Health Research Board - Health
Research Awards 2015
HRB – HRA 2015 Page 1 of 30
List of awards
HRB - Health Research Awards 2015 – Listed by Host Institution
Project Title
Principal Investigator
Host institution
1
Parent-adolescent
communication and negotiation
of self-management
responsibilities for adolescents'
with Type 1 Diabetes
Dr Veronica Lambert
Dublin City University
2
Spectroscopic imaging for
prognostic applications in breast
and oesophageal cancer
treatment (SPECPREDICT)
Professor Aidan Meade
Dublin Institute of
Technology
3
A Moment for Hand Hygiene in
the Intensive Care Unit: How Can
Compliance be Improved?
Dr Paul O'Connor
National University of
Ireland, Galway
4
EMERGE: A randomised placebo
controlled trial of the
Effectiveness of MEtformin in
addition to usual care in the
reduction of Gestational diabetes
mellitus effects.
Professor Fidelma Dunne
National University of
Ireland, Galway
5
Medically licensed mesenchymal
stem cells for the treatment of
systemic sepsis.
Dr Daniel O'Toole
National University of
Ireland, Galway
6
Traumatic spinal cord injury in
Ireland: service planning for
changing epidemiology
Dr Eimear Smith
National Rehabilitation
Hospital
7
An Inflammatory Biomarker
Study of Psychosis: a Longitudinal
Study in an At Risk Population
Professor David Cotter
Royal College of
Surgeons in Ireland
8
A translational systems biological
study to identify molecular
predictors for responsiveness to
TRAIL-receptor agonists in
colorectal cancer
Dr Markus Rehm
Royal College of
Surgeons in Ireland
9
Blood adenosine levels as a novel
diagnostic of seizures in humans
Dr Tobias Engel
Royal College of
Surgeons in Ireland
HRB – HRA 2015 Page 2 of 30
10
Breast cancer risk: The influence
of blood selenium status and
interactions between selenium
supply biomarkers and genetic
variations in the selenoprotein
gene pathway
Dr David Hughes
Royal College of
Surgeons in Ireland
11
Cold air plasma to enhance
hospital hygiene leading to
reduced surface bacterial counts
and patient acquisition of
vancomycin-resistant enterococci
and Clostridium difficile infection
Professor Hilary
Humphreys
Royal College of
Surgeons in Ireland
12
Early life stress and the
etiopathogenesis of auditory
hallucinations in young people
Professor Mary Cannon
Royal College of
Surgeons in Ireland
13
Irish Medical Career Tracking
Study (The MedTrack Study)
Professor Ruairi Brugha
Royal College of
Surgeons in Ireland
14
Oral flucloxacillin alone versus
flucloxacillin and
phenoxymethylpenicillin for the
emergency department
outpatient treatment of cellulitis:
a non-inferiority randomised
controlled trial
Dr Abel Wakai
Royal College of
Surgeons in Ireland
15
The effects of maternal and foetal Dr Mary Clarke
stress during pregnancy on adult
mental health
Royal College of
Surgeons in Ireland
16
Patient Preferences for Health
Dr Roisin Adams
St. James's Hospital
Foundation Limited
17
Prevention of Postoperative
Persistent Bowel Symptoms in
Patients with Hirschsprung’s
Disease
Professor Prem Puri
The Childrens' Medical
and Research
Foundation
18
Blood Brain Barrier Dysfunction in
Schizophrenia; A Molecular
Genetics Based Approach to
Prognosis
Dr Matthew Campbell
Trinity College Dublin
19
Defining host and microbederived immune targets for
development of improved host-
Professor Joseph Keane
Trinity College Dublin
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directed therapies and vaccines
for TB
20
Development of prognostic
Dr Margaret Dunne
screening tools to predict patient
response to neoadjuvant
chemoradiotherapy treatment for
oesophageal adenocarcinoma
Trinity College Dublin
21
Disease gene independent
generic suppression-based
therapies for retinal disorders
Professor G Jane Farrar
Trinity College Dublin
22
Evaluating metabotropic
glutamate 5 receptor-selective
drugs as a novel therapeutic
strategy for Alzheimer’s disease
Professor Michael Rowan
Trinity College Dublin
23
Evaluating the role of TLR3 L412F
in disease progression in
idiopathic pulmonary fibrosis
Professor Seamas
Donnelly
Trinity College Dublin
24
INCA: Interaction Analytics for
Automatic Assessment of
Communication Quality in
Primary Care
Dr Saturnino Luz
Trinity College Dublin
25
NIMBUS group: Neonatal
Inflammation and Multiorgan
dysfunction and Brain injUry
reSearch group
Professor Eleanor Molloy
Trinity College Dublin
26
Preclinical evaluation of a novel
therapeutic strategy for
Ulcerative Colitis
Dr Patrick Walsh
Trinity College Dublin
27
Research in Depression:
Endocrinology, Epigenetics and
neuroiMaging: the REDEEM study
Professor Veronica
O'Keane
Trinity College Dublin
28
Targeting dysregulated
bioenergetics in the inflamed RA
joint
Dr Jean Fletcher
Trinity College Dublin
29
Targeting NK cells to improve
HCV vaccine immunogenicity
Professor Clair Gardiner
Trinity College Dublin
30
Urine soluble CD163 as a
biomarker of crescentic
Professor Mark Little
Trinity College Dublin
HRB – HRA 2015 Page 4 of 30
glomerulonephritis
31
Viral Hepatitis C Associated
Neurocognitive Dysfunction in
Ireland in the DAA era
Professor Suzanne Norris
Trinity College Dublin
32
Ethnic Minority Health in Ireland Building the evidence base to
address health inequities
Professor Anne
MacFarlane
University of Limerick
33
Dysfunctional mItochondria
proVokes Inflammation iN
prEeclampsia; a novel medical
interventional target to improve
maternal and fetal diagnosis in
preeclampsia. Short title: DIVINE
Professor Louise Kenny
University College Cork
34
Preclinical characterization of
fingolimod as a potential
therapeutic agent for stroke
Dr Christian Waeber
University College Cork
35
Profiling receptive and expressive
prosodic skills in children with
spina bifida and hydrocephalus
Dr Alice Lee
University College Cork
36
PAPRICA: Protein Biomarker
Assays for Psoriatic Arthritis Clinical Evaluation and Validation
of Multiplexed Panels for
Diagnosis and Prognosis
Professor Oliver
FitzGerald
University College
Dublin
37
Towards treatment stratification
for successful smoking cessation:
Harnessing predictive
neurocognitive models
Dr Robert Whelan
University College
Dublin
HRB – HRA 2015 Page 5 of 30
Individual award details
1. Parent-adolescent communication and negotiation of self-management responsibilities for
adolescents' with Type 1 Diabetes
Principal Investigator Dr Veronica Lambert
Host Institution Dublin City University
Duration (months) 36 months
Budget Total (€) € 329,962.00
Lay Summary
Poor Type 1 Diabetes (T1D) self-care results in poor metabolic control and is particularly challenging
during adolescent years. Good metabolic control of T1D is important to prevent long-term negative
outcomes. With parents holding a central role in creating a safe learning environment and
motivating adolescents to monitor food intake, blood glucose levels and insulin administration, the
continual involvement of parents in sharing self-care responsibilities with adolescents with T1D is
recommended to ensure good metabolic control. However, often parents of adolescents with T1D
struggle with finding a balance between monitoring adolescents blood glucose control and fostering
adolescent autonomy for their own diabetes self-care. While previous studies have indicated the
need to develop an intervention to facilitate families to establish shared goals and positive parent
adolescent communication about diabetes shared care, no family based intervention is currently
available. The purpose of this study is to develop a plan for the design of a family based intervention
to support parents’ in communicating and negotiating shared self-care responsibilities with
adolescents (11-17 years) with T1D. Using the Medical Research Council guidelines for the
development of healthcare interventions this study will involve five phases; (i) a systematic review of
previous research in this subject area, (ii) clinic observations, (iii) interviews with 30 families
(mothers and/or fathers and adolescents with T1D) and audio-diaries with 10 families, (iv) a
questionnaire with about 175 parent(s) and adolescents with T1D and (v) the development of a plan
for the design of a new healthcare intervention to support parent-adolescent (with T1D)
communication about shared self-care responsibilities in T1D. The findings of this study will have
many benefits to families with adolescents living with T1D most specifically it will afford them with
an opportunity to have their needs reflected in the design of an intervention to support parentadolescent communication about diabetes shared care.
Ends.
2. Spectroscopic imaging for prognostic applications in breast and oesophageal cancer
treatment (SPECPREDICT)
Principal Investigator Professor Aidan Meade
Host Institution Dublin Institute of Technology
Duration (months) 36 months
Budget Total (€) € 329,393.00
Lay Summary
Each cancer patient has a unique response to cancer treatments such as chemotherapy and
radiotherapy. An individual patient’s response to cancer treatment is to a significant degree
determined by their own biology (genetic profile) and other environmental factors such as diet and
HRB – HRA 2015 Page 6 of 30
lifestyle. With the evolution of technologies such as gene sequencing and associated computational
methods it is now possible to link a patient’s biological profile and lifestyle characteristics to
measurements of their treatment response. This can supply clinicians with a prediction of the risk of
recurrence or probability of regression of cancer for a particular patient and for a particular
treatment option. While there are a number of costly commercial genetic tests (such as the
Oncotype DX assay) that can predict which patients have a higher risk of cancer recurrence, they fail
to predict those who have a low to intermediate risk of recurrence (at least 60% of patients). This
project will develop a novel low cost, rapid assay based on biochemical imaging of patient tissue
which will identify the risk of recurrence of breast and oesophageal cancer before treatment by
chemotherapy or radiotherapy. The project will employ Raman spectral imaging which uses laser
light to image patient tissue and does not require special labelling. A limited pilot study with the
technology has already shown that it predicts radiotherapy response in oesophageal cancer patients
with 85% accuracy. The research will deliver a revolutionary assay clinicians may use to accurately
prescribe the most appropriate therapy option for a given patient with oesophageal or breast cancer
and will form the basis of a technique which can be rolled out for other cancer types in the future.
The assay will lead to a reduced number of patients in whom inappropriate therapies are prescribed
with an associated reduction in healthcare costs.
Ends.
3. A Moment for Hand Hygiene in the Intensive Care Unit: How Can Compliance be Improved?
Principal Investigator Dr Paul O'Connor
Host Institution National University of Ireland, Galway
Duration (months) 36 months
Budget Total (€) €318,044.00
Lay Summary
Healthcare Associated Infections (HCAIs) such as Methicillin-resistant Staphylococcus Aureus (MRSA)
represent the most frequent complications experienced by hospital patients. Effective hand hygiene
practices are considered to be the most important strategy for preventing HCAIs. However,
compliance with good hand hygiene practices has been historically low, leading to a national and
international focus on improving hand hygiene.
Although the hand hygiene procedure itself is simple to carry out, the behaviour related to hand
hygiene is complex and is not readily understood, explained, or changed. International bodies have
made recommendations for how to improve hand hygiene practices, but there are serious
weaknesses in the research evidence to guide the implementation of these recommendations. As a
result, infection control practices are not based on sound scientific knowledge, may be of limited
effectiveness, and resources are not being used efficiently.
The aim of the proposed research project is to take a scientific approach to improving hand hygiene
in the Irish health service. This research will provide valid and practical methods for improving hand
hygiene compliance in Irish Intensive Care Units (ICUs). In order to address the weakness of the
research in this area:

a multi-factorial study involving all of the stakeholders (i.e. patients, nurses, doctors, and
regulators) will be carried out to identify the barriers and facilitators to effective hand
hygiene practices; and
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
based upon this research, all of the stakeholders will be involved in identifying an
sustainable intervention that is appropriate for improving hand hygiene compliance in Irish
ICUs.
The proposed approach provides direction to regulators, health service managers, and health service
providers on ‘how’ standards can be achieved rather than only defining ‘what’ standards must be
achieved. This information will be valuable to improving hand hygiene in critical care settings both
nationally and internationally.
Ends.
4. EMERGE: A randomised placebo controlled trial of the Effectiveness of MEtformin in addition
to usual care in the reduction of Gestational diabetes mellitus effects.
Principal Investigator Professor Fidelma Dunne
Host Institution National University of Ireland, Galway
Duration (months) 60 months
Budget Total (€) €799,903.00
Lay Summary
Diabetes (high blood sugars) that develops during pregnancy is called Gestational Diabetes Mellitus
(GDM).
GDM is increasing, affecting one-in-eight pregnant women in Ireland. Women with GDM have an
increased risk of complications at the time of delivery, including Caesarean section. Women with
GDM have a 7-fold increased risk of diabetes long-term. Infants of mothers with GDM have a greater
risk of being born overweight and require admission to neonatal intensive care units because of low
blood sugars, and other medical complications. The first line of managing high blood sugar levels is
diet and exercise. However, 40% of women with GDM will require insulin to maintain normal blood
sugar levels. While insulin is effective at keeping blood sugars in the normal range, it has important
side-effects and limitations for the mother (e.g. excessive weight gain, low blood sugars, delivery by
caesarean section) and baby (tendency to excess weight). A potential other treatment is a tablet
called metformin used for 30 years in diabetes and fertility treatment. In a GDM trial in New
Zealand, metformin was shown to work as well as insulin and be safe during pregnancy. Metformin
might also reduce the chance of women with GDM developing long term diabetes after pregnancy.
Two trials are on-going examining metformin in overweight women without diabetes and in women
with Type 2 diabetes during pregnancy. We wish to see if metformin is effective for all women with
GDM (not just those who are obese) if given at the time of diagnosis in addition to diet and exercise
management. We want to see also if metformin is associated with less excessive weight gain and
need for insulin. This may translate into better pregnancy outcomes, reduce progression to Type 2
Diabetes for the mother and break the circle of future diabetes in the offspring.
Ends.
5. Medically licensed mesenchymal stem cells for the treatment of systemic sepsis.
Principal Investigator Dr Daniel O'Toole
Host Institution National University of Ireland, Galway
Duration (months) 30 months
Budget Total (€) € 329,559.00
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Lay Summary
Systemic sepsis is a severe condition arising from a bacterial or fungal infection of the blood or
lymph. It commonly leads to overwhelming inflammation and multiple organ failure and can kill up
to 50% of sufferers. Toxins produced by bacteria are the major trigger for these responses in the
patient. There are currently no specific medicines available for systemic sepsis, and treatment relies
on fluid delivery and ventilation coupled with immediate broad-spectrum antibiotics. Recent studies
using adult derived stem cells (MSCs) have indicated profound anti-inflammatory, anti-bacterial and
pro-healing effects in a variety of disease conditions, including other debilitating infectious diseases
such as pneumonia. The Centre for Cell Manufacturing Ireland (CCMI) and Orbsen Therapeutics Ltd.,
both based on the NUI Galway campus, have recently initiated a collaboration to produce medically
licensed MSCs isolated by a novel and highly efficient mechanism. We hope to utilize this exciting
new potential medicine in a series of laboratory experiments to assess their potential. We will
measure anti-inflammatory and anti-biotic traits, the safety of the medicine, and the overall ability
of these MSCs to alter the sepsis disease in an animal model. We will also determine whether a
frozen cell product, a requirement for the treatment of a rapidly evolving acute condition, works as
well as the traditional freshly prepared type. If these evaluations are successful we will proceed to
seek further funding to establish clinical trials in systemic sepsis patients using this novel therapeutic
agent.
Ends.
6. Traumatic spinal cord injury in Ireland: service planning for changing epidemiology
Principal Investigator Dr Eimear Smith
Host Institution National Rehabilitation Hospital
Duration (months) 18 months
Budget Total (€) € 100,344.00
Lay Summary
This project will examine several aspects of traumatic spinal cord injury in the Irish population. The
project will look backwards (retrospective) and forwards (prospective). For the years 2010 - 2014
inclusive, the medical records of all patients with traumatic spinal cord injury discharged from the
National Rehabilitation Hospital (NRH) will be reviewed and information gathered on patient gender,
age, cause of injury, type and severity of injury, length of hospital stay and discharge destination.
During 2016, the same information will be collected as patients sustain injuries and are admitted to
the NRH. A mini-study (pilot) has already been carried out to help in deciding which years to select
for the retrospective part of the study. The 5 year period chosen from 2010 was selected because in
that year the NRH achieved international accreditation; associated with this, there was a change in
documentation in the hospital records which means that necessary data can easily be retrieved since
that time.
Once the information is gathered, statistics will be carried out to estimate how frequently spinal
cord injury occurs per head of population, average patient age when spinal cord injury occurs,
gender most affected, most common causes, types and severity of spinal cord injury. Statistics will
also be carried out to examine if there is an association between patient age or injury type/severity
and the length of hospital stay and discharge destination. For the retrospective part of the study,
results from the 2011 census will be used for statistical calculations. The prospective study coincides
with a new census in 2016.
HRB – HRA 2015 Page 9 of 30
Results of the study will give us updated information on the spinal cord injury patient population,
which we will then use to plan how we deliver rehabilitation services and to assist with discharge
planning.
Ends.
7. An Inflammatory Biomarker Study of Psychosis: a Longitudinal Study in an At Risk Population
Principal Investigator Professor David Cotter
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) € 329,048.00
Lay Summary
Schizophrenia is among the most expensive disorders in terms of quality of life and societal cost.
While treatments are inadequate, early intervention has been shown to be clinically effective.
Consequently, there is an urgent need to improve our understanding of the pathophysiology of this
disorder so that we can identify and treat earlier.
Growing evidence for an inflammatory component to the disorder has clear implications for early
identification, treatment and potentially prevention. The evidence is several-fold;
1. Prenatal maternal infection, and elevated markers of inflammatory processes during the
postnatal period and early childhood, increase the risk of subsequent schizophrenia.
2. Subjects with schizophrenia show evidence of increased blood markers of inflammation.
3. Recent postmortem brain research suggests that there may be an inflammatory subtype of
the disease.
4. Preliminary evidence suggests that anti-inflammatory agents may have therapeutic effects in
schizophrenia.
In addition there is genetic and neuroimaging support for an inflammatory contribution to the
disorder.
There are, however, important gaps in our knowledge:
Firstly, it is not clear whether raised inflammatory markers distinguish those who transition to
psychosis compared to those who do not among a population at risk of psychosis.
Secondly, we do not know how inflammatory markers change over time in individuals at risk of
psychosis. This longitudinal information is critical as it will inform us whether the proposed
vulnerability represented by raised inflammatory markers is a state- or trait-vulnerability, and the
degree to which it is modifiable.
We propose to study the pattern of change in inflammatory markers from childhood and
adolescence (age 12) and late adolescence (age 18), and early adulthood (age 25) among a cohort of
subjects at risk for psychosis. This proposal is based on longitudinal clinical characterisation and
biosampling of subjects in the Avon Longitudinal Study of Parents and Children.
Ends.
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8. A translational systems biological study to identify molecular predictors for responsiveness to
TRAIL-receptor agonists in colorectal cancer
Principal Investigator Dr Markus Rehm
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) € 329,131.00
Lay Summary
Many patients that suffer from cancer of the colon require chemotherapy. Chemotherapy is
supposed to induce the death of cancer cells by a molecularly controlled death process called
apoptosis. Apoptosis in response to chemotherapy requires the activation of cell death genes, but
colon cancer cells often can prevent these genes from being activated, resulting in the failure of
chemotherapy. Novel therapeutics such as 2nd generation activators of “death receptors” on the
surface of cancer cells provide us with the possibility to trigger apoptosis without the requirement
for gene activation. These novel drugs have been tested with great success in initial studies but are
not yet available to patients. To optimally design clinical studies in which patients are offered these
drugs alone or in combination with chemotherapy, tools are required which can predict for
individual patients whether they are likely to respond to treatment. Here, we will develop such tools
by an interdisciplinary approach that integrates the latest and most relevant colon cancer research
methodologies and superior mathematical data analysis procedures to generate reliable predictions
on treatment responsiveness. Our study builds on a substantial amount of promising preliminary
data and will set an example for how innovative research strategies can address significant clinical
needs. Assessing novel treatment options and providing these in an optimised and personalised
manner can benefit large numbers of colon cancer patients in the future.
Ends.
9. Blood adenosine levels as a novel diagnostic of seizures in humans
Principal Investigator Dr Tobias Engel
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) € 328,054.00
Lay Summary
Epilepsy is the most common life-long brain disease and its diagnosis remains challenging needing
the application of multiple criteria including patient history, seizure type and
electroencephalography (EEG) recordings. The most reliable method is long periods under video
surveillance during continuous EEG monitoring which is costly and only a limited amount of
specialised hospital beds are available. Consequently, the majority of patients thought to have
epilepsy are treated on the basis of observed behavioural changes during seizures leading to
possible misdiagnosis. Thus, there is an urgent need to develop disease predictors (biomarkers) to
accurately diagnose epilepsy. These biomarkers have to be easily accessible, easily measurable and
preferably play a causative role during disease progression. The molecule adenosine increases in the
brain after seizures and adenosine augmenting treatments have been proposed as novel therapy
options in epilepsy. Adenosine is present at very low levels in the blood; however, no data on
seizure-induced increases of adenosine in the blood have been reported to date. Most
measurements to quantify adenosine concentrations in blood were depending on techniques poorlysuited to biomarker work. Recently developed adenosine biosensors enable us now to detect
changes in blood adenosine levels rapidly and reliably. These biosensors are suitable for point of
HRB – HRA 2015 Page 11 of 30
care testing as they are easy to handle, require minimal equipment and a minimum blood volume.
Pilot data by the applicant now shows a dramatic increase in blood levels of adenosine after seizures
in different animal models and patients. The project will undertake studies to establish the
relationship between blood adenosine levels and seizure type and severity, timing of sampling and
pathologic outcome. Together, these studies will establish blood adenosine measurement as a novel,
sensitive and specific marker of seizure activity which can be used for seizure diagnosis and for
prognosis of disease progression in patients.
Ends.
10. Breast cancer risk: The influence of blood selenium status and interactions between selenium
supply biomarkers and genetic variations in the selenoprotein gene pathway
Principal Investigator Dr David Hughes
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) €329,980.00
Lay Summary
Hormonal, reproductive, and dietary factors play an important role in the aetiology of breast cancer
(BC). Selenium (Se) is an essential micronutrient thought to aid cancer prevention via its
incorporation into selenoproteins which help counter oxidative damage to DNA, proteins, and lipids.
Such DNA damage also appears to play a notable role in BC initiation and development. Although we
only need Se in small amounts, its availability in Irish and most European soils is often insufficient for
optimum dietary levels. Low Se levels and variations in the genes encoding selenoproteins may
influence a woman’s risk of developing BC, but this has not been adequately studied, especially
before cancer onset. This project will measure in blood samples from a large prospective European
cohort of women with BC (2,500 cases) matched to an equal disease-free number (2,500 controls)
two markers of Se status (levels of Se and the main Se transport protein, Selenoprotein P). The
activity of the anti-oxidant selenoprotein glutathione peroxidase will also be measured in 1,500 of
these case-control pairs as evidence suggests it could be a potential marker of cancer risk in women
taking HRT. We will additionally measure genetic differences in selenoprotein genes and related
anti-oxidant enzyme genes in available DNA from 1,496 of these case-control pairs. Appropriate
statistical data analysis methods will be used to determine if Se status levels and hereditary genetic
variation in selenoprotein genes are significantly associated with BC risk in European populations,
and if Se status and selenoprotein genetic changes together with other dietary/lifestyle factors
interact to modify BC risk. The proposal will benefit from existing extensive epidemiologic and
biomarker data for our study subjects. This project will help define the context of Se use for BC
prevention in women whose Se status is sub-optimal and also for individuals of particular
selenoprotein genotypes.
Ends.
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11. Cold air plasma to enhance hospital hygiene leading to reduced surface bacterial counts and
patient acquisition of vancomycin-resistant enterococci and Clostridium difficile infection.
Principal Investigator Professor Hilary Humphreys
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) €703,765.00
Lay Summary
Healthcare-associated infections (HCAI) affect 5-10% of patients admitted to an acute hospital but it
is about three times higher in intensive care units (ICUs). Prevention involves many strategies but
environmental hygiene is important as many bacterial causes persist on horizontal surfaces, e.g.
methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and
Clostridium difficile. Conventional approaches to hospital cleaning including the use of detergents
and disinfectants are often inadequate because of poor practice, difficulties in accessing busy clinical
areas, and challenges in decontaminating items that are heat sensitive. Cold air plasma is an
emerging approach which can reduce the numbers of viable bacteria on a surface by a factor of 100,
or more, and has been piloted in Beaumont Hospital. We propose to carry out a controlled study
which would use cold air plasma, in addition to conventional hospital cleaning to: decrease the
overall numbers of all bacteria on high risk or commonly touched surfaces in two ICUs and numbers
of VRE and C. difficile. At the same time, we will also monitor the quality of routine cleaning using a
well proven method. A second objective will be to reduce the acquisition of VRE and C. difficile
infection amongst patients admitted to the two ICUs. ‘High risk’ surfaces that are frequently in
contact with the patient, e.g. bed sides, will be targeted by the cold air plasma decontamination
process. This study will be carried out in a clinical arena, but with no danger to patients or staff, and
will confirm the usefulness of this novel decontamination approach in improving hospital hygiene,
reducing surface bacterial numbers and preventing HCAI.
Ends.
12. Early life stress and the etiopathogenesis of auditory hallucinations in young people
Principal Investigator Professor Mary Cannon
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) €329,267.00
Lay Summary
This research project aims to look at the relationship between experiencing stressful life events
during childhood and experiencing psychotic-like symptoms (like hearing voices that other people
can't hear, for example) in adolescence. Researchers have already shown that there is a relationship
between these two experiences but, up until now, no one has been able to find out exactly why and
how stressful life events in childhood put some young people at increased risk of developing
psychotic-like symptoms in their adolescent years. The team involved in this project will use
information on over 8,000 young people in Ireland to examine whether the timing, duration or types
of stressful life events are relevant in understanding why some young people who experience
stressful life events are more likely to develop psychotic symptoms than others. The team will also
examine detailed brain scan images of adolescents, both with and without psychotic symptoms, to
see whether or not they offer any clues as to why some young people experience these psychoticHRB – HRA 2015 Page 13 of 30
like experiences while others do not. The team is particularly interested in a particular area of the
brain known as the Hippocampus. This research has the potential to uncover new information about
the kinds of life experiences that place young people at particular risk for developing psychotic-like
symptoms and to identify certain processes in the brain that are associated with these experiences.
Findings from the study will be used to inform the public, clinicians and policy makers about how
best to support young people who experience early life stress.
Ends.
13. Irish Medical Career Tracking Study (The MedTrack Study)
Principal Investigator Professor Ruairi Brugha
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) €329,466.00
Lay Summary
Hardly a week goes by without a national media report on the medical staffing crisis in the Irish
health services, which is perhaps the biggest current threat to the delivery of quality health services
to the population of Ireland. With 6- and 12-monthly staff turnovers, employers are forced to recruit
staff from abroad to fill posts and most advertised consultant posts go unfilled. Meanwhile, there
are reports of large scale emigration by graduates of Irish medical schools. To address this crisis,
policy makers and planners need evidence on doctors career intentions, their specialty choices; and
the conditions that will determine their willingness to train and make their careers in Ireland.
This project aims to design and implement the first longitudinal medical career tracking study to
report, analyse and track the career choices and decisions of Irish medical graduates. It will include
estimates of the losses to the Irish exchequer from training and then losing Irish doctors. The
research will start with a survey of students before they graduate from Ireland’s six medical schools,
followed by in-depth interviews and two annual surveys to provide evidence of career and speciality
choices and intentions; and doctors’ experiences and the costs to them of postgraduate training. The
project will cost undergraduate and postgraduate training; and predict the future losses incurred by
the State, if large scale emigration and losses from the medical workforce continue.
The project will contribute much needed evidence for national workforce planning and monitoring;
and will test the feasibility of establishing an ongoing longitudinal Irish Medical Careers Tracking
Study. The project team has forged strong working relationships with the principle national decision
makers in the Department of Health, the Health Service Executive, the Medical Council of Ireland
and national training bodies.
Ends.
HRB – HRA 2015 Page 14 of 30
14. Oral flucloxacillin alone versus flucloxacillin and phenoxymethylpenicillin for the emergency
department outpatient treatment of cellulitis: a non-inferiority randomised controlled trial
Principal Investigator Dr Abel Wakai
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) €797,080.00
Lay Summary
Acute bacterial skin and skin structure infections (ABSSSIs) are commonly encountered in Emergency
Departments (EDs). In Ireland, the most common ABSSSI is cellulitis, which is a spreading bacterial
infection of the skin and tissues beneath the skin. Approximately 12 in every 1,000 ED patient
attendances in Ireland is due to cellulitis. This roughly translates to 1-2 attendances per day in an ED
seeing 40,000 new patients per year. This group of infections therefore represents a serious
healthcare and societal burden. Despite this burden, the antibiotic treatment of cellulitis and impact
it has on patients' quality of life and economic circumstances has not previously been studied in
Ireland.
The most commonly prescribed antibiotics for cellulitis in Ireland, the United Kingdom and many
parts of Europe are called flucloxacillin and phenoxymethylpenicillin. Current evidence reveals that
for patients discharged home from EDs on antibiotic treatment, doctors prescribe antibiotics in a
disparate fashion: both antibiotics are prescribed together in one-third; flucloxacillin alone in onethird; and a variety of other antibiotics to the remaining one-third. Hospital prescribing guidelines
are also contradictory and evidence from published textbooks and research papers show widespread
practice variation with no agreed consensus.
We aim to perform a randomised controlled trial (RCT) comparing oral flucloxacillin and placebo to
oral flucloxacillin and phenoxymethylpenicillin for the treatment of cellulitis, thus providing
definitive evidence to address this disparate prescribing practice. We also aim to provide important
information about how cellulitis affects a patient’s quality of life, the usefulness of a specially
designed quality-of-life instrument for patients with cellulitis, the economic impact of cellulitis on
patients, and finally, how well patients adhere to their prescribed antibiotic treatment. We have
created a unique collaboration of researchers in order to provide much needed evidence to guide
doctors treating this relatively common but understudied condition.
Ends.
15. The effects of maternal and foetal stress during pregnancy on adult mental health
Principal Investigator Dr Mary Clarke
Host Institution Royal College of Surgeons in Ireland
Duration (months) 36 months
Budget Total (€) €114,700.00
Lay Summary
The causes of both common mental illnesses like anxiety and depression and more severe mental
illnesses like schizophrenia and bipolar disorder are still unclear. We know that these illnesses are
most likely a complex mix of environmental factors working in conjunction with underlying genetic
vulnerability. The genetic input to these disorders appears to be highly complex and involves
HRB – HRA 2015 Page 15 of 30
multiple genes. The hope of early intervention to prevent these disorders seems likely to lie in the
possibility of preventing adverse events in the environment from affecting brain development in our
young people which leaves them more susceptible to mental illness in young adulthood. In this
project we look at factors during pregnancy, early infancy and in childhood which may increase the
likelihood of illnesses like depression and schizophrenia in adulthood through effects on early
neurodevelopment. In this way we hope to identify ways of better structuring our environment so
that we protect and promote mental health and wellbeing from the very beginning of a child’s life.
Ends.
16. Patient Preferences for Health
Principal Investigator Dr Roisin Adams
Host Institution St. James's Hospital Foundation Limited
Duration (months) 18 months
Budget Total (€) €125,673.00
Lay Summary
In Ireland we ask society or the general public to state their preferences for descriptions of health.
We then use these valuations or preferences to calculate the impact of technologies on quality of life
and this informs how decision makers decide what to fund. This is known as the QALY framework
and is used in most jurisdictions to determine benefit alongside value. The majority of national
societal valuation studies ask people to imagine being in a health state and the experience of being
in a health state is not explicitly captured. However it is likely that a person’s experience of being in a
health state will alter their preferences compared to those who are only imagining being in that
state. In determining whether treatments represent value for money we mainly consider societal
valuations of imagined health states and very little information is included formally from patients.
The work proposes to quantify the differences between patients valuations having experienced and
not experienced health states and the general population. It will also explore whether non-health
aspects, defined as wellbeing are captured by the QALY. Finally it will use a sub population of
patients who have cystic fibrosis or multiple sclerosis to construct a value set to test the impact on
decisions related to reimbursement of pharmaceutical technologies. The body of work proposed will
inform how we establish the Values Framework as laid down in the governments White Paper for
Universal Health Insurance.
Ends.
17. Prevention of Postoperative Persistent Bowel Symptoms in Patients with Hirschsprung’s
Disease
Principal Investigator Professor Prem Puri
Host Institution The Childrens' Medical and Research Foundation
Duration (months) 36 months
Budget Total (€) € 301,869.00
Lay Summary
Hirschsprung’s disease (HD) is a relatively common cause of intestinal obstruction in the new-born,
occurring in 1 in 4,000 live births. It is characterised by abnormal development of the nerve supply to
varying lengths of the large bowel prior to birth. The gold standard treatment for HD is an operation
to remove the diseased bowel from the anal canal until healthy bowel is reached with a normal
nerve supply, which is then joined to the anal canal to restore normal bowel function. Despite a
HRB – HRA 2015 Page 16 of 30
properly performed operation, a substantial proportion (35-48%) of patients suffer from persisting
bowel symptoms such as constipation, soiling and an inflammatory condition of the bowel known as
enterocolitis. Gastrointestinal motility is controlled by four groups of cells, the enteric nervous
system (ENS), interstitial cells of Cajal (ICCs), Platelet-derived growth factor receptor alpha-positive
cells (PDGFRα+ cells), and smooth muscle cells (SMCs). Together, these four networks of cells
regulate secretory activities and peristalsis of the bowel. The mechanisms underlying persistent
symptoms post-surgery are poorly understood and understudied. We hypothesise that the
ganglionic pulled-through bowel in HD is abnormal and therefore propose to investigate the
morphological and molecular characteristics of the entire resected bowel specimens from patients
with HD, with particular emphasis on the expression of ion channels within the smooth muscle layer,
and PDGFRα+ cells.
Ends.
18. Blood Brain Barrier Dysfunction in Schizophrenia; A Molecular Genetics Based Approach to
Prognosis
Principal Investigator Dr Matthew Campbell
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 328,345.00
Lay Summary
Schizophrenia has been estimated to affect up to 1 in 100 people in Ireland. Given its prevalence, the
underlying causes of the condition are still far from clear. Intriguingly, there exists a chromosomal
abnormality termed 22q11 deletion syndrome (22q11DS), where schizophrenia can manifest 20
times more frequently than in the general population.
Each cell of our body contains 23 pairs of chromosomes, and genetically, 22q11DS patients lack
approximately 40-60 genes within a small region in one of the pairs of chromosome 22. In effect,
22q11DS patients will have less or indeed dysfunctional expression of a selected number of genes
and this is likely the cause of their condition. It has however proven very difficult to pinpoint the
exact gene or collection of genes that together cause the clinical features of 22q11DS. It has also
proven difficult to determine why some patients develop schizophrenia while others don't. Here, we
wish to explore the role of the molecule claudin-5 in 22q11DS patients and how it may be involved in
the development of schizophrenia in certain individuals. Claudin-5 is highly important in regulating
the blood-brain and blood retina barriers (BBB/BRB) and decreased levels of the protein product of
this gene have been shown by us and others to cause "leakiness" and developmental defects in the
blood vessels associated with the brain and retina. Using genetic, molecular biology and pre-clinical
modelling approaches, we wish to establish whether there are variants (mutations) in the remaining
claudin-5 gene of a cohort of 22q11DS patients and whether these variants pre-dispose some
patients to abnormal brain and retinal blood vessels. The aim is to be in a position to establish a coordinated care pathway for patients in the future which will empower patients, their families and
the public health system.
Ends.
HRB – HRA 2015 Page 17 of 30
19. Defining host and microbe-derived immune targets for development of improved hostdirected therapies and vaccines for TB
Principal Investigator Professor Joseph Keane
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 329,980.00
Lay Summary
Almost one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb) with
almost 2 million deaths to tuberculosis (TB) annually. Over 400 patients are treated for active TB
annually in Ireland, with an increasing number of drug-resistant cases emerging. Currently treatment
involves a multi-drug course for 6 months, which is extended to 2 years in cases of multi-drug
resistant TB (MDR-TB). There is an immediate need to shorten the current TB treatment as drug
compliance for this length of time is a huge problem. Furthermore the current vaccine, BCG, works
with varying efficacy. Improved drug treatments and vaccine design are urgently required.
Specialised cells in the lung, called alveolar macrophages, are the first cells which the bacteria
encounters and are crucial to the resolution of the disease. We need to understand how these cells
responds during TB infection to develop new treatments. These cells use a number of process to get
rid of unwanted invaders. Autophagy is one of the cell’s mechanisms which can eliminate unwanted
cargo, such as cell debris or damaged cellular components. Autophagy has also been shown to play
an important role in eliminating bacteria and viruses by degrading them with acidic enzymes. The
mechanism of autophagy in human alveolar macrophages during TB disease is unclear. However
understanding this important immune mechanism will identify targets that can then be used to
develop new drug treatments and potential vaccine candidates. We will investigate whether drugs
used to treat other diseases may be used for TB by targeting autophagy to improve the immune
response of TB patients. We will also examine the bacteria to identify regions of the bacteria that are
responsible for manipulating autophagy and the immune response. This study will to contribute to
the development of improved treatment options for TB patients and vaccine design.
Ends.
20. Development of prognostic screening tools to predict patient response to neoadjuvant
chemoradiotherapy treatment for oesophageal adenocarcinoma
Principal Investigator Dr Margaret Dunne
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 310,939.00
Lay Summary
Cancer of the oesophagus, or food pipe, is an aggressive type of cancer with poor outlook and is
affecting a growing number of people. The main types of treatments are surgery, chemotherapy and
radiotherapy, which may be given alone or in combination. Although chemoradiotherapy treatments
work well for some, the majority of patients will not respond. Currently there is no way to identify
responding or non-responding patients. This means the majority of patients with oesophageal
cancer receive chemoradiotherapy treatment with no benefit. We aim to develop ways of identifying
patients who may benefit from chemoradiotherapy treatment, at the point of their diagnosis.
Previous work in our lab shows that patients who have higher levels of a certain molecule in their
tumours survive longer than patients with lower levels. This molecule is called human leukocyte
HRB – HRA 2015 Page 18 of 30
antigen (HLA-DR). HLA-DR plays an important role in the immune system but it is not known how or
why it increases in tumours. We will investigate the role of HLA-DR as a predictor of patient
responses. We will also explore other methods of predicting patient responses by tumour tissue
analysis. By analysing the levels of immune cells present in tumours, researchers have developed
scoring systems that can successfully predict patient outcomes in colorectal cancer. So far these
scoring systems have not been tested in oesophageal cancer. We will test whether such methods
can be used to predict patient responses to treatment using tumour samples collected from patients
enrolled on an on-going clinical trial testing two different treatment strategies. By developing tools
to predict patient responses to chemoradiotherapy treatment, this study will help doctors to decide
on the best treatment options for patients, as well as increasing our understanding of the role of the
immune response in tumours, which will aid development of improved treatments.
Ends.
21. Disease gene independent generic suppression-based therapies for retinal disorders.
Principal Investigator Professor G Jane Farrar
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 327,462.00
Lay Summary
Multiple mutations in over 200 genes can cause retinal degeneration, a group of diseases that result
in the death of light detecting photoreceptor cells in the retina. Mutations in more than 30 genes
can also cause optic neuropathies, a group of disorders that affect retinal ganglion cells, causing the
optic nerve to be less capable of delivering visual signals to the brain. Both sets of disorders result in
loss of vision and therefore result in significant deleterious effects with respect to patient quality of
life and costs to the health care system. Given the multiplicity of mutations giving rise to retinal
disease, the rarity of some disease genes, and the enormous costs associated with running clinical
trials, it is evident that ‘generic’ therapies for these disorders targeted at modulating common
disease mechanisms observed in many of these disorders would be relevant to a greater number of
patients and therefore would represent a breakthrough in patient care. Both retinal degeneration
and optic neuropathy show raised levels of oxidative stress prior to death of the affected cells.
Oxidative stress results in raised levels of free radicals and damage within the cell as malfunctions
due to the presence of an inherited mutation, for example rendering the cell unable to cope with the
daily demands of metabolism. The current study is concerned with exploring innovative therapies
focused on reducing the levels of oxidative stress within photoreceptor and/or retinal ganglion cells,
thereby resulting in longer cell survival times and significant delays in onset of vision loss.
Ends.
HRB – HRA 2015 Page 19 of 30
22. Evaluating metabotropic glutamate 5 receptor-selective drugs as a novel therapeutic
strategy for Alzheimer’s disease
Principal Investigator Professor Michael Rowan
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 329,996.00
Lay Summary
Clinical dementia, the majority of cases being caused by Alzheimer’s disease, seriously impairs the
lives of over 50 million people worldwide currently (costing ~1% of the aggregated global gross
domestic product). There are approximately 48,000 people with dementia and 50,000 dementia
carers in Ireland At present the lifetime risk of developing dementia is about 10% but this is
increasing rapidly as the population ages in countries like Ireland. The cost to the Irish economy is
estimated to be just over €1.69 billion per annum and growing. There is a huge unmet need for
effective therapies for Alzheimer’s disease. Patients experience a devastating progressive and
insidious loss of mental function associated with the brain deposition of misshapen proteins, in
particular, amyloid ß-protein and tau. The symptoms are caused by disruption of transmission at the
junctions between brain cells. Currently approved drugs for the treatment of Alzheimer’s disease
either boost the transmitter acetylcholine or inhibit the action of the transmitter glutamate at sites
called N-methyl-D-aspartate (NMDA) receptors, but these agents have very limited or no therapeutic
efficacy in the vast majority of patients. Recently, we and others found that reducing the action of
glutamate at sites called metabotropic glutamate 5 (mGlu5) receptors show promise as a novel
potentially disease modifying strategy. The proposed research will evaluate the therapeutic
potential of different mGlu5 drugs for Alzheimer’s disease by rigorously studying their efficacy
against the disruptive actions of amyloid ß-protein in a range of tests in live animals, including those
using patient-derived samples. This will enable us to optimise drug choice for future clinical trials of
early disease interventions. We believe that results from this study will lead directly to better ways
of targeting mGlu5 receptors in neurology and psychiatry and in particular the development of new
potential disease modifying therapies for Alzheimer’s disease.
Ends.
23. Evaluating the role of TLR3 L412F in disease progression in idiopathic pulmonary fibrosis.
Principal Investigator Professor Seamas Donnelly
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 318,797.00
Lay Summary
Idiopathic pulmonary fibrosis (IPF) is a lung disease of unknown cause which leads to excessive
scarring of the lungs, resulting in loss of lung function, respiratory failure and ultimately, death. IPF is
believed to be caused by abnormal repair of the lung after a chronic injury by an unknown agent to
the lining of the lung (the epithelium), in patients with a specific genetic defect. In many cases, IPF
has a worse prognosis than cancer.
Each year, 29 individuals per 100,000 will get IPF. Furthermore, 15% of these patients will develop a
very aggressive and rapidly progressive form of IPF and will die approximately 12 after their
diagnosis. In contrast, some patients develop a form of IPF that progresses very slowly. One of the
HRB – HRA 2015 Page 20 of 30
greatest difficulties facing clinicians today is the inability to determine at diagnosis which of their
patients will develop a very aggressive and fatal form of IPF. Certain viral infections are believed to
be associated with initiating the lung damage which causes IPF or making the existing conditions
worse.
Professor Seamas Donnelly’s research group at Trinity College Dublin has identified an anti-viral
receptor called Toll-like receptor 3 (TLR3) which, when defective, is associated with making IPF
worse and causing its rapid progression. Specifically, they have identified a genetic mutation in the
TLR3 gene (called TLR3 L412F), which when present can make IPF develop very quickly and cause
death. In this research project, our aim is to work out how TLR3 L412F causes these dreadful effects
and death in IPF patients. In the future, we hope that TLR3 L412F will help clinicians to determine
what form of IPF their patients will develop at diagnosis in order to provide these patients with the
best clinical treatment and to prevent their early death.
Ends.
24. INCA: Interaction Analytics for Automatic Assessment of Communication Quality in Primary
Care
Principal Investigator Dr Saturnino Luz
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 313,155.00
Lay Summary
Communication between physician and patient is crucial to the overall quality of primary care. An
important element of this interaction is the physician-patient interview. While there are various
opinions on what constitutes effective communication in a medical interview, sometimes supported
by formal (qualitative and quantitative) studies, empirical evidence in this area is relatively scarce.
Part of the difficulty in studying interaction in medical interviews is that, in order to analyse verbal
and non-verbal aspects of interaction which might influence patient outcomes, one must annotate
audio or video recordings of interviews in detail. In published literature, this has mostly been done
manually. As this process is time consuming and error-prone, the scale and value of such studies is
limited.
This project will investigate the feasibility of a technological mechanism for electronic gathering and
automated analysis of physician-patient interaction during medical interviews. It will apply state of
the art technology in speech processing, text analytics and social signal processing, and investigate
the impact of models through which comprehensive, data-intensive communication analysis could
be conducted. This interaction analytics research will use routinely collected audio-visual data from
consultations between patients and trainee general practitioners.
This research project involves automatic speech and text processing. A research outcome will be the
error measures of automated speech transcription and categorisation.
The non-verbal behaviour of clinicians will be examined. Outcomes include variation by clinician and
by section of the medical interview, and quantification of the frequency of each form of non-verbal
behaviour. Interview sections will be specified based on the Calgary Cambridge Guide to the Medical
Interview. Non-verbal behaviour includes attitudes (empathy), and social signals such as gaze, body
posture, facial expressions and gestures. Computational analysis will identify dimensions of physician
HRB – HRA 2015 Page 21 of 30
verbal behaviour (words) predictive of effective communication, and communication characteristics
shall be displayed visually for each physician.
Ends.
25. NIMBUS group: Neonatal Inflammation and Multiorgan dysfunction and Brain injUry
reSearch group
Principal Investigator Professor Eleanor Molloy
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 329,952.00
Lay Summary
Neonatal brain injury has a many causes and may result in cerebral palsy. Cooling therapy is the only
established treatment but 50% of babies treated will die or have disability and so new therapies to
reduce brain injury are urgently needed. New-borns who are severely affected also have problems
with their heart, liver, lung and kidney function. We plan to measure the injury to these organs in
detail using new techniques to look at the brain, heart and kidneys. This will allow us to target each
organ with specific therapies and improve outcomes. We have previously shown that inflammation
is increased in these babies and is related to the severity of brain injury and this may be a possible
target for future interventions as well as a early good marker to predict their outcome. By
understanding inflammation in these babies we can target new treatments to add to cooling therapy
to protect their brain and improve outcome.
Ends.
26. Preclinical evaluation of a novel therapeutic strategy for Ulcerative Colitis
Principal Investigator Dr Patrick Walsh
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 328,668.00
Lay Summary
Inflammatory Bowel Disease (IBD) is a chronic relapsing intestinal inflammatory condition
comprising of separate disease manifestations known as ulcerative colitis (UC) and crohns disease
(CD). Despite significant advances in our understanding of the basic mechanisms which promote
these diseases, current treatment strategies usually involve non specific suppression of the chronic
inflammatory response and are ineffective in a large number of patients. Although the reasons for
this are not fully understood, it seems likely to reflect the complex nature of chronic intestinal
inflammation. In an effort to define new, disease specific pathways in IBD, which offer potential for
therapeutic targeting, we have been investigating mechanisms associated with the earliest phases of
disease onset before chronicity has become established. We believe that this is a more likely
successful approach which will allow us to target pathways and intervene early in disease
progression before chronicity is reached. Through these studies we have identified a new pathway,
known as the IL-36 pathway, which we have found plays a significant role in the development of UC.
This proposal aims to develop a new approach to specifically target this pathway for therapeutic
intervention and improve disease outcomes.
Ends.
HRB – HRA 2015 Page 22 of 30
27. Research in Depression: Endocrinology, Epigenetics and neuroiMaging: the REDEEM study
Principal Investigator Professor Veronica O'Keane
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 317,162.00
Lay Summary
Depression is the most common psychiatric disorder in the world, accounting for approximately 90%
of deaths by suicide. Rates of depression are rising alarmingly in the OECD countries. Although
depression is considered to be a single clinical disorder, it has many underlying causes ranging from
childhood abuse through to purely genetic causes. We do not, however, understand the different
clinical features or the different neurobiological changes that may correspond to the different
pathways to depression. Neither do we have treatments for the different types of depression. The
genetic versus environment debate has now evolved to understanding how the environment alters
our gene function: a process called epigenetics. It is known that prolonged stress early in life, even
pre-birth, can change the epigenetic control of our stress systems. In this way childhood
maltreatment can change our stress responses, making an individual more prone to becoming
stressed, leading to clinical depression in adulthood. Our research group are unravelling the complex
stress/immune/brain interactions involved in the pathway from childhood maltreatment to adult
depression. Each pathway to depression has a corresponding biology in epigenetic and
stress/immune systems changes, and in the emotional circuitry in the brain. In our project we wish
to examine these systems in a group of young people presenting for the first time with a depressive
episode in relation to childhood maltreatment and other risk factors. We will have a young healthy
comparator group and will follow both groups up over an 18-month period to see how recovering
from depression, or not, may change these systems. This project is important because early
intervention with treatments directed at the specific disease processes causing depression are
needed. Otherwise, stress-sensitive systems in the body may become permanently damaged,
leading ultimately to atrophy of the emotional and memory centres in the brain.
Ends.
28. Targeting dysregulated bioenergetics in the inflamed RA joint
Principal Investigator Dr Jean Fletcher
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 329,665.00
Lay Summary
Rheumatoid arthritis (RA) is a form of inflammatory arthritis that affects approximately 45,000
people in Ireland and bears a high personal, social and economic cost. It is estimated that the cost of
treating patients with RA in Ireland is approximately €20,000 per patient per year. RA is an
inflammatory condition characterized by painful inflamed joints, resulting in joint deformity and
disability. It is an autoimmune disease, in which the immune system has become dysregulated and
attacks joint tissue. Although current therapies that target the immune response are effective in
some patients, others do not respond or experience side effects. In addition these treatments are
expensive and place a burden on the healthcare system. Thus despite many advances that have
been made, there is still a pressing need for new and more cost effective therapies for RA. In chronic
inflammation, new blood vessels grow which are abnormal and this combined with an increase in
HRB – HRA 2015 Page 23 of 30
influx of active inflammatory immune cells, results in deficiency of oxygen levels in joint tissue. Low
oxygen levels result in less cellular energy being produced, thus cells adapt by switching on
metabolic pathways that will produce energy in the absence of oxygen. We and others have shown
that low oxygen levels and changes in metabolism of the cell can be potent regulators of the
inflammatory process and can alter response to therapy. Therefore, in the current proposal we will
target the cellular energy pathways in order to develop new and more cost effective therapies for
RA. We will test different molecules that target cellular metabolism including metformin, which is a
relatively low cost drug already used to treat diabetes. Metformin has proven effective in animal
models of autoimmune disease including RA, but has not yet been tested in cells from RA patients.
Ends.
29. Targeting NK cells to improve HCV vaccine immunogenicity
Principal Investigator Professor Clair Gardiner
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 329,994.00
Lay Summary
Hepatitis C virus (HCV) infects over 170 million people in the world. Most individuals go on to
develop a chronic lifetime infection that is associated with progressive liver disease. While new
drugs have recently been developed, they are very expensive and are not a treatment option for
developing countries. In addition, there are some patient groups e.g. patients co-infected with HIV-1
and HCV, that may not be as responsive to therapy. Drug resistant variants of the virus may also
emerge. For all these reasons, there is an urgent need to develop a vaccine against HCV. While
progress has been relatively slow in terms of HCV vaccine development, a group in Oxford University
have recently developed and tested a HCV vaccine that gave promising results in clinical trials. Based
on this, they have now developed a new generation of HCV vaccines that are currently being tested
in healthy volunteers and will shortly be tested in HIV-1 positive patients. We are collaborating with
these expert researchers and indeed, one arm of the new vaccine trial is actually taking place in St.
James’s Hospital. The work proposed here will study the immune responses of both patients and
HIV-1 infected individuals in response to these new vaccines. Our collaborators are studying the later
time points of the immune response to vaccine and here, we will study the cells involved in the early
immune response to vaccine, in particular Natural Killer (NK) cells. We plan to identify how these
cells influence the immune response to vaccine and how we can potentially modulate these cells to
improve immunity induced by HCV vaccines; this may be particularly important in HIV-1 patients.
This work has the potential to translate into the clinic as an immunomodulation strategy to improve
the immune response to vaccine.
Ends.
HRB – HRA 2015 Page 24 of 30
30. Urine soluble CD163 as a biomarker of crescentic glomerulonephritis
Principal Investigator Professor Mark Little
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 329,767.00
Lay Summary
Crescentic glomerulonephritis (CGN) is a severe form of kidney failure that leaves about one third of
sufferers dependent on dialysis or needing a kidney transplant. It is currently difficult to assess the
condition without performing a kidney biopsy, which is uncomfortable, expensive and occasionally
dangerous to the patient. We have discovered that a protein present in kidneys of people with CGN,
called CD163, is shed into the urine where it can be measured by a simple test. We have investigated
this in a large group of people with one form of CGN (ANCA vasculitis) and found that the level of
CD163 in the urine predicts accurately whether active CGN is present or not.
We now wish to bring this test closer to actual patient care by doing four things: 1. We will establish
the test in the hospital setting. 2. We will assess whether the test can diagnose a flare of ANCA
vasculitis without needing a kidney biopsy. 3. We will measure the CD163 level in four separate
sample collections around the world to see whether our findings hold true in other settings. 4. We
will use the test to find out when the urine CD163 level disappears with treatment, which we hope
will guide for how long that treatment is needed. Taken together, these four strategies will place this
new test in a position where it can be used in clinical practice. Apart from helping us diagnose CGN
flare, we believe that this test will be useful in settings where access to the kidney biopsy or
specialised blood tests is limited, such as in developing countries or rural areas. Here the test may
assist in diagnosing CGN in the first place (rather than diagnosing a flare), which would greatly
increase the number of people who could benefit from it.
Ends.
31. Viral Hepatitis C Associated Neurocognitive Dysfunction in Ireland in the DAA era
Principal Investigator Professor Suzanne Norris
Host Institution Trinity College Dublin
Duration (months) 36 months
Budget Total (€) € 315,385.00
Lay Summary
Approximately 30,000-50,000 people in Ireland have hepatitis C. Although the virus mainly affects
the liver, in up to 30% of infected people the virus also affects the brain causing poor concentration,
difficulties in concentrating, poor memory. Patients often describe this as a “brain fog”. These
symptoms may lead to forgetting to attend hospital appointments and forgetting to take tablets,
which may cause poor quality of life. In the past, it was thought that poor brain function in people
with hepatitis C was because the liver had developed cirrhosis but new information suggests that the
“brain fog” happens even when there is no cirrhosis. Researchers now think the “brain fog” is due to
the virus directly infecting brain cells or the virus causing inflammation in the brain. The research
team conducting this study hope to show that drug treatment to clear virus from the liver will also
clear virus from the brain and reduce neural inflammation, and that this will stabilize or even reverse
the brain fog. The research team will invite people with hepatitis C have some brain function tests
before and after the HCV drug treatment. Some patients receiving the drugs will also be invited to
HRB – HRA 2015 Page 25 of 30
have MRI scans of their brains before and after the drug treatment. The researchers will also do
preliminary studies into the effect of exercise in helping to control or improve brain fog in hepatitis
C. It is known that exercise can improve brain function in healthy people as well as patients with
other chronic diseases. Thus hepatitis C patients will be invited to perform a similar battery of brain
function tests and will then participate in a 12 week exercise programme followed by further brain
evaluation tests to see if there has been any improvement.
Ends.
32. Ethnic Minority Health in Ireland - Building the evidence base to address health inequities
Principal Investigator Professor Anne MacFarlane
Host Institution University of Limerick
Duration (months) 36 months
Budget Total (€) €329,946.00
Lay Summary
International evidence shows that minority ethnic groups have poorer health and more difficulties
accessing healthcare than majority ethnic groups. Analysis of existing health datasets and the use of
ethnic identifiers in health care systems are promoted internationally as valuable ways to address
these differences. It is not possible to have ‘neat’ categories to describe ethnicity but, in the Irish
context, the majority ethnic community refers broadly to Irish-born white people of Irish ancestry.
The minority ethnic community refers broadly to Irish Travellers (0.6% of our population) and more
recently arrived migrants (12% of our population).
There is evidence that Travellers’ health status and experiences are poorer than the majority ethnic
community. Migrants living in socially deprived circumstances have poor health experiences but we
are lacking high-quality analyses comparing these with the majority ethnic community. In fact, there
is a lack of analysis of existing datasets that could inform us about differences between all ethnic
minority and majority groups and there is no routine use of an ethnic identifier in the Irish health
service.
The aim of the research is to advance the evidence base so we can compare the health of majority
and minority ethnic populations in Ireland. We will:
 Identify all existing national datasets with information about ethnicity
 Use one existing dataset to compare the health of minority and majority ethnic groups
 Research the implementation of an ethnic identifier to examine its utility to identify and
address health differences between majority and minority ethnic groups
 Disseminate findings in Ireland and abroad.
This project is being conducted in partnership with Traveller and migrant community organisations.
We will use knowledge from statistics, sociology and politics to achieve our objectives and produce
findings that will provide immediate relevant outputs for health service planners and policy makers.
Ends.
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33. Dysfunctional mItochondria proVokes Inflammation iN prEeclampsia; a novel medical
interventional target to improve maternal and fetal diagnosis in preeclampsia. Short title:
DIVINE
Principal Investigator Professor Louise Kenny
Host Institution University College Cork
Duration (months) 36 months
Budget Total (€) € 329,803.00
Lay Summary
Pre-eclampsia, a serious condition of late pregnancy, characterised by high blood pressure and
proteinuria in the second-half of pregnancy, affects 5% of first time mothers and is associated with
significant maternal and neonatal morbidity and mortality. A quarter of babies born to women with
pre-eclampsia do not grow properly, and a third are born prematurely. Globally, 76,000 mothers and
500,000 infants die each year as a direct result of this condition. Currently there is no treatment for
pre-eclampsia. Mitochondria are responsible for providing us with energy generated from our daily
food intake. However, this process is complex and if it fails, by-products of the energy generating
mitochondrial network can be stressful to our bodies, by increasing inflammation and blood
pressure. We have generated data, which links mitochondrial dysfunction with pre-eclampsia.
Furthermore, inflammation and high blood pressure are characteristic of conditions like preeclampsia and heart disease. Antioxidants found in vegetables and fruit can indirectly protect
mitochondria. This project is focused on a new therapy that is 100% directed towards protecting
mitochondria and enabling them to work efficiently to generate a healthy placental environment for
the growing baby. Initially we will measure levels of mitochondrial damage in the mother’s blood to
validate our previous work and quantify and relate these results with the level of inflammation and
antioxidants during pre-eclampsia. We aim to investigate the therapeutic potential of mitochondrialtargeted antioxidants in rodent models of pre-eclampsia. In the clinical segment of the project we
will merge our blood biomarker analysis with maternal and fetal clinical outcome data to improve
our interpretation of mitochondrial dysfunction in the development of pre-eclampsia. Our ultimate
goal is to 1) develop new biomarkers to help identify the disorder and 2) provide an effective
therapy for pre-eclampsia to improve the outcome of pregnancy for both mothers and babies.
Ends.
34. Preclinical characterization of fingolimod as a potential therapeutic agent for stroke
Principal Investigator Dr Christian Waeber
Host Institution University College Cork
Duration (months) 36 months
Budget Total (€) € 329,949.00
Lay Summary
Stroke is usually caused by the occlusion of a brain artery with a clot. It is the third most common
cause of death and the most common cause of acquired physical disability in Ireland. The only
available drug is only used in ~5% of patients (because most patients are either too far, or arrive too
late to a specialized treatment center). Thus, it is crucial to find new treatments for stroke that
would be effective in most patients. Fingolimod is used to treat multiple sclerosis. We and others
have found that it is effective in rodent stroke models. These findings suggest that fingolimod is one
of the most compelling stroke drug candidates ever characterized in animal studies. But hundreds of
drugs effective in animals have failed to show efficacy in humans; this has tremendously raised the
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bar to justify the considerable expenses of a clinical trials. We therefore propose to perform studies
that are now considered essential before a potential stroke drug can move from animal to human
testing. The idea behind this project is to better simulate the features of human stroke. For instance,
while stroke is usually modelled in rodents by blocking blood supply to the brain with artificial
filaments, we will mimic stroke with actual blood clots. We will also use older rodents, which have
additional diseases often found in stroke patients (diabetes, high blood pressure, high cholesterol
levels). Because stroke patients are treated with different drugs, we will study whether the presence
of these drugs affects the efficacy of fingolimod, or increases the incidence of side-effects. If
successful, our project should rapidly lead to clinical studies of fingolimod in stroke patients. Because
these trials have a strong likelihood of success, these studies could lead to the first drug that would
be effective in most patients.
Ends.
35. Profiling receptive and expressive prosodic skills in children with spina bifida and
hydrocephalus
Principal Investigator Dr Alice Lee
Host Institution University College Cork
Duration (months) 24 months
Budget Total (€) € 220,728.00
Lay Summary
This project will advance current knowledge about communication difficulties in children with spina
bifida and hydrocephalus (SBH). This condition affects the normal development of the spinal cord
and brain and is particularly relevant to the Irish context because of the high incidence in the
country – currently at least 500 children in Ireland have SBH.
Although language skills often appear strong in children with SBH, close examination of their
communication skills frequently reveals notable difficulties in conversations and in social interaction.
These difficulties can persist into adulthood, reducing their opportunities to continue in education,
gain employment and make friends.
There are many reasons why children might experience difficulties with conversation and in social
situations. However, it has been shown in previous studies that children who find it difficult to
understand or use intonation, also called tone of voice or “prosody”, also experience difficulties with
conversation and social interaction.
This project will be the first to investigate prosodic skills systematically in children with SBH. The
project will use an internationally recognised procedure – PEPS-C – to assess prosodic skills in 90
children, which includes a group with SBH and a group of age and language matched typically
developing children. The children will complete the PEPS-C assessment and standardised language
tests to build a profile of prosodic skills and their relationship to other language abilities.
The results will demonstrate for the first time how difficulties in understanding or using prosody
underlies the broader communication problems experienced by many children with SBH. It will also
provide the evidence base for best practice for assessing and treating prosody problems in children.
Providing effective services during the school years will be of significant benefit in later life in terms
of increased opportunities for education, employment, socialisation and the long term outcomes for
children with SBH.
HRB – HRA 2015 Page 28 of 30
Ends.
36. PAPRICA: Protein Biomarker Assays for Psoriatic Arthritis - Clinical Evaluation and Validation
of Multiplexed Panels for Diagnosis and Prognosis
Principal Investigator Professor Oliver FitzGerald
Host Institution University College Dublin
Duration (months) 24 months
Budget Total (€) € 220,657.00
Lay Summary
During the treatment and management of disease important clinical decisions are made, including
deciding whether a patient has a particular illness and whether they may benefit from a specific
treatment. These decisions are often made with the assistance of information from different
measurements including patient details, scans, X-rays and a range of blood tests (‘bloods’). The
‘bloods’ measure body chemicals from sugars and lipids to individual proteins - these are all called
‘biomarkers’. Inflammatory arthritis is highly prevalent in Ireland, causes much joint damage and
considerable suffering. It is widely acknowledged, by physicians and patients alike, that new tests are
needed urgently to make an accurate and early diagnosis of psoriatic arthritis and to ensure that
each individual patient receives an effective and safe medication. Our recent research has focused
on using the very latest lab-based technologies to find new biomarkers in inflammatory arthritis
specifically psoriatic arthritis that will support the development of new tests. Using the state-of-theart medical research facilities in UCD with the support of patients and by engaging teams of worldrenowned doctors, biomedical researchers and statisticians we have identified a number of proteins
that could serve as better biomarkers in psoriatic arthritis. In this project we aim to refine the
methods we use for measuring the proteins and to examine their ability to provide better blood
tests for the diagnosis of psoriatic arthritis and prediction of a patient’s likely response to treatment.
This project will enable us to bridge the gap between discovery and practical use of biomarkers in
support of our driving ambition to produce better tests for doctors to use in their assessment and
treatment of patients with the aim of improving long-term patient health and welfare.
Ends.
37. Towards treatment stratification for successful smoking cessation: Harnessing predictive
neurocognitive models
Principal Investigator Dr Robert Whelan
Host Institution University College Dublin
Duration (months) 36 months
Budget Total (€) € 329,818.00
Lay Summary
Smoking is the single biggest preventable cause of death in Ireland. There are many reasons why
someone might remain addicted to nicotine and many factors affecting each individual’s response to
withdrawal. For example, socioeconomic status, gender or life stress can all play a role. Ultimately,
nicotine has its effects by altering brain chemistry, particularly in three crucial brain systems: the
reward processing system, the cognitive control system and the stress system. Nicotine’s effects on
the brain render it highly addictive – more addictive than crystal methamphetamine (crystal meth),
cannabis or methadone. Indeed, even though a majority of smokers attempt to quit, most
(approximately 80%) do so unaided and this method results in a success rate of just 4%. The best
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smoking-cessation therapies are relatively successful, yet still have low success rates in absolute
terms (about 15-20%). A key problem is that we do not yet understand why some people respond to
therapy and why some do not, nor can we tell in advance if particular individuals are suited to
particular therapies. This study will compare two of the most promising therapies currently
available: Contingency Management and a smartphone application of Acceptance and Commitment
therapy. Importantly, these therapies target different aspects of addiction. The former provides
money for remaining abstinent, whereas the latter is a type of ‘talking therapy’. We will assign
individuals each to either type of therapy or to a ‘treatment-as-usual’ group and measure the brain
responses before and during treatment. It is then possible –using a sophisticated method called
“machine learning” – to make a prediction about who will respond successfully to a particular
treatment and who will not, based on pre-existing differences and responses to treatment. This
research will inform future attempts to assign individuals to the type of treatment that is most
suitable for them.
Ends.
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