The minds eye visual perception in Parkinsons disease

The mind’s eye – visual perception in Parkinson’s disease Neil Archibald Clinical Research Fellow Clinical Ageing Research Unit

what is visual perception? l l l vision is about more than just “seeing” we rely on accurate information being transmitted from the back of the eye to the visual cortex this part of the visual pathway can be termed the “anterior” visual system we then need to integrate this information into a visual experience or “perception” this complex process takes place in the brain itself – the “posterior” visual system

how many black dots can you count? this type of illusion is caused by tricking the anterior visual system – the retina of the eye

is this a young woman, an old hag…? or both? ?

Margaret Thatcher looks fine upside down, but. . dreadful the right way up!

so both the anterior and posterior parts of the visual system must be working properly for us to “see” and “perceive” the world around us

why Parkinson’s disease (PD)? l l l patients with PD experience a broad range of visual symptoms some are minor – like blurred vision or difficulty reading others involve disordered perception of the world around them – visuo-perceptual impairment such symptoms include feelings of “presence” in the room, fleeting sensations of movement in the “corner of the eye” and even detailed visual hallucinations these are much more common in PD patients with dementia (PDD) than in those without

what are we doing? l l we are recruiting participants with PD, PDD and healthy age-matched controls all undergo detailed visual assessment including questionnaires, eye examinations, retinal scans and electrical tests of the anterior visual system we are also documenting the degree of cognitive impairment in all participants in addition, we will be using a remote eye tracker to record visual exploration strategies when solving tests of visual perception

which of the boxes numbered 1 to 4 has the same pattern as the red box?

while you’re solving that, here is what your eyes are doing

and here is the map of where you looked

what might this tell us? l l l we think that visual exploration strategies will differ between participants with PD and those without we also believe that the strategies employed will be less effective in those with PDD than those PD participants with normal cognition we are also hypothesising that impaired visual exploration will be a risk factor for developing hallucinations irrespective of the level of cognition

why does it matter? l l l visual symptoms in PD and PDD are common and poorly understood they cause a considerable degree of morbidity and affect quality of life for patients and their families a better appreciation of how such symptoms evolve and the risk factors for their development is necessary if we are to treat them more effectively

Prof. David Burn l Prof. Urs Mosimann l Mr. Michael Clarke l The Parkinson's Disease Society for their support and funding l our patients and their families l you for watching! l

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Clinical Pharmacology Studies with Fenretinide in Children’s Cancer Nicola Harris Northern Institute of Cancer Research

What is Pharmacology? Investigating how the body metabolises a drug ‘What the body does to a drug’ E. g. How much drug will be absorbed into blood plasma? Toxic Concentrations Drug conc. in plasma Therapeutic Concentrations Patient will have toxic sideeffects Patient will have a beneficial effect without toxic side-effects Patient will not have any beneficial effect Time (Hrs)

What is Fenretinide? Based on retinoic acid (Vitamin A) Has less severe side effects than other similar drugs currently used to treat cancer Induces tumour cell death using Reactive Oxygen Species (ROS) Vitamin A is found in carrots!

Which Cancers? Neuroblastoma & Ewing’s Sarcoma – Both have low 5 year survival rates (<60%) Neuroblastoma – 90% of patients are under 5 years old – Tumours mainly occur in the abdomen, chest and pelvis Ewing’s Sarcoma – Accounts for 30% of bone cancers – Peak age of diagnosis is mid teens – Mainly occurs in long bones

What Next? Clinical trial of a new formulation of Fenretinide Problems with current formulation: – Young patients have to take a lot of large tablets – There is a large variation in drug concentrations in each patient Benefits of new formulation – Powder which can be mixed in drinks – Improves amount of drug which gets into plasma, and reduces variability

Thank you

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Inhibit Tumour New Blood Vessels Formation to Fight Against Tumour Growth and Spread Zhenhua Zhai Institute of Human Genetics, z. h. zhai@ncl. ac. uk First Supervisor: Dr. Helen Arthur (IHG) Second Supervisor: Dr. Ross Maxwell (NICR) Plasma Presentation Competition, 2009

What is Tumour Angiogenesis? Small localized tumour Tumour that can grow and spread Angiogenesis Blood vessel Signaling molecule released by cancer cells do stimulate endothelial cells to form new blood vessels Tumour Angiogenesis is Essential for Cancer Growth and Spread

Inhibit Tumour New Blood Vessels Formation to Fight Against Tumour Growth × Growth factors released by cancer cells stimulate endothelial cells to form new blood vessels New blood vessels supply nutrition and oxygen leads to tumour growth √ Block growth factors to inhibit tumour new blood vessels formation Insufficient blood supply results in necrotic tumour mass

The Angiogenesis Signaling Cascade Cancer cell aiming to block Endoglin to inhibit endothelial cells growth and reduce new blood vessels formation Growth Factors VEGF (or b. FGF) TGF-beta Receptor protein Endoglin Proteins stimulate new endothelial cell growth Relay proteins Endothelial cell surface Genes are activated in cell nucleus

Endoglin(CD 15) Expression is Upregulated During Tumour Angiogenesis Endoglin Normal colon Endoglin negative expression in normal colon tissue Endoglin Colon cancer Obvious brown staining of Endoglin positive expression in colon cancer

Use Endoglin inducible knockout mice to investigate how efficiently Endoglin depletion protects against tumour angiogenesis and growth. Normal mouse Angiogenesis-deficient mutant mouse( eng iko mice) Transplant tumour cell suspension Cancer No cancer?

X-ray CT & PET and Tissue Analysis Primary Tumour visualized by PET Scanning Mouse skeletal anatomical structure visualized by X-ray CT Primary RFP-lewis lung carcinoma cells are detected by endogenous red fluorescence, blood vessels by staining with FITC-lectin (green) and nuclei are blue (DAPI)

Prospective potential n n Endoglin is a good therapeutic target Blockade of Endoglin inhibits tumour growth and metastasis by preventing vascularization of avascular tumours and by regressing nascent blood vessels Blockade of Endoglin will normalize tumour vasculature resulting improved delivery of chemotherapy and sensitivity to radiation Anti-angiogenic therapy in the combination with chemotherapy will benefit patients with solid cancer

Thank you n n n n Helen Arthur Ben Davison Kath Allinson Marwa Mahmoud Rachael Oakenful Rachael Redgrave Ross Maxwell Sarah Watkins I would like to hear from you. . . If you have questions and feedback about this presentation’s content, suggestions for my project, please speak to me directly or send an email to z. h. zhai@ncl. ac. uk. Thank you for your attention

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Can the UKCAT Improve the Selection of Tomorrow’s Doctors? Sarah Robin Wright School of Medical Sciences Education Development

Admissions Problem Many Highly Qualified Applicants for Limited Places at Medical School • Criticisms of Commonly Used Admissions Tools: • A Level Grades – Dependent upon True Ability or Educational Quality? • Interviews - Can be Biased and Subjective • Personal Statements – Advantage to Students with More Support, and May Not be Written by Candidate These Admissions Practices were Unsustainable!

Problem Solved? In 2007, The United Kingdom Clinical Aptitude Test (UKCAT) was made an Entry Requirement at 26 UK Medical and Dental Schools. 4 Parts to the UKCAT: Quantitative Reasoning Verbal Reasoning Abstract Reasoning Decision Analysis Specifically Designed to Identify Applicants Suited to a Career in Medicine or Dentistry Intended to Add Objectivity and Reliability to Previous Admissions Processes But. . . is it Working?

How Can We Tell if it Helps Improve Admissions Decisions at Newcastle? Compare Pre-UKCAT Entrants with Post-UKCAT Entrants for Evidence of Improved Performance Monitor Performance of Students who would have been Rejected under Old Admissions Policy How Can We Tell if it Predicts Performance of Newcastle Medical Students? Perform a Regression Analysis to Determine whether the UKCAT is a Significant Predictor of Medical School Performance

First Exam Failure Rates of Pre. UKCAT Students vs. Post-UKCAT Students Percentage Failing 50% Post-UKCAT Pre-UKCAT 60% 49% 51% 47% 40% 30% 21% 20% 11% 10% 0% 2004 -2005 -2006 -2007 -2008 Year Group 2008 -2009 Large Drop in Failure Rate Since the Introduction of UKCAT

Accepted Under New Admissions Criteria Standard – Students Accepted Under Either Old or New Admissions Criteria High UKCAT – Students who would have been Rejected Under Old Admissions Criteria but were Accepted Based on High UKCAT Score High UKCAT Students Performed As Well As, if not Better Than Standard Entrants on First Year Exams

Ability of UKCAT to Predict First Year Medical School Exam Performance UKCAT Score was a Significant Predictor of Performance on all 3 First Year Exams at Newcastle Interview and Personal Statement Scores were Not Significant Predictors Regression Models Including UKCAT as a Predictor Variable Explain More Exam Score Variance than Models that do not Include UKCAT The UKCAT is Making a Contribution to the Prediction of First Year Medical Student Performance at Newcastle

Conclusions Since the Introduction of the UKCAT into Newcastle’s Admissions Policy, there has been a Drop in Failure Rates on the First Exam. Students Selected based on High UKCAT Scores, but who would have been Rejected Under Old Admissions Policy are Performing As Well As if not Better than their Peers. The UKCAT is a Significant Predictor of First Year Exam Performance at Newcastle. In its First Year, the UKCAT Appears to be a Positive Contributor to the Admissions Policy at Newcastle.

For Further Information Contact: Sarah. wright@ncl. ac. uk

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Survey of children with Langerhans Cell Histiocytosis (LCH) in the UK and Ireland Jane Salotti – Institute of Health and Society

Langerhans Cell Histiocytosis (LCH) is • a rare disorder of the immune system • it may resolve or be life-threatening • survivors may be left with sequelae National survey of children with Langerhans Cell Histiocytosis

In health Langerhans cells are dendritic cells found in the epidermis and inner lining of the respiratory and digestive tracts. In disease LCH cells accumulate and may damage other parts of the body. Eyes Pituitary Thyroid Teeth Lungs Liver Spleen Gut Skin Bone National survey of children with Langerhans Cell Histiocytosis

Why study LCH? • The aetiology of the disease is unknown. • There have been few epidemiological studies. • The rarity of LCH makes it difficult to study and population-based data on a national level are needed. National survey of children with Langerhans Cell Histiocytosis

The aims of the study were to • ascertain all childhood cases of LCH over a two-year period • describe the incidence of LCH in the UK and Ireland • identify any relevant maternal history or associated illnesses • describe presenting features, treatment, and outcome National survey of children with Langerhans Cell Histiocytosis

Four sources of data were used 1. British Paediatric Surveillance Unit (BPSU) survey of members of the Royal College of Paediatrics and Child Health (RCPCH) 2. Newcastle (NCL) survey of non-RCPCH clinicians National survey of children with Langerhans Cell Histiocytosis

Four sources of LCH data (2) 3. Cross-check with the Children’s Cancer and Leukaemia Group 4. Death registrations from the Office for National Statistics Data were collected from reporting clinicians by questionnaire National survey of children with Langerhans Cell Histiocytosis

Results of ascertainment 94 LCH cases were confirmed BPSU survey (73%) 3 6 10 36 24 NCL survey (62%) 9 6 CCLG register (80%) • No source identified all cases • Each source uniquely identified cases National survey of children with Langerhans Cell Histiocytosis

LCH cases 57 boys 37 girls M: F sex ratio 1. 5: 1 Median age at diagnosis was 5. 9 years 73% had single location bone disease 27% had multiple system disease 3 children died National survey of children with Langerhans Cell Histiocytosis

LCH incidence rates UK and Ireland 4. 12/million/year (CI: 4. 11 - 4. 13) age 0 -14 yrs 9. 9/million/year (CI: 5. 5 – 16. 3) age <1 year Compared with Denmark 5. 4/million/yr age 0 -14 years France 4. 5/million/yr age 0 -14 years Hungary 2. 2/million/yr age 0 -17 years National survey of children with Langerhans Cell Histiocytosis

Future work Data will contribute to a European/ worldwide database of LCH cases to further epidemiological and clinical studies. The study was part-funded by the Histiocytosis Research Trust. Study Team: Kevin Windebank, Mark Pearce (supervisors) Vasanta Nanduri, Watford General Hospital Richard Lynn, BPSU, London Louise Parker, Dalhousie University, Canada National survey of children with Langerhans Cell Histiocytosis

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The Physiology of Pregnancies Ana Dordea 1 st Year Ph. D student 2008 -2009

The Physiology of Pregnancies n n Premature Births: most common cause of neonatal mortality in developed countries! Costs the NHS billions of pounds yearly to care for premature infants!

The Physiology of Pregnancies n n Significant increase of Premature Births over the years! Progress made in caring for premature infants but not in reducing prevalence of preterm births!

The physiology of Pregnancies n Pregnancy: 9 -month period during which the mother nurtures the fetus to maturity through utero-placental communication.

The Physiology of Pregnancies n Mechanisms by which placenta and uterus communicate are yet uncertain. • What triggers premature birth, even though babies are NOT ready?

The Physiology of Pregnancies n n Interest: Understand how the uterine vasculature accomodates development of the newly formed placental vasculature. Research Focus: Compare placental and uterine vasculature.

• Improving our knowledge of uteroplacental vascularisation will : Improve our understanding of normal fetal development to term. Improve our understanding of problems arising throughout gestation. Thank you.

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Individual aspirations in multiorganisational collaborations Laura Lindsey

Aims of the research To explore individuals aspirations in a collaborative setting To explore the changes in the aspirations over a period of time and the possible factors affecting the change Questions of interest… How the individual’s aspirations fit the overall of the collaboration? How organisational culture influences and participation? aims aspirations

Collaboration in question A Centre for Excellence in Teaching and Learning (CETL 4 health. NE) funded for five years by HEFCE Involves the Universities of Durham, Northumbria, Sunderland Teesside with NHS partner organisations and Newcastle University as a lead partner

Methods Mixed methods Qualitative part Semi-structured interviews with 15 -20 people with varying length and level of involvement Quantitative part Questionnaire based on themes from the interviews to everyone involved in the CETL 4 health. NE

Progress Undertaken eight interviews and transcribed the interviews verbatim Preliminary analysis of the interview transcripts to see the areas and questions to focus with the remaining interviews

What has been said so far About why or how they got involved: “…I was getting into the end of term of office on the council for my professional body…this was something else to take on, you know it was an opportunity…” [interview 6] “ [line manager] had said would I be interested in joining, it would be a good opportunity both from my personal perspective but for the organisation as well” [interview 5]

What has been said so far About the organisation influence: “…because we are all big organisations so sort of get into those bits of the organisation to get the buy in is a real challenge…” [interview 8] “. . . a lot of people in the trust don’t know what it is about and they all say to me what is it? ” [interview 4]

Next steps Interview more people to build a fuller picture of how and why people got involved in the collaboration and to explore the organisational influences Construct a questionnaire based on the interview data Build a sketch of the whole collaboration based on individual aspirations Thank you for your interest! If you have any questions please email me laura. lindsey@ncl. ac. uk

Plasma Poster Competition Please go to http: //www. ncl. ac. uk/fms Where you will find links to vote for your favourite of these presentations The author of the most popular presentation wins £ 100

Plasma Poster Competition Please go to http: //www. ncl. ac. uk/fms Where you will find links to vote for your favourite of these presentations The author of the most popular presentation wins £ 100

Mitochondrial DNA depletion and the age-related decline in insulin secretion Donna Hine, Diabetes Lab

mt. DNA depletion and the age-related decline in insulin secretion “There are currently over 2. 5 million people with diabetes in the UK and there are more than half a million people with diabetes who have the condition and don’t know it. ” Diabetes UK Website

mt. DNA depletion and the age-related decline in insulin secretion There are 2 types of diabetes mellitus Type 1 patients are Type 2 patients either produce insufficient unable to produce any insulin and so, amounts of insulin, or target cells no longer need to inject it respond to insulin So what is diabetes mellitus? Blood glucose levels can no longer be maintained via homeostasis Is a consequence of insufficient / non existent insulin secretion

mt. DNA depletion and the age-related decline in insulin secretion The problems associated with diabetes include:

mt. DNA depletion and the age-related decline in insulin secretion Mitochondria are responsible for metabolising glucose… …Mitochondrial DNA (mt. DNA) is maternally inherited and encodes some of the components of the respiratory chain required for ATP synthesis… …Insulin secretion is tightly coupled to glucose metabolism, which depends on the respiratory chain… …Deletions/mutations in mt. DNA have been shown to impair insulin secretion and predispose to diabetes.

mt. DNA depletion and the age-related decline in insulin secretion l TFAM is a mitochondrial transcription factor thought to be a key initiator of mt. DNA transcription. l By knocking down Tfam gene expression in MIN 6 cells, we aim to deplete the levels of mt. DNA. l Depletion of mt. DNA has been associated with the process of ageing. But why use MIN 6 cells?

mt. DNA depletion and the age-related decline in insulin secretion MIN 6 cells are a mouse insulinoma pancreatic β-cell line that respond well to glucose and so, are a good model of how we think human β-cells are likely to react.

mt. DNA depletion and the age-related decline in insulin secretion Therefore… By knocking down Tfam gene expression, we aim to decrease the levels of mt. DNA… …mt. DNA encodes some of the components of the respiratory chain and so… …there will be limited ATP production and a predicted decrease of insulin secretion. mt. DNA

mt. DNA depletion and the age-related decline in insulin secretion Constant high levels of fatty acids are believed to reduce insulin secretion. I plan to use this Tfam knockdown cellular model in order to look at insulin secretion as well as tolerance to fatty acids. I expect to find that as the levels of mt. DNA decrease, less insulin will be secreted and the cells will become less tolerant to fatty acids (resulting in lipotoxicity).

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