structure in which non-viable cells were covered by a shell of viable cells. The results suggest that the shell of viable cells grow during the first week, stabilizes at a maximum thickness of around 80μm at day 7 of spheroid age and then declines. In contrast, the core of non-viable cells continues to grow, albeit at a slow rate during the second week. This characterisation of distinct regions within the MCTS will allow us to better interpret the results of drug and drug-carrier uptake measurements.

SS2B2 (11:55, Room C001) Systemic sclerosis serum increases endothelial cell apoptosis and activation in neutrophil-endothelial cell co-cultures: a role for interleukin 6 T Barnes, D Spiller, M Anderson, S Edwards and R Moots Keywords: systemic sclerosis, endothelial cells, interleukin-6 Purpose: Endothelial activation is pivotal to the pathogenesis of systemic sclerosis (SSc). We have demonstrated that SSc neutrophils have a functionally distinct phenotype. This study examined the potential for neutrophils to cause endothelial cell apoptosis and activation in co-cultures containing SSc serum. Methods: Human dermal microvascular endothelial cells (HDMECs) were cultured with healthy neutrophils and 25% control or SSc serum for 24hrs. AnnexinV-FITC and an APC-conjugated E-selectin antibody were used to measure apoptosis and endothelial cell activation respectively. Fluorescence was measured using confocal microscopy. Results: Co-culture of neutrophils and HDMECs with SSc serum resulted in more apoptosis (p=0.005) and E-selectin expression (p=0.01) than control serum. SSc serum alone didn’t increase endothelial cell apoptosis or E-selectin expression. The effect of SSc serum on E-selectin expression was abrogated by immunodepletion of interleukin-6 (IL6) (p=0.046) and sgp130, an inhibitor of IL6 “transignalling" (p=0.033). Conclusions: This in vitro model shows evidence of increased endothelial cell apoptosis and activation in the presence of SSc serum. IL6 plays a significant role in this effect. Endothelial cells don’t express the interleukin-6 receptor (IL6R), only responding to IL6 when bound to soluble IL6R. This “transignalling” occurs through the gp130 receptor. Neutrophils are the major source of soluble IL6R.



SS2B3 (12:10, Room C001) Investigating the effect of the immunosuppressant Mycophenolic acid on neutrophil function L Hopcraft, M Howse, A Bakran and S Edwards Keywords: neutrophils, immune function, immunosuppression, signalling Following renal transplant, patients are immuno-suppressed to prevent acute rejection. Mycophenolate mofetil (MMF) is an anti-proliferative that target T-lymphocytes (acquired immunity). However, bacterial infections are common, despite any known effect on innate immunity. Neutrophils are innate-immune cells that destroy bacteria with granule enzymes and reactive oxygen species (ROS). The active ingredient of MMF, Mycophenolic acid (MPA, 100μg/mL) decreases neutrophil ROS production (p<0.001), and their capacity to kill S.aureus by 30% (p<0.05). MPA also decreases secretion of granule enzymes (MPO, lactoferrin) (p<0.05). It is likely neutrophil degranulation is the inhibitory mechanism of MPA, as MPO is required for secondary oxidant production (e.g. HOCl). Receptors stored in granules are also effected (CD11b, CD18) (p<0.05), but no effect on molecules stored in secretory vesicles was observed (e.g. CD16). However, cleavage of cell-surface CD16 was inhibited, as this is mediated by proteases stored in granules (p<0.01). Electron micrographs showed MPA had no effect on granule number or morphology, nor any effect on phagocytosis. The number of dividing bacteria present within MPA treated cells was increased (p<0.01), indicating a lack of intra-phagosomal killing, confirming initial observations. This suggests that T-cell targeted immuno-suppression may directly cause increased susceptibility to bacterial infections via inhibition of neutrophil function.

SS2B4 (12:25, Room C001) Development of topical anti cancer medication for post operative patients with head and neck cancer MT Boyd, TM Jones, A Behrendt and J Backer Keywords: clear, focused, informative, groundbreaking Objectives To evaluate the utility of a novel epidermal growth factor receptor (EGFR)-targeted cytotoxic drug which might be applied topically to residual tumour cells exposed following surgery. Ultimately with the aim of reducing the need for post-operative adjuvant chemo-/radiotherapy. Such drugs are inherently highly toxic and thus we are investigating the protective potential of Cetuximab, a monoclonal antibody to the EGFR. Using such a combination of drugs may provide a way of targeting tumour cells and inhibiting systemic toxicity thus increasing the therapeutic envelope. Methods Laryngeal squamous carcinoma cells were treated in vitro with a novel drug: EGF-SubA to evaluate drug toxicity +/- low concentrations of Cetuximab. Cells were monitored for proliferation and viability. Results EGF-SubA inhibited growth of laryngeal squamous cells at low concentrations. The application of Cetuximab prior to the addition of EGF-SubA significantly improved cell survival (P<0.01) completely rescuing cells from the effects of EGF-SubA. Conclusions In vitro EGF-SubA is highly cytotoxic to laryngeal squamous cells. Importantly, we have demonstrated that this toxicity can be completely abrogated in vitro by low doses of Cetuximab. This is an important proof of principal for a combined toxin-protectant approach that would allow safe use of a targeted tumour therapy



SS2C1 (11:40, Room B004) Development of an integrated miniaturised real time polymerase chain reactor A Markey Keywords: miniaturisation, PCR, quantitative measurement Whilst traditional sample preparation and polymerase chain reaction (PCR) analysis has enabled great advancements in biomedical research applications several caveats, such as sample loss, contamination and the bulk preparation and analysis of heterogeneous samples, still remain which hinder an accurate quantitative analysis. A proposed solution to these problems is an integrated miniaturisation of all sample preparation and analytical steps enabling the analysis of individual cells. This will generate an absolute unit of molecules per cell, crucial for precise quantification of data. A miniaturised device has been designed and fabricated based on the principle of aqueous droplets, containing the reaction mixture, suspended in a continuous flow of immiscible oil carrier fluid. The stable production of these droplets has been achieved at various flow rates which were unaffected by the thermocycling process. The temperature ramp rate (5.83oC/second) of this device was shown to be superior to that of a conventional thermocycler (4.8oC/second) allowing faster analysis of samples. Whilst further work needs to be carried out to optimise this device for the conditions of amplification the justification for the necessity of such a device has been shown along with the initial calibration results. SS2C2 (11:55, Room B004) p53 induces cell motility and invasion by upregulation of MDM2 in renal cell carcinoma R Polanski, A Noon, M Maguire, N Vlatkovic and MT Boyd Keywords: MDM2, p53, RCC, aggressiveness, motility Co-over-expression of p53 and MDM2 correlates with poor outcome in RCC (renal cell carcinoma, the most frequent type of kidney cancer) patients. However, over-expression of p53 alone does not result in such high tumour aggressiveness. Therefore, we hypothesized that some activities of upregulated MDM2 are responsible for an aggressive phenotype of RCC and we set out to investigate the role of MDM2 in RCC. We show, that p53 is nearly always wt in p53/MDM2 over-expressing tumour samples. Moreover, we found that upregulated p53 is responsible for over-expression of MDM2 as depletion of p53 results in reduction of MDM2 levels in RCC cells. We demonstrate that elevated levels of MDM2 correlate with increased motility and invasiveness in RCC cell lines and that this can be reversed by depletion of either p53 or MDM2. Additionally, we identified a novel, MDM2 binding protein NME2. Our motility and invasion studies revealed that high levels of MDM2 in RCC cell lines can oppose NME2-mediated motility suppression. In cells that expressed lower levels of MDM2, NME2 retained its ability to act as a motility suppressor. These results suggest a possible mechanism for MDM2-mediated, motility promoting action whereby increased MDM2 expression blocks NME2 mediated motility suppression.

SS2C3 (12:10, Room B004) Characterisation of TMEM114, a protein associated with dominant congenital cataract GJ Maher, GCM Black and FDC Manson Keywords: genetics, eye, animal model, expression Introduction: Mutations in a novel transmembrane protein (TMEM114) are associated with juvenile cataract. Objectives: 1) Investigate a role for TMEM114 in development of the eye. 2) Determine the functional effect of TMEM114 missense variants found in congenital cataract patients. Methods: Developmental expression of Tmem114 determined using RT-PCR. Cellular localisation of proteins determined by expression in polarised MDCK II epithelial cells, detected using antibodies and visualised using immunofluorescence. Knockdown of Tmem114 expression in the animal model Xenopus tropicalis achieved by injection of fertilised eggs with antisense molecules directed against Tmem114. Results: TMEM114 is expressed in the developing eye of humans, mice and frogs. Knockdown of Tmem114 in frogs results in abnormal eye development, predominantly microphthalmia. In transfected mammalian cells, Tmem114 localises to the cell membrane; bioinformatic structural analysis predicts a role in cell-cell adhesion. In transfected mammalian cells, the missense variant p.A147V is expressed at lower levels than the wildtype and fails to localise to the cell membrane. Conclusions: Tmem114 is necessary for ocular development in vertebrates. The missense variant p.A147V found in cataract patients is likely to be non-functional as it is mislocalised and expressed at lower levels than the wildtype.



SS2C4 (12:25, Room B004) Phenotype-genotype correlations in Amelx and Enam murine models of Amelogenesis imperfecta TL Coxon, AH Brook and RN Smith Keywords: mineralisation, mouse models, tooth development Introduction: The tooth is an accessible model for investigating complex ectodermal-mesenchymal interactions and extracellular matrix-mediated events during development. Amelogenesis provides an excellent example of biomineralisation. Enamel defects in humans and mice have been associated with mutations in the genes Amelx and Enam which encode for the matrix proteins amelogenin and enamelin. As variation exists in humans between affected individuals with the same mutation, between the dentitions in the same individual and even between teeth in the same dentition, accurate measurement of the phenotype of mice with anomalies of these genes in comparison with wild-type mice could provide insight into the multifactorial – genetic, epigenetic and environmental – influences on amelogenesis. Objectives: To characterise and compare two Amelogenesis Imperfecta (AI) ortholog mouse model phenotypes with Amelx (OMIM300391) and Enam (OMIM606585) gene mutations; to measure the mandible and incisor dimensions, and enamel mineralisation to quantify phenotypic variation. Methods: Five left and five right hemi-mandibles and incisors were extracted from each group of Amelxwt, Amelx+/-, Amelx-/y, Amelx-/-, Enamwt, Enam+/- and Enam-/- mice. Mandibles and incisors were phenotyped by morphometric image analysis. Enamel surface mineralisation was quantified by customised colour and whiteness software and algorithm. Results: Significant variation was observed between one or more of the Amelx groups in 25% of all mandible (≤0.029), 81% of all incisor (≤0.009) and 84% of all colour and whiteness (≤0.040) variables; and between one or more of the Enam groups in 46% of all incisor (≤0.037) and 41% percent of all colour and whiteness variables (≤0.012). The novel morphometric and colour and whiteness phenotyping was validated by a high degree of multiple operator reliability. Conclusions: Enamel matrix proteins were important in tooth and alveolar bone development and morphogenesis, supporting a multifunctional role of amelogenin. Morphometric and colour and whiteness assessment explicitly related phenotype to genotype in two murine models of AI; Amelx and Enam mutations affected distinct enamel surface regions which correlated to specific stages of amelogenesis. Quantitative investigation of AI improves phenotypic discrimination and differentiation providing insight into biomineralisation.



A01 Placental vascular smooth muscle cells: Expression and function of potassium channels M Brereton, S Greenwood and M Wareing Keywords: placenta, potassium phannels, smooth muscle Fetal growth restriction (FGR), a complication of pregnancy whereby the fetus does not reach its genetic growth potential, is associated with increased vascular resistance within the fetoplacental circulation. The smooth muscle cell (SMC) layer of a vessel controls vascular resistance and its function is potentially altered in FGR. Therefore, in vitro models to freshly isolate and culture SMCs from chorionic plate arteries of the human placenta were established to study the expression and function of potassium (K+) channels, important regulators of SMC contraction. SMCs were obtained from dissected arteries by either enzyme digestion or cell outgrowths from cultured vessel explants. Immunofluorescence confirmed the cells isolated using both methods were smooth muscle, displaying positive staining for α-smooth muscle actin, and expressed Kv1.5, BKCa, KIR2.1 and KIR6.1 channel isoforms. Whole-cell current profiles of freshly isolated cells, obtained using patch-clamp techniques, were classified into four groups based on activation kinetics and current density. The Kv channel blocker 4-aminopyridine (5mM) inhibited positive outward current (66 ± 12.8%; n=4). Therefore, Kv channels, potentially Kv1.5, are functionally expressed in chorionic plate arterial SMCs of normal pregnancy. Studying Kv channels in FGR will reveal whether they could be a therapeutic target to reduce vascular resistance. A02 Development of lentiviral mediated stem cell gene therapy for Mucopolysaccharydosis Type IIIA (MPSIIIA) A Sergijenko, A Smith, K Langford, F Wilkinson, R Wynn and B Bigger Keywords: lenitiviral gene therapy, stem cells MPSIIIA is caused by a dysfunctional substrate degradation pathway in lysosomes due to the lack of sulfamidase enzyme. As no treatment is currently available, we are developing a lentiviral gene therapy to overdrive sulfamidase expression in donor haematopoietic stem cells (HSCs) prior to transplantation. We have demonstrated pre-clinical efficacy of this approach using a non-clinical lentiviral vector in mouse model of MPSIIIA. The objectives are to i) generate a clinically applicable vector, ii) develop an efficient transduction protocol for HSCs iii) assess vector safety in preparation for clinical trial. We have generated high titres (2x108 IU/ml) of a new lentiviral vector with a clinically approved backbone incorporating a human promoter. Transduction conditions have been optimised using cytokines and chemicals to improve infectivity, viability and stemness of mouse HSCs. The addition of genistein with cytokines improved transduction by 13%. This will be translated to human CD34+ cord blood-derived HSCs. The risk of vector genotoxicity was assessed using an in vitro immortalisation assay. After 4 weeks in culture, no clones were detected when using a low dose of the lentiviral vector. This is a promising therapy and future experiments are aimed at translating this mouse study into a clinical trial for MPSIIIA.

A03 Transcriptional pathways in skeletal muscle following electrical stimulation LM Fisher, AG Fisher, JM Coulson and JC Jarvis Keywords: transcription, stimulation, qRT-PCR, fibre-type, transformation A large number of transcriptional pathways have been implicated in the response of muscle to an altered activity pattern. This is not surprising in the sense that muscle plasticity involves changes in gene transcription and translation for multiple sub-cellular systems. The transformation of muscle from a fast fatiguable type to a slower more fatigue-resistant type is a paradigm in which the time course and sensitivity to stimulus can be investigated in a systematic manner: by means of an implantable stimulating device the activity dose can be closely controlled. We are searching for thresholds of activity that cause step changes in transcription. The existence of such thresholds would correspond with the observation that muscle fibres fall into a number of classes rather than showing a continuous range of phenotype in vertebrate muscles. We have measured by qRT-PCR the transcript levels in rat muscle after periods of muscle stimulation having designed qRT-PCR primer pairs to monitor the expression of key transcripts involved in the adaptive response. These include primers for the myosin heavy chains I, IIa and IIb, IGF-1, MGF, Myostatin, PPARδ and PGC1α. Our first conclusion is that transcript levels for transcription factors change more consistently after 3 hours of changed activity than transcript levels for contractile proteins. After one week of stimulation however, the changes in transcript levels for contractile proteins are also changed consistently and significantly. We have begun to investigate the time course of these responses within the first week to identify the earliest time point at which a new transcriptional state is achieved and at which it would be appropriate to perform a comparative study of the graded effect on transcription of graded activity patterns.

Abstracts Poster presentations


A04 Executive and frontal dysfunction in an fMRI study of cerebral small vessel disease G Lumley, J Goodwin, LM Parkes and HCA Emsley Keywords: cerebral small vessel disease, fMRI Cerebral small vessel disease (cSVD) is an important but under-investigated cause of lacunar stroke, leukoaraiosis and vascular dementia. We are investigating novel imaging markers of cSVD and their correlation with cognitive dysfunction. Eleven patients with cSVD and 16 age- and education-matched controls underwent a battery of cognitive tests and a 3T MRI protocol with structural and arterial spin labelling sequences, enabling collection of simultaneous blood oxygenation level dependent (BOLD) and cerebral blood flow signal during a Stroop task. Structural scans showed changes attributable to cSVD. Patients showed executive dysfunction with significant (p<0.05, two-tailed t-test) deficits on trail-making A, verbal fluency and digit symbol tests, with the latter showing the most striking difference (patients 38 ± 9, controls 57 ± 10, p<0.00005). During the Stroop task, mean accuracy was reduced and mean response time significantly increased. In frontal regions patients showed a non-significant increased BOLD response to the Stroop task, and decreased neurovascular coupling, which was significantly correlated with digit symbol score. These preliminary results suggest concordance with previous studies of structural changes in cSVD, though are limited by the small sample size. The promising results support this methodology to evaluate functional versus structural images and their correlation with cognitive dysfunction.

A05 Employing network interactions to reveal pathogenesis targets related to MYCN gene amplification in neuroblastoma N Shipillis, F Salway, H Westerhoff and PJ Day Keywords: systems biology, neuroblastoma Neuroblastoma (NB) is one the most common cancers of infancy and childhood. Possession of amplified MYCN gene sequence is related to aggressive disease and poor prognosis with a distinction established relating the poor survival of patients to increased numbers of gene copies of MYCN. It has been recently suggested that dysregulated oncogenes and their products in general might be more resistant to treatment while interaction with other genes within the affected networks could serve as better targets that could be identified using Systems Biology approaches. In this research programme we will try to establish some of the details regarding the mechanism of MYCN gene amplification in relation to NB. Firstly, the path of the MYCN gene towards functional MYCN-MAX heterodimer will be modeled, using data from different neuroblastoma cell-lines with varied genotypes and biomarkers. This model will be used for simulating MYCN gene-copy number perturbations, the findings will be tested experimentally and finally additional biomarkers will be added to the model accordingly. The outcome of this study will be to provide details about the MYCN amplification mechanism and its relation to other NB biomarkers, help to better understand NB, potentially improve prognostic and therapeutic strategies and identify new therapeutic targets.



A06 Modelling MYCN expression in neuroblastoma; perturbations with 13-cis-retinoic acid ME Kelly, PJ Day and G Baier Keywords: neuroblastoma, systems biology, 13-cis-RA, MYCN, qPCR Neuroblastoma is a common paediatric malignancy. Amplification of the MYCN gene confers a poor prognosis and automatically denotes patients as high risk. High risk patients receive 13-cis-RA treatment, but response is heterogeneous, only some patients respond. This project aimed to determine the cause of this heterogeneity using a systems biology approach. The ‘biological’ MYCN regulatory network was identified from the literature. Relevant molecules were included in the ‘computational’ network and interactions described using differential equations; simulations were executed. MYCN copy number and MYCN expression were quantified on a panel of nine neuroblastoma tumour cell lines using qPCR and the model was fitted to these data. Simulations revealed that 13-cis-RA is able to perturb the MYCN regulatory network up to a given MYCN copy number/mRNA concentration. Beyond this threshold the network displays a bistable response to 13-cis-RA perturbation. Wet experimentation and model optimisation revealed that MYCN expression is regulated by other molecules not included in this model. Bistability allows one of two possible phenotypes for the same 13-cis-RA dose, and could in part explain the heterogeneity in clinical response. MYCN copy number should not be used to stratify patients into risk groups, as it does not always predict MYCN expression.

A07 Investigating cisplatin resistance in neuroblastoma cell lines JA Logan, WB Dunn, F Salway, M Brown, R Goodacre and PJR Da Keywords: neuroblastoma, cisplatin, resistance, metabolomics, qPCR Neuroblastoma is a malignant childhood tumour with a heterogeneous clinical course. This cancer is typically sensitive to the cytotoxic agent cisplatin, but resistance can develop following treatment. The aim of this preliminary study was to identify potential mechanisms of cisplatin resistance in neuroblastoma cell lines, employing parallel analysis of the metabolome and the transcriptome. The neuroblastoma cell lines SHEP1, IMR32 and Kelly were exposed to three doses of cisplatin, generating sub-populations of cells with 1.7 to 5.3 -fold increased cisplatin resistance. Analyses were performed on the metabolic footprint, intracellular metabolites, and RNA. Cisplatin-resistant cells were both metabolically and transcriptionally distinct from their cisplatin-sensitive counterparts. Metabolic differences were more pronounced in MYCN-amplified cell lines, and included decreased intracellular levels of 4-amino butyric acid (GABA) in cisplatin-resistant cells. Differences in gene expression included increased expression of ERCC1 and GSTP1 in cisplatin-resistant cells. Expression of MYCN was also increased, but did not achieve statistical significance. Preliminary observations suggest that MYCN expression could contribute to resistance mechanisms at the level of the metabolome. Further work will clarify these potential resistance mechanisms, and translate this knowledge into clinically useful molecular biomarkers and therapeutic targets.



A08 Investigation of the differentially expressed C-FABP & FABP-PM in human prostate tissues and cell lines: Histopathological and molecular biology study MI Malki, C Foster, S Foorotan and Y Ke Keywords: prostate cancer, C-FABP, FABP-pm Prostate cancer is the most commonly occurring from non-tobacco related cancers of man in the developed world. Our understanding of the molecular pathology of prostate cancer is currently very limited. At present, clinical therapy focuses on androgen blockage by physical or pharmaceutical castration. Previous work in our pathology laboratory has led to the identification of several genes whose elevated expression may contribute to the malignant progression of the prostate cancer cells. Tow of these genes is that coding for C-FABP and FABP-pm. The work described in this research is aimed to study further the possible role of C-FABP and FABP-pm on prostate cancer tumourigencity, to investigate whether these two FABPs modulate the malignant progression of prostate cancer cells in a coordinated manner and to explore the therapeutic possibilities by manipulating their expressions in prostate cancer cells. Western blot results showed that the expression of C-FABP was significantly higher in androgen independent cell lines than that in androgen dependent cell lines whereas the expression of FABP-pm was significantly higher in androgen dependent cell lines than that observed in androgen independent cell lines. These results showed that C-FABP and FABP-pm express in opposite manner in prostate cancer progression. Immunhistochemical staining of an archival set of prostate cancer tissues have confirmed this relationship between these two genes as levels of both nuclear and cytoplasmic C-FABP expression in carcinoma tissues were significantly higher than those in normal and PBH tissues whilst the FABP-pm expression in normal and BPH tissues were significantly higher than those in carcinoma tissues. These results together seemed to suggest that the C-FABP and FABP-pm express in opposite manner in prostate cancer progression. These findings indicated that increased expression of C-FABP or decreased expression of FABP-pm maybe a valuable prognostic factor predicting the outcome in prostate cancer patients, and it may also prove to be an important target for designing effective strategies to treat the disease.

A09 The PI3K/Akt/mTOR pathway and cancer S Honap Keywords: PI3K, AKT, mTOR, cancer, treatment The PI3K/Akt/mTOR pathway is one of the key mitogenic signalling pathways involved in cell growth, proliferation and survival. Unfortunately, hyperactivation of this pathway is a common occurrence in a wide variety of human tumours which has prompted significant clinical research in developing inhibitors of PI3K components, such as PI3K itself, Akt, PDK1 and mTOR. This review will look at the successes and current status of these inhibitors. Wortmannin and LY294002, two of the best characterised PI3K inhibitors, have not made it as far as clinical trials due to problems with lack of specificity, toxicity and poor solubility. Studies are now being conducted with derivatives of these compounds in order to tackle these issues. Similar problems have arisen with inhibitors of Akt and PDK1, limiting their clinical application. Inhibition of mTOR by rapamycin analogues has been the most successful therapeutic strategy targeting the PI3K pathway. CCI-779, a rapamycin derivative, was approved by the FDA in May 2007 for the treatment of advanced renal cell carcinoma (RCC) and has entered phase III clinical trials for metastatic breast cancer. Here we will examine their relatives success compared with other PI3K pathway inhibitors and future work that is necessary for clinical use.



A10 IP-10 and INF-γ as markers of latent Tuberculosis infection in Brazil and Nepal N Abuamer, R Petrucci, R Gurgel, L Doria, M Yassin and L Cuevas Keywords: IP-10, chemokine, biomarker, LTBI Background: Children in contact with adults with pulmonary tuberculosis (PTB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-γ (INF-γ) release assays. Other biomarkers such as interferon-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections (LTBI). Objectives: To describe IP-10 concentrations in relation to TST and INF-γ responses in children recently exposed to adults with PTB in Brazil and Nepal. Methods: Two surveys using the same design were undertaken to describe TST, INF-γ, and IP-10 responses in 113 children in Brazil and 146 children in Nepal. Results: The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high (k 0.73 in Brazil and 0.80 in Nepal). IP-10 responses were higher in children with both positive TST and positive QFT-IT (medians 1434 pg/mL in Brazil and 1402 pg/mL in Nepal) and lowest in children with both negative TST and negative QFT-IT (medians 206 pg/mL in Brazil and 81 pg/mL in Nepal). Children with negative TST and positive QFT-IT had higher IP-10 concentrations than children with positive TST but negative QFT-IT. Conclusions: IP-10 is a potential marker for LTBI that is expressed in large quantities and with good agreement with QFT-IT assay.

A11 YY1 is a prognostic marker in Follicular Lymphoma K Naidoo, V Clay, JA Hoyland, R Swindle, T Illidge, and R Byers Keywords: follicular lymphoma, Yin Yang 1, quantum dots, prognosis Follicular lymphoma (FL) has a wide range of clinical behaviour, some patients having an indolent course and others developing aggressive disease. Optimal treatment stratification requires distinction between these two groups though there are presently few prognostic biomarkers available. We have reported correlation of Yin Yang 1 (YY1) mRNA levels with survival in FL, highlighting the prognostic potential of YY1.This study aimed to validate these findings at the protein level and correlate with tumour biology in FL. Quantification of the YY1 protein was carried out on 26 FL biopsy samples using quantum-dot labelled immunohistochemistry. Kaplan-Meier survival analysis showed association of higher expression levels of YY1 with better survival (p≤0.01). Dual quantum-dot based immunohistochemistry was performed for YY1 and bcl-2, and spectral imaging used to measure percentage co-localisation of YY1 and bcl-2. Kaplan-Meier survival analysis demonstrated association of higher percentage co-localisation of YY1 and bcl-2 with longer survival (p≤0.014) together with longer survival in cases with a higher level of YY1 expression within areas co-localised with bcl-2 (p≤0.017). These observations indicate the potential utility of YY1 as a clinical biomarker. They also suggest that YY1 may be negatively regulating bcl-2 in FL, suggesting that YY1 could be a potential novel therapeutic target. A12 Interpretation of microarray data from the lungs of mice infected with a gammaherpesvirus G Leeming, A Kipar, D Hughes, L Bingle, C Bingle, and J Stewart Keywords: protein expression, immunohistology, RNA-in situ hybridisation, respiratory virus, microarray Previous work in our lab showed that the M3 gene of the Gammaherpesvirus MHV-68, which encodes a viral chemokine-binding protein, has a significant effect on the host inflammatory response in the respiratory system of infected woodmice (Apodemus sylvaticus), one of the natural hosts of MHV-68. To further investigate the mechanisms that may be implicated in the differences observed, microarray analysis of RNA extracted from lung tissue was performed which identified several genes which were upregulated in wild type MHV-68 infection, compared to those of M3.stop-MHV-68 infected woodmice. This presentation discusses the methodologies used to further investigate the microarray data, including various morphological and quantitative techniques, such as immunohistology, RNA-in situ hybridisation, transmission electron microscopy and real-time PCR, and the advantages and disadvantages of these methods. Additionally, results are presented which are helping to further characterise where, when and how transcription of these genes and the proteins which they encode are altered and how this may have an effect on the pathogenesis of the disease and the host’s immune response.



B01 PAX3 is required for neuroblastoma tumour development and potential signaling pathways W Fang, S Kumar, F Salway, M Blaylock, L Zeef, T Carr and P Kumar Keywords: neuroblastoma, PAX3, chemoresistance, signaling pathways Neuroblastoma shows variable clinical behaviour, ranging from spontaneous regression to rapid tumour progression and death. The transcription factor, PAX3 is important in embryogenesis, especially in neurogenesis, myogenesis and melanogenesis, all of which require neural crest cell migration. PAX3 siRNA transfection caused marked and persistent reduction in PAX3 mRNA and protein expression in SH-EP1 cells and SH-SY5Y neuroblastoma cells. In addition, PAX3 knock-down significantly inhibited proliferation, migration and invasion of both neuroblastoma cells, induced both cells death, augmented the cytotoxic effect of chemotherapeutic drugs, and remarkably decreased the attachment of SH-EP1 cells to extra-cellular matrix proteins. Microarray analyses of the resultant gene expression in PAX3 knockdowned neuroblastoma cells revealed that PAX3 dramatically regulated thousands of genes which are involved in many signaling pathways. Among these PAX3 downstream genes, changes of 41 genes expression were further confirmed by quantitative PCR. These genes mainly participate in G1/S checkpoint cell cycle pathways, CDK/Cyclins and p53 signaling pathways, other transcription factors and growth factors regulatory processes and development signaling pathways. In summary, the present study indicates that PAX3 is essential for the neuroblastoma tumour development through regulating a variety of signaling pathways, thereby implying that PAX3 might be a potential therapeutic target for neuroblastoma.

B02 Development of microfluidics based approaches to study cell activation events S Khaliq Keywords: microfluidics, droplets, Wnt, systems biology In vivo mammalian cells are in constant receipt of signals from their local environment which stimulate the cells to perform specific biological tasks such as cell division, maturation, movement and even maintenance of survival. Understanding how these signals are integrated to give a distinct biological outcome is therefore an important issue, but one that is difficult to approach as it requires the ability to stimulate cells with multiple types and amounts of stimuli for specific lengths of time, and then track the biological outcome of the cells involved. Therefore microfluidics is used as a means of exposing cells to specific soluble stimuli in a high throughput, controllable and trackable system. The technology is manipulated further to explore means of tracking the effects of the stimuli on cell activity The system is set up using the growth factor Wnt as a stimulus to generate time-course data. The Wnt signalling pathway is important in the early developmental processes and has been implicated to have a role in stem cell fate. The focus is on cell-cell communication via the Wnt signalling pathway and with the integration of mathematical to model this data is implemented into a computer model of the pathway, existing model is initially be used to analyse the pathway, perturbing the pathway virtually and experimentally. The information gained during the cell biology experiments will be used to input into the existing models and vice versa.



B03 Student understanding of Self-Directed Learning theory is key to success B Amies, T Dornan and G Byrne Keywords: medical education, self-directed learning Introduction: Self-directed learning (SDL) and problem-based learning (PBL) were introduced into medical curricula to help overcome some of the problems that had been described in traditional courses, such as content overload and diminishing time for formal teaching. Although in theory self-direction should help to solve some of these problems and improve learning, some medical schools have reported that students have reacted adversely to the requirement to learn independently. Purpose: To explore attitudes to self-directed learning in a PBL-based clinical curriculum. Design: Focus groups with an exploratory schedule. Results: Students held some negative attitudes to important areas of the curriculum and felt that they did not learn enough in the clinical environment. Students did not seem to self-direct effectively. Discussion: These negative attitudes damaged task value beliefs which undermined the morale and motivation that SDL relies upon. However, students’ complaints were largely based upon misunderstandings of how the curriculum was designed. For example, students felt under little pressure from the Medical School, because the curriculum is designed to avoid generating ‘external’ motivation. Conclusion: A full understanding of the theory that underpins the curricular structure should alleviate misunderstandings, and improve task value beliefs and SDL.

B04 MEG spatio-temporal source reconstruction J Kan Keywords: Magnetoencephalography (MEG), inverse problem, pattern recognition My research principle is to design the method of Magnetoencephalography (MEG) source reconstruction in a new angle. MEG spatio-temporal source reconstruction is an ill-posed inverse problem that is theatrically insoluble. There are plenty of classic methods currently exist in this field which has been applied widely. However, the accuracy limitations still exist in these methods which may lead to instable and plausible results. To solve this, I apply the algorithms of pattern recognition into MEG source reconstruction. As one type of objectives of pattern recognition, the medical imaging can be analyzed in the same theories. Some particular algorithms of pattern recognition thus should be suitable for designing new methods in this area, such as Variational EM, Spherical Harmonic Basis Function (SHBF), which present outstanding features of multi-dimensional signal reconstruction. They are able to resolve the ill-posed nature of inversion process. Therefore, this application is expected to provide new possibility of developing the accuracy of MEG source reconstruction. Additionally, this study offers the new angle to explore theories of pattern recognition into medical imaging studies which may contribute for reliability of MEG technique in the research and clinic application.



B05 Assessing the impact of mortgage and rent arrears on the wellbeing of home owners and tenants in Merseyside L Dunn Keywords: housing arrears, psychological wellbeing, GHQ12 Background: Existing studies identify that mortgage arrears have a negative impact on health. Conversely, the impact of rent arrears on health has not been addressed. This study furthers existing research by assessing the impact of both rent and mortgage arrears on psychological wellbeing. Aim: To quantitatively assess the impact of mortgage and rent arrears on psychological wellbeing. Methods: A comparative case control design using quantitative data. The case group consisted of primary data gathered from homeowners and tenants with arrears in Merseyside. The control group consisted of randomly selected cases with no arrears drawn from BHPS data. The GHQ12 was used as a measure of psychological wellbeing. Findings: High GHQ12 scores (indicative of poor psychological wellbeing) were found in both the mortgage and rent arrears groups. Low GHQ12 scores (indicative of good psychological wellbeing) were found in the no arrears groups. This difference in scores was statistically significant. There was no significant difference between the scores of the mortgage arrears and rent arrears groups. Conclusion: Rent and mortgage arrears have an equally negative impact on psychological wellbeing. These findings have important implications to health, particularly as the number of households in housing arrears is predicted to rise throughout 2009.

B06 Next generation screen printed electrochemical platforms: Non-enzymatic sensing of carbohydrates using copper (II) NA Choudhry, DK Kampouris, RO Kadara, N Jenkinson and CE Banks Keywords: copper oxide screen pinted electrodes, carbohydrate sensing, glucose detection, electrochemical sensing platforms, copper oxide The first example of a copper (II) oxide screen printed electrode is reported which is characterised with microscopy and explored towards the electrochemical sensing of glucose, maltose, sucrose and fructose. It is shown that the non-enzymatic electrochemical sensing of glucose with cyclic voltammetry and amperometry is possible and through tailoring of the copper (II) oxide loading, low micro-molar up to milli-molar glucose can be readily detected which compares competitively with nanocatalyst modified electrodes. The sensing of glucose shows a modest selectivity over maltose and sucrose while fructose is not possible to be detected. This next generation screen printed electrochemical sensing platform provides a simplification over previous copper oxide systems offering a novel fabrication route for the mass production of electro-catalytic sensors for analytical and forensic applications B07 Label retaining cells in the mouse hind paw digit BH Almusalam, S Alyouha, N Alam, JK Wong and DA McGrouther Keywords: tendon, bromodeoxyuridine, label retaining cells Previous descriptions of the mouse hind paw anatomy allowed us to use it as a model to characterise the distribution of label retaining cells in the flexor tendon. The use of Bromodeoxyuridine pulse chase experiments allows the detection of this unique cell population. Bromodeoxyuridine incorporates into the DNA during S phase. The label can then be detected using standard immunohistochemistry. Following a series of intraperitoneal Bromodeoxyuridine injections, mice were sacrificed after one, four, and eight weeks of label chase. Label retaining cell density in the mouse flexor tendon was 18.5 (4.4), 28.2 (6.0), and 1.6 (0.2) cells/mm2 after one, four, and eight weeks of chase, respectively. Label retaining cell density was significantly higher at the attachment of the superficial flexor tendon than the core of the tendon (P < 0.05). In skin, label retaining cell density was significantly higher than in the flexor tendon (P < 0.05). Label retaining cell density in skin was 149.0 (12.5), 33.6 (7.7), and 15.3 (3.0) cells/mm2 after one, four, and eight weeks of label chase. Label retaining cells are present in the skin and tendon of the mouse hind paw digit.



B08 Studying plaque biofilms to improve oral health K Bakht Caries is a prevalent disease affecting the industrialised world with huge treatment costs, and is associated with the formation and accumulation of plaque on dental hard tissue. According to NHS statistics, just over half of adults and as much as 77% of children aged 8 to 15 experience tooth decay. Such social, economic and healthcare implications mean employing research into plaque formation is fundamental to lead to the development of appropriate control strategies and preventative measures. To improve our understanding of dental plaque associated with health and disease, a number of in vitro model systems have been developed including the constant depth film-fermenter (CDFF). As a closed steady state system, it can produce a large number of individual biofilms of fixed thickness, whilst allowing for the alteration of environmental factors to best mimic those found in the oral cavity. Once produced, biofilms can be evaluated via microbiological, visual and biochemical analyses. This project aims to develop a biological caries model and to investigate possible remineralisation strategies. Quantitative Light Induced Fluorescence (QLF) was employed to examine the localisation of bacteria within biofilms and can be further exploited to assess remineralisation. Project funded by BBSRC/GSK CASE B09 The effects of wearing spinal orthoses on gait B Alqaroot, M Twiste, D Howard and R Jones Keywords: spinal orthoses, restricted gait, spinal jackets, gait analysis The restraining effects of spinal orthoses on the wearer’s mobility have been studied in a number of ways. The majority of published studies reported on the effects that spinal orthoses have on the mobility during standing of the spine as a whole or between individual vertebrae. Only a few studies examined the effects on body kinetics as well as the kinematics of the lower limbs and pelvis, and not during standing but during gait. To date, there are no reports on the effects of spinal orthoses on whole body kinematics. Therefore this thesis attempts to fill the gap in the literature within this field of study by investigating the effects of wearing three different designs of spinal orthoses on the gait kinetics and whole body kinematics of a single test-participant by comparing the findings obtained from walking with an orthosis to those obtained from walking without an orthosis. Wearing an orthosis was found to affect vertical ground reaction forces as well as the normal kinematic chain responsible for interlinking the different body segments’ mobility during walking. In particular, the further an orthosis extended proximally the greater the effects were on the gait kinetics and kinematics.

B10 Risk factors for the length of hospital stay following total knee replacement T Howard Keywords: TKR, length of stay Background and purpose The measurement of length of hospital stay following total knee replacement is a marker of resource consumption and is also used as an indicator of hospital quality. This audit retrospectively analyses patients undergoing total knee replacements at Chorley District General Hospital to identify significant factors contributing to a prolonged length of stay. Methods 96 casenotes of primary total knee replacements from 2009 and 88 from 2004 were retrospectively analysed in conjunction with hospital databases to gather data. The year 2009 was compared to 2004 to highlight any changes in the demographics of patients undergoing total knee replacements. All the data was then pooled to investigate the significance of each variable. Results The median stay for 2004 was 10 days compared to 8 days in 2009. Using Cox Regression modelling, the most significant factors in a prolonged length of stay was the occurrence of a complication (p = 0.0001), the need for a transfusion (p = 0.0056), advancing age of the patient (p = 0.0036), and female gender (p = 0.0242). Conclusion Identifying risk factors for a prolonged length of hospital stay provides potential to optimise pre-operative intervention and care thus reduce the cost implications of a prolonged length of stay whilst maintaining patient satisfaction. B11 Temperature sensing fabric for heath monitoring MD Husain and T Dias Keywords: healthcare, body temperture, RTD, smart shirt, sensing element This research demonstrates the development of a biomedical sensor that can be knitted into outer and next-to-skin garments for the measurement of human body temperature. The overall objective is to produce an easy to care garment capable of providing round the clock ambulatory monitoring of a patient in all circumstances. Although the ambulatory monitoring of a patient would require a range of different sensors, the focus of the proposed research is to develop a Knitted Temperature Sensor (KTS). The KTS would be developed by laying-in a fine metal wire (as sensing element) into the knitted structure. Operating principle of KTS is based on the inherent propensity of metal to exhibit change in electrical resistance as a result of a change in its temperature.



B12 Clinical exposure helps medical students develop higher order thinking A Boles Keywords: higher order thinking, bloom assessment Introduction: Complex (or higher order) thinking skills are essential for medical practice. Assessments such as the Progress Test at Manchester Medical School act to assess this. This study aims to measure the rate of students’ acquisition of knowledge, and to assess the development of their higher order thinking by analysing longitudinal Progress Test results. Methods: Three student raters independently tagged the cognitive difficulty level of eight consecutive Progress Test papers according to the modified Bloom taxonomy. ANOVA and paired t-tests were performed to detect any association between these different levels over time. Results: The performance of students in the Progress Test demonstrated a step-wise improvement. Performance in higher order cognitive difficulty MCQs showed a steep improvement at the start of clinical training, whereas lower order cognitive difficulty MCQs showed a monotonous increase. These differences were statistically significant. Discussion: The results of the study corroborate those of previous studies. The steep improvement in higher-cognitive difficulty MCQs suggests that students rapidly develop higher order cognitive skills at the beginning of clinical training. This finding seems to support the implementation of integrated early clinical exposure in undergraduate medical curricula. C01 Characterising the role of interferon associated elements in modulation of the murine gammaherpesvirus immediate-early ORF50 lytic gene promoter B Manso, B Ebrahimi and J Stewart Keywords: to the point, schematic In gamma-herpesvirus, such as the human Kaposi’s sarcoma-associated virus and Epstein-Barr virus, the balance between lytic infection and reactivation from latency depends almost entirely on expression of an immediate-early viral gene (ORF50) encoding the Replication and Transcriptional Activator (RTA) protein. Due to its role, RTA expression is a potential target for viral replication inhibition by interferons, and previous work in a murine model, murine gamma-herpesvirus-68 (MHV-68), have shown a number of potential binding sites of IFN related factors within ORF50 promoter. Following that observation, this study aims to understand how IFNs relate to RTA gene expression. We have observed that treatment with IFNs can cause a decrease in ORF50 promoter activity and that IFNs regulatory factors such as IRF7 and IRF3 may potentially have a role in inhibiting RTA gene expression.

C02 Tumour specific T-cells for adoptive immunotherapy of metastatic melanoma EM Alcantar-Orozco, P Lorigan, G Ross, R Hawkins and D Gilham Keywords: adoptive cell therapy, T-cells, melanoma Adoptive cellular therapy (ACT) is the most effective experimental treatment for metastatic melanoma reaching objective responses in up to 70% of patients. This modality of treatment is based on the generation and expansion of tumour-reactive lymphocytes and their administration to a lymphodepleted patient in combination with interleukin (IL)-2. There are currently several approaches to the generation of tumour-reactive lymphocytes. Tumour infiltrating lymphocytes (TILs) are isolated from excised tumours and expanded in vitro with high doses of IL-2. On the other hand, genetically modified peripheral blood lymphocytes (PBLs) are artificially directed against shared tumour associated antigens. Here, we present our experience in generating tumour-reactive lymphocytes from melanoma tumours and by genetic modification of PBLs. We successfully generated TILs from 80% of melanoma tumours collected (n=8). TILs were >95% of a late stage effector phenotype. We also generated reactive cells against the melanoma antigen MART-1 by gene transfer of a MART-1 specific T-cell receptor to PBLs. These cells showed some reactivity and cytotoxicity against melanoma tumour cell lines. Both methods of generating tumour reactive T-cells seemed effective, however the continuous evaluation of protocols to generate large amounts of cells that effectively target tumour cells is essential for an efficient modality of ACT.



C03 Screening NF-κB inhibitors for effects on neuroblastoma cell fate A Salim, CA Heyward, V See, MRH White and PD Losty Keywords: neuroblastoma, NF-κB inhibitors, chemotherapy, apoptosis Background: Neuroblastoma, the commonest childhood solid tumour, remains a challenge to modern clinicians as prognosis for advanced cases remains poor despite extensive multi-modal therapy. However, some tumour cells undergo spontaneous regression, leading scientists to focus research on “switching on” apoptosis in neuroblastoma cells. Nuclear factor kappa B proteins (NF-κB) are transcription factors regulating cell cycle, immune, and inflammatory responses. Previous work has shown that NF-κB inhibition by endogenous inhibitor IκBα kills neuroblastoma cells, and etoposide, a chemotherapy agent, increases cell death in a number of neuroblastoma cell lines via activation of p53. Aim and current techniques: To develop a new therapy for neuroblastoma based on NF-κB manipulation, we are screening compounds from a chemical library for NF-κB inhibitors capable of synergistically increasing cell death in combination with etoposide treatment. Cell viability MTT assays are used to assess whether chemicals from the LOPAC1280 library can increase the extent of etoposide-induced cell death in neuroblastoma cell lines. The ability of these compounds to regulate NF-κB activity is measured using an NF-Luc reporter in a luminometry assay. Compounds demonstrating synergistic effects will be further studied by caspase assay and qPCR to determine the NF-κB –regulated genes involved and the mode of cell death.

C04 Targeting entire families: Evaluating the effectiveness of a healthy-family based project M Romeo Velilla, G Stratton, and Z Knowles Keywords: physical activity, public health, intervention Background: Liverpool Active City Strategy has recently funded projects for promoting physical activity amongst families to tackle obesity in Liverpool. This study evaluated an 18 week family-based project including physical activity and play/craft sessions with healthy meals after each session. Methods: A mixed-method evaluation was designed based on the RE-AIM framework, and piloted on 19 participants (8 adults, age 32.8 ± 11.2; 1 child, age 8.4; 6 young children, age 5.5 ± 1.3; 4 toddlers, age 1.6 ± 0.4). Self-reported physical activity was measured in 16 participants using questionnaires (adults, I-PAQ (www.ipaq.ki.se); children, PAQ-C (Kowalski et al., 2004); young children, NPAQYC (Janz et al., 2005)). Physical activity was measured in 11 participants (4 adults, 4 young children, 3 toddlers), wearing biaxial accelerometers for 7 days. Families’ needs, enjoyment, and confidence were evaluated using observation (19 participants) and semi-structured interviews (3 adults). Discussion: Data analysis highlighted that the mixed-method design did not sufficiently cover all RE-AIM elements. The intrusive nature of measuring physical activity seemed to affect the collection of qualitative data. The researchers found difficulties in building trust with participants. As a recommendation, researchers may wish to explore the notion of building rapport more comprehensively at the participant observation stage. C05 An audit to compare sporting activity and return to work after two types of hip replacement surgery M Griffin Keywords: hip replacement surgery, sport, work Hip resurfacing has been promoted as a procedure that results in a better outcome in sporting and work activity after surgery compared to total hip replacement (THR). Questionnaires were analysed from 125 metal on metal total hip replacement (THR) and 108 hip resurfacing (HR) patients regarding participation in sport and returning to work. 71 of 125 THR (57%) patients compared to 76 of 108 (70%) HR patients participated in sporting activity in the year after their surgery (p value=0.04). When including only patients that played sport before their surgery 54 of 75 (72%) THR and 66 of 83 (80%) HR patients returned to same sporting activity level after their surgery (p value=0.35). Of the patients that worked before surgery 35 of 44 (80%) THR patients compared to 70 of 74 (95%) HR patients returned work to after their surgery (p value= 0.02). There was no difference in the proportion of patients who played sport prior to their surgery returning to sport. After HR more people took up a sporting activity and at a year post surgery greater numbers of patients were taking part in sport after HR. Patients with a HR were more likely to return to work after surgery.



C06 Developing paediatric pain maps in the accident and emergency department K Kelly, S Garnder and Z Haslam Keywords: acute, pain, score, assessment, management Introduction: The College of Emergency Medicine has identified that pain scores can improve the provision of adequate analgesia in the paediatric acute care setting. The aim of this project is to record the patient’s stated pain score over time in order to identify factors that can contribute to inadequate pain control. Methods: A prospective, observational pilot study utilising convenience sampling of children aged 5 – 15 years was conducted in a single district general paediatric emergency department between the 10th of July 2009 and 24th of July 2009. It involved recording the self-reported pain scores of children presenting to the department in acute pain every 15 minutes for 4 hours, using a combination of a numeric rating scale from 0-10 and the Wong-Baker FACES pain scale. Results: During the study period 54 patients were enrolled 7.27 % (n = 743) of the attendances, with 47 completing the 4 hour pain score period, allowing pain maps to be produced and their experiences compared. Conclusions: Mapping out a patient’s pain through sequential pain scoring may provide valuable information to customise their clinical care and in the future may be facilitated by a patient controlled real time pain assessment electronic device. C07 The sugar shovel: Tryptophan as a molecular shovel in the glycosyl transfer activity of Trypanosoma cruzi trans-sialidase FL Mitchell, SM Miles, JP Neres, EV Bichenkova and RA Bryce Keywords: TcTS, rational, drug, design, tryptophan Investigations into the active site plasticity of the Trypanosoma cruzi trans-sialidase enzyme in thie current work has shown varying degrees of movement of the Trp312 loop as part of a carefully orchestrated multistep catalytic process. Trp312-loop flexibility seems to be a critical requirement of the sialic acid transfer mechanism, employing a ‘molecular shovel’ action as means of expulsion of the donor aglycone leaving group from the catalytic site. The detailed computational insights into sialyl transfer obtained from this work are hoped to shed new light on the structural understanding of TcTS and support the design of inhibitors effective against this neglected tropical disease

C08 Nano-layered inorganic-organic hybrid materials for the controlled delivery of antimicrobials to protect against healthcare associated infections. M Kinninmonth, C Liauw, V Edwards-Jones, J Verran, R Taylor and D Shaw Keywords: antimicrobial, essential oil, montmorillonite Healthcare-associated infections (HAI) are a major problem in modern medicine, with reports suggesting that approximately 10% of patients acquire a HAI. Such infections have a considerable impact both economically and socially, and therefore it is important to investigate ways in which they can be prevented. The aim of this project is to blend essential oils (EO), which have been shown to inhibit many HAI causing bacteria, in a way that will create a broad spectrum antimicrobial. The EO blend will then be adsorbed into the structure of a porous inorganic substrate. The substrate-EO complex will then be incorporated onto materials such as plastics and fibres, the treated materials could then be used to create antimicrobial surfaces and textiles for use in healthcare facilities. This would create a reduced microbe environment and help to reduce the chances of a patient getting a HAI. The Majority of the work in the first year has concentrated on finding the optimum blends from five oils (manuka, oregano, geranium, lavender, and rosewood), and combining the oil blends with man made biocides to improve the antimicrobial activity further. The next stages of the project will be looking at the adsorption of the oils onto a range of inorganic substrates to determine the optimum substrate for adsorption and controlled release.



C09 Overexpression of CYGB exerts tumour suppressor activity in lung cancer cell lines U Oleksiewicz, T Liloglou, JK Field and G Xinarianos Keywords: cytoglobin, lung cancer, tumour suppressor Cytoglobin (CYGB) is a novel member of the globin family genes, whose molecular function remains poorly understood. In human cancers, CYGB level is frequently reduced due to promoter hypermethylation and loss of heterozygosity. Recent data implied that CYGB might act as a tumour suppressor gene (TSG). However, more thorough investigations are needed to elucidate CYGB involvement in tumour biology. The aim of this study was to determine CYGB influence on cancerous phenotype (growth & death rate, migration, invasion and transformation abilities) in the lung cancer setting. We genetically restored CYGB expression in two lung cancer cell lines: Calu1 and H358. Restoration of CYGB expression did not trigger cellular death. The growth rate of CYGB+ clones was reduced, but only in H358 cell line. CYGB overexpression diminished migratory and invasive potential of all Calu1 and H358 clones. We observed as well striking depletion in transformation efficiency of CYGB+ clones. These results strongly support the hypothesis that CYGB acts as a TSG and indicate that CYGB might be considered as a potential therapuetic target. CYGB knock-down clones, as well as in vivo studies, will further improve our understanding of this novel TSG.

C10 Optimal sera samples preparation on MirrIR plate and high quality spectra obtainment using centrifugal devices and IR imaging for FTIR analysis. G Monjardez , NW Clarke , MD Brown and P Gardner Keywords: blood serum, FTIR, IR imaging, sample preparation. The aim is to improve reproducibility and quality of blood serum smearing onto MirrIR plates for FTIR analysis; increase the quality of serum by ultracentrifugation (1) to eliminate biological aggregates previously observed. This should increase the quality of FTIR spectra obtained with IR imaging. The other aim is to refine the rejection criteria based upon guidelines originally described by Naumann et al (2). 250µl of healthy blood sera was pipetted into individual centrifugal devices and centrifuged. Reference control consisted of 250 µl of uncentrifuged serum. Five spots of each type of serum were pipetted and smeared onto individual MirrIR slides. The IR imaging of the smears was taken and the quality testing applied to the spectra. The microscopic observation of the serum smears showed that although the biological aggregates mentioned above could still be seen in some of the smears, they were smaller than in the unfiltrated smears. In addition, on number of the smears observed those aggregates were no longer present. Potential of filtration devices in improving the serum smears was demonstrated. Application of IR imaging to select the homogeneous areas of the smears obtained was successful to obtain the highest quality spectra of the smear. (1) D. Naumann, Twenty years of FTIR on microorganisms at the Robert Koch Institute: Experiences gained during a successful project. 1st International workshop on spectral diagnostics (SD-1); 21-23 June 2007; Boston, USA; 2007, p.1-20. (2) W. Petrich et al, Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain, The Analyst (2009), 134, p.1092-1098.



C11 Effects of resin cement on the colour of ceramic veneers. N ALGhazali, J Lauckner, FD Jarad, PW Smith and AJ Preston Keywords: colour, porcelain veneers, resin cement Objectives: The purpose of this study was to investigate how three shades of resin cements and their related try-in pastes from three different manufacturers influenced the colour of porcelain veneers. Methods: A total of 135 porcelain veneers of one shade and 1mm thick were produced to fit bovine teeth. Veneers were positioned and separated from underlying tooth surface by air (AR), commercially available lubricating gel (AG), try-in paste (TP), uncured (UCR) and cured (CR) resin. Colours were measured spectrophotometrically for the veneers separated from underlying tooth by the different media as outlined above, then colour differences ∆E were calculated. Results: Perceptible colour differences (∆E>1) were found between CR compared with AG (∆E 1.8 -4.9); CR and TP of ‘matched’ shades (∆E 1.05 -3.34). Colour differences between UCR and CR were smaller (∆E 0.78 -1.41), but in some cases, perceptible. Conclusions: The shade of the try-in paste and resin cement produced perceptible overall shift in the colour of the veneers. Colour differences between try-in pastes and their matched resin cements were also distinguishable spectrophotometrically at levels that may be clinically perceptible. This latter finding suggests that care should be exercised when using a try-in paste to predict the overall colour of the final restoration.

C12 Interaction of 9Δtetrahydrocannabinol and buprenorphine with multidrug resistance proteins in human placenta D Thajam, CP Sibley and DE Atkinson Keywords: placenta, buprenorphine, delta-9 tetrahydrocannibidiol, multi-drug resistance proteins The multi-drug resistance proteins (MDRPs): P-glycoprotein (P-gp) and breast cancer resistance protein (BRCP) act to prevent xenobiotics in the maternal plasma reaching the fetus, at toxic concentrations. The aim of the present study was to determine whether two commonly used substances i.e. Δ9tetrahydrocannabinol (THC) and buprenorphine (BUP) interact with P-gp and/or BCRP in human placental tissue. Small villous fragments were dissected from term placentas and used to measure accumulation of 3H-vinblastine (a P-gp substrate) and 3H-mitoxantrone (a BCRP substrate) in the presence or absence of 20µM THC or BUP. BUP had no significant effect on either vinblastine or mitoxantrone accumulation at 10 or 120 mins. THC caused a significant decrease in accumulation of vinblastine at both 10 and 120 mins and a significant increase in mitoxantrone accumulation at both time points. Decreased accumulation in the presence of THC suggests stimulation of P-gp activity by this component of cannabis. Increased accumulation of mitoxantrone suggests that either THC is a substrate for BCRP and is effluxed at the expense of mitoxantrone, or whilst not itself a substrate it inhibits efflux in another way, for example by changing the binding site. D01 Re-audit of the use of intravenous morphine in paediatric pain S Gardner and T Walton Keywords: severe paediatric pain management strategy The management of paediatric pain is frequently inadequate: poorly recognised, quantified and treated. A retrospective audit of the management of paediatric pain with intravenous morphine in the Paediatric Accident and Emergency Department at Ormskirk District General Hospital was undertaken in 2006. The results showed that junior staff gave lower than expected doses of morphine than more senior staff and were also giving morphine less frequently than expected for their time in the department. Following the improvements of teaching on the prescription of morphine, the use of pain scores in children and the availability of pain parameters in the department, we chose to perform a retrospective re-audit to gauge the effect of the changes implemented. The data were taken from the department’s controlled drugs log and the patients’ emergency department admission cards. Details of the nature and cause of the pain, the recording of pain scores and both the dose of morphine administered and the use of multimodal analgesia were taken. We found that junior staff were prescribing more morphine by frequency and dose than senior staff and that the speed of administration and use of multimodal analgesia was improved since 2006.



D03 Impact of cardiothoracic ratio on response to cardiac resynchronization therapy- a prospective study K Albouaini, A Alkarmi, R Antony, M Shaw, M McGee, A Patwala, S Modi, D Barker, A Chenzbraun, DJ Wright and A Rao Keywords: biventricular pacing, heart failure, cardiothoracic ratio Aim This single-centre prospective trial assessed the influence of interventricular lead tip distance and cardiothoracic ratio on response to cardiac resynchronization therapy (CRT) in patients with advanced chronic heart failure and electrical dyssynchrony. Methods We studied 28 consecutive patients who underwent CRT. All patients had advanced heart failure (NYHA class III or IV) despite optimal medical therapy, LVEF ≤ 35%, and QRSd ≥ 120 msec. Investigations at baseline and 4-month follow-up included: echocardiogram, 12-lead ECG, 6-min walk test (6MWT), and a cardiopulmonary exercise test (CPET). Response to CRT was defined as at least 5% increase in peak oxygen consumption (PVO2) on CPET pre and 4-months post CRT and comparison made between responders and non-responders. Cardiothoracic ratio (CTR) and interventricular lead distance (ILD) were measured on chest X-ray (CXR) in both postero-anterior and lateral views on the day of implantation using digital radiology software. ILD was divided by the cardiothoracic ratio (CTR) to account for differences in cardiac and thoracic sizes. These variables were then correlated with response to CRT. Results Patients’ baseline characteristics were similar in responders and non-responders. Eighteen patients were classified as responders (64%). Responders had a significantly higher LVEF [37.7 ± 8.0 vs 28.8 ± 10.0; P=0.04] and longer 6MWT; P=0.04. At baseline, none of the measured mean ILDs were significantly different between subsequent responders and non-responders at 4 months (Table 2), However, CTR was significantly different between responders and non-responders (0.53 ± 0.05 vs 0.57 ± 0.05, P=0.04). Furthermore, there was a negative correlation between change in PVO2 and the CTR [P < 0.01 and r = 0.52]. Conclusion Interventricular lead distance at implant was not correlated with response to CRT at 4 months post implant. However, the cardiothoracic ratio was significantly correlated with response, implying that patients with largest hearts may have more advanced negative remodelling and are therefore less likely to improve with CRT.

D04 New parameters for the diagnosis of septic arthritis E Abdellatif and T Freemont Keywords: septic, ragocytes, polymorhs, heamatoidin Although septic arthritis is a challenging emergency, no established gold standard is available for accurate diagnosis. Data suggest that septic arthritis is costly as it can destroy the joint after hours from the onset of infection. Although many tests are available for diagnosing septic arthritis, synovial fluid cytology and Gram staining remain the cheapest, the quickest and the most accurate diagnostic tests. This existing test was used to establish new parameters for diagnosing septic arthritis with 100% specificity. This is a retrospective study of archival data from the diagnostic osteoarticular pathology service for Manchester, a large city-based conurbation in the NW of England. The laboratory is a central referral laboratory for the microscopic analysis of synovial fluid samples from the NW of England. During the period of the study (1988-2009 inclusive) more than 33.000 samples were statistically analyzed to establish new parameters for diagnosis with high specificity and sensitivity. From the statistical analysis of cytocentrifuge preparation of the synovial fluid it was found that the presence of haematoidin crystals, SF WBC’s ≥22.000 cells/cm3, neutrophils equal to 100% and ragocytes count equal to 100% the diagnosis of septic arthritis could be established with 100% specificity. D05 Statistical analyses of deprivation and IMR from 1949 to 2008, China R Yang, X Zheng Keywords: deprivation index; Infant Mortality Rate (IMR); statistical analyses; China Background Previous researches and observations detected that child mortality was related to poverty; however little has been done about the statistic association between poverty and child mortality in China, specifically. Methods Secondary time series data from 1949 to 2008 on China was analyzed. Multiple linear regression and Hierarchical multiple regression were applied. Findings The entered variable (DI, Year, Year after Reform) accounted for 82.5% of the variation in IMR; the influence of Year disappeared in the multiple linear regression. The hierarchical multiple regression demonstrated that DI was significantly a predictor of IMR. The addition of the quadratic and cubic resulted in significant R2 change. The complete model accounted for 93% of the variation in IMR. Interpretation The DI was an informative predicator of child mortality, supporting the polity of reducing the child mortality by eradicating the poverty in China. Certain perspectives were doing harm to child health since the Reform policy, which might be the inequality effecting the population. Lowest range of DI had an accelerative damaging effect on child health. Greater attention should be paid to the extreme poverty, the intergenerational transmission and the area effect of the poverty, so as to reduce the child mortality.



D07 AMP in practice: People's experience of practical obstacles to accessing high quality mental health services in primary care P Clarke, S Edwards, C Chew-Graham, M Kovandžić, D Hibbert, L Gask, A Catlin, and C Dowrick Keywords: access; mental health; primary care Introduction: This study is part of the AMP programme, which has confirmed that certain groups of people are less likely than others to access high quality mental health services for common mental health conditions in primary care. The aim was to investigate the challenges faced by (potential) primary care patients from identified groups, and to explore the solutions they suggest for improving access. Methods: Participants (n=29) were recruited through community organisations in Northwest England. They included women with eating disorders, homeless adults, asylum seekers and BME people (five groups). Qualitative data were collected through semi-structured interviews. Emerging themes were identified and analysed. Results: Access problems and solutions related to time, place and means of delivery. Concerns and preferences were frequently shared by several groups: length of appointments (all); waiting times (all); local provision (BME; homeless); home visits (BME); and contact that is individual over group (BME) and face-to-face rather than telephone or computer (asylum seekers; BME; homeless). Conclusions: Issues raised by this study will contribute to an intervention aimed at helping general practices examine and amend their current access procedures. The authors recognise that subsequent changes are more likely to succeed when embedded in the organisation of the practice.

D08 Polyurethane as a substrate for cell transplantation in the treatment of age related macular degeneration (AMD) E Alias, V Kearns, IM Harrison, SA Dixon , FA Laws, CM Sheridan and RL Williams Keywords: AMD, RPE transplantation, artificial substrate, polyurethane Introduction The aim of the study is to investigate polyurethane (PU) membranes to control the monolayer formation of retinal pigment epithelial (RPE) cells from both established and primary cultures for use in sub-retinal RPE cell transplantation to treat age-related macular degeneration (AMD). The aim of this study was to investigate the effect of varying the ratio of the soft and hard segments of the PU on its ability to support RPE cell attachment and proliferation, and to control the monolayer formation of epithelial cells on substrates. Material and Methods The PU used in this study was b9 (Biomer Technology Ltd.). Two different formulations of differing durometer b9 PU were provided as thin films (<100μm thick); Z3A1 and Z9A1. Z9A1 is harder than Z3A1. Substrates were adhered to the base of well plates. Tissue culture polystyrene (TCPS) was used as the control. Several types of RPE cells were used: ARPE-19, an established but non-immortalized human RPE cell line, Bovine RPE (BRPE) and bovine iris pigment epithelial cells (BIPE) and primary human RPE. The bovine cells were derived from cows’ eyes collected from an abattoir and the human RPE were derived from donor eyes. All cells were seeded onto the substrate at a seeding density of 3.33 x 104 cells/ml. Retinoic acid (RA) was added at day 4 as an anti-proliferative agent, and several concentrations of serum were tested. At certain intervals, cell morphology were assessed by light microscopy and at the end of the experiment, samples were stained accordingly. Cell cytoskeletal morphology was assessed by actin staining using Phalloidin solution. Nuclei were stained with Propidium Iodide (PI) or TO-PRO-3. Tight junction formation was assessed by fluorescent immunostaining for Zonula Occluden-1 (ZO-1). Cytokeratin staining was used to confirm the epithelial phenotype. Results and Discussions Experiments with ARPE-19 show that the substrates do support growth of cells. By modifying the serum concentration and adding RA, some patches of monolayer formation can be seen with both BRPE and BIPE (see figure 1). Using the same condition with HRPE illustrated a good monolayer formation in some areas on control surfaces and on the substrates (figure 2), but there are some problems with reproducibility with both cell lines and materials. Staining procedures on the samples demonstrated good spreading of HRPE on all surfaces with evidence of formation of junctional proteins on the cell borders with circumferential actin distributions (figure 3). Positive cytokeratin staining demonstrated epithelial phenotype when the cells attached on the substrates. Conclusions The experiments have demonstrated that b9 PU has the potential to provide a suitable surface for RPE cell growth although more work is needed on harvesting techniques on cells and production of the substrates to ensure reproducibility. Further work is planned to produce these films with a porous structure and to optimise the conditions to support a viable functional cell monolayer for transplantation. Financial support from EPSRC and Biomer Technology Ltd. are gratefully acknowledged.



D09 Regulation of neutrophil action in inflammatory disease KJ Roberts Keywords: neutrophil, inflammation, nampt, arthritis, NAD In the inflammatory disease Rheumatoid Arthritis (RA), vast numbers of neutrophils infiltrate the joint. Cytokines and immune complexes in the joint delay constitutive neutrophil apoptosis and stimulate release of anti-microbial proteases and oxygen metabolites. Sequencing of the neutrophil transcriptome from healthy individuals and RA patients was performed to gain insight into the role of neutrophils in RA. The transcript for the pleotropic protein Nampt (also known as PBEF and visfatin) was upregulated in RA samples. Nampt is an enzyme that catalyses production of NAD, an essential co-factor for many proteins influencing cytokine expression. It is proposed that Nampt also acts as a cytokine. Literature shows that serum and synovial fluid levels of Nampt are elevated in RA. It has also been shown in neutrophils that Nampt drives cytokine expression, and inflammatory cytokines TNFα, LPS and IL-1β upregulate Nampt. Here, immunoblotting shows GM-CSF and IL-6 also have a similar effect. FK866, an inhibitor of Nampt-catalysed NAD production, has been shown to dramatically alleviate symptoms in a mouse arthritis model. Here, I show that FK866 reduces production of damaging oxygen metabolites from stimulated neutrophils by luminol-dependent chemiluminescence. Nampt mediates the destructive effects of neutrophils in RA, and represents a novel inflammatory marker.

D10 Measuring toll-like receptor expression in PBMCs in Juvenile onset Systemic Lupus Erythematosus (JSLE), inflammatory and non-inflammatory controls AJ Midgley and C Thorbinson Keywords: JSLE, toll-like receptors, immunopathology Background: JSLE is a severe, multi-system autoimmune disease. The TLR family are essential components of the innate immune system and may be important in the development of autoimmunity. The most unifying feature among SLE patients is a loss of tolerance to nuclear antigens. TLR’s (3, 7- 9) can recognise autoantigens typical of SLE. Objective: To assess the expression of TLR 3,7,8 & 9 in JSLE compared to inflammatory and non-inflammatory controls. Method: PBMC’s were isolated from JSLE (n=8), Juvenile Idiopathic Arthritis (n=8; inflammatory control) and non-inflammatory controls (n=5). Quantitative PCR was used to measure TLR 3,7,8 & 9 mRNA expression and was normalised to 18s mRNA expression. Results: TLR 3(p=0.003), 8(p=0.002) & 9(p=0.002) mRNA expression was significantly higher in JSLE patients compared to non inflammatory controls. TLR 7 mRNA expression was also higher but was not statistically significant. Conclusion: Here we demonstrate increased expression of TLRs in JSLE which are consistent with adult data. However TLRs 3 & 8 which have not been shown to be significant in adult populations may have a more prominent role in JSLE. Although requiring further research, this study has raised important early data exploring the role of TLRs in the immunopathology of JSLE.



D11 Psychological distress in people with disfigurement from facial palsy L Fu and SA Sadiq Keywords: facial palsy, psychological distress Objectives Psychological distress is documented in people with facial disfigurement. However the prevalence of psychological distress in facial palsy patients has not been studied. This preliminary study aims to establish the prevalence of psychological distress and extent of anxiety and depression in a sample of facial palsy patients from the Northwest of England. Method 39 participants with facial palsy completed a questionnaire pack comprising the Illness Perception Questionnaire-Revised (IPQ-R), demographic questionnaire, and Hospital Anxiety and Depression Scale (HADS). The severity of participants’ facial palsy was measured by the House-Brackmann scale. Results 17.9% and 23.1% had significant levels of anxiety and depression, compared with the normal population levels of 16.6% and 12% respectively. The mean age of participants was 61 and 52.8% had grade 6 facial palsy. Significant associations were found between participants’ perception of consequences, emotional representations, and the level of distress. No significant associations were found between clinical severity of facial palsy and levels of distress. Conclusion There was a significant level of distress in this study group. The levels of psychological distress were higher than the levels found in the normal population. There were significant associations between participants’ illness perceptions and their level of distress.

D12 Accuracy of assessment of patient discomfort during endoscopic procedures A Sachdeva, JR Barton and K Seymour Keywords: endoscopy, discomfort, gastroenterology Introduction: Endoscopy is a safe and efficient tool in the diagnosis of gastrointestinal diseases. However, due to its invasive nature, patients sometimes experience pain and discomfort during the procedure. Endoscopists and nurses are required to record their assessment of patient discomfort, as appropriate prompt action can improve patient experience. Aim: To gauge the accuracy of assessment of patient discomfort during gastrointestinal endoscopy, as reported by endoscopy staff. Methods: Patients, endoscopists and nurses independently reported overall discomfort scores on a three-point scale, after each of 107 endoscopic procedures carried out over six consecutive days. Accuracy of staff-reported scores was assessed by comparing them to patient-reported scores. Results: Both endoscopists and nurses accurately assessed patient discomfort in 64% cases. Accurate scores were more frequently reported for female patients and those over 60 years of age. Endoscopists under-reported discomfort in 24% cases, while nurses over-reported discomfort in 21% cases. Both reported congruent scores in 68% cases, of which 48% corresponded to the patients’ experience. In 11% cases, both failed to recognise patient discomfort. Conclusion: Endoscopy staff is inaccurate in assessing patient discomfort. Endoscopists tend to under-estimate patient discomfort while nurses tend to over-estimate discomfort.



Vitae is funded by Research Councils UK (RCUK), managed by CRAC: The Career Development Organisation and delivered in partnership with regional Hub host Universities. Vitae is the first national organisation to champion the professional and career development of both doctoral researchers and research staff in higher education institutions and research institutes. The programme, currently funded by the Research Councils until 2012, builds on the previous work of UK GRAD and UKHERD. Vision and aims: Championing the development and implementation of effective policy. Enhancing higher education provision through sharing practice and resource. Providing access to development opportunities and resources. Building an evidence base to support the researcher development agenda.

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(January). Championing national or international initiatives, such as the new Concordat to support the career

development for researchers. Providing the framework to share approaches and resources via an online database. Publishing research and reviews. Providing a dedicated researchers’ portal containing information, news and opportunities. Providing a programme of national courses and activities. Facilitating a network of employers who employ researchers. Vitae national team: Based in Cambridge, the national team is responsible for bringing together partners and stakeholders of the programme and co-ordinates our national programme of activities. Contact details: Vitae c/o CRAC 2nd Floor Sheraton House Castle Park Cambridge CB3 0AX Switchboard: 01223 460277 www.vitae.ac.uk [email protected]

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Each Hub region has a Co-ordinator plus a dedicated Hub Manager based in a university, with input from a steering group of representatives of other regional HEIs. The regional Hubs work to actively engage all those with an interest in the personal, professional and career development of researchers and respond to regional needs. There are 8 Hubs covering the UK:

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Name Email address Position and institution Paul Birkett [email protected] Dean of Academic Quality and Standards,

University of Bolton

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Cliff O'Neill clifford.o'[email protected] Head of Research and scholarship University of Cumbria

Helen Woodruffe-Burton [email protected] Graduate School Director, University of Cumbria

Alistair McCulloch [email protected] Dean of Research and Knowledge Transfer, Edge Hill University

Hayley Dennis [email protected] Research Student Skills Programme Co-ordinator, Glyndŵr University

Elaine Davies [email protected] Research Staff Careers Advisor, Lancaster University

Louise Innes [email protected] Research Training Programme Manager, Lancaster University

Barbara Tigar [email protected] Research Staff Training Advisor, Lancaster University

Wendy England [email protected] Careers Advisor, University of Liverpool

Richard Hinchcliffe [email protected] Director of Postgraduate Training, University of Liverpool

Christos Petichakis [email protected] Research Staff Development, University of Liverpool

Janet Speake [email protected] Associate Dean, Postgraduate Studies, Liverpool Hope University

Sue Spiers [email protected] Head of Research Programme Development, Liverpool John Moores University

Jim Boran [email protected] Graduate Development Manager (EPS Faculty), University of Manchester

Rachel Cowen [email protected] Research Staff Training Coordinator (MHS Faculty), University of Manchester

Emma Gillaspy [email protected] Vitae NW Hub Manager, University of Manchester

Judy Williams [email protected] Vitae NW Hub Co-ordinator, University of Manchester

Clare Holdcroft [email protected] Research Degrees Officer, Manchester Metropolitan University

Kate Rowland [email protected] Development and Training Manager, Manchester Metropolitan University

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