The mind

1
The minds eye visual perception in Parkinsons
disease

• Neil Archibald
• Clinical Research Fellow
• Clinical Ageing Research Unit

2
what is visual perception?

• 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

3
For example...
4
how many black dots can you count?
this type of illusion is caused by tricking the
anterior visual system the retina of the eye
5
is this a young woman, an old hag?
or both??
6
Margaret Thatcher looks fine upside down, but..
dreadful the right way up!
7
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
8
why Parkinsons disease (PD)?

• 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

9
what are we doing?

• 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

10
For example...
11
which of the boxes numbered 1 to 4 has the same
pattern as the red box?
12
while youre solving that, here is what your eyes
are doing
13
and here is the map of where you looked
14
what might this tell us?

• 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

15
why does it matter?

• 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

16
Thanks to...

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

17
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

18
Clinical Pharmacology Studies with Fenretinide in
Childrens Cancer

• Nicola Harris
• Northern Institute of Cancer Research

19
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?

20
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)

ROS
ROS
ROS
21
Which Cancers?

• Neuroblastoma Ewings Sarcoma
• Both have low 5 year survival rates (lt60)
• Neuroblastoma
• 90 of patients are under 5 years old
• Tumours mainly occur in the abdomen, chest and
  pelvis

• Ewings Sarcoma
• Accounts for 30 of bone cancers
• Peak age of diagnosis is mid teens
• Mainly occurs in long bones

22
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

23
Thank you
24
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

25
Inhibit Tumour New Blood Vessels Formation to
Fight Against Tumour Growth and Spread

• Zhenhua Zhai
• Institute of Human Genetics, z.h.zhai_at_ncl.ac.uk
• First Supervisor Dr. Helen Arthur (IHG)
• Second Supervisor Dr. Ross Maxwell (NICR)
• Plasma Presentation Competition, 2009

26
What is Tumour Angiogenesis?
Tumour that can grow and spread
Small localized tumour
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
27
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
v
Block growth factors to inhibit tumour new blood
vessels formation
Insufficient blood supply results in necrotic
tumour mass
28
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 bFGF) TGF-beta
Receptor protein Endoglin
Endothelial cell surface
Relay proteins
Genes are activated in cell nucleus
Proteins stimulate new endothelial cell growth
29
Endoglin(CD15) Expression is Upregulated During
Tumour Angiogenesis
Endoglin
Endoglin
Normal colon
Colon cancer
Endoglin negative expression in normal colon
tissue
Obvious brown staining of Endoglin positive
expression in colon cancer
30
Use Endoglin inducible knockout mice to
investigate how efficiently Endoglin depletion
protects against tumour angiogenesis and growth.
31
X-ray CT PET and Tissue Analysis
Primary Tumour visualized by PET Scanning
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)
Mouse skeletal anatomical structure visualized by
X-ray CT
32
(No Transcript)
33
Prospective potential

• 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

34
Thank you

• 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 presentations
content, suggestions for my project, please speak
to me directly or send an e-mail to
z.h.zhai_at_ncl.ac.uk. Thank you for your attention
35
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
36
Can the UKCAT Improve the Selection of Tomorrows
Doctors?

• Sarah Robin Wright
• School of Medical Sciences Education Development

37
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!
38
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?
39
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

40
First Exam Failure Rates of Pre-UKCAT Students
vs. Post-UKCAT Students
41
Performance of Students 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

42
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

43
Conclusions

• Since the Introduction of the UKCAT into
  Newcastles 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.

44
For Further Information Contact

• Sarah.wright_at_ncl.ac.uk

45
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

46
Survey of children with Langerhans Cell
Histiocytosis (LCH) in the UK and Ireland
Jane Salotti Institute of Health and Society
47
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
48
In disease LCH cells accumulate and may damage
other parts of the body.
In health Langerhans cells are dendritic cells
found in the epidermis and inner lining of the
respiratory and digestive tracts.
Eyes Teeth
Pituitary
Lungs
Thyroid
Liver
Spleen
Gut
Skin
Bone
National survey of children with Langerhans Cell
Histiocytosis
49
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
50
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
51
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
52
Four sources of LCH data (2)
3. Cross-check with the Childrens 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
53
Results of ascertainment
94 LCH cases were confirmed
NCL survey (62)
BPSU survey (73)
3
6
10
36
24
9
CCLG register (80)
6

• No source identified all cases

• Each source uniquely identified cases

National survey of children with Langerhans Cell
Histiocytosis
54
LCH cases
57 boys 37 girls MF sex ratio 1.51
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
55
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 lt1 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
56
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
57
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

58
The Physiology of Pregnancies

• Ana Dordea
• 1st Year PhD student
• 2008-2009

59
The Physiology of Pregnancies

• Premature Births most common cause of neonatal
  mortality in developed countries!

• Costs the NHS billions of pounds yearly to care
  for premature infants!

60
The Physiology of Pregnancies

• Significant increase of Premature Births over the
  years!
• Progress made in caring for premature infants ?
  but not in reducing prevalence of preterm births!

61
The physiology of Pregnancies

• Pregnancy 9-month period during which the mother
  nurtures the fetus to maturity through
  utero-placental communication.

62
The Physiology of Pregnancies

• Mechanisms by which placenta and uterus
  communicate are yet uncertain.

• What triggers premature birth, even though babies
  are NOT ready?

63
The Physiology of Pregnancies

• Interest Understand how the uterine vasculature
  accomodates development of the newly formed
  placental vasculature.
• Research Focus Compare placental and uterine
  vasculature.

64
Thank you.

• Improving our knowledge of uteroplacental
  vascularisation will

• Improve our understanding of normal fetal
  development to term.

?Improve our understanding of problems arising
throughout gestation.
65
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

66
Individual aspirations in multi-organisational
collaborations

• Laura Lindsey

67
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 individuals aspirations fit the
  overall aims of the
  collaboration?
• How organisational culture influences
  aspirations and participation?

68
Collaboration in question

• A Centre for Excellence in Teaching and Learning
  (CETL4healthNE) funded for five years by HEFCE
• Involves the Universities of Durham, Northumbria,
  Sunderland and Teesside with NHS partner
  organisations and Newcastle University as a lead
  partner

69
Methods

• Mixed methods
• Qualitative part
• Semi-structured interviews with 15-20 people with
  varying length and level of involvement
• Quantitative part
• Questionnaire based on the themes from the
  interviews to everyone involved in the
  CETL4healthNE

70
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

71
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 bodythis 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

72
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 dont know what
  it is about and they all say to me what is it?
  interview 4

73
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_at_ncl.ac.uk

74
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

75
(No Transcript)
76
(No Transcript)
77
(No Transcript)
78
(No Transcript)
79
(No Transcript)
80
(No Transcript)
81
(No Transcript)
82
(No Transcript)
83
(No Transcript)
84
(No Transcript)
85
(No Transcript)
86
(No Transcript)
87
(No Transcript)
88
(No Transcript)
89
(No Transcript)
90
(No Transcript)
91
(No Transcript)
92
(No Transcript)
93
(No Transcript)
94
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

95
Mitochondrial DNA depletion and the age-related
decline in insulin secretion

• Donna Hine, Diabetes Lab

96
mtDNA 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 dont know it.
• Diabetes UK Website

97
mtDNA depletion and the age-related decline in
insulin secretion
Type 2 patients either produce insufficient
amounts of insulin, or target cells no longer
respond to insulin
Type 1 patients are unable to produce any insulin
and so, need to inject it
There are 2 types of diabetes mellitus
Is a consequence of insufficient / non existent
insulin secretion
Blood glucose levels can no longer be maintained
via homeostasis
98
mtDNA depletion and the age-related decline in
insulin secretion
The problems associated with diabetes include
99
mtDNA depletion and the age-related decline in
insulin secretion

• Mitochondria are responsible for
• metabolising glucose

100
mtDNA depletion and the age-related decline in
insulin secretion

• TFAM is a mitochondrial transcription factor
  thought to be a key initiator of mtDNA
  transcription.

• By knocking down Tfam gene expression in MIN6
  cells, we aim to deplete the levels of mtDNA.

• Depletion of mtDNA has been associated with the
  process of ageing.

But why use MIN6 cells?
101
mtDNA depletion and the age-related decline in
insulin secretion

• MIN6 cells are a mouse insulinoma pancreatic
  ß-cell line that respond well to glucose and so,
  are a good model of how we think human ß-cells
  are likely to react.

102
mtDNA depletion and the age-related decline in
insulin secretion

• Therefore

By knocking down Tfam gene expression, we aim to
decrease the levels of mtDNA
mtDNA encodes some of the components of the
respiratory chain and so
there will be limited ATP production and a
predicted decrease of insulin secretion.
103
mtDNA depletion and the age-related decline in
insulin secretion
104
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