2019 - Summer Student Poster Day

2019 SUMMER STUDENT

POSTER DAY

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Welcome to the 2019 Poster Day for the Summer Student Research Program. Each year we host this event to showcase unique and innovative research being conducted by undergraduate and medical students on the Oak Street campus over the summer.

The research community at BC Children’s Hospital provides students with a true ‘bench to bedside’ opportunity for research. Since the early 1990s, the Summer Student Research Program has provided 1,000+ undergraduate and medical students an opportunity to participate in research projects related to children’s and women’s health.

The diversity of the research here is remarkable. It is amazing to see the activities the students are involved with, including basic science, clinical and population health research. Poster Day provides a wonderful preview of the interdisciplinary work our students will pursue as they progress into their own careers as scientific and clinical investigators.

We are proud of the students here and we are pleased to be able to help them become leaders in their respective fields.

Sincerely, Ashley Biggerstaff, Sharon Yau and Laura Christensen Research Education Office, BC Children’s Hospital Research Institute

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2019 Summer Student Poster Day Thursday, July 25 Poster Presentations

Group 1 | 10:30 a.m. - 12 p.m.| Chieng Family Atrium Group 2 | 1:30 - 3 p.m. | Chieng Family Atrium Showcasing the outstanding work of summer students based on the Oak Street campus and their contributions to research.

Each participant has been assigned to one of 8 groups and will have 5 minutes to discuss their poster and up to 5 minutes for questions.

Awards Ceremony

3:30 p.m. | Room 2108, BC Children’s Hospital Research Institute Join us in celebrating the accomplishments of our colleagues and the positive impact of research taking place on the Oak Street campus. The award ceremony will feature the poster presentation awards.

The BC Children’s Hospital research community would like to acknowledge the following organizations for supporting training opportunities on the Oak Street Campus: BC Children’s Hospital Foundation Canucks for Kids Fund Michael Cuccione Foundation Community Child Health Endowment Research Themes: Childhood Diseases Healthy Starts Evidence to Innovation Brain, Behaviour & Development 3

Showingcasing excellence in our talented research community!

2019 Poster Participants Participant

Research Team

Abstract Title

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Azim Ahmed

Blydt-Hansen & Cote Research Teams Kobor Research Team

Lean Body Mass as a Quality of Life Predictor in Post Renal Transplant Pediatric Patients Determining sex-specific effects of food deprivation on the regulation of the foraging gene The role of the autistic gut microbiome upon the gut-brain axis and behaviours of Autism Spectrum Disorder Lights, Camera, Surgery! Video Resources Enhancing Healthcare Communication

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Clinical predictors of primary immune deficiencies: a systematic review Optimizing skin antisepsis for neonatal surgery

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Investigating Paul-Bunnell antigen specific tonsillar mononuclear cells as a link between Infectious Mononucleosis and Multiple Sclerosis Evaluation of a Clostridioides difficile Mouse Model for CDI studies The Use of Subjective Outcome Measures in the Orthopaedic Surgical Literature Home Sleep Monitoring as a Predictor of Clinically Assessed Risk of Obstructive Sleep Apnea Investigating the dynamics of infection and re-infection with murine cytomegalovirus (mCMV) in mice Challenges Faced by Families of Children with an Autoinflammatory Disease Integrated Vital Signs and Video Recording Effects of Maternal Folic Acid Supplementation on Offspring Metabolic Health Investigating the Role of STAT3 in Differentiation of Neonatal T helper 17 Cells Building better organoids: A novel strategy for enriching rarer epithelial secretory cell types

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Neeku Amanat

Francesca Bell Lewis Research Team Peters Catherine Binda, OPSEI Kimberly Nguyen & Prabhpreet Mangat Anna Branch Biggs Research Team Sophie Carr Mairead Cavinaw

Skarsgard Research Team van den Elzen Research Team

Azriel Chang

Steiner Research Team

Anjuli Chehil

Mulpuri Research Team

Aditya Chhabra & Nisha Mainra April Christiansen

Lee & Ansermino Research Teams Gantt & Citlali Marquez Research Team Tucker Research Team

Maria Clarissa Belen Benjamin Clayton Danielle Cohen

Dumont Research Team Devlin Research Team

Rachel Da Silva

Lavoie Research Team

Emily Davies

Vallance Research Team

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55 12 31 42 22 23 43 44 3

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Participant

Research Team

Selina Demetrick

Sly Research Team

Anand Dhatt Donson Dong Maria Fernanda Huicochea Munoz Hannah Foggin

Saman Fouladirad Elaine Fung Aziz Ghafoor Vivek Gill Josef Goetz Kavi Grewal Sanya Grover Emily Gubski Sabrina Hou Helen Hsiao Alex Hsu

Abstract Title

Investigating the Co-Stimulatory Effects of LPS and IVIg on FcgRIIIA Gene Variants Pike Research Team Geo-Spatial and Socioeconomic Predictors of Youth Self-Harm Hospitalizations in British Columbia Vanderwal Research Obsessive-Compulsive Disorder (OCD) in Children: A TaskTeam Based Functional Connectivity Study Wang Research Team Audit on the Effectiveness of Fetal Fibronectin to Predict Preterm Labor at BC Women’s Hospital Hutcheon Research Estimating population-level absolute risk reductions and Team numbers needed to treat for neonatal morbidity and mortality, for use in a decision aid for late preterm antenatal corticosteroids McDonald Research Transitioning of patients with hydrocephalus from pediatric to Team adult care in British Columbia: a mixed methods study Portales-Casamar Understanding the actual and perceived differences between Research Team Canadian research and quality improvement studies Yong Research Team Sexual Pain & Endometriosis: A Patient-Oriented Integrated Knowledge Translation Project Rassekh Research Team Hematopoietic Stem Cell Transplant Outcomes in Children Receiving Dexamethasone for Chemotherapy-Induced Nausea and Vomiting Devlin Research Team Maternal Exercise and Obesity During Pregnancy and Resultant Offspring Lipid Metabolism and Cardiac Remodeling Verchere Research Pancreatic hormone processing during the development of Team type 1 diabetes Lynn Research Team Uncovering Function of GRK5 in Mouse Pancreatic Beta-Cells Jacobson Research Characterization and Visualization of Enteric Organoids Team Giaschi Research Team Evaluating Visuomotor Coordination in Children with Amblyopia Woodward Research fMRI study of functional brain networks in three memory Team tasks in healthy participants Verchere Research Inducing tolerogenic dendritic cells using lipid nanoparticle as Team a potential therapy for type 1 diabetes

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Jocelyn Jia

Chan Research Team

Case study: changes in treatment over time for a pediatric patient with eosinophilic esophagitis in British Columbia, Canada

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Analisa Jia & Taylor Morrison

Kobor Research Team

A Deletion Variant of the Alpha2b-Adrenoceptor: Genetic Regulation of Emotional Conditioning

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Min Jung Kim

James Lim Research Team

Targeting the Leukemia Tumor Antigen CD47

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Participant

Research Team

Abstract Title

Page

Gurkiran K. Mann

Pike Research Team

Physician Engagement: Parent Education on the Period of PURPLE Crying

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Emma Keay

Blydt-Hansen Research Team van den Elzen Research Team

Pre-transplant clinical predictors of kidney allograft survival

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Effects of All-Trans Retinoic Acid on CD1d Expression and subsequent invariant NKT cell activation in Patients with Acute Promyelocytic Leukemia Unfolding the mRNA exportation process in the NHR-49 dependent oxidative stress response pathway Investigating the Role of a Conserved Rab5 Regulator in Selective Autophagy Can We Educate Workers Out of an Injury? A Systematic Review Natural Language Processing of Psychiatric Clinical Notes

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Evaluation of a digital triage platform in Uganda—a quality improvement initiative to reduce the time to antibiotic administration.

Sleep & Occupational Injuries: A Scoping Review Perspectives on a Type 1 Diabetes (T1D) Pediatric-to-Adult Transition Clinic in Vancouver, Canada Patient navigation: Exploring the terminology and conceptualization of services that connect children with Neurodisability and their families to needed supports: A Scoping Review Determining the incidence and severity of cognitive and emotional problems in pediatric idiopathic epilepsy using the NIH Toolbox From Beer-Pong to Vigilance-Pong. Communicating Similarities between Sleep Deprivation and Alcohol Intoxication Developmental Coordination Disorder in Preterm Infants: The Impact of Prematurity on Cerebellar Volume and Motor Deficits Stakeholder perspectives on adaptive clinical trials: a scoping review The incidence of strictures in paediatric eosinophilic esophagitis: a retrospective analysis Returning To School After Undergoing Pediatric Neurosurgical Procedures – Patient and Caregiver Perspectives Review of Iron Deficiency Guidelines in the Context of Iron Deficiency-Related Sleep/Wake-Behaviours

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Joshua Koentjoro Luxcia Kugathasan

Taubert Research Team

Anson Law

Conibear Research Team Pike Research Team

Jim (Zhang Hao) Li Esther Lin Victor Lee

Portales-Casamar Research Team Ansermino Research Team

Amanda Leong Catherine Lim

Ipsiroglu Research Team Amed Research Team

Grace Lin

Miller Research Team

Max Liu

Datta Research Team

Ruth Liu

Ipsiroglu Research Team

Alexandra Mackay

Zwicker Research Team

Tina Madani Kia

Murthy Research Team

Nikhail Mainra

Avinashi Research Team

Kheya McGill

Singhal Research Team

Scout McWilliams

Ipsiroglu Research Team

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76 15 77

35 67 27 68 36 79 37

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Participant Lindy Moxham

Research Team Kobor Research Team

Hanna Parmar

Tamber Research Team

Chantal Percival Anita Poon

Woodward Research Team Vallance Research Team

Jessica Que

Piper Research Team

Caleb Ritchie

Woodward Research Team

Brendil Sabatino

Taubert Research Team

Gabrielle Sanatani

Mulpuri Research Team

Olivia Scoten

Grunau Research Team

Sadaf Sediqi

Yong Research Team

Martina Stokes

Devlin Research Team

John Sung Gemma Tomasky

Portales-Casamar & Görges Research Teams Ipsiroglu Research Team

Kristin Vesely

Selby Research Team

Kendrew Wong

Chilvers Research Team

Jae Yun Lee

Shirley Zhi

Blydt-Hansen Research Team Schrader Research Team Maxwell Research Team

Kai Zhu

Lauder Research Team

Jeremy Zuo

Boelman Research Team

Sofía Zhang-Jiang

Abstract Title Investigating the sex-specific effects of the foraging gene on triglyceride levels Assessing the Quality of Systematic Reviews and MetaAnalyses in the Pediatric Neurosurgical Literature fMRI analysis of functional brain connectivity in two language tasks in schizophrenia Interleukin 37-SIGIRR interactions and their effects on intestinal epithelial cells The Impact of Probiotics on the Incidence and Severity of Necrotizing Enterocolitis in Preterm Infants Spatial patterns of BOLD signal activation useful for identification and classification of task-state functional brain networks Genetic dissection of an NHR-49 dependent oxidative stress response pathway in C. elegans Developmental Dysplasia of the Hip: Care Practices of Pediatric Orthopedic Surgeons in China Development of Internalizing Problems in Children Born Very Preterm: Cortisol and Parenting Nerve bundles and its associations with deep dyspareunia in endometriosis: Can a binary scoring system be useful for pathologists?

Repeated Neonatal Oral Sucrose Treatment Affects Growth and Insulin-Like Growth Factor-1 in Mice Perceptions of professional and lay users on trust of artificial intelligence for medical decision-making and risk prediction “Stroop Colour-Word Task”: Adaptation of a Clinical Test for a Game Setting Diagnostic Outcome of Muscle Gene Panel Testing in Patients with Suspected Neuromuscular Disorders MALDI-TOF for accurate hospital-based identification of Burkholderia cepacia complex Vaccine-associated de novo HLA antibodies in pediatric kidney transplant recipients: pathological or benign?

Cerebrospinal Fluid Metagenomics and Cytokine Profiling in Pediatric Patients with Central Nervous System Inflammation Targeting Centrosome Amplification in Aneuploidy Childhood Leukemia Perioperative multimodal analgesia, including intravenous lidocaine infusion, for pain management following idiopathic scoliosis correction surgery in children STXBP1.ca: The National Registry for STXBP1-Related Neurodevelopmental Disorders

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Finding a Poster Board Chieng Family Atrium

Room 2108 Patio Registration

Chan Centre for Family Health Education

Main Entrance

Reception

Refreshments

Morning Sessions: Posters are available for viewing from 10:30am - 12pm

Afternoon Sessions: Posters are available for viewing from 1:30 - 3pm

Session 01 - Basic Science | Poster Boards - #1 - 8

Session 05 - Basic Science | Poster Boards - #38 - 47

Session 02 - Clinical, Population Health & Health Services | Poster Boards - #9 - 18

Session 06 - Basic Science | Poster Boards - #48 - 56

Session 03 - Clinical, Population Health & Health Services | Poster Boards - #19 - 27 Session 04 - Clinical, Population Health & Health Services | Poster Boards - #28 - 37

Session 07 - Clinical, Population Health & Health Services | Poster Boards - #57 - 65 Session 08 - Clinical, Population Health & Health Services | Poster Boards - #66 - 74 *The drawing is intended for visual reference only and is not to scale

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Session #1

BASIC SCIENCE 10:30am - 12pm

Moderator: Dr. Martina Sundqvist Participants: Neeku Amanat Francesca Bell Peters Emily Davies Analisa Jia & Taylor Morrison Lindy Moxham Brendil Sabatino Martina Stokes Kendrew Wong

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Session #1 (Morning) | Poster Board #1 Neeku Amanat, Undergraduate Student, University of British Columbia Supervisors: Michael Kobor & Maria Aristizabal, Healthy Starts

Determining sex-specific effects of food deprivation on the regulation of the foraging gene Neeku Amanat, Maria Aristizabal, Marla Sokolowski, Michael Kobor

Our past experiences play an important role in shaping our present biology; however, the molecular mechanisms by which this occurs is still not well understood. Drosophila melanogaster is a powerful model system to understand these mechanisms by which experience gets under the skin. Here, the foraging gene (FOR) which contains four promoters and encode various isoforms of a cGMP-dependent protein kinase, is linked to the regulation of many physiological and behavioral phenotypes in a manner that is dependent on food availability. In addition, our lab found that FOR regulation is sex-specific adding an additional layer of complexity to understanding how experiences shape biology. We are interested in determining whether sex regulates the response timing to an experience, by measuring FOR promoter-specific mRNA levels by RT-qPCR following exposure to food deprivation. Using various time points, starting at one hour to eight hours of food deprivation, flies were subject to one of the five groups and RNA and protein were extracted. RT-qPCR was then performed to quantify the amount of transcript from FOR promoter 2 and 4. Overall, preliminary results revealed differences in the timing of the response between male and female flies for promoter 2 and promoter 4-derived transcripts. Future work will aim to understand the molecular mechanisms underscoring the response differences and whether these have lasting consequences for fly behavior and stress resistance. Our ultimate goal is to identify basic molecular mechanisms that function in the encoding of experience which may participate in human development and health.

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Session #1 (Morning) | Poster Board #2 Francesca Bell Peters, Medical Student, University of British Columbia Supervisor: Suzanne Lewis, Brain, Behaviour & Development

The role of the autistic gut microbiome upon the gut-brain axis and behaviours of Autism Spectrum Disorder Francesca Bell Peters, Sarah Redmond, Kristina Calli, Heather MacRitchie, Evica Rajcan-Separovic, William Mohn, Suzanne Lewis

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder affecting communication, behaviour, and social interaction. ASD is characterized by repetitive and restrictive behaviours and interests, and deficits with communication and social reciprocity. Although many contributing genetic and environmental components have been identified, the etiology of ASD is incompletely understood. Individual variation in symptom and behaviour indicates the opportunity for personalized treatment and earlier diagnosis.

Rationale: A common co-morbidity in children with ASD is gastrointestinal (GI) disturbances such as diarrhea, constipation, and abdominal pain. The prevalence of GI symptoms in ASD patients, along with the complex interaction between the gut and central nervous system (“the gut-brain axis�), has prompted investigation of the relationship between the gut microbiome and ASD. While particular microbes have been identified in dysbiosis, this relationship remains to be characterized and conflicting study results warrant further investigation. This project aims to analyze the differences in gut microbiome, metabolome, and proteome between autistic subjects and their neurotypical controls.

Design: In partnership with Microbiome Insights Co. we are using 16S rRNA gene sequencing and shotgun metagenomic sequencing to characterize the diversity and abundance of species in the gut microbiome with an integrated metabolic and functional analysis. The microbiomes, metabolomes and proteomes from 39 subjects will be analyzed (in partnership with Molecular You Co.) for over 1000 microbial species, 204 metabolites, and 137 proteins. We will relate these changes to the respective autistic phenotype, genotype and metabolic findings, and compare this to their neurotypical controls.

Future Directions: With insights gained from this project we hope to 1) develop a deeper and integrative understanding of the cause(s) of ASD by examining both genetic and environmental components, 2) obtain mechanistic insight into ASD at the levels of brain development towards identifying personalized treatments and 3) providing clinicians with earlier diagnostic tools.

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Session #1 (Morning) | Poster Board #3 Emily Davies, Undergraduate Student, University of Victoria Supervisor: Bruce Vallance, Childhood Diseases

Congratulations to Emily on receiving a BC Children’s Hospital Research Institute Summer Studentship

Building better organoids: A novel strategy for enriching rarer epithelial secretory cell types Emily Davies, Shauna Crowley, Kevin Tsai, Emily Gubski, Mariana Diaz Gomez, Xiao Han, Bruce Vallance

Background: The intestinal epithelium is composed of a single layer of cells and is crucial in the preservation of gut homeostasis. Intestinal epithelial cells (IECs) are responsible for a multitude of gut functions including nutrient absorption, mucus secretion and hormone production.

Recently, a novel in vitro system termed ‘organoids’ has been described where primary IECs are isolated and cultured as 3D ‘mini guts.’ These offer distinct advantages over cancerous cell lines due to their maintenance of epithelial microanatomy. However, current protocols generate organoids primarily composed of enterocytes and seldom contain rarer secretory IEC subtypes, which are responsible for the gut’s mucus and hormone secretion functions. Goblet cells, the most common of the secretory subtypes, produce mucins which form a barrier that coats and protects the underlying IECs. We hypothesize through manipulation of cell differentiation pathways, we can increase the prevalence of rarer IEC subtypes, such as goblet cells.

Methods: Murine organoids were derived from ileal, cecal and colonic crypts then IEC stemness or differentiation was induced through growth media modulation of the Wnt and Notch signalling pathways as well as extracellular matrix supplementation. Mature organoids were analyzed via flow cytometry and immunofluorescent staining to quantitate goblet cell incidence.

Results: Growth media induced differentiation had no significant effect on ileal organoids, however produced elevated expression of goblet cell markers (Muc2 staining as well as Aleuria aurantia lectin binding) in both cecal and colonic organoids. Notch inhibition produced increased expression of lysozyme, a Paneth cell marker, in all organoid sites. Manipulation of Wnt signalling enhanced organoid stemness as measured by Lgr5 and CD44 expression and differentiation of these ‘stem’ organoids led to a larger relative increase in secretory markers.

Conclusions: These preliminary results demonstrate that through manipulation of cell differentiation pathways we can increase the expression of rarer secretory IEC subtypes in our organoids. Future work will focus on elucidating the exact identity of the cell populations present in these differentiated organoids, optimizing this protocol for each IEC secretory subtype and applying these growth conditions to organoids derived from pediatric IBD patients.

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Session #1 (Morning) | Poster Board #4 Analisa Jia & Taylor Morrison, Undergraduate Students, University of British Columbia Supervisors: Michael Kobor & Sarah Moore, Healthy Starts

A Deletion Variant of the Alpha2b-Adrenoceptor: Genetic Regulation of Emotional Conditioning Analisa Jia, Taylor Morrison, Sarah Moore, Michael Kobor

Background: People emotionally respond to their social environments in a variety of ways; however, some can be more sensitive than others. Emotional responsivity to stimuli like physical touch, loud noises and rewards can lead to various levels of positive or negative responses. This emotional experience has been also applied to the contextual environment, ultimately leading to the formation of emotional memories. Individual differences in neural activity, including hyperactivity of the amygdala, correlate with emotional responsiveness and memory formation, which may be the result of a genetic predisposition.

Purpose: We sought to explore the genetic contribution to individual differences in emotional reactivity by studying the relationship between the alpha2b adrenoceptor (ADRA2b) deletion variant and emotional responsivity. We studied the correlation between genotype and emotional behavior to test whether carriers of the deletion are more likely to emotionally condition to the social environment compared to non-carriers.

Methods: Cornell university students were recruited to participate in a two-stage study, first completing a personal survey about their early life and behavioral attributes. Next, the participants were experimentally exposed in the laboratory to both rewards (monetary and pleasant physical brushing stimuli) and emotional stressors (popping noises emitted at an uncertain time internal). Rewards and stressors served as the unconditioned stimuli, which were paired in presentation to neutral faces (neutral stimuli). After repeated pairing, the neutral stimuli became conditioned stimuli, and elicit emotional responses themselves due to learned associations. Saliva samples were provided by the participants. The genomic DNA was extracted and genotyping was conducted via PCR followed by Pyro-sequencing.

Results: Data analysis will consist of statistical comparisons between genotype groups and respective levels of emotional conditioning from stage 2 conditioning procedures. The main outcome will be the relationship between emotional conditioning to positive and negative stimuli and the ADRA2b genotype.

Significance: We hypothesized that if carriers of the ADRA2b deletion show a stronger conditioning response compared to non-carriers, we will further support the function of the ADRA2b genetic variant on emotional responsivity. The results from this study will also give greater insight about the genetic predispositions that account for emotional responsivity among individuals.

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Session #1 (Morning) | Poster Board #5 Lindy Moxham, Undergraduate Student, University of Saskatchewan Supervisors: Michael Kobor & Maria Aristizabal, Healthy Starts

Congratulations to Lindy on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Investigating the sex-specific effects of the foraging gene on triglyceride levels Lindy Moxham, Maria Aristizabal, Michael Kobor

Men and women are plagued by different diseases through their lifespan. Understanding the causes and consequences of diseases can be complicated by the fact that males and females have differing life experiences. These differences can be in the form of lifestyle, environment, socioeconomic status, culture, and biology. The fly model allows us to study biological differences between the sexes.

FOR is a complex gene which encodes nine protein isoforms of a cGMP-dependent kinase (PGK). In Drosophila melanogaster, FOR is highly pleiotropic, being involved in feeding, locomotion, development, learning and memory, stress resistance, and metabolism. The mechanisms of how foraging affects these different phenotypes is not well understood; however, work from our lab has shown its regulation is sex-specific. We hypothesized that sex-specific differences in the regulation of FOR result in differences in metabolism between the sexes.

To determine the effects of FOR on fat metabolism, we quantified triglyceride and protein levels in the flies with and without FOR knockdown. Interestingly, preliminary results revealed FOR knockdown resulted in decreased triglyceride levels in males while having no effect on females, suggesting sex-specific roles for FOR in fat metabolism.

To better understand the role of FOR in metabolism, we will leverage mutants that increase and decrease FOR expression as well as pharmacological interventions that will activate PKG. In addition, we are interested in determining whether the effect of FOR is developmentally determined: a question we will answer by modulating FOR expression and activity in the fly juvenile form – the larvae. Ultimately, our goal is to understand the molecular mechanisms by which sex influences metabolism in men and women with consequences for disease.

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Session #1 (Morning) | Poster Board #6 Brendil Sabatino, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

Congratulations to Brendil on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Genetic dissection of an NHR-49 dependent oxidative stress response pathway in C. elegans Brendil Saabtino, Kelsie Doering, Stefan Taubert

Reactive oxygen species (ROS) are highly reactive by-products of aerobic respiration whose accumulation leads to oxidized proteins, lipids, and DNA. Oxidative stress, the build-up of ROS, plays a role in the pathogenesis of complex diseases such as cancer and diabetes; thus, understanding the molecular and cellular responses to this stress is of clinical importance. Oxidative stress responses are highly conserved across species. The nematode worm Caenorhabditis elegans is a well-studied, easily tractable model system with a fast generation time, and the wealth of tools available make it ideal for dissection of oxidative stress response pathways.

In C. elegans, SKN-1 is the master regulator of the oxidative stress response; however, evidence for parallel pathways exists. The response to the organic peroxide tert-butyl hydroperoxide (tBOOH), an oxidative stressor, is largely SKN-1 independent. Our lab determined that NHR-49 is essential for the SKN-1 independent response to tBOOH, but other genes that act in concert with NHR-49 to promote oxidative stress adaptation are not known. To map this novel response pathway, we have designed a reverse genetic screen using the GFP reporter tagged to the promoter of the highly tBOOH inducible flavin monooxygenase 2 (fmo-2) gene as a read out.

Using RNAi, I am knocking down the transcription factors and kinases in the C. elegans genome to determine if there is altered expression of fmo-2 following tBOOH exposure (by observing fluorescent intensity). Of the approximately 300 kinases and 800 transcription factors screened 16 and 81 respectively were able to alter expression of our reporter. The nuclear hormone receptor and homeobox factor families were enriched within this set. Oxidative stress survival assays are being performed with deletion mutants of genes identified by RNAi to assess functional relevance. From this, we will identify other players acting in this novel NHR-49-dependent oxidative stress response pathway, and these newly identified proteins may serve as future therapeutic targets to increase quality of life for those with a variety of different conditions.

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Session #1 (Morning) | Poster Board #7 Martina Stokes, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

Repeated Neonatal Oral Sucrose Treatment Affects Growth and InsulinLike Growth Factor-1 in Mice Martina Stokes, Cynthia Yamika Ramirez-Contreras, Ei-Xia Mussai, Alejandra M. Wiedeman, Arya Mehran, Melody Salehzadeh, Nicha Boonpattrawong, Manon Ranger, Kiran Soma, Liisa Holsti, Angela M. Devlin

In Canada, nearly 53% of preterm infants (<37 weeks of gestation) are admitted to the Neonatal Intensive Care Unit where they may experience between 8-16 painful procedures per day. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief, and approximately 0.5-2mL of a 24% sucrose solution is administered orally prior to each painful procedure. Preterm infants spend on average 10-41 days in the NICU and could receive cumulative amounts of sucrose throughout hospitalization. To this date, it is not known whether repeated neonatal oral sucrose treatment would affect growth or glucose homeostasis given that many epidemiological studies have linked sucrose consumption with obesity and diabetes. The aim of this study was to determine the long-term metabolic effects of neonatal sucrose using an animal model.

Neonatal male and female mice were randomly assigned to one of five groups (n=6-10 mice/group/sex). The groups were as follows: sham (only handled), sterile water, sucrose, fructose, or glucose. They were treated 10 times per day for the first six days of life with 0.2g/kg weight of respective treatments orally (1-4 Îźl/dose; 24% solutions), as preterm infants typically receive. Mice were then weaned onto a control diet at 3 weeks until euthanasia at 16 weeks. After treatment, we found that neonatal sucrose treatment affects growth in female mice, likely involving insulin-like growth factor 1 (Igf-1). They gained less weight when compared to watertreated mice (15.4 +/- 1.60 vs 17.4 +/- 1.90g) and had shorter tibia length (15.9 +/- 0.35 vs 16.67 +/- 0.24mm).

The serum Igf-1 was significantly lower than the water group at 16 weeks (378 +/- 98.0 vs 661 +/- 196ng/ ml). In male mice, growth was not affected by sucrose treatment. However, Igf-1 plasma levels were lower in sucrose treated mice compared to sham mice (401 +/- 143 vs 641 +/-165 ng/ml). Due to the sex difference and significant results in female mice, ongoing work will be performed to further investigate the pathway involved.

Our findings suggest that repetitive neonatal sucrose treatment may negatively affect growth in females through a pathway dependent on Igf-1.

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Session #1 (Morning) | Poster Board #8 Kendrew Wong, Undergraduate Student, University of British Columbia Supervisor: Mark Chilvers, Childhood Diseases

Congratulations to Kendrew on receiving a BC Children’s Hospital Research Institute Childhood Diseases Summer Studentship

MALDI-TOF for accurate hospital-based identification of Burkholderia cepacia complex Kendrew Wong, Suk Dhaliwal, Jocelyn Srigley, Peter Tilley, James Zlosnik, Mark Chilvers

Background: Cystic fibrosis (CF) is a genetic disorder that results in the thickening of mucus lining airway epithelial cells, making individuals more susceptible to bacterial lung infections. Burkholderia cepacia complex (Bcc) bacteria, comprised of 24 closely related species, are responsible for serious and difficult to treat infections in CF. Identifying Bcc bacteria to the species-level is crucial to understanding epidemiology, implementing infection control, and determining clinical outcomes. Matrix-assisted laser desorption ionizationtime-of-flight mass spectrometry (MALDI-TOF) is a rapid method recently introduced in clinical laboratories for accurate bacterial identification. Currently, no study has evaluated the ability of MALDI-TOF to distinguish between all 24 species of Bcc. Purpose: The aim of this project was to establish the accuracy of MALDI-TOF at BC Children’s Hospital (BCCH) in identifying the different Bcc species.

Methods: 100 Bcc isolates composed of different representatives from each of the 24 species were chosen. To select the most genetically representative isolates for capturing maximum inter-species variation, sequences for isolates within a given species were obtained from the PubMLST database, aligned via MAFFT, processed through RaxMLHPC, and clustered using k-medoids.

An isolate was chosen from each cluster, subcultured, and run through the Bruker Daltonik Microflex LT instrument in duplicate using MALDI Biotyper RT software. Identification at the genus and species-level was achieved when the best species match had an overall score of ≥2.0 and a score difference of ≥0.2 from the next best species match as per BCCH guidelines. The result of a given isolate was compared to an existing identity obtained through recA gene sequencing, the current gold standard for Bcc species identification.

Results: At the genus-level, 98.6% of identities outputted by MALDI-TOF were concordant with existent recA identities; however, only 19.7% of the isolates were correctly identified to the species-level. Species which were consistently misidentified included B. arboris, B. contaminans, B. pseudomultivorans, B. stagnalis, B. territorii, and B. ubonensis. In many, but not all, cases of species misidentification, a representative library for that species was lacking.

Conclusion: Currently, MALDI-TOF does not permit accurate species-level identification of all Bcc bacteria.

Further library development, which are the next steps of this project, may improve this.

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Session #2

CLINICAL, POPULATION HEALTH & HEALTH SERVICES 10:30am - 12pm

Moderator: Dr. Jim Potts Participants: Anna Branch Sophie Carr Anjuli Chehil Jocelyn Jia Jim (Zhang Hao) Li Catherine Lim Hanna Parmar Sofia Zhang-Jiang Kai Zhu Jeremy Zuo

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Session #2 (Morning) | Poster Board #9 Anna Branch, Medical Student, Western University Supervisor: Catherine Biggs, Healthy Starts

Congratulations to Anna on receiving a Canadian Society of Allergy and Clinical Immunology Summer Studentship & BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship

Clinical predictors of primary immune deficiencies: a systematic review Anna Branch, Bhavi Modi, Kyla Hildebrand, Stuart Turvey, Catherine Biggs

Background: Primary immunodeficiencies (PIDs) are a group of genetic disorders that affect the development and/or function of the immune system, predisposing patients to infection, cancer, autoimmunity, and inflammation. Early diagnosis is key to prevent severe, life-threatening infections and end-organ damage.

Clinical tools are needed to aid clinicians in identifying patients who may have an underlying PID. This work performs a systematic review of the literature to identify features shown to distinguish PID patients from nonPID controls.

Methods: We searched PUBMED and WEB OF SCIENCE databases for studies describing clinical features predictive of or associated with PIDs. The results were screened and excluded if they were studying disorders other than PIDs, the sample size was <20, they lacked clinical information, or they were case reports or review articles. Studies were included only if they had quantifiable data comparing human PID cases to non-PID controls.

Results: 5485 articles were identified, 1060 abstracts screened, and 8 articles were included in the final analysis. The following features were found to be predictive of PID: absolute lymphopenia or CD3+/CD4+, CD19+, or CD16+/CD56+ subsets below the 10th percentile, hypogammaglobulinemia, neutropenia, immune thrombocytopenia, splenomegaly, enteroviral or respiratory tract infections, serious bacterial, persistent fungal, or recurrent deep-seated infections, chronic diarrhea, failure to thrive/growth retardation, family history of PID, parental consanguinity, sibling death, need for IV or prolonged courses of antibiotics, immunodeficiency related score>6 (a clinical scoring system of immunodeficiency-related conditions), history of hospitalization, recurrent viral infections or atopy in adulthood, autoimmunity in childhood, and adolescent presentation of recurrent/frequent infections.

Conclusion: Combinations of clinical features can be used to detect PID patients, and this work identifies features that have evidence supporting their use. Future work will aim to integrate these features into a clinical scoring tool that will be validated in a patient cohort at BC Childrenâ&#x20AC;&#x2122;s Hospital.

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Session #2 (Morning) | Poster Board #10 Sophie Carr, Medical Student, University of British Columbia Supervisor: Erik Skarsgard, Evidence to Innovation

Congratulations to Sophie on receiving a UBC Faculty of Medicine Summer Studentship

Optimizing skin antisepsis for neonatal surgery Sophie Carr, Erik Skarsgard

Background: Preoperative skin antisepsis is routinely performed to reduce the risk of surgical site infections (SSIs). Povidone-iodine has been the antiseptic of choice for decades; however, a growing body of evidence in adults suggests that alcohol-based chlorhexidine solutions provide superior protection against SSIs. Equivalent data does not exist for the neonatal surgical population, but literature on skin antisepsis for invasive nonsurgical procedures in neonatal intensive care units (NICUs) and for prevention of newborn nosocomial infections in developing countries suggests that chlorhexidine antisepsis is safe and non-inferior to povidoneiodine in reducing hospital acquired infections.

Objective: To assess the safety (avoidance of skin injury) and effectiveness (avoidance of SSIs) of preoperative skin antisepsis with chlorhexidine-alcohol in neonates undergoing abdominal and thoracic surgery.

Methods: Our target population will include general surgery patients in the NICU at BC Women’s Hospital (BCWH) older than 30 weeks post conceptual age. Patients with known allergies to chlorhexidine gluconate (CHG) or isopropyl alcohol (IPA), open wounds, or mucosal surfaces in the prep area will be excluded. Patients will be prepped with one of two CHG-IPA formulations (2% CHG – 70% IPA or 0.5% CHG – 70% IPA) and skin integrity assessments will be performed pre- and post-application. Using BC Children’s Hospital (BCCH) data from the American College of Surgeons National Surgical Quality Improvement Pediatric Program, an analysis will be performed comparing pre- and post-implementation data to assess incidence of adverse skin reactions and SSIs. Expected Outcomes: This project will: 1) engage stakeholders from BCCH and BCWH in neonatal surgical quality improvement work, and 2) inform the development and implementation of a neonatal surgical skin preparation protocol that can be applied across surgical subspecialties to standardize practice and improve clinical outcomes (specifically reduce SSIs).

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Session #2 (Morning) | Poster Board #11 Anjuli Chehil, Medical Student, Royal College of Surgeons, Ireland Supervisor: Kishore Mulpuri, Evidence to Innovation

The Use of Subjective Outcome Measures in the Orthopaedic Surgical Literature Anjuli Chehil, Eva Habib, Emily Schaeffer, Kishore Mulpuri

Background: Outcome measures are of paramount importance in generating high quality evidence across medical literature. Objective clinical outcome measures explicitly compare results within or across studies. In spite of this, appropriate outcome measures are far less clear to identify in orthopaedic surgical literature, and it is not uncommon to see subjective outcomes used as surrogates for objective clinical outcomes. Prevalent use of subjective outcome measures can impact study quality and strength of the evidence while also creating issues with cross-study comparison or meta-analyses.

Purpose: The purpose of the study was to review the orthopaedic surgical literature to assess the prevalence and frequency of subjective outcome measures used as surrogates for objective outcome measures.

Methods: A review of orthopaedic surgical literature published in 2018 was conducted. In order to be eligible for inclusion in the study, articles must have been published in either The Journal of Bone and Joint Surgery or The Bone and Joint Journal. Articles categorized as basic science or case studies were excluded. All collected data was recorded using Microsoft Excel and classified based on criteria such as article title, article type, perceived use of subjective outcomes, primary outcomes, and survival analysis.

Results: Out of the 402 articles reviewed, 87, or 21.6% displayed subjective outcomes including revision surgery, complications, infection, or need for re-operation. Out of those 87 articles, complications, found 37 times and infection, found 31 times, were especially prevalent as subjective outcome measures.

Significance: This study is ongoing, but has taken an important first step in demonstrating that a number of articles in the orthopaedic surgical literature continue to use and rely on subjective outcome measures.

It also identifies how surgeon decision-making correlates with an increased use of subjective outcome measures. Further steps must be taken to minimize the use of subjective outcome measures as surrogates for objective clinical measures in order to strengthen evidence in orthopaedic surgical literature. This initial pilot has indicated that an in-depth systematic review of the literature is required to further identify the use of surrogate outcome measures.

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Session #2 (Morning) | Poster Board #12 Jocelyn Jia, Medical Student, University of Toronto Supervisor: Edmond Chan, Childhood Diseases

Congratulations to Jocelyn on receiving a BC Children’s Hospital Research Institute Summer Studentship

Case study: changes in treatment over time for a pediatric patient with eosinophilic esophagitis in British Columbia, Canada Jocelyn Jia, Lianne Soller, Vishal Avinashi, Elaine Hsu, Hin Hin Ko, Edmond S. Chan

Eosinophilic esophagitis (EoE) is a chronic allergic- and immune-mediated condition increasing in incidence in developed countries. Symptoms are often nonspecific and vary with age. Untreated, patients are at risk for long-term adverse events including esophageal fibrosis and strictures, which may require invasive procedures like esophageal dilation to remedy. Current treatment includes dietary options as well as swallowed topical medications. This case study of a longstanding (8 visits; 2012-2018) patient seen in the EoE clinic at BC Children’s Hospital (BCCH) will describe how treatment changed over time for a patient with multiple clinical visits.

We describe a medically complex 14-year-old male diagnosed with EoE at age 3, with a past history of atopic dermatitis, gastroparesis, constipation, developmental disorder, opposition defiant disorder, and attentiondeficit/hyperactivity disorder. He was previously followed by a non-EoE clinic physician and treated with swallowed fluticasone, a proton-pump inhibitor (PPI), oral viscous budesonide (OVB), and empiric milk elimination.

Upon initial presentation to the EoE clinic at age 8, the patient was taking OVB and was no longer symptomatic, but had ≥53 eosinophils/high powered field (eos/hpf) on esophageal biopsy. OVB was discontinued and dietary treatment initiated, primarily consisting of an elemental diet delivered through an NG-tube, with only fruits, vegetables, and potatoes consumed by mouth. This approach led to histological improvement (≤23 eos/hpf) 3 months later. A referral was made for G-tube insertion, and dietary advancement was recommended. The patient tolerated a G-tube delivered elemental diet, supplemented by oral intake of rice, fruit, vegetables, and wheat, resulting in further histological improvement (≤9 eos/hpf). However, feeding refusal, difficulty swallowing, and abdominal pain led to an increased reliance on elemental formula by the fourth clinic visit.

Medications including OVB and a PPI were added in addition to the dietary treatment in hopes of leading to symptomatic and histological improvement; however, neither were achieved.

This case study highlights an approximate progression from medication to dietary treatment, followed by a combination of the two, as the patient became older. A quantitative study is currently underway to look globally at our EoE Registry (190 participants) to describe associations between treatment choice and patient age.

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Session #2 (Morning) | Poster Board #13 Jim (Zhang Hao) Li, Medical Student, University of British Columbia Supervisor: Ian Pike, Evidence to Innovation

Congratulations to Jim on receiving a UBC Faculty of Medicine Summer Studentship

Can We Educate Workers Out of an Injury? A Systematic Review Jim Li, Jennifer Smith, Max Pang, Colleen Pawliuk, Alex Zheng, Ian Pike

Background: Occupational injuries represent a tremendous burden to society. In BC alone, there were over 150,000 workplace injuries and 158 deaths in 2017, representing over $1 billion in claims. The costs are far more than economical -- each injury or death represents a unique story of suffering and many quality years of life lost. Educational interventions are a common method to prevent injuries, however, ethical considerations limit study designs that permit a causal link to be made between education and injury outcomes.

Objectives: To determine the effectiveness of educational interventions on preventing acute unintentional workplace injuries among adult workers.

Search Methods: The databases MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, and NIOSHTIC were searched along with sources of grey literature such as ProQuest, NDLTD, WorldCat Proceedings, WorldCat PapersFirst, Clinical Trials, Google, and Google Scholar for theses, registered clinical trials, and conference abstracts. We also checked the reference lists of relevant literature to identify potential studies for inclusion.

Selection Criteria: Relevant papers must evaluate changes in occupational injury rates following an educational intervention. There are no restrictions on industry or type of injury. Owing to the logistic and ethical challenges to implementing controlled trials in real-life work situations, we included all randomized controlled trials (RCTs), non-randomized controlled trials, interrupted time studies, historically controlled studies, and uncontrolled before-and-after studies.

Preliminary Results: We included 41 studies in our systematic review. Preliminary analyses reveal that the median percent reduction of occupational injury rate by educational interventions is 36.5% with an interquartile range of 16.6%-51.7%.

Conclusions: Overall the quality of evidence is variable. There is a need for more studies that implement education alone, as opposed to in combination with confounding interventions. Studies that focus on industries other than agriculture, mining, construction, and manufacturing would be an important next step in exploring the effects of educational interventions on underrepresented industries.

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Session #2 (Morning) | Poster Board #14 Catherine Lim, Medical Student, University of British Columbia Supervisors: Shazhan Amed & Joseph Leung, Evidence to Innovation

Congratulations to Catherine on receiving a Canucks for Kids Fund Childhood Diabetes Laboratories Summer Studentship

Perspectives on a Type 1 Diabetes (T1D) Pediatric-to-Adult Transition Clinic in Vancouver, Canada Catherine Lim, Joseph MWS Leung, Tricia S Tang, Shazhan Amed

Background: Type 1 Diabetes (T1D) is a chronic disease characterized by autoimmune destruction of insulinsecreting pancreatic beta cells. Recently, there has been increasing recognition of the specific health risks associated with adolescents (ages 10-18) and emerging adults (ages 18- 25) with T1D. Deterioration in metabolic control and disengagement with healthcare have been well documented at the time of transition to adult care. This may lead to increased microvascular complications, hospitalizations, and mortality. To address these issues, numerous T1D pediatric-to-adult transition models have been proposed, however the most effective model remains unclear.

Objective: To obtain perspectives of the pediatric-to-adult transition in T1D care from adolescents, young adults, parents, and healthcare providers in BC, to provide evidence for formulating and implementing a T1D transition clinic affiliated with BC Children’s Hospital (BCCH).

Methods: In this mixed methods study, we conducted eight focus groups with adolescents/ young adults aged 16-35 (n=38), two focus groups with parents (n=10), and semi-structured interviews with healthcare professionals (n=16). In addition, participants completed a demographics form and a Transitions Intervention Survey, where they rated each transition intervention on a 10-point Likert scale. Audio recordings were transcribed, qualitative data was analyzed using the grounded theory approach, and survey results were tabulated. NVivo 12 was used for thematic content analysis.

Results: Major qualitative themes included financial difficulties, lack of psychosocial support, and stigma surrounding T1D self-care behaviours. The most appealing interventions identified in the Transitions Intervention Survey were (mean score ± SD): mental health resources (9.07±0.91), identifying a suitable adult care provider (8.97±0.99), and re-booking missed appointments (8.95±1.69).

Conclusion: Diabetes stigma and failure to understand the unique challenges of emerging adults may be detrimental to the mental and physical health of youth with T1D. A transition model that emphasizes and normalizes mental health resources may address the multi-faceted and very personal challenges associated with T1D transition and hopefully facilitate a successful transition to adult care.

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Session #2 (Morning) | Poster Board #15 Hanna Parmar, Medical Student, University of British Columbia Supervisor: Mandeep Tamber, Evidence to Innovation

Congratulations to Hanna on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship

Assessing the Quality of Systematic Reviews and Meta-Analyses in the Pediatric Neurosurgical Literature Hanna R. Parmar, Alexander Cheong, Mandeep S. Tamber

Background/Purpose: There has been a proliferation of systematic reviews (SRs) and meta-analyses of healthcare interventions. These articles inform evidence-based clinical and policy decisions; therefore, it is important to be able to reliably identify high-quality reviews. AMSTAR (A MeaSurement Tool to Assess systematic Reviews) was developed in 2007 as a standardized tool to assess the quality of SRs that include only randomized trials of interventions. A prior AMSTAR-based review of SRs in the neurosurgical literature demonstrated variable but overall poor quality. Unfortunately, only two pediatric neurosurgical SRs were assessed in this review. Moreover, the original AMSTAR criteria were inappropriate for the assessment of neurosurgical SRs, since they often also include non-randomized intervention studies. AMSTAR 2, developed in 2017, enables the assessment of SRs that include both randomized and non-randomized studies. The purpose of our study was to gauge for the first time the methodological quality of pediatric neurosurgery SRs and metaanalyses published over the last 20 years.

Methods: A comprehensive PubMed/MEDLINE search yielded 582 results. Two authors (H. R. P. and M. S. T.) screened abstracts and are assessing 204 full-text articles for eligibility. They will then independently use AMSTAR 2 to generate an overall score and quality rating (high, moderate, low or critically low) for the eligible articles. Mean AMSTAR 2 scores will be compared for articles based on the time period of publication (20002013 and 2014-2019) using an independent sample t-test, and the proportion of high quality reviews in each time period will be compared using the chi-squared test. A kappa coefficient for inter-rater agreement will also be calculated.

Expected Results: We hypothesize that the methodological quality of SRs and meta-analyses in the pediatric neurosurgical literature has improved over time.

Significance: This is the first study that will appropriately assess the methodological quality of SRs in the pediatric neurosurgical literature and whether novice and experienced raters agree on the quality of a SR.

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Session #2 (Morning) | Poster Board #16 Sofia Zhang-Jiang, Medical Student, University of British Columbia Supervisor: Dewi Schrader, Brain, Behaviour & Development

Congratulations to SofĂ­a on receiving a UBC Faculty of Medicine Summer Studentship

Cerebrospinal Fluid Metagenomics and Cytokine Profiling in Pediatric Patients with Central Nervous System Inflammation Sofia Zhang-Jiang, Conrado De Guzman Jr, Maksim Parfyonov, Millan Patel, Maryam Nabavi Nouri, Manish Sadarangani, Peter Tilley, Dewi Schrader

Background: Encephalitis, inflammation of the brain parenchyma, is associated with significant morbidity and mortality. The infectious etiology of encephalitis is diverse, and no cause is identified in over half of the patients despite a full clinical workup. Currently, identification of infectious agents relies on traditional targeted diagnostic tests, such as PCR of cerebrospinal fluid (CSF). A new unbiased screening technique called metagenomics has recently emerged. Metagenomics entails sequencing the total genetic material from a sample to identify any microorganism present and overcomes the limitations of traditional tests by allowing the identification of novel or unexpected microbes, as having prior suspicions about the type of etiologic agent is unnecessary. This enables consolidated molecular testing of most pathogens and thus is more time- and resource-efficient.

Objective: We will characterize the causes of inflammation in patients with encephalitis through metagenomics and by quantifying the expression of inflammatory cytokines in CSF. We will do this by identifying pathogens and immune markers of potential diagnostic or therapeutic use.

Methods: Immunocompetent participants, aged 1-18 years, presenting to the emergency department and/ or neurology or infectious disease divisions of BCCH with encephalitis will be eligible for prospective and retrospective enrollment in two categories of (a) patients with encephalitis and a known central nervous system (CNS) pathogen (n= 30) and (b) patients with encephalitis and an unidentifiable CNS pathogen (n= 42).

Control subjects (n=42) being investigated for developmental delay or suspected raised intracranial pressure will be recruited from neurology services when getting a lumbar puncture. CSF and serum will be obtained and medical information will be collected through a chart review.

Results: This study is ongoing. We expect that specific pathogens predispose to or cause CNS inflammation.

We also hypothesize that cytokine and chemokine profiles vary based on the type of pathogen causing inflammation, allowing the development of biomarkers.

Significance: This unique multidisciplinary study will be the first in Canada to develop and validate a CSF metagenomic technique that is both sensitive and specific. Combining comprehensive pathogen detection with the assessment of biomarkers will allow us to differentiate infectious from non-infectious inflammation and impact patient management to improve outcomes.

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Session #2 (Morning) | Poster Board #17 Kai Zhu, Medical Student, University of British Columbia Supervisor: Gillian Lauder, Evidence to Innovation

Congratulations to Kai on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Evidence to Innovation Summer Studentship

Perioperative multimodal analgesia, including intravenous lidocaine infusion, for pain management following idiopathic scoliosis correction surgery in children Kai Zhu, Andrew Poznikoff, Nicholas West, Roxane Carr, Firoz Miyanji, Gillian Lauder

Background: Posterior spinal instrumentation and fusion (PSIF) is a common surgery in our institution for the correction of scoliosis. It is a major surgical insult that requires regular assessment and management by the acute pain service and surgical team. Intravenously administered opioids, such as a morphine infusion, are a fundamental part of the postoperative analgesia regimen; however, they are associated with significant, dosedependent, side effects. These side effects can interrupt return to normal enteral function, make mobilisation and physiotherapy difficult and potentially delay overall recovery. The use of peri-operative IV lidocaine, a sodium channel blocker with analgesic, anti-inflammatory and anti-hyperalgesic properties, has been shown to improve postoperative pain and reduces postoperative opioid requirement in adults undergoing various surgical procedures; however, to our knowledge, no such studies have been conducted with adolescent scoliosis patients.

Objectives: Our primary objective is to determine if perioperative IV lidocaine therapy (P-IVLT) reduces 48-hour post-operative morphine utilization, in adolescents undergoing PSIF. Secondary objectives include describing the effect of P-IVLT on self-reported pain scores, time to documented first stand, time to first walk of greater than 15 steps, and length of hospital stay (LOS).

Methods: A placebo-controlled, double-blinded randomized control trial to compare the 48-hour postoperative morphine utilization amongst adolescents undergoing a single stage PSIF at BCCH will be conducted. Eligible participants will be randomly assigned to one of two groups: The intervention group will receive P-IVLT, started during surgery and continued into the postoperative period for 48hrs, in addition to standard multimodal analgesia. The control group will receive a normal saline placebo, made to mimic the intervention protocol above, in addition to the standard multimodal analgesia. We will recruit a total of 48 participants, with 24 in each group. As this is a blinded study, the data will not be analyzed until the end of the study.

Significance: This study aims to show that P-IVLT following PSIF can reduce postoperative morphine utilization.

The intended consequence would be decreased LOS due to reduced opioid related side effects, reduced reliance on opioids following surgery, and the potential for reduced need for prescription opioids at time of discharge from hospital.

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Session #2 (Morning) | Poster Board #18 Jeremy Zuo, Medical Student, University of British Columbia Supervisor: Cyrus Boelman, Childhood Diseases

Congratulations to Jeremy on receiving a UBC Faculty of Medicine Summer Studentship

STXBP1.ca: The National Registry for STXBP1-Related Neurodevelopmental Disorders Jeremy Zuo, Conrado de Guzman, Cyrus Boelman

Background: Early-onset epileptic encephalopathies are characterized by abnormal brain development associated with an overwhelming degree of seizure activity resulting in poor quality of life and developmental outcomes. There are multiple different causes of the seizure activity, many of which are single gene mutations. Mutations in the Syntaxin-Binding Protein 1 (STXBP1) gene are some of the most common causes of early-onset epileptic encephalopathy. STXBP1 mutations are associated with abnormal neuronal synaptic transmission and result in a still-emerging spectrum of challenges from severe early-onset epilepsy to adultonset movement disorders. Symptoms usually manifest in infancy but may also begin in childhood or early adulthood. Patients often present with epilepsy and moderate-to-severe intellectual disability, which may be accompanied by behavioral problems. It is an autosomal dominant disorder; meaning only one mutated copy of the gene is enough to cause the disorder. There is no cure; treatment often involves anti-seizure medications and supportive care regarding development and symptom management.

Aim: To better understand the spectrum of STXBP1-related neurodevelopmental disorders, their challenges and approaches to their medical management.

Methods: As a result of our previous work with the patient population, we have established a national registry of patients with STXBP1-related neurodevelopmental disorders in order to collect clinical information regarding these patients and establish objective neuropsychological measures over time. Participants are recruited through referral to our research team from mainly clinical neurologists and geneticists across the Canada, and referred through our website: STXBP1.ca. Enrolment involves participants voluntarily providing their medical histories and completing standardized neurodevelopmental questionnaires, which are administered electronically. The received information will be checked against available medical records. Updates will be sought annually. The data will be summarized qualitatively with descriptive statistics where appropriate.

Results: We are still in the early stages of the project. The website is active to help with recruitment and provide family information. We have built a REDCap electronic database with e-surveys for participants to complete. We are finalizing language in the surveys with some piloting participants to improve its use before initiating active recruitment and data collection.

Potential Outcomes: We believe that our data will inform management recommendations and provide a platform for future clinical and basic science research. We also hope that our registry will connect families with new healthcare resources and encourage families to connect with each other to find support.

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Session #3

CLINICAL, POPULATION HEALTH & HEALTH SERVICES 10:30am - 12pm

Moderator: Dr. Robine Donken Participants: Catherine Binda, Kimberly Nguyen & Prabhpreet Mangat Maria Clarissa Belen Benjamin Clayton Anand Dhatt Sabrina Hou Joshua Koentjoro Alexandra Mackay Olivia Scoten Gemma Tomasky

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Session #3 (Morning) | Poster Board #19 Catherine Binda, Kimberly Nguyen & Prabhpreet Mangat, Undergraduate Students, University of British Columbia Supervisor: Damian Duffy, Evidence to Innovation

Lights, Camera, Surgery! Video Resources Enhancing Healthcare Communication Catherine Binda, Kimberly Nguyen, Prabhpreet Mangat, Damian Duffy, Kishore Mulpuri

Background: Effectively communicating medical information to patients and their caregivers is important.

Effective communication can help regulate emotions and improve patient understanding, adherence to treatment and health outcomes. Despite the importance of communication, physicians often do not communicate satisfactorily with their patients. Video educational resources show promise as a new tool that may improve the exchange of knowledge from doctor to patient.

Purpose: To create interdisciplinary educational video resources for caregivers who are accessing surgical services at BC Children’s Hospital (BCCH). These videos, supplementing regular clinical practice, will help patients and caregivers understand their child’s condition, improve surgical outcomes, reduce stress and anxiety ​as well as reduce the financial burden of unnecessary emergency room visits.

Methods: Surgical team members and research staff from three departments at BCCH identified suitable video topics and learning objectives. Existing patient resources were combined with further research and expert opinion to create 10 video series. Videos were edited using iMovie, W ​ indows Movie Maker, Powtoons, WireWax and Adobe After Effects. Patients and caregivers were voluntarily asked for their participation and consented through signing a media release form. Completed videos were made available on the Office of Paediatric Surgery Evaluation and Innovation (OPSEI) YouTube channel and on clinic websites. URLs and QR codes were also used to connect viewers to the video resources. ​ Results: 57 videos were created in collaboration with 31 families, 7 surgeons, 3 physiotherapists, 2 occupational therapists, 5 nurses, and 5 researchers.

Future Direction: Questionnaires will be administered to patients and caregivers to evaluate the “usefulness” of the video resources. “Usefulness” will be defined by qualitative metrics relating to the patient experience and by quantitative metrics such as the number of times patients view the videos.

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Session #3 (Morning) | Poster Board #20 Maria Clarissa Belen, Undergraduate Student, Simon Fraser University Supervisor: Lori Tucker, Childhood Diseases

Challenges Faced by Families of Children with an Autoinflammatory Disease Maria Clarissa Belen, Felice Mizan, Iwona Niemietz, Martina Sundqvist, Kelly Brown, Lori Tucker

Introduction: Autoinflammatory diseases (AIDs) are a group of rare disorders that usually present in young children and are characterized by recurrent, non-infectious episodes of inflammation. Common symptoms include fever, rash, joint and muscle pain, pharyngitis, and oral ulcers. These episodes can be frequent, and many affected children will suffer lifelong poor health. AIDs are not well recognized by community health professionals, and diagnosis may be delayed for months- years. Therefore, better understanding of the challenges faced by families of children with AID around the time of diagnosis will guide the development of supportive family and patient-centered resources.

Objective: To gain insight of the challenges families have experienced prior to and after their child was diagnosed with AID. Methods: The Pediatric Rheumatology Division, British Columbia Children’s Hospital has an Autoinflammatory Diseases clinic for children with AIDs. We designed a survey for parents of children with AID clinic to identify (i) challenges faced prior to diagnosis of an AID, and (ii) resources that the families found helpful after the diagnosis. General demographic information (child’s current age, age at diagnosis, AID) was collected. Short answer questions were reviewed and grouped into themes for reporting.

Results: To date 24 families have completed the survey, and 5 different types of AIDs were represented.

Children of respondents had a median age of 11 yrs (range 5 - 18 yrs) and a median age at AID diagnosis of 5 yrs (range 1 - 16 yrs). Also the median time from the onset of AID symptoms to diagnosis was 2 yrs (range 0.5 yrs - 6 yrs). Parents reported challenges in the following theme areas: inadequate knowledge of AID among community health professionals (n= 10), inability to fully participate in daily life activities (child missing school, parent missing work); n= 6], and worry about their child’s illness (day to day managing, uncertainty of the future); n= 5]. Parents reported online parent support groups and local BC family support organizations were helpful resources, as well as the resources of the BCCH AID clinic (knowledgeable physicians, nurse, physiotherapist and occupational therapist, parent handouts).

Conclusions: Parents of children with AID share common challenges prior to their child’s diagnosis that are debilitating and can contribute to delay in diagnosis. This needs assessment provides guidance to the development of health professional education in the area of AID and BC-based parent support services that will help families feel less isolated when their child has an AID.

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Session #3 (Morning) | Poster Board #21 Benjamin Clayton, Undergraduate Student, University of Waterloo Supervisor: Guy Dumont, Healthy Starts

Congratulations to Benjamin on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award

Integrated Vital Signs and Video Recording

Benjamin H. Clayton, Dustin Dunsmuir, Pascal Lavoie, J. Mark Ansermino, Guy A. Dumont Approximately four million infants die from severe illnesses worldwide, with the highest risk of infant mortality found in the World Health Organization African Region. The chance for survival of a critically ill infant is maximized by early identification of critical signs, rapid referral, and treatment. Identifying patients with these signs can be difficult for health workers not specialized in infant care and the vast majority of these patients in Africa do not have access to specialists. Vital signs such as oxygen saturation and pulse rate are important for measuring clinical deterioration but do not offer a complete assessment of a patient. Key visual clues such as motion (voluntary and involuntary), color, tone, and respiratory effort can be identified by experts and combined with these vital signs to improve diagnostic performance. Therefore, to overcome the lack of expertise in low resource environments we need an algorithm that can detect these visual clues to rapidly and reliably identify the critically ill infant.

The goal of this project is to develop a video-based system to automatically recognize a critical-ill infant by replicating the clinical observations done by experts and combining these with measured vital signs. The specific objective is to produce a video capture application that can synchronize the capture of pulse oximetry with high definition video to identify at-risk patients. This synchronized data will enable the validation and comparison of existing video analysis techniques used to extract physiological measures. It will also enable the use of advanced machine learning techniques to extract new information from videos with integrated vital signs.

Several approaches were implemented to arrive at the final solution. Firstly, video recording on a Windows computer was used in conjunction with an Android tablet connected to a pulse oximeter, sending waveform data over a TCP/IP connection. Then, frame-by-frame raw 1080p image capture and photoplethysmography recording features were implemented to achieve synchronous data capture. Additionally, an Android application was developed to increase portability and synchronously capture all data on one device, whilst maintaining the ability to connect to a desktop to use a high-quality external camera device. Further video analysis strategies will be explored to maximize the utility of the portable video and data synchronizing tool.

In the future, this application will be used to capture images from a cohort of children that will be used for development, training, and validation of algorithms to identify critically-ill infants. This will be implemented in a variety of ongoing clinical studies in developing countries. The first real-world testing of the system will be in Malawi starting in August 2019 with data collection as part of a study on early diagnosis of neonatal sepsis.

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Session #3 (Morning) | Poster Board #22 Anand Dhatt, Undergraduate Student, University of British Columbia Supervisor: Ian Pike, Evidence to Innovation

Geo-Spatial and Socioeconomic Predictors of Youth Self-Harm Hospitalizations in British Columbia Anand Dhatt, Jennifer Smith, Denise Beaton, Ian Pike

Self-harm is defined as any act of intentional self-injury that has non-suicidal intent. In British Columbia (BC), 15% of youth (ages 12-18) reported that they self-harmed in 2018. Furthermore, there is an increased risk of future suicide attempts amongst those who self-harm. Self-harm and suicide rates/attempts have associations with various community statistics, such as socioeconomic status, ethnicity, and geography, such as rurality or urbanicity of residence. For example, in California, rates of self-harm were lower in rural areas compared to urban areas. While similar studies have been conducted in Alberta, Ireland, Australia, and Hong Kong, there is a paucity of research on self-harm rates in BC and possible associated indicators.

The objective of this study is to analyze the rates of self-harm through a geo-spatial analysis, identify clusters of self-harm, and compare the rates to various geographic, social and demographic predictors.

The Canadian Hospitals Injury Reporting and Prevention Program statistics on youth hospital admissions will be used to identify self-harm incidents. These data will then be analyzed using a geographic information system to identify any clusters of self-harm. A comprehensive internet search will identify indicators of access to care, social fragmentation, and deprivation, and assess possible correlations to the clusters of self-harm.

By studying the geo-spatial occurrence of self-harm incidents and possible determinants of self-harm, it will allow evaluation of inequities in care and possible contributing predictors to the rate of self-harm incidents in BC. The identification of such factors will inform the development of public health strategic plans to address these areas of need.

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Session #3 (Morning) | Poster Board #23 Sabrina Hou, Undergraduate Student, University of British Columbia Supervisor: Deborah Giaschi, Brain, Behaviour & Development

Congratulations to Sabrina on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Evaluating Visuomotor Coordination in Children with Amblyopia Sabrina Hou, Ewa Niechwiej-Szwedo, Yousef Shahin, Yan Zhang, Deborah Giaschi

Background: Amblyopia is a developmental disorder of the visual cortex characterized by poor vision that cannot be corrected by lenses. It affects 3-5% of the worldwide population and is the leading cause of vision loss in children. Clinically, diagnosis depends solely on differences in visual acuity between the two eyes under best corrected vision. However, in addition to visual acuity, many children with ambylopia show deficits in a number of other visual facets such as binocular vision, motion perception, and visuomotor coordination. These deficits are not targeted by current amblyopia treatment and may be responsible for high treatment failure rates.

Purpose: Through the use of a bead-threading task that has been shown to be sensitive to the disruption of binocular vision, our purpose is to: 1. Validate a protocol for assessing visuomotor coordination in children.

2. Determine the specific kinematic parameters that are the most characteristic of the disrupted visuomotor mechanisms in amblyopia.

Methods: Children with amblyopia and control participants aged 4-13 are being recruited. Each participant completes assessments of visual acuity and stereoacuity before completing 30 trials of the bead-threading task under 3 viewing conditions (binocular, right eye only, left eye only). Each trial involves grasping a small bead with two fingers and threading the bead onto a vertical needle. Hand-movement data are collected using a Leap Motion tracker and then analyzed to extract kinematic parameters of peak velocity, grasp duration, and threading duration.

Preliminary Results: Children with amblyopia (N=6) and age-matched controls (N=7) show similar average peak velocities. Quantitative analysis of the duration data is in progress; qualitative inspection suggests that children with amblyopia may be less accurate than control children during the grasping and threading phases.

A previous study examining the same task in adults found that adults with amblyopia took longer than controls to grasp and thread the bead. Thus, it is possible that children with amblyopia will show a similar pattern of deficits. Data collection and analysis are ongoing.

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Session #3 (Morning) | Poster Board #24 Joshua Koentjoro, Undergraduate Student, University of British Columbia Supervisor: Peter van den Elzen, Childhood Diseases

Effects of All-Trans Retinoic Acid on CD1d Expression and subsequent invariant NKT cell activation in Patients with Acute Promyelocytic Leukemia Koentjoro, Joshua, Johal, Bhupinder, Zheng, Dong-Jun, Narayanan, Sujaatha, van den Elzen, Peter

Background: CD1 molecules are lipid antigen-presenting molecules that are expressed on antigen-presenting cells (APCs). Previous research has shown that activation of the alpha retinoic acid receptor (RARα) on immune cells by all-trans retinoic acid (ATRA) induces an upregulation of CD1d molecules expressed on APCs. Furthermore, these changes in CD1d levels may regulate CD1d-restricted innate Natural Killer T-cell (iNKT) activity through cytokine secretion. iNKT cells have been proposed to be a main contributor in immunological responses against cancer due to their wide array of functions. Acute Promyelocytic Leukemia (APL) is characterized by an overabundance of hypergranular promyelocytes within the circulatory system.

The discovery of ATRA as a form of treatment has replaced standard chemotherapy programs and has given APL a good prognosis. Previous research has revealed that ATRA inhibits the proliferation and promotes differentiation of malignant cells into mature cells in patients with APL. This effectively reduces the abnormal cell mass and restores normal hematopoiesis.

Objectives: We aim to elucidate the possible mechanism that ATRA utilizes to induce an effect on the immune system of APL patients specifically. We expect to measure increases in CD1d expression in post-treatment samples compared to pre-treatment.

Method: In this experiment we will have access to the Vancouver General Hospital biobank’s collection of five APL patients’ peripheral blood mononuclear cell (PBMC) samples taken before and after ATRA treatment. A 12-colour flow cytometry panel is utilized and optimized to characterize B cell, monocytes and different T cell subsets. An analysis of CD1d and CD1c levels on APCs, along with activation levels on T cells in PBMCs will allow us to compare pre and post ATRA-treatment samples.

Significance: Differences in both CD1 levels on APCs and activation levels of T cells could denote a more prevalent effect that ATRA has on the immune system than previously expected. Furthermore, this could highlight its role as a bridge between the two populations that ultimately helps boost the efficiency and effectiveness of the immune system. Its effect on RARα could be important to immune therapy against not only hematologic malignancies but also other cancers due to its potential as an immunological activator.

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Session #3 (Morning) | Poster Board #25 Alexandra Mackay, Undergraduate Student, Yale University Supervisor: Jill Zwicker, Brain, Behaviour & Development

Congratulations to Alexandra on receiving a BC Children’s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Developmental Coordination Disorder in Preterm Infants: The Impact of Prematurity on Cerebellar Volume and Motor Deficits Alexandra Mackay, Kamal Gill, Steven Miller, Ruth Grunau, Anne Synnes, Jill Zwicker

Background: Developmental coordination disorder (DCD) is a chronic motor disorder that significantly interferes with activities of daily living and quality of life. Infants born very preterm (≤32 weeks gestational age) are 6-8 times more likely to develop DCD compared to term-born children. The cerebellum is thought to be implicated in this disorder due to its well-established role in motor function. Late in gestation, the cerebellum undergoes rapid growth when volume increases 5-fold. However, this period of accelerated growth is impeded by preterm birth. Accordingly, we expect that there is a relationship between lower cerebellar volume and diagnosis of DCD in preterm infants.

Objectives: To compare cerebellar volume in children born very preterm with and without developmental coordination disorder (DCD).

Study Design: Participants were assessed using the Movement Assessment Battery for Children 2nd ed.

(MABC-2); children who scored at ≤ 5th percentile and had no other neurological impairment that would explain their motor difficulties were classified as DCD. Participants with severe brain injury, cerebral palsy, or developmental delay were excluded. Using Statistical Parametric Mapping software, we conducted voxel-based morphometry (VBM) to compare differences in cerebellar gray matter volume in children with and without DCD, controlling for gestational age and birthweight.

Results: Sixty-one children met our inclusion criteria. Children with DCD (n=19) had greater cerebellar volume in four regions: right Crus I, left Crus I, left Crus II and left lobule VI. Conclusions: Children with DCD showed greater volume of gray matter in regions of the cerebellum associated with cognition, which may be a form of compensation.

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Session #3 (Morning) | Poster Board #26 Olivia Scoten, Undergraduate Student, Queen’s University Supervisor: Ruth Grunau, Brain, Behaviour & Development

Congratulations to Olivia on receiving a BC Children’s Hospital Research Institute Summer Studentship

Development of Internalizing Problems in Children Born Very Preterm: Cortisol and Parenting Olivia C. Scoten, Mia A. McLean, Cecil M.Y. Chau, Joanne Weinberg, Anne P. Synnes, Steven P. Miller, Ruth E. Grunau

Background: Internalizing problems (anxiety, depressive symptoms) are prevalent in children born very preterm, and may be linked to stress early in life. These infants undergo frequent invasive procedures (~10 per day) in the neonatal intensive care unit (NICU). Exposure to this pain-related stress alters child stress regulation via ‘programming’ of the hypothalamic-pituitary-adrenal (HPA)-axis which may contribute to the development of internalizing problems. It is unknown how parenting behaviors interact with neonatal pain-related stress to influence toddler cortisol levels and later internalizing behaviors in this vulnerable population.

Objectives: Investigate: 1) whether parenting behaviors at corrected age 1.5 years influence child cortisol levels at corrected age 3 years, in turn affecting child internalizing problems at age 4.5 years; 2) if neonatal painrelated stress and gestational age moderate this pathway.

Methods: Longitudinal prospective cohort study: After exclusions, N=101 infants born very preterm (24-32 weeks gestation), recruited at birth from BC Women’s Hospital Level III NICU, were seen at 1.5, 3, 4.5 years in the Neonatal Follow-up Program for developmental assessments. Neonatal chart review: clinical factors (e.g. number invasive procedures, infection). At 1.5 years, filmed parent-child behaviors during semi-structured teaching tasks were coded on Emotional Availability Scale IV (parent sensitivity, structuring, non-intrusiveness, non-hostility; child involvement, responsiveness). Saliva samples collected before, during, and after cognitive assessment at 3 years were assayed for cortisol. Internalizing behaviors at 4.5 years: psychologist-rated child behaviors on the Stanford-Binet Behavior Rating Scale 5th Ed, parents completed the Child Behaviour Checklist (CBCL 1.5 – 5). Exclusions: major cognitive impairment; ate/drank within 30 min of saliva collection, on a medication affecting cortisol level.

Results: Preliminary analyses using a moderated mediation model (SPSS v26 PROCESS Macro) showed that higher basal cortisol and greater change in cortisol across assessment mediated the pathway between more positive parent affect (non-hostility) and less child anxiety (psychologist-rated), but only for those born 24 – 29 weeks gestation.

Conclusions: Children born extremely preterm are more susceptible to their parenting context. Positive parenting behaviors can help reduce child internalizing problems by improving stress regulatory capacities in young children born extremely preterm. Our findings help inform parent-focused intervention programs for this at-risk population.

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Session #3 (Morning) | Poster Board #27 Gemma Tomasky, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

“Stroop Colour-Word Task”: Adaptation of a Clinical Test for a Game Setting Gemma Tomasky, Melvin Chan, Scout McWilliams, Osman S. Ipsiroglu

Introduction: Lack of sleep leads to vigilance fluctuations and increases injury risk. Accordingly, effective knowledge dissemination tools are needed to communicate the risks of sleep deprivation. In 2017, high-school students at the H-Behaviours Research Lab suggested to use the Stroop Colour-Word Task (SCWT) to measure attention, reaction time, and interference (the ability to overcome distracting stimuli). We investigated how well SCWT can be adapted into a “vigilance game” setting as part of a fun knowledge dissemination event for university or high-school students.

Method:

(A) A scoping review conducted on Medline and PubMed identified the most common methods for

measuring “sleep*” AND “attention” AND “reaction time” AND “interference” (search phrase).

(B) A SCWT game, initially suggested by students, was played at a pilot test run to investigate SCWT’s adaptability as a game and collect feedback. Interference was measured by counting the amount of errors. Reaction time was measured automatically using the downloaded computer program.

The Karolinska Sleepiness Scale and selfies were used to assess vigilance subjectively and video recordings of facial features to assess vigilance objectively. All data, expect videos and selfies, were recorded in Qualtrics on mobile devices.

(C) A Strength-Weakness-Opportunity-Threat (SWOT) analysis was conducted on the applicability of the SCWT test as a game.

Result:

(A) 15 articles were identified; 10/15 articles, responding to the content of the search phrase, were

analyzed; four RCTs used the manual and oral SCWT.

(B) Self-experience and participant feedback at the pilot test run revealed that the game instructions were clear, practice trials were needed, and separating participants to optimize concentration was necessary.

(C) A Strength-Weakness-Opportunity-Threat (SWOT) analysis was conducted on the applicability of the SCWT test as a game.

Conclusion: The adapted “SCWT-game” allows participants to observe their own vigilance fluctuations. We decided to include the SCWT-manual-method as it measures exact reaction times using a computer and allows facial signs of vigilance to be recorded on video. The next step is to implement the game into a knowledge dissemination package targeting injury prevention.

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Session #4

CLINICAL, POPULATION HEALTH & HEALTH SERVICES 10:30am - 12pm

Moderator: Dr. Bahaa Abu Raya Participants: Aditya Chhabra & Nisha Mainra Hannah Foggin Saman Fouladirad Gurkiran K. Mann Max Liu Nikhail Mainra Scout McWilliams Jessica Que Gabrielle Sanatani Kristin Vesely

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Session #4 (Morning) | Poster Board #28 Aditya Chhabra & Nisha Mainra, Medical and Undergraduate Students,

University of British Columbia Supervisors: James Lee, Mark Ansermino & Gabby Napoleone, Brain, Behaviour & Development and Healthy Starts

Congratulations to Aditya on receiving a BC Children’s Hospital Research Institute Summer Studentship

Home Sleep Monitoring as a Predictor of Clinically Assessed Risk of Obstructive Sleep Apnea Aditya Chhabra, Gabby Napoleone, Mark Ansermino, James Lee

Introduction: Tonsillectomy and/or adenoidectomy (T/A) are commonly performed procedures, the most common indication for which is suspected or diagnosed Obstructive Sleep Apnea (OSA). Polysomnography (PSG) is the gold standard for diagnosing and assessing OSA [1]. While pulse oximetry is part of the standard monitoring used during PSG, its potential as a standalone tool to diagnose those patients most at risk of postoperative respiratory events has been investigated but is yet to be fully realized [2]. We aim to determine the feasibility and value of using the Phone Oximeter-OSA app to assess children at home before T/A procedures.

Methods: Following Research Ethics Board approval and informed consent, children from 3 months to 17 years of age, planned for T/A, were enrolled in this study. A Masimo pulse oximetry sensor was attached to the participant’s first toe and connected to the Phone Oximeter. Overnight pulse oximetry data was collected on the Phone Oximeter-OSA app for three nights at home before surgery, and three consecutive nights immediately post-surgery. The app records heart rate, blood oxygen saturation (SpO2), photoplethysmography, and signal quality index (SQI). Pre and post-operative recordings lasting at least 3 hours were considered successful. Participants were stratified into two groups based on their actual post-op disposition: overnight admission to either the ward or Pediatric Intensive Care Unit for monitoring (n=42) versus discharged home day of surgery (n=63). The best preoperative recording for each participant was selected for analysis. The clinical assessment of pre-op risk as a comparison standard was determined by the anesthesiologist, who ranked patients ranked on a scale of 1-5, with 1 being low risk and 5 being high risk.

Results: 125 patients were enrolled with a mean age of 7.1 years. Only 11 (9%) had previously undergone in hospital PSG. Of 106 included patients with completed pre-operative readings, 98% had at least 1 good reading, 86% had at least 2 good readings, and 42% had 3 good readings.

Conclusion: It was feasible to obtain recordings that were of good quality using the Phone Oximeter. Next, we plan to analyze the data collected by the Phone Oximeter to predict post-op disposition as well as pre-op OSA risk. We will also compare the preoperative recordings with the OSA risk category determined by the anesthesiologist.

[1] Laryngoscope 123(10):254453, [2] J Clinic Sleep Med 2(2):145–53

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Session #4 (Morning) | Poster Board #29 Hannah Foggin, Medical Student, University of British Columbia Supervisors: Jennifer Hutcheon & Jessica Liauw, Healthy Starts

Congratulations to Hannah on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Healthy Starts Summer Studentship

Estimating population-level absolute risk reductions and numbers needed to treat for neonatal morbidity and mortality, for use in a decision aid for late preterm antenatal corticosteroids Hannah Foggin, Jessica Liauw, Jennifer Hutcheon

Background: Antenatal corticosteroids are given to women at risk of delivering their baby early to help lung maturation and reduce risk of breathing problems and other complications. Current standard of care recommends one course to women at high risk for preterm birth between 24 and 34 weeks of gestation.

Recent research suggests that antenatal corticosteroids also reduce the risk of newborn breathing problems when given to women at 35 and 36 (late preterm) weeks, but the baseline risk of adverse outcomes is lower at these gestational ages. This makes it challenging to interpret the balance of risk and benefit of this medication; communicating this via absolute risk reductions, based on population baseline rates of neonatal morbidity, would enhance clinical counselling on this issue.

Objective: To apply relative risk ratios from recent randomized controlled trials on late preterm antenatal corticosteroid use to absolute risk reductions based on population baseline risks of neonatal morbidity.

Methods: We applied relative risk estimates from recent randomized controlled trials to baseline risks of neonatal morbidity in the United States to generate absolute risk reductions (ARR) in neonatal morbidity associated with antenatal corticosteroid administration, by gestational age week. Baseline risks were calculated from approximately 8 million birth records from 2012-2013 in the U.S. linked birth/infant death database (Centers for Disease Control and Prevention). ARRs and Numbers Needed to Treat (NNTs) were calculated with 95% confidence intervals.

Results: With increasing gestational age, calculated ARRs for neonatal mortality and morbidities decreased, and NNTs increased. For those born at 34 weeksâ&#x20AC;&#x2122; gestation, 24 (95% CI, 11 to -72) and 455 (99 to -37) pregnant women would have to be treated with antenatal corticosteroids to prevent one admission to NICU and one neonatal death, respectively. At 36 weeksâ&#x20AC;&#x2122; gestation, 96 (44 to -289) and 977 (213 to -80) pregnant women would have to be treated to prevent those outcomes, respectively.

Conclusion: Calculating absolute risk measures by applying relative risks from randomized trials to population baseline risks of neonatal morbidities provides estimates that are generalizable to the general obstetrical population. These absolute risk measures may be more useful for patient counselling and clinical decision making than relative risks alone.

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Session #4 (Morning) | Poster Board #30 Saman Fouladirad, Medical Student, University of British Columbia Supervisor: Patrick McDonald, Brain, Behaviour & Development

Congratulations to Saman on receiving a Florence E. Heighway Summer Research Award

Transitioning of patients with hydrocephalus from pediatric to adult care in British Columbia: a mixed methods study Saman Fouladirad, Alexander Cheong, Patrick McDonald

Introduction: Hydrocephalus is a chronic neurological condition that affects around 6 in 10 000 live births and is one of the most common indications for pediatric brain surgery. The condition is fatal if left untreated, however surgical procedures such as cerebrospinal fluid (CSF) shunt placement and endoscopic third ventriculostomies (ETV) have increased survival rates allowing for most pediatric patients to live and transition into adulthood. Unlike other chronic conditions such as cystic fibrosis, congenital heart disease, type I diabetes, etc., the transition of adolescents with hydrocephalus from pediatric to adult care is often fragmented and disjointed and there are few studies on the process thus appropriate guidelines and models of transfer are lacking. This is particularly concerning not only due to the prevalence of hydrocephalus among the pediatric population, but the significant increase in morbidity and mortality associated post-transition with poorly handled transfers.

Methods: The study will quantify the various factors that challenge young adults with hydrocephalus as they go through this transitioning period by utilizing both a qualitative and quantitative approach. The study consists of two phases: 1) Semi-structured interviews of selected adolescent patients at BC Childrenâ&#x20AC;&#x2122;s Hospital and transitioned adult patients at Vancouver General Hospitalâ&#x20AC;&#x2122;s Adult Hydrocephalus Clinic and/or their caregivers will be done to identify themes important to this population regarding the transition process. 2) Based on the results of the interviews, a survey will be developed and administered to patients and care givers regarding the transitioning process and ways it can be improved.

Conclusions: We hypothesize that emerging themes from the data will highlight the difficulty patients have in forgoing familiar relationships/environment and becoming self-reliant. Understanding the expectations, concerns and overall input of patients is one of the many important steps that must be taken take in order to build a foundation for a transition model of care that can carefully attend to the needs of patients with hydrocephalus.

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Session #4 (Morning) | Poster Board #31 Gurkiran K. Mann, Medical Student, University of British Columbia Supervisor: Ian Pike, Evidence to Innovation

Physician Engagement: Parent Education on the Period of PURPLE Crying Gurkiran K. Mann, Claire Humphreys, Fahra Rajabali, Karen L. Sadler, Jennifer Smith, Ian Pike

Background: The Period of PURPLE Crying® program is designed to educate parents about normal, early increased crying experienced by all infants. This complimentary universal parent education program aims to reduce the incidence of abusive head trauma/shaken baby syndrome (AHT/SBS) of which infant crying is the main trigger. Since 2009, this program has been delivered to all new parents in BC via three doses/exposures: 1) maternity hospitals, 2) public health units, 3) public education campaign.

Objective: We aim to determine the experiences of physicians in BC working with new and expecting parents in their ability to educate them about AHT/SBS, normal infant crying, and soothing and coping mechanisms using the Period of PURPLE Crying program. We also hope to understand how we can better support physicians’ knowledge on and access to program materials and training as part of their practice.

Rationale: The current structure of the program does not include physicians as a main source of delivery of the educational materials. There have been modifications in BC in the delivery of well-baby checkups and immunizations away from a public health model, which is typically when nurses reinforce the Period of PURPLE Crying program messages, to one within physician practice. Thus, it is critical that we engage directly with physicians to ensure that there are no gaps in the delivery of the program materials.

Methods: We plan to gather data from resident and attending family physicians, obstetricians/gynecologists, and pediatricians. Using an explanatory sequential study design, we will conduct a web-based survey followed by in-depth telephone interviews. We implemented a pilot with seven physicians to receive feedback about the survey’s length, content, feasibility, and relevance. Through collaboration with Doctors of BC and Resident Doctors of BC, we are currently in the survey dissemination phase.

Impact: Previous studies report a lack of AHT/SBS knowledge amongst physicians; however, none examine how to address this gap. Our research aims to improve knowledge translation about AHT/SBS and the Period of PURPLE Crying, as well as provide a framework on how best to engage physicians in injury prevention efforts.

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Session #4 (Morning) | Poster Board #32 Max Liu, Medical Student, University of British Columbia Supervisor: Anita Datta, Brain, Behaviour & Development

Congratulations to Max on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Brain, Behaviour & Development Summer Studentship

Determining the incidence and severity of cognitive and emotional problems in pediatric idiopathic epilepsy using the NIH Toolbox Max Liu, Osama Al-Jawadi, Ajay Grewal, Kristina Gicas, Alasdair Barr, Mary Connolly, William Panenka, Anita Datta

Background: The primary goal of managing children with epilepsy is to obtain good seizure control, however, the consequences of epilepsy extend far beyond seizures. In many cases, cognitive and emotional problems are often more disabling than the seizures due to a complex interplay between genetics, psychosocial environmental, and medications. Therefore, early detection of cognitive difficulties or symptoms of psychopathology, which is rarely pursued in practice due to its complexities, is critical to prevent poor functional outcomes in adulthood.

In addition, the impact of inter-ictal epileptiform discharges (IEDs) on cognitive and emotional functioning is not well characterized. Ultimately, identifying and addressing the modifiable risk factors that impact cognitive and psychosocial functioning is critically important to improving outcomes for children with epilepsy.

Aim: This study will systematically screen children with idiopathic epilepsy (IE) for cognitive and emotional deficits using the NIH Toolbox and standardized psychological screening tools. Our goal is to integrate the Toolbox as a clinical screening test and investigate the impact of IED features on cognitive and emotional functioning in patients with IE. Methods: The NIH Toolbox will be administered via iPad to consenting patients ages 8-18 with an IE. The NIH Toolbox epilepsy battery consists of 8 tasks measuring executive function, attention, episodic memory, language, and processing speed. These patients will have undergone an EEG in the previous three months of participation and a spike wave count will be performed to monitor IED features. We will also screen for psychological problems using the CDI2 and MASC2 paper questionnaires.

Implications: If practicality and feasibility are demonstrated, this project will immediately change care for children in the BC epilepsy service as the NIH Toolbox is then likely to be adopted into clinical care. This study will also increase our understanding of how IEDs contribute to cognitive and emotional dysfunction in epilepsy and has the potential to inform therapies that will improve outcomes for affected children.

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Session #4 (Morning) | Poster Board #33 Nikhail Mainra, Medical Student, Royal College Of Surgeons Supervisor: Vishal Avinashi, Childhood Diseases

The incidence of strictures in paediatric eosinophilic esophagitis: a retrospective analysis Nikhail Mainra, Edmond S. Chan, Jonathan Bush, Vishal Avinashi

Background: Although our scientific understanding of the disease remains in an early stage, eosinophilic esophagitis (EoE) is being increasingly recognized as a common cause of dysphagia in older children and adults and can be recognized in younger children with symptoms of picky eating, vomiting, and abdominal pain.

Eosinophilic Obstructive Esophagitis is a newly recognized disease that is diagnosed in children and adults, however, it is increasing in prevalence with 1 out of 2,000 people being affected.

Purpose: The purpose of this study is to observe the frequency of strictures in children diagnosed with EoE. Other goals will includes focusing on structuring diseases and short term dilatations in paediatric patients 16 years and younger.

Hypothesis: We hypothesize that stricturing in EoE will be rare and that symptoms pre-diagnosis will be due to esophageal strictures and the dilatation of esophageal strictures. Another hypothesis stated is that the longer the patient has EoE, they are more likely to have a stricture.

Methods: The methods in this experiment will involve capturing clinical information on patients less than 16 years old who are diagnosed with EoE between 2015-2018.A diagnosis of EoE is made based on signs of esophageal dysfunction and biopsy containing >15 eosinophills. Strictures are then categorized into 3 grades based on the resistance of the endoscopy. To calculate the frequency of the strictures in patients newly diagnosed with EoE. We must consider the total number of patients newly diagnosed over a study period and the number of patients diagnosed with strictures Results: Within our cohort of EoE patients with a stricture, we identified 20 patients which had accurate biopsies to support that they had EoE. The group consisted of 18 boys and 2 girls with an average age of 14 years old. EoE patients first presented symptoms on average at 10 years old with 70% of patients having symptoms of dysphagia and most commonly vomiting.

Outcomes and Significance: We hope to add further information on a disease where there is limited literature available. Our goal is to better characterise the incidence of stricturing diseases and to aid in the diagnosing eosinophilic obstructive esophagitis earlier during the disease.

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Session #4 (Morning) | Poster Board #34 Scout McWilliams, Medical Student, National University of Ireland, Galway Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Review of Iron Deficiency Guidelines in the Context of Iron DeficiencyRelated Sleep/Wake-Behaviours McWilliams S, Bao S, Mattman A, Wu J, Stockler S, Ipsiroglu O

Introduction: Low stored iron levels characterize iron deficiency (ID). ID is the most common nutritional deficiency in the world, disproportionately affecting children and women. High level evidence is elucidating the role of iron and ID in restless legs syndrome (RLS) and attention-deficit hyperactivity disorder (ADHD), however, is often overlooked in the clinical setting. The goals of this scoping literature review are to (1) review to what degree RLS and ADHD have been included in national ID-guidelines; and (2) compare the biomarkers and cutoff values as they pertain to ID, RLS, and ADHD. Methods: A scoping literature review was conducted in June 2019 in PubMed (English, full text available online) using 3 separate search phrases without any date restrictions: (1) ID anemia AND (filter: guideline) (2) “RLS” AND guidelines AND consensus; (3) ADHD OR “attention deficit hyperactivity disorder” AND (filter: guideline); (4) additionally, North American and European websites of national medical affiliations were searched.

Results: A. ID guidelines: n=14;

a. As of 2015, 3/14 mentioned RLS & ADHD as comorbid conditions; 1/14 provided a serum ferritin cutoff value specific for RLS patients;

b. Main biomarker: serum ferritin, cutoff values varied; 5/14 included CRP (because ferritin is an acute phase reactant).

B. RLS guidelines: n=12; main biomarker: serum ferritin, cutoff values changed over time with advancing knowledge; iron supplementation was identified as first line treatment.

C. ADHD guidelines: n=21; 2/21 included ID as a possible cause and treatment option.

Conclusions: Elemental iron is vital for numerous processes in the human body, including dopamine synthesis and myelination in the brain, and also as a central component of the oxygen-carrying molecule, hemoglobin. ID is a physiological state that precedes anemia, and is associated with restlessness affecting day- and nighttime behaviours. Thus, iron supplementation should be used as a first line measure to alleviate symptoms of restlessness associated conditions such as RLS and ADHD. To reflect the most recent emerging evidence, guidelines, biomarkers (depending on tier-service levels), cutoff values, and clinical best practice should be rereviewed, and guidelines should be amended.

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Session #4 (Morning) | Poster Board #35 Jessica Que, Medical Student, University of British Columbia Supervisor: Hannah Piper, Healthy Starts

Congratulations to Jessica on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship

The Impact of Probiotics on the Incidence and Severity of Necrotizing Enterocolitis in Preterm Infants Jessica Que, Julia Panczuk, Hannah G Piper

Background: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants, particularly those who are very low birth weight (VLBW), weighing <1500g. While the pathogenesis of NEC is not completely understood, microbial dysbiosis has been implicated. Hence, probiotics administration has been proposed to restore microbial balance and reduce the incidence of NEC. At BC Womenâ&#x20AC;&#x2122;s Neonatal Intensive Care Unit (BCWNICU), probiotics are now given routinely to VLBW infants. However, the effect of probiotic use at BCWNICU has not been evaluated before. The purpose of this study was to assess whether probiotics decreased the incidence and severity of NEC. Methods: This is a retrospective cohort study of VLBW infants cared for at BCWNICU between 2014 and 2018; 2 years prior to, and 2 years following the introduction of probiotics. In 2016, a daily probiotic containing Bifidobacteria and Lactobacillus species was introduced as part of standard of care for all VLBW babies and were continued until the baby reached 35 weeks gestational age. Baseline characteristics and outcomes were compared between those babies managed with and without probiotics. The incidence and severity of NEC between groups as well as any infections and time to full enteral feeds were compared. Statistical analysis will be performed to determine significant differences in outcomes between groups.

Preliminary results: 358 VLBW infants were admitted before July 2016 and 311 VLBW infants were admitted after implementing probiotic use. Thus far, data has been collected for 275 patients (117 prior to, and 158 after July 2016). In this subset, the overall incidence of NEC is similar between groups (32% vs. 30%) as is the incidence of NEC >= stage 2 (4% vs. 7%). The average number of infections per patient is similar between groups (0.53 vs. 0.47). Time to full enteral feeds is slightly lower after probiotic introduction (19 vs. 17 days).

Discussion: The interim results show that the incidence of NEC and infections are similar between groups, but there is a trend towards decreased time to full enteral feeds in those babies receiving probiotics. Data collection is ongoing with plans to complete by August 2019.

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Session #4 (Morning) | Poster Board #36 Gabrielle Sanatani, Medical Student, Royal College of Surgeons, Ireland Supervisor: Kishore Mulpuri, Evidence to Innovation

Developmental Dysplasia of the Hip: Care Practices of Pediatric Orthopedic Surgeons in China

Gabrielle Sanatani, Eva Habib, Judy Katherine Wu, Jeff Fu, Emily Schaeffer, Kunye Hu, Kishore Mulpuri, Kevin Shea, Jianping Yang Background: Developmental dysplasia of the hip (DDH) is a congenital condition in which there is decreased stability of the hip joint. Significant variation in diagnostic criteria, screening, and monitoring practices exist for DDH both regionally and internationally. While guidelines have been published outlining the best practices for DDH management by the American Academy of Orthopedic Surgeons (AAOS) and American Academy of Pediatrics (AAP), the number of orthopedic surgeons following these guidelines is unknown.

Purpose: The purpose of this survey study was to evaluate DDH management practices by pediatric orthopedic surgeons in China to identify treatment variability and aid in the standardization of DDH treatment.

Methods: Surgeons from the Chinese Association of Orthopedic Surgeons (CAOS) were invited to complete a survey that evaluated demographic data, clinical scenarios, screening methods, and radiologic imaging practices. It was administered to specialized and non-specialized pediatric orthopedic surgeons who work in pediatric orthopedic departments at hospitals in China. Not all survey responses were complete, therefore data point denominators were adjusted accordingly.

Results: A total of 181 surveys (98.3% response rate) from 116 hospitals across 28 provinces in China were obtained. In total, 90/178 (50.6%) of respondents reported diagnosing over 50 new DDH cases within the past year. Most surgeons treat patients ranging from six weeks to five years of age at initial presentation. Assessing AAOS guideline usage, 91.6% (164/179) were familiar with the guidelines and 81.1% (133/164) routinely follow them in clinical practice. Additionally, 72.0% (126/175) of respondents were familiar with the AAP guidelines, with 82.5% (107/126) of them reportedly using the guidelines in practice. Almost all respondents (173/178, 97.2%) believed screening for DDH at less than three months of age is necessary and that a DDH care pathway for screening and early management of DDH in China is needed (174/175, 99.4%).

Significance: North American DDH guidelines are having an impact in clinical practice internationally; however, almost all respondents called for a Chinese-specific DDH care pathway. The implementation of a geographically-centred care pathway for standard treatment practices could improve DDH patient care by specifically working within the resources available in that region.

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Session #4 (Morning) | Poster Board #37 Kristin Vesely, Medical Student, University of British Columbia Supervisor: Kathryn Selby, Childhood Diseases

Congratulations to Kristin on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Childhood Diseases Summer Studentship

Diagnostic Outcome of Muscle Gene Panel Testing in Patients with Suspected Neuromuscular Disorders Kristin Vesely, Kathryn Selby

Introduction: Inherited neuromuscular disorders (NMD) are a group of diseases causing chronic, progressive disability. They are a clinically and genetically heterogeneous group that contain numerous causative Mendelian defects. Arriving at a specific diagnosis is vital to optimal management and maximizing prognosis.

Diagnosis can be prolonged, often involving extensive and invasive investigations. Targeted next-generation sequencing (NGS) gene panels enable efficient, concurrent analysis of several genes of interest, and could potentially aid in confirming a diagnosis in patients with atypical or rare clinical presentations.

Objective: To determine the diagnostic yield and impact on clinical management of an NGS muscle disorders gene panel for patients with suspected NMD at BC Childrenâ&#x20AC;&#x2122;s Hospital.

Methods: We conducted a retrospective chart review of 61 pediatric patients (age < 18) with suspected NMD who received an NGS muscle disorders panel covering 89 genes of interest through Sherbrooke Genomic Medicine. Diagnostic yield was calculated. An analysis of the implications of gene panel testing on clinical management was conducted to characterize management outcomes in patients for whom genetic testing confirmed a diagnosis, versus those who remain without a certain or likely diagnosis.

Results: Preliminary analysis shows that the muscle disorders gene panel resulted in a confirmed or likely diagnosis in 16/61 (26%) patients. Of patients with an identified diagnosis, further disease-specific investigations or changes in clinical management occurred in 11/16 (69%) patients. Of patients for which a genetic diagnosis was not made, additional genetic testing was sought in 14/45 (31%) patients, and further non-genetic diagnostic investigations were ordered in 12/45 (27%) patients.

Conclusions: These results support the clinical utility of targeted NGS gene panels in making a specific diagnosis in suspected NMD, and also highlight the challenges in managing patients who remain undiagnosed after gene panel testing. Future advances in genomic medicine and analysis of clinical outcomes will help further explore the application of targeted NGS panels in NMD.

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Session #5 BASIC SCIENCE 1:30 - 3pm

Moderator: Dr. Maria Aristizabal Participants: April Christiansen Danielle Cohen Rachel Da Silva Selina Demetrick Alex Hsu Min Jung Kim Anson Law Anita Poon Sadaf Sediqi Esther Lin

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Session #5 (Afternoon) | Poster Board #38 April Christiansen, Undergraduate Student, Queenâ&#x20AC;&#x2122;s University Supervisors: Soren Gantt & Citlali Marquez, Healthy Starts

Investigating the dynamics of infection and re-infection with murine cytomegalovirus (mCMV) in mice April Christiansen, Catherine Byrne, Citlali Marquez, Soren Gantt

Human cytomegalovirus (HCMV) is a common virus that can infect up to 90% of the population and has severe adverse effects on immunocompromised, premature, and congenitally infected individuals. Although often asymptomatic in immunocompetent individuals, HCMV is the most common cause of congenital infection, viral-based neurodevelopment impairment, hearing deficits in children, and has the capacity to cause significant morbidity and mortality, particularly in low-income countries. Previous infection or vaccination have unfortunately failed to provide complete protection against re-infection with the same or different strains of CMV. However, it can be seen from previous studies that prior infection or vaccination can confer partial, imperfect protection against HCMV re-infection and superinfection.

Mice models are optimal to demonstrate CMV infection & re-infection as their environments and infection periods are able to be controlled for. As well, murine cytomegalovirus (MCMV) infection in mice mimics HCMV in regards to the pathogenesis, establishment of latency, and immune response.

Taken together, we hypothesized that MCMV infected mice will confer partial resistance to re-infection with the same or different strain of MCMV, and resistance may be in part determined by amount of virus the mice are infected and re-infected with. In order to test if mice are at all resistant to re-infection with the same strain 6 week old Balb/c mice are infected with either 10^2 or 10^6 PFU/mL LUC-K181-MCMV through intraperitoneal (IP) injection and imaged daily. The MCMV is allowed to establish latency, approximately eight weeks, and re-infected with the same strain of MCMV at 10^6 PFU/mL and imaged daily. Additional in vivo re-infection and superinfection tests with different strains and titers of MCMV will be conducted to further address the hypothesis. Thus far, preliminary imaging results suggest that initial infection in mice that received 10^6 PFU/mL had a much more severe primary infection that those that received the 10^2 PFU/mL until latency. However, mice who received the higher initial dose appeared to be more protected from re-infection, noted by lower imaging signals. In doing this research, we aim to guide future research regarding CMV infection, reinfection, vaccination.

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Session #5 (Afternoon) | Poster Board #39 Danielle Cohen, Undergraduate Student, Western University Supervisor: Angela Devlin, Healthy Starts

Congratulations to Danielle on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award

Effects of Maternal Folic Acid Supplementation on Offspring Metabolic Health Danielle Cohen, Ei-Xia Mussai, Nicha Boonpattrawong, Cynthia Ramires, Arya Mehran, Angela Devlin

Folate is a B-vitamin that is important in the prevention of neural tube defects during fetal development.

Women of childbearing age are recommended to take a supplement of 0.4 mg/day folic acid. However, daily prenatal supplements in Canada contain 0.8-1.0 mg folic acid leading to the intake of higher than recommended doses. Additionally, women with pre-gestational obesity (BMI â&#x2030;Ľ30kg/m2) are recommended to take 5 mg/day folic acid. This raises concern that high folic acid supplementation during pregnancy may have adverse consequences on the developing offspring. The aim of this study is to determine the effects of maternal folic acid supplementation on offspring metabolism. We hypothesize that supplemental folic acid during pregnancy will exacerbate the adverse effects of maternal obesity on the offspring.

Female (C57BL/6J) mice were fed a control (10% kcal fat) or western (45% kcal fat) diet, either with (10 mg/ kg diet; CDF, WDF) or without (2 mg/kg diet; CD, WD) supplemental folic acid. Western diet induces excess adiposity and glucose intolerance in order to emulate pre-gestational obesity. Females were bred at 13 weeks post-weaning. Maternal tissue, fetal pups, and placentae were collected at gestational day (E) 18.5.

Following tissue collection, there were no differences found in litter size however, although not significant (p=0.125), folic acid reduced the number of pregnancy losses in control fed dams. Weighing of fetal tissue showed that female offspring from western diet fed dams had larger placentae but smaller livers (p<0.05).

Investigation into the fetal pancreas showed sex specific differences with an increase in beta cell mass for males from CDF fed dams and females from WDF fed dams. Investigation into alpha cell mass is ongoing.

Future directions for this project include assessing proliferation and apoptosis of beta cells and comparing the current fetal data to a post-natal day 7 cohort.

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Session #5 (Afternoon) | Poster Board #40 Rachel Da Silva, Undergraduate Student, University of British Columbia Supervisor: Pascal Lavoie, Healthy Starts

Congratulations to Rachel on receiving a BC Children’s Hospital Research Institute Summer Studentship

Investigating the Role of STAT3 in Differentiation of Neonatal T helper 17 Cells Rachel Da Silva, Zohreh Sharafian, Ashish Sharma, Hamid Razzaghian, Pascal M Lavoie

Background: Severe mucocutaneous fungal infections, like oral thrush and diaper rash, are common in newborns in contrast to adults. T helper 17 (Th17) cells play a crucial role in clearing these fungal infections through the production of the signaling molecules IL-17 and IL-22. IL-17 is pro-inflammatory, whereas IL-22 promotes regeneration and tissue repair. However, newborn naïve T cells lack the capacity to differentiate into Th17 cells. Our previous transcriptome analysis showed a reduced expression of Signal Transducer and Activator of Transcription 3 (STAT3) in neonatal naïve T cells compared to adults. STAT3 is a key regulator in the process of Th17 cell differentiation.

Hypothesis: We hypothesize that the lack of Th17 differentiation in newborns is due to the reduced expression of STAT3. Thus, overexpression of exogenous STAT3 in neonatal naïve T cells can restore Th17 differentiation.

Methods: Neonatal naïve T helper cells were isolated from umbilical cord blood via density centrifugation and magnetic bead separation. A GFP-tagged plasmid encoding the STAT3 gene was then transfected into neonatal naïve T helper cells through electroporation. Transfection efficiency was confirmed by flow cytometry, and transfected cells were stimulated for 3 days in the presence of Th17-polarizing cytokines (anti-CD3/CD28, IL-1β, IL-6, IL-23, +/- TGF-β). Secretion of IL-17 and IL-22 were measured by ELISA. Results: STAT3-transfected neonatal naïve T cells produced higher levels of IL-17 compared to the empty vector-transfected corresponding cells. Interestingly, we found that in the absence of exogenous STAT3, only IL-22 is produced in Th17 conditions.

Conclusion: In the absence of sufficient STAT3, neonatal naïve T cells preferentially produce IL-22 rather than IL-17, whereas overexpression of STAT3 restores IL-17 secretion. Preferential IL-22 production in newborns may help protect mucosal surfaces from the pro-inflammatory effects of IL-17, but also increases their vulnerability to fungal pathogens.

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Session #5 (Afternoon) | Poster Board #41 Selina Demetrick, Undergraduate Student, University of British Columbia Supervisor: Laura Sly, Childhood Diseases

Investigating the Co-Stimulatory Effects of LPS and IVIg on FcgRIIIA Gene Variants Selina Demetrick, Yvonne Pang, Mahdis Monajemi, Susan Menzies, Laura Sly

Inflammatory bowel disease (IBD) is a general term used to characterize inflammatory disorders of the gastrointestinal tract, most commonly Crohnâ&#x20AC;&#x2122;s disease and ulcerative colitis. These diseases arise from a dysfunctional immune response, whereby there is an overproduction of pro-inflammatory cytokines.

Intravenous immunoglobulin (IVIg) is a drug composed of pooled polyclonal IgG antibodies (>95% IgGs). It is used to treat autoimmune and inflammatory diseases but its mechanism(s) of action remain unknown. We have reported that IVIg signals through antibody receptors (FcgRs) to activate macrophages to produce high concentrations of the anti-inflammatory cytokine, IL-10, which blocks intestinal inflammation in a pre-clinical mouse model of IBD. IVIg has not been used as a first-line treatment for IBD but has been shown to reduced IBD in people, who were receiving it for other indications.

Though IVIg therapy is very effective for the treatment of immune-mediated diseases, a gene variant in a specific receptor for IgG antibodies, Fc gamma receptor IIIA (FcgRIIIA), has been shown to predispose people to risk of developing IBD. In this project, I am investigating whether disease risk is associated with a failure to induce IL-10 production by macrophages from people, who harbor the FcgRIIIA risk variant. Monocytes derived from the blood of healthy donors will be treated with LPS, IVIg, or both and cytokine production will be measured. This research aims to identify a precision medicine approach to identify individuals, who will be effectively treated by IVIg therapy. Moreover, understanding more about the mechanism of IVIg binding, with respect to Fcg receptors, could lay groundwork for future research into potential therapies, namely inhibiting the activity of inflammatory Fcg receptors.

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Session #5 (Afternoon) | Poster Board #42 Alex Hsu, Undergraduate Student, University of British Columbia

Supervisors: Bruce Verchere & Heather Denroche, Childhood Diseases

Inducing tolerogenic dendritic cells using lipid nanoparticle as a potential therapy for type 1 diabetes Alex Hsu, Heather C. Denroche, Sam Chen, Josh Zaifman, Ying Tam, Chris Tam, C. Bruce Verchere

Introduction: Antigen presenting cells (APC) are responsible for the activation of self-reactive lymphocytes and are a therapeutic target for autoimmune diseases like type 1 diabetes. Dendritic cells (DCs) are a subset of APCs that are key players in both mediating immune responses and inducing immune tolerance. The plasticity of DCs allows manipulation into tolerogenic phenotype, which can be utilized to induce autoreactive T cell apoptosis and anergy. However, it is difficult to target DCs directly in vivo. Lipid nanoparticle (LNP) drugdelivery systems are promising tools for the delivery of small molecules to DCs in vivo, which can be leveraged to increase the therapeutic index of immunomodulatory drugs. In this study, we tested two dexamethasone prodrugs (D01, D02), and calcitriol prodrugs (C01, C02), alone and in combination, encapsulated in LNPs, to determine whether the LNP formulations can induce a tolerogenic phenotype on murine bone marrow derived DCs (BMDCs).

Methods: With our industry collaborators from Integrated Nanotherapeutics, we formulated dexamethasone and calcitriol-based prodrugs into lipid nanoparticles. Murine (C57BL/6J) BMDCs were treated with the formulations, subsequently activated with LPS, and co-cultured for 3 days with allogeneic (BALB/cJ) CD4+ splenic T cells. T cell proliferation was then measured via flow cytometry.

Results: Mature, LPS-stimulated BMDCs were better promoters of T cell proliferation compared to immature, non-LPS stimulated BMDCs. Dexamethasone, or calcitriol prodrug treatment of BMDCs prevented LPSinduced allogeneic T cell proliferation, comparable to immature BMDCs. Calcitriol prodrugs were more potent compared to dexamethasone prodrugs, while the of both showed the most reduced T cell proliferation.

Specifically, D01 and C01 in combination were identified to be the most potent formulation, reducing T cell proliferation from 19.6% of to 2.9%.

Conclusion: Having identified a potent tolerogenic LNP formulation, D01+C01, future studies will explore whether this formulation can attenuate the onset of type 1 diabetes in non-obese diabetic mice.

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Session #5 (Afternoon) | Poster Board #43 Min Jung Kim, Undergraduate Student, McMaster University Supervisor: Chinten James Lim, Childhood Diseases

Congratulations to Min on receiving a BC Children’s Hospital Research Institute Summer Studentship

Targeting the Leukemia Tumor Antigen CD47 Min Jung Kim, Pascal Leclair, Chinten James Lim

Background: Acute Lymphoblastic Leukemia (ALL) is the most prevalent form of cancer among pediatric patients. It is highly treatable, achieving an overall 5 year survival rate between 80-90%. However, the prognosis for relapsed patients remain poor, often due to acquired chemoresistance. Hence, an emerging avenue for therapy involves targeting cell-surface proteins, such as CD47, in order to enhance the immunogenicity of tumor cells. CD47 is frequently upregulated in cancer cells, and modulates a “don’t eat me” signal which inhibits phagocytosis, allowing cells to evade immune recognition. However, ligation of CD47 by anti-CD47 antibodies (Abs) or thrombospondin-1 (TSP-1) derived peptides has been shown to effectively induce tumour cell death. Our study aims to characterize one of these anti-CD47-Abs: CC2C6, as well as the TSP-1-derived peptides, 4N1K and PKHB1, in order to better exploit the CD47-induced cell death pathway and optimize the therapeutic benefits of targeting CD47.

Methods and Results: Previously, the Lim laboratory had shown that CC2C6 induces CD47-dependent cell death in T-ALL cells, while others had shown that CC2C6 binding requires posttranslational modification of CD47 mediated by glutaminyl-peptide-cyclotransferase-like protein (QPCTL). Using flow cytometry, CC2C6CD47 epitope expression and apoptosis was assessed in T-ALL cells treated with SEN177, a QPCTL inhibitor.

Increasing concentrations of SEN177 resulted in decreasing cell surface expression of CC2C6-CD47 and decreasing CC2C6-mediated apoptosis, suggesting that the cell death-inducing effects of CC2C6 are dependent on QPCTL activity.

The role of 4N1K, as well as its serum-stable analog PKHB1 in mediating CD47-dependent cell death has also been investigated in prior studies. Therefore, we assessed 4N1K and PKHB1-induced cell death in two previously tested T-ALL cell lines, as well as a CD47-null cell line. However, we observed significant cell death across all cell lines tested, including our CD47-null. This result is consistent with an interpretation that 4N1K and PKHB1-induced cell death is not dependent on CD47 as the presumptive receptor.

Significance: The results of our study inform further development of CC2C6 as a therapeutic agent for leukemia, as we confirm its ability to induce CD47-dependent cell death, and describe a possible role of QPCTL in mediating the effects of CC2C6. Additionally, our findings suggest that the peptides 4N1K and PKHB1, which are frequently used to study CD47-mediated effects, are non-specific to CD47 and demonstrate CD47independent effects.

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Session #5 (Afternoon) | Poster Board #44 Anson Law, Undergraduate Student, University of British Columbia Supervisor: Elizabeth Conibear, Childhood Diseases

Congratulations to Anson on receiving a BC Children’s Hospital Research Institute Summer Studentship

Investigating the Role of a Conserved Rab5 Regulator in Selective Autophagy Anson Law, Shawn Shortill, Elizabeth Conibear

Autophagy is a highly conserved intracellular process responsible for the degradation of cytosolic contents and defects in autophagy have emerging links to many human diseases such as pulmonary disease, a variety of cancers, Parkinson’s disease and Huntington’s disease. Despite increasing interest, the molecular mechanisms of autophagy and its regulation are still incompletely understood. Recently, Rab5 GTPases and their effectors have been shown to be key players in the autophagic pathway. Previous work in the Conibear lab uncovered a novel Rab5 activator protein, a guanine nucleotide exchange factor (GEF), in the budding yeast S. cerevisiae that is absent in laboratory strains. This activator was termed Vrl1 due to homology to the human protein VARP, which also regulates Rab5 activity.

Through a genome-wide yeast screen for proteins that physically interact with Vrl1, new candidate interactors were identified – two proteins of unknown function and a third protein implicated in a specialized form of autophagy. All three proteins – Snx51, Gvp36, and Cue5 respectively – are conserved in humans. I hypothesize that these genes may work with Vrl1 to regulate a specialized autophagy pathway that specifically targets protein aggregates. Thus, my research aims were to confirm whether Vrl1 physically interacts with these proteins, whether Vrl1 changes their localization within the cell and to investigate a Vrl1-specific role in autophagy.

Fluorescence microscopy showed that Vrl1 increased fluorescent signal from Gvp36 relative to the same strain without Vrl1, and N-terminally tagged Gvp36 resulted in minimal signal regardless of Vrl1. Additionally, Vrl1 changed localization of Snx51 but not for Cue5 and Gvp36 and immunoprecipitated with Snx51. Future experiments involve inducing autophagy before experimentation and quantifying the increased Gvp36. The reintroduction of Vrl1 and GEF domain inactivated Vrl1 in a strain lacking other Rab5 GEFs will also allow us to determine if this novel Rab5-GEF can provide the sole GEF activity for various types of autophagy. The discovery of a novel autophagy pathway in yeast may highlight shared machinery due to the conserved nature of human and yeast autophagy. Thus, by understanding aggregate degradation mechanisms in yeast, we may further our understanding of human autophagy and its implications in disease.

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Session #5 (Afternoon) | Poster Board #45 Anita Poon, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

Congratulations to Anita on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award

Interleukin 37-SIGIRR interactions and their effects on intestinal epithelial cells Anita Poon, Joannie Allaire, Bruce Vallance

Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract caused by excess inflammation in response to the gut microbiota. In a healthy gut, intestinal epithelial cells do not respond to commensal bacteria, in part due to the strong expression of the Single Immunoglobulin Interleukin-1 Relation Receptor (SIGIRR). SIGIRR is known for its anti-inflammatory effect by negatively regulating IL-1 and Toll-like receptor signalling. Interleukin (IL)37, a newly recognized anti-inflammatory cytokine, has been shown to interact with the IL-18 receptor and SIGIRR to reduce inflammation. The goal of this project was to study the anti-inflammatory effects of IL37 on intestinal epithelial cells and the interaction between IL-37 and SIGIRR. Methods: Using primary intestinal epithelial organoids derived from mouse (SIGIRR wildtype (WT) or knockout (KO)) and human (healthy control or IBD patient), we examined the anti-inflammatory effects of IL37 on innate immune signaling in intestinal epithelial cells. Intestinal organoids were stimulated with the inflammatory cytokine IL-1β or the bacterial product FliC in the presence or absence of IL37. Cytokine and chemokine mRNA and protein levels were measured using qPCR and cell supernatants for ELISA. Monolayers derived from mouse organoids were stained for the transcription factor Nfκb to evaluate innate immune activation.

Results: In WT organoids, IL37 caused a reduction in inflammatory cytokine and chemokine (Cxcl1, TNFα) levels and reduced NFκB activation in response to IL1β stimulation. These effects were dependent on SIGIRR expression since IL37 did not have a significant effect on SIGIRR KO organoids. In human organoids, IL37 was able to reduce the expression of the neutrophil attracting chemokine IL8 after FliC stimulation in healthy control organoids whereas IBD derived organoids were non-responsive to IL37 and responded aberrantly to stimulation.

Relevance: These experiments show that IL37 exerts an anti-inflammatory effect on mouse and human intestinal epithelial cells. Moreover, these results show that SIGIRR expression is needed for the IL37 effect.

Future studies will define the basis for the lack of IL-37 responsiveness of IBD derived organoids, and explore its potential involvement in the pathogenesis of IBD.

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Session #5 (Afternoon) | Poster Board #46 Sadaf Sediqi, Undergraduate Student, University of British Columbia Supervisor: Paul Yong, Healthy Starts

Congratulations to Sadaf on receiving a UBC Faculty of Medicine Summer Studentship

Nerve bundles and its associations with deep dyspareunia in endometriosis: Can a binary scoring system be useful for pathologists?

Sadaf Sediqi, Fahad T. Alotaibi, Anna F. Lee, Paul J. Yong

Introduction: Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial tissue outside of its normally-occurring region in the uterus. Symptoms include chronic pelvic pain, dyspareunia (painful sexual activity), dysmenorrhea (painful menstrual cramps). Therapeutics are available to women – however these treatments are not effective in many women, which may be due to the lack of understanding of how endometriosis causes pain. Our lab previously reported that nerve bundle density utilizing an individual counting method of each nerve bundle, is positively correlated with patients who report higher pain scores of deep dyspareunia​and higher expression of a pro-inflammatory cytokine, Interleukin-1β (IL-1β). This nerve bundle counting system, however, requires prolonged time and effort and thus not practical for pathologists in clinical practice. We proposed a modified methodology that is more efficient and could be translated to clinical pathology.

Aims: A pilot study to determine the association between nerve bundles, using a proposed binary scoring system, and other variables such as deep dyspareunia score and IL-1β Histoscores.

Methods: Pain scores were obtained from endometriosis patients’ questionnaires which included severity of deep dyspareunia (sexual pain). Immunohistochemistry (IHC) slides stained with specific neuronal markers and IL-1β markers respectively were scored for this study. A T-test was used to compare means of both IL-1β Histoscores and clinical pain scores.

Results: There was a significant increase in IL-1β histoscores in endometriosis epithelial cells and stromal cells in patients who had nerve bundles within a 10x field of endometriosis lesions (n=23, p=0.04 for endometriosis epithelial cells, and n=23 and p=0.02 for endometriosis stromal cells). Trends towards increased deep dyspareunia score in patients who had nerve bundles within a 10x field of endometriosis lesions, although it did not reach statistical significance.

Conclusion: In this pilot study, a simple-to-use binary system for quantifying nerve bundles around endometriosis was associated with increased IL-1β expression in endometriosis, with a trend towards increased pain scores. If the findings are validated, the binary system could be used by pathologists to define a sub-type of endometriosis that is associated with IL-1B induced neurogenesis (“neuroproliferative” subtype).

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Session #5 (Afternoon) | Poster Board #47 Esther Lin, Undergraduate Student, University of British Columbia Supervisor: Elodie Portales-Casamar, Evidence to Innovation

Natural Language Processing of Psychiatric Clinical Notes

Elodie Portales-Casamar, Rebecca Lin, Esther Lin, Ali Mussavi, Sinead Nugent, Ali Eslami The Child and Adolescent Psychiatric Emergency (CAPE) unit at BC Childrenâ&#x20AC;&#x2122;s Hospital provides emergency intervention and stabilization for youth in psychiatric crises. At admission and discharge, patients receive extensive diagnostic assessments largely recorded as free-text clinical notes. The reports are difficult to incorporate in large-scale analyses, as manual information extraction is laborious and prone to error. Hence, our study explores applications of text mining in extracting accurate, structured data from psychiatric clinical records. We aim to develop an automated data extraction pipeline to distill clinically relevant information from CAPE records, and, ultimately, apply the extracted data in developing machine learning algorithms to predict patient suicidality.

Our preliminary dataset consists of 1559 clinical records. We first programmatically de-identified each text and performed section segmentation, sentence tokenization, and stop word removal to clean the records. Then we detected medical entities, including symptoms, diseases, diagnoses, and medications, through retrieving ontology-based annotations from a local implementation of the National Centre of Biomedical Ontology (NCBO) BioPortal. Lastly, we adapted context-detecting algorithms to determine the negation, experiencer, and temporal status for each extracted terminology.

For evaluation and optimization, study results are compared to an existing repository of annotated patient records from CAPE. Thus far, our investigation indicates that text mining could be an effective tool in analyzing psychiatric records. Moreover, through automating data extraction processes at CAPE, we would be able to produce the structured information researchers require to conduct large-scale analyses, generate patient statistics, and construct predict models in support of pediatric mental health.

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Session #6 BASIC SCIENCE 1:30 - 3pm

Moderator: Dr. Sarah Moore Participants: Azim Ahmed Mairead Cavinaw Azriel Chang Josef Goetz Kavi Grewal Sanya Grover Emily Gubski Luxcia Kugathasan Shirley Zhi

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Session #6 (Afternoon) | Poster Board #48 Azim Ahmed, Undergraduate Student, University of British Columbia

Supervisors: Tom Blydt-Hansen & Anita Cote, Childhood Diseases & Evidence to Innovation

Lean Body Mass as a Quality of Life Predictor in Post Renal Transplant Pediatric Patients Azim Ahmed, Tom Blydt-Hansen, Anita Cote

Background: Kidney transplantation has an incredibly high success rate at around 90%. Although kidney transplantation increases quality of life, post-transplant patients experience an increase in co-morbidities.

To improve patient wellbeing post transplant, looking at various ways in which these co-morbidities can be reduced is the next step in renal transplant research. Body composition, specifically lean body mass (LBM), may be a potential target. Previous studies investigating the impact of lean body mass, observed an increase in lean body mass post-transplant. However, the reduced height and subsequent lower lean body mass in renal transplant patients compared to the general population was not accounted for. Height acts as a confounding variable and needs to be adjusted for. The impact of physical activity on LBM has not been explored in the pediatric renal transplant population. In other populations, the relationship between physical activity and lean body mass is unclear with some studies reporting increases in LBM while others reporting no change.

Purpose and Aims: This study investigates whether physical activity levels are associated with lean body mass measurements after transplantation, and if these body composition changes affect kidney function.

Methodology: Individuals who had received a kidney transplantation before the age of 21 were identified.

Of those patients, 24 had a recent Dual X-ray Absorptiometry (DXA) scan completed and had answered a Physical Activity Questionnaire (PAQ) and the data from these individuals was used to examine the relationship between lean body mass and exercise post-transplant. Both lean body mass and bone density were adjusted for height. 9 Individuals were identified who had more than one DXA scans and the data was used to determine the effect of LBM with clinical factors such as creatinine, albumin, hemoglobin, as well as immunosuppressant use.

Preliminary Results: After regression analysis, no association between LBM and physical activity levels were found.

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Session #6 (Afternoon) | Poster Board #49 Mairead Cavinaw, Undergraduate Student, University of British Columbia Supervisor: Peter van den Elzen, Childhood Diseases

Investigating Paul-Bunnell antigen specific tonsillar mononuclear cells as a link between Infectious Mononucleosis and Multiple Sclerosis Mairead Cavinaw, Rana Minab, Dong-Jun Zheng, Peter van den Elzen

Background: Multiple sclerosis (MS) is a devastating autoimmune disease characterized by the destruction of myelin, the glycolipid-rich sheath around neuronal fibres in the brain and spinal cord. Importantly, virtually everyone with MS is also infected with Epstein-Barr virus (EBV). EBV is a common viral infection that is largely innocuous, but 75% of young adults develop typical infectious mononucleosis (IM) after primary EBV infection. Among those individuals, the risk of MS is increased by two to three-fold, making it the strongest environmental risk factor. IM can be diagnosed by the presence of heterophile antibodies which target antigens of other mammalian erythrocytes, specifically the Paul-Bunnell (P-B) antigen. The P-B antigen is a glycolipid that is structurally akin to certain myelin gangliosides. We suspect that EBV infection primes the immune system to attack myelin, through the heterophile antibody produced during IM cross-reacting with myelin gangliosides.

Objectives: We aim to understand the differences between B cell populations in EBV infected and uninfected people, focusing on whether certain cells are preferentially infected and their specificities, and compare these differences to the cell populations seen in EBV infections that led to IM. Methods: Sera of patients who underwent tonsillectomies at BC Childrenâ&#x20AC;&#x2122;s Hospital were tested to identify EBV infected and noninfected patients. The matched tonsillar mononuclear cells were separated based on specificity for the P-B antigen using bovine red blood cells, which naturally express P-B antigen, and Ficoll density gradient centrifugation. The separated cells from EBV infected patients were cultured for spontaneous outgrowth, while the EBV uninfected cells were cultured and infected with fluorescently tagged EBV. The supernatants of the cultures were tested for the presence of heterophile antibody. Using flow cytometry, the cell markers of the EBV uninfected and infected cells were compared.

Expected Results: EBV will preferentially infect B cells with P-B antigen specificity and induce the production of heterophile antibodies.

Impact: Understanding the mechanism of heterophile antibody production in EBV infection will inform further investigations into what determines susceptibility for developing IM, with the hope of preventing IM as a means of preventing MS.

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Session #6 (Afternoon) | Poster Board #50 Azriel Chang, Undergraduate Student, University of British Columbia Supervisor: Theodore Steiner, Childhood Diseases

Congratulations to Azriel on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Childhood Diseases Summer Studentship

Evaluation of a Clostridioides difficile Mouse Model for CDI studies Azriel Chang, Daniel Lisko, Theodore Steiner

Background: Clostridioides difficile, an obligate anaerobe, is a major cause of hospital acquired infections worldwide. Disruption of the microbiome by antibiotic use depletes beneficial bacteria and permits the colonization, growth, and toxin production by C. difficile. Ironically, the standard treatment for C. difficile infection (CDI) is antibiotics, which has resulted in increased antibiotic resistance and healthcare burden.

Therefore, animal models of CDI are important to develop and evaluate alternative treatments for CDI. Aim: The aim of this project is to evaluate a C57BL/6 model of CDI, taking into consideration the microbiome, to determine if this model would be appropriate for future CDI studies.

Methods: C57BL/6 mice were administered cefoperazone for 10 days in drinking water, and then switched back to regular water for 2 days. Intraperitoneal (I.P.) injections of clindamycin were performed 24 hours prior to oral gavage of varying doses of C. difficile strain ATCC 9689. Mice were monitored daily for CDI symptoms and weight loss, while stools were collected to analyze the microbiome and C. difficile load. Quantitative Polymerase Chain Reaction (qPCR) targeting the 16s rRNA and toxin B (tcdB) genes was used to quantify the microbiome and C. difficile load, respectively. Mice were euthanized 12 days post-infection and intestines collected for histology.

Results: Infected mice showed CDI symptoms and substantial weight loss during the first three days postinfection but returned to baseline within 5 days. qPCR results show that the antibiotics depleted the microbiome and that C. difficile colonized infected mice, but not long enough to establish a long-term infection. Additionally, qPCR results showed that the intestinal microbiome recovered by day 5 post-infection.

The dosage of C. difficile spores required for symptomatic infection in this study was higher than doses reported in literature, indicating that the virulence of ATCC 9689 was possibly being attenuated in this model due to competition from other intestinal microbes.

Future Directions: Further experiments will be conducted with C. difficile strain VPI 10463, a strain known to produce copious amounts of toxin, to determine if the attenuated virulence of ATCC 9689 was the cause of failure to establish long-term infection in the model.

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Session #6 (Afternoon) | Poster Board #51 Josef Goetz, Undergraduate Student, University of Toronto Supervisor: Angela Devlin, Healthy Starts

Congratulations to Josef on receiving a Community Child Health Endowment Summer Studentship

Maternal Exercise and Obesity During Pregnancy and Resultant Offspring Lipid Metabolism and Cardiac Remodeling Josef Goetz, Nicha Boonpattrawong, Angela M. Devlin, Ismail Laher

The developmental origins of health and disease theory suggests that prenatal and early postnatal environments pose far-reaching consequences on future health. For example, evidence indicates that maternal obesity forges a uterine environment that increases the risk of children developing cardiovascular disease in adulthood. With approximately 50% of women of childbearing age having overweight or obesity in Canada, the scale of this concern becomes too great to ignore. Studies in rodents have shown exercise to be a possible mitigating factor on the adverse effects maternal obesity poses to offspring adiposity, glucose tolerance, and cardiac hypertrophy. Our lab has additionally described improved glucose tolerance and vascular function in male offspring from exercising dams with diet-induced obesity during pregnancy and lactation; however, the mechanisms underlying this effect remain unknown.

We hypothesize that maternal exercise mitigates adverse effects of obesity on offspring health through effects on liver lipid metabolism and cardiac remodeling.

Female C57BL/6N mice were fed a control (10% kcal fat) or western (45% kcal fat) diet from weaning, with or without access to an exercise wheel. Dams were maintained on the diet for 12 weeks post-weaning before exercise/breeding, ensuring increased adiposity and glucose intolerance at the time of conception. The offspring were weaned onto the control or western diet and fed for 13 weeks. Tissue was collected from female and male offspring tissue and frozen for later analysis ( n=5-6/group/sex). From liver tissue, mRNA expression of key genes governing lipid metabolism were quantified using qPCR analysis. The triglyceride and Bradford protein assays were performed on homogenized left ventricle to assess lipid accumulation and cardiac remodeling.

We are currently completing the analysis of the qPCR data. Depending on our findings, we will conclude as to whether varying metabolic gene expression in the liver might be a mechanism by which exercise mitigates the adverse effects of maternal obesity on offspring. Histological analysis of cardiomyocytes via wheat germ agglutinin-staining will be conducted and protein expression will be assessed in left ventricle by western blot.

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Session #6 (Afternoon) | Poster Board #52 Kavi Grewal, Undergraduate Student, University of British Columbia Supervisors: Bruce Verchere & Yi-Chun Chen, Childhood Diseases

Pancreatic hormone processing during the development of type 1 diabetes Kavi Grewal, Yi-Chun Chen, Bruce Verchere

Introduction: Type 1 diabetes (T1D) is characterized by autoimmune attack, which leads to the dysfunction and death of insulin producing beta cells in the pancreas. In beta cells, insulin is first synthesized as a large precursor protein called proinsulin. Proinsulin processing enzymes such as proprotein convertase 1/3 (PC1/3), proprotein convertase 2 (PC2), and carboxypeptidase E (CPE) then process proinsulin to mature insulin. Despite near-absolute loss of insulin production in T1D, proinsulin is still detectable, suggesting the islet prohormone processing machinery is likely impaired. Therefore, we hypothesized that in the pancreas of persons with T1D, a residual amount of beta cells have sustained proinsulin expression, associated with decreased expression of the enzymes that process the prohormone (PC1/3, PC2, and CPE).

Methods: Human pancreas tissue sections from sex, age, and BMI-matched non-diabetic control, autoantibody positive, short duration (< 5 years after disease onset) T1D, long duration ( >15 years after disease onset) T1D, and type 2 diabetes (T2D) donors were obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD). Immunofluorescent staining was performed using antibodies specific to insulin, proinsulin, and PC1/3. Whole pancreas and high resolution islet images were acquired via fluorescence and confocal microscopy. PC1/3-positive and/or insulin positive islet number and islet area, as well as PC1/3 expression levels were quantified using image processing software with custom processing pipelines.

Results: Insulin, proinsulin, and PC1/3 expression profiles are comparable in the pancreatic islet sections of non-diabetic, auto-antibody positive, and T2D donors. While expression of insulin and proinsulin is greatly decreased in the islets of short and long-duration T1D donors, expression of PC1/3 showed only modest reduction.

Conclusions: In the islets of longstanding T1D donors, where insulin expression is significantly decreased, PC1/3 levels remain detectable. Our findings suggest that the reduced prohormone processing during T1D may be associated with events other than the loss of PC1/3 expression in islets.

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Session #6 (Afternoon) | Poster Board #53 Sanya Grover, Undergraduate Student, McMaster University Supervisor: Francis Lynn, Childhood Diseases

Congratulations to Sanya on receiving a Canucks for Kids Fund Childhood Diabetes Laboratories Summer Studentship & Centre for Blood Research-School of Biomedical Engineering Summer Studentship

Uncovering Function of GRK5 in Mouse Pancreatic Beta-Cells Sanya Grover, Shugo Sasaki, Cuilan Nian, Helena Winata, Eric E. Xu, Francis Lynn

Background: The prevalence of diabetes is rapidly growing, with 4.2 million Canadians estimated to be affected by 2020. One of diabetesâ&#x20AC;&#x2122; major pathogenesis is the loss of functional beta-cells in the pancreas. However, mechanisms of beta-cell mass regulation are not fully understood. Our laboratory has previously found that transcription factor SOX4 allows facultative beta-cell proliferation through the repression of cell cycle inhibitor gene Cdkn1a. RNA-sequencing of SOX4 KO islets at the earlier stage demonstrated that G protein-coupled receptor kinase 5 (GRK5) was one of the genes downregulated in KO islets. Previous literature used GWAS to identify GRK5 as a type 2 diabetes susceptibility gene. Thus, we hypothesized that GRK5 regulates beta-cell mass.

Methods: To investigate GRK5 function in beta-cells, we generated beta-cell GRK5 KO mice using PDX1-CreER; GRK5flox/flox mouse lines. An oral glucose tolerance test (OGTT) was performed in KO and control mice at 6, 10, 14, and 18 weeks of age. Using ELISA, serum insulin levels before and after glucose stimulation (at 0 and 10 minutes respectively) were determined. Number of insulin and pancreatic cells at 18 weeks was found.

Results: Prior to genetic GRK5 deletion at 6 weeks of age, no difference was observed between the glucose levels of mice. During OGTT, glucose levels were increased significantly in GRK5 KO mice at 14 weeks of age as compared to the control, which continues into 18 weeks of age. A lower serum insulin level was seen in KO mice at 14 and 18 weeks of age after stimulation when compared to the control. The number of beta-cells was lower in KO mice versus control.

Conclusions: Impaired glucose tolerance was demonstrated in GRK5 KO mice. There was no increase of insulin to compensate for higher glucose levels. Beta-cell mass also reduced in KO. Thus, GRK5 KO mice have impaired insulin secretion through beta-cell mass regulation which is what causes them to be glucose intolerant. Our future analyses include bulk-RNA sequencing with isolated islets to reveal changes in the transcriptome pattern. If successful, GRK5 could become a potential target of cell therapy to preserve functional betaâ&#x20AC;&#x201C;cells during diabetes.

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Session #6 (Afternoon) | Poster Board #54 Emily Gubski, Undergraduate Student, University of British Columbia Supervisor: Kevan Jacobson, Childhood Diseases

Congratulations to Emily on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship

Characterization and Visualization of Enteric Organoids

Emily Gubski, Emily Davies, Xiao Han, Mariana Diaz Gomez, Shauna Crowley, Kevin Tsai, Bruce Vallance, Kevan Jacobson Background: Inflammatory bowel disease (IBD) is a painful condition caused by chronic inflammation of the digestive tract. It is widely believed that disruption and defects within the epithelial barrier caused by a combination of environmental, hereditary and microbial factors play a key role in causing the disease.

Traditionally, IBD studies are conducted using cell lines, animal models and in some cases human subjects.

While studies conducted on human subjects are the most informative, ethical considerations often limit what kind of experiment can be conducted. To overcome this problem, IBD researchers are currently developing a new model system called enteroids. Enteroids are an in-vitro three-dimensional cell culture grown from intestinal stem cells. They are thought to contain the same cell types found within the intestinal epithelial layer of a person and can, therefore, respond to treatments in a similar way. Although enteriods can be successfully derived from stem cells, there is currently no effective way to characterize the enteroids to assess whether they resemble the actual intestinal epithelial cell layer. To remedy this issue, we developed a set of multi-colour flow cytometry panels to simultaneously assess several parameters related to cell death, cell differentiation, and effector molecule production.

Aim: Use flow cytometry to assess how successfully organoids have differentiated into various intestinal epithelial cell lineages.

Methods: Enterioids derived from mice or human subjects are harvested, disassociated into single-cell suspensions and stained with antibodies specific for stem cell markers (CD24, CD44, LGR5), differentiation markers (Mucin 2 (MUC2), lysozyme, and Aleuria Aurantia Lectin (AAL)). Data was collected using flow cytometry and analyzed.

Results and Conclusion: Flow cytometry analyses of our enteroid cultures revealed that their expression of stem markers (CD24, CD44, LGR5) can be downregulated through inhibitor treatment, while the same treatment can increase the expression of differentiation markers such as lysozyme, AAL and MUC2. These results suggest that we can direct the cell fates of enteroids towards certain intestinal epithelial cell lineages such as goblet cells (MUC2+) and paneth cells (Lysozyme+).

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Session #6 (Afternoon) | Poster Board #55 Luxcia Kugathasan, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

Congratulations to Luxcia on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award

Unfolding the mRNA exportation process in the NHR-49 dependent oxidative stress response pathway Luxcia Kugathasan, Kelsie Doering, Stefan Taubert

Background: The basis of Caenorhabditis elegans survival in several environmental stresses is paramount to understanding cellular responses in complex organisms, for instance, the oxidative stress response pathway.

Oxidative stress, an imbalance of reactive oxygen species (ROS) and antioxidants, occurs in diseases such as cancer and diabetes. Despite its evident simplicity, C. elegans; microscopic nematode worms, serve as an important in-vivo model in biomedical research as it conserves many stress response pathways in human pathology.

The nuclear hormone receptor transcription factor NHR-49 is required in ROS detoxification in the presence of tert-butyl hydroperoxide (tBOOH); an oxidative stress inducer, including induction of the stress response gene fmo-2. Other factors that work with NHR-49 in the stress response pathway are unknown.

Expression of fmo-2 is directly dependent on the nuclear pore complex (NPC) to regulate and export mRNA for translation. P granules, a conserved ribonucleoprotein (RNP) cluster with NPC proteins (NPP) holding its integrity, localize at nuclear pores and collects newly synthesized mRNA prior to their release to the cytoplasm.

It may also be involved in mRNA translation, modification and degradation (de-capping).

Method: I am investigating ~450 transcriptional co-regulators through RNA interference (RNAi) screening. By marking fmo-2 with green fluorescent protein, I identify co-regulators that are required for tBOOH-induced fmo-2 expression which may be involved in the NHR-49 pathway.

Results: I have identified ~80 potential hits that I will validate. Interestingly, of 25 C. elegans NPPs, 9 were identified in my screen, thus revealing a potential role for the NPP in the NHR-49 pathway. Additionally, all nuclear cap binding proteins and 4 RNP of the 7 in C. elegans are potential hits.

Conclusion: The identified hits greatly suggest NPPâ&#x20AC;&#x2122;s role in the mRNA assembly and exportation process under oxidative stress. In brief, identifying factors that are involved in the oxidative stress response in C. elegans can serve to understand and treat human diseases that emulate the similar conserved pathway.

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Session #6 (Afternoon) | Poster Board #56 Shirley Zhi, Undergraduate Student, University of British Columbia Supervisor: Christopher Maxwell, Childhood Diseases

Targeting Centrosome Amplification in Aneuploidy Childhood Leukemia Shirley Zhi, Maria Guo, Christopher Maxwell

Backgrounds: Acute lymphoblastic leukemia (ALL) is defined by immature T and B precursors accumulated in bone marrow. It is the most common malignancy in children and is low risk. Yet, survival rate for relapsed and refractory ALL is poor. Additionally, current treatments can lead to tissue damage and pathologies after the child is cured. Therefore, we aim to understand the molecular lesion in B-ALL cells to help develop new treatment to meet current clinical needs.

Our study focuses on aneuploid B-ALL. Abnormal chromosome number is likely generated by a defective mitosis which also gives rise to an abnormal number or size of centrosomes. During cell division, cancer cells have developed mechanisms to cluster extra centrosomes to mimic bipolar spindle formation. Such clustering process is required for viability in B-ALL cells. We hypothesize that centrosome amplification is a common feature of aneuploid B-ALL. Inhibitors of centrosome clustering may be a specific treatment to target the proliferation of aneuploid B-ALL. Thus, we hypothesize resistant aneuploid B-ALL cells will be prone to genomic instability and immunogenicity.

Aims: 1. To determine the frequency of centrosome amplification in aneuploid B-ALL cells 2. To characterize genomic instability (micronuclei percentage) and immunogenicity ( cGAS/STING activation) for resistant B-ALL cells.

Methods: Immortal hyperdiploid 289 B-ALL cell line from Emu-ret mice was immunostained with centrosome markers. Centrosome amplification was evaluated in mitotic and interphase cells, based on size and number (3+). To model the refractory tumor progression, 289 B-ALL cells resist to inhibitors (AZ82 and Stattic, centrosome clustering inhibitors; PJ34 and Olaparib, PARB inhibitors) were generated. Micronuclei formation in wildtype and resistant cells was analyzed using high-content imaging. Cell lysates from wild type and resistant cells were collected for western blot analysis on phosphorylated TBK/IFR3 level which is part of the cGAS/ STING pathway.

Results and Future Directions: Our data suggests centrosome amplification is common among aneuploid B-ALL. Cells that resist to inhibitors have significantly increased micronuclei levels. Future experiments include localizing cGAS using immunostaining technique and investigating Type 1 interferon level using PCR of wildtype and resistant cells.

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Session #7

CLINICAL, POPULATION HEALTH & HEALTH SERVICES 1:30 - 3pm

Moderator: Dr. Matthew Smyth Participants: Maria Fernanda Huicochea Munoz Aziz Ghafoor Helen Hsiao Caleb Ritchie Ruth Liu Tina Madani Kia John Sung Jae Yun Lee

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Session #7 (Afternoon) | Poster Board #57 Maria Fernanda Huicochea Munoz, Undergraduate Student, McMaster University Supervisor: Li Wang, Healthy Starts

Congratulations to Maria on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Audit on the Effectiveness of Fetal Fibronectin to Predict Preterm Labor at BC Women’s Hospital Maria F. Huicochea Munoz, Jeffrey Bone, Anna F. Lee, Ken Lim, Joseph Ting, Li Wang

Background: The fetal fibronectin (fFN) test has been used since 2008 at BC Women’s Hospital (BCWH) to help stratify the risk of preterm delivery in patients presenting with threatened preterm labor (TPTL). Risk stratification helps to better identify those who require treatment/hospitalization and those that do not.

However, recent literature suggests that the fFN test does not reduce unnecessary treatment or improve health outcomes, and that its use in clinical practice is not justifiable.

Objectives: 1. Assess the predictive ability of the fFN testing at BCWH. 2. Determine if fFN results correlate with TPTL management, neonatal outcomes and placental pathologies. 3. Compare the predictive accuracy of fFN alone with that of other preterm labor indicators.

Methods: Women who received an fFN test at BCWH in 2017 were included in the study (n=158). Sensitivity (Sn), specificity (Sp) and positive/negative predictive values (PPV/NPV) of the fFN test were calculated.

Correlation between fFN results and TPTL management was determined by logistic regression. Correlation analyses between fFN results and adverse neonatal outcomes and placental pathology, are pending.

Comparison of fFN with other preterm labor indicators is pending.

Results: The fFN test had Sn=0.500, Sp=0.767, PPV=0.077, NPV=0.975 for birth within 7 days of testing, and Sn=0.750, Sp=0.798, PPV=0.231, NPV=0.975 for birth within 14 days of testing (n=103 cases reviewed to date).

Patients with a negative test were hospitalized for 51 fewer hours (CI 99.54-3.42; p=0.037), compared to patients with a positive test (n=60 cases reviewed to date). Compared to 0% of patients with a negative test, 76.9% (p<0.001) and 42.9% (p<0.001) of patients with a positive test received corticosteroids and tocolytics, respectively (n=52 cases reviewed to date).

Conclusion: Consistent with previous studies, the fFN test has a high specificity and NPV. Negative fFN correlates with reduced length of hospitalization and treatment administration.

Significance: Our results suggest that a negative fFN test is associated with low risk of preterm delivery within 7 and 14 days of testing. The main value of this test is its high NPV, which helps to identify patients who do not require further hospitalization and/or treatment.

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Session #7 (Afternoon) | Poster Board #58 Aziz Ghafoor, Undergraduate Student, University of the Fraser Valley Supervisors: Paul Yong & Fuchsia Howard, Healthy Starts

Congratulations to Aziz on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship

Sexual Pain & Endometriosis: A Patient-Oriented Integrated Knowledge Translation Project Aziz Ghafoor, Fuchsia Howard, Heather Noga, Endometriosis Patient Research Advisory Board, Kiran Parmar, Paul Yong

Background: Endometriosis is a gynaecological disease that affects 1 in 10 women in Canada and is characterized by the presence of endometrial cells outside of the uterus leading to painful menstrual cramps, chronic pelvic pain, and sexual pain. Deep dyspareunia (pelvic pain due to deep penetration during sexual intercourse), occurs in approximately 50% of women with endometriosis, negatively influencing their sexual functioning and interpersonal relationships. Despite the prevalence and impact of deep dyspareunia, there is limited accessible, evidence-based information specific to sexual pain to assist individuals to understand and manage their symptoms, seek appropriate health care, and make treatment decisions.

Aim: Guided by the tenants of patient-oriented research, the aim of this integrated knowledge translation project was to develop a patient-centred online platform for people with endometriosis-related sexual pain.

This online platform will help them understand their condition, feel empowered, and find validation, thus improving well-being and quality of life.

Methods: Firstly, we conducted stakeholder focus groups with patients, clinicians, researchers and endometriosis organizations to determine the appropriate audience, content, key messages, mood and feel of the online platform. Secondly, we identified and evaluated existing online resources specific to endometriosisrelated sexual pain for readability, suitability, and quality using the eHealth tools SMOG, JAMA benchmarks, SAM and DISCERN. Finally, we developed the content for the online platform informed by principals of usercentred iterative design.

Results: We developed an inclusive online platform for a diverse audience related to age, ethnicity, gender identity, relationship status, sexual pain experience, and endometriosis diagnosis. To meet patient content needs, we developed plain language explanations of the types of sexual pain, physical and psychological mechanisms, management and treatment options, and resources. Hope, de-stigmatization, empowerment, and connectedness were conveyed through short messages, visual images and design. Preliminary online resource evaluation suggests that existing online resources use medical/technical language, offer limited content, include long blocks of text and are not visually appealing.

Next Steps: Further agile development of our online platform will be based on our user experience/user interface testing, as well as qualitative interviews with a diverse sample to determine additional sexual pain information, support and self-management strategies.

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Session #7 (Afternoon) | Poster Board #59 Helen Hsiao, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

fMRI study of functional brain networks in three memory tasks in healthy participants Helen Hsiao, Todd Woodward

Background: Certain processes tend to be specialized to one side of the brain or the other. The right hemisphere plays a dominant role in interpreting visual information and spatial processing, as well as facial recognition and perception of upright unfamiliar faces. Language functions such as grammar, vocabulary and literal meaning are typically specialized to the left hemisphere.

Objective: To identify functional brain networks that are deferentially activated in response to memory for faces, scenes and words in the fMRI Midnight Scanning Club dataset.

Hypothesis: Brain networks involved in language memory will demonstrate left hemisphere dominance, and networks involved in scene and face memory will demonstrate right hemisphere dominance.

Methods: 10 healthy subjects completed three Incidental Memory tasks: memory scenes, memory faces, and memory words tasks. In memory scenes, subjects indicated whether a picture was an indoor or outdoor scene.

For faces, subjects indicated whether the face presented was male or female. For words, subjects indicated whether the word was abstract or concrete. fMRI-CPCA was used to determine functional brain networks and associated hemodynamic responses engaged in the memory tasks independently, as well as merged in a single dataset. Statistical significance of hemodynamic responses will be determined with SPSS. The correlation between network activity and neuropsychological tests will be assessed.

Significance: This study will improve our understanding of the lateralization of functional brain networks. This will contribute to the future use of neuromodulation to increase or decrease activation of brain networks as a possible intervention to treat brain disorders affecting a certain hemisphere of the brain.

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Session #7 (Afternoon) | Poster Board #60 Caleb Ritchie, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

Congratulations to Caleb on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award

Spatial patterns of BOLD signal activation useful for identification and classification of task-state functional brain networks Caleb Ritchie, Todd Woodward

Functional magnetic resonance imaging (fMRI) has revealed that the human brain is organized into networks of spatially distributed areas which activate and deactivate in unison. The blood oxygen level dependent (BOLD) signal detects the difference in magnetic field produced oxygenated versus deoxygenated blood, which can used to infer which areas of the brain are more or less active than others. Analyzing healthy individuals in a resting (mind-wandering, non-directed) state has revealed seven non-overlapping networks which have been labelled for function based on brain region. Currently, the relationship of resting-state networks with the task-state brain is not widely understood, nor is the extent to which the names given to the resting-state networks are truly representative of function, since mind-wandering is a purely private experience. Using carefully coordinated tasks, our lab is able to infer function by observing the magnitude and relative timing of activity for a given network between different task conditions revealed by the hemodynamic response curve.

Previous studies have shown that there is a consistent set of task-state networks that can be extracted by fMRI-CPCA and can be classified into categories based on cognitive function, and also show distinct patterns of spatial activity. The importance of the present study is the reinforcement of the idea that ts-fMRI reveals networks not explained by the resting-state paradigm, and the simplification of network classification which is an ongoing challenge. The goal of this study was to identify the extent to which patterns of spatial activity can be distilled into reliable principles of identification for networks revealed by task-state fMRI-CPCA. Methods relied on manually sorting through images thought to represent each network in order to observe key brain regions that show reliable patterns. Novel techniques were used to enhance the visualization of such patterns.

Main findings reveal 3-4 brain regions which differ predictably between networks including the cingulate cortex, supplemental motor area, superior parietal cortex, and the insular cortex. Investigation is ongoing to strengthen these findings and identify other key regions of interest.

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Session #7 (Afternoon) | Poster Board #61 Ruth Liu, Undergraduate Student, McMaster University

Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

From Beer-Pong to Vigilance-Pong. Communicating Similarities between Sleep Deprivation and Alcohol Intoxication Ruth Liu, Osman S. Ipsiroglu, Scout McWilliams, Melvin Chan

Introduction: Vigilance (similar to alertness) is impaired by lack of sleep. Vigilance fluctuations increase the risk of motor vehicle accidents. Sleep deprivation and alcohol consumption have similar effects on handeye coordination (HEC). In 2017, high-school students at the H-Behaviours Research Lab created “VigilancePong” in order to communicate this similarity. The degree to which “Vigilance-Pong” would be suitable as a knowledge dissemination event was investigated.

Methods:

(A) A scoping review was conducted on Medline and PubMed to identify the most common method for measuring HEC due to fatigue and due to alcohol consumption (search phrase: “fatigue” AND “alcohol” AND (“performance” OR “hand-eye coordination”)).

(B) “Pong”, as initially suggested, was investigated at the pilot test run to allow self-experience and structured feedback. The number of balls that were successfully tossed into a Pong set was counted and recorded in Qualtrics on mobile devices. Similarly, the Karolinska Sleepiness Scale and selfies were used for assessing vigilance subjectively.

(C) A Strength-Weakness-Opportunity-Threat (SWOT) analysis was conducted for the original and potential game adaptation.

Result:

(A) For the scoping review, 317 results were identified. 7 RCT were included, assessing HEC under influences of both fatigue and alcohol. The common testing methodology was computerized tracking, which involves centering a cursor on a constantly moving target.

(B) Self-experience at the pilot test run revealed that the “Vigilance-Pong’s” set-up was operational, and the game’s name association to alcohol sparked interest. Participants feedback suggested recording the total number of throws attempted, and minimizing practice effect by incorporating practice throws.

(C) Pong SWOT-analysis. S: effective communication strategy; W: HEC-measurement not standardized; O: appeal to adolescent new drivers; T: might be perceived negatively due to association with drinking.

Tracking SWOT-analysis. S: based on literature; W: insensitive to moderate levels of fatigue; O: simple instructions; T: unengaging. Based on SWOT analysis, “Pong” retained its original procedures, but was adapted to incorporate participant suggestions for further improvement.

Conclusion: Participation in “Vigilance-Pong” is a unique way for raising awareness on vigilance fluctuations, as the game’s analogy of alcohol consumption further associates the discussion with motor vehicle accident prevention. The next step is to implement “Vigilance-Pong” as a game package for youths.

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Session #7 (Afternoon) | Poster Board #62 Tina Madani Kia, Undergraduate Student, University of British Columbia Supervisor: Srinivas Murthy, Healthy Starts

Congratulations to Tina on receiving a Canadian Institutes of Health Research Summer Studentship

Stakeholder perspectives on adaptive clinical trials: a scoping review Tina Madani Kia, Srinivas Murthy

Introduction: Adaptive clinical trials represent an emerging approach to trial design where accumulating data is used to make decisions about future conduct. Adaptations can include comparisons of multiple dose tiers, response adaptive randomization, sample size re-estimation, and efficacy/futility stopping rules. The objective of this scoping review is to assess attitudes, perspectives and understanding of stakeholders about adaptive studies. The term “stakeholders” encompasses the broad medical trial community and includes but is not limited to physicians, researchers, statisticians, review board members and patient advocates Methods: To identify relevant studies, a computerized search was conducted of library databases. Our team retrieved 166 titles in total from the database search. Of those, 146 were non-duplicate citations. 120 were not given full-text reviews as their titles and abstracts indicated they did not meet the inclusion criteria. 27 articles were carefully examined for relevance and of those, 12 were chosen to be part of the analysis with the remaining 15 excluded as they were not relevant upon closer inspection. Following review of articles, the primary findings of each article were coded for study design, purpose, and primary implications.

Results: This review shows major perceived advantages to adaptive designs (AD’s) such as limiting ineffective treatments and efficiency in answering the research question, as well as many perceived barriers including insufficient sample size for secondary outcomes, issues of consent, potential for bias, cost and time to adaptively design trials, unclear rationales for using AD’s and most importantly, a lack of education regarding AD’s among stakeholders within the clinical trial community.

Conclusion: There are diverse perceptions regarding AD’s among stakeholders. Further training, guidelines and toolkits about the proper use of AD’s are needed at all levels to overcome many of these barriers. While education for principal investigators is important, it is also crucial to educate other groups in the community as well such as clinicians and staff involved in the daily implementation.

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Session #7 (Afternoon) | Poster Board #64 John Sung, Undergraduate Student, University of British Columbia

Supervisors: Elodie Portales-Casamar & Matthias GĂśrges, Evidence to Innovation

Congratulations to John on receiving a Centre for Blood Research â&#x20AC;&#x201C; School of Biomedical Engineering Summer Studentship Award

Perceptions of professional and lay users on trust of artificial intelligence for medical decision-making and risk prediction John Sung, Elodie Portales-Casamar, Matthias GĂśrges

Background: Artificial intelligence (AI) is a computing technique showing rapid uptake across all sectors including healthcare. AI adoption in medicine is driven by many factors including the increasing digitalization of medical imaging and health records, as well as the ready availability of deep learning software packages and computing power. One application of AI is to assist in clinical decision-making, with the promise of reducing medical errors and improving health outcomes. Despite the positive outlook, there exists a disconnect between the developing technology and the key stakeholders who are expected to use this innovation.

Motivation: Physicians might be hesitant to trust artificial intelligence technology. This may be due to the inherent difficulty in understanding the complexity of the underlying algorithm or constructed model and the predictions derived from it. The decision process might be unfamiliar and the route the AI takes to the proposed solution may be obscured from the user. Likewise, patients who are at the receiving end of the technology may also harbor the same hesitance of having AI being involved in their care; especially when it comes to making riskier decisions.

Aim: The primary goal of this study is to assess the perception of physicians and the general public on the use of AI to assist clinical decision making, in particular as it relates to the notion of risk uncertainty in predictions, and how it might influence treatment decisions.

Methods: We will be distributing scenario-based surveys to local respondents. The data collected will be analyzed quantitatively and using thematic analyses of free text answers.

Expected results: The project serves as a pilot study examining the readiness of health practitioners and the general public in accepting AI-assisted healthcare. Unexpected survey responses may uncover avenues for future in-depth investigations and suggest actions that AI developers can take to make their technology more acceptable in the healthcare domain.

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Session #7 (Afternoon) | Poster Board #65 Jae Yun Lee, Undergraduate Student, McMaster University Supervisor: Tom Blydt-Hansen, Childhood Diseases

Congratulations to Jae Yun on receiving a BC Children’s Hospital Research Institute Summer Studentship

Vaccine-associated de novo HLA antibodies in pediatric kidney transplant recipients: pathological or benign?

Jae Yun Lee, Karen Sherwood, Franz Fenninger, Lenka Allan, James Lan, Soren Gantt, Paul Keown, Tom Blydt-Hansen Introduction: HLA antibodies associated with human tissue sensitization can restrict patient access to suitable organ donors for transplantation. Incidence of de novo HLA antibodies (dnHLA Ab) without human sensitization may be due to heterologous immune response to infectious pathogens. Similarly, we have observed dnHLA Ab associated with vaccination during pre-transplant evaluation, which often have lower mean fluorescence intensity (MFI) and persistence. We hypothesized that these vaccine-associated dnHLA Ab do not confer the same pathogenic risk as dnHLA Ab formed from human sensitization.

Methods: Pediatric patients (age ≤ 18) who received a kidney pre-transplant assessment at BC Children’s Hospital between 2015-2019 were included. All patients received baseline HLA Ab testing at referral and subsequent single antigen bead (SAB) assays, which were used to identify potential dnHLA Ab. The MFI trends of dnHLA Ab were studied through retrospective data collection of SAB assays. The most frequent alleles from each HLA gene were epitope-mapped using HLA Matchmaker v02, and common epitopes were compared.

Recent vaccinations (< 4 months before HLA test) were included for evaluation.

Results: 21 patients were eligible for inclusion, but 9 patients with no history of sensitization and/or no HLA antibody at the baseline test were selected for initial analysis. 26 vaccinations were administered to the 9 patients during the observation period. 34 dnHLA Ab (15 Class I and 19 Class II) were detected by SAB assays, 29 of which occurred within 4 months of a vaccination. Secondary endpoint measured as ≥ 350 MFI increase from baseline showed a total of 48 Class I HLA antigens (36 unique antigens) and 150 Class II antigens (54 unique antigens). The median MFI increase for secondary endpoint antigens were 490 for class I and 671 for class II. Frequency analysis showed 4 Class 1 and 11 Class 2 alleles occurring in more than 50% of the cohort.

From these Class I and II antigens, 16 and 37 unique epitopes were identified, respectively. 5/16 epitopes of Class I were common, compared to the 15/37 epitopes of Class II. All 9 patients included in the study proceeded to transplant.

Conclusions and Future Directions: The MFI trends of dnHLA Ab post-vaccination showed a broad, nonspecific increase in the intensity of multiple alleles. Epitope-mapping using HLA Matchmaker did not detect many commonly shared epitopes among the most frequent alleles, indicating that the increase in MFI postvaccination is unlikely antigen-specific. To better determine pathogenic risk, future analysis will include conducting surrogate flow crossmatch on patient sera containing SAB-recognized dnHLA Ab with an MFI > 2000.

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Session #8

CLINICAL, POPULATION HEALTH & HEALTH SERVICES 1:30 - 3pm

Moderator: Dr. Bahaa Abu Raya Participants: Donson Dong Vivek Gill Emma Keay Victor Lee Amanda Leong Grace Lin Chantal Percival Kheya McGill Elaine Fung

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Session #8 (Afternoon) | Poster Board #66 Donson Dong, Undergraduate Student, University of British Columbia Supervisor: Tamara Vanderwal, Brain, Behaviour & Development

Congratulations to Donson on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship

Obsessive-Compulsive Disorder (OCD) in Children: A Task-Based Functional Connectivity Study Donson Dong, Jeffrey Eilbott, Tamara Vanderwal

Obsessive-compulsive disorder (OCD) is a child psychiatric illness that can affect childrenâ&#x20AC;&#x2122;s learning abilities and daily lives. Many brain imaging studies have found differences in the functional connectivity (FC) of OCD patients compared with healthy controls (HC) in adults, but FC data in children with OCD is scarce. In this study, we analyzed FC in children with OCD compared to HC using the Tower of London (ToL) task, a well-known task that targets problem-solving and planning. We were interested in studying FC of the anterior cingulate cortex (ACC). The ACC is one of the most densely connected regions of the brain, and it is known to change dynamically during childhood and adolescence. This study used a seed-based analysis of FC, in which the FC between a seed region and every other voxel in the brain is interrogated. Two seeds of the anterior cingulate cortex (ACC), S3 and S5, were selected because these particular seed-based networks are responsible for the self-regulatory control of cognition, and conflict monitoring respectively, important functions in the ToL task.

These whole-brain seed-based FC networks were compared between OCD patients (n=24) and HC (n=24). Our hypothesis was that there would be strength differences between the FC of the HC and OCD patients in both the S3 and S5 networks and that there would be spatial differences in the FC of the S5 network. Both seeds generated FC networks that were similar to previous resting state studies for both OCD and HC groups. We found no significant group differences for S3. For S5, the conflict monitoring network, HC had significantly stronger FC in the parahippocampal region compared to the OCD patients. Future analyses will explore this robust focal finding, and try to identify correlations with OCD symptoms and severity.

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Session #8 (Afternoon) | Poster Board #67 Vivek Gill, Undergraduate Student, Western University Supervisor: Rod Rassekh, Childhood Diseases

Congratulations to Vivek on receiving a Michael Cuccione Childhood Cancer Research Program Summer Studentship

Hematopoietic Stem Cell Transplant Outcomes in Children Receiving Dexamethasone for Chemotherapy-Induced Nausea and Vomiting

Vivek Gill, Edric Paw Cho Sing, Tal Schechter, Muhammad Ali, Andrew Willan, Martin Offringa, Lillian Sung, L.L. Dupuis, Rod Rassekh Background: Recipients of hematopoietic stem cell transplants (HSCT) undergo conditioning regimens consisting of highly emetogenic chemotherapy, with nearly all experiencing chemotherapy-induced nausea and vomiting (CINV). CINV is often ineffectively managed, leading to malnourishment or reliance on parenteral nutrition, exposing patients to infection and toxicity. Controlling CINV improves quality of life and HSCT outcomes. Dexamethasone is a highly efficacious anti-emetic agent that increases the likelihood of controlling CINV by 2-fold in children. However, its application has been approached with hesitancy due to concerns over adverse effects including immunosuppression, increased invasive fungal disease (IFD) rates, and graft failure.

Objectives: Our primary aim is to understand the influence Dexamethasone has on 1-year overall survival (OS) by comparing children who received Dexamethasone to those who did not. Our secondary objectives are to assess the difference in 1-year event-free survival (EFS), the incidence of acute graft-versus-host disease (aGvHD), and the incidence of IFD. We hypothesize that there is no significant difference in OS and adverse HSCT outcomes between both groups. We anticipate our results will alleviate concerns over using Dexamethasone in HSCT. Methods: This is a multi-center, retrospective study in which BCCH health records were reviewed for all eligible HSCTs between January 2012 and July 2017. Descriptive statistics were performed. Differences in adverse HSCT outcomes between exposed and unexposed groups were measured and odds ratios were calculated. KaplanMeier analysis was performed to assess the difference in time from HSCT to relapse.

Results: 43 patients were eligible for our study, of whom 35 (81%) were exposed to Dexamethasone. 1-year OS was 80% in the exposed group and 50% in the unexposed group (OR: 0.25, p=0.09). 1-year EFS was 71% in the exposed group and 25% in the unexposed group (OR: 0.13, p=0.02). Four patients developed IFD, with 2 in each group (OR: 0.19, p=0.13). Rates of aGvHD were similar in both groups.

Conclusions: The data thus far suggests better HSCT outcomes in those who received Dexamethasone, including improved OS and EFS, lower rates of IFD, and comparable rates of aGvHD. Our results will be combined with centers in Toronto, Calgary, Israel and Holland for definitive conclusions.

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Session #8 (Afternoon) | Poster Board #68 Emma Keay, Undergraduate Student, Pepperdine University Supervisor: Tom Blydt-Hansen, Childhood Diseases

Pre-transplant clinical predictors of kidney allograft survival Emma Keay, Or Golan, Tom Blydt-Hansen

Background: Kidney transplants are lifesaving, but approximately 30% will fail within ten years, mostly due to alloimmune causes. Some risk factors for graft survival at the time of transplant include HLA matching, donor source (deceased or living) and donor quality (e.g. age, comorbidity), but explain only a portion of the variability in outcome. Other risk factors to do with cachexia, uremia, lipids and other nutritional indicators have been studied in isolation, but may directly impact on risk for inflammation or adaptive alloimmune regulation. Their inter-relatedness has not been studied systematically.

Hypothesis: Patterns of pre-transplant clinical and laboratory indicator changes reflecting nutritional and uremic burdens can enhance predictive assessment of graft failure in kidney transplant recipients, compared with standard risk assessment.

Objectives: 1. To develop a model utilizing clinical features and laboratory testing pre-transplant to predict allograft survival.

2. To determine whether clinical/laboratory features improve predictive accuracy of a model utilizing standard baseline clinical predictors of survival.

Methods: This is a retrospective cohort study of pediatric kidney transplant recipients at BC Childrenâ&#x20AC;&#x2122;s Hospital in the past 20 years. We will collect pre-transplant data related to demographics, diagnosis, time on dialysis, modality type, nutritional status (including lipid profile), immunologic risk (HLA epitopes), donor characteristics, initial immunosuppression, rejection episodes, reason/time to graft loss and renal function.

The primary outcome is onset of donor-specific antibodies, chronic mixed antibody rejection or presumed alloimmune graft failure. Graft failure non-alloimmune causes will be censored. A machine learning approach will be utilized to identify patterns of pre-transplant clinical variability that associate with allograft failure and multivariable regression modelling for predictors of allograft outcome.

Discussion: Aside from direct alloimmune and donor kidney risk factors, predictive models for allograft survival utilizing informative pre-transplant characteristics have not been developed. Determining how clinical risk factors contribute to alloimmune survival risk may enable us to better model short-term effects to long-term outcome risk. This will be the first study to examine these particular variables collectively, which may provide clinicians with a better method for risk-assessment in patients and translate to improved long-term outcomes.

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Session #8 (Afternoon) | Poster Board #69 Victor Lee, Undergraduate Student, University of British Columbia Supervisor: Mark Ansermino, Healthy Starts

Congratulations to Victor on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award and a BC Children’s Hospital Research Institute Summer Studentship

Evaluation of a digital triage platform in Uganda—a quality improvement initiative to reduce the time to antibiotic administration.

Lee V., Dunsmuir D., Johnson T., Businge S., Karugaba J., Krepiakevich A., Bone J., Kissoon N., Görges M., Ansermino J.M.

Background: Sepsis is the leading cause of death in children under five, disproportionately affecting lowand middle-income countries, where resources are scarce. Highly effective interventions to treat sepsis are available; however, timely delivery may not occur when the sickest children are not prioritized. Our team has developed a digital triage platform, PocketDoc, to rapidly identify critically ill children, with the intention of reducing time to interventions such as intravenous antibiotics (IVA). Here, we evaluate the impact of PocketDoc, when implemented at Holy Innocents Children’s Hospital (HICH) in Uganda, as part of a prospective quality improvement study occurring over an 11-week pre-intervention and 11-week post-intervention period, separated by an implementation and transition phase.

Methods: The PocketDoc mobile application collects signs, symptoms, and vital signs to prioritize children into triage categories through a combination of emergency triggers and predictive risk models. Details of each triage are sent to an accompanying dashboard, which allows clinicians to improve resource allocation by prioritizing patients and tracking treatments provided. Patients presenting at the HICH outpatient department were triaged by PocketDoc and the primary outcome was the time from triage to IVA administration. Data were analyzed using R. Results: Of the 5698 children triaged in the pre-intervention phase, 497 children (57.5% male, median age 12.0 months) received IVA, and of the 5104 children in the post-intervention phase, 351 children (58.7% male, 13.8 months) received IVA. We found a decrease in median time to IVA from 51 to 44 minutes, a difference of -11 minutes between the distributions (95% CI, -16.0 to -6.0, p<0.001). After statistical normalization between the two phases, there was a 21.5% decrease in the number of children who waited more than an hour for IVA after implementation. Segmented regression analysis showed an immediate 2-minute decrease post-intervention with a continued negative trend throughout the period.

Conclusion: The use of a digital triage mobile app was effective in reducing time to IVA. HICH was already highly efficient in the pre-intervention phase, limiting the potential impact of the PocketDoc implementation.

Therefore, the triage platform is likely to have more significant effects in facilities with less efficient treatment procedures, as is commonly encountered in low resource settings.

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Session #8 (Afternoon) | Poster Board #70 Amanda Leong, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Sleep & Occupational Injuries: A Scoping Review Gemma Tomasky, Amanda Leong, Melvin Chan, Osman S. Ipsiroglu

Introduction: Occupational injuries are defined as injuries that occur in the context of work or during the commute to work, often due to having impaired vigilance similar to low alertness. Impaired vigilance, due to lack of sleep by workers, has lead to catastrophic, yet preventable, occupational accidents, such as Chernobyl, Three Mile Island, and the Challenger explosion -- all of which were the result of key personnel being sleep deprived. The purpose of our scoping review is to capture existing literature on the relationship between sleep and occupational injuries.

Methods: (A) Medline was searched from inception to May 2019 using the pilot search phrase (“sleep*” OR “vigilance” OR “attention”) AND “injur*”.

(B) A second focused search phrase, (“sleep*” OR “vigilance” OR “circadian rhythm” OR “fatigue”) AND (“injur*” OR “accident” OR “prevention” OR “risk factor”), was created by combining key terms from review articles found through the pilot search.

(C) Study results were grouped into themes.

Results: The focused search phrase led to 1068 review articles, which 28 met the eligible inclusion criteria. The three main themes that emerged from the included literature were night shift work, motor-vehicle accidents, and hospital shifts. These articles suggest impairment of circadian rhythm, as a result of night shift work, leads to a significant increase in the risk of work-related accidents. In addition, the risk of motor vehicle accidents are observed to rise with increasing levels of driver fatigue. Lastly, reducing the duration of hospital shifts has lead to a decrease in errors that could have harmed patients, suggesting further restrictions are beneficial.

Conclusion: Using a scoping review, we found that regulation in shift work duration and distribution that allow workers to sleep longer or take naps decrease the risk of preventable work injuries. Many articles highlight the need to increase public awareness of the importance of sleep. Accordingly, our next step is to create a group of vigilance testing games for the classroom setting, a self-experiential way to learn about the effects of sleep deprivation with the aim of decreasing the risk of preventable work injuries.

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Session #8 (Afternoon) | Poster Board #71 Grace Lin, Undergraduate Student, McMaster University Supervisor: Anton Miller, Brain, Behaviour & Development

Congratulations to Grace on receiving a Kids Brain Health Network Summer Internship Award

Patient navigation: Exploring the terminology and conceptualization of services that connect children with Neurodisability and their families to needed supports: A Scoping Review Grace Lin, Emily Gardiner, Vivian Wong, Anton Miller

Background: Children with neurodisability represent a significant population with a demonstrated need for coordinated external support. Patient navigation is a concept that was founded on the principles of coordinating care for patients based on individual needs. Despite the history of patient navigation programs, the diverse ways in which it has been implemented has resulted in a lack of definition for the concept itself.

Moreover, children with neurodisability and their families are often not the target population of navigation and coordination initiatives leading to a gap in knowledge on the terminology and concept of navigation-related services specific to this population.

Purpose: This scoping review aims to fill this gap in knowledge by examining published articles on navigationtype resources for children with neurodisability and their families, looking particularly for the description(s) of the terminology and conceptualizations being used.

Methods: A preliminary search was completed on Pubmed, OVID (Medline), and CINAHL to find initial search terms, upon which a full search strategy was developed. Search results were screened for peer-reviewed articles, published in English, published on or after 1990, and relevant to both children with neurodisability/ their families and navigation-related resources through a 2-step process. A full text review of relevant articles will be conducted and data will be extracted using a data extraction tool. Extracted terminology and concepts will be analyzed to be compiled into a working definition of navigational services as related to children with neurodisability and their families.

Implications: The results of this study will be used to inform and enable progress of a current initiative to improve transition processes for children with neurodisability and their families in western Canada â&#x20AC;&#x201C; the â&#x20AC;&#x153;Kids Brain Health Network Navigation - Sunny Hill Health Centre Improving Transitions Project â&#x20AC;? Project (KNIT).

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Session #8 (Afternoon) | Poster Board #72 Chantal Percival, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

fMRI analysis of functional brain connectivity in two language tasks in schizophrenia Chantal Percival, Todd Woodward

Introduction: Schizophrenia is often considered a disorder of connectivity of large-scale brain networks. The current investigation examined functional brain networks underlying two language experiments in healthy controls and schizophrenia patients. Merging datasets allows for comparison and differentiation between brain networks and corresponding cognitive processes.

Methods: In the semantic association experiment, participants indicated which potential semantic match word was most closely related to a prompt word. In the thought generating task experiment (TGT), participants either mentally generated or listened to a definition of an object noun. Functional brain networks and their associated hemodynamic responses were determined with fMRI Constrained Principal Component Analysis (fMRI-CPCA).

Results: Functional brain networks included the external volitional attention network, response network, default mode network, language and cognitive evaluation network, and auditory network. Schizophrenia patients demonstrated hyperactivity in the external volitional attention network in TGT. Patients with recent hallucinations indicated hyperactivity when presented with external auditory stimuli.

Conclusion: Results suggest that schizophrenia patients require additional cognitive resources to pay attention to presented visual stimuli, and that hyperactivity in auditory brain networks may be related to a lack of control exerted over auditory stimuli.

Implication: Identification of functional brain networks with fMRI increases understanding of functional connectivity in schizophrenia patients. Future areas of investigation should merge additional fMRI datasets and perform multi-modal analyses such as fMRI-EEG. Further, due to the limited efficacy of both pharmaceuticals and cognitive therapy for schizophrenia, there is a need to both improve current treatment options as well as investigate effective alternatives, one such being neuromodulation. Our understanding of functional brain networks by virtue of fMRI will influence such methods.

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Session #8 (Afternoon) | Poster Board #73 Kheya McGill, Undergraduate Student, University of British Columbia Supervisor: Ash Singhal, Brain, Behaviour & Development

Returning To School After Undergoing Pediatric Neurosurgical Procedures â&#x20AC;&#x201C; Patient and Caregiver Perspectives Kheya McGill, Ash Singhal, Alexander Cheong

Background and Aim: Neurosurgical procedures are often accompanied with long recovery periods, with symptoms which vary between patient, diagnoses, and procedures. Return-to-school decisions made by physicians are often based on general estimates and anecdotal evidence. Studies have shown varying consequences of returning to school after traumatic brain injuries. However, there has been no research done on the experience of pediatric patients returning to school after undergoing neurosurgery. By understanding past experiences of patients, neurosurgical teams may be able to make more informed recommendations about when patients are able to return school and their likely experiences following this return.

Methods: This study used a qualitative framework to better understand when patients return to school after surgery, and the outcome of that experience. Semi-structured interviews were conducted with volunteer patients (and their caregivers) who previously underwent elective neurosurgery. Interviews were audio recorded and transcribed verbatim. The study was continued until thematic saturation, at which point data was analysed through an inductive and holistic review of the text.

Results: Thematic saturation was achieved after 12 interviews. With regards to guidance from the neurosurgical team, a consistent theme was that return to school information was vague and did not particularly help with decision making of timing. The stated benefits of returning to school are all within the theme of normalization (routine, socialization, physical and academic activity). The challenges of returning to school were within the themes of safety (concern about injury to the surgical site), physical symptoms (fatigue, pain), and cosmesis/self-consciousness. It is remarkable that no respondents (patient or caregiver) expressed concern regarding academic performance. While most patients and caregivers found that return to school timing was appropriate, there was some variability, with caregivers commonly feeling children were returning to school prematurely for their own comfort/anxiety.

Future Directions: The second phase of this study intends to distribute a survey to Pediatric Neurosurgeons that practice in Canada in order to gain information about when surgeons recommend their patients return to school and why. A series of clinical scenarios will be presented with a request to define the timing of return to school.

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Session #8 (Afternoon) | Poster Board #74 Elaine Fung, Undergraduate Student, University of British Columbia Supervisor: Elodie Portales-Casamar, Evidence to Innovation

Understanding the actual and perceived differences between Canadian research and quality improvement studies Elaine Fung, Elodie Portales-Casamar, Elizabeth Kinney, Holly Longstaff

Background: Across Canada, health care practitioners endeavor to better understand our health systems, care delivery, and treatment. Often this work is classified as quality improvement (QI), or research in an effort to ensure that the appropriate legal and ethics issues are addressed and risks of harm are minimized. While these activities have one objective in mind, to better patient care, a delineation between research and QI is often made. What is unclear is (1) whether these classifications have legitimacy, and (2) add any actual value to the overall conduct of the study.

Objective: To investigate the basis for differentiation between research and QI studies through a scoping review and stakeholder engagement, as well as evaluate whether such differentiation is necessary and adequate within an academic health care environment.

Methods: To explore the current understanding and practices, we plan to conduct expert interviews and surveys with Provincial Health Services Authority researchers and stakeholders including privacy, ethics, and legal experts, data stewards and custodians, operational leaders, and clinician researchers. Interviews will be semi-structured with some multiple-choice and some open-ended questions. Interview voice recordings will be transcribed using NVivo to identify themes. Participants also have the option to complete an online survey.

Expected Results/Future Directions: It is hypothesized that there is a great deal of confusion concerning the differences between research and QI classification, and that the current practice is not well aligned with current ethics guidance according to the TCPS 2 (2014)â&#x20AC;&#x201D; the latest edition of Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans . This study provides an opportunity to explore the perceived differences between research and QI according to experts and stakeholders working within a health authority environment. In addition, it will help understand the personal experiences of PHSA research and QI stakeholders in their role in adjudicating, supervising, and/or supporting research and QI studies. Potential implications include a better understanding of the research and QI oversight at PHSA, where findings could be used to guide future research governance policies and procedures.

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