2018 Summer Student Research Program Poster Day

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Welcome to the 2018 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.

Jennifer Myers Research Education Manager, BC Children’s Hospital Research Institute 2

2018 Summer Student Poster Day Thursday, July 26 Poster Presentations

1:00 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 7 groups and will have 5 minutes to discuss their poster and up to 5 minutes for questions

Awards Ceremony

3:30 p.m. | Chan Centre for Family Health Education

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 Research Themes: Childhood Diseases Healthy Starts Evidence to Innovation Brain, Behaviour & Development Canucks for Kids Fund Michael Cuccione Foundation Community Child Health Endowment 3

Showingcasing excellence in our talented research community!

2018 Poster Participants Participant

Research Team

Meilin An

Hoffman Research Team Armstrong Research Team Rassekh Research Team

Anmar Batawi Savvy Benipal Eric Bhatti Mackenzie Blydt-Hansen Meghan Boersma Maye Cheng Christine Cheung Paul Clerc Danielle Cohen Zoe DeBoer Michael Doyle Darson Du Avarna Fernandes Isobel Fishman

Abstract Title

Binding of the Trithorax Group to β-Cell Transcription Factors is Sensitive to Oxidative Stress A Retrospective Analysis of Cardiac Function in Pediatric Heart Transplant Recipients Spinal Low-Grade Gliomas in Canadian Children: A Retrospective Review Goldfarb Research Blood culture collection practice and yield at a tertiary Team pediatric centre before and after implementation of an evidence-based blood culture protocol Amed Research Team Driving Healthcare Improvement in Pediatric Diabetes in British Columbia – Harnessing the Power of Data and Benchmarking Loock Research Team Surgical Correction of Velopharyngeal Dysfunction in Children with 22q11.2DS Lavoie Research Team The effects of cellular metabolism on MALT1 protein expression in neonatal immune response Priatel Research Team The Loss of Intestinal Mucus Production Results in Dysfunctional Splenic Antigen-Presenting Cells Goldman Research A Pragmatic Randomized Controlled Trial of Virtual Reality Team vs. Standard-of-Care for Comfort During Minor Plastic Surgery Procedures in Children Deyell Research Team Prognostic Role of Activated Beta-Catenin in Pediatric Osteosarcoma Taubert Research Team Genetic dissection of a new oxidative stress response pathway in Caenorhabditis elegans Kobor Research Team Investigating the effect of natural variation in the oxidative stress response Lehman Research Team Diagnostic rate and inheritance patterns in siblings with developmental disorders undergoing genetic sequencing Coelho Research Team Improvements in functional impairments in youth with eating disorders: Effectiveness of a pediatric day program Zwicker Research Team Retrospective Review of Children’s Diagnostic Assessments for Autism Spectrum Disorder in BC: Are We Identifying Cooccurring Motor Deficits?

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Participant Justin Fong

Research Team Brown Research Team

Saman Fouladirad

Woodward Research Team

Alexandra Franiek

Blydt-Hansen Research Team Armstrong Research Team Blydt-Hansen Research Team Pike Research Team

Claire Galvin Tara Gholamian Karanvir Gill Marina Godard Hajir Adl Golchin Amanda Hage-Hassan Nicole Hemphill Jasia Ho Thomas Hoang Mikayla Hong Alice Huang Farnaz Javadian Jocelyn Jia Rohan Kakkar Mehima Kang Amy Ker

Abstract Title A prospective, observational pilot study of non-invasive microcirculation monitoring using near-infrared absorption spectrophotometry (NIRS) during scoliosis correction surgery Altered Functional Connectivity in Brain Networks of Schizophrenic Patients During Hypersalience Decision Making Urinary metabolomics to develop predictors for pediatric acute kidney injury Texting and Connecting

Urinary metabolite markers for chronic kidney disease in a pediatric population Safety Preparedness of Recreational Boaters in BC: Who’s Missing What?

Ipsiroglu Research Team Rethinking the SleepSmart Study Consent Form to Enhance Participatory Research Armstrong Research Dysautonomia of Adolescence: A Multidisciplinary Team Approach Woodward Research fMRI Investigation of a Controlled Semantic Integration Task Team in Healthy and Schizophrenia Patients Harris Research Team Executive Function Correlates with Quality of Life, not Physical Activity in Children with Congenital Heart Disease Steiner Research Team A4-Fla2, a Dominant Antigen in Crohn’s Disease, Evades TLR5 Stimulation Finlay Research Team Bacterial Metabolism as a Contributor to Environmental Enteric Dysfunction Ipsiroglu Research Team Rethinking the BCCH BioBank Consent Form to Encourage Participatory Research Taubert Research Team Elucidating the molecular mechanism regulated by eE2K/ EFK-1 Giaschi Research Team Do motion perception and binocular function share common processing mechanisms?

Chan Research Team Transitioning from Child to Adult Care for Eosinophilic Esophagitis Hursh Research Team Barriers in Adherence to a Gluten-Free Diet in Children with Type 1 Diabetes and Celiac Disease Compared to Children with only Celiac Disease Panagiotopoulos Evaluation of bone health and bisphosphonate use in Research Team pediatric patients with Duchenne muscular dystrophy Lang Research Team Effects of Antipsychotics and Exercise on the Entorhinal Cortex of Rats

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Participant

Research Team

Abstract Title

Page

Jocelyn Kerr

Collet Research Team

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Tina Madani Kia

Mimi Kuan

Jacobson Research Team Verchere Research Team Harris Research Team

Monica Lai

Harris Research Team

Madeline Lauener Iris Lee

Schultz Research Team Devlin Research Team

Michelle Lee

Lynn Research Team

Jessica Leung

Sly Research Team

Wendy Li

Mah Research Team

Rebecca Lim

Devlin Research Team

Rebecca Lin

Portales-Casamar Research Team Robinson Research Team

The Link Between Executive Functions and Social Cognition, and Its Relevance to Child Development: A Rapid Review The impact of murine gut microbiota composition on susceptibility to DSS-induced colitis Targeting the NLRP3 Inflammasome as a Potential Treatment for Diabetes Physical Activity and Aortic Stiffness in Children with Congenital Heart Disease What Do Adolescents and their Parents Know About Their Heart Condition?

CD56bright NKreg cell regulation of cGvHD Maternal Exercise During Pregnancy and Offspring Adiposity Single-cell transcriptomic changes of human pancreatic islet cells in response to glucose and calcium signaling The role of MALT1 expression in inflammatory bowel disease Gaps and gains in Chinese-immigrant parents' ADHD literacy: a cross-cultural comparison Effects of Maternal Obesity and Folic Acid Supplementation on Offspring Metabolic Health Text Mining Psychiatric Clinical Notes

Comparative analysis of normalization methods for Infinium 850K DNA methylation data in placental samples from multiple cohorts Carleton Research Team Pharmacogenomic Analysis of ACYP2 and WFS1 Variants in the Development of Cisplatin Induced Ototoxicity amongst Pediatric Cancer Patients Ogilvie Research Team Impact of the human papillomavirus immunization program on rates of genital warts in British Columbia, 2000-2017 Karakochuk Research Measuring folate status in children with sickle-cell disease: Team a pilot study Ipsiroglu Research Team Are smartphone- and computer-based data collection methods feasible for capturing sleep/wake-behaviours?

Vercauteren Research Determining the Quality of Biobanked Tissue Specimens Team Yong Research Team Endometriosis and negative perception of the medical profession Carleton Research Team Predicting Veno-Occlusive Disease in Pediatric Patients undergoing Cancer Chemotherapy Schrader Research The Use of Advanced, Automated Magnetic Resonance Team Image Processing Techniques for the Detection of Focal Epileptogenic Lesions in Children

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Nahae Kim

Ziqi Liu Cody Lo Christine Lukac Cara Mayer Dylan Meng Paige Muir Nicole Ng Tom Ouellette Katie Pezarro

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Participant

Research Team

August Pierik

Piper Research Team

Abstract Tile

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The Utility of Instructional Videos for Reducing Central Line Associated Complications in Children with Intestinal Failure Harris Research Team Conducting Discordant Twin Pair Comparisons to Understand the Factors that Affect Quality of Life in Children with Congenital Heart Disease.

Gantt Research Team The role of B cell activation in HIV-induced KSHV replication and KS Schultz Research Team "Characterization of donor IFNgamma producing Th1 cell suppression of chronic graft versus host disease (cGvHD) in blood and marrow transplantation (BMT)" Siden Research Team Impact of a Diagnosis among Parents of Children with Severe, Progressive Life-Limiting Diseases Vallance Research Team Improving the intestinal environment: A potential therapy for IBD McDonald Research Imaging Practices for Hydrocephalus at BC Children’s Team Hospital- A Comparison of Two Historical Epochs Devlin Research Team Long-term metabolic effects of neonatal sucrose treatment

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Mulpuri Research Team Assessing the need for orthopedic follow-up in the management of pediatric femoral fractures Zoe Schmidt Elango Research Team Arginine supplementation in pyridoxine dependent epilepsy: is there a benefit?

Kyle Scoten Babul Research Team Optimizing the Concussion Awareness Training Tool (CATT) Using the 2017 BC Hockey Concussion Mandate Evaluation Stephen Siu Ting Research Team Predictors of successful closure of patent ductus arteriosus with non-steroidal anti-inflammatory drugs Michaela Skarlicki Arneja Research Team A Modified Pharyngeal Flap Technique for the Treatment of Velopharyngeal Incompetence Madeleine Tan Panagiotopoulos Diabetes Distress in Youth with Type 1 Diabetes Research Team Chris GJ Tang Sly Research Team "Investigating the contribution of bacteria to ileal inflammation in SHIP-deficient mice" Mikayla Wohlleben Ipsiroglu Research Team Self-injurious behaviour - understanding clinical patterns Sean Wong Murthy Research Team Impact of transport time on patient outcomes in BCCH PICU Kevin Xiao Ipsiroglu Research Team Rethinking the MRI Consent Form: How Better Design and Added Visuals Can Enhance User Understanding and Comfort Janine Xu Vallance Research Team The role of SIGIRR in controlling the intestinal mucus barrier Chloe Xinyuan You Kobor Research Team Effects of Short Term Diesel Exhaust and Allergen Exposure on DNA Methylation in Human Bronchial Epithelial Cells Sofía Zhang-Jiang Synnes Research Team Developing Vignettes to Evaluate Parental Perception of Disability Severity in Preterm Babies Kai Zhu Verchere Research Effects of PAM Haploinsufficiency on Islet Amyloid and Team β-cell Failure

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Ana Pozas Habibur Rahman Aryan Riahi

Veronica Romines James Sader Anahat Sahota Melody Salehzadeh Gabrielle Sanatani

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Finding a Poster Board Chieng Family Atrium

Room 2108 Patio Registration

Chan Centre for Family Health Education Session 01 - Basic Science Poster Boards - #1 - 12 Session 02 - Basic Science Poster Boards - #13 - 25 Session 03 - Clinical, Population Health & Health Services #26 - 36

Main Entrance

Reception

Refreshments

Session 05 - Clinical, Population Health & Health Services #47 - 57 Session 06 - Clinical, Population Health & Health Services #58 - 67 Session 07 - Clinical, Population Health & Health Services #68 - 77

Session 04 - Clinical, Population Health & Health Services #37 - 46 The drawing is intended for visual reference only, it is not to scale 8

Session 01 BASIC SCIENCE

Moderator: Dr. Laura Cook Participants: Meilin An Maye Cheng Christine Cheung Amanda Hage-Hassan Alice Huang Madeline Lauener Iris Lee Cara Mayer James Sader Melody Salehzadeh Chris GJ Tang Kai Zhu

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Poster Board #1 Meilin An, Undergraduate Student, University of British Columbia Supervisor: Brad Hoffman, Childhood Diseases

Binding of the Trithorax Group to β-Cell Transcription Factors is Sensitive to Oxidative Stress Meilin An, Ben Vanderkruk, Brad G. Hoffman

Background and Aims: Insulin is secreted by pancreatic β-cells in response to elevated glucose and insulin transcription is driven by key β-cell transcription factors, including Mafa, Nkx6-1 and Pdx1. The highly specialized β-cell gene expression program maintains β-cell identity and disruptions to this program lead to β-cell dysfunction. In type 2 diabetes (T2D), β-cells experience oxidative stress and expression of Mafa, Nkx61 and Pdx1 are reduced, likely contributing to decreased insulin release and β-cell dysfunction. In addition, we have observed reductions in histone 3 lysine 4 (H3K4) methylation in human T2D islets and in a mouse model of diabetes. The Trithorax Group (TrxG) protein complex is a transcriptional coregulator that catalyzes methylation of H3K4 and is associated with active transcription. In this study, we hypothesized that cellular stresses that drive T2D will alter the interaction between TrxG complexes with transcription factors in β-cells.

Methods: To determine how H3K4 methylation is reduced in T2D β-cells, we assessed changes in interactions between the TrxG subunit Wdr5 with transcription factors that are known to be modified by T2D-like stresses such as NeuroD, Nkx2-2 and Foxo1. MIN-6 cells (mouse β-cell line) were treated with 35μM hydrogen peroxide for 90 minutes to mimic conditions of oxidative stress. Protein concentrations of cell lysates were measured with BCA assay and an equal amount of protein was analyzed for all co-IP samples. Samples were immunoprecipitated with an antibody against Wdr5 and immunoblotted with antibodies against target transcription factors.

Results: We found that treatment with hydrogen peroxide decreased the interactions between Wdr5 and transcription factors Pax6 and Nkx2-2. Conversely, interactions between Wdr5 and transcription factors NeuroD, Foxo1 and FoxA2 were increased under these conditions.

Conclusions and Future Directions: Our results suggest that the TrxG protein complex interacts with critical β-cell transcription factors, and that certain interactions are modified under T2D-like cell stressors. We predict that alterations to the interaction of the TrxG complex with β-cell transcription factors can alter recruitment of TrxG complex to certain β-cell target genes, affecting overall β-cell transcriptional activity. Future experiments will further confirm the interactions identified in MIN6 cells by repeating similar co-IP experiments with mouse and human β-cells, and to also determine if recruitment of TrxG complex to target genes is affected by oxidative stress.

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Poster Board #2 Maye Cheng, Undergraduate Student, University of British Columbia Supervisor: Pascal Lavoie, Healthy Starts

Congratulations to Maye on receiving a UBC Faculty of Medicine Summer Studentship!

The effects of cellular metabolism on MALT1 protein expression in neonatal immune response Maye Cheng, Christina Michalski, Bernard Kan, Pascal Lavoie

Background: Premature babies are known to be more susceptible to fungal infections than term newborns and healthy adults. Little research has been conducted on premature infant’s immune responses to fungi. Candida species (spp.) is the most common cause of fungal infections worldwide and a leading cause of infectionrelated mortality in neonates. The detection of Candida by the dectin-1 receptor activates the MALT1/Bcl19/ CARD9 signalosome complex, resulting in the production of pro-inflammatory cytokines including IL-1β.

Interestingly, MALT1 protein expression is reduced in monocytes from preterm neonates despite comparable mRNA expression. Additionally, rapid energy and metabolic intermediates are essential to quickly translate immune response proteins for an effective innate immune response. This is achieved by upregulating cellular glycolysis upon stimulation. We have previously shown that glycolytic activity was lower in preterm monocytes compared to adults. We hypothesized that the low glycolytic activity reduces the translation of key immune response proteins, such as MALT1.

Methods and Results: Monocytes isolated from healthy ault donors were stimulated for 8 h, 16 h or 19 h with either 2-deoxy-D-glucose (2-DG), a glucose analog that inhibits glycolysis, or cycloheximide (CHX), which blocks all protein synthesis. Western Blot analysis and flow cytometry demonstrated a decrease in MALT1 protein with 2-DG and CHX stimulation; however, the protein levels of β-actin, a control gene, did not change.

A lactate assay was performed to assess whether blocking MALT1 reciprocally reduces glycolysis. We showed no change in glycolytic capacity in the cells both at rest and after LPS stimulation upon inhibiting MALT1. As a control, an ELISA was performed on parallel Candida-stimulated cells to confirm that MALT1 blocking was efficient in these experiments.

Conclusion: Inhibition of glycolysis resulted in a loss of MALT1 protein expression and conversely, inhibition of MALT1 did not affect glycolysis. These findings suggest that the low MALT1 protein expression in preterm monocytes is due to a decrease in glycolytic capacity of neonate’s immune cells. Further studies on the mechanism and relationship regarding the decrease of MALT1 protein expression and glycolysis could lead to new therapeutic options for augmenting premature infants’ immune reactivity.

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Poster Board #3 Christine Cheung, Undergraduate Student, University of California, Berkeley Supervisor: John Priatel, Childhood Diseases

The Loss of Intestinal Mucus Production Results in Dysfunctional Splenic Antigen-Presenting Cells Christine Cheung, Kevin Tsai, Caixia Ma, Bruce A. Vallance, John J. Priatel

Severe, chronic inflammation of the intestinal tract is a defining hallmark of inflammatory bowel diseases (IBD) and thought to result from a complex combination of environmental and genetic factors. A layer of mucus functions to segregate contents of the intestinal lumen from the intestinal epithelium and decreased mucus production has been associated with the pathogenesis of IBD. MUC2 is the primary constituent of intestinal mucin and acts as a structural scaffold for mucus forming a physical barrier to shield the intestinal wall. Thus, MUC2 may be critical for limiting bacterial stimulation of the mucosal immune system and preservation of normal immune cell function. Significantly, we have previously found that oral administration of a model antigen resulted in its rapid dissemination in the blood of Muc2-/- but not wild type mice. Hence, we hypothesized that the leaky gut of Muc2-/- mice might alter the function of splenic antigen-presenting cells (APCs) through increased exposure to intestinally derived microbial antigens. Our results demonstrate that splenic dendritic cells from Muc2-/- mice express considerably reduced levels of costimulatory molecules that are necessary for initiating adaptive immunity. Further, we found that MUC2-deficient splenic APCs are defective in priming naĂŻve CD8 T cells to initiate antigen-driven proliferation and differentiation. Consequently, these findings indicate that MUC2-deficiency may contribute to IBD pathogenesis by impairing the function of peripheral APCs resulting in systemic immunodeficiency. Altogether, our studies provide a better understanding of how intestinal mucus production influences innate and adaptive immune systems at distal sites.

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Poster Board #4 Amanda Hage-Hassan, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

fMRI Investigation of a Controlled Semantic Integration Task in Healthy and Schizophrenia Patients Amanda Hage-Hassan, Jessica Luk, Todd Woodward

Background: Schizophrenia is a neuropsychiatric disorder associated with global cognitive deficits. Disturbances in speech have been considered a key feature of the disorder. These functional deficits are characterized by an inability to organize and express thoughts, referred to as thought disorder, and impairments in associating semantic concepts is an important aspect of thought disorder. Previous studies examined automatic semantic association using semantic priming and found hyperactivity in the frontotemporal (language) regions. This suggests the hyperactivity in a language network may be underlying the abnormal associative activity observed in schizophrenia and thought disorder.

Goal: To conduct an exploratory analysis to identify the functional brain networks underlying controlled semantic association.

Methods: In the current study, 30 healthy controls, and 28 participants with schizophrenia completed a controlled semantic association task which required them to match word pairs that varied in semantic distance (distant vs. close). Outside the scanner, participants were asked to recall as many word-pairs from the association task. The fMRI-data was further organized according to the behavioral results from the memory task. Constrained principal component analysis for fMRI (fMRI-CPCA) was used to separate distinct, and simultaneously-active, task-based networks.

Results: This analysis revealed three networks: volitional visual attention network, default mode network (DMN), and a language network. Across all three networks, peak activation was significantly greater in low compared to high association conditions (p < 0.001). There were no differences in brain activity between groups for the first two networks, but there was decreased activity in patients for recalled relative non-recalled words in the third (language) network. The hypoactivity found in the frontotemporal language regions during controlled semantic association could be linked to thought disorder in schizophrenia.

Significance: These results are important as they provide a better understanding of the pathological hallmarks of schizophrenia on a neural level. This can potentially help with creating interventions to treat symptoms of schizophrenia.

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Poster Board #5 Alice Huang, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

Congratulations to Alice on receiving a NSERC Undergraduate Student Research Award!

Elucidating the molecular mechanism regulated by eE2K/EFK-1 Alice Huang, Forum Bhanshali, Andy An, Amy Walker, Poul Sorensen, Stefan Taubert

Developing tumors need to adapt to microenvironmental stress in order to survive and initiate the process of metastasis. Protein translation is one of the most energy-consuming processes in a cell; thus, the translation machinery is regulated for surviving nutrient-scarce conditions. The eukaryotic elongation factor 2 kinase (eEF2K) negatively regulates the the elongation step in translation by phosphorylating the eukaryotic elongation factor 2 (eEF2). Furthermore, eEF2K expression is increased in various cancers and is activated by stressors such as starvation and hypoxia to aid in tumor cell adaptation. Therefore, it is consequential to identify the targets that are regulated by eEF2K, and to elucidate its regulatory pathway.

To study eEF2K in vivo, we are using the model organism Caenorhabditis elegans, a nematode worm.

Previously, we found that the C. elegans ortholog of eEF2K/efk-1 mediates protection against starvation, as mutant worms lacking efk-1 are starvation sensitive. In addition, mutant worms lacking zip-2 and cebp-2; two transcription factors which we hypothesize to act downstream of efk-1, are also sensitive to starvation. To further study the interaction between efk-1 and the transcription factors, we have generated a double mutant worm lacking both zip-2 and efk-1, which we are using in functional assays to elucidate epistasis with efk-1.

These functional assays will also be complete with a cebp-2; efk-1 double mutant.

Secondly, to identify the downstream targets of efk-1, we performed unbiased transcriptome profiling by RNA sequencing in wild-type and efk-1 mutants in fed and starved conditions. We found 310 genes that were modulated by efk-1 in starvation. Currently, we are validating some of these genes by real-time quantitative PCR. Gene ontology analysis indicates that efk-1 regulated genes may have a role in metabolism and in immune response pathways. These results also further support the possibility of a relationship between efk-1, cebp-2, and zip-2 because the latter two are known innate immune response transcription factors. Mapping the specific interactions between these genes may help to design future pharmacological targets for various cancers in the future.

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Poster Board #6 Madeline Lauener, Undergraduate Student, Simon Fraser University Supervisor: Kirk Schultz, Childhood Diseases

CD56bright NKreg cell regulation of cGvHD Madeline Lauener, Amina Kariminia, Kirk Schultz

Background: We have shown in three separate cohort studies that increased peripheral blood CD56bright NKreg cells strongly correlate with suppression of cGvHD. While peripheral CD56bright NKreg cells can be isolated from adult blood, cord blood and tonsils, it is uncertain which may be the optimal source for ex vivo expansion and with the potential of adoptive transfer to inhibit cGvHD. In addition, data has shown that soluble HLA-G (sHLA-G) modifies NK function to a regulatory phenotype. Correlation of sHLA-G with lower acute GvHD has been demonstrated, but it is not known whether it interacts with CD56bright NKreg cells or whether it correlates with lower cGvHD. Hypothesis: CD56bright NKreg cells can be isolated and expanded for cellular immune-therapy after BMT to minimize cGvHD without decreasing graft-vs-leukemia (GVL) effect.

Objectives: Optimizing in vitro expansion of CD56bright NKreg cell population with regulatory function.

Methods: CD56 Bright NK cells were isolated from peripheral adult blood, cord blood, and tonsils. Different culture conditions were used for CD56bright expansion. The function of expanded cells was then analyzed including cytokine production, cytotoxicity against K562 and differentiation.

Results: The optimal CD56bright NKreg cell source, in terms of highest purity and cell frequency was adult peripheral blood. CD56 bright NKreg cells cultured in the presence of IL-2, IL-12, IL-15, antiCD335, antiCD2, and conditioned medium showed the greatest expansion, being a mean 38-fold increase. CD56bright NKreg cells that were cultured with IL-2 had the greatest cytotoxic activity (62% live K562 after 24hr incubation with 1NK/1K562), and CD56bright NKreg cells that were cultured with IL-2, IL-12, and IL-15 had less cytotoxic activity (82% live K562 after 24hr incubation with 1NK/1K562). When CD56+ total NK cells were cultured in the presence of IL-2 + IL-12, or IL-2 + IL-15, they differentiate towards the bright population, as 78% of cells are CD56 bright. When the cells are cultured in the presence of just IL-2 74% of cells are CD56 bright. Culturing CD56bright NKreg cells in the presence of IL-12 and/or Pam3 leads to much IFNg production, while just culturing with IL-2 results in minimal IFNg production. Culturing CD56bright NKreg cells in the presence of IL12, IL-15, and/or Pam3 results in an increase of LIF production, especially the addition of Pam3, while culturing the cells only in the presence of IL-2 results in little LIF production.

Conclusion: CD56bright NKreg cells can be isolated and expanded in vitro. Adult peripheral blood is the optimal source of CD56bright NKreg cells, in terms of purity and cell frequency. Culturing the isolated cells in the presence of IL-2, IL-12, IL-15, antiCD335CD2, and conditioned medium results in good expansion, low cytotoxic activity, increased production of IFNg and LIF, and differentiation of CD56+ total NK cells towards the bright population.

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Poster Board #7 Iris Lee, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

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

Maternal Exercise During Pregnancy and Offspring Adiposity Iris Lee, Nicha Boonpattrawong, Ismail Laher, Angela Devlin

In Canada, approximately 50% of women of childbearing age are overweight or obese. This is concerning as studies have shown that maternal obesity leads to increased adiposity and decreased insulin sensitivity in the offspring. While exercise is known to prevent obesity-related complications, more studies are needed to investigate the effect of maternal exercise on offspring. Our preliminary study tested whether maternal exercise would mitigate the adverse effects of obesity in offspring. We fed female mice (C57BI/6N) a control diet (10% kcal fat) or a western diet (45% kcal fat), with or without voluntary exercise (access to running wheel) throughout breeding, pregnancy, and lactation. Offspring were weaned onto either the control or western diet.

Interestingly, we found a bimodal distribution of adiposity in the control diet-fed offspring; some of the mice had greater adiposity than others within the same experimental group, especially in the groups where dams exercised. Previous research has investigated the differential response to exercise in human using insulin sensitivity as a phenotype to identify responders and non-responders to exercise. They found that Tgf-β was upregulated in the skeletal muscle of non-responders, which downregulates exercise-dependent, mitochondrial genes such as Pgc-1ɑ. We hypothesized that differences in the offspring adiposity is associated with variable responses to exercise in dams during pregnancy.

We observed bimodal distribution of adiposity in offspring from both control diet-fed and western diet-fed dams that exercised. Within each group, offspring with the higher adiposity levels were matched with their dams (labelled non-responders) and the offspring with the lower adiposity levels were matched with their dams (labelled responders). Skeletal muscle tissue from these dams were analyzed. Gene expression of Tgf-β and Pgc-1ɑ were assessed by qPCR and were used as indicators of variable response to exercise.

Expression of Tgf-β was higher in the non-responders compared to the responders in both groups, but was not statistically significant. Pgc-1ɑ levels were similar for non-responders and responders. From our findings, variable response to exercise does not seem to account for differences in offspring adiposity. We will next investigate the expression of genes involved in lipid synthesis in the offspring adipocytes.

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Poster Board #8 Cara Mayer, Undergraduate Student, University of British Columbia Supervisor: Crystal Karakochuk, Healthy Starts

Measuring folate status in children with sickle-cell disease: a pilot study Cara Mayer, Crystal Karakochuk

Sickle-cell disease (SCD) is an autosomal recessive disorder that results in the production of dysfunctional ‘sickled’ red blood cells (RBCs). An increased risk of hemolysis and higher RBC turnover (a folate-dependent process) is thought to cause high folate requirements. Thus, folic acid supplementation with 1-5 mg/day folic acid has been the longstanding recommendation for individuals with SCD. However, there is growing concern about whether Canadian children with SCD need such high doses of folic acid, especially following the mandatory folic acid fortification of flour in 1998. Further, children may not need such high doses due to the development of new medications in the past decade, such as hydroxyurea, which prolong the lifespan of the sickled RBC. Doses of folic acid beyond what the body can process (>0.2 mg folic acid) have been shown to result in accumulation of unmetabolized folic acid in the blood, which can have adverse effects.

Our aim was to measure the folate status of children with SCD who were consuming high-dose folic acid supplements. We obtained permission to use blood samples from the BCCH Biobank that were collected from children with SCD attending BCCH. We report the preliminary results of the samples collected to date (n=6 children). Folate was measured in serum with use of an Abbott i1000 autoanalyzer. The mean±SD serum folate concentration was 99±145 nmol/L; values ranged from 32.4 nmol/L to 394 nmol/L. As the standard values for serum folate are 7-46.4 nmol/L, these preliminary data are on the high side of normal, with a mean much higher than normal due to one extremely elevated value.

Our next steps will include the analysis of more samples (total n=20 children), including the measurement of RBC folate and unmetabolized folic acid using LC-MS. Ultimately, the results from this pilot study will help to determine whether the current folic acid supplementation guidelines warrant reassessment.

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Poster Board #9 James Sader, Undergraduate Student, University of Victoria Supervisor: Bruce Vallance, Childhood Diseases

Congratulations to James on receiving a BC Childrenâ&#x20AC;&#x2122;s Hosptial Research Institute Summer Studentship!

Improving the intestinal environment: A potential therapy for IBD James Sader, HT Law

Background: Inflammatory bowel disease (IBD) is a recurring condition that affects an estimated 1 in 150 Canadians with many children under 10 years old being newly diagnosed. Because of the high failure rate, there is a considerable need for novel therapeutic options to help maintain remission over a patientâ&#x20AC;&#x2122;s lifetime.

Not only do IBD patients have unusually elevated levels of bacteria attached to the intestinal surface, some individuals have a thinner intestinal mucus layer suggesting that dysfunction in the mucus barrier could allow inflammation and dysbiosis to persist.

Hypothesis: We hypothesize that oral administration of fucose-rich polysaccharide (FRP) can select for beneficial commensal microbes that help dampen gut inflammation in IBD. Objectives: To determine how administration of FRP affects (1) host inflammatory response, and (2) gut microbiota balance in IBD murine models.

Methods: Cecal and colonic tissues were removed from FRP-treated or untreated wild type C57BL/6 and spontaneous colitis MUC2-/- mice. RNA was extracted from tissue homogenates, and complementary DNA was synthesized by reverse transcription PCR. Quantitative PCR was used to measure expression levels of inflammation-associated genes in colonic tissues. Droplet digital PCR will be used to quantify gut bacterial abundances from luminal samples.

Results: We observed a general increase in TNF-a expression in colonic tissues of FRP-treated mice. However, TNF-a levels of treated MUC2-/- mice that were co-housed with treated C57BL/6 mice were similar to WT levels. Hypoxia inducible factor-1a (HIF-1a) showed increased expression in treated MUC2-/- co-housed mice.

We found no significant change in trefoil factor 3 expression (TFF3, an indicator of goblet cell quantities) in treated MUC2-/- mice but slightly elevated expression in treated WT mice. Antimicrobial peptide, b-defensin, showed elevated expression in treated MUC2-/- mice.

Future Directions: We will increase sample size to obtain statistically significant data. ddPCR and metagenomic sequencing will be performed to understand the effects of FRP on the microbiome. Protein analyses will augment gene expression data. Further investigations may lead to expansion and enhancement of clinical treatments for IBD.

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Poster Board #10 Melody Salehzadeh, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

Long-term metabolic effects of neonatal sucrose treatment

Melody Salehzadeh, Cynthia Y. RamĂ­rez, Arya E. Mehran, Ei-Xia Mussai, Nicha P. Boonpattrawong, Liisa Holsti, Kiran K. Soma, Angela M. Devlin Background: Nearly 16,000 preterm newborns enter neonatal intensive care units (NICUs) across Canada each year, where they undergo painful procedures up to ten times a day. Oral sucrose solutions (12-24%) are commonly used as an analgesic for minor procedures in neonates; throughout hospitalization, babies can be exposed to high and cumulative volumes of sucrose. Preterm neonates have immature metabolic and physiologic homeostasis and are likely to have poor sucrose disposition as it is not typically found in breast milk. There are no studies on the long-term metabolic effects of repeated neonatal sucrose treatment in animals or humans, and whether it impairs metabolic processes or increases risk for metabolic disorders.

Preterm birth has been associated to obesity and metabolic dysregulation independently of sugar exposure.

We hypothesized that this analgesic intervention may exacerbate such risks.

Methods: Female (F) and male (M) mice (C57BL/6J) were randomly assigned to five groups: sham (only handled) (n=4F/4M), sterile water (n=1F/5M), sucrose (24% in sterile water) (n=2F/5M), fructose (24% in sterile water) (n=4F/3M) and glucose (24% in sterile water) (n=3F/3M). Pups were treated ten times per day for six days (postnatal day [PND] 1-6) with 0.83ÎźL/g weight of respective treatments orally with a micropipette.

Animals were weighed daily until weaning and weekly thereafter. Glucose homeostasis was assessed by intraperitoneal glucose and insulin tolerance tests at weaning and adulthood. Plasma, adipose tissue, skeletal muscle, fixed liver, fixed pancreas, and brain were harvested from all animals at 16 weeks.

Preliminary results: No reliable conclusions could be made in the female mice due to low sample sizes.

Sucrose-treated males were smaller (weight and length) throughout development, had greater glucose tolerance at weaning and in adulthood, and were more insulin sensitive at weaning, compared to other groups.

Conclusions and future directions: Repeated early-life sucrose treatment was associated with physiological and metabolic differences in males when compared to controls, yet further investigation is required to determine mechanisms of neonatal sucrose action. We plan on repeating this experiment with two more cohorts of mice.

Once all collected, we will analyze tissues harvested for metabolic markers.

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Poster Board #11 Chris GJ Tang, Undergraduate Student, University of British Columbia Supervisor: Laura Sly, Childhood Diseases

Investigating the contribution of bacteria to ileal inflammation in SHIPdeficient mice Chris GJ Tang, Peter Dobranowski, Susan C Menzies, Laura M Sly

Introduction: Crohn’s disease, a form of Inflammatory Bowel Disease (IBD), is a chronic, incurable inflammatory disease characterized by inflammation along the intestinal tract. Genome-wide association studies have found over 170 gene polymorphisms associated with IBD. In fact, the production and activity of one gene product, SHIP, has been found to be reduced in patients with Crohn’s disease. SHIP is a hematopoietic-specific lipid phosphatase that downregulated immune activation. Mice deficient in SHIP develop spontaneous ileal inflammation like that seen in patients with ileal Crohn’s disease. Previous work from our lab has found that SHIP-deficient mice have an altered gut microbial composition, but no definitive role of bacteria in causing or preventing inflammation was established. In the wider context of host-microbe interactions, we aim to contribute to the growing knowledge that specific bacterial populations cause IBD in mice.

Hypothesis: We predict that modulating the microbiome of SHIP-deficient mice will attenuate spontaneous ileitis.

Objectives: To address our hypothesis, we have three experimental objectives: 1. Determine if reducing the gut bacterial load of SHIP-deficient mice using broad-spectrum antibiotics will attenuate ileal inflammation.

2. Determine if transferring ileal contents from SHIP-deficient mice to germ-free wild type mice to confirm if the gut microbiota is sufficient to cause ileal inflammation.

3. Determine if dietary antioxidant supplementation in SHIP-deficient mice will attenuate dysbiosis and ileal inflammation.

These studies will identify the pro-inflammatory nature of the SHIP-deficient microbiota. With this knowledge, we will build on our lab’s previous 16S rRNA gene analysis and leverage microbiota modulation as a potential therapeutic strategy for Crohn’s disease patients with reduced SHIP activity.

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Poster Board #12 Kai Zhu, Undergraduate Student, University of British Columbia Supervisor: Bruce Verchere, Childhood Diseases

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

Effects of PAM Haploinsufficiency on Islet Amyloid and β-cell Failure Kai Zhu, Yi-Chun Chen, Bruce Verchere

Background: A primary pathological feature of type 2 diabetes is the deposition of amyloid plaques in pancreatic islets. Amyloid plaques are made of insoluble aggregates of islet amyloid polypeptide (IAPP), which is first synthesized as a prohormone in β-cells and processed to the mature, bioactive form by various processing enzymes. One of these enzymes, peptidylglycine α-amidating monooxygenase (PAM) removes a glycine residue and mediates the amidation of the C-terminus of IAPP. Hence, deficiency in PAM may cause accumulation of non-amidated intermediates of IAPP. Recently, two genetic variants in PAM (Ser539Trp and Asp563Gly) were found in humans to be associated with low insulin secretion and risk of T2D. We aim to elucidate the roles of PAM in regulating insulin secretion and whether deficiency of PAM contributes to β-cell failure and diabetes.

Methods: The aggregation patterns and fibril forming kinetics of both mature and non-amidated forms of IAPP were monitored using electron microscopy and thioflavin T assay, respectively. Amyloid prevalence and severity in the pancreatic sections of PAM Ser539Trp variant carriers and BMI-matched control subjects were measured by immunofluorescence staining. Glucose-stimulated insulin secretion of pancreatic islets of Pam+/hIAPP transgenic (Pam+/- hIAPP Tg/0) and control (Pam+/+ hIAPP Tg/0) mice were determined by ELISA. Results: Mature IAPP formed amyloid fibrils in vitro, whereas non-amidated IAPP did not. Interestingly, the fibril forming properties of mature IAPP were inhibited when incubated together with non-amidated IAPP. However, histological analysis displayed no differences in the amyloid prevalence and severity between the pancreatic tissue sections from the human PAM variant carriers and their BMI-matched control subjects.

Glucose-stimulated insulin secretion was comparable in islets isolated from Pam+/- hIAPP Tg/0 and Pam+/+ hIAPP Tg/0 mice.

Conclusions: Despite the inhibitory effects of non-amidated IAPP on the aggregation of mature IAPP in vitro, PAM haploinsufficiency does not have an effect on glucose-stimulated insulin secretion in hIAPP-exressing islets, suggesting that one copy of PAM may be sufficient to properly regulate metabolism and β-cell function.

Further analysis is required to elucidate whether PAM variant carriers have altered amyloid prevalence and severity.

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Session 02 BASIC SCIENCE

Moderator: Dr. HT Law Participants: Zoe DeBoer Michael Doyle Jasia Ho Thomas Hoang Nahae Kim Michelle Lee Jessica Leung Rebecca Lim Ziqi Liu Tina Madani Kia Paige Muir Aryan Riahi Janine Xu

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Poster Board #13 Zoe DeBoer, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

Genetic dissection of a new oxidative stress response pathway in Caenorhabditis elegans Zoe DeBoer, Kelsie Doering, Grace Ying-Shyen Goh, Regina Lai, Stefan Taubert

Organisms encounter a variety of environmental stresses, and in order to survive they must mount specific cellular responses. Oxidative stress occurs when reactive oxygen species (ROS), by-products of normal aerobic respiration, accumulate within the cell. In vivo, an overproduction or accumulation of ROS and impaired defense mechanisms can cause cellular damage by oxidizing lipids, proteins and DNA. From this, oxidative stress exasperates many diseases such as childhood cancers and diabetes.

The specific response pathways that allow the cell to adapt to oxidative stress are evolutionary conserved across species from humans to Caenorhabditis elegans. C. elegans is a microscopic nematode worm that is transparent, genetically highly tractable, and has a short life cycle. These features make the worm an excellent live model to explore oxidative stress response pathways.

Oxidative stress responses in C. elegans usually require the transcription factor skinhead-1 (SKN-1), the ortholog of human nuclear factor erythroid-2-related factor 2 (Nrf2), which is considered the master regulator of oxidative stress responses. However, the response to the oxidative stressor tert-butyl hydroperoxide (tBOOH) is largely SKN-1-independent. Our lab has found that the transcription factor nuclear hormone receptor NHR-49 is required for both a) worm survival on, and b) to induce a transcriptional response to tBOOH, including the induction of the stress response gene fmo-2.

Other factors that act with NHR-49 in this new response pathway remain unknown. The aim of my project is to dissect the role of NHR-49 in this response to tBOOH and to identify new players in this pathway. I am currently performing a reverse genetic screen using RNA interference to identify such players. As readout, I am using a transcriptional reporter of GFP fused to the promoter of fmo-2. From this, we will identify which of the wormâ&#x20AC;&#x2122;s ~900 transcription factors, ~400 kinases and ~500 transcriptional co-regulators are required for the induction of fmo-2 on tBOOH, and may be involved in the NHR-49-pathway. Thus far, I have screened all kinases, revealing ~30 potential candidates to be validated. Identifying novel factors in this pathway in the worm may lead to potential new targets for drugs and therapies in humans.

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Poster Board #14 Michael Doyle, Undergraduate Student, University of British Columbia Supervisor: Michael Kobor, Healthy Starts

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

Investigating the effect of natural variation in the oxidative stress response Michael Doyle, Maria Aristizabal, Marla Sokolowski, Michael Kobor

A delicate interplay exists between an organism’s genes and its environment. In the case of fruit flies (Drosophila melanogaster), natural variation in the foraging gene (FOR), confers differences in foraging behaviour, metabolism, stress resistance, life span and memory in relation to food availability. FOR encodes for a cGMP-dependent kinase (PKG) and interestingly naturally occurring alleles (rover and sitter), produce different PKG isoform profiles.

FOR has been studied in relation to a variety of stress conditions including food and sleep deprivation and osmotic stress, however its role, if any, in oxidative stress has not been explored. Oxidative stress plays an important role in disease and aging and it occurs when an organism’s protective antioxidants are overwhelmed, leading to structural damage to DNA, proteins and lipids. Suggesting a possible role for FOR in oxidative stress, rover and sitter flies show differences in life expectancy. Furthermore, a target of PKG, protein phosphatase 2A (PP2A), has been suggested to function in the oxidative stress response, with oxidative stress deactivating PP2A via phosphorylation.

We hypothesized that rovers and sitters vary in their response to oxidative stress. To explore this possibility, we will interrogate how exposure to oxidative stress affects various points in the FOR pathway. Exposure to the herbicide paraquat is a common method to induce oxidative stress in flies. Therefore, we will collect paraquat treated rovers and sitters to asses changes in known oxidative stress pathways and FOR-associated pathways.

In particular, I will use RT-qPCR and immunoblotting of superoxide dismutase 1 (SOD1), a known marker of oxidative stress to assess the efficacy and dosage of the paraquat treatments. Then I will look at the effect of FOR allele sequence in SOD1 protein and mRNA levels, as well as PP2A phosphorylation. In addition, I will also focus on phosphorylation of serine 10 on histone H3 (H3S10p), a substrate of PP2A. This will extend our study to include downstream epigenetic consequences of oxidative stress and a potential transgenerational effect.

All together, this study presents a new opportunity to extend the role of FOR in the cell and link it to potential consequences in aging and disease.

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Poster Board #15 Jasia Ho, Undergraduate Student, University of British Columbia Supervisor: Ted Steiner, Childhood Diseases

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

A4-Fla2, a Dominant Antigen in Crohn’s Disease, Evades TLR5 Stimulation Jasia Ho, William Rees, Theodore Steiner

Inflammatory bowel diseases (IBD) are disorders hallmarked by the chronic inflammation and ulceration of intestinal mucosa that the body is unable to control. It is found in its two main forms, ulcerative colitis (UC) and Crohn’s disease (CD). IBD’s characteristic inflammatory symptoms are driven by cytokine activity, which seems to arise from an intolerant relationship between gut microbiota and the mucosal immune system. Microbial components can be shown to trigger the onset of IBD. Thus, various markers, such as bacterial flagellin, are used to test seroreactivity to different microbial antigens in IBD patients.

Bacterial flagellin can cause heightened inflammatory responses in IBD patients. A4-Fla2, a flagellin protein produced by a Lachnospiraceae A4 strain, is an important antigen in patients with CD. However, preliminary research suggests that it is not recognized by TLR5, a prominent protein in the innate immune response that usually mediates flagellin recognition. This interesting phenomenon suggests that flagellin evasion of the innate immune plays a key role in IBD pathophysiology. Our aim is to investigate how A4-Fla2 is avoiding this innate immune recognition.

Homology modelling shows that A4-Fla2 has structural regions distinct from those in Salmonella FliC, a flagellin protein readily recognized by TLR5. We made different recombinant chimeric flagellin proteins by replacing residues in FliC with corresponding residues found in A4-Fla2 through site-directed mutagenesis. HEK cells will be transfected with TLR5 and then stimulated with different chimeric flagellin proteins to measure release of IL-8 (CXCL8), an inflammatory cytokine. This is a marker of TLR5 activation in these cells.The hypothesis is that some of the chimeras will yield low IL-8 concentrations, which will identify the residues responsible for TLR5 evasion The findings from this project will provide more insight on the mechanisms of flagellin and TLR5 interaction in relation to IBD. The newfound information of certain antigenic microbial proteins evading stimulation of the innate immune system opens up new possibilities in decoding the etiology of IBD.

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Poster Board #16 Thomas Hoang, Undergraduate Student, University of British Columbia Supervisor: Brett Finlay

Congratulations to Thomas on receiving a Canadian Association of Gastroenterology Summer Studentship!

Bacterial Metabolism as a Contributor to Environmental Enteric Dysfunction Thomas Hoang, Kelsey Huus, Brett Finlay

Malnutrition is a global health crisis responsible for 45% of childhood deaths under the age of five. In developing countries with poor sanitation, chronic fecal-oral contamination exacerbates malnutrition, enabling overgrowth of pathobionts like E. coli that can contribute to intestinal inflammation. Environmental enteric dysfunction (EED) is a subclinical inflammatory disease of the small intestine, characterized by villous blunting, increased gut permeability, and nutrient malabsorption. EED is linked to poor sanitation, rendering renourishment programs in low-income countries unsuccessful. Despite its prevalence, underlying disease mechanisms are poorly understood. This project explores a potential microbial etiology, examining how carbohydrate cross-feeding in the microbiota of malnourished individuals contributes to EED by promoting E. coli proliferation.

Our lab has shown a specific combination of commensal bacteria (5 Bacteroidales and 2 E. coli strains) can induce EED features in malnourished mice fed a carbohydrate-rich diet. To determine whether Bacteroidales could promote E. coli growth, we co-cultured the seven bacteria in media containing various host or dietary carbohydrates as the sole carbon source and quantified stationary-phase E. coli by CFU counting. Our findings indicate Bacteroidales promote E. coli growth in mucins, as well as the dietary carbohydrates inulin, starch, and cellulose. Given the abundance of these polysaccharides in a malnourished gut environment, liberation of monosaccharides by Bacteroidales could fuel E. coli overgrowth to exacerbate inflammation.

To identify metabolites potentially mediating this cross-feeding, we generated E. coli deletion mutants unable to metabolize fucose, N-acetylglucosamine (NAG) and sialic acid, which are all monosaccharides shown to promote E. coli growth in vivo. Competition experiments were performed using these mutants to assess for any fitness defects in Bacteroidales-facilitated carbohydrate growth. We found that sialic acid, fucose, and NAG alone are not key contributors to these metabolic interactions.

Together, our results show carbohydrates can fuel a Bacteroidales-E. coli cross-feeding, with potential relevance in a low-protein, malnourished gut environment. Future experiments will utilize transposonsequencing to identify metabolic genes that confer an E. coli growth advantage in host and dietary carbohydrates. These results will inform in vivo experiments investigating how E. coli expansion might contribute to EED, as well as elucidate putative disease biomarkers.

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Poster Board #17 Nahae Kim, Undergraduate Student, University of British Columbia Supervisor: C. Bruce Verchere, Childhood Diseases

Targeting the NLRP3 Inflammasome as a Potential Treatment for Diabetes

Nahae Kim, Heather C. Denroche, Josh Zaifman., Sam Chen, Ying Tam, Chris Tam, C. Bruce Verchere Introduction: The NLRP3 inflammasome is a large multi-molecular protein complex that mediates the release of interleukin-1 beta (IL-1 beta), a major pro-inflammatory cytokine, from stimulated macrophages. It is activated by various pathogen or danger associated molecular patterns, some of which are elevated in type 2 diabetes. Chronic activation of the NLRP3 inflammasome in type 2 diabetes is thought to result in local inflammation within pancreatic islets, impairing beta cell function. Therefore, the NLRP3 inflammasome may be a valuable therapeutic target for type 2 diabetes.

Objective: We aimed to develop and identify novel NLRP3 inhibitors and assess their therapeutic potential for limiting IL-1 beta release in stimulated macrophages and subsequently in a mouse model of type 2 diabetes.

Methods: Several glyburide- and rhodanine-derived compounds have been shown to selectively inhibit the NLRP3 inflammasome. With our industry collaborators from Integrated Nanotherapeutics, we synthesized these along with five new glyburide derivatives and an additional rhodanine derivative. LPS-primed murine (C57BL/6J) bone marrow-derived macrophages were treated with this series of compounds, after which ATP was added to activate the NLRP3 inflammasome. Supernatants were then measured for secreted IL-1 beta by ELISA. Results: Relative to the stimulated control, glyburide completely blocked IL-1 beta secretion at 400 micromolar and reduced it by 83% at 20 micromolar. However, published glyburide-derived inhibitors (compounds 1 to 3) and novel compounds 4, 5, 7, and 8 did not significantly reduce IL-1beta secretion at 400 micromolar. In contrast, compound 6 diminished IL-1 beta secretion by 72%, and compound 9 completely blocked it at 400 micromolar.

Published rhodanine derivative (compound 10) decreased IL-1 beta secretion by 92% at 20 micromolar, while interestingly, our new rhodanine derivative (compound 11) exhibited complete inhibition at the same concentration; concentration-response curves revealed their half maximal inhibitory concentrations to be 10.4 and 3.6 micromolar, respectively.

Conclusion: Having identified two potent novel NLRP3 inhibitors, compounds 9 and 11, future experiments will investigate the ability of these lead compounds to attenuate islet inflammation and beta cell dysfunction in a mouse model of type 2 diabetes, as well as the mechanism of action by which they inhibit the NLRP3 inflammasome.

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Poster Board #18 Michelle Lee, Undergraduate Student, University of British Columbia Supervisor: Francis Lynn, Childhood Diseases

Congratulations to Michelle on receiving a BC Children’s Hospital Research Institute Childhood Diseases Summer Studentship and a UBC Faculty of Medicine Summer Studentship!

Single-cell transcriptomic changes of human pancreatic islet cells in response to glucose and calcium signaling Michelle Lee, Ji Soo Yoon, Thilo Speckmann, Francis Lynn

Diabetes is growing in prevalence worldwide; currently, the disease affects 415 million people and will affect approximately 600 million by 2040. Diabetes occurs when pancreatic endocrine cells(islets) fail to regulate blood glucose levels, leading to high glucose levels that become toxic to cells in the body. In order to understand the impaired islet function during diabetes and possible treatments, we need to understand their normal physiology. In healthy islets, glucose stimulates islet hormone secretion and triggers various secondary processes. Calcium signaling, which is downstream of glucose uptake and directly causes hormone secretion, is also a secondary messenger. This coupling of glucose and calcium pathways in islets has caused difficulties in studying the separate effects of the inducers.

To investigate the effect of glucose stimulation and calcium signaling on islet physiology separately, human islets are placed under three conditions for 1 hour: 1) a basal control where the islets remain in low glucose, 2) a “positive” condition where high glucose and KCl trigger both glucose and calcium signaling, and 3) a “negative” condition where the calcium chelator egtazic acid is added with high glucose and KCl to stimulate glucose signaling but inhibit calcium signaling. These three groups of cells undergo single-cell RNA-sequencing and are analyzed.

Sequencing data from all cells are pooled and divided into clusters based on gene expression similarity. 10 cell types are identified, confirming islet heterogeneity. All endocrine cell types are found in expected proportions: 40% beta(β)-cells, 40% alpha(α)- cells, 4.5% delta-cells, 1.5% PP-cells and a novel 1% insulin and glucagon double-positive cells. Two and three subtypes of β-cells and α-cells are found respectively. The β-cell subtypes in basal condition have significant gene expression differences for 50 genes, with several glucose-stimulated genes having the highest fold-change differences. The α-cell subtypes differ more substantially, with 400 differentially expressed genes. Furthermore, 12 genes are found to be calcium-signaling dependent in β-cells and 8 in α-cells, with 5 of these genes expressed in both cell types. We plan to sequence more human islets for biological replicates and to investigate the identity of the interesting insulin and glucagon double-positive cluster.

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Poster Board #19 Jessica Leung, Medical Student, National University of Ireland, Galway Supervisor: Laura Sly & Mahdis Monajemi, Childhood Diseases

Congratulations to Jessica on receiving a Canadian Association of Gastroenterology Summer Studentship!

The role of MALT1 expression in inflammatory bowel disease Jessica Leung, Mahdis Monajemi, Yvonne Pang, Susan Menzies, Kevin Jacobson, Laura M Sly

Background and Rationale: Inflammatory bowel disease (IBD) is characterized by inflammation of unknown etiology along the gastrointestinal tract. Current research shows that the gene encoding mucosa associated lymphoid tissue (Malt1) plays an essential role in activating the transcription factor, nuclear factor ÎşB (NFÎşB), which is associated with pro-inflammatory cytokine production. Our laboratory has found that in vitro, Malt1 is dramatically induced in macrophages downstream of innate immune receptors, dectin-1 and toll-like receptor 4 (TLR4). This suggests that Malt1 may contribute to intestinal inflammation, which is largely driven by macrophages. However, we do not know whether Malt1 induction occurs in mice in vivo during intestinal inflammation or the consequences of its induction.

Hypothesis: We hypothesize that Malt1 mRNA and protein expression are increased during intestinal inflammation in response to innate immune stimuli in both mice and human.

Aims: 1. To investigate the role of Malt1 induction on innate immune responses in vivo in mice during DSS-induced colitis 2. To study the level of Malt1 expression in intestinal tissues from patients with IBD, compared with healthy individuals.

Methods and Results: Malt1+/+ mice at 8 weeks of age were given dextran sodium sulphate (DSS) to their drinking water for seven days to induce intestinal inflammation. In humans, biopsy samples from the intestines of IBD patients were used. To study the effects of inflammation of Malt1 expression in intestinal tissues, Western blot and qPCR techniques were then used to measure Malt1 protein levels and mRNA expression, respectively. Thus far, our data shows that Malt1 expression in vivo in mice and humans is not associated with intestinal inflammation.

Future Directions: Collectively, these studies will help determine the role of Malt1 in macrophages in vitro and in the intestines in vivo. This will provide insight into the mechanism(s) driving inflammation, and may identify novel targets that we can use to dampen down intestinal inflammation, like that which characterizes IBD.

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Poster Board #20 Rebecca Lim, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

Congratulations to Rebecca on receiving a NSERC Undergraduate Student Research Award!

Effects of Maternal Obesity and Folic Acid Supplementation on Offspring Metabolic Health Rebecca Lim, Ei-Xia Mussai, Angela Devlin

Maternal obesity (BMIâ&#x2030;Ľ30kg/m2) has been shown to have negative effects on offspring health, such as increased susceptibility to adiposity, dysfunctional metabolic development, and impaired glucose homeostasis.

Pregnant women and women of childbearing age are recommended to take supplements containing 0.4 mg of folic acid per day to prevent neural tube defects. However, women with pre-gestational obesity are recommended to take 5 mg of folic acid per day, which is 12.5x the recommended daily intake. There is little evidence to support this recommendation and no study has been conducted to examine the effect of folic acid in the context of maternal obesity. Our goals are to determine if folic acid supplementation during pregnancy exacerbates the adverse effects of maternal adiposity on the placenta and the offspring.

For this study, female C57BL/6J mice were fed a control diet (10% energy from fat) or a Western diet (45% energy from fat) from weaning to induce excess adiposity and glucose intolerance. The diets were formulated with (10mg/kg diet) or without (2mg/kg diet) supplemental folic acid. Female mice were bred at 13 weeks of age. After 18 days of pregnancy, dams were euthanized and maternal tissue, placentae, and fetal mice were collected and stored. Glucose and insulin tolerance were analyzed using intraperitoneal glucose and insulin tolerance tests respectively. The SRY gene was genotyped in the fetal mice to determine sex.

At 13 weeks on diet, female mice fed the Western diet were found to have greater fat mass (n=8-10, p<0.05) and body weight (p<0.05) than mice fed the control diet. This was accompanied by greater fasting blood glucose (p<0.05) and glucose intolerance (p<0.05) with greater area under the curve (p=0.001). When normalized for baseline fasting glucose, no difference in insulin tolerance was observed between groups.

There was no effect of folic acid supplementation. In Western-fed dams, gonadal, inguinal and retroperitoneal fat pads were significantly larger (p<0.05). These results confirm our mouse model of diet-induced obesity.

Maternal diet had no effect on litter size, placental, fetal brain and fetal liver weights (n=5-8).

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Poster Board #21 Ziqi Liu, Undergraduate Student, University of Toronto Supervisor: Wendy Robinson, Healthy Starts

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

Comparative analysis of normalization methods for Infinium 850K DNA methylation data in placental samples from multiple cohorts Ziqi Liu, Victor Yuan, E. Magda Price, Johanna M. Schuetz, Elodie Portales-Casamar, Cathy Vaillancourt, Tim F. Oberlander, Wendy P. Robinson

Background: DNA methylation (DNAm) is an epigenetic modification to the human genome that affects gene expression without changing the DNA sequence. Methylation occurs at cytosine-guanine dinucleotides (CpGs) and can be assayed using the Illumina Infinium MethylationEPIC (850K) Beadchip which measures methylation at 866,091 CpGs in the human genome. However, due to the intrinsic design of 2 different types of probe chemistry in the 850K, data normalization to remove background intensity and correct for probe type bias is an important step to consider before data analysis. Several normalization methods exist, but it is unclear which method performs best in placental samples from multiple cohorts.

Objectives: To determine the most effective normalization method for 850K DNAm data in the placenta Methods: We collected 850K DNAm data from 3 cohorts totaling 182 placental villi samples. We filtered out 3,759 poor quality probes, 38,807 cross-hybridizing probes and 70,441 placenta-specific invariable probes, leaving 755,478 remaining. Six normalization methods were applied to the filtered data: Subset-quantile within array normalization (SWAN), Noob normalization (Noob), Functional normalization (Funnorm), Beta-mixture quantile dilation (BMIQ), Noob with BMIQ (BMIQ.N), and Functional normalization with BMIQ (BMIQ.F). Both qualitative and quantitative analyses were completed through performing principal component analysis (PCA) and examining inter-replicate correlation and probe densities to determine the most effective normalization method.

Results & Significance: After comparing normalization methods, we found that BMIQ.N yielded the best data quality. PCA showed that it was effective in removing confounding technical factors while preserving biological factors. Qualitative analysis of the probe type density plots revealed that BMIQ.N was the most successful at correcting for bias between type I and type II probes. BMIQ.N also increased inter-replicate correlation, another indicator that some technical factors were removed. Out of all the normalization methods, SWAN performed the most poorly, decreasing the effect technical factors had on DNAm the least. BMIQ.F performed just as well as BMIQ.N, however in attempting to correct for probe bias BMIQ.F was too stringent. These results provide a point of reference for the processing

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Poster Board #22 Tina Madani Kia, Undergraduate Student, University of British Columbia Supervisor: Kevan Jacobson, Childhood Diseases

Congratulations to Tina on receiving a NSERC Undergraduate Student Research Award!

The impact of murine gut microbiota composition on susceptibility to DSS-induced colitis Tina Madani Kia, Genelle Healey, Kevan Jacobson

Background: Dextran sulfate sodium (DSS) induced colitis in mice is commonly used to study the pathobiology of inflammatory bowel disease (IBD). However, very little research has been undertaken in mouse models to determine whether baseline gut microbiota composition influences the severity of DSS-induced colitis. This introduces a likely confounding factor when determining the true efficacy of an intervention which aims to reduce the severity of colitis. We hypothesize that baseline gut microbiota composition and DSS-induced changes in gut microbiota will have an influence on the severity of DSS-induced colitis.

Objectives: 1. Demonstrate whether there are differences in the severity of DSS-induced colitis between groups of mice under the same experimental conditions.

2. Optimise and determine the specificity of several bacterial primer sets which will be used to demonstrate gut microbiota variability Methods: Three groups (group 1, 2 and 3) of male C57BL/6 mice (n = 5 per group) were given DSS in drinking water for five days and monitored for seven days following DSS. Stool samples were collected at three time points: Pre-DSS (day 0), Post-DSS (day 5) and one week following DSS (day 12). Bacterial DNA was extracted from stool samples using the Omega E.N.Z.A Soil DNA kit. Body weight, DSS containing water intake and disease activity scores were recorded each day. Mice were sacrificed at day 12; colonic and cecal lengths were measured and colonic tissue was collected. Primer set specificity and optimal annealing temperatures were determined using the BioRad CFX96 real-time PCR system.

Preliminary Results: Group 3 had a significantly lower (p < 0.05) disease activity score and body weight loss, and increased colon and cecum length when compared to group 1 and 2. There were no significant differences (p > 0.05) in DSS containing water intake between the three groups. Furthermore, primers for various bacterial taxa were shown to be specific to the target bacteria only.

Conclusion: Significant differences in severity of DSS-induced colitis was demonstrated between the three groups of mice. Future work will use Droplet Digitalâ&#x201E;˘ PCR to determine if there are any differences in baseline gut microbiota between the three groups of mice and whether these differences correlate with disease severity.

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Poster Board #23 Paige Muir, Undergraduate Student, University of British Columbia Supervisor: Suzanne Vercauteren, Childhood Diseases

Congratulations to Paige on receiving a BC Children’s Hospital Research Summer Studentship!

Determining the Quality of Biobanked Tissue Specimens

Paige Muir, Thomas Soroski, Jonathan Bush, Philipp Lange, Jefferson Terry, Tamsin Tarling, Suzanne Vercauteren Delays between pathological examination of specimens and sample processing for research are inevitable in a hospital setting and this can influence the quality of tissue being used in research. It has been found that DNA yield, purity and integrity as well as RNA yield and purity can be preserved in saline over a 7 day period when using tonsil samples. RNA integrity on the other hand only remains robust for up to 3 days in saline and declines significantly 7 days post-collection. Even with the research that has already been conducted, the effects of ex vivo ischemia time on RNA integrity and protein quality are still not well understood for biobanking purposes. Our goal is to determine how rapidly tissue quality declines with time so that a standardized protocol can be put into place to collect high quality samples at the BC Children’s Hospital BioBank while minimizing interference with hospital workflow. We have collected ten placentas and tissue punches have been taken from each one at different time points. The first punches were frozen immediately after collection outside of the Operating Room and the rest of the tissue sample was divided in two and placed either in saline solution or protein preservation buffer. The remaining punches were taken at 0.5, 2, 24, 48, 72, and 168 hours after collection to simulate short and long term delays in specimen procurement at the BioBank. We are working on extractions to isolate DNA, RNA and protein so that quantitative and qualitative analyses can be used to determine their yield, integrity and purity. Finally, we will use ANOVA and post-hoc Tukey analysis to determine the significance of our results. In the end, we hope to determine the most efficient collection protocol to ensure that samples of the highest quality are being used for research purposes here at BC Children’s and Women’s Hospitals.

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Poster Board #24 Aryan Riahi, Medical Student, University of British Columbia Supervisor: Kirk Schultz, Childhood Diseases

Congratulations to Aryan on receiving a UBC Faculty of Medicine Summer Studentship!

Characterization of donor IFNgamma producing Th1 cell suppression of chronic graft versus host disease (cGvHD) in blood and marrow transplantation (BMT) Kirk Schultz, Amina Kariminia, Aryan Riahi

Introduction: When children battle with leukemia, treatment called bone marrow transplants (BMT) involves transplanting blood or bone marrow from a donor. This “cure” can lead to a fatal disease. An estimated 25% of children and 60% of adults receiving BMT will develop a disease where the recipient’s tissue is rejected by the donor’s immune system, called chronic Grafts-versus-Host Disease (cGvHD). The effects of cGVHD are multisystemic. With approximately 22,000 pediatric BMT survivors, novel approaches to eliminate cGvHD are direly needed.

Background: The Schultz Research Team has previously found a negative correlation between IFN-gamma producing helper T (Th1) cells and CD56bright NKreg cells. This opens the potential for ex vivo expansion of these cell populations post BMT to lower rates of cGvHD after performing BMT. This association was previously found in adults. We aim to find the same association in 64 pediatric donor samples.

Also, we are currently uncertain of the specific type of IFNgamma Th1 cell subpopulation responsible for the association. While previous literature suggests that IFNgamma-secreting Th1 cells play a pro-inflammatory role, we hypothesize that it plays a regulatory role.

Methods: Blood was collected from pediatric donors who did or did not induce cGVHD in the recipients (GVHD+ or GVHD-). Cord blood (CB), bone marrow (BM), and peripheral blood mononuclear cells (PBMC) was isolated using ficoll. PBMC includes T cells which contains our population of Th1 cells of interest. The PBMC was cultured with a potent antigen, PMA ionomycin. IFNgamma secretion by Th1 cells was detected with detection antibodies. The results were processed with flow cytometry.

Conclusion: The differences seen in adults for IFNg secreting Th1 cell populations in patients with and without cGVHD was not reproducible in a pediatric cohort. The experiment conducted last year demonstrated a negative correlation between IFN-gamma producing helper T (Th1) cells and the incidence of cGVHD in recipients. Interestingly, the adult population was not replicated. An opposite trend was found in the small pediatric population tested. One possible reason for this may be differences in the immune system of pediatric vs. adult populations. T cell development in children is a dynamic process that answers the demands of a maturing and proliferating immune system. The role of Th1 cells may differ in the two populations for similar reasons.

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Poster Board #25 Janine Xu, Undergraduate Student, McGill University

Supervisor: Bruce Vallance & Joannie Allaire, Childhood Diseases

Congratulations to Janine on receiving a NSERC Undergraduate Student Research Award!

The role of SIGIRR in controlling the intestinal mucus barrier Janine Xu, Joannie M Allaire, Bruce A Vallance

Background: Intestinal mucus is the first layer of the gastrointestinal (GI) tract, forming an important barrier to protect intestinal epithelial cells (IECs) from direct contact with pathogens. The principal component that forms the mucus layer is Muc2, a protein secreted by IECs. Muc2 is heavily glycosylated to form a dense, protective network that serves both as a food source and as a barrier for gut microbes. Defects in this mucus layer are often implicated in inflammatory bowel disease (IBD) and have been suggested to appear before the onset of inflammation. However, it is not clear what key elements control the integrity of the mucus layer.

Single immunoglobulin IL-1 related receptor (SIGIRR) is a negative regulator of TLR/IL-1R signaling, and suppresses inflammatory responses in the GI tract. Sigirr-/- mice are shown to be more susceptible to Campylobacter jejuni infections and display more bacterial penetration into the epithelium, suggesting that their mucus layer is affected. However, the specific role played by SIGIRR in controlling host-microbe interactions at the mucosal surface is still unknown. We hypothesize that SIGIRR, mostly expressed in IECs, participates in establishing a proper mucus layer, thus directly influencing commensal population within the gut and protecting against pathogen infection.

Objective: To investigate the role of SIGIRR in the proper formation of the intestinal mucus layer by examining the integrity of the mucus layer and changes in Muc2 glycosylation.

Methods: We visualized mucus protein and glycosylation of C57BL/6 versus Sigirr-/- mice, using lectin staining of Carnoyâ&#x20AC;&#x2122;s fixed colon and cecum sections. qPCR analysis was used to compare and quantify gene expression levels of specific enzymes responsible for mucus glycosylation, such as Fut2, a gene involved in fucosylation of Muc2.

Results: Mucus measurement and Muc2 staining showed no differences in mucus production of Sigirr-/mice. Lectin staining of colon and cecum sections showed decrease in fucosylation in Sigirr-/- mice with no differences in expression of Fut2 mRNA levels.

Conclusion: The preliminary results show that the glycosylation pattern of the GI mucus is affected by the absence of SIGIRR; however, these results do not correlate with gene expression of their specific enzymes.

Further work will determine if SIGIRR impacts the integrity of the mucus layer by modifying the mucus secretion or turnover rate.

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Session 03

Clinical, Population Health & Health Services

Moderator: Dr. Bahaa Abu Raya Participants: Darson Du Karanvir Gill Amy Ker Mimi Kuan Wendy Li Rebecca Lin Cody Lo Dylan Meng Habibur Rahman Veronica Romines Madeleine Tan

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Poster Board #26 Darson Du, Medical Student, University of British Columbia Supervisor: Anna Lehman, Childhood Diseases

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

Diagnostic rate and inheritance patterns in siblings with developmental disorders undergoing genetic sequencing Darson Du, Shelin Adam, Christele Du Souich, Jill Mwenifumbo, Tanya Nelson, Clara Van Karnebeek, Alison Elliott, Jan Friedman, Anna Lehman

Background: Monogenic disorders are estimated to affect 4% of total births worldwide. Genome-wide sequencing has been effective in elucidating a diagnosis in many of these patients. A history of a similarly affected sibling is generally taken as an indicator of an autosomal recessive disorder. However, the overall incidence of autosomal recessive disorders in outbred populations is low, particularly relative to the frequency of de novo genetic disorders.

Methods: In a translational care study (CAUSES), genome-wide sequencing was performed in 462 families, of which 29 had 2 affected siblings sequenced. All had a congenital or developmental disorder with a presumed genetic cause. Variant classification was performed by a clinical laboratory using ACMG guidelines, and overall diagnostic impression was determined by clinical geneticists. Diagnostic rate and inheritance patterns in families with affected siblings versus a single affected offspring were compared.

Results: We identified pathogenic variants in 20 of the 58 (34.5%) siblings that were sequenced. Autosomal dominant disorders were observed in 9 of the 20 (45.0%) patients diagnosed in the QUAD-WES/QUAD-WGS group. Autosomal recessive disorders account for 8 (40.0%) of these patients, while 3 (15.0%) patients were diagnosed with X-linked recessive disorders.

Conclusion: Genetic diagnostic rates in families with 2 affected siblings sequenced is lower than in families with a single affected child sequenced (196/404, 48.5%). Although autosomal dominant disorders are the most common inheritance pattern in both groups, families with multiple affected children are less likely to be diagnosed with an autosomal dominant disorder.

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Poster Board #27 Karanvir Gill, Undergraduate Student, University of British Columbia Supervisor: Ian Pike, Evidence to Innovation

Congratulations to Karanvir on receiving a BC Injury Research and Prevention Unit Studentship!

Safety Preparedness of Recreational Boaters in BC: Who’s Missing What?

Karanvir Gill, Joseph Janssen, Jennifer Smith, Ian Pike

Nearly one third (32%) of drowning deaths each year in British Columbia (BC) are related to recreational boating. The leading risk factors are: not wearing a personal flotation device (PFD), and alcohol consumption.

Secondary analysis of Pleasure Craft Safety Checks conducted by the Royal Canadian Marine Search and Rescue (RCMSAR), was undertaken in order to better understand the safety preparedness and knowledge of recreational boaters in BC. RCMSAR volunteers conduct safety checks of recreational vessels at marinas throughout BC upon request of the vessel operator. Survey forms collect information about the vessel and safety equipment on board, as well as operator knowledge and certification. The data were electronically aggregated and de-identified in REDCap (Version 8.1.19) prior to analysis. Descriptive analyses were conducted using the R Project for Statistical Computing Software (Version 3.3.3).

A total of 2,824 forms were included in the analysis. The most common vessel types were powerboats with an inboard motor (70%) and sailboats (24%). Almost all safety checks (>98%) were for pleasure crafts operating in coastal waters, with homeports in Vancouver (38%), North Vancouver (27%), other parts of the Greater Vancouver area (10%), Vancouver/Gulf Islands (7%), and Washington, USA (2%).

Ninety-one per cent (91%) of all boaters in this study achieved a “complete” on their form, to indicate that they passed the safety check. In order to attain a pass on this check, operators were expected to have the required personal lifesaving appliances, visual signals, vessel safety equipment, navigation equipment, firefighting equipment, other compulsory equipment where applicable, and some proof of competency, per the requirements of Transport Canada. Notably, 95% of vessels were equipped with the appropriate sized PFDs for all passengers on board, and 93% of all boat operators expressed awareness about the dangers of alcohol while boating. The majority (95%) of boaters had proof of competency.

The results of this study suggest that, despite high safety awareness and preparedness among recreational boaters, a compliance gap remains. Future studies should seek to clarify what safety factors are ignored and why, in order to better tailor messaging to boaters so as to prevent further tragedies.

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Poster Board #28 Amy Ker, Undergraduate Student, McGill University

Supervisor: Donna Lang, Brain, Behaviour & Development

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

Effects of Antipsychotics and Exercise on the Entorhinal Cortex of Rats Ker AH, Woodward ML, Barr AM, Beasley CL, Hercher C, Wu CH, Wong C, Boyda HN, Ramos-Migual A, Procyshyn R, Honer WG, Lang DJ

Background: Aerobic exercise promotes neurogenesis, enhances synaptic plasticity in the hippocampus, and increases dendritic spine density in the entorhinal cortex. Further, aerobic exercise has been shown to improve memory and cognition,and reduce depression and anxiety. Individuals with schizophrenia commonly have reduced hippocampal and entorhinal cortex volume. Atypical antipsychotics are prescribed to individuals with schizophrenia to relieve the symptoms of psychosis but there are negative side effects associated with this treatment. Atypical antipsychotic medication worsens hippocampal volume deficits in individuals with schizophrenia but both human and animal models have demonstrated the potential for exercise to increase hippocampal volume.

The entorhinal cortex acts a mediator of communication to and from the hippocampus. Differences in the morphology and connectivity of the layers, and medial and lateral subregions of the entorhinal cortex suggests differences in function. Preliminary evidence suggest that atypical antipsychotic treatment may increase the thickness of the entorhinal cortex in drug-naĂŻve patients. The impact of atypical antipsychotics and exercise on the entorhinal-hippocampal connectivity remains unclear.

Objective: Determine the effects of the atypical antipsychotic, olanzapine, and aerobic exercise on the thickness of the entorhinal cortex and its subregions in rats.

Methods: Adult female rats were treated with olanzapine or vehicle for 9 weeks and completed no exercise, 1 hour, or 3 hours of daily wheel-running. Rats were then perfused and brain slices were prepared with Cresyl Violet staining. Microscopy of the slices was performed and BoneJ was used to determine the thickness of the full entorhinal cortex, lateral entorhinal cortex, medial entorhinal cortex, and layer II. Conclusions: Analysis of data is still ongoing. The findings of this study will help inform on how atypical antipsychotics and exercise impact the entorhinal cortex-hippocampal connectivity. The results will provide insight into using aerobic exercise as an adjunct therapy for individuals on atypical antipsychotic medication to help mitigate some of the negative side-effects.

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Poster Board #29 Mimi Kuan, Graduate Student, University of British Columbia Supervisor: Kevin Harris, Evidence to Innovation

Physical Activity and Aortic Stiffness in Children with Congenital Heart Disease Mimi Kuan, Jimmy Lopez, Christine Voss, Nicole Hemphill, Ana Pozas, Stephanie Duncombe, Kevin Harris

Background: Through medical advances, survival rates of children with congenital heart disease (CHD) have significantly increased; however, they are at an increased cardiovascular risk at an early age. One method of assessing their cardiovascular health is to measure the elasticity of their aorta. Stiffening of the aorta often indicates vascular dysfunction, which is predictive of early cardiovascular events and death. It has been shown that physical activity is an important determinant of optimal vascular health. In children with CHD, the relationship between physical activity and aortic stiffness is not known.

Objective: To determine whether aortic stiffness is associated with objectively measured physical activity.

Methods: Children (9 – 16 years old) diagnosed with one of the following CHDs: Fontan circulation (FON), Coarctation of the Aorta (COA), Tetralogy of Fallot (TET), and Transposition of the Great Arteries (TGA), were recruited at BC Children’s Hospital and partnership clinics across BC and the Yukon. Aortic stiffness was assessed by calculating the aortic pulse wave velocity (PWV) using standard echocardiography and Doppler equipment. Physical activity level was quantified by fitting the participants with an ActiGraph accelerometer worn over the right hip for 7 days, followed by commercial trackers (FitBit) for long-term monitoring.

Participants also completed a set of questionnaires to assess their lifestyle behaviours.

Results: 71 individuals completed baseline assessments (12.5±2.4years; 41% female; FON n=21, COA n=19, TOF n=19, TGA n=12). Median PWV was 547 cm/s (interquartile range: 419-738 cm/s), which was significantly higher than children without CHD (~360cm/s, p<0.001). Median moderate-to-vigorous physical activity (MVPA) was 44 min/d and 27% met physical activity guidelines (>=60 min/d). Lower PWV values were related to higher levels of MVPA per day (rho=-0.3007, p=0.0108).

Conclusion: Our data demonstrate that children with CHD who have higher levels of MVPA levels have better vascular health. This association is important for all children with CHD, who are known to be at increased cardiovascular risk. Interventions that increase physical activity levels in children may have cardioprotective benefits.

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Poster Board #30 Wendy Li, Undergraduate Student, University of British Columbia Supervisor: Janet Mah, Brain, Behaviour & Development

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

Gaps and gains in Chinese-immigrant parents’ ADHD literacy: A cross-cultural comparison Wendy Li, Janet Mah

Background: Mental health literacy, which includes both knowledge and beliefs about mental health disorders, impacts prevention and help-seeking behaviours. Chinese populations consistently demonstrate low levels of mental health literacy and service usage in comparison to Western populations. It is important to consider cultural differences in parents’ literacy of childhood ADHD because they are the main help-seekers for the 5 to 7% of children worldwide who have the disorder, impairment from which can last into adulthood if left untreated. Psychoeducational interventions have been shown to be effective at improving ADHD literacy, but this effect has yet to be studied cross-culturally.

Objectives: To compare Chinese-immigrant and Caucasian-Canadian parents’ knowledge and beliefs about childhood ADHD, and to assess the impact of an ADHD psychoeducational resource on ADHD literacy.

Methods: Participants were Chinese-immigrant (n = 28) and Caucasian-Canadian parents (n = 28) of undiagnosed children aged 6-12 years recruited from Metro Vancouver. Parents completed questionnaires measuring ADHD knowledge, treatment acceptability, and perceived stigma. Measurements were taken at baseline and after participants read an ADHD information pamphlet.

Results: While both Chinese-immigrant and Caucasian-Canadian parents increased in ADHD knowledge and medication acceptability at post-test, the effect was greater for Chinese parents. Parent training acceptability was consistently high across time for both groups. Chinese parents perceived more stigma than Caucasian parents at both time points, although both groups increased in stigma at post-test.

Conclusions: Psychoeducation was an effective means of increasing ADHD knowledge and acceptability of medication, even more so for Chinese parents than for Caucasian parents. For both cultural groups, psychoeducation increased perceived stigma, and did not change their positive attitudes towards parent training.

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Poster Board #31 Rebecca Lin, Undergraduate Student, University of British Columbia Supervisor: Elodie Portales-Casamar, Evidence to Innovation

Congratulations to Rebecca on receiving a BC Childrenâ&#x20AC;&#x2122;s Hospital Research Summer Studentship & UBC Faculty of Medicine Summer Studentship!

Text Mining Psychiatric Clinical Notes Rebecca Lin, Ali Eslami, Elodie Portales-Casamar

Suicide is the second-leading cause of death for adolescents in Canada. The Child and Adolescent Psychiatric Emergency (CAPE) unit at BC Childrenâ&#x20AC;&#x2122;s Hospital (BCCH) provides stabilization and emergency intervention for youth in psychiatric crisis across BC and the Yukon. Approximately 45% of patients are admitted annually to CAPE for suicidality.

At admission and discharge, CAPE patients receive diagnostic assessments largely recorded as free-text clinical notes. Such form of data is difficult to incorporate in large-scale analyses. Therefore, our feasibility study investigates medical applications of text mining, an area which relies on analysis methodologies such as natural language processing (NLP) and information extraction. Using these methodologies, we aim to extract meaningful information from clinical notes and, ultimately, use the information in developing statistical models to predict patient suicidality.

Our data set contains around 400 admission and discharge notes for patients admitted to CAPE since 2015. We started our study with a literature review of existing NLP tools, such as Apache cTAKES, CLAMP, and GATE. We used this information to develop our own Python-based NLP pipeline. Clinical notes were first preprocessed to derive syntactic and lexical information. Techniques included section segmentation, sentence tokenization, and part-of-speech (POS) tagging. Then, medical named entities (drugs, symptoms, diagnoses, etc.) were detected through dictionary- and ontology-based mapping. We built customized lexicon with DSM-5, RxNorm, and the US National Library of Medicine. Annotations from SNOMED-CT and ICD-10 were retrieved via the NCBO application programming interface (API).

Our next step is to explore the context of the extracted terms. We will be developing algorithms to determine negation, experiencer, and temporal status for all data. Modes, dosages, and side-effects will be analyzed for medications.

For evaluation and optimization, our study results will be compared to an existing repository of manuallyannotated patient records from CAPE. If successful, our approach can be applied to automate extraction of structured data from clinical notes and support further analyses. In future studies, we aim to use our extracted results and machine-learning techniques to estimate suicide risk. The project would be valuable in pediatric mental health and potentially mitigate the increasing rate of youth suicide.

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Poster Board #32 Cody Lo, Medical Student, University of British Columbia Supervisor: Bruce Carleton, Evidence to Innovation

Congratulations to Cody on receiving a UBC Faculty of Medicine Mach‐Gaensslen Foundation of Canada Award!

Pharmacogenomic Analysis of ACYP2 and WFS1 Variants in the Development of Cisplatin Induced Ototoxicity amongst Pediatric Cancer Patients Cody Lo, Britt I. Drögemöller, Amit P. Bhavsar, Jong W. Lee, Galen E.B. Wright, Folefac Aminkeng, Shahrad R. Rassekh, Yuling Li, Xiaohua Han, Fudan Miao, Michelle Higginson, Nasim Massah, Henk Visscher, Beth Brooks, Colin J.D. Ross, Bruce C. Carleton and The Canadian Pharmacogenomics Network for Drug Safety Consortium Introduction: Cisplatin is a commonly used chemotherapeutic drug in adult and pediatric cancer populations, that is also one of the most ototoxic. Genetic variation has been shown to play a role in the development of cisplatin-induced ototoxicity (CIO). Previous pharmacogenomic analyses have implicated genes such as TPMT and more recent genome-wide association analyses have found that SNPs in WFS1 (rs62283056) and ACYP2 (rs1872328) contribute to development of CIO. While the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has replicated the WFS1 and ACYP2 findings in a group of adult testicular cancer patients, this study will investigate their role in pediatric patient populations from the CPNDS. Methods: A total of 597 pediatric cancer patients receiving cisplatin were available for inclusion in this study.

Cisplatin exposure was characterized and follow up audiograms were collected retrospectively to allow for an audiologist, clinical pharmacologist, and oncologist to determine cases of CIO using the CTCAE criteria. A subset of participants (n=393) had GWAS data including WFS1 (rs62283056) and ACYP2 (rs1872328) available for preliminary analysis. Logistic regression was performed to investigate the association of these variants with CIO. Preliminary Results: We found that age at start of cisplatin treatment (P=2.22x10-9), use of vincristine (P=1.29x10-13), and use of aminoglycoside antibiotics (P=0.0004) were all associated with the development of CIO. Using the preliminary GWAS data for a subset of the cohort (n=393), logistic regression found no significant association with development of CIO for the ACYP2 (P = 0.718, OR = 3.29, 95% CI = 0.89-12.25) or WFS1 (P = 0.5873, OR = 87, 95% CI = 0.52-1.44) SNPs. Conclusions and Future Directions: ACYP2 and WFS1 SNPs previously found to be significantly associated with adult-onset CIO did not replicate in the pediatric cohort. ACYP2 is a rare variant so a larger sample could increase statistical power. To investigate these results further, The full cohort (n=597) will be genotyped with a Taqman genotyping assay. Further analyses will be performed to investigate specific risk groups, such as those not receiving cranial radiation therapy, to closely match discovery cohorts and further elucidate the relationship between WFS1 and ACYP2 variants and CIO.

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Poster Board #33 Dylan Meng, Medical Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Are smartphone- and computer-based data collection methods feasible for capturing sleep/wake-behaviours?

Dylan Meng, Krystal Go, Marina Godard, Renee Boldut, Alyana Lalani, Sayeed Mavani, Mikayla Hong, Harvey Lee, Sabrina Chan, Kevin Xiao, Michelle Ngai, Andrea Garcia, Gerhard Klösch, Osman S. Ipsiroglu - in collaboration with: Audrey Basic, Jyhyun Cho, Roman Johnson, Chris Leong, Mikayla Wohlleben, Kaylin Xu

Background: Changes in vigilance throughout the day are affected by the quality and amount of nighttime sleep. Declines in vigilance are characteristics of fatigue but can be observed in an individual’s facial appearance before he/she experiences fatigue subjectively. Although vigilance changes are often measured objectively using EEG, facial analysis and subjective measures are less frequently used. We tested the feasibility of available at home data collection tools for our Vienna-Vancouver-Vigilance Project (vigilance data collection at the World Sleep Day in 2019).

Methods: We pilot tested user-friendliness of two applications designed for research: Ethica, a commercial smartphone app and SWAPP and SHARE, two free web browser-based services. Within the VSSS-2018 endeavour, five high school and six university student research assistants (RAs) tested both apps for seven days. (A) Bi-weekly group interviews were conducted during the test period to ask about general impressions and possible barriers. (B) Eight RAs completed surveys at the end of the test period using a five-point scale requesting ratings for: (i) convenience; (ii) how likely they would be to participate in a study using each app; (iii) overall impression. (C) Open-ended surveys were also conducted asking: (i) what was the largest barrier to using each app; (ii) which app was preferred and why.

Results: All RAs preferred Ethica over SWAPP and SHARE. 3/8 RAs cited convenience and 5/8 mobile friendliness as the reason for their choice. This was mirrored in the barriers to use of SWAPP and SHARE with inconvenience, e.g., lack of mobile-friendliness or having to use two applications, which also reduced motivation. This understanding was shared by all members of the VSSS-2018 endeavour.

Conclusion: All RA’s preferred working on a smartphone more than working on a computer and cited ’convenience’ as the most common reason for their decisions. RAs all rated themselves as more likely to use Ethica in future studies indicating that mobile- and user-friendliness may be the key for developing successful apps for participatory research.

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Poster Board #34 Habibur Rahman, Undergraduate Student, University of British Columbia Supervisor: Soren Gantt, Healthy Starts

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

The role of B cell activation in HIV-induced KSHV replication and KS Habibur Rahman, Raidan Alyazidi, Soren Gantt

Background: Kaposi’s sarcoma (KS) is an endothelial cell cancer, caused by Kaposi’s sarcoma herpesvirus (KSHV) infection. KS is the most common malignancy in people infected with human immunodeficiency virus (HIV).

KSHV infects B cells and usually remains latent, rarely causing KS in healthy people. However, HIV infection leads to B cell activation, and induces latent KSHV to undergo active (lytic) replication in vitro. Detection of KSHV in saliva or plasma reflects lytic viral replication, which is associated with the development of KS. We conducted a pilot study to explore the relationship between B cell activation and KSHV lytic replication in vivo, in HIV-infected and uninfected individuals.

Hypothesis: B cell activation due to HIV infection drives KSHV replication, and is a major mechanism by which HIV increases the risk of KS. Methods: KSHV oral and plasma samples, as well as information about KS tumor and HIV infection status were collected from 41 Ugandan subjects. Oral and plasma KSHV viral loads were measured by quantitative PCR, and levels of soluble markers of B cell activation, including CD21, CD23, CD27, CD30, and CD44, and B cell activating factor (BAFF), will be measured using a sandwich enzyme-linked immunosorbent assay (ELISA). The association between KSHV viral loads and markers of B cell activation will be analyzed using linear regression.

Expected results: Levels of B cell activation markers are higher in HIV-infected compared to the uninfected individuals, and are positively correlated with KSHV viral load in plasma and saliva.

Impact: This study could inform the use of B cell activation markers to predict the risk of KS, as well as interventions to reduce B cell activation to prevent disease in people co-infected with KSHV and HIV.

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Poster Board #35 Veronica Romines, Undergraduate Student, Hobart and William Smith Colleges Supervisor: Hal Siden, Brain, Behaviour & Development

Impact of a Diagnosis among Parents of Children with Severe, Progressive Life-Limiting Diseases Veronica Romines, Clara Van Karnebeek, Hal Siden, Shelin Adam, Patricia Birch, Gail Andrews

Background: Children affected by severe, progressive life-limiting diseases experience a variety of symptoms and disease trajectories that are not well understood or described. Many of these children do not have a specific medical diagnosis, but are assigned a broad diagnosis that simply describes a cluster of their symptoms (e.g. “Severe Epilepsy”). Parents of these children may experience exclusion from their community, and feelings of helplessness, because their child does not have an “explainable” disease.

Aim: The objective of this study is to examine the impact and importance of a diagnosis on the parents of children with undiagnosed conditions, who were eligible for genetic testing.

Method: Eligible children had neurological impairment, limited communication, full-time caregivers and typically mobilized in wheelchairs. Children ranged in age from 5-20 years, with an average age of 11.5, and the average number of years since their symptoms first appeared is 11.2 years. Six parents were given a semistructured interview by a genetic counselor in order to further understand their experience with their child’s condition and how reaching a diagnosis might impact their life and their child’s life. The parents were also given the opportunity to participate in genome-wide sequencing to potentially achieve a specific diagnosis for their child. The interview data was transcribed and coded into themes using the grounded theory approach.

Results: Five out of six of the parents interviewed felt a diagnosis for their child was of no, or very little, importance. All six parents felt school resources would not be impacted by a diagnosis and five of the parents felt community support would not be impacted either. The most influential reason to pursue a diagnosis was the chance to be better prepared for the child’s future and to have more insight into the future trajectory of the child’s condition. This reason was presented by all four parents who decided to undergo genome-wide sequencing.

Conclusion: Further research should look into comparing the parents’ experiences between younger affected children and older affected children to see if there is a greater level of acceptance associated among parents of children who have been affected for much longer.

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Poster Board #36 Madeleine Tan, Undergraduate Student, University of British Columbia Supervisor: Constadina Panagiotopoulos, Childhood Diseases

Diabetes Distress in Youth with Type 1 Diabetes

Madeleine Tan, Amanda Henderson, Olivier Couture, Tricia Tang, Constadina Panagiotopoulos Background: Living with type 1 diabetes (T1D) requires near constant attention to many self-management activities such as monitoring blood sugar, administering insulin, staying physically active and maintaining a healthy diet. Feelings of frustration, anger and hopelessness are not uncommon in individuals with diabetes, and these feelings can be intensified by lack of understanding from friends, family and health professionals.

The term ‘diabetes distress’ (DD) refers to the often-hidden emotional burdens of living with diabetes.

Previous studies have shown that DD is associated with suboptimal glycemic control and may lead to further psychological problems (i.e. anxiety).

Objective: The 2018 Diabetes Canada Guidelines recommend that youth with T1D be screened regularly for psychosocial and psychological disorders, and when required, referred to an expert in mental health and/ or psychosocial issues for intervention. However, the BC Children’s Hospital (BCCH) Diabetes Unit currently has limited social work (SW) and psychology support. The objective of this study is to conduct a quality improvement (QI) project to ascertain the prevalence and severity of DD among adolescents with T1D, and understand the staffing requirements for properly assessing and treating DD in the BCCH Diabetes program.

Methods: The Problem Areas in Diabetes-Teen scale (PAID-T), a survey previously validated for assessing DD in youth aged 11-17, will be administered as part of routine clinical care. Previously established cut-points will determine symptom severity. The surveys will be scored upon arrival to clinic, and the diabetes team/ social worker will be notified of scores ≥70 (moderate-to-high). SW time spent with family, referrals to external psychological support, and types and impact of interventions initiated will be evaluated through PDSA [PlanDo-Study-Act] cycles.

Expected Results/Conclusion: We hypothesize a high prevalence of DD (≥ 50% of youth). These data will identify problem areas in living with diabetes, open dialogue between patients, families, and healthcare providers to guide treatment recommendations, and aid in implementing early intervention strategies to boost diabetes self-care skills and reduce current/future levels of DD. Finally, we anticipate that this QI initiative will provide valuable baseline data to create a business case for securing more psychological support for youth and their families living with T1D.

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Session 04

Clinical, Population Health & Health Services

Moderator: Dr. Rebecca Ronsley Participants: Anmar Batawi Mackenzie Blydt-Hansen Paul Clerc Isobel Fishman Mikayla Hong Jocelyn Jia Nicole Ng Katie Pezarro Ana Pozas Kyle Scoten

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Poster Board #37 Anmar Batawi, Medical Student, Umm Al-Qura University (UQU) Supervisor: Kathryn Armstrong, Evidence to Innovation

Congratulations to Anmar on receiving a Mitacs Globalink Internship!

A Retrospective Analysis of Cardiac Function in Pediatric Heart Transplant Recipients Anmar Batawi, Anita Cote, Astrid De Souza, Kathryn Armstrong

Background: Heart transplantation remains the only therapy offering a normal quality of life and long-term survival for children with end-stage heart failure. Pediatric heart transplant patients (HTx) require lifelong immunosuppression to avoid rejection of the allograft. They also require ongoing screening for transplant related comorbidities, which include cellular rejection, infection, malignancies, renal disease and cardiac allograft vasculopathy (CAV). CAV is often the cause of death in HTx but there is no way to predict who is susceptible to CAV. Echocardiography is a non-invasive test that is routinely used to assess cardiac function and may help in the assessment of those at risk of CAV. Standard M-mode measures of ejection and shortening fraction are the gold standard for evaluating ventricular systolic function, with pulsed wave Doppler measures of mitral inflow being the mainstay of diastolic function assessment. Tissue Doppler imaging (TDI) has emerged to be a sensitive and reproducible measure of diastolic cardiac function as it is less load-dependent but few studies have evaluated this in HTx. The aim of this study is to retrospectively measure cardiac diastolic function by TDI in HTx. Methods: We reviewed data from 34 pediatric heart transplant patients. Patient demographics (time since transplant, age at transplant, medications, episodes of rejection), renal function and comorbidities were recorded from a retrospective chart review. Resting echocardiographic data and basic anthropometrics were obtained from a clinical database. Tissue Doppler velocities were recorded from the septal, left ventricular (LV) lateral and right ventricular (RV) walls.

Results and Next Steps: Currently we have data recorded for 18 subjects (age range: 5-18yrs; 61% female) followed annually for 4-14 years post transplant. At this time we are only able to provide a descriptive summary of the cross sectional TDI data. We have not evaluated trends over time or correlated findings with clinical outcomes. When compared to a previous study of TDI in transplant patients the Septal E’, LV E’ and RV E’ were all higher (6.3cm/s vs 10.9cm/s, 8.9cm/s vs 15.5cm/s, 6.4cm/s vs 10.5cm/s , respectively).

This study will determine if TDI is a useful non-invasive indicator of clinical outcomes in these patients.

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Poster Board #38 Mackenzie Blydt-Hansen, Undergraduate Student, Queen’s University Supervisor: Shazhan Amed, Evidence to Innovation

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

Driving Healthcare Improvement in Pediatric Diabetes in British Columbia – Harnessing the Power of Data and Benchmarking Mackenzie Blydt-Hansen, Daniel Metzger, Elodie Portales-Casamar, Shazhan Amed

Rationale: Diabetes is a common disease in Canadian children that is associated with serious long-term complications, particularly if blood sugar levels are poorly controlled during childhood. Providing high quality care is essential for diabetes management in the pediatric population, as it can help improve blood sugar control, which decreases the risk of developing complications. Currently, there is a discrepancy between evidence-based pediatric diabetes care and the actual delivery of care in BC. Closing this quality gap is critical to improving health outcomes in children with diabetes.

Objective: The objective of the SWEET study is to develop a BC Pediatric Diabetes Registry and to improve the quality of pediatric diabetes care in BC through provincial and international benchmarking. Benchmarking will be used to compare key quality indicators between pediatric diabetes clinics across BC and around the world. By examining and sharing the analysis of quality-of-care indicators, participating clinics can identify performance gaps and guide quality improvement initiatives.

Methods: Clinical data was collected from consenting patients at the pediatric diabetes clinic located at BC Children’s Hospital. Data was then anonymized and securely uploaded to the provincial clinical registry located on-site. The Microsoft program Power BI was used to analyze and visualize quality-of-care indicators and relationships in the provincial clinical data. Collections of visualizations (reports) will be published to an on-site Power BI Reports Server and communicated to provincial stakeholders to conduct province-level benchmarking.

Results: This pilot study is currently in the recruitment phase, with clinical data collected from 389 consented patients and 1485 total clinical visits at the BC Children’s Hospital pediatric diabetes clinic. The current data has been used to generate reports that visualize quality-of-care indicators (e.g. average clinic A1C, frequency of hypoglycemia) and relationships between clinical variables (e.g. months between visits vs. average clinic A1C).

Conclusion and Future Directions: The reports generated using Power BI have given valuable insight into the quality of care that is provided at the clinic. We are currently working to broaden the scope of the provincial registry by involving other pediatric diabetes clinics across BC.

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Poster Board #39 Paul Clerc, Medical Student, University of British Columbia Supervisor: Ran Goldman, Evidence to Innovation

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

A Pragmatic Randomized Controlled Trial of Virtual Reality vs. Standardof-Care for Comfort During Minor Plastic Surgery Procedures in Children Paul Clerc, Amir Behboudi, Jugpal Arneja, Ran Goldman

Background: Children often undergo painful medical procedures in healthcare settings such as intravenous catheterization, burn dressing changes, immunizations, and lumbar punctures. If pain is not adequately controlled, analgesic medications may have reduced effectiveness in subsequent procedures. Distraction is routinely used by healthcare professionals by using books, songs, TV or videogames. Recently, analgesic and anxiolytic properties of Virtual Reality (VR) have been investigated in painful medical procedures.

While many analgesics interrupt pain signalling through the C-fibre pathway, distraction is thought to act on perception of pain directly, and indirectly through changes in attention, emotion, concentration and memory.

VR provides audio, visual, and positional sensory stimuli and may therefore enhance distraction and reduce pain experienced by children. These results are supported by a functional MRI study showing reduced pain related brain activity and several randomized controlled trials. While results generally favour improved pain control, virtual reality has yet to be investigated in minor plastic surgeries.

Objective: To determine if experience with a Virtual Reality device in the plastic surgery clinic will facilitate reduced pain, among children 6-16 years of age, while going through a minor pre-scheduled plastic surgery procedure, compared to standard of care.

Methods: Children 6-16 years of age scheduled for elective minor plastic surgeries are randomized to watch VR during the procedure or to receive standard of care. In both arms, analgesic medications are at the discretion of the surgeon.

Outcome measures are recorded immediately following the procedure and include pain (Faces Pain Scale Revised), anxiety (Venham Situational Anxiety), duration of the procedure, type and amount of medication used, and satisfaction with using the VR headset.

Results: Recruitment is ongoing. Upon study completion, data will show whether using VR for distraction provides additional pain control in children undergoing minor plastic surgery.

Future Directions: There are three ongoing studies on VR in painful medical procedures; minor plastic surgery, laceration repair in the ER, intravenous catheterization in the ER. Future studies (sedation, immunization, young children 2-6) are planned to identify the types of procedures that may benefit from VR as distraction and if a subset of individuals has a greater response.

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Poster Board #40 Isobel Fishman, Undergraduate Student, Queen’s University Supervisor: Jill Zwicker, Brain, Behaviour & Development

Congratulations to Isobel on receiving a BC Children’s Hospital Research Summer Studentship!

Retrospective Review of Children’s Diagnostic Assessments for Autism Spectrum Disorder in BC: Are We Identifying Co-occurring Motor Deficits?

Isobel Fishman, Whitney Weikum, Elizabeth Mickelson, Jill G. Zwicker

Objective: Up to 79% of children with Autism Spectrum Disorder (ASD) have motor difficulties, but these are not part of the core symptoms of the disorder and are rarely addressed in therapy. A co-occurring diagnosis of Developmental Coordination Disorder (DCD) may be warranted for children whose motor deficits significantly interfere with daily life and are not better explained by another disorder. The current study: (1) examines the prevalence of motor difficulties in children diagnosed with ASD; and (2) determines how many of these children received a co-occurring diagnosis of DCD. Methods: The study was conducted using retrospective medical chart and clinical database review of children assessed for ASD in British Columbia between 2010 and 2014. A total of 4173 children with complete ASD assessments were included for data analysis.

Results: Clinicians reported 753/2227 (34%) of individuals who received an ASD diagnosis as having cooccurring motor difficulties. After excluding 232 individuals whose motor difficulties may be better explained by intellectual disability, global developmental delay, visual impairment, and/or a genetic or neurologic condition affecting movement, 163/521 (31%) of the remaining individuals received a DCD diagnosis or were considered “rule out DCD”.

Conclusion: These results suggest that BC clinicians are identifying motor difficulties in children with autism, but with less frequency than the literature suggests. Results are limited by the retrospective nature of the study and may under-represent motor concerns; motor data were not explicitly collected and may thus be under-reported in the dataset. Given the high occurrence of motor difficulties in children with autism, use of a brief parent questionnaire called the Developmental Coordination Disorder Questionnaire (DCDQ) for children aged 5 to 15 years old or the Little DCDQ for 3-4 year old children may be useful to include as part of the ASD assessment to screen for functional motor problems. If the child scores in the “suspected” or “indicative” range, further assessment by an occupational therapist and consideration of a DCD diagnosis may be warranted.

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Poster Board #41 Mikayla Hong, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Rethinking the BCCH BioBank Consent Form to Encourage Participatory Research

Mikayla Hong, Chris Leong, Michelle Ngai, Mikayla Wohlleben, Augusta Lutynski, Tasmin Tarling, Suzanne Vercauteren, Osman S. Ipsiroglu - in collaboration with: Audrey Basic, Renee Boldut, Sabrina Chan, Jyhyun Cho, Andrea Garcia, Krystal Go, Marina Godard, Kanak Jaitli, Roman Johnson, Alyana Lalani, Harvey Lee, Sayeed Mavani, Dylan Meng, Kevin Xiao, Kaylin Xu Introduction: Iron deficiency is a common factor between ADHD and Restless Legs Syndrome. Routine bloodwork is necessary to monitor iron status. The BCCH BioBank is a collection of de-identified information and samples that scientists can access for research to continue improving treatments and therapies. Barriers that discourage patients from donating to the BioBank include the timing of sample collection, dissemination of information, and the complexity of consent/assent forms. In order to better facilitate data collection and improve communication between researchers and participants, we investigated the forms with the goal to make them easier to understand and more accessible.

Methods: A team of four university students worked on the redesign of these forms as part of the Vancouver Summer Sleep School (VSSS). This was done using a modified Delphi process: (i) Condensing the form and rewriting it in plain language. (ii) Visualization of the forms was done by consulting a team of designers (iii) Drafts were reviewed by 7 high school and 6 additional university students. (iv) Changes were made to address feedback. This process was repeated three times. (v) The redesigned assent form was sent to the original authors for review.

Results: The redesigned assent form applies design principles to create a more inviting experience for the reader without the loss of any important information. With patient experience in mind, we identified areas of concern and designed the form accordingly. For example, we implemented a Questions and Answers page at the end of the assent form. This provides solutions to common concerns participants may have, such as addressing fears around the blood collections procedure, information about donating, and other general inquiries.

Conclusion: There is a gap between those who conduct research and their recipients. We tried to overcome this with a participatory approach by putting ourselves in the position of potential participants. By reviewing possible barriers which affect involvement, we believe we will be able to communicate with more ease.

An online version of the form is also in development to address the challenges surrounding the timing of information dissemination. The redesigned assent form was well received by the BioBank team and will be sent to REB for review and approval.

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Poster Board #42 Jocelyn Jia, Medical Student, University of Toronto Supervisor: Edmond S Chan, Childhood Diseases

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

Transitioning from Child to Adult Care for Eosinophilic Esophagitis Jocelyn Jia, Lianne Soller, Elaine Hsu, Hin Hin Ko, Vishal Avinashi, Edmond S. Chan

Eosinophilic esophagitis (EoE) is a chronic allergic condition of increasing incidence, characterized by eosinophilic infiltration (white blood cells), inflammation, and narrowing of the esophagus. Patients present with a number of symptoms including trouble swallowing, painful swallowing, vomiting, and regurgitation, which can decrease quality of life. EoE can be diagnosed at any age, and usually persists through adulthood.

However, there have not been any prospective studies following EoE patients during their critical transition from child to adult care.

Our EoE registry was created in 2013 to facilitate retrospective and prospective data collection for BC Children’s Hospital (BCCH) patients seen in the EoE clinic. Variables of interest include demographics, medical history, and allergic background; their collection allows us to describe the care of EoE within the Canadian public health system. We currently have >160 patients in our registry, with approximately 20-30 new patients added annually. As some patients have reached the age of majority, our objective is to extend our EoE registry to include BCCH patients who have transitioned to the adult gastroenterology clinic at St. Paul’s Hospital (SPH), so that we can better understand and prepare adolescents for the natural history of EoE during this transition.

Our primary outcome will be the proportion of adolescents who are successfully transitioned to adult care.

Secondary outcomes will include symptoms, allergic conditions, choice of therapy, and biopsy results, and barriers to follow-up for those unsuccessfully transitioned.

We have begun to re-consent patients ≥18 years old, who are currently being followed at SPH, for continued participation in our registry. For SPH patients who have re-consented, we are conducting chart reviews to collect outcome measures and patient variables. Recently, we also received ethics approval to re-consent former BCCH EoE clinic patients who are not being followed at SPH. Once these patients are re-consented, we will send all our adult patients a survey with questions aimed at describing the transition process and tracking clinical outcomes. Ultimately, our research will inform BCCH healthcare professionals about the unique challenges EoE patients face during their transition and assess whether a formal disease-specific transition program is needed for EoE at BCCH.

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Poster Board #43 Nicole Ng, Medical Student, University of British Columbia Supervisor: Paul Yong, Healthy Starts

Congratulations to Nicole on receiving a UBC Faculty of Medicine Summer Studentship!

Endometriosis and negative perception of the medical profession

Nicole Ng, Kate Wahl, Natasha L. Orr, Heather Noga, Christina Williams, Catherine Allaire, Mohamed M. Bedaiwy, Paul J. Yong Background: Endometriosis is a gynecological condition affecting approximately 10% of reproductive-aged females and commonly leads to pelvic pain which could negatively affect patientsâ&#x20AC;&#x2122; quality of life. Delay in diagnosis may result in inadequate or inappropriate treatments that may lead to patientsâ&#x20AC;&#x2122; negative perceptions of the medical profession.

Aim: To identify factors associated with negative impressions of the medical profession in females with endometriosis.

Study design and main outcome measure: Cross-sectional analysis of a prospective data registry at a tertiary referral centre for pelvic pain and endometriosis. The main outcome variable was negative feelings about the medical profession, measured with the 4-item subscale of the Endometriosis Health Profile-30. The outcome variable was divided into 3 groups: no (0%), some (<50%), and many (>50%) negative impressions.

Methods: Inclusion criteria: completion of baseline questionnaire between December 2013 and June 2017 and surgically-staged diagnosis of endometriosis at the centre. Exclusion criteria: postmenopausal (spontaneous or surgical) and incomplete data. Bivariate analyses determined significant associations with the main outcome.

Variables with significant association (p<0.05) were put into ordinal logistic regression with sequential backwards elimination.

Results: Previous visits to a complementary healthcare provider (OR 2.83, 95% CI 1.58-5.06, p<0.0005), discontinuation of continuous oral contraception because of side effects/ineffective (OR 1.96, 95% CI 1.043.69, p=0.038), presentation to an emergency department in the past 3 months (OR 2.03, 95% CI 1.063.88, p=0.032), higher depression severity questionnaire score (OR 1.08, 95% CI 1.03-1.12, p=0.001), and more severe deep dyspareunia (OR 1.11, 95% CI 1.01-1.22, p=0.038) were associated with more negative impressions of the medical profession. Conversely, current or previous effective use of continuous oral contraception (OR 0.33, 95% CI 0.13-0.83, p=0.018) was associated with less negative impressions of the medical profession.

Conclusion: Among females with endometriosis, a variety of factors were found to be associated with negative impressions of the medical profession. In chronic pain conditions, physician-patient relationships can be lifelong and the quality of these relationships have been found to affect patient outcomes. Thus, the factors identified here may be important indicators/predictors of negative impressions of the medical profession that should be addressed as part of effective treatment.

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Poster Board #44 Katie Pezarro, Medical Student, Western University

Supervisor: Dewi Schrader, Brain, Behaviour & Development

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

The Use of Advanced, Automated Magnetic Resonance Image Processing Techniques for the Detection of Focal Epileptogenic Lesions in Children Katie Pezarro, Kevin Poskitt, Dewi Schrader, Andrea Bernasconi, Mary Connolly

Introduction: Epilepsy is a prevalent neurological condition affecting 0.6% of Canadian children. Surgery to remove the epileptogenic focus is considered the most effective treatment, showing better rates of seizure freedom than medical therapy and beneficial effects on development and behaviour. Focal cortical dysplasia (FCD), a malformation due to abnormal neuroglial proliferation in utero, is the most frequent lesion in children with intractable extra-temporal epilepsy. Magnetic resonance imaging (MRI) has allowed the detection of an FCD lesion in many epilepsy cases previously considered to be cryptogenic. However, histopathological studies indicate that in about 60% of “MRI-negative” cases, subtle FCD is found in resected tissue from regions where no lesion was seen. Thus, more accurate detection of lesions would increase the potential for successful surgical treatment in these patients.

Dr. Bernasconi’s group at McGill University has developed advanced automated MRI processing techniques to improve the sensitivity of FCD detection in adult patients with epilepsy. The purpose of this study is to test these new processing techniques in the pediatric population. We hypothesize that these techniques will result in increased detection of epileptogenic lesions in the developing brain compared to visual inspection alone.

Methods: We utilized the Epilepsy Surgery Database at BC Children’s Hospital to retrospectively identify patients who had epilepsy surgery with clear lesions on conventional MRI. We also identified MRI-negative patients found to have abnormalities on histopathological examination of the resected tissue. Lastly, we identified MRI-negative patients with clinical suspicion of focal cortical dysplasia who have not yet undergone surgery. 3D FLAIR/3T MRI data for all 41 patients (26 male; mean ± SD age 12 ± 6 years) will undergo advanced analysis at the Montreal Neurological Institute, using methods previously developed for the analysis of epileptogenic lesions in adults.

Results: Better identification of epileptogenic lesions on MRI would increase the potential for successful surgical treatment, lower the length of hospitalization, and decrease the need for dangerous and costly investigations. It would also make the benefits of curative surgery accessible to a larger number of patients with epilepsy, which would result in significant improvements in quality of life for patients and families.

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Poster Board #45 Ana Pozas, Undergraduate Student, University of British Columbia Supervisor: Kevin Harris, Evidence to Innovation

Conducting Discordant Twin Pair Comparisons to Understand the Factors that Affect Quality of Life in Children with Congenital Heart Disease.

Ana Pozas, Christine Voss, Penny Sneddon, Kevin Harris

Background: One in 100 children are born with congenital heart disease (CHD). Medical advances allow these children to survive into adulthood, but they are at higher risk of physical and mental health complications.

Children with CHD show lower executive function skills than healthy peers, especially those who had cardiac surgery at a young age. Lower executive function is associated with lower quality of life, and physical and mental health interventions improve quality of life. Physical activity has also been shown to improve executive function in healthy children. In children with CHD, it is challenging to understand the factors that influence quality of life since it is difficult to isolate the effects of their medical condition from environmental factors affecting their physical and mental health. Discordant twin pair comparisons, where one has CHD and the other does not, are ideal study designs for isolating these effects and understanding the main contributing factors to their quality of life.

Objective: We aim to observe the longitudinal relationships between CHD, quality of life, executive function and physical activity within discordant twin pairs.

Methods: An estimate of 15 eligible discordant twin pairs (5-19 years) will be recruited from the Childrenâ&#x20AC;&#x2122;s Heart Center at BC Childrenâ&#x20AC;&#x2122;s Hospital. Physical activity, executive function and quality of life questionnaires will be completed by both twins and their parent. Twins will wear accelerometers to objectively track their physical activity for 7 days. Optional anthropometric measures will compare physical health differences between the twins. An optional interview portion will target the psychosocial factors influencing quality of life.

All quantitative measures will be taken annually for 5 years.

Impact: This study will inform health care professionals about the main contributing medical and environmental factors impacting quality of life in children with CHD. This knowledge may inform practices to enhance medical care, preventive cardiovascular strategies and quality of life.

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Poster Board #46 Kyle Scoten, Undergraduate Student, Queen’s University Supervisor: Shelina Babul, Evidence to Innovation

Congratulations to Kyle on receiving a Canadian Child Health Summer Studentship!

Optimizing the Concussion Awareness Training Tool (CATT) Using the 2017 BC Hockey Concussion Mandate Evaluation Kyle Scoten, Kate Turcotte, Shelina Babul

Introduction: Concussion in youth sport is a prevalent concern. Between 2004 and 2014, football, soccer, and hockey experienced a >40% increase in rates of reported head injury among Canadian youth. Therefore, a valid and standardized tool for the recognition, treatment, and management of concussion is needed in the sporting community.

The Concussion Awareness Training Tool (CATT) is an accessible online educational tool that provides e-learning modules on the recognition, treatment, and management of concussion. In June 2016, CATT for Coaches was mandated by BC Hockey as a training tool to be completed by all team officials (approximately 14,000 individuals) prior to their participation in the 2016 – 2017 season. Following the 2016 – 2017 hockey season, a survey was distributed to evaluate the efficacy of the CATT for Coaches course.

Objectives: To assess the effectiveness of CATT as an educational tool for BC Hockey team officials. To perform a literature review of current concussion management guidelines. To update and optimize the CATT website and e-learning modules.

Methods: A survey was developed to solicit feedback on CATT as mandated concussion training for BC Hockey officials. Quantitative and qualitative analysis were performed on the data. Additionally, a comprehensive literature review of the latest evidence on concussion management in pediatric populations was completed.

Findings from both the survey data analysis and literature review were incorporated to update information in the CATT modules.

Results: The survey had a >10% response rate (n=1,593). The CATT training led to a significant increase in selfreported concussion knowledge among BC Hockey team officials (p<0.001). 84.1% of officials who encountered a suspected concussion incident reported that CATT effectively prepared them for the situation. Findings suggest that a resource package relevant to coaches would also be beneficial. Meanwhile, the literature review resulted in updates to information on the CATT website, notably recommendations for baseline testing and rest following a concussion.

Conclusions: Our findings from the survey suggest that CATT for Coaches was an effective educational tool, improving knowledge and awareness of concussions. Meanwhile, results from the survey and literature review provided the basis for updates and improvements to the CATT website.

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Session 05

Clinical, Population Health & Health Services

Moderator: Dr. Kathy Wan-Chun Chang Participants: Eric Bhatti Meghan Boersma Danielle Cohen Avarna Fernandes Claire Galvin Nicole Hemphill Alexandra Franiek Gabrielle Sanatani Michaela Skarlicki Kevin Xiao

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Poster Board #48 Eric Bhatti, Medical Student, University of Ottawa Supervisor: David Goldfarb, Healthy Starts

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

Blood culture collection practice and yield at a tertiary pediatric centre before and after implementation of an evidence-based blood culture protocol Eric Bhatti, Laura Book, Peter Tilley, D. M. Goldfarb

Background: Blood cultures are an important clinical tool used to diagnose potentially life-threatening infections and select both medical and non-medical management of patients. The volume collected in blood cultures remains the most important factor in affecting sensitivity in detecting microorganisms. Specifically, as volume increases, the yield of microorganisms detected also increases. Thus, it is essential to optimize this clinical tool to ensure patients receive appropriate medical management.

Objectives: Phase One: To evaluate baseline blood culture practices at BCCH by measuring total blood volumes collected as a correlate of patient weight and age, and determine rates of contamination and pathogen detection. Phase Two: After the implementation of an evidence-based blood culture protocol, the goal is to reevaluate the blood culture practices.

Methods/Design: BactecTM blood culture bottles were labelled and weighed prior to placement on acute care wards across BCCH. After receiving them in the microbiology lab, they were re-weighed. Any blood cultures received on the same day were considered as part of the same set when calculating total blood volume collected. These blood volumes were then correlated with patient demographics and weight and compared with both current guidelines in the literature and the new BCCH blood culture protocol. A follow-up audit is currently being conducted to re-evaluate blood culture practices following implementation of the new protocol.

Results: Between June 9 and August 8, 2017, 365 bottles were collected and 36 were excluded due to administrative error or lack of patient weight collected. Of the remaining 329 bottles, 197 culture sets were identified of which 136 had all blood culture bottles collected. There was a 12/197 = 6.1% yield and 5/197 = 2.5% contamination rate. The median total blood volume collected among 136 culture sets was 1.65 grams (interquartile range 0.4 to 4.45 grams). 2.9% of blood culture sets met the new blood volume recommendations.

Conclusion: Baseline evaluation revealed a significant gap between last yearâ&#x20AC;&#x2122;s blood culture practices and the new evidence and weight based BCCH blood volume recommendations.

Future Directions: Results of the blood cultures will be reviewed to determine if rates of pathogen detection have improved and contamination rates have decreased.

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Poster Board #49 Meghan Boersma, Undergraduate Student, Baylor University Supervisor: Christine Loock, Brain, Behaviour & Development

Congratulations to Meghan on receiving a Rare Disease Foundation Summer Studentship & BC Children’s Hospital Research Institute Summer Studentship!

Surgical Correction of Velopharyngeal Dysfunction in Children with 22q11.2DS

Meghan L. Boersma, Sheryl Palm, Rebecca Courtemanche, Marija Bucevska, Christine Loock, Douglas J. Courtemanche Background: Up to 90% of patients with 22q11.2DS (22q) present with velopharyngeal dysfunction (VPD) and may require speech therapy and/or surgery. A recent systematic review found that no single surgical technique yielded better speech outcomes with fewer complications. This study aimed to determine whether any preoperative factors influence speech.

Methods: This 20-year retrospective study reviewed patients with a 22q diagnosis who underwent speech surgery at BC Children’s Hospital. Improvements in speech score, categorized by the SLP-3 Scale, were compared against surgical technique, pre-operative closure anatomy, gap size, and developmental delay.

Results: Twenty-two patients met the inclusion criteria. Post-operatively, 68% had competent speech, 18% had borderline speech, and 18% had incompetent speech. There were no significant association between the improvement in speech outcomes and surgical technique, pre-operative closure anatomy, gap size, and developmental delay. There was no association between a patient’s pre-operative anatomy and a surgeon’s choice of technique.

Conclusions: Acceptable speech can be attained for patients with 22q and no single pre-operative factor individually influences speech outcomes. Prior systematic reviews and our findings did not identify one surgical technique to be better at improving speech. Therefore, we suggest that a surgeon’s choice of technique with which (s)he is most familiar may lead to a superior speech outcome.

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Poster Board #50 Danielle Cohen, Undergraduate Student, Western University Supervisor: Rebecca Deyell, Childhood Diseases

Congratulations to Danielle on receiving a Michael Cuccione Childhood Cancer Research Foundation Summer Studentship!

Prognostic Role of Activated Beta-Catenin in Pediatric Osteosarcoma Danielle Cohen, Sujata Persad, Jon Bush, Rebecca Deyell

Osteosarcoma (OS) is an aggressive bone cancer seen most commonly in children and adolescents. Patients presenting with metastatic disease have poor outcomes with an estimated 5-year event free survival of <30%. Furthermore, patients with localized OS may progress or relapse despite intensive treatment. Yet, there are no baseline biologic prognostic markers that can identify higher risk tumors. This highlights the need to develop markers that would facilitate risk stratification and recognize patient groups in which novel therapeutic interventions are most desperately needed. This study investigates the role of the Wnt/β-catenin pathway, specifically looking at the transcriptionally active form of the protein β-Cat, Activated β-Cat (ABC).

The Wnt/β-Cat pathway plays a crucial role in skeletal development and is shown to be deregulated in OS. We hypothesize that increased ABC expression is correlated with poor post-chemotherapy necrosis response (<90%) in subsequent resection specimens. Thirty archival OS specimens have been identified from pediatric patients diagnosed between 2005 – 2018 and were split into 2 cohorts: 1) good necrosis responses (≥90%, n=15) and 2) poor necrosis (<90%, n=15). Of 30 patients, 15 were male and the median age at diagnosis was 13 (range: 7-17). Six presented with metastatic disease at diagnosis. Patients were followed for a median of 4.5 years (range: 1 -11) and at their last follow up 6 had died of disease, 2 were alive with disease and the rest had no evidence of disease. Patient tumor samples will be used to evaluate the β-Cat and ABC expression by immunohistochemistry. Correlation between ABC levels at diagnosis and post-therapy necrosis response will then be determined. Preceding in vitro studies have shown that aggressive OS cell lines have increased nuclear ABC expression thereby supporting our hypothesis. This study may help identify a novel marker for risk stratification that could be explored in a larger study, and may also inform novel targeted therapy options for patients with high risk disease.

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Poster Board #51 Avarna Fernandes, Undergraduate Student, University of British Columbia Supervisor: Jennifer Coelho, Brain, Behaviour & Development

Congratulations to Avarna on receiving a UBC Faculty of Medicine Summer Studentship!

Improvements in functional impairments in youth with eating disorders: Effectiveness of a pediatric day program Avarna Fernandes, Jennifer Coelho

Background: Eating disorders are characterized by a disturbance in eating-related thoughts and behaviours, which consequently impact patientsâ&#x20AC;&#x2122; physical health and psychosocial functioning. These disorders ultimately lead to impaired quality of life. Despite questions surrounding symptomology and functional ability arising often in the context of mental illness, limited research exists on the intersection of functional impairment measures and mental health practice. The Canadian Occupational Performance Measure (COPM) is an evidence-based, client-centred, personalized measure, assessing patientsâ&#x20AC;&#x2122; self-perception of performance in daily life, over time. It provides a basis to establish recovery goals (for patients) and intervention goals (for clinicians). The use of this measure provides unique insight into an individualâ&#x20AC;&#x2122;s experience.

Objectives: This study evaluates the role of the COPM as a measure of functional impairments in mental health practice, and to determine whether this measure contributes to the assessment of eating disorder treatment outcomes.

Research Questions: Do functional impairments exist in youth with eating disorders? If so, do these improve over the course of a day treatment program?

Methods: Participants received an initial assessment with an occupational therapist, using the COPM. Through this measure, participants self-identified up to five impairments under the categories of leisure, self-care and productivity. Impairments were then developed into goals to work towards while in treatment and were scored based on performance and satisfaction. Upon discharge, a second assessment was completed where participants reviewed their goals and re-scored their performance and satisfaction.

Results: This study is ongoing. Of the 61 participants in this study who have been discharged from the program, 41 completed a full COPM assessment (admission and discharge). The average age of patients at admission was 15.5 years old (SD=1.64). Seventy-four percent (n=45) of the sample was diagnosed with anorexia nervosa, and 87% (n=55) had been previously treated for an eating disorder, predominantly in outpatient settings.

Anticipated results of this study are an increase in understanding of the types of functional impairments pediatric eating disorder patients experience and support towards treatment outcome evaluations.

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Poster Board #52 Claire Galvin, Graduate Student, University of British Columbia Supervisor: Kathryn Armstrong, Evidence to Innovation

Texting and Connecting

Claire Galvin, Kathryn Armstrong, Astrid De Souza, Shubhayan Sanatani, Penny Sneddon, Pat Eastman Background: Dysautonomia of Adolescence (DAOA) results from an imbalance of the autonomic nervous system during puberty; symptoms affect multiple organ systems and significantly reduce quality of life (QoL).

The BCCH Dysautonomia Clinic, established in January 2017, is the first pediatric clinic in Canada. The clinic incorporates a multidisciplinary team that focuses on lifestyle modifications including careful attention to fluid and salt, strength training and psychological support. DAOA patients require considerable clinical support and resources as symptoms can persist for years and cause severe disruption in their daily lives. Ongoing communication is needed between patients and their Health Care Providers (HCP) to help manage symptoms and monitor behaviour changes.

Implementation of a Short Message Service (SMS) platform allows for two-way communication between adolescents and HCP. It allows adolescents to take an active role in their health and ultimately may improve QoL. Additionally, use of a SMS platform can improve patient management by allowing HCP to individualize care and streamline workflow.

Objectives: 1. To monitor quality of life (QoL) and symptom burden in DAOA patients following implementation of a SMS platform 2. To determine the feasibility and acceptability of using a SMS platform for communication between adolescents and their HCP. Methods: This is a prospective randomized control study. Participants will be recruited from the Dysautonomia Clinic and randomized to two groups: (1) SMS platform or (2) standard of care. After 6 months, standard of care patients, will receive the SMS intervention. The SMS platform will be provided by WelTel Inc. QoL and symptom burden will be assessed using the PedsQL and a symptom burden questionnaire at baseline, 6 months, and 1 year. Response rate and satisfaction of patients and HCP will be used to assess the feasibility and acceptability of the SMS platform.

Significance: Implementing a SMS platform allows adolescents to contact their HCP using an easy and accessible communication form. Additionally, it may help streamline HCP workflow by reducing time spent in communication with patients and families. If successful, a SMS platform could be translated to other clinics within BCCH as a new and effective tool to communicate with adolescent patients.

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Poster Board #53 Nicole Hemphill, Undergraduate Student, University of British Columbia Supervisor: Kevin Harris, Evidence to Innovation

Executive Function Correlates with Quality of Life, not Physical Activity in Children with Congenital Heart Disease Nicole M. Hemphill, Christine Voss, Jimmy Lopez, Ana L. Pozas, Penny Sneddon, Kevin C. Harris

Background: Children with congenital heart disease (CHD) have higher risk of secondary health complications, including neurological deficits. Specific deficiencies in higher level cognitive skills, like executive function, have been observed. Executive function includes important skills for planning, organization, task management, and self-regulation. In healthy children, these skills have been shown to improve with increased physical activity.

Children with CHD also report lower quality of life (QoL) than their healthy peers. No study has investigated the relationships between all of these factors in children with CHD. Objective: We aim to investigate associations between physical activity, perceived executive function, and QoL in children with CHD. Methods: We recruited participants (ages 5-16 and with a CHD diagnosis) from the BC Children’s Heart Centre and affiliated clinics in BC and the Yukon. Patients with syndromic comorbidities, or those who were unable to complete study measures were excluded. Participants wore an accelerometer for 7 days to objectively measure physical activity. Their caregiver completed questionnaires about demographics, their child’s QoL (PedsQL) and their perception of their child’s executive function (Behaviour Rating Inventory of Executive Function (BRIEF)).

Results: 17 participants (median age 7.0 (IQR: 6.6-8.5), 12 male) have completed measures to date. All participants had a moderate or complex CHD (Coarctation of the Aorta (n=1), Transposition of the Great Arteries (n = 4), a Single Ventricle Physiology (n = 3) or a Fontan Circulation (n = 9)). Physical activity varied widely (range: 12.5-93.0 min/day). 6 participants (35%) met physical activity guidelines (≥60 min/day).

There was no significant difference between participants’ BRIEF scores and the norm. General BRIEF scores correlated with parents’ ratings of their child’s overall QoL (rho = -0.7649, p=0.0003), with better perceived executive function related to better QoL. There was no correlation between BRIEF scores and physical activity or between physical activity and QoL. Conclusion: In children with CHD, perceived executive function was related to QoL, but not physical activity.

This may indicate that targeting executive functions could improve QoL in this patient population.

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Poster Board #54 Alexandra Franiek, Medical Student, University of St. Andrews Supervisor: Tom Blydt-Hansen, Childhood Diseases

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

Urinary metabolomics to develop predictors for pediatric acute kidney injury Alexandra Franiek, Tom Blydt-Hansen, Atul Sharma, Michael Zappitelli, Taariq Shaikh

Background: Acute kidney injury (AKI) is an abrupt decline in renal function and affects 10-20% of pediatric intensive care unit (PICU) patients. AKI is associated with poor outcomes including: progression to chronic kidney disease, longer hospital stay and increased morbidity and mortality. Severity of AKI is classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, which incorporates fluctuations in serum creatinine (SCr) and urine output. These functional markers are incapable of distinguishing between etiologies and only appear after significant damage has occurred. Since existing biomarkers cannot predict incipient AKI, there is a need for novel tests to allow for early diagnosis and more timely intervention.

Quantitative urinary metabolomics provides a phenotypic snapshot of kidney health and injury status, with potential to develop a diagnostic tool for early AKI. Objectives: To determine whether urinary metabolite profiles acquired during early PICU admission can predict the subsequent development and severity of AKI. Methods: We drew from two prospective pediatric intensive care patient cohort studies. The first was performed at the Montreal Childrenâ&#x20AC;&#x2122;s Hospital between November 2007 and September 2010 (n=204). The second study was performed at 4 Canadian centers (n=128) between July 2013 and September 2014. AKI status was determined using the KDIGO SCr criteria. 110 urine samples from 63 participants were available for analysis, and were assayed for 199 metabolites by quantitative mass spectrometry. Metabolite profiling was done using partial least squares-discriminant analysis, and the resultant discriminant score was evaluated using the receiver operating characteristic curve area under the curve (AUC) and leave-one-out cross validation.

Preliminary Results: Urine samples from 11 patients prior to AKI onset and 30 controls (no AKI) were used for training. Metabolite discrimination scores significantly differentiated AKI vs control (AUC=0.99, 95% CI=0.96-1), with similar accuracy on LOOCV (AUC=0.93; 95% CI=0.85-1).

Future Directions: Urinary metabolomics demonstrates potential as an earlier, non-invasive diagnostic test for AKI. A regression analysis including addition of clinical variables will be included to improve performance of classifiers.

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Poster Board #55 Gabrielle Sanatani, Medical Student, Royal College of Surgeons in Ireland Supervisor: Kishore Mulpuri, Evidence to Innovation

Congratulations to Gabrielle on receiving a Richard Beauchamp Summer Student Scholarship in Pediatric Orthopedics!

Assessing the need for orthopedic follow-up in the management of pediatric femoral fractures Gabrielle Sanatani, Eva Habib, Emily Schaeffer, Kishore Mulpuri

Background: Pediatric femoral fractures are a common complication of significant trauma. These fractures always require intervention, and there are a variety of treatment options available. Hip spica casting, traction, and surgical fixation are all used to treat this condition. This variety in treatment options leads to a vast potential for variability in management decisions among surgeons and has prevented effective comparative studies to show which treatment methods provide optimal outcomes for patients.

Purpose: We sought to review the initial surgical treatment, subsequent management and outcomes of pediatric patients with femoral fractures. We sought to determine potential advantages of the different treatment methods, as well as identify risk factors for complications. This study will aid in the development of a comprehensive, prospective, evidence-based pathway for the management of pediatric femoral fractures.

Methods: We performed a retrospective chart review, including all imaging studies, of all patients treated surgically for isolated femoral fractures between January 1, 2010 and December 31, 2015 at BC Childrenâ&#x20AC;&#x2122;s Hospital. This timeframe allowed for a reasonable length of follow-up data to be collected. Patients were identified from a surgical database. Patients were included if there was no pre-existing pathology and no history of previous femoral fracture. Radiographic images and reports were analyzed to determine fracture classification and imaging parameters.

Results: Data including demographics, operative details, post-operative management, and clinical outcomes will be analyzed. The primary outcome is variability in treatment. This includes the number of follow-up appointments and length of follow-up. Preliminary results show that of 134 included patients (101=male), 55 had a right femoral fracture, 76 had a left femoral fracture, and 3 had bilateral femoral fractures. The median follow-up time was 32.8 weeks with an median of 3 follow-up visits.

Significance: Initial data analysis has shown marked variability in treatment at our centre. The findings from this study will inform treatment decisions for children presenting with femoral fractures and may lead to improved long-term outcomes for this patient group. The findings will also identify knowledge gaps for the development of prospective studies examining long-term functionality and quality of life outcomes under specific management decisions.

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Poster Board #56 Michaela Skarlicki, Undergraduate Student, University of Western Ontario Supervisor: Jugpal Arneja, Evidence to Innovation

Congratulations to Michaela on receiving a OPSEI Summer Studentship!

A Modified Pharyngeal Flap Technique for the Treatment of Velopharyngeal Incompetence Michael Carr, Michaela Skarlicki, Marija Bucevska, Sheryl Palm, Jugpal Arneja, Arun Gosain

Background: Numerous surgical interventions are described for the management of velopharyngeal incompetence (VPI), though there is no definitive superior option. Our group previously described a novel approach for effectively managing VPI in children with 22q11.2 deletion syndrome (22qDS): a modified high pharyngeal flap with through-and-through dissection of the soft palate for flap inset. Here we report speech and surgical outcomes in a consecutive series of non-22qDS patients with severe VPI treated with our modified pharyngeal flap technique.

Methods: In this single surgeon retrospective case series, we explore outcomes in non-22qDS patients with severe VPI treated during the last six years with our modified pharyngeal flap. Preoperative velopharyngeal dynamics were assessed by videofluoroscopy or nasoendoscopy. A trained speech language pathologist conducted perpetual speech assessments using the SLP-3 scale with a minimum 6 month follow-up.

Results: Thirty patients met the inclusion criteria with a mean age of 6.7 years at the time of surgery (range, 3.8 - 16.7 years). All patients had severe VPI with a mean preoperative SLP-3 score of 10.6 out of 13 (range, 7 to 13), improving to a mean postoperative score of 1.6 (range, 0 to 7). Velopharyngeal competence was restored in 25 patients (83%), with borderline competence in 3 patients (10%), and persistent VPI in 2 patients (7%). Significant surgical complications included one fistula requiring revision, as well as one case of mild OSA that did not require flap takedown. Mean skin-to-skin operative time was 74.9 minutes +/- 12.4 (mean +/- SD; range, 55 to 95), for patients with the pharyngeal flap procedure exclusively (60%) and 84.9 minutes +/- 22.5 (mean +/- SD; range, 55 to 164), for patients who received an additional procedure at the time of the pharyngeal flap surgery (40%). An average of 52.3 hour length of stay was noted after surgery.

Conclusions: This modified pharyngeal flap with though-and-through dissection of the soft palate allows direct visualization of flap placement which leads to effective restoration of VP competency with low complication rates, and low operative time.

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Poster Board #57 Kevin Xiao, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Rethinking the MRI Consent Form: How Better Design and Added Visuals Can Enhance User Understanding and Comfort

Kevin Xiao, Dylan Meng, Kanak Jaitli, Michelle Lau, Alexander Mark Weber, Alexander Rauscher, Osman S. Ipsiroglu - in collaboration with: Audrey Basic, Renee Boldut, Sabrina Chan, Jyhyun Cho, Andrea Garcia, Krystal Go, Marina Godard, Mikayla Hong, Roman Johnson, Alyana Lalani, Harvey Lee, Chris Leong, Augusta Lutynski, Sayeed Mavani, Michelle Ngai, Mikayla Wohlleben, Kaylin Xu Introduction: ADHD and RLS are often associated with iron deficiency; however, many aspects of this association are unclear and need further investigations. Brain MRI can provide a direct and effective measure of biochemical markers like iron. MRI consent forms are necessary to explain study procedures and inform potential participants about their rights as a volunteer, and the risks they may encounter, before they agree to participate. Current forms can be perceived as complex and difficult to understand, which potentially introduces ethical issues around consent. To bridge communication gaps, we investigated existing consent forms to make them more informative by being easier to understand.

Methods: The Brain MRI Team (3/20 students, including a design student) spearheaded the project using a modified Delphi process: (i) Rewriting the form in plain language while maintaining all essential information; (ii) adding a Q&A page to address common concerns; (ii) visualizing the forms; (iii) reviewing of drafts by seven high school and eight additional university students; (iv) making changes based on the feedback received; (v) reviewing and updating the process three times; (vi) and finally sending the redesigned consent form to the original authors for review.

Results: We redesigned the form using design elements such as white space, pictograms, and sectioning of information. This helped to address barriers identified by the student teams such as poor prioritization of information and a focus on potential problems that lead to increased barriers to entry. In particular, common concerns like claustrophobia and keeping still during the scan were addressed in detail in the added Q&A page.

We included an image of an MRI to familiarize potential participants with the machine and further reduce concerns they might have.

Conclusions: The redesigned consent form was perceived as clear and visually appealing by the VSSS-team and faculty members. By putting ourselves in the perspective of potential participants, we identified and tried to overcome communication gaps. We put a larger focus on solutions for common concerns to enhance recruitment. The redesigned consent form will be sent to REB for review and approval.

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Session 06

Clinical, Population Health & Health Services

Moderator: Dr. Mohamed Elgendi Participants: Savvy Benipal Hajir Adl Golchin Justin Fong Tara Gholamian Marina Godard Rohan Kakkar Mehima Kang Jocelyn Kerr Monica Lai Tom Ouellette Anahat Sahota

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Poster Board #58A Savvy Benipal, Medical Student, Royal College of Surgeons in Ireland Supervisor: Rod Rassekh, Evidence to Innovation

Spinal Low-Grade Gliomas in Canadian Children: A Retrospective Review Savvy Benipal, Hallie Coltin, Juliette Hukin, Sylvia Cheng, Chris Fryer, Donna Johnston, S Rod Rassekh

Background: Low-grade glioma (LGG) is the most common pediatric central nervous system tumour. Spinal tumours are rare, representing only 4.5% of all primary CNS tumours, and can be difficult to treat. With no definitive protocol in place, the treatment of spinal LGG remains controversial and is a significant source of morbidity in children.

Objectives/Hypotheses: The Canadian Pediatric Brain Tumour Consortium (CPBTC) decided to undertake a multi-center retrospective review of spinal LGG to examine the incidence, pathological subtypes, treatment, and outcomes of these tumours. The primary aim of this study is to identify prognostic factors for these patients. We hypothesize that five-year progression free survival and overall survival of spinal LGG will be better than published data on intracranial LGG. Chemotherapy and radiation therapy will show similar efficacy, and that there will be a trend towards less aggressive therapy over time.

Methods: After obtaining REB approval, a retrospective chart review was performed. All patients with a primary spinal LGG under the age of 18 treated at BC Childrenâ&#x20AC;&#x2122;s Hospital between the years 1990 and 2015 were included. Data collected includes date of diagnosis, age at diagnosis, gender, known tumour predisposition syndrome, clinical symptoms, time to imaging, imaging, stage, pathology, treatment, postoperative symptoms, neurological recovery, study enrolment, recurrence or progression, treatment of recurrence or progression, and if died of disease. Descriptive statistics was performed.

Results: Preliminary results from the first 28 subjects with spinal LGG reviewed shows that 89% of patients are alive, with 3 patients dying from complications of disease. Metastatic disease was seen in 3 (10.7%). Only 32% were able to have a gross total resection. 57% of subjects had recurrent disease. The most common presenting complaint was pain (64%), followed by weakness (54%) and scoliosis (36%). The majority (54%) had over 6 months of symptoms prior to imaging being performed.

Conclusions: Children with spinal tumours have good survival outcomes, despite a low number of them having gross total resections. Disease recurrence requiring further surgery, chemotherapy or radiation therapy is common. There was a marked delay in diagnosis. Children with back pain, weakness or scoliosis should have prompt neuroimaging performed.

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Poster Board #58 Hajir Adl Golchin, Medical Student, University of British Columbia Supervisor: Kathryn Armstrong, Evidence to Innovation

Dysautonomia of Adolescence: A Multidisciplinary Approach

Hajir Adl Golchin, Astrid M De Souza, Claire Galvin, Pat Eastman, Penny Sneddon, Kathryn R Armstrong Background: The Autonomic Nervous System (ANS) controls all involuntary or visceral body functions. The ANS can temporarily malfunction during adolescence resulting in an under-recognized symptom complex, which includes pre-syncope, syncope, fatigue, dizziness, tachycardia, and digestive issues which we refer to as Dysautonomia of Adolesence. Many adolescents are extremely debilitated by their symptoms resulting in them missing school, sports, and social activities. These children often have extensive investigations performed by multiple specialists without ever receiving a diagnosis and useful treatment. The Dysautonomia Clinic at BC Childrenâ&#x20AC;&#x2122;s Hospital was started in January 2017. It is the first DAOA pediatric clinic in Canada, and the multidisciplinary team includes a nurse, exercise physiologist, psychologist, and physician. The aim of this clinic is to make the diagnosis early, and to offer a treatment plan to improve their quality of life (QoL).

Objective: To retrospectively review 18 months of the Dysautonomia clinic, and to determine its effect on symptom burden, exercise capacity, and QoL. Methodology: All clinic charts from January 2017 to present will be reviewed. QoL, exercise capacity, and symptom burden will be compared at presentation and at 6 month follow up.

Preliminary Results: A total of 69 patients were seen; 36 patients are being actively followed, 33 have been discharged.

Eight of those discharged were seen at 6 month follow-up. We have only evaluated the PEDsQL scores and treadmill time for the 8 patients who were discharged. At the time of discharge, patients reported an improvement in QoL [total 53.3 (39.0-73.9) vs 62.5 (39.8-71.7); p=0.99; physical 42.2 (25.0-78.1) vs 53.1 (32.068.8); p=0.80; psychosocial 62.5 (45.4-74.2) vs 58.3 (46.7-77.5); p=0.79]. Parent proxy reports were relatively stable with improvements noted in physical functioning [total 46.2 (39.1-66.0) vs 49.5 (44.30-70.9); p=0.84; physical 29.7 (21.9-68.0) vs 43.9 (27.3-71.1); p=0.58; psychosocial 51.7 (42.9-65.0) vs 56.3 (53.8-64.6); p=0.74].

Treadmill times also improved from initial presentation to the six month follow up (10.13 vs 11.17 minutes; p=0.63).

Outlook: Preliminary results show an improvement in QoL and treadmill time following review in the DAOA clinic. Further analysis is needed to determine if this is a statistically significant finding in the whole population.

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Poster Board #59 Justin Fong, Medical Student, University of British Columbia Supervisor: Zoë Brown, Evidence to Innovation

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

A prospective, observational pilot study of non-invasive microcirculation monitoring using near-infrared absorption spectrophotometry (NIRS) during scoliosis correction surgery Fong J., Dumbarton T., Görges M., Whyte S., Poznikoff A., Brown Z.

Introduction: Surgical correction of scoliosis, a lateral deformity of the spine, is a long procedure with potential for significant blood loss. To maintain intra-operative homeostasis, anesthesiologists titrate fluids, drugs, and blood, if required, based on clinical judgement. However, blood transfusion is not without its risks. Nearinfrared spectroscopy (NIRS) measures microcirculatory oxygenation in tissue and may help guide decision making about whether and when to transfuse blood. Our study objectives are to compare NIRS cerebral (ScO2) and muscle (SmO2) oxygenation in response to blood loss and transfusion, and to determine a ScO2/ SmO2 threshold for transfusion.

Methods: A prospective, observational, single-blinded pilot study was conducted. 48 children undergoing single-stage scoliosis were recruited. NIRS sensors were placed on the forehead and forearm to measure ScO2 and SmO2, respectively. Anesthesiologists were blinded to NIRS values. Intra-operative management, including the decision to give an autologous blood transfusion (ABT), remained unchanged. NIRS and hemodynamic values were collected throughout the procedure. NIRS values immediately before and after time-stamped interventions were compared using one-way repeated measures ANOVA. Results: Data from 18 children, 10 female, with median (IQR) age of 16.4 (13.7 – 17.9) years, and weight 50.7 (40.7 - 62.0) kg were available for analysis. A weak, negative linear association (r = -0.402) was found between final estimated blood loss and ScO2. No association (r = 0.066) was found between estimated blood loss and SmO2. ABT was given to 7 children at a median (IQR) ScO2 of 65 (61 – 67) % and SmO2 of 73 (71 – 77) %, causing a median (IQR) change of 4 (-1 – 12) % and 2 (0 – 4) %, respectively. One child received 2 additional intra-operative allogeneic transfusions.

Discussion: Compared to SmO2, ScO2 appears more responsive to blood loss and ABT. Compensatory mechanisms, which affect ScO2, may be in place to protect cerebral tissue. Increased oxygen utilization, in light of blood loss, may reduce cerebral NIRS signal. Blood from ABT could be preferentially redirected to cerebral tissue, increasing cerebral NIRS. Changes in ScO2 could be useful in deriving a threshold for transfusion.

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Poster Board #60 Tara Gholamian, Undergraduate Student, The University of British Columbia Supervisor: Tom Blydt-Hansen, Childhood Diseases

Congratulations to Tara on receiving a UBC Faculty of Medicine Summer Studentship!

Urinary metabolite markers for chronic kidney disease in a pediatric population Tara Gholamian, Atul Sharma, Tom Blydt-Hansen

Background: Chronic Kidney Disease (CKD) is defined as a decrease in kidney function for at least 3 months, independent of the underlying cause observed as a clinical value of glomerular filtration rate (GFR) below 60ml/min/1.73m2. As a progressive and irreversible disease, CKD tends to worsen over time with an end stage marked by dialysis or a kidney transplant. Current diagnosis and staging of CKD is primarily based on urinary albumin excretion and estimated GFR. These methods fail to give an early biomarker for CKD detection and determination of CKD progression, with dependencies on non-GFR determinants. Recent findings have identified metabolomics to be an efficient method of analysis in order to find improved biomarkers of disease and increased accuracy of progression estimation. The objective of this study is to identify metabolomic signatures and clinical comorbidities associated with CKD progression in the pediatric population.

Methods: The patient population (n=708) comprises of patients aged 0-18 enrolled in the CKiD study, a prospective and observational study. Data collection began in 2006 at 48 pediatric nephrology centers across North America with annual follow-up and careful annotation of clinical, laboratory, and GFR measurements with biobanked samples of urine for study analysis. Inclusion is a multi-step process that includes an interview with the participant and their guardians and a review of medical history. Urine was analyzed using targeted metabolomics testing by gas-chromatography (GC-MS) and liquid-chromatography (LC-MS), providing quantitation of ~180 metabolites per sample.

The first statistical method used is a survival analysis with the COX model to perform a multivariable analysis to determine new clinical variables significant in CKD progression in conjunction with known obligate predictors.

These candidate predictors include CKD comorbidities and uncontrolled clinical values. The second statistical analysis includes the determination of an estimating equation for GFR using metabolomics profiles in another multivariable analysis.

Future Directions: The majority of the analysis for this project will be done in August. The goal of this project is to obtain reliant methods of estimating the progression of CKD that will allow for early detection, improved patient care, improved disease progression monitoring, and allow for anticipatory guidance.

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Poster Board #61 Marina Godard, Undergraduate Student, Simon Fraser University Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Rethinking the SleepSmart Study Consent Form to Enhance Participatory Research Marina Godard, Jyhyun Cho, Harvey Lee, Sabrina Chan, Andrea Garcia, Nadia Beyzaei, Gerhard Klösch, Mike Van der Loos, Alex Lee, Leonid Sigal, Osman S. Ipsiroglu- in collaboration with: Audrey Basic, Renee Boldut, Krystal Go, Mikayla Hong, Kanak Jaitli, Roman Johnson, Alyana Lalani, Chris Leong, Augusta Lutynski, Sayeed Mavani, Dylan Meng, Mikayla Wohlleben, Kevin Xiao, Kaylin Xu

Background: ADHD and Restless Legs Syndrome share common characteristics of restlessness and disturbed sleep. In order to distinguish between the two, we are developing protocols. The SleepSmart study investigates day and night-time behaviours and movement patterns via 2D- and 3D-video-recordings in two structured situations (sitting on a chair and lying on a bed fitted with sensors). The background of a research study is usually communicated to participants via consent/assent forms which can be difficult to read and understand.

We investigated how the current forms are structured and how we could make them more attractive and inviting to potential participants.

Methods: Four university students from the Vancouver Summer Sleep School (VSSS) used a modified Delphi process: (i) Condensing the form and rewriting it in plain language. (ii) Concepts for visualization were reviewed using “principles of design.” This was done by consulting a team of three design students. (iii) Drafts were reviewed by 7 high school and an additional 6 university students. (iv) Changes were made to address the feedback. This process was repeated three times. (v) The redesigned form was sent to the original authors for review.

Results: The redesigned form applies design elements, including pictograms and increased white space, to create a more inviting experience for the reader without the loss of details in anonymization and deidentification, study design, and protocol information. Changes were made to address concerns and were iterated upon through further review cycles. Efforts were made to ensure the participant knew how their information could be de-identified.

Conclusion: The redesigned form was perceived as inviting and visually appealing by the VSSS team and faculty members. Reviewing these consent forms lead us to highlight the importance between anonymity and de-identification in data collection with videos or photos which plays an important role in phenotyping.

Communicating proper procedures with participants is key; by putting ourselves in the position of participants, we identified and overcame communication gaps. The redesigned form will be sent to the Ethics Committee for review and approval.

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Poster Board #62 Rohan Kakkar, Undergraduate Student, University of British Columbia Supervisor: Brenden Hursh, Childhood Diseases

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

Barriers in Adherence to a Gluten-Free Diet in Children with Type 1 Diabetes and Celiac Disease Compared to Children with only Celiac Disease Rohan Kakkar, Brenden Hursh, Alice Foster, Collin Barker

Background: Type 1 Diabetes (T1D) and Celiac Disease (CD) are both autoimmune diseases with treatment plans heavily based on diet management. A strict gluten-free diet (GFD) is recommended for patients with CD, which increases dietary restrictions for children already managing T1D. Children with diabetes who are not able to comply with a GFD have worse health outcomes including reduced glycemic control and lower quality of life. Rates of adherence to a GFD are reported to be greater than 70% in patients with CD and below 50% for patients with T1D and CD. Much of the data, however, is drawn from adult samples.

Purpose: For children living with T1D and CD, it is not known why there is a difference in adherence rate compared to those with CD only. It is also unclear whether there are any differences in the major challenges these two groups face in adhering to a gluten-free diet. Through this study, we hope to understand any differences between these groups which can help them and their health care teams better prepare them for living with T1D and CD. Methods: Children (aged 1-18 years) with T1D and biopsy-proven CD OR with biopsy-proven CD only will be invited to complete a survey online. This survey assesses overall adherence to a GFD, household status, and barriers to adherence in different settings such as at home, at school, and in restaurants.

If participants provide optional consent, additional information including A1C levels, TTG levels, biopsy results (Marsh Criteria histological grade), height, weight and other medical conditions will be collected from their medical records.

Significance: We anticipate the results will inform patient care directly. While it has been reported that patients with a dual diagnosis of T1D and CD may be less adherent to the GFD, this will be the first study to characterize GFD adherence in children with T1D and CD. We hope to identify specific areas on which the health care team can provide additional support to children and their families who are living with T1D and CD.

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Poster Board #63 Mehima Kang, Undergraduate Student, Queen’s University Supervisor: Constadina Panagiotopoulos, Childhood Diseases

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

Evaluation of bone health and bisphosphonate use in pediatric patients with Duchenne muscular dystrophy Mehima Kang, Rebecca Ronsley, Brianna Cameron, Kathryn Selby, Helen Nadel, Christopher Reilly, Daniel Metzger, Constadina Panagiotopoulos

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by a progressive loss of skeletal and cardiac muscle. Children with DMD have lower bone mineral density (BMD) and increased fragility fracture (FF) risk. Glucocorticoids are used to slow disease progression, though this treatment exacerbates osteopenia and FF risk. Bisphosphonate therapy (BT), such as zoledronic acid (ZA) and pamidronate (PAM) infusions, is widely used to treat low BMD. However, no large-scale study exists evaluating the impact of intravenous BT in the DMD population.

Objectives: 1. To describe the impact of BT on BMD and FF in children with DMD before and after BT 2. To delineate trends in FF, including timing and choice of BT. Methods: This study is a 10-year retrospective chart review of patients with DMD followed at BC Children’s Hospital. Data collection included FF rate, steroid treatment, laboratory values, BMD Z-scores, and type and duration of BT. Data analysis compared BMD and fractures before and after BT between ZA- and PAM-treated subjects.

Results: Of the 38 DMD subjects on BT [mean age: 17.4 (SD 4.4) years], 7 used PAM, 17 used ZA, and 14 used combination therapy (CT), switching from PAM to ZA. The duration of BT was 3.6±2.5 (mean ± SD) years. The frequency of FF was significantly reduced after using PAM (p=0.0039) [median pre: 6.0 (IQR 4.5, 7.0); median post: 0 (IQR 0, 0)] and ZA (p=0.009) [median pre: 3.0 (IQR 1.0, 5.0); median post: 0 (IQR 0, 1.0)]; there was no significant difference in FF after CT. The BMD z-scores for L1–L4 [mean pre: −2.33 ± 0.91; mean post: −2.71 ± 0.93] decreased slightly with BT. The total left hip BMD z-score [mean pre: −4.57 ± 1.24; mean post: −4.17 ± 1.04] increased with BT. Conclusion: BT is associated with significantly decreased rates of fragility fractures. There was no significant change in BMD z-scores during therapy. These data may inform development of guidelines for bone health monitoring in children with DMD. Further work comparing BMD and bone pain over time in DMD patients with and without BT is needed.

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Poster Board #64 Jocelyn Kerr, Undergraduate Student, University of Western Ontario Supervisor: Jean-Paul Collet, Brain, Behaviour & Development

The Link Between Executive Functions and Social Cognition, and Its Relevance to Child Development: A Rapid Review Jocelyn Kerr, Mojgan Gitimoghaddam, Jean-Paul Collet

Background: Executive functions and social cognition both play a key role in successful daily life function.

Current literature shows that a relationship exists between executive functions and social cognition; higher executive functions are associated with higher social cognition and the reciprocal. However, the mechanism of this relationship has not been clearly described. Because children with neurodevelopmental disabilities (NDD) often experience deficits in both executive functions and social cognition, developing a better understanding of this relationship could help to promote the development of children with NDD. Objective: To develop a better understanding of how executive functions impact social cognition, how social cognition impacts executive functions, and the relevance of this relationship to child development.

Methods/Results: Appropriate search strategies were developed for PsycINFO, ERIC, and PubMed using MESH terms and keywords related to executive functions, social cognition, and child development. Limits for selecting publications were that they must have had an age range within birth-18years, been peer-reviewed, and been published online and in English, within the last 5 years. The rapid review process is currently being conducted by two independent researchers, who will review the abstracts of all identified articles for selection according to specific criteria. After reconciliation, the two reviewers will independently read the full text to extract the relevant information. A preliminary summary of relevant literature concerning the relationship between executive functions and social cognition will be presented.

Future Directions: Developing our knowledge of the relationship between executive functions and social cognition will help us to plan more efficient interventions for children with NDD. Furthermore, this rapid review may reveal new areas of research to better document the relationship between executive functions and social cognition.

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Poster Board #65 Monica Lai, Undergraduate Student, University of British Columbia Supervisor: Kevin Harris, Evidence to Innovation

What Do Adolescents and their Parents Know About Their Heart Condition?

Monica Lai, Eimear McGovern, Christine Voss, Nicole Hemphill, Jimmy Lopez, Kevin Harris

Background: Adolescents with heart disease knowledge about their heart condition and potential complications is important for their engagement with the medical team and cardiovascular health. Patient education helps facilitate adolescents to take responsibility for their heart condition and contributes towards a smooth transition to adult care with uninterrupted follow-up. Parents are known to be highly involved in their child’s care, however, it is not known whether parental level of knowledge of their child’s heart disease is associated with the adolescent’s own level of heart disease knowledge. Certain lifestyle behaviours developed during adolescence are more likely to stay with the individual than if developed later on, and there is a positive association between improved health behaviours and increased heart disease-related knowledge.

Objectives: Our objectives include a) to assess the association between the adolescent’s level of knowledge of their heart disease to their parent’s level of heart disease knowledge and b) to assess the association between adolescent knowledge of their heart disease to their cardiovascular risk factor behaviours.

Methods: 13-19 year olds with heart disease and their parents were recruited through the BC Children’s Heart Centre. Adolescents and their parents were each instructed to individually complete a knowledge questionnaire regarding the adolescent’s heart disease. Knowledge questionnaires were later scored by a medical expert in cardiology. Adolescents self-reported their cardiovascular risk factor behaviours through a second questionnaire assessed via the CANHEART Health Index (scored 0=poor, 4=ideal) and Physical Activity Questionnaire for Adolescents (PAQ-A, scored 1=low, 5=high). Pertinent clinical data was collected through review of medical charts.

Expected Outcomes: We hypothesize that higher parental knowledge will be associated with higher adolescent knowledge and that increased knowledge score will be associated with increased scores in heart-healthy behaviours. This study will inform practice through helping to improve patient education and development of heart-healthy behaviours through increased awareness on where adolescents are currently lacking in knowledge regarding their heart disease and making changes accordingly to target these areas. This study will also guide further research on investigating the influence of parents and their role in adolescent care.

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Poster Board #66 Tom Ouellette, Undergraduate Student, University of British Columbia Supervisor: Bruce Carleton, Evidence to Innovation

Predicting Veno-Occlusive Disease in Pediatric Patients undergoing Cancer Chemotherapy Tom Ouellette, Reo Tanoshima, Amna Khan, Nicole McGoldrick, Jessica Trueman, Bruce Carleton

The development of severe hepatic veno-occlusive disease (VOD) in pediatric patients undergoing cancer chemotherapy confers a >80% mortality rate. In addition, severe VOD in pediatric patients has limited treatment options, lacks biomarkers with sufficient prognostic value, and poses a significant economic burden on patients and hospitals. VOD is primarily caused by thioguanine (TG), d-actinomycin (ACT), and hematopoietic stem cell transplantation (HSCT) conditioning agents, such as busulfan and cyclophosphamide.

Pediatric patients who undergo myeloablative HSCT have the highest incidence, which ranges from 10 to 60%.

As well, the incidence of severe VOD is reported to range from 2% to 6% in allogeneic HSCT patients. Previous literature has attributed some of the interindividual variation in the manifestation of VOD to genetics, but a comprehensive polygenic association study has yet to be performed. Thus, the purpose of this case-control study is to identify genetic markers predictive of VOD in pediatric patients undergoing cancer chemotherapy To compare cases and drug-matched controls, patient data was extracted from the Canadian Network for Pharmacogenomics Network for Drug Safety (CPNDS) database. A VOD case definition compromised of clinical and diagnostic information was also written and distributed to the CPNDS clinical surveillance team to facilitate ongoing patient enrolment and case validation. To date, 32 cases and 1141 drug-matched controls have been collected (781 TG; 264 ACT; 96 HSCT). Preliminary analysis shows no difference in dose between groups, supporting an idiosyncratic, and possibly genetic, link between VOD occurrence and TG, ACT, or HSCT conditioning exposure. In addition, data exploration revealed that mucositis may be a useful indicator for VOD development following HSCT, corroborating previous findings by Wingard et al. (1991).

Patient enrolment and data collection will continue until a sample size with sufficient power to detect a genetic association is reached and a replication cohort can be assembled. DNA collected from VOD cases and drug-matched controls will be undergo genome-wide SNP genotyping following clinical characterization and validation. Genotype analysis will be performed to identify genetic associations with odds ratios greater than 3 and a predictive risk model will be derived â&#x20AC;&#x201C; with the intention of being implemented in future clinical guidelines.

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Poster Board #67 Anahat Sahota, Medical Student, University of British Columbia Supervisor: Patrick McDonald, Brain, Behaviour & Development

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

Imaging Practices for Hydrocephalus at BC Childrenâ&#x20AC;&#x2122;s Hospital A Comparison of Two Historical Epochs Anahat Sahota, Alexander Cheong, Patrick J. McDonald

Introduction: Hydrocephalus is a common condition affecting children, characterized by excess cerebral spinal fluid build up in the ventricles of the brain resulting in increased intracranial pressure and commonly treated surgically. Hydrocephalus is followed with computed tomography (CT) scans, magnetic resonance (MR) imaging, ultrasounds, and plain x-ray films. While CT scans are a more available and quicker imaging modality, there are concerns regarding the risks of radiation exposure in children. MR imaging does not expose patients to radiation, however take longer to complete- potentially requiring sedation of young patients, and is less accessible than CT scans. Ultrasounds can be used to image infantsâ&#x20AC;&#x2122; brains while their fontanelles are open.

X-rays and shunt series are easily accessible with a small amount of radiation. This study aims to examine the trends in imaging practices for children diagnosed with hydrocephalus and treated at BCCH over two temporal epochs, with the hypothesis that both the frequency of imaging and the modality used, changed over time.

Methods: A retrospective chart review is ongoing of all patients at BCCH with a diagnosis of hydrocephalus, whose first surgical intervention was at BCCH between 1990-1994 (Cohort 1) and 2010-2014 (Cohort 2).

Data collected includes etiology of hydrocephalus, imaging modality used to diagnose, number of MRs, CTs, ultrasounds, and x-rays or shunt series, initial treatment, and number of surgical interventions for hydrocephalus.

Results: Preliminary analysis shows that compared to Cohort 1, the use of MR imaging in Cohort 2 has significantly increased (p<0.0001), the use of CT images has significantly decreased (p<0.0001), the use of x-rays has significantly decreased (p=0.0001), while the use of ultrasound and the frequency of overall imaging has not significantly changed between the two cohorts.

Conclusions: The preliminary results support our hypothesis that frequencies of imaging modalities have changed over time, as MRs have become more prevalent and CTs and x-rays used less frequently. However, ultrasound imaging has remained stable over time, which may be due to the low risk and ease of use in infants.

While preliminary results show that overall imaging frequency has not changed, this may change as the study progresses.

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Session 07

Clinical, Population Health & Health Services

Moderator: Dr. Jim Potts Participants: Zoe Schmidt Saman Fouladirad Farnaz Javadian Christine Lukac August Pierik Stephen Siu Mikayla Wohlleben Sean Wong Chloe Xinyuan You SofĂ­a Zhang-Jiang

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Poster Board #68 Zoe Schmidt, Undergraduate Student, University of British Columbia Supervisor: Rajavel Elango, Healthy Starts

Congratulations to Zoe on receiving a UBC Faculty of Medicine Sheila Innis Studentship for Biomedical Research Endowment!

Arginine supplementation in pyridoxine dependent epilepsy: is there a benefit?

Zoe Schmidt, Rajavel Elango, Sylvia Stockler-Ipsiroglu

Background: Pyridoxine-dependent epilepsy (PDE) is an inborn error of metabolism characterized by seizures that respond to the administration of pyridoxine. PDE is caused by mutation to gene ALDHA71 encoding the enzyme α-aminoadipic semialdehyde dehydrogenase in the lysine catabolic pathway. This leads to increased levels of toxic compounds, like α-aminoadipic semialdehyde. PDE patients follow a lysine-restricted diet but a newer therapy, arginine supplementation, has proven effective in reports from clinical practice. The underlying principle being that arginine competes with lysine because they share the same transporter across membranes. Recommended arginine dosing is not established and it’s interaction with lysine at the intestinal level remains unclear.

Objectives: This study will investigate arginine’s proposed mechanism of action in PDE treatment by measuring, at different doses of arginine, the metabolism of lysine with the use of an in-vivo stable isotope tracer L-113C-Lysine in healthy males as a proof-of-concept study. We aim to see changes in the metabolism of lysine following graded arginine doses, with potential bio-markers in urine and plasma.

Methods: Three healthy adult participants are scheduled to take part in 6 study days each; one arginine dose per day. Throughout the day, participants eat only the provided diet (8 meals) which includes the arginine dose and stable isotope tracer. Baseline measurements of lysine oxidation are taken before the stable isotope is introduced at meal 5. An indirect calorimeter is used to measure participant’s metabolic rate and CO2 expenditure. Breath samples are collected and analyzed for L-1-13C-Lysine oxidation to 13CO2, using an isotope ratio mass spectrometer. Urine and blood samples will be analyzed for potential biomarkers using an LC-MS/MS. Expected Results: As arginine doses increase, we hope to see decreased lysine metabolism exhibited by a decrease in the levels of L-1-13C-Lysine in the breath.

Conclusion: The findings could support the use of arginine supplementation as a therapy for PDE patients by providing empirical evidence of its competitive inhibition with lysine at the intestinal level. These findings could also suggest a safe dosing range for arginine supplementation and could improve the neurological developmental outcomes of patients with PDE.

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Poster Board #69 Saman Fouladirad, Medical Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

Congratulations to Saman on receiving a UBC Faculty of Medicine Summer Studentship!

Altered Functional Connectivity in Brain Networks of Schizophrenic Patients During Hypersalience Decision Making Saman Fouladirad, Todd S. Woodward

It has been documented that patients with schizophrenia make decisions based on little evidence due to the salience of the stimuli (Speechley et al., 2010). Schizophrenia patients with delusional symptoms are noted to have increased dopaminergic activity leading to hypersalience, meaning that the item of interest stands out much more (Kapur, 2003). This study assessed the activity of the networks involved in hypersalience decisionmaking by examining the brains of patients with delusional symptoms as they conducted a probabilistic reasoning task known to create hypersalience. The study consisted of delusional (n=15) and non-delusional (n=15) schizophrenic patients completing a FISH task inside an fMRI scanner. The tasks consist of a central fish between two lakes, blue and green, containing different proportions of black and white fish and the participants had to choose which lake the central fish came from. Hypersalience condition is created when the color of the central fish is similar to the color of the majority of the fish in the lake that itâ&#x20AC;&#x2122;s pointing to. Four brain networks were extracted from the analysis and ANOVA measures for network 1 revealed a significant difference between delusional and non-delusional patients in the hypersalience condition: F(1,150.224) = 4.973, p < 0.05. This was characterized to be the cognitive-evaluation network. A possible explanation for these results is that delusional patients are unable to suppress cognitive-evaluation when there is a strong match between evidence and hypothesis. Implications of understanding the cognitive underpinnings of patientsâ&#x20AC;&#x2122; decision-making include optimizing alternative forms of psychological therapeutic interventions.

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Poster Board #70 Farnaz Javadian, Medical Student, University of British Columbia Supervisor: Deborah Giaschi, Brain, Behaviour & Development

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

Do motion perception and binocular function share common processing mechanisms?

Farnaz Javadian, Arijit Chakraborty, Deborah Giaschi

Introduction: Amblyopia is a developmental disorder characterized by one eye having decreased visual acuity that cannot be corrected with glasses (amblyopic eye), while the other has normal visual acuity (fellow eye); deficits in binocular vision are common. The Giaschi lab discovered that amblyopia also disrupts motion perception. This deficit is unexpected because it affects both eyes and involves different brain regions than those involved in visual acuity. We hypothesize that deficits in motion perception are related to disrupted binocular vision. The current study was conducted to determine whether motion perception and binocular function are correlated in typical or atypical vision.

Methods: Statistical analyses were run on data obtained from past studies in our lab on motion perception and stereopsis to determine if there are any correlations, as well as to see which factors predict whether an individual has amblyopia. For the motion tasks, the goal was to determine the coherence threshold, which is the lowest proportion of signal dots on the screen needed to accurately determine the correct direction or orientation of motion. For assessing binocular function, participantsâ&#x20AC;&#x2122; depth discrimination (stereopsis) was determined using a 3D computer task.

Results: Stereopsis and motion perception were correlated in both the amblyopia group and controls. Both aspects of perception were also shown to be independent predictors of whether an individual has amblyopia.

Conclusion: Overall, our results suggest an association between motion perception and binocular function, indicating a shared processing mechanism. Neuroimaging studies may be able to determine which areas of the brain are common to processing both motion perception and binocular function. There are also treatment implications because deficits in stereopsis and motion perception often persist following standard patching therapy for amblyopia. We hypothesize that these deficits contribute to treatment failure and to amblyopia recurrence.

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Poster Board #71 Christine Lukac, Medical Student, University of British Columbia Supervisor: Gina Ogilvie, Healthy Starts

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

Impact of the human papillomavirus immunization program on rates of genital warts in British Columbia, 2000-2017 Christine Lukac, Robine Donken, Michael Otterstatter, Olga Mazo, Stanley Wong, Monika Naus, Deborah Money, Fawziah Lalji, Mel Krajden, Mark Gilbert, Troy Grennan, Jason Wong, Laurie Smith, Gina Ogilvie

Background: The majority of genital warts (GWs) caused by the human papillomavirus (HPV) serotypes 6 and 11 are preventable with GARDASILÂŽ4 vaccine. In 2008, a school-based HPV immunization program was implemented across BC among girls in grades six (born in 1997) and nine (born in 1994). The HPV immunization program is ongoing and in 2017 the first birth cohorts of immunized girls turned 20 and 23 years of age.

Objective: To describe the rates of GWs in BC before and during the implementation of the HPV immunization program as an indicator of impact on subpopulations: women who have sex with men (WSM), men who have sex with women (MSW), and men who have sex with men (MSM).

Method: Data on GW diagnoses between January 2000 and December 2017 were accessed via the Sexually Transmitted Infection Information System - an electronic medical record system used at all public health clinics in BC. Rates were calculated by age groups (14-46), year of clinic visit (2000-2017), and birth cohort (19701999) for each subpopulation. Age-period-cohort Poisson modeling produced adjusted relative rates for each subpopulation.

Results: Age effects were similar across subpopulations. With increasing age, the overall rates of GWs first increased between ages 14-22 and then decreased until age 46 (4.29, 6.64, and 0.74 cases per 100 person years for ages groups 14-16, 20-22 and 44-46 respectively). Birth cohort effects were specific to subpopulations. Compared to individuals born in 1988-93, rates of GWs decreased by 63% among WSM born in 1994-99 who were targeted by the HPV immunization program, and by 48% among MSW born in 1994-99 who benefited from herd immunity. There was no change in rates of GWs among MSM. Period effects adjusted or age and birth cohort were specific to subpopulations. The overall adjusted relative rates of GWs were 0.74 (95%CI: 0.60, 0.92) in 2012-2014 and 0.47 (95%CI: 0.36, 0.60) in 2015-2017 compared to rates in 2000-2002.

Similar decreased rates were observed among WSM and MSW. Impact: Preliminary findings suggest that the HPV immunization program has achieved its intended impact, decreasing the rates of GWs among WSM and MSW.

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Poster Board #72 August Pierik, Medical Student, University of British Columbia Supervisor: Hannah Piper, Healthy Starts

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

The Utility of Instructional Videos for Reducing Central Line Associated Complications in Children with Intestinal Failure August Pierik, Hannah G. Piper

Background: Children with intestinal failure (IF) frequently require prolonged parenteral nutrition (PN) support to sustain normal growth and development. A functional central venous line (CVL) is essential for PN administration, but these catheters can be the source of significant morbidity. CVL associated complications are the most common cause of re-admission to the hospital, despite parents/caregivers participating in an educational program prior to going home. The curriculum currently includes one-on-one teaching and printed materials describing all skills. The objective of this study is to evaluate the effect of instructional videos as an adjunct to the current curriculum in reducing CVL associated complications.

Methods: A retrospective review of children with IF on home PN who are part of the Intestinal Rehabilitation Program at BC Childrenâ&#x20AC;&#x2122;s Hospital was performed to determine the incidence of CVL associated complications in the past 2 years. Family members and/or caregivers were then surveyed to determine interest in educational videos. Educational CVL care videos were then created, incorporating input from stakeholders (families, IV access team, patient experience specialist). Access to the teaching videos will be provided to families for 12 months, at which point CVL associated complications will be re-calculated for this time period. Complication rates will be compared pre- and post-video implementation.

Results: A total of 16 children with IF on home PN between 2016-2018 were reviewed, accounting for 7238 catheter days. 75% of patients had at least 1 CVL associated complication and 63% had two or more.

Complication rates were 5.4 per 1000 catheter days for line breakages, 1.4 per 1000 catheter days for line occlusions, and 1.1 per 1000 catheter days for bloodstream infections. Twelve parents who had received home PN training in the past 3 years were surveyed. 30% of parents reported feeling uncertainty with required skills upon arriving home. 80% believed teaching videos would have been helpful.

Conclusions: Children with IF on home TPN are at high risk for CVL associated complications. Parents expressed interest in video based teaching tools. Completion of this study will include re-evaluating complication rates after video distribution and soliciting family feedback.

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Poster Board #73 Stephen Siu, Undergraduate Student,

Supervisor: Joseph Ting, Evidence to Innovation

Predictors of successful closure of patent ductus arteriosus with nonsteroidal anti-inflammatory drugs Stephen Siu, Joseph Ting

The patent ductus arteriosus (PDA) diverts blood from the main pulmonary artery to the descending aorta in intrauterine life and closes 1-2 days after birth. Failure of PDA closure (50-70% <28 weeks) causes shunting of blood from the left heart to the right heart and can induce heart failure, lung diseases and increased mechanical ventilation which causes higher mortality and morbidities. Recent in-vitro studies show that antibiotics may counteract the responses of NSAIDs, which are used for closing the PDA. The objective of this research is to determine whether treatment with both antibiotics and NSAIDs within the first week of birth is associated with higher failure rates of PDA closure. A retrospective chart review is conducted, in which data is collected from January 2010 to December 2016. Preterm infants with birth weight <1.5kg who received an NSAID for treatment of the PDA during the first 14 days of life in BC Womenâ&#x20AC;&#x2122;s Hospital Neonatal Intensive Care Unit (NICU) are included, while infants with moribund status, cardiac lesions other than patent foramen ovale or those undergoing surgical PDA ligation are excluded. Clinical characteristics of infants are described using mean/standard deviation or median/interquartile ranges. Characteristics of infants who achieved ductal closure using NSAIDs are compared with those who failed NSAIDs treatment using Pearson Chi-square test or Fisherâ&#x20AC;&#x2122;s exact test for categorical variables and t-test or Mann-Whitney U test, as appropriate, for continuous variables. A regression model is conducted to identify the predictive variables for PDA closure. This research is likely the first clinical study to investigate the role of early empirical antibiotics and the response of medical treatment for PDA closure. More investigation and data analysis will be done to further determine the full effects of NSAIDs and antibiotics on PDA closure.

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Poster Board #74 Mikayla Wohlleben, Medical Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Congratulations to Mikayla on receiving a UBC Faculty of Medicine Summer Studentship!

Self-injurious behaviour - understanding clinical patterns

Mikayla Wohlleben, Dr. Osman Ipsiroglu, Dr. Robin Friedlander, Dr. Anamaria Richardson, Dr. Mary Connoly, Dr. Tim Oberlander, Dr. Suzanne Lewis, Mary Glasgow Brown, Katie Allen, Alison Whitlock, Vinni Panikkar Background: Self-Injurious behaviours (SIBs) stands for intentionally causing harm to oneself. In children and adolescents with neurodevelopmental disorders, common presentations of SIB include head banging, biting, hitting and kneeing themselves. SIBs not only cause significant stress for the patients, but also for the family and the involved health care professionals. The SIB Clinic at BCCH is a multi-professional team that investigates SIB in children with neurodevelopmental and/ or psychiatric disorders.

Aim: To identify patterns of clinical presentation in complex chronic care patients presenting with SIB. Methods: A retrospective chart review was completed on 15 patients (between ages 4-16) from the SIB (n=12) and Sleep Clinics (n=3). Narrative case reports were created to form an overview of complex clinical presentations. From these summaries, comparison tables were made, delineating main clinical characteristics.

Final tables were constructed after completing a structured chart review.

Results: 15/15 patients presented with (a) sensory processing abnormalities (tactile/noise/light sensitivity or mouthing behaviours) (b) hyperactivity, impulsivity, and lack of concentration (12/15 were diagnosed with ADHD) and (c) insomnia (difficulties with sleep initiation, maintenance, early morning awakenings).

13/15 patients presented with iron deficiency (ferritin < 50 ng/mL); 2/15 patients lacked iron studies in their charts. Clinical characteristics like PICA behaviours, shifted pain threshold, anxiety, and OCD-like are under investigation.

Significance: This analysis helped in shaping the protocol for prospective investigations, which will include video-recordings of SIBs, sleep/wake-data and targeting sleep during the wait-time for the SIB clinic, and brain iron studies (via post-processing of routine MRI data). Currently, we are working on the ethics consent forms for these prospective protocols in conjunction with the Vancouver Summer Sleep School.

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Poster Board #75 Sean Wong, Medical Student, University of Western Ontario Supervisor: Srinivas Murthy, Healthy Starts

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

Impact of transport time on patient outcomes in BCCH PICU Sean Wong, Srinivas Murthy

Transportation of ill patients is a basic, yet undeniably critical step in the delivery of optimal healthcare.

Unfortunately, transportation is often a barrier to healthcare access, a major consequence of which being delayed care. Delays in clinical intervention, in the context of conditions requiring admission to the Intensive Care Unit (ICU), may result in poorer patient outcomes, particularly in geographically large health regions.

For example, bacterial meningitis is a condition for which admission to the ICU is necessary. It has been demonstrated that early management of bacterial meningitis with both antibacterial and supportive care can decrease morbidity and mortality. For bacterial meningitis and other such conditions requiring admission to ICU, early intervention can often lead to improved patient outcomes and fewer complications in patient management. Another well-defined example demonstrating the negative impact of increased transit time on patient outcomes are those involving adverse cardiovascular events, including myocardial infarction and stroke patients. For example, longer ambulance transport time was associated with poorer outcomes in stroke patients as measured by discharge modified Rankin Score and hospital mortality. There are a number of factors that could impart a negative impact on transit time which could in turn lead to poorer health outcomes.

For example, it has been suggested that ill-defined prehospital destination criteria and protocol could be a contributing factor. While the necessity for earlier interventions has been proven, the specific impact of transportation time on patient outcomes has yet to be explored in a Canadian context.

We hypothesize that increased duration of transport, as measured by transit time, will have a negative impact on patient-specific outcomes, as measured by length-of-stay in children admitted to the Pediatric Intensive Care Unit (PICU) at BC Childrenâ&#x20AC;&#x2122;s Hospital (BCCH). It is suspected that barriers of transportation may delay care and enhance risk of adverse events, thus contributing towards poorer patient outcomes. Through retrospective examination of critically ill children, we aim to clarify the relationship between transport time and patient outcomes and highlight its importance for future improvements to care in British Columbia

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Poster Board #76 Chloe Xinyuan You, Undergraduate Student, University of British Columbia Supervisor: Michael Kobor, Healthy Starts

Congratulations to Chloe Xinyuan on receiving a AllerGen Undergraduate Summer Studentships!

Effects of Short Term Diesel Exhaust and Allergen Exposure on DNA Methylation in Human Bronchial Epithelial Cells

Chloe X. You, Rachel D. Edgar, Lisa M. McEwen, Christopher F. Rider, Agnes C. Y. Yuen, David T.S. Lin, Julia L. MacIsaac, Katia E. Ramadori, Michael S. Kobor, Christopher Carlsten Previous studies have shown that air pollution and allergens have significant effects on DNA methylation.

The aim of this study is to build upon previous diesel exhaust studies to further understand the underlying mechanisms of DNA methylation. In this randomized, controlled, human crossover experiment study, we determined the changes in DNA methylation in bronchial epithelial cells after short term co-exposures to diesel exhaust and allergen. Thirteen volunteers underwent four co-exposure conditions in a randomized order over four visits: filtered air and saline (control group FA-S), filtered air and allergen (FA-A), diesel exhaust and allergen (DE-A), particle depleted diesel exhaust and allergen(PDDE-A). Bronchial brushings (consisting of ~96% bronchial epithelial cells) were then collected and samples run on the Infinium Methylation EPIC bead chip array to generate DNA methylation profiles at ~850,000 sites. A preliminary analysis was performed on preprocessed data in RStudio and 7 CpG sites were identified with biological significance (delta beta>0.05) and under the statistical threshold (p<0.00001). Among the seven hits, five were within a gene body; a 1000 bp sliding window was applied on the other two CpG sites to study the associated differential methylation region. While comparing DNAm levels of the seven hits between the four different co-exposure conditions, we saw that the average methylation level of PDDE-A group was consistently lower than the control group and the average methylation level of FA-A and DE-A group was lower than the control group among most of the discovered hits. Moving forward, the pathways of the significantly modulated genes will be examined.

Significant hits will be validated in other tissues collected from the same cohort.

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Poster Board #77 Sofía Zhang-Jiang, Undergraduate Student, McMaster University Supervisor: Anne Synnes, Brain, Behaviour & Development

Congratulations to Sofía on receiving a CHILD-BRIGHT Summer Studentship!

Developing Vignettes to Evaluate Parental Perception of Disability Severity in Preterm Babies

Sofía Zhang-Jiang, Dallas Genereaux, Thuy Mai Luu, Annie Janvier, Claude Julie Bourque, Paige Church, Kate Robson, Anne Synnes Introduction: Neurodevelopmental impairment (NDI) occurs in 46% of children born very preterm at less than 29 weeks’ gestation, and the risk of severe NDI is used to make critical health care decisions. There is no consensus on how to measure, define, and report outcomes. Parents have never been asked to voice which outcomes they perceive to be important. The Parent-EPIQ research projects are engaging parents of preterm children to define which outcomes are most meaningful to them. This pilot study aims to evaluate parental perceptions of the severity of a variety of possible outcomes in 18-month-old children.

Methods: We developed 11 clinical vignettes that encompass the 6 components of NDI, the 4 most common multiple impairments, and one normal case scenario. The vignettes were drafted in survey form after review of medical and patient-written literature and edited after review by clinical (n=10) and research staff (n= 6) for clinical validity. Parent feedback was obtained via BC Women’s Hospital Family Engagement Advisors (n=8) and the Canadian Premature Babies Foundation (n=3). Parent reviewers evaluated the language, length, and suitability of the vignettes and pilot-tested the survey. They rated the severity of each vignette on a scale of 0 – 10 and answered whether they thought it was a severe disability and whether the described outcome would be important for parents to know.

Results to Date: Eleven vignettes have been created on REDcap and reviewed for clinical validity. Parent reviewer feedback has been sought with results due by July 25. The research team will review results and finalize the survey by July 31. In the fall of 2019, the anonymous survey will be distributed to 150 parents of preterm children aged 18 months to 5 years in three Canadian cities. Median scores and rankings will be computed for each vignette to evaluate relative severity, and feedback will determine which outcomes should be reported clinically and in research.

Conclusions: Findings will allow the research team to co-create definitions of NDI that are relevant to parents.

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The Research Education Office, at the BC Children’s Hospital Research Institute, supports the development of an enriched, multidisciplinary learning environment for researchers onsite How do we support the research community?

• Offer a curriculum for graduate students and postdoctoral fellows to help build analytical capacity and enchance career development skills • Coordinate training resources and professional development opportunities for clinical researchers • Bridge the gap between basic science and clinical research with unique networking and funding opportunities

• Provide a foundation for investigators to produce skilled and confident graduates • Introduce undergraduate and medical students to research across disciplines, maximizing the connections with peers and mentors • Lead the development of outreach programs, engaging high school students and the public with world-class researchers and clinicians

800 336 100% $950,000+

Dedication to Research Education

High school students participated in programs intended to broaden their knowledge of research this year

Trainees in 2016 - 2017

410 Registered summer students between 2012 - 2016

Budget for training and awards in 2017 - 2018

785 Alumni trainees

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Hours of professional development and research skills trainining offered in 2016 - 2017

Research Education Office BC Children’s Hospital Research Institute Room A2-143, 950 West 28th Avenue Vancouver, BC V5Z 4H4 www.bcchr.ca 604-875-2000 x5397 | reseduc@bcchr.ca

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