ROYAL ACADEMY OF MEDICINE IN IRELAND IRISH JOURNAL OF MEDICAL SCIENCE

UCD School of Medicine

Summer Student Research Awards 2016 (SSRA) 13th October 2016 UCD Dublin Ireland

Irish Journal of Medical Science Volume 186 Supplement 1 DOI 10.1007/s11845-016-1532-5

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39

Disclosure Statement The UCD School of Medicine supported the running of the Summer Student Research Awards (SSRA) 2016.

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 DOI 10.1007/s11845-016-1532-5

ABSTRACTS

UCD School of Medicine Summer Student Research Awards, SSRA 2016

Ó Royal Academy of Medicine in Ireland 2017

1. CHARACTERISING BIOMARKERS OF OOCYTE QUALITY TO IMPROVE EMBRYO SELECTION DURING ASSISTED REPRODUCTION O’Riordan A1, Longhurst G1, O’Shea LC1,2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

Being able to accurately predetermine an embryo’s viability prior to transfer remains a major obstacle to overcome in assisted reproductive technology clinics. In order to facilitate selection of high quality oocytes potential biomarkers indicative of developmental competence were previously identified (O’Shea et al. 2012). The aim of this project is to validate biomarkers of oocyte developmental competence using the bovine model system and optimise the collection of human granulosa cells for future analysis. Immunohistochemistry studies performed on bovine oocytes showed the putative biomarker, AVEN, to be localized to the cytoplasmic area of MII oocytes, and the corresponding cumulus cells. Immunoblotting studies performed on bovine ovarian tissue showed dynamic regulation of BCL-xL protein in response to altered culture conditions (i.e. time, temperature and cryopreservation). Human granulosa cells were collected (n = X) with associated embryonic development tracked for future validation of these biomarkers in a clinical setting. In conclusion, AVEN and BCL-xL expression in cumulus/granulosa cells could potentially act as a non-invasive method for embryo selection during human assisted reproduction. Reference: O’Shea, L.C., et al., Developmental competence in oocytes and cumulus cells: candidate genes and networks. Syst Biol Reprod Med, 2012. 58(2): pp. 88–101.

Individuals with Cystic Fibrosis (CF) are very prone to bacterial infection of the respiratory tract. Pseudomonas aeruginosa is the bacteria most commonly associated with chronic airway infection in CF patients which leads to a decline in lung function. In the CF lung, the organism forms biofilm and becomes resistant to antimicrobials. Consequently, such infections are virtually impossible to eradicate. The airway surface liquid (ASL) in the lungs of individuals with CF is more acidic than the lungs of non CF individuals1. Using a porcine model of CF, this acidic ASL has been shown to impair bacterial killing2, thus contributing to chronic infection. The aim of this research was to test the hypothesis that the acidic environment of the CF lung promotes biofilm formation by P. aeruginosa. Biofilm formation and alginate production by both clinical and laboratory isolates were assessed under acidic and neutral pH conditions using a number of different assays. This study revealed that considerable variation exists between strains in terms of how pH alters their ability to form biofilm. Some strains tested showed a marked tendency to form more biofilm at acidic pH than at neutral pH. Future work should aim to identify mechanisms employed, by which P. aeruginosa alters its behaviour at an acidic pH. Identification of strains which respond to acidic pH suggests that screening of CF patients for such strains may be useful for the development of novel therapeutic strategies to modify the pH of the lung, which could thereby reduce the risk of chronic infections by P. aeruginosa. Acknowledgements: The author would like to acknowledge funding from the Wellcome Trust’s biomedical vacation scholarship. References: 1. Tate S, MacGregor G, Davis M, Innes JA, Greening AP. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax. 2002 Nov;57(11):926–9. 2. Robinson NB, DiMango E. Prevalence of gastroesophageal reflux in cystic fibrosis and implications for lung disease. Ann Am Thorac Soc. 2014 Jul;11(6):964–8

Presenting Author: Mr Anthony O’Riordan Supervisor: Dr Lynne C. O’Shea

Presenting Author: Ms Shauna NicAoga´in Supervisor: Dr Marguerite Clyne Co-Supervisor: Dr Gordon Cooke

2. THE EFFECT OF pH ON BIOFILM FORMATION BY PSEUDOMONAS AERUGINOSA

3. HEALTHCARE EXPERIENCES OF PATIENTS WITH MULTIPLE SCLEROSIS IN IRELAND

NicAoga´in S1, Cooke G2, Clyne M2

McCarthy M1, Larkin A2, Doig H2

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2MS Ireland, 80 Northumberland Rd, Dublin Southside, Dublin 4

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S4 Multiple sclerosis is a chronic disabling neurological disease with an estimated prevalence of 9308 people in Ireland, though this figure is thought to be an underestimation1. Despite the prevalence of MS in Ireland having been described as ‘very high’2, there has been a notable lack of research focusing on the healthcare experiences of people with MS (pwMS) in Ireland. The aim of this research was to provide an insight into the healthcare experiences of pwMS and to produce research indications for MS Ireland. It utilised a specially formulated quantitative survey tool that assessed quality of healthcare, diagnosis, medication, access to healthcare services and quality of life. An additional assessment was made on the transition into secondary progressive MS. A number of qualitative responses were also recorded. Respondents were generally favourable towards the quality of their healthcare, but an association was found between subtype and perceived quality of healthcare (p = 0.017, Fisher’s Exact Test), with the secondary progressive with relapses subtype expressing a greater dissatisfaction than other subtypes. Communication issues were problematic, one such during the transition into secondary progressive MS, with some respondents who saw their neurologist less without having the reasons communicated to them expressing feelings of abandonment. Patient experiences may not be utilised in the Irish healthcare system as much as needed. Attention should focus on understanding the quality of healthcare differences between subgroups of pwMS, such as subtype, for they may provide distinctive challenges in the healthcare system for both the patient and physician that are overlooked. References: 1. MS Ireland, UCD, Novartis. Societal costs of multiple sclerosis in Ireland 2015. 2015; Available at: http://www.ms-society.ie/ pages/living-with-ms/information-centre/our-publications 2. Wade BJ. Spatial analysis of global prevalence of multiple sclerosis suggests need for an updated prevalence scale. Mult Sclr Int. 2014; 2014: 124578 Presenting Author: Mr Matthew McCarthy Supervisor: Ms Harriet Doig Co-supervisor: Mr Aidan Larkin

4. RETROSPECTIVE ANALYSIS OF INVASIVE AND NON-INVASIVE ASSESSMENT OF CORONARY PHYSIOLOGY IN PATIENTS WITH DIABETES MELLITUS McPhedran R1, Timmerman N2, Wu K2, de Kemp R3, Beanlands R3, Chong AY3 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Faculty of Medicine, University of Ottawa, Ottawa, Canada. 3University of Ottawa Heart Institute, Ottawa, Canada Fractional flow reserve (FFR) is currently recommended to assess the functional significance of a coronary stenosis prior to revascularization. Its utility and safety has been demonstrated in the FAME studies [1]. Recently however, concerns have been raised on the discordance between FFR assessment and non-invasive measurement of myocardial flow reserve (MFR) by cardiac positron emission tomography (PET). Rather than technique, it is believed that the discordance may be due to differences in the predominant pattern of coronary artery disease; i.e. focal versus diffuse [2]. We hypothesized that the discordance of FFR (a ratio of distal coronary pressure to aortic pressure at maximal hyperemia) and MFR (a ratio of myocardial blood flow during hyperemia and at rest) is

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 greater in patients with diabetes due to the higher prevalence of diffuse disease. We undertook a retrospective analysis of patients who have undergone both cardiac PET and FFR at the University of Ottawa Heart Institute. Data was obtained from the PET registry and catheterization reports between 1 July 2012 and 30 April 2016. An initial search using a 3-month window between both investigations revealed only 72 out of the 804 patients who have undergone FFR assessment. Hence, the timeframe was widened to 12 months. Patients will be stratified according to their diabetic status but other comorbidities and cardiovascular risk factors will be recorded for analysis. Comparison between groups will be performed using Chi squared test and correlations by Spearman’s test. The data obtained from this research will be used to design future studies to determine whether FFR or MFR is more reliable in patients with diabetes, and to investigate how revascularization strategies could be tailored to the pattern of disease. References: 1. De Bruyne B, Fearon WF, Pijls NHJ, Barbato E, Tonino P, Piroth Z, et al. Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease. N Engl J Med [Internet]. Massachusetts Medical Society; 2014 Sep 25 [cited 2016 Aug 14];371(13):1208–17. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa14 08758 2. Johnson NP, Kirkeeide RL, Gould KL. Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology? JACC Cardiovasc Imaging [Internet]. Elsevier Inc.; 2012;5(2): 193–202. Available from: http://dx.doi.org/10.1016/j.jcmg.2011. 09.020 Presenting Author: Ms Rachel McPhedran Supervisor: Dr Aun-Yeong Chong

5. DEVELOPMENT OF DURABLE USER-SPECIFIC 3D-PRINTED ANKLE FOOT ORTHOSES Giles Doran C1, Keaveney S1, Kinsella B2, O’Cearbhaill E1 1 UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, Belfield, Dublin 4. 2Orthotic Solutions Ltd, Unit 1, Pineview Business Park, Firhouse Road, Templeogue, Dublin 16

Ankle foot orthoses (AFO) are special braces used for anatomical corrections and physical support. A low-cost 3D-printing method, fused deposition modelling (FDM) offers an alternative manufacturing process to the current casting and fitting procedure, however the mechanical performance of printed orthotics and the effect of printing parameter variation are yet to be fully elucidated. The purpose of this study is (1) to investigate the influence of material and processing parameters on AFO quality; (2) to investigate the application of 3D scanning towards the digitisation of the 3Dprinting manufacturing process; and (3) to develop a reliable method to assess the functional performance of 3D-printed AFOs. Using a light-structured 3D scanner, we 3D-scanned a conventionally manufactured AFO and subsequently 3D-printed a geometrically identical AFO using additive manufacturing. The tensile properties of the following AFO materials were investigated and analysed: 3D-printed polylactic acid and polypropylene, and laser-cut samples from sheets of homopolymer and copolymer polypropylene. Drawing inspiration from the B.R.U.C.E.[1] method, we designed an

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 AFO-specific testing rig which aimed to approximate ankle biomechanics during the gait cycle. Results showed the homopolymer and copolymer polypropylene sheet materials to have an 85% and 43% greater ultimate tensile strength, respectively relative to the 3D-printed polypropylene, identifying a need for optimisation of the 3D-printing filament. The printing of custom AFOs using FDM based on a 3D scan is possible, but not without digital enhancement post-scan. The design for the AFO-specific testing rig was successfully manufactured and will provide a foundation for future validation of FDM AFO designs. Acknowledgements: Health Research Board for the funding provided for this project. References: 1. Bregman, D.J.J., Rozumalski, A., Koops, D., de Groot, V., Schwartz, M. & Harlaar, J. A new method for evaluating ankle foot orthosis characteristics: BRUCE. Gait & Posture. 2009; 30(2):144–149. Presenting Author: Miss Ciara Giles Doran Supervisor: Dr Eoin O’Cearbhaill Co-Supervisor: Dr Shane Keaveney

6. DEVELOPING INJECTABLE BIOMIMETIC COLLAGEN-BASED SCAFFOLDS AS A NONINVASIVE TECHNOLOGY FOR BONE TISSUE ENGINEERING Ibrahim A1, Tiernan C2, Murphy C3, Rice K4 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4 Bone tissue engineering (BTE) aims to regenerate/repair damaged bone. Traditional approaches utilise implantable biomaterial, which requires open surgery and hence, increases risk of infection. The aim of this research was to develop a minimally invasive thermoresponsive collagen-Hydroxyapatite (HA) gel as an injectable system in BTE. It was hypothesised that HA effects the gels in vivo and enhances mechanical properties. Specifically aiming to optimise the fabrication protocol of collagen HA (CHA) gels and investigate the effect of HA concentration and particle size on thermoresponsive properties. HA concentration within the CHA scaffolds was varied as a weight percentage of collagen, resulting in two distinct scaffolds, 100 wt % HA and 200 wt % HA. Both micro and nano HA particle size were evaluated. Four groups were developed and assessed; micro100 HA, micro200 HA, nano100HA, nano200HA. The thermoresponsive properties of the gels were investigated using a rheometer, which determined the physical state of each gel at incremented temperatures, at a single temperature, and the shear stress variation due to a varying force. To investigate the diffusion of fluids through the gels, 1 ml of dye was placed on the gels and monitored over 5 h. Results demonstrated that increasing HA concentration decreased the gelation temperature of the gels. Adding HA increased gel fluidity. Nano HA improved dye dispersion through the gels compared to micro HA, where the nano100 HA indicated a faster diffusion rate than the nano200 HA. Based on these results the nano100 gels proved to have the most superior properties compared to the other groups assessed. References:

S5 2. Krebs MD, Sutter KA, Lin ASP, Guldberg RE, Alsberg E. Injectable poly(lactic-co-glycolic) acid scaffolds with in situ pore formation for tissue engineering. Acta Biomaterialia 2009;5(8): 2847–59. Presenting Author: Mr Anas Ibrahim Supervisor: Dr Ciara Murphy Co-Supervisor: Dr Caitriona Tiernan

7. CHARACTERISATION OF THE IMPACT OF HTLV-1 HBZ AND TAX1 PROTEINS ON THE PHOSPHORYLATION LEVELS OF IRF3, AND IRF7 Freegrove A1, Alisari A2, Sheehy N2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Centre for Research in Infectious Diseases, UCD School of Medicine, University College Dublin, Belfield, Dublin 4

Type 1 interferons (IFNs), IFNa and IFNb are innate antiviral cytokines that represent the first line of defence against infection[1]. The role of IFNs in human T cell lymphotropic virus type-1 (HTLV1) infection, the development of HTLV-1 associated myelopathy/ tropical spastic paraparesis and adult T-cell leukaemia/lymphoma has yet to be fully understood[2]. Based on the importance of IRF7 and IRF3 as regulators of IFNa and IFNb production respectively, it is hypothesised that HTLV-1 modulates IFN responses in vivo via interactions between the viral regulatory proteins HTLV-1 basic leucine zipper factor (HBZ) and Tax1 and the IFN regulatory factors (IRFs) 3 and 7. The aim of this research was to investigate the effect of HBZ and Tax1 on the phosphorylation status of IRF3 and IRF7. 293T cells were seeded and transiently transfected with plasmid DNA encoding IRF3, Flag-IRF7, His-Tax1, Flag-HBZ and Flag-TANK binding kinase using LipofectamineTM 2000. The cells were lysed using passive lysis buffer and the protein expression levels were analysed by immunoblotting (SDS-PAGE). It was discovered that phosphorylated-IRF3 (P-IRF3) expression levels were downregulated in the presence of both HBZ and Tax1. However, P-IRF3 expression was decreased in the presence of HBZ alone and increased in the presence of Tax1 alone. P-IRF7 levels were unable to be visualised using the optimised protocol. In conclusion, HTLV-1 infection modulates the IFN pathway by decreasing the expression of the activated/phosphorylated form of a main regulatory factor, IRF3. Further experiments are required to determine the effect of HBZ and Tax1 on P-IRF7, and to validate these results. Acknowledgements: The author would like to acknowledge funding from the Welcome Trust Biomedical Vacation Scholarship. References: 1. Taylor K, Mossman K. Recent advances in understanding viral evasion of type I interferon. Immunology. 2013;138(3):190–197. 2. Journo C, Mahieux R. HTLV-1 and Innate Immunity. Viruses. 2011;3(12):1374–1394. Presenting Author: Mr Adam Freegrove Co-Supervisor: Ms Ahlam Alisari Supervisor: Dr Noreen Sheehy

1. Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: An update. Injury; 2005;36(3): S20–S7.

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8. EXOSOME-ENCAPSULATED microRNA-451a AS A CIRCULATING BIOMARKER FOR BREAST CANCER Naughton E1, Moloney BM2, Gilligan KE2, Joyce DP2, Kerin MJ2, Dwyer RM2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Discipline of Surgery, School of Medicine, Lambe Institute for Translational Research, National University of Ireland Galway Exosomes are tiny vesicles secreted by cells that contain genetic material including microRNAs(miRNAs, miRs). Exosome-encapsulated miRNAs secreted into the circulation by breast tumour cells have immense potential as biomarkers of disease. Recent studies by this group have highlighted the presence of miR-451a in exosomes secreted by breast cancer cells in vitro. The aim of this research was to isolate exosomes from the serum of breast cancer patients and healthy controls, and to investigate the miR-451a content of the circulating exosomes. Serum samples were collected from breast cancer patients (n = 40) and healthy volunteers (n = 12) following ethical approval and informed consent. Serum exosomes were isolated by a process of differential centrifugation, microfiltration, and ultracentrifugation. Exosome concentration was determined by protein assay and nanoparticle tracking analysis, which also measured particle size. RNA was extracted from exosomes using the MagNA Pure Compact System, and RQ-PCR targeting miR-451a performed. Exosomes were successfully isolated from all serum samples, and confirmed to be of the expected 30–120 nm size. There was no significant difference between the overall exosome yield of serum from patients compared to healthy controls, with a broad range of concentrations detected from the same volume of serum. miR-451a was detected in exosomes derived from 48/52 samples analysed, with higher levels of expression detected in circulating exosomes from breast cancer patients compared to healthy controls. The promising preliminary data presented highlights exosomal miR-451a as a potential circulating biomarker of disease. Analysis of increased numbers of samples, along with investigation of any association with patient clinicopathological characteristics is warranted. Acknowledgements: The author would like to acknowledge funding from the Health Research Board and Breast Cancer Research. Presenting Author: Ms Erin Naughton Supervisor: Dr Ro´isı´n Dwyer

9. THE FUTURE OF VASCULAR BYPASS: CREATING BIOLOGICAL ARTERIAL GRAFT FROM ANIMAL SOURCE Tan CJ1, Hassanbhai AM2, Teoh SH2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2NTU School of Chemical and Biomedical Engineering, National Technological University, Singapore

Decellularisation could generate alternatives to overcome limitations in bypass operations of small-diameter grafts (\6 mm) [1]. However, traditional techniques often fail to preserve the energy-storage protein—elastin. Hence, we aim to generate a biological scaffold for acellular graft, via chemical decellularisation, using porcine common carotid arteries while preserving elastin.

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Samples were agitated in 1% Triton X-100 then 2% sodium dodecyl sulfate. Washing involved 1% Triton X-100 and phosphate buffered saline. Thereafter, elastin, collagen and remnant DNA were measured by spectrometry. Morphology was studied with histology (H&E) and Scanning Electron Microscopy. Biomechanical properties such as ring opening angle and burst pressure were also examined. Their pressure-withstanding ability was retained (98.75%) and high percentage of elastin was preserved (48.83 ± 6.88%). Most collagen was removed (94.84 ± 0.52%), thus creating a porous scaffold while preserving 20.0% of ring opening angle. Cell lysis was efficient but DNA (90.10 ± 6.20%) was trapped in the well preserved extracellular matrix. Taken together, high elastin preservation and burst pressure indicate biomechanical function as elastic vessels was retained. Hence, decellularised vessels could be more durable and compatible to the circulatory environment than alternatives. Furthermore, since presence of collagen hinders cell seeding [2], this porous scaffold could enhance cell seeding to restore physiological and biochemical properties such as patency and residual stress. Nucleases would be helpful to fragmentize trapped DNA and reduce antigenicity. In conclusion, the protocol was successful as a preliminary trial and we are positive about generating superior acellular grafts via chemical means in time to come. References: 1. Francesco Moroni T. Decellularized matrices for cardiovascular tissue engineering. American Journal of Stem Cells [Internet]. 2014 [cited 25 July 2016]; 3(1):1. Available from: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3960753/ 2. Ting-Hsien Chuang D. Polyphenol-Stabilized Tubular Elastin Scaffolds for Tissue Engineered Vascular Grafts. Tissue Engineering Part A [Internet]. 2009 [cited 8 September 2016];15(10): 2837. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2792047 Presenting Author: Mr Chong Jin Tan Supervisor: Prof Swee Hin Teoh Co-Supervisor: Dr Ammar Mansoor Hassanbhai

10. INVESTIGATION INTO THE EFFECTS OF HYPERCAPNIA (ELEVATED CO2) ON IMMUNE CELL FUNCTION Dunne OM1, Cummins EP1,2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

Hypercapnia, elevated blood and tissue CO2, occurs frequently in severe lung disease e.g. chronic obstructive pulmonary disease. Patients with hypercapnia commonly develop lung infections and generally experience a worse patient outcome [1]. Immune signalling is perturbed by hypercapnia; however, the mechanisms underlying this process are poorly understood. One possible mechanism is via altered nuclear receptor signalling. Nuclear receptor family members are involved in transcriptional regulation of inflammatory genes, and have been reported to be sensitive to hypercapnia [2]. The aim of this research was to elucidate the effects of hypercapnia on immune cell function as measured by cytokine expression, and to determine the contribution of nuclear receptor family member NR4A2 to this response. Human THP-1 monocytes stably expressing a scrambled shRNA or shRNA targeted to NR4A2, were cultured in varying CO2

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 environments (0.03% CO2 (hypocapnia), 5% CO2 (normocapnia), 10% and 15% CO2 (hypercapnia)) and with/without lipopolysaccharide (LPS 2.5ug/ml) for up to 24 h. The effects of hypercapnia on IL6, IL-8, IL-10, IP-10 and CCL20 expression was determined using cytokine specific ELISAs. Elevated CO2 resulted in an inhibition of IL-6 expression in scrambled THP-1 cells in comparison to NR4A2 knockdown THP-1 cells. IL-8 expression was shown to increase in hypercapnia in both scrambled and NR4A2 knockdown cell lines. The level of CCL20 expression was increased in normocapnic and hypercapnic samples in comparison to hypocapnic samples. IL-10 was not detected at the incubation period used. The preliminary results demonstrate that hypercapnia regulates specific cytokines independent of NR4A2 expression. Acknowledgements: The author would like to acknowledge funding from UCD Research and UCD School of Medicine. References: 1. Cummins E, Keogh C, Crean D, Taylor C. The role of HIF in immunity and inflammation. Molecular Aspects of Medicine. 2016;47–48:24–34. 2. Sharabi K, Hurwitz A, Simon A, Beitel G, Morimoto R, Rechavi G Et al. Elevated CO2 levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans. Proceedings of the National Academy of Sciences. 2009;106(10):4024– 4029. Presenting Author: Ms Orla Dunne Supervisor: Dr Eoin Cummins

11. THE EFFECTS OF HYPERCAPNIA ON CACO-2 CELL (HUMAN COLORECTAL CANCER) CHEMORESISTANCE AND MITOCHONDRIAL REDUCTASE ACTIVITY Loh MHY1, Halligan D2, Keogh C2, Cummins EP1,2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

As a tumour enlarges, its growth outstrips its blood supply. Reduced blood flow and increased metabolic demand result in hypoxia (decreased O2), and hypercapnia (increased CO2). Apart from hypercapnia, interfering with hypoxia signaling, little is known about its effect on chemoresistance and mitochondrial reductase activity. The aim of this research is to investigate the effects of hypercapnia on chemoresistance as measured by rhodamine efflux and mitochondrial reductase activity as measured by MTT assay. In the Rhodamine assay, Caco-2 cells were seeded in 6 well plates and treated with DMSO (vehicle) or DMOG (hypoxia mimetic) in normocapnia (5% CO2) or hypercapnia (10% CO2). After 24 h, 10 uM Rhodamine was added to the cells. Media was sampled to measure rhodamine efflux over time (6 h) using fluorimetry. Hypercapnia appeared to cause a decrease in rhodamine efflux. DMOG did not increase rhodamine efflux as hypothesised, however HIF western blots indicate that DMOG did not significantly stabilise HIF-1a in control experiments. For the MTT assay, cells were seeded in 96 well plates and treated with DMSO, DMOG (1 mM) and/or Etoposide (a chemotherapeutic drug) (100 uM and 300 uM) in normocapnia or hypercapnia. Cells were treated for 24 and 48 h, with MTT activity higher in

S7 normocapnia in the 48 h group. More mitochondrial reductase activity was evident in normocapnia compared to hypercapnia at 24 h and especially 48 h. The exception being wells containing both DMOG and Etoposide. These data give insight into the effects of hypercapnia on cancer cell function, which may have implications for cancer therapy. Presenting Author: Mr Marcus Hin Yeung Loh Supervisor: Dr Eoin Cummins

12. EXPLORING THE INTERFACE OF CARE FOR CHILDREN WITH ATTENTION DEFICIT/ HYPERACTIVITY DISORDER (ADHD): AN INTEGRATIVE REVIEW Victoria Heffron1, Maria Brenner2, Kate Frazer2, Stine Lundstrøm Kamionka3 1

UCD School of Medicine and Medical Sciences. 2UCD School of Nursing, Midwifery & Health Systems. 3University of Southern Denmark The UN Convention on the Rights of the Child defines the highest attainable standard of health care as a fundamental right of every child. The extent to which this requirement is met in practice by national health care systems varies considerably among the countries of Europe, and is the core purpose of the Horizon 2020 funded project Models Of Child Health Appraised (MOCHA). One aspect of the MOCHA study is to examine the interface of care for children with ADHD. We have carried out an integrative review of peer-reviewed literature on the interface between primary and secondary care for children and adolescents with ADHD. This covers assessment, diagnosis, treatment, on-going management and follow up care. A total of 1042 non-duplicate citations were screened for their relevance to this study, of which 17 were included in the study. Key themes identified were: the requirement for increased education for all professionals involved; the primary care provider should be the key professional involved, with access to secondary care when required; a care coordinator should liaise between primary and secondary care on behalf of the patient and parents; and cases should be managed by a multi-disciplinary team. In conclusion, the assessment, diagnosis, treatment and on-going management of ADHD varies across countries in Europe and around the world. This project identifies some key themes emerging from the most recent peer-reviewed literature on the integrative care pathways being used in ADHD. Action on these themes could institute a more efficient service for patients with ADHD. Presenting author: MsVictoria Heffron Supervisor: Dr Maria Brenner Co-Supervisor: Dr Kate Frazer

13. ‘‘NEUROPHOBIA’’: MORE NURTURE THAN NATURE? Conway S1, Tubridy N2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Neurology, St. Vincent’s University Hospital, Elm Park, Merrion Rd, Dublin 4

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S8 ‘‘Neurophobia’’ is a fear of studying neurology by medical students (1, 2). The aim of this study was to investigate if neurology now has a stigma attached to it causing medical students to have a preconceived phobia of the subject. An online questionnaire was circulated among medical students through social media and by email. Questions focused on students’ perceptions of neurology before and after studying the subject. There were 137 responses. The percentage of students who say that they would not consider neurology as a specialisation in the future rises from 20% in preclinical students to 26% in early clinical students and 56% in clinical students showing a gradual decrease in interest in neurology throughout the medical training. Neurophysiology (38%) and neuroanatomy (32%) were felt to be the most difficult aspects of neurology. 49% said that a stronger emphasis on neurology in their basic science modules in first year would have prepared them for the subject while only 15% said it would not. Almost half of respondents agreed that a change in the methods of teaching could help to promote neurology in a more positive light while fewer than 9% disagreed with this. The results indicate that, contrary to our initial hypothesis, ‘‘neurophobia’’ is not innate in medical students but is acquired during the course of their medical training. The implication is that while medical students show an interest in neurology, current medical training is not adequately preparing students for clinical neurology and is discouraging students from pursuing a career in neurology. References: 1. Flanagan E, Walsh C, Tubridy N. ‘Neurophobia’–attitudes of medical students and doctors in Ireland to neurological teaching. Eur J Neurol. 2007;14(10):1109–12. 2. Pakpoor J, Handel AE, Disanto G, Davenport RJ, Giovannoni G, Ramagopalan SV, et al. National survey of UK medical students on the perception of neurology. BMC Med Educ. 2014;14:225. Presenting Author: Ms Sarah Conway Supervisor: Prof Niall Tubridy

14. MEDICALLY UNEXPLAINED SYMPTOMS: DO DOCTORS HAVE A LOT TO LEARN? Conway S1, Tubridy N2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Neurology, St. Vincent’s University Hospital, Elm Park, Dublin 4 Medically unexplained symptoms (MUS) are symptoms experienced by a patient which have no definitive organic pathology. Thirty to fifty percent of outpatients have MUS(1). Their management comes at a high economic cost and is often considered challenging and frustrating for clinicians(2). This study was designed to investigate medical students’ perception of their training for the management of MUS. An online questionnaire was distributed via social media and email to 157 medical students. The survey focused on awareness of MUS, attitudes about MUS and communication with these patients. Thirty-eight percent of students had not had the terms MUS, Functional symptoms, psychosomatic disorder or somatoform disorder explained to them. Almost three quarters do not believe that they received adequate training for communication with patients with MUS. Half of students who had completed clinical training reported witnessing negative attitudes from doctors about MUS. Eighty-three percent stated that they had not had training on how to appropriately manage the psychiatric needs of a patient with MUS. Over half of

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 students reported low confidence in their ability to manage a patient with MUS. The highest rated suggestions on how to improve training for MUS management were: Case-based classes (66%), communication skills classes (51%) and tutorials (46%). Medical students feel that there is a deficit in their training for the management of patients with MUS. These results are not only relevant to neurology but also other specialities with conditions like irritable bowel, fibromyalgia syndrome and chronic pelvic pain all falling under the umbrella term ‘‘MUS’’. References: 1. Nimnuan C, Hotopf M, Wessely S. Medically unexplained symptoms: an epidemiological study in seven specialities. J Psychosom Res. 2001;51(1):361–7. 2. Stone J, Carson A, Sharpe M. Functional symptoms and signs in neurology: assessment and diagnosis. J Neurol Neurosurg Psychiatry. 2005;76 Suppl 1:i2–12. Presenting Author: Ms Sarah Conway Supervisor: Prof Niall Tubridy

15. INVESTIGATING THE EFFECTS OF ETHANOL EXPOSURE ON THE PRIMARY CILIUM Kutubi A1, Brennan D1 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4

The adverse effects of ethanol on early ocular embryogenesis leads to disruption of the retinal pigmented epithelium (RPE) of the eye [1]. Sonic hedgehog (Shh) is a key gene of ocular development which is perturbed following ethanol exposure [2]. The Shh pathway acts through the primary cilium, which functions in relaying signals from the surrounding cellular microenvironment. This study explores whether ethanol-associated disruption of Shh signalling is related to primary ciliary disturbances by analysing the ciliary marker acetylated alpha-tubulin. Immortalised hTERT-RPE1 cells were cultured according to manufacturer’s guidelines. For experimental purposes, cells were serum restricted overnight in 1% fetal bovine serum and subsequently treated with 0, 1, 5, 10 and 20% ethanol added to the serum restricted media. After 24 h, cells were fixed in 4% paraformaldehyde and processed for immunohistochemical analysis. Treated cells were dual stained using a goat polyclonal Shh antibody (Abcam), a mouse monoclonal acetylated alpha-tubulin antibody (Sigma) and hoechst nuclear counterstain and observed using fluorescent microscopy. Results showed there was a dose-dependent increase in the expression of acetylated alpha-tubulin in all ethanol treatment groups when compared to control counterparts. The expression of Shh was more difficult to visualise and no apparent differences between groups could be established. In conclusion, our work indicates an ethanol-induced perturbation of primary cilia, denoted by disrupted alpha-tubulin expression patterns in our RPE cell line. The observed increase in the ciliary protein acetylated alpha-tubulin, suggests that ethanol is inducing structural alterations to the morphology and overall length of the primary cilium. References: 1. Kennelly K, Brennan D, Chummun K, Giles S. Histological characterisation of the ethanol-induced microphthalmia phenotype in a chick embryo model system. Reprod Toxicol. 2011;32(2):227–34.

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 2. Brennan D, Giles S. Sonic hedgehog expression is disrupted following in ovo ethanol exposure during early chick eye development. Reprod Toxicol. 2013;41:49–56. Presenting Author: Mr Abdubadie Kutubi Supervisor: Dr Deirdre Brennan

16. WOMEN’S EXPERIENCE OF A DIAGNOSIS OF GESTATIONAL DIABETES: A QUALITATIVE STUDY Feighan C1, Devine H2, Curren S2, Harrington L2, Daniel U3, Rutter E3, Coveney C3, Hatunic M4, McAuliffe F5, Higgins M5 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Dietetics, National Maternity Hospital, Holles Street, Dublin 2. 3Midwifery, National Maternity Hospital, Holles Street, Dublin 2. 4Endocrinology, Mater Misercordiae Hospital, Eccles Street, Dublin 7. 5UCD Obstetrics and Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital The objective of this research was to gain an insight into the emotional impact of a diagnosis of gestational diabetes mellitus (GDM) at different stages of pregnancy. In this cross-sectional qualitative study, women who had been diagnosed with GDM in the National Maternity Hospital (NMH) in Ireland were interviewed. A total of 94 women, grouped into three cohorts based on the stage of their pregnancy, participated. Women were interviewed within a week of diagnosis (Group 1), several weeks after diagnosis (Group 2), or in the days following delivery (Group 3). Consenting women were asked to describe their emotions relating to their diagnosis of GDM. Ethics approval was received from the NMH. Worry and fear were the predominant emotions of Group 1; secondary themes included upset, a sense of responsibility and frustration. In Group 2 the strongest themes were acceptance, adjusting to the lifestyle and commitment to continue with the necessary lifestyle changes. These themes, and feeling supported, were common to Groups 2 and 3. After delivery the primary theme was relief: that their baby was alright and that their GDM was at an end. There was some apprehension and worry of developing diabetes in the future. This study explored the emotional experience of having GDM. With time, support and information the initial feelings of anxiety, annoyance and guilt can be diminished to present a view of GDM as a manageable part of the pregnancy. Women also realised that the diagnosis had significant implications for their future health. Presenting Author: Ms Ciara Feighan Supervisor: Dr Mary Higgins Co-Supervisor: Ms Usha Daniel

17. ANALYSIS OF ‘‘THE BREAKFAST CLUB’’, A HOSPITAL BASED GLUCOSE MONITORING FOR WOMEN WITH GESTATIONAL DIABETES: A MIXED METHOD STUDY IN A TERTIARY LEVEL UNIT Leonard C1, Devine H2, Curran S2, Harrington L2, Daniel U3, Rutter E3, Coveney C3, Hatunic M4, Higgins M5

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Dietetics, National Maternity Hospital, Holles Street, Dublin 2. 3Midwifery, National Maternity Hospital, Holles Street, Dublin 2. 4Endocrinology, Mater Misercordiae Hospital, Eccles Street, Dublin 7. 5UCD Obstetrics and Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital Gestational diabetes (GDM) is increasing worldwide. Good glycaemic control, often achieved with diet and lifestyle modification, significantly decreases maternal and foetal morbidity associated with the disease. Controversy exists regarding glycaemic thresholds and monitoring techniques. Techniques used are hospital based monitoring and self-bloodglucose monitoring (SBGM). The aim of this study was to analyse a GDM hospital based service in Dublin. Participants included women attending the clinic for fasting and postprandial blood glucose measurements, and its clinical staff. Grounded theory methodology was used to assess qualitative semistructured interviews with participants. Quantitative analysis included costing of the service, questionnaires establishing breakfast consumption by patients, timing of postprandial sampling and assessment of ketosis on fasting urine samples. Patients interviewed (n = 10) discussed the positive interaction and support of the clinic, but questioned the logistics and time involved. Staff (n = 9) noted the importance of accurate glucose monitoring to inform therapeutic decisions. Concerns were also raised that the initial concept of the clinic was becoming difficult to achieve, due to the increasing numbers of patients. Total costs per week of the clinic ranged from €1730 to €1847. Questionnaires (n = 57) revealed inaccuracies in food consumed by some women; however the majority (86%) achieved the 30 g carbohydrate load required for accurate postprandial glucose testing. The mean time to obtain a ‘‘one hour postprandial sample’’ was 74 min (range 58–122 min) (n = 107). Urinalysis (n = 220) showed 26% of samples had ketones present, with 12% having significant ketonuria. This study has raised questions about hospital based GDM monitoring, which may inform future practice. Presenting Author: Ms Carol Leonard Supervisor: Dr Mary Higgins Co-Supervisor: Ms Hilary Devine

18. ANALYSIS OF A POTENTIAL ROLE OF KETOACIDS IN THE DIFFERENTIATION OF LONG SLENDER BLOODSTREAM FORM OF TRYPANOSOMA BRUCEI BRUCEI TO THE SHORT STUMPY BLOODSTREAM FORM O’Byrne R1, Barry PJG2, Nolan DP2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2School of Biochemistry and Immunology, Trinity Biosciences Institute, Trinity College Dublin, Dublin 2

Trypanosoma brucei is a clade of flagellated protozoan parasites which includes the causative agents of human African trypanosomiasis (sleeping sickness) Trypanosoma brucei gambiense and T. b. rhodesiense. T. b. brucei, which maintains the clade’s infectivity to the majority of mammals, is non-infective to humans and is therefore the prototypical species used for the study of trypanosomes. This laboratory has recently shown that ketoacids secreted by T. b. brucei have immunomodulatory effects in the host, suppressing host immune

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S10 responses. For this present study, the ketoacids phenylpyruvate and 4-hydroxyphenylpyruvate were tested for their ability to induce transformation of long slender bloodstream form trypanosomes to the non-proliferative short stumpy form. Differentiation of trypanosomes to short stumpy forms, under a number of ketoacid treatment conditions, was monitored by phase contrast microscopy and by Western blotting for the stumpy form marker protein PAD1. While long slender bloodstream form trypanosomes were successfully differentiated in some conditions, neither phenylpyruvate or 4-hydroxyhyenylpyruvate were found to play a role in the differentiation process under the conditions tested. This study highlights that differentiation to the short stumpy form is not induced by phenylpyruvate or 4-hydroxphenylpyruvate at physiological, or slightly decreased, hydrogen ion concentrations. Presenting Author: Mr Robert O’Byrne Supervisor: Dr Derek P. Nolan Co-Supervisor: Mr Paul J.G. Barry

19. TREES AND ENCLOSURES: AN EXAMINATION OF STUDENT ATTITUDES TOWARDS DIFFERENT INTERACTIVE GRAPHIC REPRESENTATIONS OF HIERARCHIES AND BRANCHED MODELS IN MEDICAL EDUCATION Lai FY1, Last J1, Holloway P1 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4 The classification of disease is a key outcome in medical education. Previous work by this group showed that online interactive E-learning resources for the classification and study of pathology were more favorably viewed by students than non-interactive equivalents. While the tree-based graphical metaphor studied is prevalent it may not be optimal and other graphical metaphors such as the enclosure-based ones exist. This study sought to evaluate student attitudes towards the acceptability and potential utility of tree-based and enclosure-based metaphors for the study and classification of lymphoma. In this study, tree-based and enclosure-based online interactive graphical resources were developed to illustrate the classification and features of lymphoma. Students who were naı¨ve to the content from UCD School of Medicine’s medicine programs (n = 291) were invited by email to review both resources anonymously. They were then requested to complete a 15-question online survey consisting of Likert scales and open-ended questions to assess their attitudes towards the utility and acceptability of both resources. Survey data was subsequently analysed using a Wilcoxon signed-rank test. Preliminary results show 19 respondents. Both resources were reported as aiding understanding of classification and features of lymphoma, and thought to be useful as study aids. However, statistical test show the tree-based metaphor was significantly better regarded for understanding classification of lymphoma (Z = -2.179, p = 0.02) and of greater perceived utility (Z = -3.02, p = 0.003) than the enclosure-based one. The study showed a positive reception for both models. Further work could assess if one or both resources effectively increases students’ knowledge of lymphoma.

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 References: 1. Johnson LR. Using mind maps to teach medical students. Medical Education. 2014; 48:1124–1125. 2. Ahern CW, Tattersall A, Holloway P. A novel mind-mapslideshow hybrid for the standardised, interactive, and graphical presentation of pathology topics. Irish Journal of Medical Science. 2014; 183(12):556. Presenting Author: Ms Fei Ya Lai Supervisor: Dr Peter Holloway Co-Supervisor: Prof Jason Last

20. LIFELINES: EVALUATION OF AN ONLINE LEARNING RESOURCE FOR EMBRYOLOGY Tan, JYC1, Last J1, Holloway P1 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4

Embryology is a vital yet challenging area in medical education. Research shows that students prefer multimedia rich embryology e-learning resources as they are highly interactive and engaging [1]. Previous work by this group also identified a need for an integrated learning resource so that the overall embryonic development can be better appreciated in a systems-based curriculum [2]. To address this issue, Lifelines, an interactive online learning tool featuring timelines was developed. Besides enabling users to keep track of developmental processes, timelines also help express and quantify chronological relationships. This study aimed to evaluate students’ attitudes towards Lifelines in comparison to a static PDF resource containing identical content. In this study, online timeline-based interactive and static resources were developed to demonstrate the time-overlapping processes which occur during embryogenesis. Students from UCD’s medicine programs (n = 434) were invited by email to review the two resources anonymously. They were then requested to complete a 15-question online survey consisting of Likert scales and open-ended questions to assess the acceptability and perceived utility of both resources. Survey data were subsequently analysed using Wilcoxon signed-rank test. Preliminary results (n = 24) showed that both resources were perceived as helpful with Lifelines statistically significantly of greater perceived utility as a general study aid and to enable respondents to view simultaneous developmental processes across different systems (Z = -3.573, p = \0.005 and Z = -3.535, p = \0.005, respectively). The study showed a positive reception for an interactive timelinebased embryology resource. Further work could assess if such a resource effectively increases students’ knowledge of embryology. References: 1. Sagar T, Viveka S. Assisted E-Learning Computer Program as a Teaching–Learning Resource on Human Embryology. Indian Journal of Applied Research. 2015; 5(12):540–544. 2. McCaffrey F, Winston E, Giles S, Tattersal A, Lynch C, Last J. ‘Embryology Is Like A Language Of Its Own On Top Of The Language Of Anatomy, It’s Like A Dialect’: Identifying And Addressing Barriers To The Effective Learning Of Human Development. Irish Journal of Medical Science. 2014; 183 (Suppl 12):556.

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Presenting Author: Ms Janet Yoke Cheng Tan Supervisor: Dr Peter Holloway Co-supervisor: Prof Jason Last

21. AN EXPLORATION OF INFLUENCES ON RADIO-OPACITY OF CENTRAL VENOUS AND OTHER CATHETERS VISUALISED ON A CHEST RADIOGRAPH 1

1

Connolly A , Matthews K

1 Diagnostic Imaging, UCD School of Medicine, University College Dublin, Belfield, Dublin 4

In Irish hospitals, many patients have central venous and other catheters inserted. Chest radiography is frequently undertaken to check the position of these catheters. Of their construction, most catheters are slightly radio-opaque, and international standards direct an acceptable level of radiopacity1, and how this is measured2. Published research addressing influences on catheter radiopacity is not apparent. The objectives of the current study are to investigate: 1. Influences on radio-opacity of catheters; 2. Whether voluntary standards of radio-opacity are displayed on catheter packaging; 3. Whether similar catheters display uniform radio-opacity. Structured interviews were conducted with medical, nursing and radiography staff, and representatives of catheter manufacturers and distributors. Thematic analysis of the transcripts was undertaken to establish whether radio-opacity is a key feature in the marketing and use of catheters. Examples of catheters were sited on a tissue equivalent anthropomorphic phantom, and exposed in UCD Radiography with an optimal exposure derived from clinical practice. Catheter images were evaluated using a standard approach to compare pixel intensity in regions of interest over the catheter and beside the catheter2. Medical and nursing staff perceived no issues with radio-opacity of central venous catheters, but did report limited visibility of nasogastric tubes. The radiographer reported limited visibility of central lines when examining female patients with dense breast tissue, and concurred that more issues arise with naso-gastric tubes. However, prevailing advice is that the site of naso-gastric tubes should not be routinely confirmed with radiography. No clinical staff were aware of advisory standards concerning radiopacity. Manufacturers reported testing the radio-opacity of catheters as required by ISO 20131, but not in the method recommended by ASTM 20122. However, they did not publish this information when marketing catheters. Laboratory exposure of a range of catheters revealed varying radio-opacity depending on manufacturer and purpose. It seems that radio-opacity is an issue with some catheters but not others. Consequently, manufacturer statements of radio-opacity could influence catheter choice and may carry benefits for clinical users. References:

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22. GENE AND TONIC: EXPLORING THE MOLECULAR MECHANISMS UNDERLYING FETAL ALCOHOL SYNDROME Judge L1, Brennan D1 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4

Ocular defects are a common manifestation of Fetal Alcohol Syndrome (FAS). Bone morphogenetic protein 4 (Bmp4) is crucial for formation of the retinal pigmented epithelium (RPE). Concurrently, paired box gene 2 (Pax2) is vital for neural retina (NR) development. RPE and NR disruption have previously been reported in FAS models [1, 2]. We hypothesise that these key genes may be perturbed following early-stage ethanol exposure. The aim of this study was to (i) optimise an in vivo model of ethanol-induced ocular defects using the chick embryo and examine the resulting ocular phenotype (ii) qualitatively evaluate Bmp4 and Pax2 expression throughout the eye. Fertile chicken eggs (n = 60) were pre-incubated for 24 h at 38 °C and injected with either 10 ll of chick saline (0.73% NaCl), 1, 5, 10 or 20% ethanol solution in ovo. Eggs were further incubated for 40 h (n = 25) or 5 days (n = 35) and processed for wax histology. Bmp4 and Pax2 expression patterns were analysed by immunohistochemistry and immunofluorescence, respectively. Aberrant ocular morphology (microphthalmia, anophthalmia) was noted in the 5–20% ethanol groups thus verifying the creation of an optimal treatment regime for FAS-related eye defects. Examination of Bmp4 expression patterns revealed ethanol is exerting its detrimental effects on the developing embryonic eye by inducing its misexpression at doses of 5–20%. A marked dose-dependent decrease in Pax2 expression was found upon examination of the neural retina in all ethanol treatment groups. We conclude that molecular deficits of Bmp4 and Pax2 are a consequence of ethanol exposure, potentially inducing eye dysmorphology. References: 1. Kennelly K, Brennan D, Chummun K, Giles S. Histological characterization of the ethanol-induced microphthalmia phenotype in a chick embryo model system. Reprod Toxicol. 2011 Sep;32(2):227–34. 2. Brennan D, Giles S. Ocular involvement in fetal alcohol spectrum disorder: a review. Curr Pharm Des. 2014;20(34):5377–87. Presenting Author: Ms Leia Judge Supervisor: Dr Deirdre Brennan

23. CHARACTERISING KEY SIGNALLING PATHWAYS REGULATING DEVELOPMENTAL COMPETENCE IN OOCYTES AND CUMULUS CELLS

1. European Standard ISO 10555-1 (2013) Intravascular catheters— Sterile and single use catheters—Part 1: General requirements, National Standards Authority Ireland (NSAI), Dublin. 2. ASTM International, F640-12 (2012) Standard Test Methods for Determining Radiopacity for Medical Use, West Conshohocken, PA, United States

Ryan A1, Longhurst G1, O’Shea LC1,2

Presenting Author: Ms Aileen Connolly Supervisor: Dr Kate Matthews

The ability of an embryo to develop successfully greatly relies on the quality of the oocyte from which it has been generated. Currently it is

1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

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S12 not possible to accurately predetermine an embryo’s ability to provide a viable pregnancy prior to transfer. By performing a meta-analysis on published microarray data, candidate genes and signalling networks associated with oocyte quality were previously identified (O’Shea et al. 2012). The objective of this project was to characterise candidate proteins expressed in cumulus oocyte complexes, which may be linked to the ability of an oocyte to develop following fertilisation. Immunohistochemistry studies performed on bovine and human oocytes showed ATRX to be localised to the chromosomal area of GV oocytes, and highly expressed in the corresponding cumulus cells. Immunoblotting studies performed on Xenopus oocytes, bovine oocytes and ovarian tissue showed dynamic regulation of candidate biomarkers ATRX, AVEN, Caspase 1 and P53 in response to altered culture conditions prior to cryopreservatiom; time (4 vs 24 h) and temperature (four degrees celcuis versus body temperature) of transportation from collection point to laboratory. In conclusion, ATRX detection in the cumulus cells could potentially act as a non-invasive method for improved oocyte selection during assisted reproduction technologies, resulting in increased take home baby rate. Acknowledgements: The author would like to acknowledge funding from the Wellcome Trust Biomedical Vacation Scholarship. References: O’Shea, L.C., et al., Developmental competence in oocytes and cumulus cells: candidate genes and networks. Syst Biol Reprod Med, 2012. 58(2): pp. 88–101. Presenting Author: Ms Aisling Ryan Supervisor: Dr Lynne C. O’Shea

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 10.8% of paediatric oncology patients were identified with a congenital anomaly. There were more neurological anomalies associated with a CNS tumour compared to other cancer subtypes (p = 0.004). There was a significant association between males diagnosed with a neurological congenital anomaly and CNS tumours (p = 0.03). This study demonstrates further evidence of an association between congenital abnormalities and paediatric cancer. It additionally identifies a previously unrecognised relationship between males diagnosed with a neurological anomaly and CNS tumours. Future research will focus on identifying the mechanisms of early childhood cancers and gender differences. Acknowledgements: The author would like to acknowledge funding from Institute for Public Health at Washington University in St. Louis, the Global Health Center at the Institute for Public Health, Mallinckrodt Pharmaceuticals Charitable Giving Program and Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital. Reference: 1. Botto L, Flood T, Little J, Fluchel M, Krikov S, Feldkamp M et al. Cancer Risk in Children and Adolescents with Birth Defects: A Population-Based Cohort Study. PLoS ONE. 2013;8(7):e69077. Presenting Author: Ms Nicole Cousins Supervisor: Dr Todd Druley

25. ENGAGEMENT OF AFRICAN AMERICAN WOMEN IN A BREAST CANCER GENETICS STUDY Powderly A1, Muller L1, Bierut, L2

24. RETROSPECTIVE ANALYSIS OF PAEDIATRIC CANCER AND CNS CONGENITAL ANOMALIES Cousins N1, Druley T2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Center for Genome Sciences and Systems Biology, Division of Hematology and Oncology, Department of Pediatrics, Washington University in St. Louis, 4515 McKinley Ave, St. Louis MO, 63110 Congenital anomalies and paediatric cancer both contribute to paediatric hospitalizations and significant disease burden and have been recognised as global priorities by the World Health Organization. Unlike many adult malignancies, paediatric cases demonstrate fewer somatic mutations and are more often associated with germline mutations. Previous research demonstrates an association between non-chromosomal congenital abnormalities and cancer, suggesting a common disease aetiology[1]. This study examined the association between neurological congenital anomalies and paediatric cancer. It was hypothesized that the prevalence of central nervous system (CNS) anomalies would be higher among patients with a neurologic tumour compared to those diagnosed with another cancer subtype. Electronic medical records of 854 paediatric oncology patients at St. Louis Children’s Hospital (SLCH) from January 1, 2004 to October 14, 2010 were accessed. They were evaluated for a congenital anomaly diagnosis and verified using ICD-9 hospitalisation codes. Bivariate analysis was used to examine differences between patients with neurological anomalies and those without, and those with CNS tumours.

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Institute for Public Health, Washington University School of Medicine, 4940 Children’s Pl, St. Louis, MO 63110, United States Genetic mutations, such as BRCA1/BRCA2, confer a high risk for the development of breast cancer in carriers. However, most data comes from studies of Caucasian women. To better understand the acceptability of genetic testing for breast cancer risk in African American (AA) women, we characterized women who agreed to participate in a pilot study that offered free genetic testing to all AA women who have been diagnosed with breast cancer. We recruited 36 women who provided saliva samples for analysis by Color Genomics. We surveyed educational status, family history of cancer and psychosocial characteristics. We analyzed whether participants had received prior genetic testing. Finally, we assessed if women had availed of complementary genetic counseling having received their results. Of the 36 participants, 61.1% reported a biological parent or sibling who had cancer and 30.5% of the participants had engaged in previous genetic testing. All of the women had graduated high school with 52% of the women having completed a bachelor’s degree. This figure compares to the 19.9% of AA women with a Bachelor’s degree or higher in the St. Louis Metropolitan area. Amongst the 22 women who obtained their genetic results to date, two women have received a positive result for a mutation and seven have engaged with genetic counselling. Women who participated in this pilot study had a higher level of education than the general population. Expansion of this study will require a greater effort to attract less informed women in order to generate a representative patient population.

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Presenting Author: Ms Ailis Powderly Supervisor: Dr Laura Bierut

Presenting Author: Ms Laura Muller Supervisor: Dr Laura Bierut

26. WHO PARTICIPATES IN GENETIC TESTING? AFRICAN AMERICAN WOMEN AND BREAST CANCER GENETICS: A PILOT STUDY

27. MAGNETOENCEPHALOGRAPHY DETECTS EVOKED RESPONSE FIELD IN EXPERIMENTS PROVIDING VERBAL STIMULI FOR COGNITIVE TASKS FOR VALIDATION OF A COMBINED PARADIGM

Muller L1, Powderly A1, Bierut L2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Psychiatry, Washington University School of Medicine, 4940 Children’s Pl, St. Louis, MO 63110, United States

Precision medicine has the potential to revolutionise medical care. To extend knowledge about underlying genetic risk and ascertain potential barriers to genetic testing, African American women diagnosed with breast cancer were invited to undergo complimentary genetic testing. Our aim is to identify known variants increasing risk to breast cancer development, and compile data for future detection of unknown variants specific to this population. This study endeavors to determine who elects to participate and to decipher the characteristics of women who are receptive to genetic testing. Variables analyzed include age, referral source, zip code and reasons for refusal. Data was analyzed from a recruitment call log to determine participant reachability and common reasons for refusal. We tested to uncover whether age, referral source, and poverty status influence participation. We observed a 25% participation rate among women 40 years of age and under, while participation rates were 34% in women ages 41–60, 21% in women ages 61–75, and 12.5% in women over age 75. Women referred by their doctor were 26% more likely to participate than those who were referred by a non-physician source. No significant association between poverty status and participation was found. As genetic testing enters medical care, it is crucial to understand potential factors that limit participation in testing. Greater understanding of age-specific variation in receptiveness to genetic testing is warranted. As linking referrals to clinical care generates higher participation, we encourage oncologists to recommend genetic testing to patients, and emphasize the need for testing to take place during the medical consultation. References: 1. Akinyemiju T, Moore J, Ojesina A, Waterbor J, Altekruse S. Racial disparities in individual breast cancer outcomes by hormone-receptor subtype, area-level socio-economic status and healthcare resources. Breast Cancer Res Treat. 2016;157(3): 575–586. 2. King M, Levy-Lahad E, Lahad A. Population-Based Screening for BRCA1 and BRCA2. JAMA. 2014;312(11):1091 Acknowledgements: University College Dublin Dean’s Summer Research Scholarship, Institute for Public Health at Washington University in St. Louis, The Global Health Center at the Institute for Public Health, Mallinckrodt Pharmaceuticals Charitable Giving Program, Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital, Siteman Cancer Center, Foundation for Barnes Jewish Hospital.

Conroy L1, Cheung T2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2School of Engineering Sciences, Simon Fraser University, Burnaby BC, Canada Magnetoencephalography (MEG) is a technique that provides functional neuroimaging of the brain by measuring the magnetic fields that are generated by neuroelectrical activity. A previously recorded dataset was provided for the study in which a single subject had been presented with a set of verbal stimuli that consisted of paired words. Approximately half of the word pairs featured congruent pairs e.g. ‘‘Cat’’ followed by ‘‘Dog’’, while the other half featured incongruent pairs e.g. ‘‘Cotton’’ followed by ‘‘Telephone’’. The study design sought to examine whether the incongruent pairs elicit a larger neuronal activity response than the congruent pairs1. Analysis2 was performed on the dataset (151 Channel MEG continuous recording at 1200 Hz for 480 s) using proprietary CTF MEG software tools. The raw channel data was inspected for eyeblinks/saccadic movement noise artefacts (none found). Signal processing was performed to remove the noise artefacts that were introduced to the signal by the head localisation system. Markers were added to the data to identify the individual trials for 1) congruent word pairs and 2) incongruent word pairs and separate datasets of the averaged trials were created. Preliminary inspection of the averaged trials indicate that this technique can identify an N400 component in the incongruent trials data and is highlighted by comparison to the congruent trial averages. This study provides a base-line response for this experimental protocol. This base-line can be used in further experiments to verify whether multiple experimental protocols can be administered to a subject simultaneously without compromising the validity of the protocols. Acknowledgements: The author would like to acknowledge funding from the UCD School of Medicine via the Dean’s 2016 SSRA International Summer Research Scholarship and from the Canadian MITACS Accelerate Research Program. References: 1. Luck SJ. Ten simple rules for designing ERP experiments. Eventrelated potentials: A methods handbook. 2005;262083337. 2. Cohen MX. Analysing neural time series data: theory and practice. MIT Press; 2014 Jan 17. Presenting Author: Mr Luke Conroy Supervisor: Dr Teresa Cheung

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28. EFFECT OF EKMAN FACES ON INHIBITORY CONTROL IN CHILDREN WITH AUTISM SPECTRUM DISORDER: DATA ANALYSIS: CRITERION Hamilton T1, Smith A1, Morris J1, Moreno S2, Doesburg S2, Peatfield N2, Fickling S2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Digital Health Hub, School of Engineering Science, Simon Fraser University, Surrey, British Columbia, Canada Autism Spectrum Disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviors and restrictive interests.(1) It has been suggested that impaired inhibition may exacerbate the behaviors typical of ASDs (1). Individuals with ASD have impairments in focusing attention on faces and in face processing (2). The aim of this research was to investigate the effect of Ekman faces on the responses of children (7–12 years old) with ASD in a go/no-go task. EEG and behavioral data (i.e. Reaction times, accuracy) from 33 children with ASD and a control group of 40 typically developing children was collected. This data was obtained during a go/no-go task, which included angry or happy Ekman faces in the background. After exclusion criteria, the data from 20 children (n = 20) in the ASD group was used for data analysis. Data analysis of behavioral data was used to find criterion values and a paired t-test was carried out. Reaction times* and d’(signal detection sensitivity)** were also analysed by the team. The average criterion for trials containing happy and angry Ekman faces in the go/no-go task was -0.41 and -0.53, respectively. These results indicate that both angry and happy face trials had a liberal bias but that angry face trials had significantly greater liberal bias (P = 0.0048, t (df) = 3.1877(19)). These results suggest that the happy and angry Ekman faces did affect the bias of the ASD group. These results will be compared with the control group to elucidate their implications. Acknowledgements: This authors would like to acknowledge funding from the Dean’s SSRA 2016 International Summer Research Scholarship, UCD. References: 1. Vara AS, Pang EW, Doyle-Thomas KA, Vidal J, Taylor MJ, Anagnostou E. Is inhibitory control a ‘no-go’in adolescents with autism spectrum disorder? Molecular autism. 2014;5(1):1. 2. Kikuchi Y, Senju A, Akechi H, Tojo Y, Osanai H, Hasegawa T. Atypical disengagement from faces and its modulation by the control of eye fixation in children with autism spectrum disorder. Journal of autism and developmental disorders. 2011;41(5): 629–45. Presenting Author: Ms Tara Hamilton Supervisor: Dr Sylvain Moreno Co-supervisor: Mr Shaun Fickling

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 1

UCD School of Engineering and Architecture, University College Dublin, Belfield, Dublin 4. 2Behavioural Cognitive Neuroscience Institute, Simon Fraser University, Burnaby, British Columbia The purpose of this project is to enable real-time data analysis for MEG and EEG signals and to examine the signal for live feedback between subject and computer. The data analysis and feedback is provided through a GUI. Data acquisition, processing and display software were created using a combination of Matlab programming and a buffer code in C. The buffer code was provided by ‘Fieldtrip’s’ open source software toolbox [1]. The buffer allows for single threaded software tools such as Matlab to behave as a multithreaded software program by allowing for simultaneous writing and processing of data. The GUI is created through Matlab to display the incoming data and to offer preprocessing options. The preprocessing options allow for filtering and artefact removal of the incoming signal. The projects results were successful in applying filters to offline sample data. Further research is needed to see the success of the program at filtering and displaying the data from subjects in an online study. Continuing analysis aims to use the processed signal to show active areas of the brain during stimulation in the form of a 3D interactive display. Utilising an online adaptive synthetic aperture magnetometry (SAM) beamformer [2]. This project is to be used as tool by researchers to improve data acquisition when the data is examined in real-time situations. Matlab is not a platform specific tool and therefore can be used in conjunction with bio-instruments from different manufacturers [3]. The flexibility the program offers creates an easy to use platform that is aesthetically pleasing and allows for further programs to be built in. Acknowledgements: The author would like to acknowledge funding from the Dean of Medicine’s SSRA 2016 International Summer Research Scholarship. References: 1. Overview of Realtime Buffer—FieldTrip [Internet]. http://Field triptoolbox.org. 2016 [cited 15 June 2016]. Available from: http://www.fieldtriptoolbox.org/development/realtime/buffer_over view 2. Robinson S.E., Vrba, J. Functional neuroimaging by synthetic aperture magnetometry (SAM). In: Yoshimoto T, Kotani M, Kuriki S, Karibe H, Nakasato N, editors. Recent Advances in Biomagnetism. Sendai: Tohoku University Press; 1998. pp. 302–305 Presenting Author: Mr Mel Farrell Supervisor: Dr Nicholas Peatfield

30. EFFECT OF EMOTION ON THE REACTION TIMES OF CHILDREN WITH AUTISM SYNDROME DISORDER IN A GO-NOGO TASK Smith A1, Hamilton T1, Morris J1, Moreno S2, Doesburg S2, Peatfield N2, Fickling S2 1

29. REAL-TIME DATA ACQUISITION AND PROCESSING BY CONSTRUCTION OF A GRAPHICAL USER INTERFACE (GUI) FOR MAGNETOENCEPHALOGRAPHY (MEG) AND ELECTROENCEPHALOGRAM (EEG) Farrell M1, Peatfield N2

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2School of Engineering Science, Simon Fraser University, Surrey, BC, Canada Autism Spectrum Disorder (ASD) refers to a wide range of neurodevelopmental conditions such as social communication deficits, repetitive behaviours and restricted interests [1]. Literature reports suggest that individuals with ASD have decreased sensitivity to emotions causing difficulty with common social communicative abilities

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 [2]. Research has shown the presence of an atypical, restricted inhibitory network in adolescents with ASD compared with normal controls [1]. The aim of this project was to examine the reaction time to a stimulus during a Go-NoGo task in children with ASD. The task required participants (n = 33) to press a button when a circle was shown (go trial) and not to respond when a square appeared (nogo trial). The shapes were superimposed on Eckman faces displaying happy or angry expressions. Both EEG and behavioural data were collected during the trials. Reaction time was calculated from the onset of the stimulus. The mean reaction time for go trials displaying happy or angry faces were compared. Data from 20 participants met the minimum criteria for inclusion in analysis. The mean reaction time, measured in seconds between the two variables were similar (happy = 0.366 ± 0.056, angry = 0.370 ± 0.059, p = 0.365). A paired t test was performed to calculate the p value. Our findings are consistent with previous research examining sensitivity to emotions in children with ASD. These findings will be compared to data from the control group. Analysis of EEG scans will determine whether the ASD group differed in electrical activity in the brain when compared to controls. Acknowledgements: The author would like to acknowledge funding from the Dean of Medicine’s SSRA 2016 International Summer Research Scholarship, UCD. References: 1. Vara AS, Pang EW, Doyle-Thomas KAR, Vidal J, Taylor MJ and Anagnostou E. Is inhibitory control a ‘no-go’ in adolescents with autism spectrum disorder? Molecular Autism. 2014; 5(1)1–10. 2. Kennedy DP, Adolphs R. Perception of emotions from facial expressions in high-functioning adults with autism. Neuropsychologia. 2012; 50(14)3313–9.

S15 significant difference between the D’ (signal detection sensitivity) of the ASD group while performing the Go/No-go task superimposed on happy (D’ = 1.93), or angry (D’ = 2.05), Ekman faces (P = 0.21, t(df) = 1.31(19)). Selection bias (criterion)*, and reaction time**, data from the ASD group was also analysed by our team. These results imply that happy or angry faces did not significantly disturb the ASD group’s capacity for signal detection. Further analysis will include comparison to the control group behavioural data. Indicators of altered inhibitory control neural processing from the EEG data will also be examined for group differences between the ASD and control group, and correlated with the behavioural data. Acknowledgements: The author would like to acknowledge funding from the Dean’s SSRA 2016 International Summer Research Scholarship, UCD. References: 1. Chan AS, Han YM, Leung WW-m, Leung C, Wong VC, Cheung M-c. Abnormalities in the anterior cingulate cortex associated with attentional and inhibitory control deficits: a neurophysiological study on children with autism spectrum disorders. Research in Autism Spectrum Disorders. 2011;5(1):254–66. 2. Dawson G, Webb SJ, McPartland J. Understanding the nature of face processing impairment in autism: insights from behavioral and electrophysiological studies. Developmental neuropsychology. 2005;27(3):403–24. Presenting Author: Mr James Morris Supervisor: Dr Sylvain Moreno Co-Supervisor: Mr Shaun Fickling

Presenting Author: Ms Aneesa Smith Supervisor: Dr Sylvain Moreno

32. SYMSTEMATIC REVIEW AND PROPOSED STUDY DESIGN FOR NEUROMODULATION THERAPY IN DEMENTIA

31. EFFECT OF EKMAN FACES ON INHIBITIORY CONTROL IN CHILDREN WITH AUTISM SPECTRUM DISORDERS: DATA ANALYSIS: SIGNAL SENSITIVITY (D’)

Sheehan D1, Fickling S2, Livingstone A3, Tannouri P3

Morris J1, Hamilton T1*, Smith, A1**, Doesburg S2, Fickling S2, Peatfield N2, Moreno S2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Digital Health Hub, School of Engineering, Simon Fraser University, Surrey, British Columbia Behavioural symptoms of Autism Spectrum Disorder (ASD) include difficulties with socialisation, communication, and a tendency towards repetitive behaviours and interests. Impaired inhibition control is thought to represent a fundamental deficit in ASD originating early in childhood (1). Additionally, it has been seen that individuals with ASD have impairments in focusing attention on faces, and facial processing (2). Therefore, the aim of the experiment was to analyse inhibitory control using a Go/No-Go task superimposed upon emotionally valent (happy/ angry) Ekman faces in an ASD paediatric (age 7–12) population. Typically Developing Children (n = 40) were compared to ASD (n = 33, post exclusion criterion; n = 20) children on an inhibition primed Go/No-Go task (4:1 Go/No-Go, 400 trials). Electroencephalogram (EEG), and behavioural data was collected while participants were performing the task. Behavioural data from the ASD group (n = 20) was analysed by our group according to Signal Detection Theory (SDT). There was no

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Digital Health Hub, School of Engineering, Simon Fraser University, Surrey, British Columbia. 3Healthtech Connex, Unit 1500, City Centre 1, 13737 96th Avenue Surrey B.C. Canada The aim of this research was to (a) investigate the methodologies of previous dementia research using electroencephalography (EEG) event related potentials (ERPs) and previous Neuromodulation therapy research design and (b) to propose a framework for a study combining these two areas. ERPs are small voltages which are evoked in the brain by specific stimuli or events (1). This study involves a systematic review of the study design methodologies and procedures involved in specific ERP recordings in patients with probable Alzheimer’s. In particular the P300 and N400 ERP components were of interest and further analysed. A neuromodulation device is used for Cranial-Nerve non-invasive neuromodulation to induce neural activity in the trigeminal (CN-V) and facial (CN-VII) nerves. It does so by electrostimulation using 143 gold-plated electrodes in contact with the anterior-dorsal aspect of the tongue. This aims to induce neuroplasticity and neuronal regeneration. CN-NINM has been evidenced to enhance and accelerate neural recovery with numerous impairments caused by brain injury (2). This study reviews previous study designs with an emphasis on areas with potential application for Dementia treatment. Resulting from this current work is the proposed study design to investigate whether routine neuromodulation exposure can halt or slow the progression of Dementia in individuals with probable

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S16 Alzheimer’s. This study framework involves monitoring each participant’s P300 and N400 amplitudes and latencies alongside the Mini-mental status examination and Clinical Frailty index scores. The study would take place over a period of 24 weeks with an active neuromodulation group, and an inactive control group. Acknowledgements: The author would like to acknowledge funding from the Dean’s SSRA 2016 International Summer Research Scholorship, UCD. References: 1. Teplan M. Fundamentals of EEG measurement. Measurement science review. 2002;2(2):1–1. 2. Danilov Y, Tyler M, Kaczmarek K. Cranial nerve non-invasive neuromodulation (CN-NINM): New approach to neurorehabilitation. International Journal of Psychophysiology. 2008;69(3): 301–302. Presenting Author: Mr David Sheehan Supervisor: Ms Ashley Livingstone Co-Supervisor: Mr Shaun Fickling

33. HIV CURE: TARGETING HIV LATENT RESERVOIRS WITH NEW CLASSES OF LATENCY REVERSAL AGENTS Crowley N1, McCartin A1, Le Douce V1, Gautier VW1 1

UCD Centre for Research in Infectious Diseases, UCD School of Medicine, University College Dublin, Belfield, Dublin 4 HIV has the ability to establish latent cellular reservoirs where it remains epigenetically silent and evades both the immune system and antiretroviral therapy.1 Current HIV CURE research aims to eliminate these reservoirs, by forcing viral gene expression using Latency Reversing Agents (LRAs).1 The aim of my research project was to validate a novel cellular contributor to HIV latency (Y) as a druggable target, using its inhibitor Drug X (X). We employed J-LAT models of HIV latency, which contain an integrated HIV-1 viral promoter fused to a GFP reporter gene, allowing us to detect reactivation of the HIV-1 promoter via increases in GFP levels monitored by FACS. We tested X at different concentrations, different exposure times and in combination with known LRAs including TNF-a and the HDAC inhibitor SAHA. X (50uM) in mono-treatment de-repressed the HIV-1 promoter in up to 15% of cells after 16 h exposure. Remarkably, X (20uM) enhanced TNF-a mediated reactivation of the HIV-1 Promoter by up to 200%. However, X limited SAHA-mediated reactivation of the HIV-1 promoter by 12%. Cell viability was unaffected by concentrations of X up to 20uM. The Western Blots revealed a modulation of SUMOylated proteins in a dose-dependent manner. Our results supported Y as a druggable target for HIV latency reversal. Further investigations could include sequential exposure to X with TNF-a or other LRAs and RT-qPCR and ChIP-qPCR analysis to look at X-induced changes at transcriptional and chromatin levels, respectively. References: 1. Van Lint C, Bouchat S, & Marcello A (2013) HIV-1 transcription and latency: an update. Retrovirology, 10:67. 2. Suzawa et al. (2015) A gene-expression screen identifies a nontoxic sumoylation inhibitor that mimics SUMO-less human LRH1 in liver, eLife 2015;4:e09003

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Presenting Author: Ms Niamh Crowley Supervisor: Dr Virginie Gautier Co-Supervisor: Dr Valentin Le Douce

34. TEMPORAL CHANGES IN THE RETINA IN THE ZUCKER DIABETIC FATTY RAT MODEL OF DIABETIC COMPLICATIONS Mylod E1, Gorman D1, Le Roux CW1, Docherty NG1 1

Diabetes Complications Research Centre, UCD School of Medicine, University College Dublin, Belfield, Dublin 4 Impaired metabolic and cardiovascular control contributes significantly to microvascular complications of type 2 diabetes mellitus (T2DM). Animal models offer a means of studying, in a controlled fashion, the changes in retinal gene expression and how they correlate to changes in retinal structure during the natural history of the development of diabetic retinopathy (DR). Zucker Diabetic Fatty Rats (ZDF) are used as a model of obesity related T2DM and associated complications. A comprehensive study of structural and gene expression based evidence of DR has not yet been undertaken. The aim of this research is to examine time dependent changes in gene expression in ZDF rats. This data will allow for analysis of correlation of gene expression changes to retinal injury based on data from the lab that has shown evidence of vascular degeneration. Vascular endothelial growth factor (VEGF), Intercellular Adhesion Molecule 1 (ICAM-1), Neutrophil cytosolic factor 1 (p47phox) and Neural antigen 2 (NG2) expression were examined in obese diabetic male ZDF fa/fa rat retinal samples at 12, 20 and 24 weeks of age. There was no significant change in expression in these genes of interest across the three time points. The rank order of the expression for the targets is as follows: NG2, p47phox, ICAM, VEGF. It was hypothesised there would be an increase in VEGF, ICAM-1 and p47phox expression and a decrease in NG2 expression from 12 to 24 weeks. These results indicate there is no significant change in retinal gene expression from onset to later stages of diabetes in ZDF rat samples. Acknowledgements: The authors would like to acknowledge funding from Science Foundation Ireland. Presenting Author: Ms Eimear Mylod Supervisor: Dr Neil Docherty Co-Supervisor: Prof Carel le Roux

35. PROTECTING MYOCARDIAL CELLS DURING PERIOPERATIVE ISCHAEMIA/REPERFUSION: THE ROLE OF ANAESTHETIC AGENTS PROPOFOL AND SEVOFLURANE Hewitt K1, MacDonagh L2, Breen EP2, O’Sullivan KE3, Hurley JP3, Gallagher HC1,2,4, Buggy DJ1,2,4,5 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4. 3Department of Cardiothoracic Surgery, Mater Private Hospital, Eccles Street, Dublin 7. 4Department of Anaesthesia, Mater Misericordiae University Hospital, Dublin 7. 5Outcomes Research Consortium, Cleveland Clinic, Ohio, USA

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Perioperative myocardial ischaemia can increase morbidity and mortality following surgery. Research has shown that volatile anaesthetic agents, including sevoflurane, can induce a cardioprotective phenomenon, attenuating the effects of ischaemia1. The aims of this project were to compare the cardioprotective effects of sevoflurane and propofol and assess the clinical relevance of H9C2 and Cor4U in vitro models of Ischaemia/reperfusion (I-R). H9c2 rat cardiomyocytes and human induced pluripotent stem cell (iPS)-derived cardiomyocytes (Cor4U, Axiogenesis, Germany) were treated with sevoflurane (2.5% via medical air) or propofol (3 lg/ml) or left untreated for 4 h. Cells were then exposed to hypoxia (1% O2) and glucose-free ischaemic-conditioned media for 1 h prior to reperfusion and reintroduction of nutrients for 2 h. Cardiomyocyte metabolism and viability was assessed by Cell TitreGlo luminescent assay (Promega). Apoptosis was assessed by measuring annexin-V/PI staining by flow cytometry. Ischaemic stress was confirmed by detecting protein expression of hypoxia-inducible factor 1a (HIF1a) by ELISA assay. I-R did not significantly induce apoptosis, alter cellular metabolism/viability or cause upregulation of HIF1a in H9C2 cells. Preliminary statistical analysis of Cor4U cells showed increased HIF1a expression and decreased cellular metabolism/viability following I-R relative to untreated non-ischaemic control. Although the H9C2 cell line is a widely accepted in vitro cardiomyocyte model2, it does not adhere to the clinical timelines of anesthetic or hypoxic exposure. Our results indicate that the Cor4U line may be a more clinically relevant in vitro cardiomyocyte model. Further studies will be required to elucidate relevant signalling pathways underlying cardioprotection by volatile anaesthetic agents. References: 1. De Hert SG, Turani F, Mathur S, Stowe DF. Cardioprotection with volatile anesthetics: mechanisms and clinical implications. Anesth Analg. 2005 100(6):1584–93. 2. Zordoky BNM, El-Kadi AOS. H9c2 cell line is a valuable in vitro model to study the drug metabolizing enzymes in the heart. J Pharmacol Toxicol Methods. 2007; 56(3):317–22. Presenting Author: Ms Katie Hewitt Supervisor: Prof Donal Buggy Co-Supervisor: Dr Helen Gallagher

36. A ROBOTIC HAND EXOSKELETON FOR REHABILITATION FOLLOWING STROKE Gilmartin B1, Rankin I2, Lennon O3, Severini G4, Holland D2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD School of Mechanical and Materials Engineering, University College Dublin, Belfield, Dublin 4. 3UCD School of Public Health, Physiotherapy and Sports Science, University College Dublin, Belfield, Dublin 4. 4UCD School of Electrical and Electronic Engineering, University College Dublin, Belfield, Dublin 4 Following a stroke the loss of grasping ability negatively impacts quality of life. Rehabilitation can help restore lost function through repetitive task practice. Robotic exoskeletons can assist patients in performing such practice. The aim of this project was to develop a low-cost and lightweight hand exoskeleton by leveraging recent advances in underactuated robotic graspers [1], textile-based ‘‘exosuits’’, and lightweight electromechanical actuators [2]. In collaboration with clinical experts it was decided to concentrate on tip-to-tip pinch grip involving the thumb, index and middle finger. Functional requirements of the device included proper alignment of

S17 the arches of the hand and wrist, and allowing for tactile sensation at the pads of the fingers and thumb. A prototype exoskeleton was developed through an iterative process of designing, building, and testing. The wrist and hand were fixed into a functional position for gripping using a custom-made splint. The exoskeleton consisted of series of cords, which served as ‘‘exo-tendons,’’ attached to a leather golf glove. Twisted string actuators [2] attached to the splint produced tension in the exo-tendons, thereby assisting with flexion and extension of the index and middle finger. The arrangement of exo-tendons represents an improvement over previous work in this area, allowing for the pads of the fingers to remain exposed. The positioning of the hand and wrist through custom splinting allows a functional position to be achieved which is an advance on other soft robotic systems. The resulting soft exoskeleton prototype will serve as a research platform for future rehabilitation studies in UCD. Acknowledgments: The authors kindly acknowledge funding for this research from the Health Research Board by awarding Mr. Gilmartin with the HRB Summer Student Scholarship (SS) 2016. References: 1. Gafford J, Ding Y, Harris A, McKenna T, Polygerinos P, Holland D, Walsh C, Moser A. Shape Deposition Manufacturing of a Soft, Atraumatic, and Deployable Surgical Grasper. Journal of Mechanisms and Robotics. 2015; 7(2), p. 021006. 2. Gaponov I, Popov D, Ryu J H. Twisted string actuation systems: A study of the mathematical model and a comparison of twisted strings. IEEE/ASME Transactions on Mechatronics. 2014; 19(4), 1331–1342. Presenting Author: Brian Gilmartin Supervisor: Dr Donal Holland Co-Supervisor: Dr Giacomo Severini Clinical Collaborator: Dr Olive Lennon

37. 3D PRINTING AND DESIGN OF FIBERREINFORCED PNEUMATIC ARTIFICIAL MUSCLES FOR USE IN SURGICAL AND ANATOMICAL SIMULATORS Glynn M1, Byrne O2, Coulter F2, Jones JFX1, O’Cearbhaill E2, Holland D2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD School of Mechanical and Materials Engineering, University College Dublin, Belfield, Dublin 4

Fiber-reinforced pneumatic artificial muscles are a class of soft actuator consisting of an elastomer bladder wrapped with inextensible reinforcements. Due to their compliancy and flexibility, they are suitable actuators for use in endoscopy, soft robotic exoskeletons for assistance and rehabilitation, and non-passive anatomical and surgical training models. Traditionally, fabrication involves a time-consuming process of moulding and casting. The aims of this project were to replicate the motions of these actuators using an additive manufacturing process and determine their optimal design characteristics. A low-cost 3D-printer was modified to print with liquid silicone under pressurized air on a rotating mandrel. A silicone inner tube layer was first printed, followed by a fiber reinforcement layer consisting of thermoplastic elastomer (TPE). This was then sealed with an outer silicone layer to maintain the integrity of the artificial muscle. Alternative fiber-reinforcement geometries were modeled using computer-aided design (CAD) software. Testing involved

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S18 inflation of the artificial muscles to characterize the behavior of these alternative geometries. The motions of contraction and axial extension were achieved by arranging fibers longitudinally and circumferentially, respectively. Helical fiber orientations (0° \ h \ 90°) resulted in twisting motions, in addition to varying degrees of axial extension and contraction. Bending motions were achieved with asymmetrical geometries. Preliminary qualitative test results indicate that 3D-printed actuators are stronger than their moulded equivalents. Results establish 3D printing as an effective manufacturing process for fiber-reinforced actuators. This will reduce the time, costs and human error previously involved in their fabrication. Miniaturized models were also fabricated, demonstrating scalability of the design. Presenting Author: Mr Mark Glynn Supervisor: Dr Donal Holland Co-Supervisors: Prof James FX Jones Dr Eoin O’Cearbhaill

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 early adolescence: Sex differences and normative values. Clinical Biomechanics. 2015; 30(5):469–474. 2. Holden S, Boreham C, Delahunt E. Sex Differences in Landing Biomechanics and Postural Stability During Adolescence: A Systematic Review with Meta-Analyses. Sports Med. 2015; 46(2):241–253. Presenting Author: Ms Sukhanya Sureish Supervisor: Dr Donal Holland Co-Supervisor: Dr Eamonn Delahunt

39. CLINICAL SIGNIFICANCE OF GUIDELINE NON-COMPLIANCE IN BIOELECTRICAL IMPEDANCE Haque M1, Joyce D1,2, Walsh D2 1

38. A ROBOTIC KNEE BRACE TO REDUCE ACL INJURIES AMONG ATHLETES Sureish S1, Delahunt E2, Holland D3 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD School of Public Health, Physiotherapy and Sports Science, University College Dublin, Belfield, Dublin 4. 3UCD School of Mechanical and Materials Engineering, University College Dublin, Belfield, Dublin 4

Female athletes are about 4 times more likely to sustain a non-contact anterior cruciate ligament (ACL) injury when compared to age and activity matched male athletes [1]. The increased risk can be attributed to aberrant landing biomechanics. Specifically, increased knee valgus angle and decreased knee and hip flexion during landing [2]. Many studies have analysed the biomechanics of the lower limb during the loading phase of landing. The purpose of this study, however, was to analyse the pre-loading phase of landing and thereby define the functional requirements of a robotic knee brace that can alter the biomechanics of the lower limb, during the unloaded phase, to reduce the risk of a non-contact ACL injury. Pre-existing data was analysed using the codamotion software. The movements analysed were the drop land, diagonal hop and drop vertical jump. The duration analysed was 500 ms prior to initial contact with the ground, which was defined as when 10 N was first recorded. During this 500 ms, the variables calculated were segment rotation, joint rotational velocity and joint rotational acceleration of the hip and knee in the sagittal plane and segment rotation of the hip and knee in the frontal plane. A report was produced that included the range of values for healthy subjects for each of the variables, which will be used by a team of engineers to guide the design of the brace. Using these values as target values for desirable landing biomechanics, the brace will hopefully be able to reduce non-contact ACL injuries. References: 1. Holden S, Boreham C, Doherty C, Wang D, Delahunt E. Clinical assessment of countermovement jump landing kinematics in

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Academic Department of Palliative Medicine, Our Lady’s Hospice & Care Services, Dublin 2 Bioelectrical impedance analysis (BIA) is an objective measure of body composition1. It utilises a portable device which passes electrical current through the body and reports resistance and reactance. From this, phase angle (PA) is calculated. This is a measure of hydration level, providing vital information for treatment. Guidelines for BIA are; measurements taken from right side of body, lying supine, bladder voided and patient fasted. However, studies show that many critically ill patients, those who may benefit most from this technology, are unable to comply with these guidelines2. Our aim is to quantify the clinical effects of non-compliance, using statistical tests for equivalence and to determine if this technology can be extended to critically ill patients. 10 healthy participants asked to fast prior to test, void bladder and remove jewelry. 5 measurements taken at 1 min intervals when they were 1) in compliance with guidelines 2) on their left hand side 3) upright 4) after a glass of water 5) after a snack. Resistance and reactance was noted. PA was calculated, results analyzed for equivalence. Chosen margin of equivalence for PA was 1o degree because of small clinical difference. RHS vs LHS: 8/10 equivalent Supine vs upright: 8/10 equivalent Water intake vs voided bladder: 9/10 equivalent Fasting vs after snack: 8/10 equivalent High equivalence is demonstrated, however, there is a need to investigate the causes of non-equivalence before recommending routine clinical use amongst a population that cannot comply. Further testing requires; Larger sample size and Statistical analysis of nonequivalent subgroups. References: 1. Gupta D, Lis C.G, Dahlk S.L, Vashi P.G, Grutsch J.F, Lammersfield C.A. Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer. British Journal of Nutrition 2004; (92): 960. 2. O’Donnell M, Lorton C, O’Connor B, Ui Dhuibhir P, Balding L, Fenton A et al. (2015) ‘Assessment of hydration in advanced cancer patients: The role of bioelectrical impedance vector analysis’

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Presenting Author: Meshkat Haque Supervisor: Prof Declan Walsh Co-Supervisor: Dr David Joyce

40. NO ASSOCIATION OF SNP RS3761847 WITH THE EXPRESSION OF THE TRAF1-C5 LOCUS AND INVASION OF RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS (RASF) Ferry D1, Trenkmann M2, Creevey K2, Wilson G2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

TNF Receptor Associated Factor 1-Complement C5 (TRAF1-C5) locus polymorphisms have been associated with RA susceptibility. The SNP rs3761847, located in the first intron of the TRAF1 gene, was associated with an increased risk of ACPA-positive RA in a genome-wide association study.1 Studies on the relationship of rs3761847 with joint damage are contradictory. Invasion of RASF into cartilage is key in the pathogenesis of RA and joint destruction.2 The aim of this research was to determine whether the genotype at rs3761847 was associated with differences in invasive capacity of RASF or the expression of TRAF1-C5 genes. 54 RA patients were genotyped using a TaqMan Allelic Discrimination Assay. Invasion assays using Matrigel invasion chambers were performed on 43 RASF lines. The expression of TRAF1 (total), TRAF1 variant 2, and complement C5 mRNA was determined by SYBR Green qPCR (n = 34). rs3761847 genotype frequencies (0.407 AA, 0.463 AG, and 0.130 GG), were in Hardy–Weinberg equilibrium (p = 0.98). The expression of TRAF1, TRAF1_var2, and C5 mRNA was not significantly different between the three genotypes (p = 0.929, p = 0.583, p = 0.980, respectively). This was also the case for invasion of RASF (p = 0.548). There was no correlation of genotype with RA biomarkers (CRP p = 0.718, ESR p = 0.179, RF titre p = 0.466, ACPA titre p = 0.712). Our findings suggest no relationship between genotype at rs3761847 and invasive capacity or the expression of TRAF1-C5 genes in RASF. Studies in other cell types implicated in the pathogenesis of RA, primarily innate and adaptive immune cells, are required to elucidate the mechanism of association of this locus. References: 1. Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, et al. TRAF1-C5 as a Risk Locus for Rheumatoid Arthritis—A Genomewide Study. N Engl J Med 2007;357: 1199–209. 2. Huber LC, Distler O, Tarner I, Gay RE, Gay S, Pap T. Synovial Fibroblasts: Key Players in Rheumatoid Arthritis. Rheumatology 2006;45:669–675. Presenting Author: Mr Daniel Ferry Supervisor: Prof Gerry Wilson Co-Supervisor: Dr Michelle Trenkmann

41. NOVEL GREMLIN-1 MUTANTS AS THERAPEUTICS IN DIABETIC KIDNEY DISEASE Phelan D1, Crean D2, Godson C2

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4

Diabetic kidney disease affects &40% of those with diabetes and is the leading cause of end stage renal disease. The bone morphogenic protein (BMP) antagonist Gremlin-1 is a key driver of Diabetic Nephropathy (DN) in experimental models and human disease. Increased Gremlin-1 expression drives fibrotic responses of renal cells antagonizing the activity of BMP agonists (1). The aim of this research was to develop a model to assess the inhibitory effects of Gremlin-1 on BMP-2 and -7 activity. This model would then be used to assess the interference of Gremlin-1 mutants on this effect. The effect of Gremlin-1 on BMP-2 and BMP-7 in HK-2 cells was assessed by measuring pSMAD-1,5,9 output after treatment with various concentrations. HK-2 cells were seeded (5 9 104 cells/ml with 4mls per dish) in 60 ml plates in HK-2 growth media. A 30-minute pretreatment involved combining 10 ng of BMP-2/7 with decreasing concentrations of Gremlin-1. The control was a treatment containing only the vehicle (Histidin). The cells were treated for 30 min. The p-SMAD output was measured by Western Blot, with confidence in the samples tested by staining with Ponceau Red following the transfer stage. In both the BMP-2 and BMP-7 treated cells, there was a dose dependent inhibition of pSMAD-1,5,9 with Gremlin-1. The results produced a model which can be used to assess the interference of Gremlin-1 mutants on the inhibitory effect of Gremlin1 on BMP signalling. This will allow for validation of Gremlin-1 mutants as therapeutics for diabetic kidney disease to be tested. Acknowledgements: The author would like to acknowledge funding from the Wellcome Trust Biomedical Vacation Scholarship Programme. References: 1. Dolan, Vincent et al. ‘‘Expression of Gremlin, A Bone Morphogenetic Protein Antagonist, In Human Diabetic Nephropathy’’. American Journal of Kidney Diseases 45.6 (2005): 1034–1039. Web. Presenting Author: Mr David Phelan Supervisor: Dr Daniel Crean Co-Supervisor: Prof Catherine Godson

42. NINTENDO WII FIT AS A DIAGNOSTIC TOOL FOR MYELOPATHY Cloete-Wakefield B, Severini G, Synnott K, Cashman K 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4. 3Mater Misericordiae University Hospital, Eccles St, Dublin 7. 4Department of Bioengineering, University College Dublin, Belfield, Dublin 4 Myelopathy is a disorder of the spinal cord. Currently, the diagnosis and monitoring of myelopathy is performed primarily through a neurological physical exam including but not limited to a gait exam, testing clonus, deep tendon reflex, inverted supinator, Babinski sign, Hoffman’s and Romberg’s test. The Nintendo Wii Fit, designed for the purpose of fun and fitness, is a relatively cheap, portable and easily accessible tool. The Nintendo Wii Balance board (WBB) offers a readily available cheaper alternative to the conventional Force Plate.

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This study aims to assess the use of the Nintendo Wii Fit in performing Romberg’s Test to aid in the diagnosis of Myelopathy. This study was conducted in conjunction with UCD Department of Bioengineering and compared myelopathic (n = 6) and non-myelopathic (n = 6) patient cohorts from the Orthopaedics Department of Mater Misericordiae University Hospital. Comparison of the two groups demonstrates deterioration of balance in both patient groups when performing a Romberg’s test. This change was not statistically significant comparing the two groups (p = 0.5780) using Welch’s t test. The stabilograms recorded showed an increased instability in a myelopathic patient compared to the more concise centre of pressure in a non-myelopathic patient. The Nintendo Wii Balance Board proved to be an easily available and reliable tool in assessing balance in both myelopathic and nonmyelopathic patients. The data collected showed promising results, however a continuation of the study with a larger patient group would be important to accurately assess the WBB’s ability to perform the Romberg’s Test to aid in diagnosis of myelopathy.

The high satisfaction rates associated with the Masterclass highlighted the importance of multidisciplinary-based approaches to HCV and allowed the subsequent development of an educational online platform. Presenting Author: Bashayer Almaazmi Supervisor: Prof Walter Cullen Co-Supervisor: Dr Geoff McCombe

Presenting Author: Bronte Cloete Wakefield Supervisor: Mr James Cashman Co-Supervisor: Mr Keith Synnott

At any one time, 3–9% of adolescents meet the criteria for depression [1]. Although primary care is considered well-placed for early intervention, the identification and management of adolescent depression can be a challenge for Primary Care Practitioners (PCPs). A systematic review of PubMed was conducted to determine the effectiveness of educational interventions for PCPs in this area. PubMed was searched to July 2016 for studies of educational interventions targeted at PCPs to improve the identification and/or treatment of depression among adolescents (aged 12–18). Retrieved citations were screened and full text articles reviewed for eligibility by two reviewers independently. A third reviewer arbitrated where there was disagreement. Two reviewers independently extracted data from included studies. The search resulted in 473 citations. Six studies were eligible and included in the qualitative synthesis, all of which were non-controlled before-and-after studies. Educational interventions were delivered in the format of a group seminar or workshop. Two included a standardised patient interview and feedback session. Of five studies measuring PCP confidence and knowledge in this area, all found improvements postintervention. Four studies measured and reported an increase in PCP identification of depression. Three studies assessed depression screening rates among adolescents and found improvements after training. The evidence base for included studies was low due to small sample size and study methodology. Findings indicate that educational interventions in the format of seminars and workshops prove effective in improving identification and management of adolescent depression in primary care, but further research is required for more conclusive evidence. Reference:

43. IMPLEMENTATION AND EVALUATION OF A MULTIDISCIPLINARY EDUCATIONAL MASTERCLASS SERIES AND THE SUBSEQUENT DEVELOPMENT OF AN ONLINE EDUCATIONAL TOOL Almaazmi B1, McCombe G1,2, Lambert JS1,2, Avramovic G2, Murphy C2, O’Connor M2, Perry N3, Cullen W1,2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Centre for Infectious Diseases Research, Catherine McAuley Centre, Mater Misericordiae University Hospital. 3 Community Response primary alcohol and hepatitis C service, Dublin 2

Recent research highlights how community-based approaches to HCV can optimise access, adherence and outcomes of HCV patients. A Multidisciplinary Educational Masterclass Series was organised for healthcare professionals (HP) working in primary care. An online educational tool was then developed from the outcomes of the Masterclass Series. From local general practice: NGOs, Addiction Treatment Services, GPs and other HPs working in primary care (n = 34) were invited to two one-day symposiums (Hepatitis C Masterclass) that examined: how to prevent new infections, why/how to screen, new approaches to diagnosis and treatment and treating coexisting problem alcohol use. Their feedback informed the development of an educational online tool to enhance multidisciplinary approaches to HCV treatment. The tool was constructed and forwarded to a panel of select HPs whose feedback further developed the tool. An evaluation tool was then produced to assess the feasibility of the educational tool. A majority of HPs ‘strongly agreed/agreed’ that the Masterclass helped HPs ‘appreciate the role of primary care’ and ‘secondary care’ in ‘the management of patients with HCV’ as well as ‘describing new approaches’ to HCV ‘assessment (Fibroscan)’ and ‘treatment’. Assigning a ‘designated nurse to liaise with hospital services’ was deemed ‘useful/very useful’ by a majority of participants. Some expanded on the topic claiming that a nurse liaison is ‘vital’ when ‘joining the dots’ of a patient’s treatment and is needed to ‘ease communications’ between different sectors of care.

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44. THE EFFECTIVENESS OF EDUCATIONAL INTERVENTIONS TO IMPROVE THE DETECTION AND/OR TREATMENT OF ADOLESCENT DEPRESSION IN PRIMARY CARE Kelly D1, Swan D1, Cullen W1 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4

1. Zuckerbrot RA, Jensen PS. Improving recognition of adolescent depression in primary care. Arch Pediatr Adolesc Med. 2006; 160:694–704 Presenting Author: Mr Damien Kelly Supervisor: Dr Davina Swan Co-Supervisor: Prof Walter Cullen

45. SURVIVAL AND BODY COMPOSITION ANALYSIS IN HEPATOCELLULAR CARCINOMA PATIENTS WITH MYOSTEATOSIS Gopaul A1, Stretch C1, Bathe O1 1 Department of Oncology, University of Calgary, Calgary, AB, Canada

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Cancer is commonly associated with body composition changes such as cachexia, sarcopenia and myosteatosis. Myosteatosis is characterized by an increase in lipid droplet accumulation in skeletal muscle tissue. This results in a decrease in the patient’s mean skeletal muscle radiation attenuation, which is associated with lower muscle quality. Moreover, this ectopic lipid droplet displacement in muscle may induce an increase in lipid mobilization to satisfy metabolic demands of cancer cells. In order to explore the relationship between myosteatosis and cancer survival, we have analysed the body composition of 62 patients with hepatocelluar carcinomas and compared them to available genetic and clinical data. Patients were dichotomised into those with myosteatosis and those without. Publicly available CT scans archived by the TCIA (The Cancer Imaging Archive) were downloaded, and images were analysed using SliceOMatic imaging analysis software. In future, these data will be linked to genomic information from tumours corresponding to the same patients (publicly available data from The Cancer Genome Atlas Project (TCGA)) to identify the associated molecular changes in tumours.

S21 interactions. Emerging mathematical models can provide quantitative assessments to guide the sequencing of these drugs to obtain synergy or avoid antagonism. Acknowledgements: Funding was provided in part by grant R01CA198096 from the US National Cancer Institute, National Institutes of Health, and the Deans SSRA 2016 International Research Scholarship, UCD. References: 1. Conroy T; Desseigne F; Ychou M; Bouche O; Guimbaud R; Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364: 1817–25 (2011). 2. Chakraborty A; Jusko WJ. Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferation. J Pharm Sci 91: 1334–42 (2002). Presenting Author: Ms Eimear Byrne Supervisor: Prof Robert M. Straubinger, PhD

Presenting Author: Mr Aquila Gopaul Supervisor: Dr Oliver Bathe

46. MECHANISTIC EXAMINATION OF THE FOLFIRINOX CHEMOTHERAPEUTIC DRUG REGIMEN ON PANCREATIC DUCTAL ADENOCARCINOMA CELLS

47. A COMPARISON OF FRACTURE RISK ESTIMATES IN HIV-POSITIVE AND HIVNEGATIVE SUBJECTS; DATA FROM HIV UPBEAT (UNDERSTANDING THE PATHOLOGY OF BONE DISEASE IN HIV-INFECTED SUBJECTS)

Byrne E1, Roy Chaudhuri T2, Lin Q2, Vaidya T2, Trueman S2, Straubinger N2, Straubinger R2

Shannon D1, Cotter AG1,2, McGinty T1, Macken A1, Kavanagh E2, Brady JJ2, Sabin CA3, Mallon PWG1,2 on behalf of the HIV UPBEAT Study Group

1

1

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the US, because detection and treatment are challenging. FOLFIRINOX(1) is a 4-drug standard-of-care regimen that extends lifespan but has high toxicity. This study developed an approach to evaluate drug administration regimens mechanistically for possible additive, synergistic, or antagonistic drug interactions. PANC-1 PDAC cells were exposed in vitro to varying concentrations and combinations of the FOLFIRINOX drugs (oxaliplatin, 5-fluorouracil, irinotecan, and leucovorin) for 72 h, and cell growth inhibition was quantified from cell count. Cell cycle distribution effects of drugs were examined by flow cytometry. Prism GraphPad 7 was used to establish the IC50 (concentration of drug inhibiting cell proliferation by 50%) graphically, and Phoenix WinNonlinÒ was used to identify Imax (maximal drug effect) and a drug interaction parameter, w(2). Two growth inhibition assay formats were investigated, and IC50 values of 62.25 lM and 200 lM were obtained for Oxaliplatin and 5-Fluorouracil (respectively). The combination of 5FU and Irinotecan appeared to be antagonistic based upon graphical analysis; 5FU alone inhibited PANC-1 cell growth more than did combinations with 0.1, 1, and 10 lM Irinotecan. However, data modelling using WinNonlinÒ derived a drug interaction value w = 9.938, which indicates additivity (w = 1) or slight synergy (w \ 1). These studies identified assay conditions and an analysis workflow for investigating FOLFIRINOX drug interactions quantitatively in vitro. Cell cycle analysis provides additional information on drug

Low bone mineral density (BMD) and fractures are more common in HIV-positive individuals (1). Fracture prediction tools validated in the general population, may not be accurately predict fracture in a younger HIV-positive cohort (2). We aimed to compare major osteoporotic and hip fracture risk in HIV-positive and -negative individuals utilising available online tools. HIV UPBEAT is a cohort study of HIV positive (HIV +) and negative (HIV-) subjects from similar demographic backgrounds; demographic, clinical, medication and laboratory data were collected and BMD was measured by dual energy x-ray absorptiometry. For each study subject, data was entered into online fracture risk tools: Fracture Risk Assessment Tool (FRAX), Garvan and QFracture. We assessed between-group differences in 10-year major osteoporotic fracture and hip fracture estimates using Wilcoxon. 474 subjects were recruited from February 2011 to July 2012. The HIV+ group (N = 210) was 58% male, 40% African, aged 39[33, 46] years; the HIV- group (N = 264) was 43% male, 25% African and aged 42[34, 49] years. Femoral neck BMD was significantly lower in the HIV+ group (P = 0.003, \0.0001 and 0.001, respectively). 10-year fracture risk estimates are presented in table 1. There was no difference in major osteoporotic risk between the HIV+ and HIVgroups. However, after incorporating FN BMD values (FRAX + FNBMD, Garvan), there was a significantly greater hip fracture risk in HIV+ subjects. Currently available fracture prediction tools may underestimate fracture risk in HIV+ individuals. Utilizing tools that incorporate

UCD School of Medicine, University College Dublin, UCD, Dublin 4, Ireland 2 Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214

HIV Molecular Research Group, UCD School of Medicine. 2Mater Misericordiae University Hospital, Eccles St., Dublin 7. 3Research Department of Infection and Population Health, UCL Medical School, London

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BMD may improve the ability to demonstrate increased fracture risk in this population. Table 1. Fracture risk estimates in HIV-positive and HIV-negative groups 10-year probability of fracture median P (IQR) % HIV+ (n = 263)

HIV- (n = 203)

Major osteoporotic fracture risk: FRAX

2.9 (2.5, 5.3)

2.7 (2.4, 5.1)

0.36

FRAX + FN BMD 3.2 (2.5, 5.3) QFracture 0.6 (0.3, 1.1)

2.9 (2.5, 4.8) 0.5 (0.4, 1.0)

0.11 0.27

Garvan*

2.0 (1.0, 3.0)

0.92

2.0 (1.0, 3.0)

Hip fracture risk: FRAX

0.2 (0.1, 0.6)

0.2 (0.1, 0.5)

0.08

FRAX + FN BMD 0.2 (0.0, 0.5)

0.1 (0.0, 0.3)

0.0001

QFracture Garvan*

0 (0.0, 0.1)

0 (0.0, 0.1)

0.95

0.1 (0.0, 0.1)

0 (0.0, 0.1)

0.02

FN BMD, femoral neck bone mineral density; * Garvan incorporates BMD

autonomic symptoms (AS) and OH, and to ascertain whether OH and HRV are equivocally reliable for diagnosis of AD. Consecutive ambulant adults attending day-hospice or in-patient services were recruited. Interviews established demographics and AS. Objective tests for HRV and BP measurement were conducted. Postural symptoms during testing were noted. 22 (12 male, 10 female) participants were recruited. Median age was 70 (33–89). Eight had OH, three of these had POH. None with OH reported postural symptoms. Mean number of AS reported in non-persistent-OH group (n = 5) and POH group (n = 3) was 8 and 12, respectively. Mean SDNN (n = 20) was 25.53 ms. OH is prevalent in advanced cancer. No association was found between AS and OH. HRV is associated with OH. Active stand test was tolerated by participants and could be considered for routine screening for AD in advanced cancer. HRV screening could be an alternative for frailer patients. AS profile is not a useful tool for assessing AD. References: 1. Stone CA, Kenny RA, Nolan B, Lawlor PG. Autonomic dysfunction in patients with advanced cancer; prevalence, clinical correlates and challenges in assessment. BMC Palliative Care. 2012; 11:3 2. Walsh D, Nelson KA. Autonomic nervous system dysfunction in advanced cancer. Support Care Cancer. 2002; 10(7):523–8 Presenting Author: Mr Chang Sheng Leong Supervisor: Prof Declan Walsh Co-Supervisor: Ms Michelle Barrett

References: 1. Compston J. Osteoprosis and Fracture Risk Associated with HIV Infection and Treatment. Endocrinology and Metabolism Clinics of North America. 2014, vol 43(3):769–780. 2. McGinty T, Mallon P. Protecting bone in long-term HIV positive patients receiving antiretrovirals. Expert Review of Anti-Infective Therapy. 2016, vol 14(6):587–599.

49. FUNCTIONAL ANALYSIS OF THE PHOSPHORYLATION OF COPPER CHAPERONE OF SUPEROXIDE DISMUTASE (CCS) AND THE ROLE OF COPPER FOR PLATELET FUNCTION

Presenting Author: Dylan Shannon Supervisor: Dr Aoife Cotter

Tan LY1, Smolenski A1,2

48. ORTHOSTATIC HYPOTENSION AND HEART RATE VARIABILITY IN THE DIAGNOSIS OF AUTONOMIC DYSFUNCTION IN ADVANCED CANCER Leong CS1, Barrett M2,3, Walsh D1,2,3 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2School of Medicine, Trinity College Dublin, College Green, Dublin 2. 3Our Lady’s Hospice & Care Services, Harold’s Cross, D6W

Autonomic dysfunction (AD), a negative prognostic indicator, is common in advanced cancer [1, 2]. Cardiovascular signs include loss of heart rate variability (HRV) and later, orthostatic hypotension (OH). OH increases risk of falls and mortality. HRV is the time difference between successive heartbeats, measured as a standard deviation (SDNN). OH is a decrease of at least 20 mmHg in systolic and/or 10 mmHg in diastolic blood pressure (BP) upon orthostatic stress. Persistence of OH (POH) is OH beyond 3 min. This prospective, observational study aimed to identify prevalence of OH and proportion of POH, examine the relationship between

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UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4 Activation of cyclic nucleotide dependent protein kinases (PKA/ PKG) by the prostacyclin and nitric oxide signalling pathways initiates a phosphorylation cascade resulting in platelet inhibition. Recently CCS was identified as a new substrate of PKA/PKG in blood platelets [1], leading to the hypothesis that CCS phosphorylation might contribute to platelet inhibition. CCS protein transfers copper ions to superoxide dismutase 1 (SOD1), an antioxidant enzyme in cytosol, and subsequently activating it [2]. Our research focus was to (a) elucidate the role of CCS phosphorylation in the interaction between CCS-SOD1 using wild-type CCS and Serine267 phosphorylation site mutants of CCS in transfected HEK293 cells, (b) identify new binding proteins of CCS by pull down and mass spectrometry and (c) investigate the role of copper in platelet function using copper chelator tetraethylenepentamine (TEPA). We found no significant difference between the interaction of SOD1 with wt-CCS or mutant CCS. Forskolin-induced phosphorylation did not affect the SOD1/CCS interaction. A single band of approximately 130 kDa was observed in both wt-CCS and mutant S267/8EE-CCS pull-down experiments and Coomassie staining. This was identified as Ceruloplasmin (122 kDa), a copper-binding protein normally present in plasma. Lastly, platelets exposed to high copper

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 or TEPA concentration (100 and 500 lM) at RT or 37 °C for 1–2 h showed no difference in their aggregation response to adenosine diphosphate (ADP) or thrombin. In conclusion, alterations to S267 phosphorylation site do not affect SOD1/CCS interaction and platelet aggregation remains unaffected by short-term changes of extracellular copper concentration. A possible link between Ceruloplasmin and CCS needs to be investigated further. References: 1. Beck F, Geiger J, Gambaryan S, Veit J, Vaudel M, Nollau P, Kohlbacher O, Martens L, Walter U, Sickmann A, Zahedi RP. Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways. Blood. 2014 Jan 30; 123(5):e1-e10. 2. Lamb AL, Wernimont AK, Pufahl RA, Culotta VC, O’Halloran TV, Rosenzweig AC. Crystal structure of the copper chaperone for superoxide dismutase. Nature Structural and Molecular Biology. 1999 Aug 1; 6(8):724–9. Presenting Author: Ms Lok Yi Tan Supervisor: Dr Albert Smolenski

50. ASSESSMENT OF EFFECTIVENESS OF LIFESTYLE MODIFICATION EDUCATION FOR WOMEN WITH NEWLY DIAGNOSED GESTATIONAL DIABETES Alayoub H1, Daniels U2, Corcoran C2, Rutter E2, Coffey M2, Harrington L3, Devine H3, Curran S3, Hatunic M4, Higgins M5 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Midwifery, National Maternity Hospital. 3Dietitian, National Maternity Hospital. 4Endocrinology, Mater Misericordiae University Hospital. 5UCD Obstetrics and Gynaecology, School of Medicine, University College Dublin, Belfield, Dublin 4, National Maternity Hospital

Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy and resolves following delivery.[1,2] It increases maternal and foetal morbidity and is associated with an increased risk of future type 2 diabetes.[2] Women diagnosed with GDM need high quality multidisciplinary education in order to have ownership of their diagnosis. The aim of this study was to assess the effect of such an educational intervention on women’s knowledge of GDM. All women with a diagnosis of GDM are invited to attend an educational session aiming to impart knowledge on GDM management. For the initial stage of the study, all pregnant women diagnosed with gestational diabetes were invited to complete a questionnaire before and after the educational intervention; only individuals who have completed both have been included. The questionnaire reviewed knowledge of suitable foods, implications of GDM diagnosis and management of GDM. Total of 716 women completed both questionnaires; mean age of the participants was 34 ± 5 years. Just under a half (46.9%, n = 333) were primiparous. The majority of the patients (62.5%, n = 439) were Irish; 53.4% (n = 382) presented with a family history of diabetes. There was a significant increase in median score for knowledge following the educational intervention (pre-intervention score 8 (-2 to 12); post-intervention score 12 (1–12); p \ 0.001). The initial study demonstrates the benefits of an educational session in reinforcing and expanding the patients’ knowledge in GDM.

S23 The next stage of the study is to validate a questionnaire allowing comparison between other units both nationally and internationally. References: 1. McPhee AJ, Crowther CA, Middleton P, Tieu J. Screening and subsequent management for gestational diabetes for improving maternal and infant health. Cochrane Database of Systematic Reviews. 2014 Feb 11. 2. Bernstein JA, McCloskey L, Gebel CM, Iverson RE, Lee-Parritz A. Lost opportunities to prevent early onset type 2 diabetes mellitus after a pregnancy complicated by gestational diabetes: Table 1. BMJ Open Diabetes Research and Care. 2016 Jun; 4(1):e000250. Presenting Author: Mr Hamed Alayoub Supervisor: Prof Mary Higgins Co-Supervisor Ms Usha Daniels

51. EXAMINING THE RELATIONSHIP BETWEEN DOPPLER ULTRASOUND AND HBA1C LEVELS IN DIABETIC PRENANCIES McDonnell B1, Sharkey L1, Russell N2, Mulcahy C3, McAuliffe FM4, Higgins MF4 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Cork University Maternity Hospital. 3Midwifery, National Maternity Hospital. 4UCD Obstetrics and Gynaecology, School of Medicine, National Maternity Hospital

Pre-gestational diabetes (PGDM) is associated with an increased risk of fetal and neonatal morbidity and mortality [1]. The aim of this study was to assess fetal vascular Doppler ultrasound measurements (measured at 30, 33 and 36 gestational weeks) based on glycaemic control in early pregnancy (booking HbA1c). Serial third trimester ultrasound measurements of 231 pregnancies affected with maternal PGDM were analysed; clinical measurements were recorded including measures of glycaemic control (HbA1c). Umbilical Artery Pulsatility Index (UAPI), Middle Cerebral Artery Pulsatility Index (MCAPI) and Middle Cerebral Artery Peak Systolic Velocity (MCAPSV) measurements at 30,33 and 36 weeks were studied and compared based on booking HbA1c (\ 6.5% as a marker of ‘‘good glycaemic control’’ and C 6.5% as ‘‘poorer control’’). Subgroup analysis was performed based on type of PGDM (Type 1 diabetes (T1DM), n = 167; Type 2 diabetes (T2DM), n = 64) There was no consistent pattern of significant differences in UAPI, MCAPI and MCAPSV between groups based on booking glycaemic control. Women with HbA1c [6.5% had a statistically significant increased 33 week MCAPI measurements (MCAPI ‘‘good control’’ 1.87 ± 0.263; MCAPI ‘‘poorer control’’ 1.86 ± 0.376; p = 0.02); this difference held in women with T1DM (p \ 0.01) but not in T2DM. No consistent pattern has yet been identified in Doppler ultrasound measurements based on booking glycaemic control in PGDM pregnancies. This study is ongoing. Reference: 1. Higgins M, Galvin D, McAuliffe F et al. Pregnancy in women with Type 1 and Type 2 diabetes in Dublin. Ir J Med Sci. 2011; vol 180: 469–473 Presenting Author: Mr Brian McDonnell Supervisor: Dr Mary Higgins Co-Supervisor: Dr Noirin Russell

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52. ULCERATIONS AND CROHN’S DISEASE ACTIVITY INDEX IN PEDIATRIC PATIENTS Saleh R1, Raftery T2, Broderick A2, Bourke B2, Hussey S2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Gastroenterology, Hepatology and Nutrition Unit, Our Lady’s Children’s Hospital, Crumlin, Dublin 12 Gastrointestinal ulcers are early markers for the diagnosis of Crohn’s disease (CD); however, endoscopic severity does not correlate with prognosis or predict clinical response to therapy [1]. The aim of this study is to compare severity and therapeutic response for patients who have gastrointestinal ulcers versus patients without. Severity was determined by patients’ PCDAI (Pediatric Crohn Disease Activity Index) score at diagnosis and therapeutic response at follow-up. Data from a national cohort database, which included children diagnosed from 01 Jan 2012 to 2016 at Our Lady’s Children’s Hospital in Dublin, were retrospectively reviewed. Data on clinical presentation, endoscopic features, and types of treatment used were recorded. Patients were followed up and PCDAI scores were measured at each visit. ANOVA analysis was performed for statistical significance. A total of 180 patients with CD were included. The mean age was 11.9 year ± SD 3.4 at diagnosis, and 133 patients (73.9%) were boys. Forty-three (23.9%) had no ulcers and 137 (76.1%) had at least one ulcer within their gastrointestinal tract. Of the latter group, 64 (53.3%) had superficial ulcers, 29 (21.2%) had deep ulcers and 44 (32.1%) had both. There were no significant differences in PCDAI scores among groups at baseline (p = 0.24). However, mean PCDAI scores were significantly different between the superficial (9.0) and deep (32.5) ulcer groups at 3 month follow-up (p = 0.05). The presence and type of ulcers did not affect patients’ PCDAI scores at baseline, but did have an affect at follow-up. Further analysis of data from follow-ups is needed to confirm causality. Reference: 1. Landi B, Anh TN, Cortot A, et al. Endoscopic monitoring of Crohn’s disease treatment: a prospective, randomized clinical trial. The Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives. Gastroenterology. 1992; 102:1647–1653. Presenting Author: Ms Raneem Saleh Supervisor: Dr Seamus Hussey Co-Supervisor: Dr Tara Raftery

53. PAEDIATRIC EOSINOPHILIC OESOPHAGITIS IN IRELAND: A 10 YEAR REVIEW OF PRESENTING SYMPTOMS, PHENOTYPE AND MANAGEMENT AT DIAGNOSIS Keane F1, O’Malley A2, Casey A2, O’Flynn K1, Sugrue S1, McDermott M3, O’Sullivan M3, Raftery T4, Mahony M5, Quinn S6, Broderick AM1,4, Bourke B1,4, Hussey S1,4,7 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2School of Biological Sciences, Dublin Institute of Technology, Kevin Street, Dublin 8. 3Department of Pathology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland. 4 National Centre for Paediatric Gastroenterology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12. 5Paediatric Department, The Children’s Ark, University Hospital Limerick, Co. Limerick,.

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Tallaght Children’s Hospital, Tallaght, Dublin 24, 7Department of Paediatrics, Royal College of Surgeons, Ireland, Dublin 2

Eosinophilic oesophagitis (EoE) is a poorly understood, chronic immune-mediated condition resulting in inflammation and swelling caused by excess eosinophilic infiltration of the oesophageal mucosa. Little international epidemiological data exists, and no Irish national data available to-date. This study aims to establish the national incidence of paediatric EoE in Ireland from 01.01.2006 to 31.12.2015 inclusive, and to profile the symptoms, phenotype, and management at diagnosis. Paediatric endoscopy occurs in three approved centres nationally, representing the national paediatric cohort. All patients were identified using endoscopy and histological records. A retrospective chart review was performed using a specially designed case report form. Those \6 years were compared to [6 years. Overall, 358 children were diagnosed with EoE with full chart data available on 343 (95.8%) patients. A sustained increase in incidence over time was observed. Male: female ratio was 3:1, and 36% were under \6 years. Pain was the most common symptom (45%), occurring more frequently in those [6 years (P \ 0.001); vomiting was more common in those\6 years (P \ 0.001). Endoscopically, an inflammatory phenotype was predominant (93%) with a stricturing phenotype occurring in 7%. Seventy-eight percent were treated with swallowed fluticasone propionate alone or in combination with a proton pump inhibitor. Nine percent were treated with a PPI alone while 12.7% were not given any medication. This profiles novel data on paediatric EoE in Ireland. A male preponderance was observed. There are marked age specific differences in presenting symptoms with 36%\6 years. Further research is necessary regarding outcomes of this national cohort. Presenting Author: Ms Francesca Keane Supervisor: Dr Seamus Hussey Co-Supervisor: Dr Tara Raftery

54. A CLINICAL AUDIT OF XEROSTOMIA ASSESSMENT AND TREATMENT PRACTICES AMONGST ADVANCED CANCER PATIENTS IN A PALLIATIVE CARE SETTING Mukerji N1, Kenny C2, Walsh D2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Academic Department of Palliative Medicine, Our Lady’s Hospice & Care Services, Harold’s Cross, Dublin 6 W

Xerostomia is the subjective sensation of dry mouth. It is the fourth most common symptom in advanced cancer patients and impacts negatively on physical and psychosocial wellbeing [1]. Older age and polypharmacy are risk factors for dry mouth and are common in advanced disease. This study aims to evaluate prevalence of xerostomia, as well as compliance with assessment and treatment practices. A retrospective chart audit was conducted on 173 admissions from an in-patient palliative care unit. Data were collected pertaining to patient demographics, cancer diagnosis, medications, oral health assessment and xerostomia treatment. Audit standards were based on local policy as follows: Oral Health Assessment Tool (OHAT) completed on all patients; OHAT completed within one day of admission; oral care plan completed if problem diagnosed; xerostomia treatment prescribed where necessary. Descriptive statistics were used to report compliance with standards. Cohen’s Kappa and Intraclass Correlation Coefficient were used for inter-rater reliability based on a 10% sample of the dataset.

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 86% of admissions had OHAT completed and 91% of these were on day of admission. Care plans were completed for 76% of patients with oral care needs. Appropriate medications were prescribed for 34% of patients with dry mouth. Inter-rater reliability was high or perfect for all primary outcomes. Results indicate that oral health is evaluated in the majority of patients, however treatment appears low. This may be due to poor instrument design, where non-prescription treatments or ‘treatment unnecessary’ cannot be documented. Existing tools could be amended to reflect patient care needs more accurately. Reference: 1. Davies A, Finlay I. Oral care in advanced disease. Oxford: Oxford University Press; 2005. Presenting Author: Ms Narayani Mukerji Supervisor: Mr Ciaran Kenny Co-Supervisor: Prof Declan Walsh

55. OUTCOMES OF CHRONIC DIALYSIS IN INFANTS UNDER 2 YEARS Van de Hoef D1, Gallibois C2, Jawa N3, Noone DG3 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2School of Medicine, Royal College of Surgeons in Ireland, Dublin 2. 3Division of Nephrology, The Hospital for Sick Children, Toronto

Infants with end-stage renal disease require dialysis until transplantation by age 2. Infant dialysis has significant morbidity and mortality [1,2]. The objective of this study was to review outcomes of chronic dialysis, both peritoneal dialysis (PD) and hemodialysis (HD), in a contemporary cohort of infants at the Hospital for Sick Children, Toronto. Infants who underwent chronic dialysis, under age 2, from 2005 to 2015 were included. Demographic, dialysis-related and outcome data were extracted from the electronic patient chart. Summary statistics were analyzed using Stata 12. Median with interquartile range is provided. 28 infants, 18 (64.3%) male were included. 20 (71.4%) had an antenatal diagnosis. Time from birth to dialysis initiation was 13.5 (10, 67) days. 14 (50%) were initiated on PD and 14 (50%) on HD. 8 infants switched modalities a median of 3 (range 2–11) times. The peritonitis rate was 1 episode/22 patient months for those on PD. 11 (64.7%) required a hemodialysis central line change and the central line associated blood stream infection rate was 1.48 per 1000 central line days. Median time in hospital from dialysis initiation until death/transplant was 8.5 (3.6, 16.7) months. 6 (21.4%) infants died, 17 (61%) were transplanted and 5 (17.9%) remain on dialysis. Median time to transplantation was 2.1 (1.8, 2.7) years. There has been an increase in the use of HD. Survival and transplantation rates have improved over time, however, this is associated with prolonged hospital stays and multiple switches between dialysis modality in a significant number. References: 1. Feinstein S, Rinat C, Becker-Cohen R, Ben-Shalom E, Schwartz SB, Frishberg Y. The outcome of chronic dialysis in infants and toddlers–advantages and drawbacks of haemodialysis. Nephrol Dial Transplant. 2008; 23(4): 1336–45. 2. Al-Hermi BE, Al-Saran K, Secker D, Geary DF. Hemodialysis for end-stage renal disease in children weighing less than 10 kg. Pediatr Nephrol 1999; 13(5): 401–3.

S25 Presenting Author: Ms Dayna van de Hoef Supervisor: Dr Damien Noone

56. HOW DOES THE INTRODUCTION OF FREE GP CARE FOR CHILDREN IMPACT ON PATIENTS AND PRACTICES? A QUALITATIVE STUDY Conneally N1, McCombe G1, Leahy D1, Behan W1, Maloney D1, Beame C2, McGrane C1, Clendennen N1, Cullen W1 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Complete GP Clinical Software Access to primary healthcare services in Ireland has traditionally been highly inequitable, with patients either paying for the full cost of services, receiving a GP visit card or having their full medical costs covered under the General Medical Scheme (GMS)1,2. In July 2015, free GP care for all children under 6 years old was introduced in Ireland. This study aims to investigate GPs’ views of the free GP care for children under six scheme and how it has impacted on their practice. 16 GPs were recruited from general practices across Ireland. Semistructured interviews were conducted and analysed using thematic analysis. Most GPs reported experiencing increased pressure on their service and dissatisfaction with resourcing of the scheme. However this effect was reduced in practices with low paediatric populations or higher populations of GMS patients. The majority of GPs stated that children under six are now presenting earlier with more trivial illnesses. Many GPs also reported increased use of Out Of Hours (OOH) services by parents after the working day. However, many GPs report that they now experience less pressure to prescribe antibiotics to children under six. This is the first study of this type on GPs’ views of the free care scheme; many report dissatisfaction with the introduction of the scheme and find implementing it challenging, with those with the most paediatric patients experiencing most pressure. There is particular pressure on OOH services. However, some positive changes are being reported by GPs, such as reductions in antibiotic prescribing. References: 1. Layte R, Nolan B. (2004). Equity in the Utilisation of Health Care in Ireland. The Economic and Social Review. 25 (2), 111–134. 2. Nolan A, Smith S. (2012). The effect of differential eligibility for free GP services on GP utilisation in Ireland. Social Science and Medicine. 74, 1644–1651. Presenting Author: Ms Neasa Conneally Supervisor: Prof Walter Cullen Co-Supervisor: Dr Geoff McCombe

57. EFFECT OF T-CELL INHIBITORS ON PLASMA N-GLYCOME IN RHEUMATOID ARTHRITIS PATIENTS O’ Meara C1, Haakensen VD2, Nigrovic P3, Rudd PM4, Saldova R4, O’Flaherty R4 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Institute for Cancer Research and Department of Cancer

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S26 Genetics, Oslo University Hospital, The Norwegian Radium Hospital, Oslo N-0424, Norway. 3Harvard Medical School, MA 02115, Boston, USA. 4NIBRT Glycoscience Group, National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Dublin 4 Rheumatoid arthritis (RA) is an autoimmune disorder characterized by symmetrical inflammation of the synovial joints. Glycans are emerging as important biomarkers for certain diseases such as inflammatory arthritic conditions and cancers. The first link between changes in glycosylation and RA was reported by Parekh in 1985 where it was shown that RA patient samples have a greater proportion of agalactosylated immunoglobulin G glycans [1]. Treatment of RA usually commences with traditional disease modifying anti-rheumatic drugs (e.g. methotrexate) and can be proceeded with biologic agents such as tumour necrosis factor or T-cell inhibitors if found to be ineffective. Glycosylation analysis can give important mechanistic insights for their mode of actions. The aim of this study was to release, purify and analyse N-glycans from the plasma of patients with RA (n = 14) before and after treatment with T-cell inhibitors to determine if there was a statistical difference in their glycosylation profiles using t-test, with Bonferroni and false discovery rate (FDR) corrections on statistical software R. The N-glycans from patient plasma pre and post T-cell inhibitor treatment were purified, enzymatically released and fluorescently labeled using the in-gel-block high-throughput method [2]. Ultra-HighPerformance Liquid Chromatography was used to analyze the labeled N-glycans. The results showed no statistical significance for the comparison of glycosylation before and after treatment with the T-cell inhibitors with Bonferroni or FDR corrected t-tests. This suggests that the T-cell inhibitors, in this cohort, may not alter glycosylation through their mechanism of action; however a larger sample set would be required for validation. Acknowledgements: RS acknowledges funding from the Science foundation Ireland Starting Investigator Research grant (SFI SIRG) under grant number 13/SIRG/2164 and ROF acknowledges EU FP7 program HighGlycan, grant no. 278535, for funding this work.

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Competence is prominent in determining the preparedness of housemen for their subsequent performance in medical practice [1, 2]. This study investigates the self-perception of medical school graduates regarding their own competencies which reflect their preparedness in venturing into their housemanship. This cross-sectional study was conducted in Penang General Hospital with housemen from all departments as respondents. The questionnaire is based on the ‘‘Transition to Residency and Internship and Preparation for Life’’ (TRIPLE) course in John Hopkins University with scale-based score from 1 to 5; 1—least well and 5— very well for 17 questions divided into patient-care, management and self-care skills. The questionnaires were given out to 250 housemen in PGH. 187 (74.8%) responses were received but only 170 (64%) officers completed the form. 111 respondents graduated from Malaysian universities while the rest graduated internationally. Results for Malaysian graduates showed mean scores of 3.14 (SD = 0.42) for patient-care skills, 3.37 (SD = 0.15) for management skills and 3.24 (SD = 0.07) for self-care skills. There is no significant difference between the housemen’s competency that graduated internationally and locally (p [ 0.05). Preparation for Internship (PRINT) literature demonstrates a score of 3.8 indicating ‘students can perform their clinical skills unsupervised’. Based on this, house officers were considered adequately prepared in medical school to a certain extent. Overall, the tasks that housemen are less proficient in are related to patient-care skills especially the catheters’ insertion which had the lowest score, 2.15 (SD = 0.89). To improve this, simulation-based learning could be integrated in Malaysia’s medical education curriculum. Standardised patients and models are used to help students in mastering practical skills through repetitive training. References: 1. Adewale A, Abd. Manaf N, Omar A. Competence in Medical Practice as Perceived by Malaysian Medical Interns: A Measurement Invariance Analysis. Journal of Education and Vocational Research. 2012;3(7):226. 2. Tohda S, Suzuki T, Nara N. The Current Medical Education System in the World. J Med Dent Sci 2011, (58):79–83.

References:

Presenting Author: Ms Najhan Rosli Supervisor: Prof William Oliver Kirwan Co-supervisor: Prof Premnath Nagalingam

1. Parekh RB, et al.: Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 1985, 316:452–457. 2. Royle L, Campbell MP, Radcliffe CM, White DM, Harvey DJ, et al.: HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database software. Anal Biochem 2008, 376:1–12.

59. ESTABLISHING A NEW METRIC FOR CT IMAGE QUALITY

Presenting Author: Ms Cherise O’Meara Supervisor: Dr Roisin O’Flaherty Co-Supervisor Dr Radka Saldova

58. GRADUATE PREPAREDNESS FOR HOUSEMANSHIP Rosli N1, Premnath N2, Kirwan W2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Penang Medical College, 3 Jalan Sepoy Lines, 10450 George Town, Penang, Malaysia

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Healy R1, Stowe J1, Rainford L1, Henrikson Fredheim KM2, Vestbøstad M2, Rygh C2, Oynes M2 1 Diagnostic Imaging, UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Health and Social Care, Bergen University College, Inndalsveien 28, 5063 Bergen, Norway

Computed Tomography (CT) image quality is controlled by a number of parameters such as kVp, mAs, and image slice thickness. These are known to affect patient radiation dose and also the spatial and contrast resolution of images. Spatial resolution is the ability for an imaging system to display fine details separately [1] while contrast resolution is the ability to demonstrate small changes in tissue contrast [2]. The aim of this research was to analyse CT images from (a) an anthropomorphic CT abdomen phantom and (b) a CatphanÒ quality assurance (QA) phantom in an attempt to find the optimal parameter

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 selection for scanning. Following this research, a CT simulation teaching tool will be developed to teach the impact of these imaging parameters on image quality, QA and patient dose. CT images were analysed using the software RadWorks 5.1. Soft tissue and bone densities were measured for the liver, kidney, retroperitoneal space, medullary bone and cortical bone. Image noise and resolution were measured on the CatphanÒ spatial and contrast resolution images. Resulting figures were recorded and then plotted on graphs. Images with a B40 s standard reconstruction kernel are considered ‘truth’ and were used to determine signal loss with kernel and parameter changes. The results enable visualisation of the ‘sweet spot’ of optimal parameter selection when considering spatial resolution, contrast resolution or both in tandem. Image measurements will also enable the teaching tool to demonstrate to the student in a hands on fashion the background to advanced CT concepts such as Dual Energy and Iterative Reconstruction. References:

S27 ABCA1, which it requires for function. Real-Time PCR showed that there was an increase in expression of ABCA1 by high concentrations of glucose in both cell lines. This study found that cholesterol transporter function and expression were increased in a hyperglycemic setting, which may account for the increased expression of ABCA1 in adipose derived M1 macrophages. Increased cellular cholesterol efflux via ABCA1 in metabolically activated cells may contribute to increased circulating cholesterol levels in obesity. Reference: 1. Kratz M, Coats B, Hisert K, Hagman D, Mutskov V, Peris E et al. Metabolic Dysfunction Drives a Mechanistically Distinct Proinflammatory Phenotype in Adipose Tissue Macrophages. Cell Metabolism. 2014;20(4):614–625. Presenting Author: Ms Katie Hughes Supervisor: Dr Fiona McGillicuddy

1. Kalender WA. Computed tomography: Fundamentals, system technology, image quality, applications. 3rd ed. Germany: Publicis MCD Verlag, Germany; 2011 Jul 1. ISBN: 9783895783173. 2. Seeram E. Computed tomography: Physical principles, clinical applications, and quality control. 2nd ed. Philadelphia: Saunders (W.B.) Co; 2001 Jan 15. ISBN: 9780721681733.

61. DEVELOPMENT OF A TOOLKIT TO SUPPORT PHYSICIAN DECISION MAKING ABOUT SAFE DRIVING IN SENIORS WITH DIABETES PHASE I: SYSTEMATIC SEARCH AND REVIEW

Presenting Author: Ms Rachel Healy Supervisor: Dr John Stowe

Corcoran N1, Regalado S2, Maxwell H3,4, Dubois S2,3,4, Stinchcombe A4, Gibbons C3,4, Migay M4, Weaver B2,3,4, Be´dard M2,3,4

60. TO INVESTIGATE THE EFFECTS OF METABOLIC STRESSORS SUCH AS INSULIN AND LIPIDS ON CHOLESTEROL EFFLUX CAPACITY Hughes K1, O’Reilly M1,2, McGillicuddy F2 1

Diabetes Complications Research Centre, UCD Conway Institute, UCD School of Medicine, University College Dublin, Belfield, Dublin 4. Nutrigenomics Research Group, UCD Conway Institute

2

Expression of the cholesterol transporter ABCA1 in adipose derived M1 macrophages was found to be increased, while its expression in cystic fibrosis M1 macrophages was reduced [1]. M1 pro-inflammatory macrophages found in adipose tissue in obese people have a profoundly different molecular signature to classical M1-macrophages from cystic fibrosis lungs, demonstrating remarkable heterogeneity dependent in an in vivo environment. The aim of the study was to investigate the effects of metabolic stressors on cholesterol efflux from macrophages and adipocytes. Cholesterol efflux was measured in J774.2 macrophage and 3T3L1 adipocyte cell lines which were labeled with 3H cholesterol (1 lCi/ml) for 24 h then co-treated ± cAMP (0.3 mM) ± metabolic stressors, glucose (4 mM, 25 mM), insulin (1 nM), palmitic acid (1 lM, 5 lM) for 18 h. Cells were incubated with serum (2.5%), MEM and APOA1 (25 lg/ml) for 4 h and percentage 3H cholesterol efflux was determined by liquid scintillation counting. Expression of cholesterol transporters, ABCA1 and ABCG1, was measured by western blot and real-time PCR. ABCA1 dependent cholesterol efflux was increased in both macrophages and adipocytes after treatment by glucose. Efflux assays suggested an increase in transporter protein expression was to be expected in adipocytes following insulin treatment, but this was not seen in western blots. Palmitic acid did not increase transporter expression, but was thought to limit the supply of ATP available to

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Northern Ontario School of Medicine, Thunder Bay, ON, Canada. 3Centre for Applied Health Research, St. Joseph’s Care Group, Thunder Bay, ON, Canada. 4Centre for Research on Safe Driving, Lakehead University, Thunder Bay, ON, Canada

Older adults are at an increased risk of diabetes and diabetic complications which may impact their ability to safely drive a vehicle. The purpose of this study is to create a comprehensive toolkit for physicians to support decision making regarding fitness to drive in seniors with diabetes. Phase 1 aimed to conduct a gap analysis of the available literature and establish an evidence base for later toolkit development. A systematic search and review for primary research regarding diabetes and driving was conducted. Databases included Ovid Medline, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL. The search strategy: included a combination of subject headings and key terms related to diabetes and driving; was consistent across databases; and was peer-reviewed. International English language databases of grey literature and clinical trial registries were also searched. Results were then screened for inclusion criteria and critically appraised using the AGREE II, Downs and Black, and GRADE tools. The search yielded 20,299 results. 6315 results are estimated to pass through screening. The results indicate that there is significant research into the subject of diabetes and driving in seniors, and therefore a sufficient evidence base for development of a toolkit. The next step will be to translate the generated knowledge for physicians. It will also be necessary to analyze the content of the research papers for potential gaps in the literature. Ultimately, this evidence will be used to develop a physician-targeted toolkit supporting decision making on diabetes and safe driving. Acknowledgements: The author would like to acknowledge funding from the Northern Ontario Academic Medicine Association.

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S28 Presenting Author: Ms Niamh Corcoran Supervisor: Dr Michel Be´dard Co-Supervisor: Ms Hillary Maxwell

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39

63. SCREENING FOR MACROSOMIA IN DIABETIC PREGNANCY Sharkey L1, McDonnell B1, Russell N2, Mulcahy C3, McAuliffe F2, Higgins M2

62. IMPACT OF METABOLIC HEALTH IN OBESITY ON HIGH-DENSITY LIPOPROTEIN PARTICLE EFFLUX FUNCTION AND APOA1 COMPOSITION Thomas R1, Guo W2, O’Shea D3, McGillicuddy F1,2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4. 3Obesity and Endocrinology Group, St. Vincent’s University Hospital, Elm Park, Dublin 4 High density lipoprotein (HDL) particles protect against cardiovascular disease (CVD) by promoting efflux of cholesterol from peripheral tissues and transporting acquired lipid back to the liver for excretion [1, 2]. This study aimed to examine the relationship between metabolic health on the composition and function of HDL particles in the obese state. Small-to-large HDL particles were isolated from serum samples obtained from lean controls, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) individuals by fast protein liquid chromatography (FPLC). ApoA1 protein levels were determined in small, medium and large particles by western blot (n = 8 per group). The efflux capacity of HDL-containing FPLC fractions was determined by assessing 3H-cholesterol movement from pre-labelled J774 macrophages onto 30% (v/v) FPLC fraction in minimum essential media. ApoA1 concentration was significantly decreased in the largest HDL fraction of both MHO (-55.85 ± 13.01%, *p \ 0.05) and MUO (-68.82 ± 8.19%, **p \ 0.01) individuals compared to lean controls. ApoA1 in medium and small sized particles remained unchanged. Cholesterol efflux to larger HDL particles via ABCA1-independent pathways was reduced in MUO, but not MHO, compared to lean controls. A compensatory increase in ABCA1-dependent efflux to medium sized particles was observed in MUO, and to a lesser extent MHO, compared to lean controls. The ability of HDL particles to promote efflux via ABCA1-independent pathways is reduced in MUO coincident with reduced ApoA1 on larger HDL particles. That withstanding there was a compensatory increase in the ability of MUO-derived HDL to promote efflux via the ABCA1-dependent pathway, coupled with retention of ApoA1 on smaller HDL particles. References: 1. McGillicuddy FC, de la Llera-Moya M, Hinkle CC, Joshi MR, Chiquoine EH, Billheimer JT, et al. ‘‘Inflammation Impairs Reverse Cholesterol Transport In Vivo.’’ Circulation 119, no. 8 (2009): 1135–45. 2. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. ‘‘Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis.’’ The New England Journal of Medicine 364, no. 2 (2011): 127–35. Presenting Author: Mr Robbie Thomas Supervisor: Dr Fiona Mc Gillicuddy Co-Supervisor: Dr Weili Guo

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1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Obstetrics and Gynaecology, UCD School of Medicine, University College Dublin, Belfield, Dublin 4, National Maternity Hospital. 3Midwifery, Fetal Assessment Unit, National Maternity Hospital

Pre-gestational diabetes mellitus (PGDM) is associated with an increased risk of fetal macrosomia1. The purpose of the study was to assess whether third trimester biometric measurements could predict macrosomia in diabetic pregnancy. A total of 230 PGDM mothers (167 Type 1 Diabetes and 63 Type 2 Diabetes) underwent routine serial third trimester ultrasound examination (30, 33 and 36 weeks gestation). Standard biometry measurements included abdominal circumference (AC) allowing an estimation of fetal weight (EFW). Two additional measurements, the anterior abdominal wall thickness (AAW) and AAW:AC ratio were also assessed. Macrosomia was defined as birth weight greater than the 90th centile for gestation and gender. The measurements of AC, EFW and AAW were significantly higher in women delivering infants with macrosomia compared to non-macrosomic infants (p \ 0.01), whilst there was no difference with the AAW: AC ratio (p = 0.60). ROC curve analysis revealed AC as the best predictor of birth weight at 30, 33 and 36 weeks, followed by EFW and AAW. The poorest predictor of macrosomia was AAW:AC (see Table 1). The accuracy of AC, EFW and AAW in predicting macrosomia improved with increased gestational age. In conclusion, in women with PGDM pregnancies the measurement of AC was a better predictor of macrosomia than EFW. This would suggest that AC should be weighed more heavily in the formula used to derive EFW in women with a PGDM pregnancy. The measurements of AAW and AAW:AC were not as sensitive in prediction of macrosomia.

Table 1: ROC Curve Analysis (AUC) at different gestational ages for AC (abdominal circumference), EFW (estimated fetal weight), AAW (anterior abdominal wall thickness) and ratio (AAW:AC). Gestational age (Wks)

AC

EFW

AAW

RATIO

30

0.71

0.70

0.61

0.52

33

0.77

0.74

0.70

0.50

36

0.85

0.84

0.62

0.50

References: 1. Higgins M, Galvin D, McAuliffe F, Coffey M, Firth R, Daly S, et al. Pregnancy in women with Type 1 and Type 2 diabetes in Dublin. Ir J Med Sci. 2011 Jun; 180(2):469–73. Presenting Author: Mr Liam Sharkey Supervisor: Dr Mary Higgins Co-Supervisor: Dr No´irı´n Russell

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64. HALLUCINATION ASSOCIATED DISTRESS AS A PREDICTOR OF THE PERSISTENCE OF PSYCHOTIC LIKE EXPERIENCES FROM EARLY THROUGH TO MID-ADOLESCENCE

S29 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Child and Adolescent Psychiatry and Geary Institute, University College Dublin, Belfield, Dublin 4. 3Department of Child Psychiatry, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Lucena Clinic Rathgar, Geary Institute and University College Dublin, Belfield, Dublin 4

Fitzgerald C1, Healy C2, Kelleher H2, Clarke M2, Cannon M2 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland 2 Sub-clinical psychotic-like experiences (PLEs) are present in the population, particularly in the adolescent population. PLEs are fleeting experiences for most people, with the persistence of experiences having been associated with poorer psychiatric and functional outcomes. Currently, there is a dearth of research that identifies factors associated with persistence. This study aims to investigate if hallucination associated distress is associated with PLE persistence. Participants were selected from the longitudinal ‘‘Adolescent Brain Development’’ Study1. Participants who had previously reported PLEs and completed a measure of hallucination associated distress during phase 1 were selected. Hallucination associated distress at baseline was examined as a possible predictor of persisting and remitting experiences at follow-up. Fourteen participants reported PLEs at baseline ( xage = 11.71). At follow-up, Four reported persisting experiences and ten reported remitting experiences ( xage = 15.29). Participants were matched for age and gender (p [ 0.9 and p [ 0.9, respectively). Participants with persistent experiences at follow-up reported more distressing experiences at baseline (p = 0.49). ROC analysis revealed that an area under the curve of 0.85 could be accounted for by Hallucination Associated Distress (p = 0.048; 95% CI: 0.643–[0.99). This study provides longitudinal evidence suggesting that hallucination associated distress may differentiate persisting PLEs from transient experiences. Furthermore, the rate of persistence is congruent with current literature. High levels of hallucination associated distress are seen in the need for care population2. The identification of those who will persistently endorse PLEs over time may aid in the development and implementation of early intervention programs. Acknowledgements: The Authors would like to acknowledge funding from the Health Research Board of Ireland. References: 1. Kelleher I, Murtagh A, Molloy C, Roddy S, Clarke MC, Harley M, Cannon M. Identification and characterization of prodromal risk syndromes in young adolescents in the community: a population-based clinical interview study. Schizophrenia bulletin. 2012 Mar 1;38(2):239–46. 2. Johns, L. C., Kompus, K., Connell, M., Humpston, C., Lincoln, T. M., Longden, E., & Fernyhough, C. (2014). Auditory verbal hallucinations in persons with and without a need for care. Schizophrenia bulletin,40(Suppl 4), S255-S264. Presenting Author: Mr Ciaran Fitzgerald Supervisor: Dr Mary Cannon Co-Supervisor: Dr Mary Clarke

65. ADHD: IS THERE AN APP FOR THAT?

There is increasing focus on the usage of mobile software applications (Apps) across a wide range of health conditions. Despite showing particular promise and existing usage [notably for both monitoring1 and self-management2], there is little published research on Apps for Attention Deficit Hyperactivity Disorder (ADHD). We therefore sought to evaluate existing Apps developed for ADHD and identify current usage patterns. The Google App store was searched using the keyword ADHD and relevant apps were evaluated. The three most active online discussion forums for ADHD were identified and systemically searched for posts relating to the usage of Apps. Thirty-four Apps were identified and these were each compared based on review ratings, usage level, functionality and cost. The ten most frequently discussed Apps on the forums were separately identified and evaluated. The majority of ADHD specific apps currently available have poor user reviews and/or low usage levels. Despite this, discussions on online forums suggest extensive usage by users of popular non ADHD specific apps to assist in managing the condition, particularly for productivity, time and task management. There appears to be a gap for the development of an ADHD specific App incorporating the functionality of the most successful existing apps that are in use. As a highly cost effective intervention, clinicians should consider whether it may be appropriate to recommend the usage of certain Apps. Though there is not yet an evidence base, individuals report significant benefits in their usage and the functionality of the most popular Apps mirrors that of existing recommended ‘pen and paper’ interventions already in use. References: 1. Simons L, Valentine AZ, Falconer CJ, Groom M, Daley D, Craven MP, et al. Developing mHealth Remote Monitoring Technology for Attention Deficit Hyperactivity Disorder: A Qualitative Study Eliciting User Priorities and Needs. JMIR Mhealth Uhealth [Internet]. 2016 Mar 23; 4(1):e31. Available from: http://mhealth.jmir.org/2016/1/e31 2. Kumaragama K, Dasanayake P. IOS Applications (Apps) For Attention Deficit Hyperactivity Disorder (ADHD/ADD): A Preliminary Investigation From Australia. Journal Mobile Technology in Medicine [Internet]. July 2015; 4:2:33–39. Available from: http://www.journalmtm.com/2015/ios-applications-appsfor-attention-deficit-hyperactivity-disorder-adhdadd-a-preliminaryinvestigation-from-australia/ Presenting Author: Mr David Hogan Supervisor: Prof Fiona McNicholas Co-Supervisor: Dr Bla´naid Gavin

66. UTILISING DETAILED PHENOTYPING TO INTERPRET VARIANTS IN PATIENTS WITH RARE OVERGROWTH SYNDROMES Agbahovbe R1,2,3, Cohen ASA2,3, Gibson WT2,3 1

1

2

Hogan D , Gavin B , McNicholas F

3

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2BC Children’s Hospital Research, Vancouver, BC,

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S30 Canada. 3Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Overgrowth syndromes are characterised by excessive growth, macrocephaly and other congenital features. They usually occur sporadically, thus family studies are not informative. With nextgeneration sequencing technologies, we can now examine all of an individual’s genes at once and in a cost-effective manner, using whole-exome sequencing (WES) 1. However, every individual has hundreds of unique variants in their exome, most of which are benign and reflect normal variation, making results difficult to interpret. The overall success rate for WES in identifying new causes of disease is only 25% 2. To address this, we utilised detailed phenotyping of patients with undiagnosed overgrowth to help us interpret the variants identified via WES, and prioritise those that may cause disease. We performed WES in the 12 patients that showed the most severe clinical presentation. As expected, for most patients there was no obvious causative variant. We then thoroughly examined the patients’ clinical records to identify unique characteristics that may direct us to novel candidate genes. After further mining of the WES data, we prioritised 2–4 possible disease causing variants per patient, based on the known biological function of the gene and likelihood of affecting the protein’s function. These variants were validated in the proband using Sanger Sequencing, and subsequently in the parents to determine if the variant was sporadic in origin. Of the five patients that we have analysed so far, the most promising candidate is a rare de novo variant in gene X, which may well represent a novel overgrowth gene. Acknowledgements: The author would like to acknowledge funding from the Canadian Institute of Health Research and The Dean’s SSRA 2016 International Scholarship. References: 1. Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. Journal of Human Genetics. 2013;59(1):5–15. 2. Yang Y, Muzny D, Reid J, Bainbridge M, Willis A, Ward P et al. Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders. New England Journal of Medicine. 2013;369(16):1502–1511. Presenting Author: Ruky Agbahovbe Supervisor: Dr William T. Gibson Co-Supervisor: Ms Ana SA Cohen

67. DETERMINING ASSOCIATIONS BETWEEN DIETARY INTAKE AND INTESTINAL PERMEABILITY (IP) IN HEALTHY FIRSTDEGREE RELATIVES OF CROHN’S DISEASE PATIENTS Howarth N1, Turpin W2, Smith M3 and Croitoru K1,2, On behalf of the GEM Project Research Consortium 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada. 3Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Intestinal permeability (IP) is associated with several diseases. In a previous study, IP was found to be associated with age and smoking [1]. The aim of this study was to investigate whether specific dietary nutrients are associated with IP in healthy first-degree relatives (FDRs) of Crohn’s Disease (CD) patients. Food frequency questionnaires (FFQs) were used to quantify consumption of 45 nutrients over a 1-year period. The ratio of fractional excretion of lactulose: mannitol (LacMan) was used to measure IP [1]. Subjects were excluded if FFQ plausibility score was [4. Association analysis was performed within R software v3.3.0 using a linear regression model corrected for age, smoking, caloric intake, sex, and BMI/centile. The cohort comprised 958 subjects aged 6–35 (515 F, 443 M). Statistical significance was defined as q B 0.0025. No associations were found between the nutrients analysed and IP. To increase study power, 20 of the nutrients were selected based on literature review of plausible influence on IP; however, no associations were significant. Separate analysis of children \18 years and adults failed to show associations. FFQ data provides crude intake estimates, while the LacMan ratio renders an objective snapshot of IP. Comparing LacMan ratio to nutrient intake from a 24-h dietary recall may be more useful for future analysis. Healthy individuals without risk factors should also be assessed, as predisposition of FDRs to develop CD may affect nutrient metabolism, thereby altering IP. The results of this study indicate that individual constituents of dietary intake are not associated with changes in IP. Reference: Kevans, David. Determinants of Intestinal Permeability in Healthy First-degree Relatives of Individuals with Crohn’s Disease. Inflammatory Bowel Diseases. 2015;21(7):1673. Presenting Author: Ms Nisha Howarth Supervisor: Dr Kenneth Croitoru, MD

68. REGULATION OF DNA METHYLATION BY HYPOXIA AND IMPACT ON MIGRATION IN TRIPLE NEGATIVE BREAST CANCER Creagh-Flynn J1, Greville G2, Rudd PM2, McCann A1, Saldova R2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Dublin 4

Twenty percent of all breast cancer cases are triple negative1. Triple negative breast cancer (TNBC) is an aggressive disease with higher rates of metastases than non-TNBC1. Breast cancers that are belonging to this group are harder to treat due to the lack of receptors for which targeted therapies have been developed. TNBC are known to have poorer survival rates than non-TNBC, due to treatment options being limited to chemotherapy, radiotherapy, and surgery, and the fact that they are more prone to be aggressive1. Hypoxia is well known to promote tumour progression in cancer. There has been increasing evidence that hypoxia and epigenetics interplay with each other2. Our goal was to determine effect of hypoxia on DNA methylation and migration of TNBC cells. To assess the methylation induced by the exposure, flow cytometry was employed. Cell migration in normoxic and differential hypoxic conditions was also examined. Results have shown the same pattern across differential hypoxic conditions and among all cell lines where an initial hypermethylation

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 was observed followed by a hypomethylation. Migration was found to be promoted by the hypoxic conditions. Interestingly, the results showed that the MDA-MB-231 cell line has approximately twice as strong of a promotion of migration in response to hypoxia as the MDA-MB 436 cell line. Acknowledgements: Authors would like to acknowledge funding from University College Dublin and from the Science foundation Ireland Starting Investigator Research grant (SFI SIRG) under grant number 13/SIRG/2164. References: 1. Mirzania, M. Approach to the Triple Negative Breast Cancer in New Drugs Area. Int J Hematol Oncol Stem Cell Res. 2016 Apr 1; 10(2): 115–119. 2. Jenny A. Watson, Chris J. Watson, Amanda McCann and John Baugh. Epigenetics, the epicenter of the hypoxic response Epigenetics. 2010 5:4, 293–296 Presenting Author: Mr Jack Creagh-Flynn Supervisor: Dr Radka Fahey Mr Gordon Greville Co-supervisor: Dr Amanda McCann

69. TOO YOUNG TO GET CANCER?’’ UNDERSTANDING THE CHALLENGE OF ACHIEVING A TIMELY DIAGNOSIS FOR TEENAGERS AND YOUNG ADULTS (TYA) IN THE SOUTH WEST OF ENGLAND Nechowska A1, Pring H2, Cargill J2, Cox R3, Wint A4, Stevens M2, Dommett R3 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2TYA Cancer Service South West, Bristol Haematology and Oncology Centre. 3Department of Paediatric Haematology, Oncology and Bone Marrow Transplant Bristol Royal Hospital for Children. 4Macmillan Cancer Lead, South Gloucestershire

The journey for many teenagers and young adults (TYA) diagnosed with cancer is unsatisfactory, or perceived to be, by patients and their families. As part of the Accelerate, Coordinate, Evaluate Programme (NHS England, Cancer Research UK, Macmillan), the project was undertaken as an analysis of cancer diagnosis in TYA across the South West. Retrospective data was collected from patients referred to the TYA Multidisciplinary Advisory Team in the Principal Treatment Centre. With permission from patients, General Practitioners and Caldicott guardians, primary and secondary records were reviewed by the team and details of all healthcare contacts from presentation to first cancer treatment noted. These were translated into pathway maps, which were reviewed by a clinical panel to identify potential missed opportunities for earlier diagnosis, highlight good practice and define key events in the diagnostic pathway [1]. 104 TYA were recruited (53 male, 51 female) and data was accessed from 8 NHS Trusts. Lymphomas represent the largest diagnostic group (27%). The longest pathways were seen in ovarian cancers (~ x = 109). Approximately 39% of patients were diagnosed via Two Week Wait referral and 27% via Emergency presentation (16% classified as potentially avoidable and 24% unavoidable). This is the first study to interrogate whole pathways and analysis has exposed practice in both primary and secondary care relevant to TYA. Our findings will help to inform the design of interventions and

S31 a better understanding of the pre-diagnostic use of primary healthcare by patients and of referral pathways will help to identify ways to minimise potential delays. Reference: Weller D, Vedsted P, Rubin G, Walter F, Emery J, Scott S et al. The Aarhus statement: improving design and reporting of studies on early cancer diagnosis. Br J Cancer. 2012;106(7):1262–1267. Presenting Author: Ms Aoife Nechowska Supervisor: Dr Rachel Dommett Co-Supervisor: Ms Hannah Pring

70. PREDICTION OF COGNITIVE AND PHYSICAL DISABILITY IN EARLY RELAPSING REMITTING MULTIPLE SCLEROSIS Saba L1, Said M2, Ayoubi N2, Khoury SJ2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon

Prevention of long-term disability is the goal of therapeutic intervention in relapsing remitting multiple sclerosis (RRMS). The Bayesian Risk Estimate for MS at Onset (BREMSO)1 score was designed to give an individual risk score to predict disease evolution, however, a tool that anticipates early physical and cognitive deterioration is lacking. The aim of this study is to investigate whether BREMSO correlates with physical as well as cognitive dysfunction during the early disease course. We studied 100 patients with RRMS or clinically isolated syndrome who were enrolled in the Nehme and Therese Tohme MS Center AMIR study from January 2012, with at least 3 years of follow-up and disease duration of less than 6 years. BREMSO was calculated for all participants at disease onset. At each visit, cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), and physical disability using the Multiple Sclerosis Severity Score (MSSS), 25 Foot Walk Test (25FWT) and 9 Hole Peg Test (9HPT). The mean (SD) age was 28.1 (11.19) years, Expanded Disability Status Scale was 1.28 (1.03), and disease duration was 2.4 (1.78) years. In multivariate linear regression analyses, BREMSO correlated negatively with SDMT, controlling for age and education, at visit 1 (b = -0.33 p = 0.019), visit 2 (b = -0.34 p = 0.017), and visit 3 (b = -0.34 p = 0.014). BREMSO correlated positively with MSSS at visit 1 (r = 0.38, p = 0.006), visit 2 (r = 0.47, p \ 0.0001), and visit 3 (r = 0.42, p = 0.002), but did not correlate with 25FWT and 9HPT. Thus, the BREMSO score predicted physical and cognitive disability in early multiple sclerosis. Acknowledgements: The author would like to acknowledge funding from the Dean’s SSRA 2016 International Summer Research Scholarship, UCD. Reference: 1. Bergamaschi R, Montomoli C, Mallucci G, Lugaresi A, Izquierdo G, Grand’Maison F, et al. BREMSO: a simple score to predict early the natural course of multiple sclerosis. Eur J Neurol. 2015;22(6):981–9. Presenting Author: Ms. Leslie Saba Supervisor: Dr. Samia J. Khoury Co-Supervisor: Dr. Marianne Said

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71. BARRIERS TO THE IMPLEMENTATION OF ONLINE LEARNING IN MEDICAL EDUCATION: ARE THERE SOLUTIONS?

Table 1: continued

Marie Dromey1, Diane O’Doherty2, Ailish Hannigan2, Jason Last1, Deirdre McGrath2

Solutions Collaboration (n = 5)

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Graduate Entry Medical School, University of Limerick, Ireland

There has been a recent shift in medical education from face-to-face teaching to include online, distance or electronic learning. This integrative review of the literature explores and identify the known barriers and solutions that face educators when developing and implementing online learning programs for medical students. Methodology was developed through an inter-university steering group. The database search included Science Direct, Scopus, BioMedical, PubMed, Medline (EBSCO and Ovid), ERIC, LISA, EBSCO, Google Scholar, Proquest A&I, Proquest UK&Ireland, UL Institutional Repository (IR), UCDIR and the All Aboard Report. Keywords included commonly used alternatives for online learning, medical educators, development, barriers, solutions and digital literacy. The search was carried out independently by two reviewers and yielded 3101 abstracts. Eleven full-text papers met the inclusion criteria. Data appraisal was performed using the Critical Appraisal Skills Programme (CASP) Qualitative Research Checklist [1] and NHMRC Appraisal Evidence Matrix [2]. Data extraction was completed on 8 papers of high methodological quality using the Cochrane Data Extraction Form and a modified extraction tool informed by systematic review. Results (Table 1) show barriers facing educators in providing and maintaining quality online content include their own digital skills, time commitments and technical issues. Solutions include collaboration and communication, the existence of an institutional strategy regarding online learning programs and developing good teaching skills/style. The literature has already demonstrated the need for institutional strategy, faculty incentivisation and a range of other solutions. Noting the points regarding faculty skills, our next step is a national exploration of medical educator digital literacy. Table 1: Preliminary findings (n = number of times the theme is referred to in the literature) Developing online learning Barriers Poor Digital Skills Held by Educator (n = 5) Time Management/ Existing Commitment (n = 5)

Implementing online learning Adapting to Blended Roles and New Ways of Doing Things (n = 3) Restrictive Design of Elearning Materials (n = 4)

Communication Challenges Lack of Institutional (n = 3) Support/ Communication (n = 4) Technical Issues (n = 4) Poor Infrastructure (n = 3)

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Developing online learning

Faculty Reward and Acknowledgment for Efforts (n = 1) Institutional Strategies (n = 6) Accessibility of ELearning Materials (n = 2) Technology (n = 1)

Implementing online learning Cost Effectiveness (n = 1) Developing Teaching Skills/ Style (n = 3) Building Collaborative Relationships Between Faculty and Students (n = 3) Good Time Management (n = 3) Inter-group Collaboration (n = 2)

Educator Skills/Openness Flexibility (n = 5) (n = 4) Pedagogical Underpinning Existing Skills and (n = 6) Experience (n = 2) New Approaches (n = 2) Positive Attitudes and Expectations (5)

References: 1. Critical Appraisal Skills Programme (CASP). CASP Qualitative Research Checklist 31.05.13 Oxford: CASP UK; 2014. Available From: http://media.wix.com/ugd/dded87_29c5b002d99342f788c 6ac670e49f274.pdf. 2. National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Australia: NHMRC; Dec, 2009. Presenting Author: Ms Marie Dromey Supervisor: Prof Jason Last

72. POSTNATAL BLOOD TRANSFUSION IN A TERTIARY UNIT Kelly S1, Higgins MF2, McMorrow R3,4, Culliton M5, Carew B5, O’Donovan B5, Fitzgerald J5 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Obstetrics and Gynaecology, School of Medicine, University College Dublin. 3Department of Anaesthesia, National Maternity Hospital, Dublin 2. 4Department of Pathology and Laboratory Medicine, National Maternity Hospital. 5 Haemovigilance Department, National Maternity Hospital, Dublin 2

Fears over shortages in the national blood supply have led to calls for greater prudence in the conservation of the available stock. The circumstances in which a physician decides to transfuse have been shown to vary greatly dependent on both physician and patient factors. Obstetrics is unique in that the time period where the patient will be at increased risk of anaemia requiring red cell transfusion (RCC)

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 can be predicted more easily. This study’s aim was to review transfusion practices correlated to clinical outcomes over a 1-year period. Retrospective review of transfusions administered to postpartum women delivering in the National Maternity Hospital was performed. Obstetric women who received a red cell transfusion in 2015 were identified. Demographics, blood transfusion events and blood tests were retrieved and recorded with transfusion location, prescribing physician, reason for transfusion, record of consent and record of iron intake. 166 women received a RCC transfusion in 2015; results are presented on 113 women. Anaemia was the most common indication (77.8%), 25 women were transfused with active bleeding. Consultants had a lower Haemoglobin transfusion threshold than trainee grades (Consultant median Hb 6.6 g/dL, residents 7.0 g/dL; p = 0.185). In the absence of active bleeding, \11% of women had their haemoglobin rechecked after the first unit of blood transfusion. Half of those with antenatal anaemia had documented iron therapy. Several factors have been highlighted that may reduce the number of future RCC transfusions, decreasing demand on blood supply and reducing risk to patients. Acknowledgements: The author would like to acknowledge the support from the National Maternity Hospital, Holles Street. Reference: Royal College of Obstetricians and Gynaecologists, Blood Transfusion in Obstetrics. Green Top Guideline. 2015. Presenting Author: Mr Shane Kelly Supervisor: Dr Joan Fitzgerald Co-Supervisor: Dr Mary Higgins

73. INVESTIGATION OF MAIT CELL FREQUENCY IN ADULT OBESITY Jones M1,2, Tobin L1,2, Hogan A1,2, O’Shea D1,2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD School of Medicine Obesity and Immunology Research Group, St. Vincent’s University Hospital, Elm Park, Dublin 4

Obesity is a multi-faceted disease that is associated with chronic, lowgrade inflammation constitutively activated in patients. In Ireland, two in three adults and one in three children are currently overweight or obese, and in the future, the WHO predicts that the obesity crisis will worsen, with Ireland at the forefront as the most obese country in the EU. Mucosal associated invariant T (MAIT) cells are innate MHC-unrestricted cells that are capable of producing cytokines to regulate the immune response. For this reason, they are a subject of interest in the study of obesity and the chronic low-grade inflammation with which it is associated. Furthermore, obesity is also associated with the state of being metabolically unhealthy, defined by fulfilling three out of five of the criteria, including BMI greater than 30, raised blood pressure, impaired fasting glucose, raised triglycerides, and reduced HDL cholesterol. The aim of this study was to determine whether an association exists between any of these five criteria and MAIT cell frequencies and/or CD8+ cell frequencies. Blood samples and clinical data were collected from obese patients at St. Colmcille’s hospital. Immune cell frequencies were gathered by isolating the immune cells, surface staining for specific markers and then performing flow cytometry. The data was pooled

S33 together, and correlation studies were performed with Graph Pad Prism 7 software. Although MAIT cell frequencies are reduced in adult obesity, ultimately, no association between immune cell frequencies and clinical data was discovered. Presenting Author: Mr Michael Jones Supervisor: Prof Donal O’Shea Co-Supervisor: Dr Andy Hogan

74. THE DEVELOPMENT OF A DATABASE TO FACILITATE INVESTIGATION OF WHETHER THE DEGREE OF BREAST ARTERIAL CALCIFICATION ON SCREENING MAMMOGRAPHY CAN PREDICT FINDINGS ON CT CORONARY ANGIOGRAPHY AND THUS CORONARY ARTERY DISEASE IN THE BREAST CHECK SCREENING COHORT Scanlon E1, Kelly B2, Simpson D2, Dodd J2, Mc Dermott E3, McNally S2,4, O’Doherty A2,4, Prichard R3 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Radiology, St Vincent’s University Hospital, Elm Park, Dublin 4. 3Department of Breast, Endocrine and General Surgery St Vincent’s University Hospital, Elm Park, Dublin 4. 4Breast Check, St Vincent’s Healthcare Group, Elm Park, Dublin 4 Breast arterial calcifications (BAC) are a type of medial arterial calcification observed at mammography. They are thought to be associated with an increased risk of coronary artery disease (CAD) and thus cardiovascular disease. We aimed to investigate the association of BAC with coronary artery calcification and cardiovascular disease within the Breast Check screening cohort. Data was found by examining records of women aged 50–64 who underwent CT coronary angiography between 2014 and 2015 and cross-referencing with Breast Check data. A cohort of patients who had both examinations was identified. BAC was scored as absent, mild, moderate or severe by specialist breast radiologists (1). CT coronary angiograms were scored according to the CAD-RADs system incorporating findings found to be significant in the CONFIRM trial (2). We also obtained Agaston scores for a subset of patients. History of chronic kidney disease, diabetes, hypertension, hypercholesterolaemia and smoking were noted so that they can be controlled for in future analysis. We have identified 120 Breast Check patients who have had both mammography and CT Coronary Angiograms. We have developed a database of BAC and CTCA scores and also through chart and medical record review identified patients’ other cardiac risk factors. This database will be used to identify whether BAC can predict CAD in this cohort. In the future this information could be used to communicate cardiac risk to patients’ primary care physicians through the medium of the mammogram report to identify potentially undiagnosed CAD. References: 1. Loberant, N., Salamon, V., Carmi, N., Chernihovsky, A. Prevalence and Degree of Breast Arterial Calcifications on Mammography: A Cross-sectional Analysis. Journal of Clinical Imaging Science 2013; 3(1).

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S34 2. Cury, R. C. Abbara, S. Achenbach, S. Agatston, A. Berman, D. S. Budoff et al. CAD-RADS(TM) Coronary Artery Disease— Reporting and Data System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed by the American College of Cardiology. Journal of Cardiovascular Computed Tomography 2016; 10(4): Presenting Author: Ms Emer Scanlon Supervisor: Dr Brendan Kelly Co-Supervisor: Mr Enda McDermott

75. AN ANALYSIS OF THE USE OF THE MODIFIED IOTN FOR PATIENT REFERRAL TO TWO HSE ORTHODONTIC UNITS Murray D2,3, Mc Sherry K1,3

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Presenting Author: Mr Kenneth McSherry Supervisor: Dr Dylan Murray Co-Supervisor: Dr Patrick McSherry

76. 3D PRINTING OF RENAL MALIGNANCIES AND THEIR ARTERIAL SUPPLY TO IMPROVE OUTCOMES IN LAPAROSCOPIC PARTIAL NEPHRECTOMY: A PROOF OF CONCEPT PRELIMINARY STUDY Casey C1, Kelly B2, Simpson D2, O’Cearbhaill E3, McCann J2, Mulvin D4 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Radiology, St. Vincent’s University Hospital, Elm Park, Dublin 4. 3UCD College of Engineering, University College Dublin, Belfield, Dublin 4. 4Department of Urology, St. Vincent’s University Hospital, Elm Park, Dublin 4

1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Mater Misericordiae University Hospital, Eccles Street, Dublin 7. 3Craniofacial Research Group, Mater Misericordiae University Hospital, Eccles Street, Dublin 7 The Index of Orthodontic Treatment Need (IOTN) is an objective method of scoring HSE orthodontic patients in accordance with their level of treatment need [1]. Only those deemed to be of sufficiently high need, i.e. those in Grade 5 and 4 of the modified HSE criteria qualify for treatment [2]. This study was undertaken to determine the IOTN breakdown, from March 2013 to December 2015, of patients presenting for treatment from two regional orthodontic units in Navan and Dundalk. The aims of this research was to (a) provide a detailed analysis of the case profile of presenting patients (b) confirm the eligibility of presenting patients and (c) measure the success of referring dentists in identifying the correct IOTN classification, and make recommendations based on these findings. Records of 1690 patients were assessed. 1152 (67.91%) were deemed eligible for treatment after screening by the orthodontist, and 538 (32.09%) deemed not eligible. Patients were predominantly female (52.60%), with a mean age of 11.9 years. The majority (44.03%) were classified as Grade 5A, followed by 4C (18.22%), 4D (10.99%), and 4F (8.11%). Grade 4B had the lowest diagnosis success (27.27%), followed by 4C at 48.56% and 4F at 61.29%. These results demonstrate that re-calibration of dentists is needed to make maximum use of available resources, in particular, in the eligibility requirements for categories 4D and 5i. 4C, 4B, 4 M and 5 M categories require added emphasis to correctly distinguish between the IOTN grades and ensure patients are correctly categorised. References: 1. Scott C. Understanding the IOTN. Journal of the Irish Dental Association. 2015; vol 61(5):236–9. 2. Health Service Executive (HSE) Orthodontic Review Group. Orthodontic Review Group Report 2007; [cited 2016 Aug 2]. Available from: http://lenus.ie/hse/bitstream/10147/44938/1/664 7.pdf.

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The arterial supply of the kidneys has variable anatomy potentially proving challenging when preforming laparoscopic partial nephrectomy. The technique of 3D printing renal malignancies has been proven in concept (1) and the potential for their use as a preoperative tool has also been raised (2). This study aimed to investigate whether specific demonstration of the arterial supply has the potential to improve outcomes in laparoscopic partial nephrectomy by providing the surgeon with a physical model prior to the operation. Full IRB ethical approval was obtained. Patients were identified from the urology weekly radiology conference. The usual CT angiograms that occur as preoperative scans were used to isolate the designated kidney and its arterial supply. Confidential alpha-numerical coding was used to identify each kidney model. Using powder and filament based 3D printers a number of models were printed. A digital 3D model of one patient’s kidney was developed. We then printed the model using a number of different techniques, including manual colourisation allowing specific vessels to be highlighted on the model. The final model was then reviewed for anatomical accuracy by a specialist radiologist and for suitability for surgical planning by the department of Urology. We achieved a successful 3D print, demonstrating the potential use of similar models in the future to aid in preoperative planning. Models can be produced with minimal patient interference, have suitable anatomical accuracy and have the potential to improve surgical outcomes in the future. Acknowledgements: The author would like to acknowledgement the help provided by UCD College of Engineering and UCD School of Medicine, especially Prof. James Jones. References: 1. Zhang, Yi, et al. ‘‘Evaluation of three-dimensional printing for laparoscopic partial nephrectomy of renal tumors: a preliminary report.’’ World journal of urology (2015): 1–5. 2. Silberstein, Jonathan L., et al. ‘‘Physical models of renal malignancies using standard cross-sectional imaging and 3-dimensional printers: a pilot study.’’ Urology 84.2 (2014): 268–273.

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Presenting Author: Mr Cillian Casey Supervisor: Dr Brendan Kelly Co-Supervisor: Mr David Mulvin

77. HOW STRONG IS THE EVIDENCE OF EFFICACY FOR FAMILY-BASED TREATMENT (FBT) IN THE CONTEXT OF EATING DISORDERS: A CRITICAL REVIEW OF THE LITERATURE EXAMINING FIDELITY TO FBT APPROACH AND ITS APPLICATION IN A CLINICAL SETTING 1

1

1,2,3

Zambre AS , O’Hara L , McNicholas F

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Child Psychiatry, Our Lady’s Hospital for Sick Children, Crumlin, 3Lucena Clinic Rathgar, Dublin 6

Family-Based Treatment (FBT) is considered first line treatment for children/adolescents with Anorexia Nervosa (AN)1. Key components include seeing the family as a resource, regular patient weighing, initial focus on parental symptom management facilitating eating and weight gain, prior to considering other adolescent/family difficulties2. Despite the existence of evidenced based treatments (EBT), clinicians frequently diverge from the evidenced model, especially as treatment moves from research to community settings. This study aimed to review literature where FBT is offered as treatment for AN and examine whether fidelity to the manualised approach can be ascertained. PubMed, Web of Science, PsycINFO and PsycARTICLES were searched and 18 studies met inclusion criteria. A fidelity checklist containing the fundamental tenets guiding FBT1 was developed to rate FBT fidelity. Studies were grouped into 50, 75 and 100% fidelity. FBT was deemed successful in all studies examined, with weight restoration, return of menses and psychological symptom improvement. Although 16 studies referenced the treatment manual, no study provided sufficient information to achieve 100% fidelity, the majority (16) having scores below \50%. Fidelity ratings did not correlate with more positive outcomes. Parents showed increased self-efficacy during treatment which correlated with positive outcomes. Finding the essential ingredients of EBT is key, to ensure that community delivery maintains these features. Despite frequent use of FBT, and associated positive outcomes, few studies reported adherence to the EBT, limiting the estimation of treatment fidelity. Routine use of a fidelity checklist would improve confidence in study results and help in ascertaining essential model ingredients. References: 1. Agras WS, Lock J, Brandt H, Bryson SW, Dodge E, Halmi KA, et al. Comparison of 2 family therapies for adolescent anorexia nervosa: A randomized parallel trial. JAMA Psychiatry. 2014;71(11):1279–86. 2. Lock J, Le Grange D. Treatment manual for anorexia nervosa: a family-based approach. New York: The Guilford Press; 2013. Presenting Author: Mr Afeeq Shaszwan Zambre Supervisor: Prof Fiona McNicholas Co-supervisor: Dr Lesley O’Hara

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78. BANDS OF FONTANA IN PERIPHERAL NERVES ARE A CONSEQUENCE OF THE INPHASE SINUSOIDAL PATH OF AXONS: EVIDENCE FROM MICROSCOPIC ANALYSIS AND PHYSICAL NERVE MODELLING Tobin-O’Brien C1, Alvey L1, Pickering M1 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4

The exact cause of the bands of Fontana, a spiral banding visible on the surface of peripheral nerves, has eluded researchers to date. The discovery of axons’ sinusoidal paths along a nerve led to us investigating if this path, along with the curved 3D geometry of a nerve’s surface, could be responsible. To prove our hypothesis conclusively, that the bands are formed as an optical artefact of the sinusoidal axon paths only and not due to any other related factor, we decided to create a model with only the axonal paths in place and demonstrate band formation. Our model’s sinusoidal paths were made to accurately represent those in a rat’s sciatic nerve, done by extracting nerves, fixing and staining them with lipophilic DiO stain and viewing the axonal path under confocal microscopy. From this examination, a realistic model was formed by 3D-printing a cast in PLA and moulding it in black silicone. Under oblique illumination of our model, the spiral banding so typical of the bands of Fontana could be clearly seen. Illumination from the opposite side revealed the characteristic reversing of the bands seen with the bands of Fontana, confirming our hypothesis. As the bands are so closely aligned to axon path, this raises the possibility that axon path, and hence true axon length, can be deduced from simple oblique illumination of nerves. This has important implications for peripheral neuropathies with impaired conduction, such as Charcot Marie Tooth disease, where band pattern is known to be disrupted [1]. Acknowledgements: The author would like to acknowledge funding from the Wellcome Trust. References: 1. Power BJ, O’Reilly G, Murphy R, Murphy K, Pickering M, Jones J. Normal nerve striations are altered in the Trembler-J Mouse, a model of Charcot-Marie-Tooth disease. Muscle Nerve. 2015; 51:246–252 Presenting Author: Mr Cathal Tobin-O’Brien Supervisor: Dr Mark Pickering Co-Supervisor: Dr Tom Flanagan

79. THE EXTENT TO WHICH MUSIC HAS PENETRATED MEDICAL RESEARCH: A BIBLIOMETRIC REVIEW Campbell MA1, Alter DA2 1

Toronto Rehabilitation Institute, University Health Network, Toronto, Canada. 2UCD School of Medicine, University College Dublin, Belfield, Dublin 4

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S36 The growth of music in medical research in recent years has been extensive. This research has explored music processing, music therapy techniques and more. This project therefore set out to quantify the extent to which music has penetrated medical research. All biomedical publications relevant to music on GoPubMed from 1970 to 2015 were searched. 400 abstracts were chosen randomly by one researcher and manually searched by another. The inclusion criteria was adjusted until a bibliometric filter with [90% precision and recall was achieved. We measured the yearly number of music medicine publications and performed a time trends analysis of this growth. Time trends analysis was also performed for all GoPubMed publications, and publications relating to drug therapy, to compare growth rates. Finally, we investigated which journals music medicine publications appeared in over time, and how study methodologies have changed. Music medicine publications increased from 96 in 1970 to 734 in 2005 and 1595 in 2015: a 1560% increase 1970–2015 and a 117% increase 2005–2015. Music medicine research grew more rapidly since 1970 and 2005 than the growth of all research. While relative research interest is lower than drug therapy, music medicine research grew more rapidly since 1970 and 2005. While many music medicine publications appear in lower-impact journals, the proportion of publications in mid-impact journals has increased. Finally, music medicine research has shifted from pre-clinical to more clinical and randomized control trials. These findings imply that as a society we may be beginning to accept music more in medical research and application. Acknowledgements: The author would like to acknowledge Dr. David Alter and his research team at the Cardiac Rehab Centre at the Toronto Research Institute, UHN. Presenting Author: Ms Mackenzie Campbell Supervisor: Dr David Alter

80. THE ROLE OF FIBROCYTE DERIVED EXOSOMES IN THE DEVELOPMENT OF IDIOPATHIC PULMONARY FIBROSIS Harford J1, Cooke G1,2, Kane R1,2, Keane MP2,3 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2UCD Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4. 3Department of Respiratory Medicine, St. Vincent’s University Hospital, Elm Park, Dublin 4

Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease characterised by progressive interstitial fibrosis of unknown aetiology. Initial injury leads to aberrant activation of epithelial cells, creating a profibrotic environment with accumulation of fibroblasts and myofibroblasts. Potential sources of myofibroblasts include transitioned epithelial cells and fibrocytes(1). Circulating levels of fibrocytes in serum also correlate with disease severity and prognosis(2). The aim of this project was to extract and compare the exosomes from TGF-beta (b) 1 stimulated and unstimulated fibrocytes, and to investigate the effects of these exosomes on A549 epithelial cells. Exosomes were isolated, using ultracentrifugation, from the supernatant of fibrocytes cultured for 24 h with/without TGF-b1. These exosomes were quantified and characterised by western blotting for known exosome markers. A549 epithelial cells were treated with 10 lg/mL of exosomes for 48 h. A549 cell lysates were then

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 analysed for markers of epithelial-mesenchymal transition (EMT) by western blotting. We show that both sets of fibrocyte derived exosomes downregulated E-cadherin and ZO-1 in A549 cells, with concomitant upregulation of N-cadherin, indicative of early EMT. These changes suggest that fibrocyte exosomes have the potential to induce EMT in the lung parenchyma, and therefore suggests a role for fibrocyte exosome signalling in activating abnormal tissue repair and subsequent fibrosis. References: 1. Kage H, Borok Z. EMT and interstitial lung disease: a mysterious relationship. Current Opinion in Pulmonary Medicine. 2012;18(5):517–23. 2. Strieter RM, Keeley EC, Hughes MA, Burdick MD, Mehrad B. The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis. Journal of Leukocyte Biology. 2009;86(5):1111–8. Presenting Author: Mr John Harford Supervisor: Dr Gordon Cooke Co-supervisor: Dr Rosemary Kane

81. COMPARISON OF THE SEVERITY AND RELAPSE RATE OF PAEDIATRIC ULCERATIVE COLITIS BASED ON GENDER IN AN IRISH COHORT OF PATIENTS USING THE PUCAI SCORING SYSTEM Doherty E1, Hussey S2, Raftery T2, Carey A2, Hamzawi M2, Kiernan S2, O’Driscoll2, Broderick A2, Bourke B2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Gastroenterology, Hepatology and Nutrition Team, Our Lady’s Children’s Hospital, Crumlin, Dublin 12

Ulcerative colitis (UC) is graded using the PUCAI scoring system(1) to indicate the severity of the condition. Data from the DOCHAS project of Irish paediatric patients diagnosed with UC were used to compare similarities and differences of gender on patients presenting with non-severe (\65) and acute-severe phenotypes (C65) of UC. Data from the DOCHAS project were analysed using Chi squared analysis in SPSS comparing gender in both non-severe and acutesevere forms of UC in two age-related categories (B10 and [10 years). Data from 149 patients with a diagnosis of UC of which 70 (47%) were male and 79 (53%) female were categorized, with 111 non-severe and 38 acute-severe cases. The distribution of nonsevere cases was similar in males and females; 56 (50.5%) male and 55 (49.5%) female. However, 24 (63.2%) females were affected by the acute-severe form of UC compared to 14 (36.8%) males, although this trend was not statistically significant (P = 0.10). The distribution of the pre-menarchal (11) and postmenarchal (10) acute-severe cases indicates that menstruation was unlikely to be a contributing factor. The relapse rate for cases (excluding follow up data) was 33 (22%) of which 21 were female compared to 12 males. The results demonstrate that the acute-severe form of UC is overrepresented in older females regardless of their menarchial status. Although not statistically significant, the higher acute-severe presentation and relapse rate in females may be worthy of further investigation.

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Reference: 1. Levine A1, Griffiths A, Markowitz J, Wilson DC, Turner D, Russell RK, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011 Jun;17(6):1314–21. Presenting Author: Ms Elinor Doherty Supervisor: Dr Se´amus Hussey Co-supervisor: Ms Tara Raftery

82. VOLTAGE-DEPENDENT A-TYPE KV4.2 AND KV4.3 CHANNEL EXPRESSION IN HIRSCHSPRUNG’S DISEASE Parekh B1, O’Donnell AM2, Puri P1,2 1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12

Hirschsprung’s Disease (HSCR) is a relatively common congenital condition characterised by the absence of enteric ganglia in the distal colon, leading to impaired peristalsis and intestinal obstruction in the newborn1. A-type K+ channels (KV4.1-KV4.3) have been documented within murine colonic myocytes2. No data exists regarding A-type K+ channel expression in the ENS of the human colon. This study investigated the expression of KV4.2 and KV4.3 channels in normal human colon and in HSCR colon. KV4.2 and KV4.3 protein expression was investigated in pullthrough specimens from HSCR patients using the proximal-most ganglionic segment and distal-most aganglionic segment, and in healthy control specimens from patients who underwent colostomy closure for imperforate anus. Antibodies against KV4.2 and KV4.3 were used for immunofluorescence, followed by confocal microscopy to investigate their distribution. In order to quantify their expression, proteins were extracted from each region of the HSCR colon and western blot analysis was used to determine the concentration of each channel in the HSCR samples versus normal control colon samples. Expression of KV4.2 predominantly co-localised with ICCs in the circular muscle layer, neurons in the myenteric plexus, and PDGFRa+ cells. KV4.3 predominantly co-localized with ICCs in the circular muscle layer, neurons in the myenteric plexus, and smooth muscle cells. KV4.2 expression was markedly reduced in the aganglionic bowel of patient specimens compared to the ganglionic region and healthy controls, while KV4.3 was not reduced in the aganglionic or ganglionic bowel of patient specimens. These findings implicate voltage-dependent A-type channel KV4.2 in the pathogenesis of HSCR. References:

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83. LOWER EXTREMITY JOINT KINEMATICS: EVALUATING THE DIFFERENCE BETWEEN COUNTERMOVEMENT JUMP TYPES Davis D1, Mann B1, Razu S1, Bean K1, Guess T1 1 University of Missouri, Department of Physical Therapy and Orthopaedic Surgery Columbia, MO, USA

Countermovement jump tests are frequently used as athletic metrics in the sports community. This applies to the medical community as these tests may help identify musculoskeletal pathologies before an athlete returns to play[1]. A persistent performance difference remains between countermovement jumps where the athlete is allowed to swing their arms (CMA) and where the arms are restricted (CM). The purpose of this study was to determine the effect of summed lower extremity instantaneous joint power on the performance difference between CMA and CM. 23 female Division 1 soccer athletes performed 5 trials of each jump type. A Vicon camera system and AMTI Optima force plates were used to analyse motion. Jump distance was calculated via a pelvic coordinate system and normalized to subject height. Instantaneous power of the lower extremity joints from peak knee flexion was calculated. Values were plotted against jump distance to assess performance difference in CMA and CM. Student’s t-test determined statistical significance. Power and jump showed a modest correlation for CMA (R2 = *0.5) but none for CM (R2 = .02). Mean jump distance (ttest = 4.63e-9) and summed joint power values (t-test = 4.14e-12) differed significantly (p \ 0.05) between jump types. Joint angle values were greater for CM yet power and distance jumped (0.05 m ± 0.02) values were greater for CMA. Despite CMA having larger average power there was little to no correlation with either jump type. This additional power may result from an added load from the arm swing[2]. Future should further examine upper extremity kinematics on the difference in CMA and CM. Acknowledgements: The author would like to acknowledge funding from the UCD’s SSRA programme. References: 1. Labanca L, Laudani L, Menotti F, Rocchi J, Mariani PP, Giombini A, et al. Asymmetrical Lower Extremity Loading Early After Anterior Cruciate Ligament Reconstruction Is a Significant Predictor of Asymmetrical Loading at the Time of Return to Sport. Am J Phys Med Rehabil Assoc Acad Physiatr. 2016 Apr;95(4):248–55. 2. Hara M, Shibayama A, Takeshita D, Fukashiro S. The effect of arm swing on lower extremities in vertical jumping. J Biomech. 2006 Jan 1;39(13):2503–11. Presenting Author: Mr Derick Davis Supervisor: Dr Trent Guess

1. Puri P, Gosemann JH. Variants of Hirschsprung disease. Semin Pediatr Surg. 2012; 21(4):310–318. 2. Amberg GC, Koh SD, Hatton WJ, Murray KJ, Monaghan K, Horowitz B, et al. Contribution of KV4 channels toward the A-type potassium current in murine colonic myocytes. J Physiol. 2002. 544(2):403–15.

84. 7 YEAR TRENDS IN SUBDURAL HAEMORRHAGE: INCIDENCE AND ASSOCIATION WITH ANTICOAGULATION USAGE

Presenting Author: Ms Bina Parekh Supervisor: Dr Anne Marie O’Donnell Co-Supervisor: Prof Prem Puri

Byrne MO1, Cooney MT1,2, Clark S3, Barry M4, Cronin J5, Doyle RM1,2,6

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Ir J Med Sci (2017) 186 (Suppl 1):S1–S39

1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Geriatrics, St Vincent’s University Hospital, Elm Park, Dublin 4. 3Medicines Management Program (MMP), HSE, Dublin. 4National Centre for Pharmacoeconomics, Dublin. 5Department of Emergency Medicine, St Vincent’s University Hospital, Elm Park, Dublin 4. 6St. Columcille’s Hospital, Loughlinstown, Dublin More older people now receive anticoagulation, particularly for stroke prevention in atrial fibrillation. The introduction of direct oral anticoagulants (DOACs) and the aging population further increases this number. Our aim was to calculate incidence rate of subdural haemorrhage (SDH) on a background of increasing anticoagulation prescription. We identified through HIPE, patients in South-East Dublin and (most of) Wicklow presenting to St. Vincent’s University Hospital and St. Columcille’s Hospital between 2009 and 2015 with first acute SDH. Clinical information including demographics, medical comorbidities, medications, examination, radiological severity, in-hospital outcome (mortality and disability) and discharge destination, was collected. Rates of SDH were calculated, using the age structure of the catchment area population from the 2011 Census and agestandardised using direct method and the European Standard Population. 313 patients presented with SDH from a catchment area of 330632 people (mean age 68.68 years, 43.77% women). The age-standardised rate for SDH overall was 11.86; 1.98 for anticoagulant-associated SDH. 25% gave no history of trauma. There was a possible nonsignificant trend towards increasing rates (p = 0.1) in SDHs overall, however these excess SDHs were trauma-related and occurred in younger people. There was no indication of an increasing trend in anticoagulant-associated SDHs over the 7 years (p = 0.82), see table. Between 2010 and 2016 anticoagulation usage nationally increased by 53% [1]. However, the expected parallel increase in SDH has not been demonstrated thus far. The shift from warfarin to DOAC (1% DOACs in 2010 compared to 48% in 2016[1]) provides a potential explanation for this, however ongoing monitoring is required.

Reference: MMP and Department of Pharmacoeconomics, Dublin. Presenting author: Ms Muireann Byrne Supervisor: Dr Marie Therese Cooney Co-Supervisor: Dr Rachael Doyle

85. ADHD IN CAMHS IN IRELAND: AN EVALUATION OF CURRENT PRACTICE Ahmad Shafiai SA1,4, Neto FH1, Gavin B1, McNicholas F1,2,3,4 1

UCD School of Medicine, University College Dublin, Belfield, Dublin 4. 2Department of Child Psychiatry, Our Lady’s Hospital for Sick Children, Crumlin. 3Lucena Clinic Rathgar, Dublin 6. 4UCD Geary Institute for Public Policy, Belfield, Dublin ADHD accounts for up to 1/3rd of presentations to CAMHS [1]. Recommended treatment is multi-modal combining medication and parenting [2]. This study aimed to compare the most recently available published HSE data [1] with current ADHD case load and typical management of ADHD by HSE region. A study specific questionnaire was designed and sent to all Consultant Child Psychiatrists (N = 71). Data analysed included information on dedicated ADHD clinics, estimated ADHD open case, and typical treatments offered. 34 consultants responded (response rate 48%). 26 (76%) operated a dedicated ADHD clinic, with an average of 88 ADHD cases per respondent. 24 consultants (71%) reported ‘usually or always’ initiating medication and 16 (47%) parenting groups. Fewer ‘usually or always’ offered either occupational (10, 29%) or speech and language therapy (6, 18%). Comparing practice in 2016 with earlier records, suggest similar rates of dedicated clinics (80% in 2011; 78% in 2012), although significant regional variation existed.

Table: Age-standardised rates of SDH Total Subdural Haemorrhages Year

Number of events

Anticoagulated-associated Subdural Haemorrhages Age-standardised rate per 100,000

% fatal

Number of events of those anticoagulated as % of the total

Age-standardised rate per 100,000

2009

35

9.1

9/35 (25.7%)

2.0

2010

37

10.3

7/37 (18.9%)

1.9

2011

48

12.4

12/48 (25.0%)

2.9

2012

37

9.6

4/37 (10.8%)

1.0

2013

30

7.7

6/30 (20.0%)

1.4

2014 2015

60 66

15.9 18.0

6/60 (10.0%) 14/66 (21.2%)

1.2 3.4

Total

313

123

23.6

58

% fatal

37.9

Ir J Med Sci (2017) 186 (Suppl 1):S1–S39 Open ADHD case load was 3025 in Nov. 2011 and 2710 in 2012, giving a rate of 54 cases in 2011 and 47 in 2012 per CAMHS team. There was no standardised treatment data collected in the HSE reports. This postal survey adds some additional data to the management of ADHD in CAMHS with regional variation, but is limited by the restricted focus, respondent report and moderate response rate. It highlights the importance of clinical audits and national systems collecting standardized data on clinical treatment and outcomes to ensure services are providing effective and evidenced based care. References:

S39 1. Health Service Executive. Fifth Annual Child and Adolescent Mental Health Service Report 2012–2013. Dublin: Health Service Executive; 2013. 2. National Institute for Health and Care Excellence. Attention Deficit Hyperactivity Disorder: Diagnosis and Management. London: NICE; 2008. Presenting Author: Suhail Anwaar Ahmad Shafiai Supervisor: Prof Fiona McNicholas Co-Supervisors: Dr Blanaid Gavin/Fabiola Honorio Neto

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