Conference Abstract Booklet: 2nd Student Medical Summit 2019

The following abstracts are those that were presented at the research competition of the Student Medical Summit held in University College Dublin on the 9th February 2019. For more information about the Student Medical Summit visit www.studentmedicalsummit.org or contact info@studentmedicalsummit.org.


Is heart rate variability (HRV) a predictor of intraventricular haemorrhage (IVH) in preterm infants?
Sarah E. Donoghue, BSc Student [1], John M. O' Toole, PhD [2], Eugene Dempsey, Professor [3] [1] School of Medicine, University College Cork, Ireland [2] Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Ireland [3] Department of Paediatrics and Child Health, University College Cork, Ireland Introduction:  Intraventricular haemorrhage (IVH) occurs in up to 15-20% of babies born before 32 weeks.  Injury can cause detrimental short and long-term health outcomes.  Heart rate variability (HRV) is a measure of autonomic function controlled by cardiorespiratory reflexes.  Depressions and decelerations in HRV are sometimes witnessed clinically with acute central nervous system injury, such as haemorrhage. Methods: This project analysed ECG data from 28 preterm infants (<32 weeks gestation) who have been enrolled a prospective randomised trial of umbilical cord management in CUMH. The HRV was computed from the ECG. This was achieved by: 1) Extracting a 15-minute epoch of ECG free from major artefacts from the long-duration recordings. 2) Identifying the ECG R-peaks by visual inspection using a HRV Analysis (a UCC software package designed specifically for this task) 3) Extract quantitative HRV features from the R-R interval 4) Two time points were chosen, 6 hours and 12 hours. The 7 HRV features were defined in 1996 by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Results: Nine of the twenty-eight babies developed Grade 1/2 IVH. There were no statistically significant differences in the features between infants with and without low grades of IVH. Conclusion: We found no association between HRV characteristics at 6 and 12 hours of age and low grades of IVH in preterm infants <32 weeks. Future work is needed to explore the relationship between HRV and severe IVH (Grade 3/4).

Shoulder pathology in recreational wheelchair athletes: comprehensive clinical assessment using a communitybased, athlete-centered approach
Fiona C. Doolan, MBBCh, BSc [1], Nida Naushad, MD, BSc [2], Yetsa A. Tuakli-Wosornu, MD, PhD, BSc [2,3] [1] School of Medicine, Trinity College Dublin, Dublin, Ireland [2] School of Medicine, Yale University, New Haven, Connecticut, United States [3] Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States Introduction: Physical activity and sport participation has proven health benefits for wheelchair users and is recommended by the WHO, however, wheelchair athletes are especially vulnerable to activity-restricting injury because they employ their shoulders as principal weight-bearing joints. The aim of this study was to examine the feasibility of a protocol for shoulder examinations for wheelchair athletes in a community setting, and to identify potential modifiable risk factors for injury in this population. Methods: Eight athletes underwent bilateral 1) 12-point ultrasonographic shoulder examination and 2) complete shoulder physical examination. They completed 3) the Wheelchair Users Shoulder Pain Index to screen for symptomatic shoulder pain 4) an environmental questionnaire to assess the accessibility of their environment, and 5) a satisfaction survey. The study was carried out in a wheelchair-friendly community fitness center. Results: 6 of 8 participants had experienced pain in one or both shoulders over the past 2 weeks. Of the 6, all exhibited ultrasonographic findings on the painful shoulder(s). 5 of 6 had at least one physical exam finding on the painful shoulder(s). Additionally, 1 participant who self-reported no pain, had positive findings on both US and PE. Among symptomatic participants, over half reported pain when pushing their chairs over grass or carpet, the latter a surface encountered with high frequency by 7 of 8 participants. All participants were satisfied with study participation. Conclusion: This pilot study suggests broad implementation of community-based shoulder screening may be effective at identifying both symptomatic and pre-symptomatic shoulder injury among wheelchair athletes, and that environment modification presents a prevention target.

Increased glycolytic metabolism in RA patients, mechanisms that may precede clinical manifestations
Rochelle Dowding [1], Sharon Ansboro [1], Douglas Veale [2], Ursula Fearon [1] [1] Molecular Rheumatology, Trinity College Dublin [2] Centre for Arthritis and Rheumatic Diseases, St Vincent University Hospital, Dublin Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial proliferation and degradation of articular cartilage/bone. Emerging evidence suggests that in inflammatory diseases, cells adapt their metabolic status in order to maintain activity. This study examines the inflammatory and metabolic profiles of circulatory immune-cells and synovial-tissue from patients with RA, OA, and from at-risk RA subjects (arthralgia). Methods: Peripheral blood mononuclear-cells (PBMC) were isolated from blood of healthy controls (HC), RA, OA and atrisk individuals (arthralgia-ACPA+/RF+, normal CRP, no-synovitis). In addition, synovial-tissue was obtained from RA, OA and arthralgia patients undergoing arthroscopy. Cytokines IL-6,-IL-8 and MCP-1 mRNA expression were quantified by RT-PCR. Metabolic markers Glut-1,-LDHA,-PFKFB3,-PKM2 mRNA and/or protein expression were quantified by RT-PCR and histology. Results: IL-6,-IL-8, the glycolytic enzyme PFKFB3 and the glucose-receptor Glut-1 were significantly increased in RA vs HC and OA (all p<0.05). Interestingly, a trend for increases in IL-8 and MCP-1, along with PFKFB3 and LDHA was also observed in arthralgia patients compared to OA and HC. IL-6,-IL-8 and MCP-1 were significantly higher in RA synovium vs OA, paralleled by increases in PFKFB3, Glut-1 and LDHA (all p<0.05). Histological expression of PFKFB3, Glut-1 and PKM2 were significantly increased in RA vs OA (p<0.05), expression of which were inhibited in TNFi responder compared to non-responders (p<0.05). Conclusion: This study demonstrates significant increases in the metabolic profile of circulatory mononuclear-cells and synovial-tissue from patients with RA. Furthermore, the increase in inflammatory/metabolic markers in arthralgia subjects suggests that cells may already be primed pre-onset of RA.

Fast acquisition abdominal MRI study for the investigation of suspected acute appendicitis in paediatric patients: Prospective, randomised assessment of the diagnostic accuracy and clinical efficacy
Aoife Feeley, BSc Student [1], Brian Carey, MB, MCh, BAO, MRCS [2] [1] University College Cork, Cork [2] Department of Radiology, Cork University Hospital, Cork Introduction: Acute appendicitis is the most common surgical diagnosis in children presenting with abdominal pain. Radiological investigations are often required to accurately identify cases of appendicitis due to varied presentations in the paediatric population. Ultrasound is currently used first line; although research is currently focused on finding alternative imaging modalities with higher diagnostic accuracy. CT is second line in many centres, however MRI has been shown to have similar sensitivity and specificity to CT, without risk of radiation exposure. Methods: This was a prospective study carried out in CUH across a 6-month period. Inclusion criteria: patients aged 5-16 (inclusive), acute appendicitis as a differential diagnosis, requiring ultrasound assessment; as dictated by the referring clinician. Exclusion criteria: Patients with cognitive deficits, history of previous abdominal surgery. Patients provided informed consent prior to investigations. Participants underwent abdominal ultrasound and were divided into two MRI groups of sequences with free breathing, or breath holding. Conclusion: MRI has higher diagnostic accuracy in acute appendicitis in the paediatric population than ultrasound. Allowing patients to breath freely also increases diagnostic accuracy. Introduction of MRI protocol for patients admitted with suspected appendicitis can result in faster diagnoses, and treatment. Additionally, with higher specificity, use of MRI can reduce the number of negative appendicectomies carried out in tertiary centres.

Should surgical site infection wound bundles become mandatory in colorectal surgery? A meta-analysis.
Deirdre Foley [1,2], Madga Bucholc [3], Randal Parlour [4], Caroline McIntyre [1,2], Alison Johnston MSc [1], Michael Sugrue MD FRSCI FRAS [1,4]  The global impact of surgical site infection (SSI) is increasingly recognized, both in terms of post-operative complications and oncological outcomes. Reducing SSIs is multifactorial, with a cumulative additive benefit of each bundle element. While other meta-analyses have been performed looking at surgical wound bundles most relate to interventions before 2016. This study therefore undertook an up to date meta-analysis looking at existing bundle impact on SSI. Methods: An ethically approved PROSPERO-registered(ID:CRD42018104923) meta-analysis following PRISMA guidelines and using databases PubMed, Scopus and Web of Science, from January 2008 to July 2018, was undertaken. Articles scoring ≥ 17 using MINORS criteria were included. Results: 5,104 articles were reviewed and 27 studies met inclusion criteria. There was a significant decrease in SSI rates with implementation of a wound bundle (17.5% vs 9.7%). Sub-analysis showed a significant reduction in superficial SSIs by 54% (p<0.00001) and in organ-space SSIs by 42% (p=0.0006). The use of a wound bundle also significantly reduced hospital lengths of stay (MD = −0.79; p<0.00001). Conclusion: This meta-analysis shows that use of an evidence-based, surgical care wound bundle in patients undergoing colorectal surgery significantly reduces the risk of SSI and length of hospital stay. They should become mandatory.
28. An analysis of potential drug-drug interactions in an aging HIV cohort Pádraig Gardiner [1], Dr. Gabriella Rizzo [2] [1] University College Cork, Cork [2] Cork University Hospital Introduction: The advent of antiretroviral drugs has transformed the treatment of HIV and has led to a dramatic increase in life expectancy of patients. As a result patients are more likely to acquire comorbidities which require pharmacological management. This increased pill burden is likely to lead to an increase in potential drug-drug interactions (PDDIs) between prescribed medicines. Methods: The files of HIV patients aged 50+ (n=128) were examined to obtain demographic data and their ART regimens and co-medications. Interactions were then screened for and categorised according to severity. Results: 72.3% (94/128) of patients took at least one co-medication with 49.2% (63/128) of patients having at least one PDDI. A total of 23 category yellow, 81 category orange and 6 category red interactions were detected. Statins and Colecalciferol were the co-medications found to contribute the most to PDDIs, leading to 19.1% and 17.3% of all PDDIs respectively. Cobicistat (29.4%) and integrase inhibitors (32.2%) were found to be the ART agents most likely to lead to a PDDI. A correlation was found to exist between the total number of PDDIs and the number of co-medications prescribed (R= 0.621, p= <0.0001) and between number of PDDIs and a decreased CD4 count (R= -0.207 p=0.019) while age and gender were found not influence on the number of PDDIs. Conclusion: Owing to the necessity to prescribe for co-morbid conditions, it is almost inevitable that some of these medications will interact. It is therefore advisable to utilise an interaction checker database as well as clinical monitoring to optimise patient outcome. Introduction: The prevalence of antipsychotic polypharmacy in the treatment of schizophrenia is increasing worldwide. This is against most guidelines as it is associated with higher mortality and shorter patient survival, however there is little research on why multiple antipsychotics are still used. This study aimed to examine the prevalence and correlated factors of antipsychotic polypharmacy. Methods: A retrospective chart review of current adult psychiatric inpatients with a primary diagnosis of schizophrenia or schizoaffective disorder was conducted, examining number and type of antipsychotic medications prescribed, reasons for additional prescription, side effects, symptom control, and adjunct therapy. Data was analysed in SPSS using independent t test, chi-square analysis and Fisher's exact test. Results: The prevalence of antipsychotic polypharmacy was 77.8% (n=27). The mean age sampled was 43.9 +/-2.2 years, with an age range of 27 -66; There was no significant relationship between antipsychotic polypharmacy and age. 70.4% of patients were male. No significant difference was found in gender or rates of compliance, extra-pyramidal symptoms, type 2 diabetes mellitus, weight gain, other side effects, use of valproate, use of benzodiazepines, or adequate control of symptoms between those on one antipsychotic or those on polypharmacy. Conclusion: The prevalence of antipsychotic polypharmacy observed is higher than the EU average, which may be due to the inpatient population. No significant correlates were found. These are preliminary results, and data collection is ongoing.

Introduction:
The cingulum bundle of the brain is an association pathway of the limbic system which communicates with areas all over the brain. Areas of communication within the cingulum bundle are involved in spatial orientation, emotion processing, pain processing, attention, memory, autonomic function and skelomotor function. Few studies involving the cingulum have coherently determined its partitions as well as related vicissitudes throughout life's cycle. Research has instead been centred around associations and functions such as phasic pain and goal-mediated attention. Studies have shown that the cingulum bundle can be divided into subdivisions in animals based on corticocortical connections but this is yet to be shown in humans. Aim of this investigation is to use diffusion tensor imaging to separate the human cingulum bundle into subdivisions through surrounding anatomical features and to determine structural alterations of these regions during maturation into adulthood. Methods: A total of 50 healthy (25 female) participants aged 15 -40 years, were scanned using a High Angular Radial Diffusion Imaging (HARDI) protocol. Following constrained spherical deconvolution whole brain tractography, the cingulum bundle was reconstructed. The cingulum was divided into anatomico-functional segments (subgenual, retrosplenial, parahippocampal) by two independent raters. Cingulum dimensions and diffusion metrics (measures of structural integrity) were calculated. Ethical approval for this investigation came under the remit of the REDEEM study at Trinity College Dublin. Results: Excellent inter-rater reliability in tract reconstruction and segmentation was demonstrated. Regional changes in diffusion metrics such as fractional anisotropy and mean diffusivity occurred with age, suggesting a global maturation of the cingulum in the mid-twenties, followed by decline. Anatomically specific variations in maturation and stability also occurred along the cingulum tract. Conclusion: Findings suggest that the cingulum does not mature consistently throughout its structure. Different partitions evolve at different rates. Understanding the normal variation in maturation of cingulum may underlie the difficulties in emotional control that occurs during normal adolescence but may also underlie pathological abnormalities in neurodevelopmental disorders. Introduction: Diabetic foot ulcers (DFU) occur in 5-10% of diabetics and are the most common precursor of amputation. Texas wound grade (TWG) classifies DFU -0 is healed, 1 is superficial, 2 penetrates to tendon or joint capsule, and 3 penetrates to bone or joint. This study aims to characterise demographic and pathologic risk factors associated with increased TWG on initial referral to the specialist diabetic foot clinic (SDFC) at Cork University Hospital (CUH). Methods: Data was collected from active CUH SDFC files between 2012 and 2018. Sample without specific features were excluded. Demographics included sex, age, medical coverage, residence location, marital status, employment status, referral type, and smoking. Pathologic features included HbA1c, diabetes duration, Texas wound stage (TWS), number of ulcers, hypertension, peripheral neuropathy and macrovascular, microvascular, or peripheral vascular disease. Categorical variables were compared by Chi-Squared and Fisher's exact test; continuous variables were compared by Kruskal-Wallis. Results: Demographic differences between TWG included martial status (p=0.011) and referral type (p<0.000). TWG increased in single (TWG1=10%, 2=38%, and 3=31%) inpatients (TWG1=13%, 2=54%, 3=54%). Pathologic differences included shorter diabetes duration with TWG2 (11.9y±11.4, p=0.029), and TWG3 (10.3y±0.023, p=0.026) compared to TWG1 (16.8y±11.3). Ischaemia TWS was common with TWG1 (38%) but was infective for TWG2 (42%) and 3 (50%) (p<0.000). Conclusion: Being a single and inpatient are demographic risk factors for initial referral to CUH SDFC with high-grade DFU compared to pathologic features of diabetes. The risk of infection and shorter diabetes duration suggest screening and early intervention could have could reducing initial high TWG DFU.

Cardiovascular risk assessment in asymptomatic patients with inflammatory arthritis
Tommy Harty [1], Dr Miriam O Sullivan [2], Dr Sinead Harney [3] [1] University College Cork, Cork [2] Our Lady's Hospital, Co. Leitrim [3] Cork University Hospital, Cork Introduction: Cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD), is significantly increased compared to the general population. For RA, the extent of this increased risk is comparable to that reported for patients with diabetes mellitus (DM), and requires immediate and targeted cardiovascular (CV) risk management. Methods: The SURF-RA questionnaire regarding traditional cardiovascular risks and current and past medications was distributed to all patients with a IJD attending the Rheumatology Clinic at CUH.. Traditional and rheumatoid specific CVD blood markers were assessed in this cohort of patients. Disease activity was measured using the DAS28 formula. Comparisons of patients with varying levels of disease activity with respect to their CV risk profile was examined using Mann Whitney U tests. Correlation testing was used to assess CV risk and disease activity. Results: The analysis included 116 patients with IJD. Of which, 75 had a diagnosis of RA, 22 had a diagnosis of psoriatic arthritis (PsA), 17 had a diagnosis of ankylosing spondylitis. Disease activity was positively correlated to HbA1c level [r = .294, p < 0.05] and to QRISK3 score [r = .252], however this result was not statistically significant.. No significant association was found whem comparing different rheumatological treatments and with varying degrees of disease activity. Patients with IJD were found to be under-managed in terms of medicating for specific CV risk factors. Conclusion: Patients with a higher level of disease activity had a higher cardiovascular event risk profile. Comorbidities in patients with chronic diseases including RA have been shown to be under-recognised and under-treated.This remains the case in the population examined and cardiovascular management in patients with IJD requires re-evaluation in line with EULAR recommendations. Introduction: Anterior Cruciate Ligament (ACL) injuries are a common reason for surgery. ACL-deficient knees are associated with pain, reduced quadriceps strength, neuromuscular dysfunction and poor proprioception, biomechanical mal-adaptations, and reduced knee function. An increased risk of reduced ambulatory function and osteoarthritis also exists in this population. Post-operative physiotherapy for ACL reconstruction is beneficial in the management of ACL injuries, but literature is lacking on whether pre-operative physiotherapy (prehabilitation) is beneficial. Methods: Electronic databases EBSCO and Medline were searched, from inception to July 1, 2018. Research reports and other articles that were excluded included single case reports, duplicates, animal studies, and those articles that did not focus on prehabilitation. Additional studies were added based on preliminary readings and reviewing the references in these readings. The selected relevant articles were reviewed and the results summarized before conclusions were made. Results: Of 47 citations identified by the search, a total of 14 studies or articles were initially eligible for this review. Upon closer inspection, only 12 studies contained post-operative results; the literature varied from clinical and narrative reviews, an editorial, and clinical cohort or randomized control studies. Conclusion: In patients undergoing ACL reconstruction surgery, there may be beneficial effects from prehabilitation. These effects include increased quadriceps strength, improved gait, facilitating return to sport, improved patient reported outcomes, and possible decreased need for surgery. No harmful effects of prehabilitation were found; the cost-benefit ratio of prehabilitation was not discussed. Randomized control trials are needed to further establish the immediate and long-term effects of prehabilitation in patients undergoing ACL reconstruction.

Lamina cribrosa cell bioenergetics in glaucoma: Glycolysis and glutaminolysis
Diarmaid Hickey [1,2], Mustapha Irnaten [1,2], Deirdre Brennan [3], Deborah Wallace [2], Abe Clark [4] Introduction: In glaucoma, the lamina cribrosa (LC) region undergoes considerable 3D structural changes relating to significant alterations in the extracellular matrix and associated cupping. Cells mediating this cupping include astrocytes and LC cells. We have previously shown mitochondrial dysfunction and an increased rate of proliferation in glaucomatous LC cells (GLC). Rapidly proliferating cells utilise alternative metabolic pathways to meet energy requirements. Monocarboxylate transporter 1 (MCT1) and glutaminase 2 (GLS2) are known to play an essential role in cancer cell metabolism. Glycolysis (the Warburg effect) results in high lactate levels, increasing the expression of MCT1. Glutamine uptake and metabolism is a key part of biomass accumulation in rapidly proliferating cells. The purpose of our research was to investigate the expression of markers (MCT1 and GLS2) associated with an enhanced glycolysis and glutaminolysis phenotype. Methods: Human primary LC cells derived from normal and glaucomatous age-matched donors were cultured between passages 4-8. At confluence, cells were subject to either RNA extraction or protein isolation. MCT1 and GLS2 expression levels were quantified using quantitative real time (qRT-PCR) and western immunoblotting.

1] School of Medicine, University College Cork, Cork, Ireland [2] School of Public Health, University College Cork, Cork, Ireland [3] National Suicide Research Foundation, 4.28 Western Gateway Building, University College Cork, Cork, Ireland
Introduction: Self-harm is common in adolescence with increasing rates in teenage years. Alcohol involvement is among factors known to be often involved in hospital-treated self-harm. It is essential to establish the role of alcohol in self-harm as well as exploring the different characteristic between presentations with and without alcohol. Methods: Data on self-harm presentations to acute hospitals Emergency Departments in Ireland from 1 January 2013 to 31 December 2016 were analysed. The characteristic of self-harm patients presenting with and without alcohol consumption were compared. The factors associated with alcohol-involved self-harm were identified using univariate analysis and multivariate logistic regression. Results: A total of 15415 self-harm presentations between the age of 10 to 24 years old were recorded. Alcohol was present in 3448 (22.4%) of the presentations. The major factors associated with alcohol consumption being involved is male, age 20-24 years old, having engaged in drug overdose and attempted drowning and presenting in Irish towns. Alcohol involvement were more likely to be associated with presentations made out of hours and during the weekend. Patients with alcohol on board were more likely to be brought in by ambulance and other emergency services but were less likely to be admitted under general or psychiatric admission. Conclusion: This study highlighted the prevalence of alcohol involvement in self-harm presentation (1 in 5) under the age 25 years and identified the factors associated with presentations involving alcohol. Appropriate out-of-hours services were required to manage these presentations including ambulances, psychiatric assessments and paediatric services. The consumption of alcohol in patients <18 years old also addresses the issue of illegal age for drinking and the need for tighter alcohol control, as well as to study the consumption pattern in town areas. Introduction: At present, there is a general consensus that multiple genes, as well as environmental influences, are involved in the development of Autism Spectrum Disorders (ASD). It has recently been suggested that one such influence may be the microbiota-gut-brain axis. Exposure of infants to altered gut microbiota through maternal presence of Irritable Bowel Syndrome (IBS) has therefore been reasoned as a possible source of aberrant fetal neurodevelopment 2 and a possible ASD risk factor. Methods: This study involved a retrospective analysis of data extracted from the UK Millennium Cohort Study (MCS). Data on self-reported maternal IBS and relevant potential confounding variables was collected from the first MCS survey, when cohort members were 9 months old. Data on ASD was collected from survey four, when children were 7 years old. Cases used for analysis included children whose parents reported that their child had been previously diagnosed with ASD. Crude and adjusted logistic regression analysis was then conducted to assess for associations between ASD and Maternal IBS, and to control for relevant confounders, including maternal age, education level, ethnicity, BMI, smoking history, depression, depression treatment and household income. Results: There were 13,098 singleton mother-child pairs from the first sweep of MCS data collection who also responded with regards to ASD in the fourth sweep, providing 199 ASD cases. Maternal IBS was associated with an increased risk of ASD in offspring in both crude analysis (OR 1.88 95% CI 1.20-2.95) and adjusted analysis (aOR 1.73 95% CI 1.10-2.74). Conclusion: This study demonstrated a link between maternal IBS and ASD in offspring which warrants further investigation. Introduction: Large loop excision of the transformation zone (LLETZ) is the gold standard for treatment of cervical intraepithelial neoplasia (CIN), a premalignant condition of the uterine cervix. Excision depths should not exceed 12mm to minimise future obstetric risk. Prognosis is determined by the presence or absence of CIN at the margin of conisation. The aim of this study is to audit the LLETZ procedure in St Finbarr's colposcopy clinic by assessing depth of excision and margin rates and comparing these with current guidelines. Methods: A retrospective study of all LLETZ performed between January 2016 -March 2018. The following factors were analysed: age, indication for LLETZ, colposcopist seniority, disease severity, margin status, specimen dimensions and number of excisions. Results: 694 LLETZ met criteria for inclusion in the study. The mean depth of excision was 8.57mm (SD: 4.4). 576 (83%) were ≤12mm. In total, there were 551 (79.4%) cases of CIN with 375 (68.1%) of these having high-grade dysplasia (CIN 3). Excisions were deeper when performed as a repeat LLETZ compared with first excision (mean 9.91mm versus 8.34mm, P = 0.001). Positive margins were found in 212 (30.5%) excisions. Deeper excisions, high grade CIN and colposcopist seniority were not found to influence margin status. Conclusion: Compliance with current guidelines on the use of LLETZ is good. However, excision depths exceeded 12mm in a number of cases. Depth of excision was greater in repeat LLETZ. No predictive factors for margin involvement were identified.

Diagnostic yield of neuronal ceroid lipofuscinoses genetic testing: phenotype and genotype of neuronal ceroid lipofuscinoses
Abdulhakim Jilani, MB, BCh, BAO Student [1,2], Diana Matviychuk, MSc [3], Susan Blaser, MD [4] Introduction: Neuronal ceroid lipofuscinoses (NCL) are inherited neurodegenerative disorders characterized by developmental regression, seizures, visual loss, and early death. We performed a retrospective cohort study to determine the diagnostic yield of genetic testing in NCL. Methods: Molecular Genetics Laboratory Database was reviewed for NCL genetic tests. Electronic Patients Charts were reviewed for the patients at our Institution. Physicians from outside Institutions were contacted if they had a genetically confirmed NCL patient. Verbal phone and release of information consent forms and Research Electronic Data Capture (REDCap) questionnaires were completed. All variants were reclassified. (MFSD8) (n=9), and CLN8 (n=3) associated diseases. CLN2 (TPP1) associated disease was the most common NCL subtype. Phenotype of 33 patients were summarized. Juvenile onset CLN1 (PPT1) and adult onset CLN6 associated diseases were nonclassical phenotypes. Conclusion: The diagnostic yield of NCL genetic testing was 24.5%. Application of next generation sequencing will likely identify more patients with non-classical phenotypes of NCL.
39. Comparison of patient experience (PE) and health-related quality of life (HRQoL) with severe factor IX deficiency before and after switchover to extended half-life (EHL) clotting factor IX (FIX) concentrate. Kate Johnston, Medical Student, BSc Student [1], Evelyn Singleton [2], Kevin Ryan [2], Niamh O'Connell [2] [1] School of Medicine, Trinity College Dublin, Dublin, Ireland [2] National Coagulation Centre (NCC), St. James's Hospital, Dublin, Ireland Introduction: EHL FIX prophylaxis in people with severe FIX deficiency may improve HRQoL. In 2017 an en-masse switch to rFIX Fc fusion protein (Alprolix®, SOBI) was undertaken in Ireland. Methods: Patients with severe FIX deficiency completed switchover from standard half-life rFIX to rFIXFc (n=29). EuroQoL EQ5D5L questionnaires were completed pre and 3 months post-switchover (n=24/29). Data analysis involved descriptive statistics and EQ5D5L Crosswalk Index Calculator. On-demand factor usage for bleeding episodes was analysed 12 months pre and post-switchover. Results: Pre-switchover, EQ5D5L dimensions "mobility" and "self-care" had the most and least problems respectively. EQVAS mean was 71, with differences seen in mean values for patients with "no problems" vs those with "at least one problem" (88 vs 69). The mean EQ5D5L Index value was 0.7. 3 months post-switchover, dimensions "mobility" and "self-care" had the most and least problems respectively. The overall EQVAS mean, mean for patients with "no problems", mean for patients with "at least one problem" and mean EQ5D5L Index value were unchanged. No minimally clinical important difference was observed in EQ5D5L data pre and post-switchover (3 months). However PE reports high levels of satisfaction with reduced infusion burden. The number of on-demand infusions used to resolve bleeding episodes decreased. Prior to switchover, 90.2% of bleeding episodes were resolved by 1 or 2 injections vs 97.6% post-switchover. Conclusion: Despite the EQ5D5L data, PE suggests that HRQoL improvements have occurred post rFIXFc switchover. We aim to repeat EQ5D5L questionnaires 12 months post-switchover and complete qualitative, semi-structured interviews, focusing on HRQoL and chronic pain coping strategies. Introduction: Glioblastoma is the most common high-grade primary brain tumor in adults. Current treatment results in transient tumor control but inevitably cascades to disease progression. Interests in alternative therapeutic avenues demanded the exploration into anti-angiogenic therapies such as bevacizumab. We sought to determine the efficacy of bevacizumab as treatment for glioblastoma. Methods: PubMed and Google Scholar were used to identify RCTs investigating the safety and efficacy of bevacizumab in the treatment of adult patients with both newly diagnosed and recurrent glioblastoma. Only Level I data that reported progression-free survival (PFS) and overall survival (OS) were included for analysis. Random effects meta-analyses were conducted in R 2 to estimate the hazard ratio (HR).

Adherence to intertemporal discounting guidelines in cost-effectiveness analysis: A research study
Michelle Kwok [1], Mistura A. Kareem [1], Michael J. Cash [1], Fiona Lafferty [1], James F. O'Mahony PhD [1,2] [1] School of Medicine, University of Dublin, Dublin, Ireland [2] Centre of Health Policy and Management, University of Dublin, Dublin, Ireland Introduction: Cost-effectiveness analysis (CEA) is used by healthcare decision makers to guide decisions on the prioritisation of funding medical interventions. Discounting is applied to account for time preference when calculating the value of costs and health consequences in the future. This paper analyses adherence to discounting rates by published papers in selected countries with established CEA guidelines. Methods: The Tufts Medical Centre CEA Registry was interrogated to collect data on discounting rates used in CEA in seven countries. Factors associated with non-compliance to guidelines were analysed by binary logistic regression.

Results:
The percentage of adherent studies ranged from 44% to 93% between the countries. There was a sharp contrast in the rates of neighbouring countries Australia and New Zealand, whose rates were 79% and 44%, respectively. The Netherlands' adherence rate was 79% while using equal discounting, rising to 91% when differential discounting was adopted in 2006. Belgium had an adherence rate of 93%. When studies were analysed by publication year, there was a steady increase in adherent studies over time. Conclusion: This paper highlights that there is scope for improvement in adherence to official CEA guidelines. Type of funding, country of study, and year of publication were found to be statistically significant variables. An overall improvement in adherence rates was observed over time. Geographical proximity is not correlated with similar adherence rates. Increased adherence rates were linked to studies funded by pharmaceutical manufacturers over non-manufacturers. Better adherence was correlated to countries applying differential discounting.
Introduction: Therapy directed against oncogenic FLT3 has been shown to induce response in patients with acute myeloid leukemia (AML), but these responses are almost always transient. To address the mechanism of FLT3 inhibitor resistance, we generated two resistant AML cell lines by sustained treatment with the FLT3 inhibitor sorafenib. Parental cell lines carry the FLT3-ITD (tandem duplication) mutation and are highly responsive to FLT3 inhibitors, whereas resistant cell lines display resistance to multiple FLT3 inhibitors. Methods: Sanger Sequencing, protein mass-spectrometry, cell culture, immunoprecipitation, western blott, microarrays, mouse models, flow cytometry. Results: Sanger sequencing and protein mass-spectrometry did not identify any acquired mutations in FLT3 in the resistant cells. Moreover, sorafenib treatment effectively blocked FLT3 activation in resistant cells, whereas it was unable to block colony formation or cell survival, suggesting that the resistant cells are no longer FLT3 dependent. Gene expression analysis of sensitive and resistant cell lines, as well as of blasts from patients with sorafenib-resistant AML, suggested an enrichment of the PI3K/mTOR pathway in the resistant phenotype, which was further supported by next-generation sequencing and phospho-specific-antibody array analysis. Furthermore, a selective PI3K/mTOR inhibitor, gedatolisib, efficiently blocked proliferation, colony and tumor formation, and induced apoptosis in resistant cell lines. Gedatolisib significantly extended survival of mice in a sorafenib-resistant AML patient-derived xenograft model. Conclusion: Taken together, our data suggest that aberrant activation of the PI3K/mTOR pathway in FLT3-ITD-dependent AML results in resistance to drugs targeting FLT3. Introduction: Laparoscopic cholecystectomy is one of the most commonly performed surgical procedures. Despite this, the pattern of readmission to hospital following laparoscopic cholecystectomy is not well defined. This meta-analysis aimed to determine rates and predictors of readmission. Methods: An ethically approved PROSPERO-registered meta-analysis was undertaken searching PubMed, Scopus, Web of Science and Cochrane Library databases from January 2013-June 2018 and followed the PRISMA flow diagram format. Published literature potentially suitable for data analysis was graded using methodological index for non-randomised studies (MI-NORS) criteria; papers scoring ≥ 16/24 were included. The odds ratio (OR) using random-effects, Mantel-Haenszel method with 95% confidence intervals (CI) were computed for each potential risk factors using RevMan5. Results: 3,632 articles were reduced to 44 studies qualifying for a final analysis of 1,573,715 laparoscopic cholecystectomies from 25 countries. Overall readmission rate was 3.3% (range: 0.0%-11.7%); 52,628 readmissions out of 1,573,715 laparoscopic cholecystectomies performed. Surgical complications accounted for 76% of reported reasons for readmission, predominantly bile duct complications (33%), wound infection (17%) and nausea and vomiting (9%). Pain (15%) and cardiorespiratory complications (8%) account for the remainder. Obesity, single port laparoscopic cholecystectomy and day case laparoscopic cholecystectomy did not increase rates of readmission. Conclusion: Surgical complications are the most common causes for readmission, however causes are inconsistently reported. No statistically significant risk factors were identified. The mean readmission rate of 3.3% may act as a quality benchmark for improving laparoscopic cholecystectomies and clearer reporting of reasons for readmission may aid in their reduction.

Buddy operating within gynaecological oncology: a retrospective review of hysterectomies and associated outcomes Michael McLarnon, Medical Student [1], Lauren Christie, Medical Student [1] Mark McComiskey, Kelly Reilly [2] Nick Reid [1] School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Co. Antrim [2] Department of Gynaecology, Belfast City Hospital, Belfast, Co. Antrim, Northern Ireland
Introduction: Gynaecological laparoscopic surgery has evolved substantially in the last number of decades from its use in minimal diagnostic procedures to major operations. The Belfast Trust team of consultants decided to launch an initiative of 'Buddy Operating'a surgical procedure involving two or more consultant specialists-with the aim to demonstrate that Buddy Operating will have a positive impact on patient outcomes, specifically a reduction in cases involving major surgery; shorter post-operative length of stays and a reduction in intra-operative blood loss.

The functional effects of circular RNA HNF4a in colorectal cancer cells Fara I. Meor Faiza, MB, BCh, BAO Student [1], Norahayu Othman, PhD [2], Nadiah Abu, PhD [2], Nurul S. Ab Mutalib [2], A. Rahman A. Jamal, PhD [2] [1] School of Medicine and Medical Science, University College Dublin, Belfield, Dublin, Ireland D04 V1W8 [2] UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia 56000
Circular RNAs (circRNA) are a re-emerging type of non-coding RNA formed by covalent circularisation of pre-mRNA. It has been reported that cell lines and tissues from colorectal cancer (CRC), the third most commonly diagnosed cancer, show a global reduction in circRNA compared to normal colon mucosa. The hepatocyte nuclear factor 4-a (HNF4A) gene has also been linked to the progression of CRC and appear to regulate chemoresistance towards the FOLFOX regimen. Therefore, we postulate that the circular RNA version of the HNF4A gene may also play a role in CRC pathogenesis, particularly drug resistance. The objectives of this research were to (a) investigate the expression of circHNF4A in CRC cell line HCT116 and (b) investigate its effects on drug sensitivity to 5-Fluorouracil (5-FU) and Oxaliplatin. HCT116 was cultured and a secondary FOLFOX-resistant variant was induced through regular treatment with 5FU combined with oxaliplatin. Samples of each were transfected with circHNF4A siRNA to reduce its expression, then qPCR carried out to measure levels of circHNF4A in both non-transfected and transfected cells. Cell viability was assessed using the XTT assay, prepared with descending concentrations of 5FU and oxaliplatin. CircHNF4A expression was found to be low in parental cells and attenuated in the resistant counterpart. No circHNF4A readings were detected when siRNA-transfected, though sensitivity to both drugs slightly increased. circHNF4A may thus play a role in increasing CRC resistance to 5-FU and oxaliplatin, however, may not be a causative factor. Further optimisation and repeats are needed to confirm this conclusion.

Diagnosing colon cancer using CT colonography and neural networks JH Miao [1], KH Miao [1,2] [1] Cornell University, Ithaca, NY, USA 14853 [2] New York University School of Medicine, New York, NY, USA 10016
Introduction: Globally, colon cancer is the third most common cancer and is among the most deadly. In the United States, colon cancer is among the most common cancers, causing over 130,000 new cases and over 50,000 deaths annually. When diagnosed in early stages, it is curable with a 92% survival rate. Thus, early detection of colon cancer polyps can enhance the long-term survival outcomes of patients. Methods: Colonography, also known as virtual colonoscopy, is a detection method that involves CT scans to view the intestine internally and visualize polyps. In this research, to enhance the diagnostic accuracy of colon cancer using colonography, an artificial intelligence approach using neural network algorithms was used to analyze 794 images of clinical patient data and develop the computational model. For the training process, a random selection of 50% of the dataset was utilized, and the remainder 50% was used as the testing dataset to diagnose colon cancer. Results: Diagnosing colon cancer in patients, the developed neural network model achieved 87.78% accuracy based on the training dataset and 84.59% accuracy based on the testing dataset. Conclusion: Thus, the neural network models can be used in conjunction with CT colonography to help healthcare professionals with early detection and diagnostic accuracy of colon cancer in patients.

Skin cancer diagnosis and prognosis using deep machine learning KH Miao [1,2], JH Miao [1] [1] Cornell University, Ithaca, NY, USA 14853 [2] New York University School of Medicine, New York, NY 10016
Introduction: According to the World Health Organization, skin cancer is the most common kind of cancer, affecting over 3 million annually. Melanoma, a malignant skin cancer, causes more than 75% of skin cancer deaths. When detected at early stages, patients with melanoma have a five-year survival rate of 99%. Thus, early detection and diagnosis of melanoma is important for improving patient outcomes. Methods: Visually, melanoma can be difficult to distinguish from non-cancer skin lesions due to similarity in appearances. In this research, a computational model built using deep machine learning and clinical patient data is used to help healthcare professionals in early detection of skin cancers as well as enhancing consistency and diagnostic accuracy of melanoma from benign skin lesions. Clinical data, including 1,938 patients [364 melanoma, 1574 benign] from medical institutions, was used to build, train, and test the computational model. To train the model, 50% of the data was randomly selected and utilized while the remaining 50% of patient data was utilized for testing the melanoma prediction capabilities of the model. Results: In diagnosing skin cancer in patients, the machine learning model equipped with neural network algorithms was able to achieve an overall accuracy of 90.2% among the training group and 85.6% among the testing group performance results with the novel clinical patient data. Conclusion: Thus, models based on machine learning algorithms may be used to aid medical professionals for enhancing early detection and accuracy of skin cancer diagnoses in patients.

Using ultraviolet C light as a treatment method for pro-inflammatory cells in a perfusion system
Tess Montminy [1], Marcos Galasso [2,3], Allen Duong [2,3], Aadil Ali [2,3], Yu Zhang [2], Shaf Keshavjee [2,3,4] Introduction: Lung transplantation is a successful therapy for end-stage lung diseases. Ex vivo lung perfusion (EVLP) has increased organ utilization, expanding the donor pool. The Toronto EVLP technique uses a leucocyte filter as a scavenger, however it may not be effective throughout the entire treatment. Ultraviolet C (UVC) light has been shown to induce apoptosis in human lymphoid cells and is a realistic approach for leucocyte reduction in EVLP. Methods: Two mini-EVLPs were primed with perfusate from clinical EVLPs, and divided in two groups (n=5, each, for 3h): 1. UVC, 2. Control (no light). EVLP perfusate samples were also collected from standard and UVC-irradiated human EVLPs (n=3, each, for 5h). UVC was delivered with custom UVC illumination devices. Samples from both circuit types were taken at different time points and analysed using flow cytometry for cell population assessments, and ELISA to detect perfusate cytokines. Results: UVC-irradiated circuits had increased late apoptotic cells (233±73 vs. 111±7%) and decreased total live cells (71±16 vs. 98±12%) and neutrophils (45±26 vs. 138±73%). ELISA analysis showed reduction of IL-1, IL-6 and IL-8 over time in the UVC-irradiated circuits compared to control (IL-1= 37±33 vs. 50±27%, IL-6= 88±8 vs.101±3%, IL-8= 84±12 vs. 108±19%). Conclusion: This study depicts UVC as an effective approach to treat pro-inflammatory cells in a perfusion system, leading to cytokine decrease. This suggests that UVC light may offer a substitute to the traditional leucocyte filter during EVLP, potentially leading to better lung transplantation outcomes.

A clinical audit of xerostomia assessment and treatment practices amongst advanced cancer patients in a palliative care setting N Mukerji [1], C Kenny [2], D Walsh [2] [1] UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 [2] Academic Department of Palliative Medicine, Our Lady's Hospice & Care Services, Harold's Cross, Dublin 6W
Introduction: 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. 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. Methods: 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. Results: 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. Interrater reliability was high or perfect for all primary outcomes. Conclusion: 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 policy tools were amended to reflect patient care needs more accurately.

Inflammasome product IL-1β increases oligodendroglial lineage cell number and promotes their differentiation
Ger Mullan, Medical Student MRes [1], Marie Dittmer, PhD [1], Daniel Crooks, PhD Student [1], Denise C. Fitzgerald, PhD [1], Yvonne Dombrowski, PhD [1] [1] Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, BT97BL Introduction: The inflammasome is a multimeric protein complex that initiates immune responses to danger signals by releasing the cytokines interleukin-1β (IL-1β) and IL-18. Inflammasomes are thought to be involved in multiple sclerosis (MS), an immune-mediated, demyelinating disorder. Some studies have shown that inflammasome activity can promote CNS repair. We hypothesised that inflammasomes can be stimulated in CNS cells, and that inflammasome activity promotes oligodendrocyte progenitor cell (OPC) proliferation and/or differentiation. Methods: Mixed glial cultures were generated from wild-type (WT) and Il1r1 -/neonatal mouse brains. Cells were stimulated either with IL-1β to test glial response to inflammasome activity, or with inflammasome triggers to test endogenous inflammasome response in glial cells. Cells were then immunofluorescently stained for oligodendrocyte and inflammasome markers, respectively. Results: Glial cells mounted an inflammasome response upon danger signal sensing. The formation of putative ASC specks denoted inflammasome activation. IL-1β increased oligodendrocyte lineage cell (OLC) numbers, promoted OPC differentiation and increased myelin production in vitro, mediated via IL-1 receptor 1 (IL-1R1). Conclusion: Our results suggest a role for inflammasomes in glial cells, demonstrating that they can react both to danger signals via inflammasome activation, and to inflammasome products. Future work will investigate the impact of endogenous inflammasome activation on oligodendrocytes.

Investigating the therapeutic potential of cannabinoids on neuroinflammation in Alzheimer's disease Aoife Mulvagh BSc (Hons), Medical Student [1] [1] Conway Institute, University College Dublin, Ireland
Introduction: Alzheimer's disease is a neurodegenerative condition with an often-overlooked inflammatory component. Microglial cells are implicated here, with the activation of microglial toll-like receptors thought to play a major part. This study aimed to replicate the Alzheimer's-associated neuroinflammatory condition in vitro and investigate the therapeutic potential of cannabidiol (CBD). Methods: BV2 microglia and hippocampal HPL neurons were investigated using cell treatments, Western Immunoblot and Enzyme-Linked Immunosorbent Assays (ELISAs). BV2 microglia were treated with lipoteichoic acid (LTA) +/-amyloid beta (Aβ) +/-CBD. HPL neurons were treated with LTA +/-Aβ and with conditioned media (CM) from activated microglia to determine the impact of microglial-derived mediators on neuronal integrity. Results: Treatment of BV2 microglia with LTA and Aβ resulted in an increase in the expression of COX-2, iNOS and phospho-p38 and the release of IL-6 and TNF-α. These increases were attenuated with CBD treatment. HPL neurons treated with LTA and Aβ showed an increase in drebrin, syntaxin, PSD95 and phospho-ERK and a decrease in phospho-AKT. HPL treatments with CM had little impact on these proteins. Conclusion: In HPL neurons, LTA and Aβ treatment resulted in what was interpreted as an increase in cellular proliferation, dendritic growth and synaptic signalling. While experiments regarding HPL neurons stimulated with CM were inconclusive, the potential of CBD to reduce the inflammatory condition in BV2 cells in response to our stimulants was clear. CBD therefore appears to be a promising drug candidate in meeting the large unmet clinical demand in AD and its associated inflammatory condition.

, Karen Horsburgh [1], Jill Fowler [1] [1] Centre for Neuroregeneration, University of Edinburgh, Edinburgh, Scotland [2] School of Pharmacy, University of Wisconsin-Madison [3] UK Dementia Research Institute at the University of Edinburgh
Introduction: Stroke (cerebral ischemia) is a leading cause of death and disability. Two key pathophysiological mechanisms of ischemic brain damage are inflammation and oxidative stress. The transcription factor Nrf2 upregulates a battery of over 200 antioxidant and anti-inflammatory proteins. In vitro studies show that the neuroprotective effects of Nrf2 are dependent on glia, notably astrocytes. Moreover, preliminary studies show neuroprotection in mice that overexpress Nrf2 specifically in astrocytes (GFAP-Nrf2) after ischemic stroke. Methods: In the present study, we hypothesized that the neuroprotective effect observed in GFAP-Nrf2 mice after acute ischemic stroke was due to decreased oxidative stress and inflammation. The aim was to characterize the extent of oxidative stress (3-Nitrotyrosine) and gliosis (GFAP-reactive astrocytes and Iba-1microglia/macrophages) with immunostaining following acute ischemic stroke (60 mins of middle cerebral artery with 23-hour survival) or sham surgery in GFAP-Nrf2 mice and wild type (C57Bl/6J) mice (n= 7-15/group). Results: Ischemic stroke increased oxidative stress, assessed with 3-nitrotyrosine, however, there was a significant reduction in oxidative stress in GFAP-Nrf2 mice compared with WT mice. Reactive astrocytes were increased after ischemic stroke in the peri-infarct region and significantly increased in GFAP-Nrf2 mice compare to their WT counterparts. Ischemic stroke did not alter microglia/macrophages in GFAP-Nrf2 mice compared with WT mice. Conclusion: Therefore, Nrf2 overexpression in GFAP-astrocytes has neuroprotective effects due to the alleviation of oxidative stress following an ischemic stroke. There was no evidence that this neuroprotection was caused by reduced inflammation, however there were increased reactive astrocytes GFAP-Nrf2 mice following ischemic stroke.

] Department of Anatomy, Trinity College Dublin
Introduction: Considered the primary pathway of communication between bilateral hippocampi, the dorsal hippocampal commissure (DHC) crosses the midline on the lyra of the fornix. Numerous studies have been conducted on it in animals, however, there is a paucity of research in humans. Although it is recognised primarily to be the hippocampal commissure, animal studies have shown that most fibres are parahippocampal in origin. The purpose of this investigation was to determine which key limbic regions are connected by this commissure. Data has been correlated with age and gender. Another aim was to determine whether differences exist between its structure in the depressed and healthy cohorts. Methods: High-resolution T1, T2 and HARDI were used to scan 43 healthy controls and 31 depressed subjects. CSD was used to formulate tracts. After isolating the DHC using an anatomically derived protocol, volumes of various regions were used to calculate the proportion of fibres originating from each region. Results: In keeping with animal studies, the parahippocampal region is the primary site of origin of the DHC. There are significant reductions in volume and FA with age but no significant differences between the depressed and the healthy cohort. Conclusion: Our findings suggest that the parahippocampal gyrus may exert more influence on the human contralateral limbic system than previously thought, with consequences in how we conceive of limbic circuitry. Though there is no effect in depression, our technique and results may have implications for memory, clinical (Alzheimer's and other neurodegenerative diseases) and epilepsy research, as well as putative treatment.

An investigation into the effectiveness of the 'Hello My Name Is' campaign and its impact on doctor-patient relationships in St. James's Hospital, Dublin, Ireland Emily Nguyen, MB BCh BAO Student [1], Elva McCabe, MB BCh BAO Student [1] Maria Kane, BSN [2] [1] School of Medicine, Trinity College Dublin, Dublin, Ireland [2] Quality Improvement and Safety Directorate, St. James's Hospital, Dublin, Ireland
Introduction: The "Hello My Name Is" campaign was first established in 2013 by Dr. Kate Granger to remind hospital staff about the importance of introductions in healthcare. Current research highlights the importance of introductions in establishing rapport, which is essential to forming strong and successful therapeutic relationships. Strong patient-clinician communication has been associated with better health outcomes, reduced medical costs, and a decreased risk for malpractice claims. In June 2016, the campaign was launched in St.James's Hospital in Dublin. Objective: To determine whether the Hello My Name Is campaign has seen an increase in the number of healthcare workers introducing themselves to patients. A secondary objective will be to investigate the campaign's effect on communication between patients and staff within the hospital. Methods: The survey was carried out using convenience sampling and quantitative collection methods. A total of 199 participants (93 patients, 12 visitors and 92 staff) from nine randomly selected hospital areas in SJH were surveyed. Results: 44.64% (n=25) of patients who attended SJH before and after the campaign launch reported an improvement in the number of hospital staff introducing themselves. Since the campaign launch, 78.3% (n=78) of the 92 staff members surveyed said that they had made more of an effort to introduce themselves. 47.8% (n=11) of staff who either sometimes or never introduced themselves before the campaign launch, reported they now always introduced themselves to patients. Conclusion: The Hello My Name Is campaign proved to be effective in encouraging more staff to introduce themselves to patients.

An audit of proton pump inhibitor use in a primary care setting
Meadhbh Ní Fhlatharta, [1], Clodagh Buckley, [2], Michelle Quinlan, [2] [1] Graduate Entry Medical School, University of Limerick, Limerick, Ireland [2] Cedarville Medical Centre, Abbeyfeale, Limerick, Ireland Introduction: Proton pump inhibitors (PPIs) are one of the most frequently prescribed drugs in Primary Care. There has been a marked increase in PPI prescribing in recent years. PPIs have various associated side effects such as vitamin and mineral malabsorption, diarrheal illnesses and renal disease. Thus appropriate prescription is crucial for such a commonly prescribed drug with such side effects. Methods: This audit was carried out in a rural GP practice in Ireland (n=120). Aims of this audit included analysis of PPI administration in a general practice setting. Gender, length of treatment, PPI type, dosage and indication for treatment were recorded. Administered doses and length of treatment were compared to NICE guidelines of 2014. Results: Results showed that 73% of patients had a clinically appropriate indication for treatment, with 68% of those patients being prescribed an appropriate dose of PPI and 55% of those being on the PPI for an appropriate duration of time. These results were in line with similar studies carried out in similar settings. Conclusion: Inappropriate use of PPIs i.e. automatic prescription, renewal and/or inappropriate indications is a concern in healthcare in general. Considering the side effect profile and increased risk of polypharmacy, it is therefore important to be aware of this in prescribing PPIs and to taper off and/or discontinue treatment appropriately in practice. Due to the results seen in this audit but also results seen in published literature, further initiatives should be developed in terms of appropriate PPI prescription and also adoption of strategies for tapering-off of prescribed PPIs.  Introduction: In 2017, 7502 children were seriously burned or scalded in the UK. [1] It has been identified that a Core Outcome Set for burn care research is needed. [2] However, minimal research investigating how to involve children and identify what is important to them has been conducted. We aimed to develop a method to ensure the engagement of young people participating in the development of a Burn-specific COS. Methods: A literature review was carried out on Core Outcome Sets studies for children aged 0-18, on the COMET database. Studies were selected if they included a rating scale within the Delphi Study. This literature review was used to inform PPI and develop a survey. The survey was administered in a semi-structured interview to young people aged 10-16 years and their parents. It had two questions: which scale they preferred to use when rating importance, how they would like to receive feedback between rounds within the Delphi study. Results: The results of the literature review established that two main rating scales are used, a 1-5 rating scale and 1-9 rating scale. Feedback included graphs, numbers or both. The results from the PPI work was that young people and their parents prefer to rate using the 1-9 adapted traffic light scale and feedback preference was a 1-5 Likert scale presented graphically. Conclusion: Adaptations to Delphi Questionnaires for children should be made to ensure that they understand what is being asked and can participate in COS studies. Further work is needed to standardise methods in children.
Introduction: Aims and Objectives: Dialysis is indicated as the main avenue of treatment for patients suffering symptoms of End Stage Renal Disease. The identification of dialysis patients at the highest risk of mortality is essential for their subsequent care and management. To date, a comorbidity analysis on the Irish dialysis patient population has yet to be carried out with the burden of comorbidity and its effects on mortality still yet to be determined. The main objectives of this study were to: 1) Explore the differences in comorbid conditions among Irish patients undergoing dialysis 2) Determine the association of vascular access with mortality 3) Determine the association of each of these comorbidities with mortality Methods: Data from the National Kidney Disease Surveillance System was analyzed retrospectively using a cohort of chronic hemodialysis patients treated for at least 90 days between the 01 January 2015 and the 31 December 2016 (n=528). The primary outcome of interest was mortality with covariates of interest centered upon co-morbidities present in the sample population prior to dialysis initiation, and the method of vascular access used. Results: Patients were divided into groups according to their vascular access type at day 90 of incident dialysis. The patient's vascular access was divided into two categories -Central Venous Catheter (CVC) (n=401) and Arteriovenous Fistula (AVF) (n=127). Of the comorbidities compromising the sample population, Hypertension (56.06%), Diabetes (36.17%) and Atherosclerotic Heart Disease (16.67%) were the most prevalent across both the CVC and AVF groups. Between the two groups 89 deaths were recorded, 13 patients died in the AVF and 72 patients died in the CVC group out. The study revealed a mortality rate of dialysis patients in the Irish health system between the 01 January 2015 and the 31 December 2016 to be 16.85% (approximately 1 in 6 patients), higher in patients who received vascular access via a CVC than an AVF, increased in patients with a higher age and male gender, and was not significantly affected by the burden of comorbidityapart from peripheral vascular disease. Conclusion: This study was the first analysis into comorbidities and mortality in Irish haemodialysis patients, comparing AVF vs. CVC access to mortality in terms of comorbidity burden. It demonstrates the major comorbidities present in the Irish dialysis population and the variability of their effect on mortality. It highlights the necessity for future investigation in order to monitor the prevalence and effect of comorbidity on the Irish dialysis cohort. Community-Acquired Pneumonia (REMAP-CAP) which uses multiple interventions simultaneously to determine the most effective treatments for ICU patients with CAP. Methods: Embedded in the Irish Critical Care Clinical Trials Network, I conducted a qualitative stakeholder analysis to identify and map the key features of the REMAP-CAP trial. Data were collected through observation, analysis of trial documentation and six semi-structured interviews with essential personnel. Recurring themes and considerations were grouped and linked to specific stages of trial design. Results: The findings highlight the multitude of components and considerations required for the successful running of multisite trials like REMAP-CAP. Implicit but important considerations are; the implications of the novel trial design, multi-site variance in ethics and contracts, understanding within the consent process, staff engagement with the trial, randomisation and recruitment. Critical issues running throughout the trial process included time-sensitivity, feasibility of practical trial requirements, and communication between clinicians and sites. Conclusion: Each component of REMAP-CAP is fundamental to its overall success. Stakeholders involved at different levels and sites are often unaware of the range of components of a multi-site trial. This study will inform future trial stakeholders by providing a framework of key considerations for a multi-site trial thereby helping to optimise integration of clinical research into a pandemic response. Acknowledgement: PREPARE is an EU-FP7 funded network conducting inter-pandemic clinical research on infectious diseases (http://www.prepare-europe.eu/).

Do nutrient and health claims have an impact on the perceived healthiness and the amount of food consumed by adults on the island of Ireland? An experimental breakfast study
R Dharsshini [1], W Sinead [2], B Tony [3], S Michelle [3], D Moira [3], W Jayne [2] [1] Queen's University Belfast, Belfast, Northern Ireland [2] Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland [3] Institute for Global Food Security, Queen's University Belfast, Belfast, Northern Ireland

Introduction:
A previous study has demonstrated that when people thought they were eating a low-calorie milkshake (versus a high-calorie labelled equivalent though same product) their physiological satiety, as measured by the gut peptide ghrelin, was consistent with what they believed they were consuming rather than the actual nutritional value. The aim of the current study was therefore to replicate this experiment using a different type of food. Methods: On two separate occasions, participants (N=50) were asked to consume a 380 calorie yoghurt and granola breakfast product under the pretence that it is either a 500 calorie 'indulgent' breakfast or a 250 calorie 'sensible' breakfast . At each visit blood samples were collected at three time-points to measure acylated ghrelin. The blood samples were labelled baseline, anticipatory and after post-consumption. Participants were asked to complete self-reported appetite measures (visual analogue scales) 10 minutes prior to each blood sample. Results: From anticipatory to post-consumption participants reported a significantly higher mean change in self-reported fullness score for the 'indulgent' breakfast than the 'sensible' breakfast (p = 0.030). This relationship was not observed for the other self-reported appetite measures at any of the time points. Mean change in acylated ghrelin was not significantly different between the breakfasts at any of the time points.
Conclusion: This experimental study demonstrated an increase in self-reported fullness after consuming the 'indulgent' breakfast compared to the 'sensible' breakfast. A physiological response, however, was not observed as mean change in acylated ghrelin was not significantly different between the breakfasts.

Proteomic analysis of MYCN in neuroblastoma
Sian Roberts-Walsh, MB BCh BAO Student [1], Melinda Halasz, MD, PhD [1,2]  on BE(2)-C cells alone or in combination with aurora kinase inhibitors Tozasertib and alisertib was determined using microscopic phenotypic observation and cell death analysis by flow cytometry. Results: 96 proteins were identified as MYCN interactors in BE(2)-C cells. IPA identified that the MYCN binding proteins participate in mTOR signalling and regulation of the cell cycle. All tested mono-and co-treatments decreased proliferation and increased cell death compared to the control. Aurora kinase inhibitors increased differentiation more than Rapamycin alone and co-treatments more than mono-treatments. Alisertib and Rapamycin co-treatment (48.75%) increased cell death compared to Alisertib (36.6%) or Rapamycin (10.65%) alone while there was no marked difference between Toszasertib mono-and cotreatments. Conclusion: Targeting signalling pathways which orchestrate MYCN's oncogenic functions is an effective way to inhibit neuroblastoma growth. Further validation in pre-clinical trials is necessary to verify the synergistic potential of these new drug combinations. Acknowledgements: The authors would like to acknowledge funding from the Pathological Society of Great Britain and Ireland and the Wellcome Trust.

Hippocampal substructures: Changes over the normal human lifespan
Elena Roman, MB BCh BAO Student [1], Bernard Adegbemi, MB BCh BAO Student [1], Roisin King, MB BCh BAO Student [1], Caoimhe Gaughan, MB BCh BAO Student [1], Anurag Nasa, MB BCh BAO Student [1], Kirk Levins, MD, MSc [2], Denis Barry, PhD [3], Veronica O'Keane, MD, PhD [1], Darren William Roddy, MD, PhD [1,4] Introduction: The hippocampus is fundamental for human cognition, consisting of multiple interacting substructures working in concert deep within the medial temporal lobe. The hippocampus is vulnerable to changes during ageing, however, little is known about the alterations that occur within the substructures over the lifespan. Analysis of constituent substructures may yield more accurate information than the hippocampus as a whole. Neuroimaging advances allows for accurate delineation and volumetric quantification of these individual structures in vivo. The purpose of this study therefore is to examine the effect of age in these substructures under normal conditions. Methods: High resolution magnetic resonance imaging was carried out on 100 healthy participants ranging from 15 to 65 years. High resolution T1 and T2 MRI data was obtained and automatic hippocampal segmentation was achieved using the Freesurfer 6.0 image analysis suite. The generated hippocampal subfields, including cornu ammonis 1-4, dentate and subiculum, were subsequently analysed with respect to age. Results: Age and sex both had a significant effect on substructural volumes, with individual subfields changing over time, in particular reducing with age. Most substructures reduced linearly with age until dropping dramatically after age 60. Conclusion: These age related substructural volumetric changes show that the hippocampus is dynamic overtime at the microstructural level. As the hippocampus consists of many interacting circuits of combined substructures, these variations may effect memory, spatial awareness, and emotion over time. These findings can be used as a means of differentiation between normal age-related cognitive decline and neurodegenerative conditions such as Alzheimer's disease. To assess staff opinion on pregnancy loss alert symbols and the electronic record. 2. To determine how accessible information relating to stillbirth can be found on the electronic record by staff. Methods: A survey was distributed to staff in CUMH where opinions were sought on topics such as the teardrop symbol, the electronic record and staff opinion on the use of a specific alert symbol highlight stillbirth on the e-record. In addition, a retrospective chart review of the 2017 CUMH stillbirth cohort (28 women) was carried out. This involved identifying certain variables around risk factors in the chart, and quantifying how easy it was to extract this information Results: 92.9% of participants stated previous use of the teardrop symbol was extremely helpful in clinical practice and 96.8% stating that an alert symbol on the e-record would also be helpful. 55.5% of staff found specific information difficult to find on the e-record. For the chart review, 35.7% of charts had a generic alert symbol for end-of-life however, for 64.3% of these alerts it took greater than 20 clicks to access it. 14.3% of files were identified as still continuing a pregnancy, despite the pregnancy ending in a stillbirth in 2017. Conclusion: The introduction of a specific alert symbol would benefit clinical practice greatly as the current alert system is not working. There is a need for further education and training in navigating the e-record, so that important information can be easily sought out and to improve staff efficacy of care. Introduction: Vomiting is the forceful expulsion of gastric contents which may represent a complete or partial obstruction of the gastrointestinal tract, and, when bilious, should be assumed mainly to be due to intestinal obstruction (mechanical or functional) until proved otherwise. Possible causes are determined either from surgical or medical aspects. Accurate and swift workup of bilious vomiting is crucial as any delay or inefficiency in diagnosing may result in death of the patient. Therefore, the purpose of this review is to analyse and summate the current literature surrounding bilious vomiting in infancy and create a basic algorithm for its diagnostic workup. Methods: A literature search was performed using PubMed to find articles that investigated the strategies being employed to produce optimal workup for infants with bilious vomiting. Altogether, 194 articles were found, of which 174 articles were excluded and a total of 20 articles were included. Results: Upon appraising the articles in full detail, an algorithm was created as a basic guideline to the optimal workup on diagnosing bilious vomiting in infancy. The advantages, disadvantages and possible issues with respect to application of different imaging modalities are taken into account when producing the most appropriate workup. This includes findings in history taking and physical examination. The initial preferred methods of investigation apart from haematological and urine tests are Plain Abdominal Film (PFA) X-ray and ultimately, Upper Gastrointestinal Series (UGS). However, the use of abdominal ultrasound (US), and contrast enema are still useful in excluding certain differential diagnoses. Conclusion: Above all, UGS is deemed to be the gold-standard test to exclude the most important diagnosis of intestinal obstruction.

Depression, anxiety and quality of life in a palliative population: A comparative study across different settings -Community and hospital
Caoimhe Salmon [1], Leona O'Reilly [2,3], Eimear McMahon [4], Dymphna Waldron [2,3], Anne M Doherty [4] [1] School of Medicine, National Univerity of Ireland Galway [2] Department of Palliative Care, Galway University Hospital [3] Galway Hospice Foundation, Renmore [4] Department of Psychiatry, Galway University Hospital Introduction: Palliative care patients commonly experience fluctuating moods due to the nature of their diagnosis. Management plans prioritise keeping physical pain at bay, resulting in the patient's mental health being overlooked. Understanding adjustment and depressive disorders in this population better may be an important target for improved quality-of-life. Methods: Patients in the West of Ireland were approached in this ethically approved cross-sectional study. The scales used were Hospital Anxiety and Depression Scale (HADS), the short form of the Adjustment Disorder-New Module scale (ADMN-6) and the EQ-5D to measure quality of life. The HADS focuses on the patient's recent emotional responses experienced whereas the EQ-5D is a 5-item validated scale which explores functioning in activities of daily living and related quality of life. Results: Of all patients approached 30 agreed to participate in the study. Adjustment disorder-New module 6 (ADNM-6) highlighted 63.13% of patients whose situation was a burden to them. 52.63% of patients admit to 'supressing' their feelings with others while but only 15.79% of participants say they have withdrawn from friends and family. The Quality-of-Life questionnaire reported 42.11% of patients to be moderately depressed. Finally, when asked to rate their current health on a scale, a mean of 56 was obtained. Conclusion: Working with a sensitive and acutely ill cohort has its challenges. This pilot study will deepen our understanding of the psychological and overall care requirements of palliative care patients. The data collected suggests that end-of-life patients require mental health care to complement their physical management. Introduction: Breast cancer is one of the leading causes of death in women. Anti-endocrine therapies such as Tamoxifen are often used to treat it. However, 30% of them develop resistance, posing a significant challenge clinically. Early events in endocrine resistance are poorly understood. Previous work in this lab has identified SSEA1+ cells as drivers of tamoxifen resistance in ER+ breast cancer. It was found that these cells were not de novo resistant, but rather acquired this feature. This led us to asking ''Are ER+ breast cancer cells in additional tissue culture models and patient tissue samples de novo resistant or do they acquire their resistance to Tamoxifen therapy?'' Methods: Tissue culture and flow cytometry was performed on the T47D cell line in vehicle, estrogen and estrogen and Tamoxifen. The cells were subsequently stained with DCO and anti-SSEA1-APC to measure progress through the cell cycle with respect to SSEA1 marked sub-populations. Immunohistochemistry/Immunofluorescence was also performed using primary and secondary antibodies against SSEA1 and Ki-67. Results: Analysis of the T47D cell line confirmed the previous findings that SSEA1+ cells are not de novo resistant. Unfortunately, there was insufficient proliferation in ex vivo tumour samples to confirm or reject the hypothesis. Conclusion: This study has helped in understanding this particular cell type (SSEA1+)that drives endocrine resistance in breast cancer. RNA sequencing could further be employed to understand key genes that differ between SSEA1+ and SSEA-cell types which could potentially be used as biomarkers of prognosis or targets of therapy in the future. Introduction: Early satiety is a common symptom of cancer that is rarely recognised in medical practice and poorly elucidated in the literature. It is defined as the desire to eat with the inability to eat appropriate amounts due to premature fullness. The present review aims to highlight the clinical importance of early satiety and outline appropriate therapeutic treatment. Methods: A literature search was conducted on October 27, 2017 using EMBASE, CINAHL and SCOPUS to determine therapeutic management of early satiety in cancer. The search was limited to English language and peer-reviewed journals. Articles were screened in four stages by two reviewers. Results: Of 486 articles identified, 5 full-text articles were included comprising of 3 original articles and 2 reviews. Targeting central and peripheral mechanisms are key to symptom management. Peripherally acting prokinetics such as metoclopramide are considered first line therapy. Immunomodulators such as OHR118 and thalidomide have positive effects, however large randomised trials are necessary to validate these findings. Agents that target gastric accommodation such as clonidine, sumatriptan and sildenafil may also be useful. Centrally acting pharmacological agents affect hormones associated with digestion. Examples include: progesterone receptor agonists such as megastrerol acetate, cannabinoids that downregulate corticotropinreleasing hormone and ghrelin agonists. Conclusion: Overall, early satiety is an under-recognised but an important symptom in cancer. High quality studies outlining appropriate therapeutic management are not currently available, yet are necessary to establish standardised treatment protocols. Translational research is required to improve our understanding of early satiety and uncover novel therapies.

Investigating the effects of FTY270 and BAF312 in a mouse model of Alzheimer's disease
Eva G. Timmons [1], Kumlesh K. Dev [1] [1] Drug Development, Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland Introduction: Alzheimer's disease is a chronic neurodegenerative disease that results in deterioration of cognitive processes leading to memory, language, learning and behavioural dysfunction. Sphingosine-1-phosphate is a signalling sphingolipid that Introduction and Objectives: Hookup culture has normalized casual sexual encounters on college campuses. These sexual encounters are associated with increased risk of victimization. Sexual coercion is a form of sexual victimization that occurs at equal or higher rates than sexual assault. The objectives of this study were 1) determine the incidence of verbal sexual coercion within hook up culture and 2) improve the understanding of students experience of verbal sexual coercion. Methods: A sample of 208 undergraduate students at a mid-sized urban campus in the United States completed an online survey about their experience with two specific coercion scripts. Script 1: feeling pressure to go beyond your comfort zone in a hookup because the other person asked multiple times. Script 2: feeling pressure to go beyond your comfort zone in a hookup because the person expressed they had feelings for you. Results: Of the 208 participants, 63.5% had engaged in a hookup within the last 12 months. Of those participants 46% had experienced one or both verbal sexual coercion scripts. When asked how they felt after these hookups and how they would categorize them the majority of subjects did not feel positively (89.9%) yet categorized the hook up as normal (87.3%).

Potential regulation of glutamine synthetase levels by miR-21 in epilepsy
Lynch S [1], E Langa [2], N Connolly [2], GP Brennan [2], DC Henshall [2] [1] School of Medicine, University College Dublin [2] Dept of Physiology and Medical Physics, Royal College of Surgeons Ireland Introduction: A reduction in glutamine synthetase (GS) levels in astrocytes has been implicated in the pathogenesis of mesial temporal lobe epilepsy (MTLE) according to the glutamate hypothesis. The hypothesis infers that as GS is responsible for glutamate clearance and glutamate-glutamine cycling, seizures can occur as a result of the amplification of glutamatergic activity in the hippocampus. With growing understanding of the role of micro-RNAs (miRNAs) in post-translational modification and silencing of genes, we hypothesise that this may be the mechanism by which glutamine synthetase is reduced in patients with refractory MTLE. Methods: MiRNA target prediction results obtained from TargetScan, miRtarbase and microRNA.org were compared with miRNA found to be elevated in epilepsy in literature and in the epimirRNA database. Following this, miR-21 was identified as a possible target for the GLUL gene which encodes GS. QPCR and immunohistochemistry were performed on samples from a kainic acid mouse model and a human TLE patient to observe differences in the levels of GS, GLUL mRNA and miR-21 at different time points post-status epilepticus (SE), compared to a PBS-injected control. Results: Levels of both miR-21-5p and GLUL mRNA associated to the RISC complex increased at 72 hours post-SE. A quantitative Western Blot showed decreased levels of glutamine synthetase in the hippocampus, with lowest levels at 72 hours post-SE. Conclusion: As there appears to be a correlation between increased levels of miR-21 and decreased levels of GS in the hippocampus at 72 hours post-SE, miR-21 may play a role in downregulating GS and increasing glutamatergic signalling in the brain. Patients with medically refractory epilepsy may therefore benefit from treatment with a miR-21 antagomir which could block miR-21 from binding to GLUL mRNA, increasing expression of glutamine synthetase, preventing excessive epileptogenic glutamatergic activity.

Conflicts of Interest
The authors declare that they have no conflict of interests.

Authors' Contributions
NQ: Served as a planning committee member for the conference, negotiated sponsorship deals for the conference, invited speakers for the conference, assisted authors with their abstract submissions, drafted the conference abstract booklet, and gave final approval of the version to be published. SC: Served as a planning committee member for the conference, organised the judging panel for the conference, invited speakers for the conference, assisted authors with their abstract submissions, drafted the conference abstract booklet, and gave final approval of the version to be published. SL: Served as a planning committee member for the conference & UCD Medical Society Secretary, organised the judging panel for the conference, and gave final approval of the version to be published. ED: Served as a planning committee member for the conference & UCD Medical Society Treasurer, negotiated sponsorship deals for the conference, and gave final approval of the version to be published. TBY: Served as a planning committee member for the conference & UCD Medical Society Auditor and gave final approval of the version to be published.