2020 - Summer Student Poster Day

Title Page

2020 SUMMER STUDENT E-POSTER DAY

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Welcome to the 2020 Virtual 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 over the summer — and this year we’re doing it virtually for the first time!

Over the past few months, the COVID-19 pandemic has caused rapid changes at the Research Institute and has greatly impacted all areas of research on the Oak Street Campus. As the health and safety of the research community is our first priority, we were able to work with our partner organizations to adjust all aspects of the summer program so it could still be held virtually. Despite the challenges, we realize the important contributions our summer students make each year, and hope the research community at BC Children’s Hospital has provided students with valuable research opportunities and learning experiences.

Since the early 1990s, the Summer Student Research Program has provided undergraduate and medical students an opportunity to participate in research projects related to children’s and women’s health. 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 fields.

Sincerely, Ashley Biggerstaff, Sharon Yau and Laura Christensen www.bcchr.ca/posterday Research Education Team, BC Children’s Hospital Research Institute

Summer Student Poster Day Thursday, July 30, 2020 Watch Presentations Online - www.bcchr.ca/posterday

Morning Sessions

Showcasing the outstanding work of summer students and their contributions to research. Each participant will have 5 minutes to discuss their poster and up to 5 minutes for questions.

9:00 - 10:30 am

Session 1: Basic Science Session 2: Clinical, Population Health & Health Services

10:45 am - 12:00 pm

Session 3: Basic Science Session 4: Clinical, Population Health & Health Services

Afternoon Sessions

1:00 - 2:30 pm

Session 5: Basic Science Session 6: Clinical, Population Health & Health Services

2:30 - 4:00 pm

Session 7: Clinical, Population Health & Health Services

Awards Ceremony

4:30 pm

Join us in celebrating the accomplishments of our colleagues and the positive impact of research taking place in our community. The award ceremony will feature the poster presentation awards. www.bcchr.ca/posterday

Since 1987, the Summer Student Research Program has provided 1,500+ students with the opportunity to participate in projects related to child and family health under the supervision of researchers on the Oak Street Campus.

2020 Program Details

90

63 Undergraduate Students 22 Medical Students 5 Alumni & Graduate Students

Registered Summer Student Research Program participants

55

Research community presenters, moderators, facilitators, panelists and judges

29

BCCHR-administrated Summer Studentships

12

Offsite research projects

27

Represented universities

90

32

Virtual hours of seminars, professional development workshops and networking opportunities

Research projects pursuing new discoveries and innovations

Participant Universities Concordia University Cornell University Dalhousie University Emily Carr University Harvard University McGill University McMaster University National University of Ireland Queen's University Quinnipiac University

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Royal College of Surgeons in Ireland Simon Fraser University University College Dublin University College London University of Birmingham University of British Columbia (Vancouver & Okanagan) University of California University of Guelph

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University of Ottawa University of Pennsylvania University of Saskatchewan University of Texas University of Toronto University of Victoria University of Waterloo Western University

Showingcasing excellence in our talented research community!

2020 Poster Participants Participant Azim Ahmed

Sanjit Bains Matthew Cheng Rachel Cheng Claire Cheung Sara (Seungwon) Choi Danielle Cohen Luke Enns

Risa Fox Gurmaan Gill Umara Hansen Bob Hoogenes Parnian Hosseini Ashley Jang Jennifer Jiang Abhay Katyal Katherine Ketchum Gurman Khera

Research Team

Abstract Title

Blydt-Hansen Research Team

The Associations of Exercise and Contemporaneous Factors transplant with Height-Adjusted Lean Body Mass in Pediatric Kidney Transplant Patients Kobor Research Team Chronic Stress Interacts with Alpha Synuclein Overexpression to Alter Epigenetic Regulation in Parkinson's Model Mice Stockler-Ipsiroglu Repurpose-able drug screening for cerebral creatine transporter Research Team (SLC6A8) related intellectual disability Taubert Research Team The C. elegans Nuclear Hormone Receptor, NHR-49, and Cellular Stress Response Lavoie Research Team SARS-CoV-2 Seroprevalence in the Greater Vancouver Area Piper Research Team Using urine sodium to creatinine ratio as a marker of total body sodium to improve growth in babies with short bowel syndrome Devlin Research Team Sex-Specific Effects of Maternal Folic Acid Supplementation on Pancreatic Alpha and Beta Cell Mass in Fetal Offspring Verchere Research Team The role of type 2 diabetes risk gene peptidylglycine ι-amidating monooxygenase in pancreatic insulin-secreting β-cells in the development of diabetes Eng Research Team Effects of epidural stimulation to restore meaningful function after spinal cord injury: A systematic review Lange Research Team How Degradomics Studies Contribute to Our Understanding of Cell Death Mechanisms Stewart Research Team Assessing the utility and consistency of teacher rating scales relative to clinician ratings in pediatric obsessive-compulsive disorder Eng Research Team COVID-19 and spinal cord injury: clinical presentation, clinical course and outcomes: A rapid review Ansermino Research Team Review on the Implementation of Patient Tracking Systems in Healthcare Devlin Research Team Early postnatal programming of pancreatic islets by maternal exercise Luciani Research Team Applying Super Resolution Imaging by Radial Fluctuations (SRRF) for Analysis of Mitochondria-Lysosome Interactions in Living Beta Cells Sanatani Research Team Alterations of the Autonomic Nervous System in Adolescents with Unexplained Palpitations Siden Research Team Optimizing the Management of Pain and Irritability in Children with Severe Neurological Impairment Jacobson Research Team Infliximab Dose Optimization During Maintenance Therapy In Children With Inflammatory Bowel Disease

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BC Children’s Hospital Foundation

The BC Children’s Hospital research community would like to acknowledge the following organizations for supporting training opportunities on the Oak Street Campus:

Participant

Research Team

Min Jung Kim Jennifer Krentz

Lim Research Team Nicholls Research Team

Salina Kung Soomin Lee

Barakauskas Research Team Vallance Research Team

Angella Lee

Lamers Research Team

Rebecca Lim

Bettinger Research Team

Johnson Liu

Eng Research Team

Gita Manhas

Eng Research Team

Victoria McCann

Whyte Research Team

Scout McWilliams

Ipsiroglu Research Team

Lindy Moxham Lulu Pei Evelyne Piret

Kobor Research Team Karakochuk Research Team Ogilvie Research Team

Stephanie Quon

Dumont Research Team

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Canucks for Kids Fund Childhood Diabetes Laboratories Community Child Health Endowment Research Themes: Brain, Behaviour & Development Childhood Diseases Healthy Starts Evidence to Innovation

Abstract Title BH3 Profiling as a Tool for Precision Treatment in Pediatric Oncology Attendance to Risk Factors and Protective Factors in Reports for NCRMD Patients Pregnancy and Pediatric Reference Intervals for Safe Medicine (P2RISM) Exploring the potential for an inulin-enriched diet to delay the development of spontaneous colitis in Muc2 deficient mice Investigating the differences in maternal dietary intake for women of different BMI statuses 1.5 years after delivery Knowledge and attitudes of children and adolescents towards vaccines: A systematic review Does accelerometer measurement of upper extremity use capture changes following stroke? A systematic review Investigating the relationship between step counts, standing time, and functional outcomes during stroke rehabilitation Genetic Differences in Pharmacodynamic Safety Endpoints with Propofol Anaesthesia in Children Sleep an Outcome Measure in Interventional ADHD Randomized Controlled Trials (RCTs): Scoping Review Methodology Building a Genetic Ancestry Predictor Using DNA Methylation Data Baseline iron biomarkers as predictors of a hemoglobin response to 12 weeks of daily iron supplementation in Cambodian women Acceptability and side effects of thermal ablation for the treatment of cervical precancerous lesions in low- and middle-income countries: a systematic review Smartphone Video-Based Respiratory Rate Tracking for Infants

Participant

Research Team

Kathryn Reilly

Leveille Research Team

Lise Rutherford

Vercauteren Research Team Leveille Research Team

Frances Scheepers Donna Seraj & Harman Grewal Matt Sha Mikayla Shymka Sydney Sparanese

Jacques Research Team

Rene Tandun & Enoch Yau Miranda Tsuyuki

Steiner Research Team

Gibson Research Team Harris Research Team Doan Research Team

Amir Wachtel

Matsubara Research Team Arneja Research Team

Sarah Wissmann

Bajno Research Team

Sandy Wu

Yong Research Team

Lily Yip

Woodward Research Team Goldowitz Research Team

Zehan Zhou

Abstract Title Quadriceps realignment and rectus femoris re-routing: description of a novel procedure for proximal extensor mechanism realignment in skeletally immature patients Assessment of Single Cell Tissue Processing Methods Split Tibialis Posterior Tendon Transfer (SPOTT) for Equinovarus Foot in Cerebral Palsy Reduction of Mucosal Barrier Injuries in Pediatric Oncology/ Hematology/BMT Patients Genetic Characterization of Rare Overgrowth Syndromes Assessing the Utility of 3D Cardiac Models in Medical Education Using MyHEARTSMAP to measure the association between psychosocial factors and persistent post-concussive symptoms in children TUDCA and Tr1 cell supernatants as potential therapeutics to ameliorate intestinal epithelial cell ER stress Granzyme B Promotes Early Stages of AMD in Bruch’s Membrane and RPE in Mouse Models Predicting Unplanned Hospital Readmissions at BC Children's Hospital Access to diagnostic ultrasound in infants with developmental dysplasia of the hip: A road too far?

Pathways for patient-centered diagnosis and management of endometriosis-associated deep dyspareunia: A pilot randomized trial Functional connectivity of the brain: fMRI analysis of two language tasks Chromosome 2 as a Contributor to Whole Cerebellar Volume in P30 Mice

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Session #1 BASIC SCIENCE Moderator: Dr. Anuli Uzozie Participants: Matthew Cheng Rachel Cheng Luke Enns Ashley Jang Soomin Lee Lindy Moxham Watch Presentations Online: Thursday, July 30 | 9:00 am www.bcchr.ca/posterday

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Session #1 | Poster #1 Matthew Cheng, Undergraduate Student, University of Pennsylvania Supervisor: Sylvia Stockler-Ipsiroglu, Childhood Diseases

Repurpose-able drug screening for cerebral creatine transporter (SLC6A8) related intellectual disability Matthew Cheng, Peter Axerio-Cilies, Sylvia Stockler-Ipsiroglu

Background: Creatine transporter deficiency is an X-linked disorder that prevents transport of creatine to the brain, resulting from mutations in the SLC6A8 gene. SLC6A8 related conditions are mainly characterized by brain creatine deficiency, intellectual disability, autism and related behavioural issues, and seizures. Treatment with supraphysiological doses of creatine and its metabolic precursors arginine and glycine is ineffective in improving brain creatine levels and clinical outcomes; therefore, therapeutic alternatives are needed.

Our group has developed a patch-clamp method to assess SLC6A8 function in transfected human embryonic kidney (HEK) cells by measuring electrochemical signals produced during the SLC6A8 mediated creatine transport. Via virtual drug screening, we will identify candidate molecules for potential rescue of SLC6A8 function and test them in experimental settings.

Purpose & Aim: To identify the most suitable SLC6A8 mutations for our drug screening project.

Methods: We used the LOV Database (Netherlands) and the Baylor Database (United States, courtesy of Dr. Lee-Jun C. Wong, PhD) to investigate SLC6A8 variants. We grouped these variants according to pathogenicity, number of affected patients, type of variant, and functional validation. Among the selected variants, we searched for those found in patients accessible for clinical trials.

Results: The LOVD classified 75 pathogenic or likely pathogenic SLC6A8 variants, while the Baylor database included 66 variants of varying pathogenicity, totalling 170+ unique variants. Based on our selection criteria, we focused on two deletion variants (c.1006_1008del and c.1222_1224del), observed in 26 and 19 individuals respectively, and on two missense variants (c.1661C>T, c.1169C>T), which have both been observed in 13 individuals. We additionally selected the c.1699T>C variant, which has been observed in a single patient who is potentially accessible for a clinical n=1 trial. All these variants have been validated with DNA sequence analyses.

Conclusion & Future Research: The selected variants will be used for drug modelling and expressed in HEK cells to be screened for responses to various pharmacological substances. Drug candidates which recover mutant SLC6A8 function will then be tested on individuals carrying the respective variant, with single experimental study design (n=1 trials) using core and personally meaningful outcomes.

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Session #1 | Poster #2 Rachel Cheng, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert & Kelsie Doering, Healthy Starts

The C. elegans Nuclear Hormone Receptor, NHR-49, and Cellular Stress Response Rachel Cheng, Kelsie Doering, Stefan Taubert

Cells are constantly subjected to a variety of stresses such as infection, starvation, hypoxia (low oxygen), and oxidative stress; the ability to mount a specific response is paramount to survival. Many of these stress response pathways have been evolutionarily conserved from humans to Caenorhabditis elegans, a microscopic nematode. These nematodes are an ideal in vivo model to study said pathways with additional benefits including a fast life cycle, large brood size, and genetic traceability. The C. elegans nuclear hormone receptor NHR-49 has two human orthologs, HNF4α (Hepatocyte Nuclear Factor 4 alpha) and PPARα (Peroxisome Proliferator-activated Receptor alpha). Both are vital in liver function where HNF4α regulates hepatic cell development and PPARα regulates lipid metabolism. Previously, NHR-49 was studied for its role in lipid metabolism where it regulates lipid transportation, activation, and β-oxidation.

However, it was recently determined to be required for both the survival and induction of response genes in starvation, hypoxia, Staphylococcus aureus and Pseudomonas aeruginosa infection, and oxidative stress (induced by tert-butyl hydroperoxide; tBOOH). The conserved detoxification gene fmo-2 (Flavin MonoOxygenase 2) is highly induced in an NHR-49 dependent manner in these stresses, and thus, is an excellent reporter for identifying other factors in these NHR-49 dependent response pathways. GFP was tagged to the promoter of fmo-2 to create a transcriptional reporter strain. Recently, a reverse genetic RNAi (RNA interference) screen was conducted in tBOOH oxidative stress using the fmo-2 reporter strain to test the ~900 transcription factors, ~400 kinases, and ~500 transcriptional co-regulators of the worm genome, as these protein subclasses are known to play vital roles in stress response pathways. 118 triple validated hits were found. In future work, these hits will be tested for fmo-2 induction in the aforementioned NHR-49 dependent stresses and NHR-49 independent stresses (e.g. hydrogen sulfide). In turn, this will better define NHR-49 dependent stress responses by identifying additional players in each pathway, determining factors unique to certain NHR-49 controlled responses, and those common amongst all.

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Session #1 | Poster #3 Luke Enns, Undergraduate Student, University of British Columbia Supervisor: Bruce Verchere, Childhood Diseases

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

The role of type 2 diabetes risk gene peptidylglycine α-amidating monooxygenase in pancreatic insulin-secreting β-cells in the development of diabetes Luke Enns, Yi-Chun Chen, C. Bruce Verchere

Introduction: Patients with type-2 diabetes have elevated blood glucose levels that are normally regulated by insulin, a peptide hormone secreted by pancreatic beta cells in the islets of Langerhans. Recent large-scale genomic and population studies showed that humans carrying a variant form of the amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), have a higher risk of developing type 2 diabetes, associated with impaired insulin secretion from the pancreas. We aim to determine the role of PAM in insulin secretion from pancreatic beta cells and the development of diabetes. We hypothesize that deficiency of PAM in pancreatic beta cells in mice will lead to impaired insulin secretion and accelerated diabetes development.

Methods: To create a model of PAM beta cell deficiency in the face of obesity-induced insulin resistance, beta-cell specific PAM KO (βPamKO; Ins1Cre/+ x Pamflox/flox) and littermate wild-type (Wt; Ins1+/+ x Pamflox/flox) control mice were fed high-fat diet (45% fat) or control diet (10% fat) for 20 weeks, and their fasting blood glucose levels, body weight, glucose tolerance, insulin tolerance, and body mass compositions were analyzed. At the end of the study, mouse pancreata were collected for histological analyses to examine beta cell morphology.

Results: While mice receiving high-fat diet became obese and displayed increased fasting blood glucose levels, our preliminary data suggest that after 10 weeks on diet, βPamKO had comparable glucose tolerance and body weight compared to Wt mice. Upon completion of 20 weeks of high-fat diet, we hope that further metabolic study of these mice will enable a better understanding of PAM in the development of obesity-induced diabetes. Ongoing experiments include assessment of insulin secretion, histological examination of mouse pancreas (by immunostaining of pancreas sections), and electron microscopic analysis of islet beta cells. These studies should help elucidate the roles of PAM in islet function and dysfunction in diabetes.

Conclusion: Beta-cell specific deletion of PAM in mice does not result in greater glucose intolerance compared to Wt mice, however, ongoing experiments will shed light on the role of PAM in beta cell insulin secretion and islet morphology.

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Session #1 | Poster #4 Ashley Jang, Undergraduate Student, University of British Columbia Supervisor: Angela Devlin, Healthy Starts

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

Early postnatal programming of pancreatic islets by maternal exercise Hyoun Joon (Ashley) Jang, Nicha Boonpattrawong, Angela M. Devlin

Background: The theory of developmental programming suggests that risk for chronic diseases, such as type 2 diabetes, may be influenced by fetal and early postnatal environment. Studies in humans and rodents reported that obesity during pregnancy increases the risk for glucose intolerance and type 2 diabetes in the adult offspring. Exercise is recommended for pregnant women, but it is unclear whether exercise during pregnancy can improve offspring health. Previous research in the Devlin lab has found that voluntary exercise in dams during pregnancy mitigates the adverse effects of maternal obesity on male offspring glucose tolerance. Building on this work, I determined whether the effect of maternal exercise on glucose homeostasis begins during the early postnatal period.

Hypothesis: Developmental programming of pancreatic islets in offspring by maternal obesity and exercise begins during the suckling period, specifically postnatal day 7 (P7).

Methods: Female mice (dams) were fed either a control diet (10% kcal fat) or western diet (45% kcal fat) for 13 weeks to induce excess adiposity and put into cages with or without access to running wheel for voluntary exercise one week before breeding. Dams were bred with age-matched male mice. Male and female offspring were sacrificed at P7 because this is the suckling period (mice are weaned at age of 21 days), the sole source of nutrition for the mice is maternal milk, and the mice are large enough to obtain enough tissue for analyses. Tissues have been collected and 1 male and 1 female pup from each dam will be assessed. Pancreatic beta and alpha cell mass were quantified using immunohistochemistry by staining for insulin and glucagon, respectively. The effect of maternal diet and exercise on offspring outcomes were analyzed by two-way ANOVA. Results: Male offspring from exercised dams had significantly (P<0.05) larger beta cell area compared to offspring from sedentary dams. There was no effect of maternal diet or exercise on the male offspring alpha cell area or pancreatic islet density. These outcomes will also be assessed in the female P7 offspring to infer sex-specific differences in the programming of pancreatic islets by maternal diet and exercise.

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Session #1 | Poster #5 Soomin Lee, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

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

Exploring the potential for an inulin-enriched diet to delay the development of spontaneous colitis in Muc2 deficient mice Soomin Lee, Genelle Healey, Bruce Vallance

Background: Mucin (Muc)-2 is a vital component of colonic mucus, providing a key barrier between colonic luminal contents (i.e. gut microbiota and food antigens) and the underlying mucosa. Muc2 deficient (-/-) mice thus lack colonic mucus and correspondingly suffer an imbalance (dysbiosis) in their gut microbiota. The lack of a mucus barrier also increases host exposure to antigens, inducing a pro-inflammatory response that leads to the development of spontaneous colitis. Muc2-/- mice have become an important model to study the efficacy of potential interventions on colitis development. Inulin is a dietary fiber known to reduce microbial dysbiosis and stimulate the production of butyrate and anti-inflammatory cytokines. We therefore hypothesized that an inulin-enriched diet might lead to lower rates of spontaneous colitis in Muc2-/- mice as compared to a fiber-free diet.

Objective: Utilize Muc2-/- mice to investigate whether an inulin-enriched diet reduces spontaneous colitis development as compared to mice fed a fiber-free diet.

Methods: Muc2-/- mice were fed a fiber-free diet or an inulin-enriched diet (10% inulin) from weaning (3-weeks old).

The study continued until day 10, when the first mouse reached its humane endpoint. Body weight and disease activity scores (DAS) were monitored. Stool samples were collected on day 7 and 10 and cecal contents were collected on day 10.

Colon lengths were measured, and colonic tissue was collected for future histopathology scoring, cytometric bead array (CBA) and qPCR analysis. Mesenteric lymph nodes and the spleen were collected for future CBA analysis.

Results: An inulin-enriched diet led to a significantly lower DAS (p=0.0471), higher body weight (p=0.0092) and calorie intakes (p=0.0197), as well as longer colon lengths (p=0.0318) compared to fiber-free fed mice.

Conclusion: An inulin-enriched diet prevented colitis development, as compared to the rapid colitis seen in Muc2 -/mice fed a fiber-free diet. To better define the mechanisms of action, samples of stool, tissue and cecal contents were collected and stored at -80oC for future gut microbiota, pro- and anti-inflammatory cytokine, tight barrier junction and short-fatty acid analysis, respectively.

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Session #1 | Poster #6 Lindy Moxham, Undergraduate Student, University of Saskatchewan Supervisor: Michael Kobor & Kendrix Kek, Healthy Starts

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

Building a Genetic Ancestry Predictor Using DNA Methylation Data Lindy Moxham, Michael Kobor, Kendrix Kek

Early life is a sensitive period during which environmental factors, including stress and socioeconomic status, can leave a biological footprint in the form of DNA methylation. DNA methylation is a heritable epigenetic mechanism that involves the addition of a methyl group onto DNA nucleotides, altering its activity without changing its sequence. Abnormal methylation patterns are linked to a variety of human diseases.

When studying the human epigenome, a common confounder is population stratification. To avoid picking up false correlations due to population stratification, self-reported ancestry information is used to normalize study samples across a phenotype of interest. However, genetic ancestry information is often missing/complicated due to an inconsistent definition of ancestral categories or self-reporting of more than one ancestral background. The goal of our project is to develop a pan-tissue predictor that can be used when genetic ancestry information is unavailable.

To begin working on the project, a list of publicly available DNA methylation datasets was compiled. Any DNA methylation datasets that used whole blood as the tissue and had ancestry as one of the variables were included. After compiling an extensive list, it was determined which datasets had genotyping data. The data was cleaned and formatted in preparation for analysis, and different methods were compared that had been previously used to build predictors of ancestral background using DNA methylation.

As we continue to build and refine the predictor, different tissues besides whole blood will be incorporated. After building and refining the training dataset, we will move on to validating the model using a validation set. Once the model has been created, we will use a testing set to provide an unbiased evaluation of the final model fit on the training dataset. Once everything is complete, we will have a predictor that will accurately predict the ancestral background of anyone using any tissue provided, helping us and other scientists to learn more about the epigenome and the effect of different social factors on our health.

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Session #2

CLINICAL, POPULATION HEALTH & HEALTH SERVICES Moderator: Dr. Emily Schaeffer Participants: Azim Ahmed Claire Cheung Bob Hoogenes Abhay Katyal Katherine Ketchum Jennifer Krentz Matt Sha Watch Presentations Online: Thursday, July 30 | 9:00 am www.bcchr.ca/posterday

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Session #2 | Poster #7 Azim Ahmed, Undergraduate Student, University of British Columbia Supervisor: Tom Blydt-Hansen, Childhood Diseases

The Associations of Exercise and Contemporaneous Factors transplant with Height-Adjusted Lean Body Mass in Pediatric Kidney Transplant Patients Azim Ahmed, Tom Blydt-Hansen, Anita Cote

Background: Lean body mass (LBM) has been shown to be associated with numerous health benefits in various populations, including the kidney transplant (KT) population. Due to both uremic and non-uremic factors, kidney transplant recipients are expected to have lower LBM, which may predispose them to co-morbidity, frailty, and a lower quality of life. Physical activity has numerous health benefits and may play a role in the accrual of LBM. Studies assessing factors associated with post-transplant LBM, specifically height-adjusted LBM (ht-LBM) are limited. The aim of this study was to assess ht-LBM levels in the pediatric population and identify baseline and contemporaneous factors that are associated with ht-LBM, determine the effects of exercise on ht-LBM, as well as explore changes that occur in ht-LBM before and after transplantation.

Methods: A retrospective cross-sectional review was performed on 46 pediatric kidney transplant patients, and a longitudinal review was performed on 21 patients which had multiple ht-LBM data points and 11 patients with pretransplant and post-transplant data points. Ht-LBM was measured using dual energy x-ray absorptiometry (DXA) scans, while exercise levels were measured using physical activity questionnaires (PAQ) for both children and adolescents.

Results: Kidney transplant recipients were 16.00 (12.25, 17.00) at the time of completing their most recent DXA scan.

Mean ht-LBM was 15.08 ÂŹÂą2.48 kg/m2 and there were no significant differences in ht-LBM between genders. Ht-LBM was associated with age at time of transplant (r=0.48, p<0.01), age at time of scan (r=0.63, P<0.01), PAQ (r=0.49, p-0.047) as well as inversely associated with annualized eGFR decline (p=-0.44, p<0.01). A significant difference was observed between the earliest and the most recent post-transplant ht-LBM. Conclusions: Individuals who exercise more, have higher ht-LBM and ht-LBM may influence kidney function in the pediatric kidney transplant population.

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Session #2 | Poster #8 Claire Cheung, Undergraduate Student, University of British Columbia Supervisor: Pascal Lavoie, Healthy Starts

Congratulations to Claire on receiving a BC Children’s Hospital Research Institute Summer Studentship & UBC Faculty of Medicine Summer Studentship

SARS-CoV-2 Seroprevalence in the Greater Vancouver Area

Claire Cheung, Abdelilah Majdoubi, Christina Michalski, Sarah Dada, Jean Gelinas, Disha Metha, Sarah O’Connell, Sandeep Napala, Matthias Görges, Adrian McDermott, Pascal M Lavoie Background: Declared a global pandemic on March 11, 2020, the coronavirus disease 2019 (COVID-19) has resulted in over 12.4 million cases and over 557,000 deaths worldwide. Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease presents with varying levels of severity, with the majority of infections being mildly symptomatic or completely asymptomatic. Such cases often go unscreened, therefore underestimating the true number of infections. Serological tests have been used to estimate local rates of seroconversion (the presence of antiSARS-CoV-2 antibodies in blood); in various populations of the USA, Europe, and Asia, the reported seroprevalence ranges from 0.26% to 24.4%. To our knowledge, there are currently no data for Canada.

Objective: To determine the SARS-CoV-2 seroprevalence in a subset of Greater Vancouver.

Methods and Results: Our cohort consisted of the first 276 non-symptomatic participants to respond to a recruitment email sent to staff at BC Children’s and Women’s and Surrey Memorial Hospital, as well as members of the Healthy Starts theme at BCCHR. Three additional PCR-confirmed convalescent COVID-19 cases were added to this analysis as positive controls. Blood sampling was done between May 17 and June 19, 2020. Metadata (e.g. participant’s age, gender, occupation, COVID-19 history) were obtained through a questionnaire. Antibodies against proteins from SARS-CoV-2, SARS-CoV-1, and four common human coronaviruses were measured. Six individuals displayed high antibody levels against SARS-CoV-2 proteins, five of which had previously tested PCR positive (including the controls); the remaining seroconverted participant was asymptomatic. Excluding the positive controls, the seroprevalence of this cohort was determined to be 1.1%. Mean duration of antibodies was 80 days (range: 57 to 100 days). Approximately one-third of participants displayed low detectable levels of antibodies against one of four SARS-CoV-2 antigens and also aboveaverage levels of antibodies against common coronaviruses, suggesting potential cross-reactivity between these antibodies.

Conclusion: The seroprevalence of 1.1% in our cohort agrees with reports from other regions of the world, though our small sample size and non-random study population limits generalization. Further studies will evaluate both the potential cross-reactivity and neutralizing capacity of these anti-SARS-CoV-2 antibodies.

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Session #2 | Poster #9 Bob Hoogenes, Medical Student, University of British Columbia & University of Amsterdam Supervisor: Janice Eng

COVID-19 and spinal cord injury: clinical presentation, clinical course and outcomes: A rapid review Bob Hoogenes, Matthew Querée, Andrea Townson, Rhonda Willms, Janice Eng

Introduction: The COVID-19 pandemic is a rapidly evolving worldwide phenomenon. We are swiftly gaining knowledge of the clinical characteristics and risk factors in the able-bodied population, but for people with spinal cord injury (SCI) that information is still lacking. Presenting symptoms may be different and additional risk factors may be present for severe COVID-19 due to secondary health conditions specific to SCI such as difficulty clearing airways, respiratory insufficiency, thermodysregulation, and an altered immune response. Known risk factors for severe COVID-19, such as obesity, cardiovascular disease and metabolic syndrome also disproportionally affect people with SCI. Objective: To investigate the clinical presentation, course and outcomes of COVID-19 in people with SCI and to identify risk factors for severe COVID-19 disease and mortality in people with SCI. Methods: A comprehensive search (rapid review) was performed of the English literature (MEDLINE, Embase, CINAHL, CENTRAL and JBI Evidence Based Practice Database), the Spanish and Portuguese literature (SciELO, LILACS, Redylac, E-revistas, Imbiomed and Google Scholar) and the Chinese literature (Google Scholar and Chinese Medical Journal Network) using the keywords “spinal cord injury” or “SCI” and “COVID-19”, “SARS-CoV-2” or “coronavirus”. The first author screened 100 abstracts (BH) and two reviewers (BH,MQ) assessed 11 articles for full-text eligibility. Four studies were included: one case-series and three case-reports.

Results: We identified a small number of studies, all descriptive and with a small total number of patients (N = 10). Most patients had fever (9/10), other common symptoms include dyspnea (5/10), cough (4/10) and fatigue (4/10) . SCI specific secondary health conditions data was missing. Eight patients showed abnormalities on imaging. Nine out of 10 patients survived, no severe adverse events were reported, and no patient required mechanical ventilation or ICU admission.

Conclusions: Information on COVID-19 in people with SCI is limited. At present, SCI patients do not show a high percentage of severe COVID-19 disease and mortality. Due to the lack of information, we could not draw any conclusions on prognostic factors.

Future directions: More data on COVID-19 in SCI is needed. Future studies should be as inclusive as possible in reporting SCI specific health conditions and outcomes.

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Session #2 | Poster #10 Abhay Katyal, Undergraduate Student, University of Toronto Supervisor: Shubhayan Sanatani, Childhood Diseases

Alterations of the Autonomic Nervous System in Adolescents with Unexplained Palpitations Abhay Katyal, Nolan Lee, Sonia Franciosi, Victoria Claydon, Kathryn Armstrong, Shubhayan Sanatani

Background: Palpitations are the sensation of irregular, rapid, or forceful pulsations in the chest, and are a common complaint amongst adolescents. Both branches of the autonomic nervous system (ANS) have been shown to have significant cardiac effects including modulating heart rate, conduction, and rhythm. In abnormal hearts such as those with inherited arrhythmia, sympathetic drive is an effective driver for arrhythmias in both atria and ventricles, conceivably by increasing dispersion of repolarization. On balance, parasympathetic action has been shown to act as a proarrhythmic in atria and antiarrhythmic in ventricles through opposing effects on an effective refractory period in the two-chamber types. Knowing that the autonomic nervous system can generate and modulate arrhythmias and that palpitations are often a symptom of an arrhythmia, we postulate that the autonomic nervous system may play a part in patients with unexplained palpitations.

Objective: The aim of this pilot study is to examine the potential role of the ANS in generating and modulating palpitations which remain unexplained after clinical review including confirmation of normal sinus rhythm.

Methods: Participants are asked to wear a 24 hour Holter monitor, which records their heart rate variability (HRV). We would then compare the HRV between adolescents with unexplained palpitations and healthy controls. Participants are also scheduled for autonomic testing, which will allow us to then investigate cardiovascular autonomic reflexesâ&#x20AC;&#x2122; responses to a variety of physiological stimuli through analysis of changes in arterial pressure and heart rate.

Results: This study is ongoing. It is hoped that the results of this study will ultimately aid in the diagnosis and management of autonomic impairment in children and adolescents, and play a role in the illum­ination of the role of the autonomic nervous system in unexplained palpitations.

Significance: This study is significant as it will add to the lack of literature on the relationship between HRV and palpitations in the pediatric population. Clinical significance could come from potentially linking abnormalities in HRV and autonomic testing with adolescents experiencing palpitations despite normal sinus rhythm, offering an explanation of such palpitations for these patients and their families.

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Session #2 | Poster #11 Katherine Ketchum, Medical Student, University College Dublin Supervisor: Harold Siden, Brain, Behaviour & Development

Congratulations to Katherine on receiving a CHILD-BRIGHT Network Summer Studentship

Optimizing the Management of Pain and Irritability in Children with Severe Neurological Impairment Hal Siden, Tim Oberlander, Bruce Carleton, Tammie Dewan, Vithya Gnanakumar, Liisa Holsti, Julia Orkin, Christina Vadeboncoeur Severe neurological impairment (SNI) can result from a variety of conditions, such as hypoxic-ischemic encephalopathies, traumatic brain injuries and childhood neurodegenerative diseases. Children with SNI are typically non-verbal, nonmobile and have limited cognitive abilities. In addition to this, many children with SNI experience pain-like sensations on a daily basis. Nociceptive-inflammatory pain, which is pain one would feel from a broken bone or burned skin, does not entirely explain the unpleasant sensations witnessed in these children. Therefore, researchers use the term Pain and Irritability of Unknown Origin (PIUO).

When working with children with SNI, we cannot make the same assumptions about pain signals as we might with a typical child, and the process of investigating PIUO lacks standardization. To address these challenges, our team created the PIUO Pathway, an integrated clinical pathway for assessing and treating PIUO. The PIUO Pathway is a stepwise process that begins with history-taking and physical examination and progresses to screening tests and pharmacological intervention. The current study was designed to judge the efficacy of this pathway.

We used a waitlist-controlled RCT design, with children randomized to PIUO Pathway or waitlist (standard care) treatment arms. We used the Washington Group Extended Question Set on Functioning (WGES-F) and adapted this into a two-question Pain Survey for parents and caregivers to complete throughout the trial. Participants were deemed a success if they scored within the two lowest categories of the Pain Survey (little or no pain) on two consecutive visits.

This trial is ongoing, but preliminary results are promising. Of the 19 children who have completed the PIUO Pathway, five had their source of pain identified, of which four were successfully treated and their PIUO resolved. The remaining participant is awaiting treatment. Many of the children who complete this pathway still have PIUO. To address this, our team plans to conduct a trial investigating the efficacy of gabapentin in relieving PIUO in children with SNI.

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Session #2 | Poster #12 Jennifer Krentz, Undergraduate Student, Simon Fraser University Supervisor: Tonia Nicholls, Brain, Behaviour & Development

Congratulations to Jennifer on receiving a BC Mental Health and Substance Use Services Studentship & Derek Eaves Student Research Grant

Attendance to Risk Factors and Protective Factors in Reports for NCRMD Patients Jennifer R. Krentz, Tonia L. Nicholls

Background: In Canada, Review Boards (RBs) determine dispositions (custody, conditional discharge, absolute discharge) for individuals found Not Criminally Responsible on Account of Mental Disorder (NCRMD). To do so, RBs rely on expert reports written by the accused’s treatment team that should assess risk of violence using empirically supported risk factors and protective factors, as professional guidelines recommend attending to both within assessments. Previous research suggests experts often exclude empirically supported risk-relevant items from their reports; however, few studies have examined the inclusion of protective factors in experts’ reports.

Objective: Our aim was to assess if there was a difference in the mean number of risk factors mentioned versus the mean number of protective factors mentioned in experts’ reports submitted to the RB. As prior research suggests protective factors are rarely mentioned in experts’ reports, we hypothesized more risk factors than protective factors would be mentioned.

Methods: Archival file information was reviewed for 68 NCRMD patients who were residing at the Forensic Psychiatric Hospital in Coquitlam, B.C. The Short-Term Assessment of Risk and Treatability (START), a risk assessment tool empirically supported for use with forensic patients, was used to measure both risk factors (START Vulnerabilities) and protective factors (START Strengths). Research assistants examined experts’ reports to the RB for the first hearing following the NCRMD verdict to code whether each START Vulnerability and START Strength was mentioned or not mentioned.

Results: Results showed significantly more START Vulnerabilities (M = 15.54, SD = 3.58, range = 2-20) were mentioned than START Strengths (M = 11.65, SD = 4.67, range = 0-20; t = 7.36, 95% CI [2.84, 4.95], p < 0.0005, ES = 0.89) in RB reports.

Implications: As hypothesized, significantly more risk factors than protective factors were mentioned within experts’ reports. These results suggest that, contrary to best practice guidelines that require assessors to conduct balanced assessments, experts inadequately considered empirically supported protective factors that facilitate patient-centered care and may serve to prevent risk over-estimation. Due to the minimal research conducted in this area, as well as the interprovincial differences across forensic systems, similar studies should be conducted in other provinces.

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Session #2 | Poster #13 Matt Sha, Undergraduate Student, University of British Columbia Supervisor: William T. Gibson, Childhood Diseases

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

Genetic Characterization of Rare Overgrowth Syndromes Matthew Sha, Sharri S. Cyrus, William T. Gibson

Rare overgrowth and intellectual disability (OGID) syndromes manifest dysmorphic facial features, excessive growth, and developmental delay. Our lab has assembled a cohort of 86 patients with OGID syndromes; to date, 37 of these patients have been solved (i.e. found to have a known or novel diagnosis). Among the unsolved patients, 18 researchgrade exomes/genomes were collected for rare variant analysis. Inclusion criteria for our cohort require 2 out of 3 of the following: height ≥+2SD, head circumference ≥+2SD, body-mass index ≥+3SD, along with at least 1 of the following: intellectual disability, facial dysmorphism, congenital malformations, or any tumour onset < 30 years. Identification of de novo coding mutations in epigenetic regulators has defined several new OGID syndromes. We hypothesized that reanalysis of rare variants lists among our OGID cohort in light of recent syndromic descriptions would solve additional patients and might also lead to novel gene-disease pairings.

I first compiled genes from diagnostic laboratory panels for overgrowth and macrocephaly, then reviewed the literature from January 2018 to present in search of genes newly implicated in OGID syndromes. Fifty-one genes met these criteria, most of which encoded epigenetic regulators. I have reviewed 6 out of 18 exomes to date; so far, all variants identified in these candidate genes were predicted to be benign. However, as rare de novo variants cause OGID syndromes, I filtered each exome to investigate heterozygous variants with a minor allele frequency of 0 that were also predicted to be damaging/deleterious by the computational tools PolyPhen and SIFT. Filtration reduced the number of variants in each exome from ~20,000 to ~100 variants per exome for further analysis. CADD scores will then be applied to each variant, and those with a CADD score of > 25 in epigenetic regulators will be prioritized for validation in the proband using Sanger sequencing, then repeated in the parents to determine if the variant is de novo or inherited. Using the aforementioned strategy, I will further interrogate the remaining 12 exomes.

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Session #3 BASIC SCIENCE

Moderator: Dr. Martina Sundqvist Participants: Danielle Cohen Jennifer Jiang Min Jung Kim Lise Rutherford Rene Tandun & Enoch Yau Zehan Zhou Watch Presentations Online: Thursday, July 30 | 10:45 am www.bcchr.ca/posterday

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Session #3 | Poster #14 Danielle Cohen, Undergraduate Student, Western University Supervisor: Angela Devlin, Healthy Starts

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

Sex-Specific Effects of Maternal Folic Acid Supplementation on Pancreatic Alpha and Beta Cell Mass in Fetal Offspring Danielle Cohen, Ei-Xia Mussai, Angela Devlin

Folate is an important B-vitamin for proper development, including the prevention of birth defects. Women with pre-gestational obesity (BMI ≥30kg/m^2) are at a higher risk of having a birth defect-affected pregnancy and are recommended to take up to 5mg/day folic acid. There is concern that high folic acid supplementation during pregnancy may have adverse consequences on the offspring’s metabolic health. The aim of this study was to determine the effect of maternal folic acid supplementation on fetal offspring pancreatic alpha and beta cell mass. These cells are responsible for the production of glucagon and insulin, respectively, and disturbances during development could have long term negative impacts on the risk for type 2 diabetes.

Female (C57BL/6J) mice were fed a control (10% kcal fat) or western (45% kcal fat) diet, either with (10mg/ kg diet; CDF, WDF) or without (2mg/kg diet; CD, WD) supplemental folic acid. The western diet was used to induce excess adiposity and glucose intolerance. Females were bred at 13 weeks post-weaning. Fetal pancreata were collected at gestational day 18.5 and processed for immunohistochemical analysis.

The fetal pancreas displayed sex-specific differences. Males from WDF fed dams had decreased beta cell mass and fewer large islets compared to those from CDF fed dams (p<0.05). Females from WDF fed dams had increased beta cell mass compared to those from CDF fed dams (p=0.14), however, showed no differences in islet density or size distribution. Males from CDF fed dams had increased alpha cell mass (p=0.078) compared to those from WDF fed dams while females from CDF fed dams had decreased alpha cell mass (p<0.05) compared to females from WDF fed dams. Sample analysis is ongoing.

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Session #3 | Poster #15 Jennifer Jiang, Undergraduate Student, McGill University Supervisor: Dan S. Luciani, Childhood Diseases

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

Applying Super Resolution Imaging by Radial Fluctuations (SRRF) for Analysis of Mitochondria-Lysosome Interactions in Living Beta Cells Jennifer Jiang, Dan S. Luciani

Beta cells are insulin-secreting cells that regulate blood glucose, and beta cell failure can lead to diabetes, a disease that impacts over 400 million people in the world. Mitochondria are organelles that regulate cellular respiration, and lysosomes recycle cellular waste. Recently, transient mitochondria-lysosome interactions have been observed in yeast and mammalian cells, but little is known about the functions of these contacts. We hypothesize that they regulate beta-cell metabolism and thereby also insulin secretion. To study mitochondria-lysosome interactions by fluorescence microscopy we must be able to accurately identify and resolve the organelles. The diffraction limit of conventional fluorescence microscopy is approximately 200 nm, but mitochondria and lysosomes can be as small as 100 nm.

Super resolution techniques such as STED and SIM can achieve resolutions down to 50 nm, but these methods are not readily available to most laboratories and generally require illumination intensities that cause photodamage to living cells. The goal of my summer research project is to overcome these limitations by using a novel computational approach called Super Resolution Imaging by Radial Fluctuations (SRRF) to analyze images of beta-cell mitochondria and lysosomes. SRRF can generate super resolution images using conventional confocal or widefield microscopes and low-intensity illumination that circumvents phototoxicity. To date, I have installed the NanoJ- SRRF software plugin on our labâ&#x20AC;&#x2122;s image analysis workstation and applied it to downloadable test data with the goal of understanding and optimizing parameter values for different types of images. To get a quantitative measure of SRRF accuracy, I have used another software package, NanoJ-SQUIRREL, to generate correlating error maps between the original confocal image and the SRRF-corrected image. The next step in these optimizations will be to use SQUIRREL to quantitatively analyze how SRRF parameter settings affect the accuracy of the resulting super resolution images. Finally, I will apply SRRF to beta-cell mitochondria-lysosome time-lapse images and evaluate if this improves our ability to accurately identify and track contacts between the organelles. This project will help us understand how improvement in resolution affect the detection of inter-organelle contacts and shed light on the function of these in insulin-secreting pancreatic beta-cells.

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Session #3 | Poster #16 Min Jung Kim, Undergraduate Student, McMaster University Supervisor: Chinten James Lim, Childhood Diseases

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

BH3 Profiling as a Tool for Precision Treatment in Pediatric Oncology Min Jung Kim, Pascal Leclair, Chinten James Lim

Specific biomarkers are used to assign precision therapy; however, those developed for the adult patient population are often poor predictors of clinical response in pediatric patients. Furthermore, children who initially respond to standard-of-care treatment are not evaluated for precision therapy at diagnosis; therefore when a relapse occurs, they have limited time to undergo profiling and identify suitable drugs which target their specific cancer type. However, conventional prospective drug screening requires several days, resulting in loss of crucial time and risking significant disease progression. Therefore, there is an urgent need for a more efficient and targeted approach for evaluating drug sensitivities and informing treatment options for pediatric cancer patients.

One potential tool being examined for drug screening is BH3 profiling. The assay can be used to help identify suitable drugs which target the patient’s cancer cells with a fast turnaround time, generating results within 16 hours. The BH3 profiling assay allows for evaluation of the cancer cell’s dependence on anti-apoptotic B cell leukemia/lymphoma-2 (BCL-2) family proteins. The BCL-2 family of proteins are key mediators of programmed cell death and the mitochondrial pathway of apoptosis. Therefore, identification of these cancer-specific apoptotic blocks can allow for effective targeting of tumour cells.

The BH3 profiling assay employs BH3 domain peptides from BCL-2 protein family members as antagonists of protein function in order to determine how reliant the cell is on each anti-apoptotic protein for survival. In our assay, cells were incubated with drug agents, and cytochrome c release was measured by flow cytometry after incubation with BH3 peptides. BH3 profiling will be conducted on both ALL cell lines and xenograft-expanded primary ALL cells to evaluate sensitivity of the cancer cells to chemotherapeutic agents and identify drugs that are optimized for the cancer cell’s characteristics. Thus, the study aims to optimize BH3 profiling in ALL cells as a comprehensive and efficient drug screening process allowing for earlier identification of targeted treatment strategies.

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Session #3 | Poster #17 Lise Rutherford, Undergraduate Student, Western University Supervisor: Suzanne Vercauteren, Childhood Diseases

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

Assessment of Single Cell Tissue Processing Methods

Lise Rutherford, James Lim, Jonathan Bush, Veronica Lee, Vi Nguyen, Suzanne Vercauteren Storage methods for tissue collected from cancer patients for research purposes at the BC Childrenâ&#x20AC;&#x2122;s Hospital BioBank currently involves preserving the sample in large chunks as either fresh frozen or formalin fixed. However, tissue stored in this way is only suitable for some research uses, such as genomic and histologic studies, and cannot be reanimated for in vivo uses such as xenografting and cell cultures. Although fresh tissue can also be used for transplantation, there is only a short period of time after receiving the tissue for it to be effectively grafted or cultured. As well, methods for cryopreservation of chunks of tissue has very low viability due to the cryoprotectantâ&#x20AC;&#x2122;s inability to penetrate through to the inner layer of cells. Our goal is to process tumour tissue down to single cells to allow for successful cryopreservation and use in future research involving functional assays such as xenografting and culturing of cells. We collected tissue from newly diagnosed cancer patients and processed them using four different methods: aggressive dissociation, gentle dissociation, dissociation using ficoll and cutting into 1mm strips. Tissue from each of these four methods was then frozen and stored in liquid nitrogen for at least one week. We are currently working on xenografting samples using a CAM assay, as well as growing cell cultures using samples from all four methods. Tissue processed by each method will be compared based on whether the transplant or culture was successful, and if successful, we will compare daily growth rate and health of the newly grown cells. In the end, we hope to find the most effective and efficient single cell tissue processing method that the Biobank can use to store tumour tissue for future research involving functional assays.

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Session #3 | Poster #18 Rene Tandun & Enoch Yau, Undergraduate Students, University of British Columbia Supervisor: Theodore Steiner, Childhood Diseases

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

TUDCA and Tr1 cell supernatants as potential therapeutics to ameliorate intestinal epithelial cell ER stress Rene Tandun, Enoch Yau, William D. Rees, Theodore S. Steiner

Inflammatory bowel disease (IBD) pathogenesis is associated with a number of cellular and molecular perturbations, including altered inflammatory chemokine and cytokine production, microbial community dysbiosis, and risk-conferring genetic polymorphisms that affect the function of intestinal epithelial cells (IECs). IECs rely on danger signals such as extracellular ATP and endoplasmic reticulum (ER) stress to have a coordinated and robust immune response to pathogens. ER stress in IECs activates the unfolded protein response (UPR), a cellular protection pathway that allows ER stressed cells to return to homeostasis. However, an overactive UPR has been shown to lead to IBD. Recent evidence suggests that Type 1 regulatory (Tr1) cells and the pharmacological inhibitor Tauroursodeoxycholic acid (TUDCA) may have a protective role against ER stress in IECs, although the exact mechanisms of how they ameliorate ER stress, as well as the impact on downstream adaptive immune responses remain largely unknown.

We propose that Tr1 supernatant and TUDCA treatments may have a protective effect on cellular ER stress by dampening the UPR, and decreasing flagellin-induced inflammation. Caco-2 cells were pre-treated with Tr1 cell supernatants or TUDCA prior to thapsigargin (Tg) (ER stress inducer) treatment. Subsequently, UPR markers GRP78, CHOP, and Xbp1s/us, were measured via qPCR, and IL-8 and CCL20 chemokine levels in response to TLR agonist flagellin (FliC) were measured via ELISA. Caco-2 cells pre-treated with Tr1 supernatants 1 hour prior to Tg treatment did not alter mRNA expression in the UPR pathway, but partially reversed ER-stress-mediated changes in IL-8 and CCL20 expression. Caco-2 cells pre-treated with 100mÎ&#x153;- 2ÎźM TUDCA for 2-6 hr prior to overnight Tg treatment and FliC stimulation showed similar protective effects. Collectively, these data suggest that TUDCA or Tr1 cells could be used as potential therapeutics in mitigating ER stress and inflammation in IBD patients.

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Session #3 | Poster #19 Zehan Zhou, Undergraduate Student, Harvard University Supervisor: Dan Goldowitz, Brain, Behaviour & Development

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

Chromosome 2 as a Contributor to Whole Cerebellar Volume in P30 Mice Miguel Ramirez, Zehan Zhou, Dan Goldowitz

Background: The cerebellum, and defects thereof, are involved in the etiology of several neural disabilities. The development of the cerebellum, encoded by specific genes, can offer explanations behind the disease states. We hypothesize that if a significant Quantitative Trait Locus (QTL), a region of DNA that is associated with a trait, is found and linked to a phenotypic trait, then that could indicate a gene influential to cerebellar development.

Methods: Cerebellar sections from 65 different mouse strains, including the parental C57BL6 and DBA2 mouse strains, and 63 recombinant inbred strains were taken across different ages. Cells from every 30th section were counted to gain an estimate about the cellular composition, density, and volume. All the data were recorded into an Excel file and QTLs were calculated via processing by GeneNetwork, an open access online database which contains the strain information of both parents. LRS (likelihood ratio statistics) were calculated to see which loci are significant. Upon finding a significant locus, all the genes in that area would be compared to existing expression data so as to check for their phenotypic expression via the VLookup function.

Results: We ran the QTL analysis on the whole cerebellar volume at E12, E15, and P30, the rhombic lip at E15, the External Granule Layer at E15, the Inner Granule Layer at P30, the Purkinje Cell layer at P30, and the Molecular layer at P30. The only significant LRS values were seen on Chromosome 2 for the whole cerebellum volume at P30. There is a good probability that one or more genes in the region between 125.5 to 131.5Mb contribute to the observed trait.

Future Directions: We plan to engage in further staining and sectioning. We seek to obtain more data on embryonic development of the inner granule layer, the Purkinje cell layer, and the molecular layer, and data on the postnatal development of the external granule layer. We also aim to conduct qrtPCR for genes of interest to focus on the best candidate genes. This would lead to subsequent work in producing Knockout mice.

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Session #4

CLINICAL, POPULATION HEALTH & HEALTH SERVICES Moderator: Dr. Katelynn Boerner Participants: Risa Fox Gurman Khera Salina Kung Rebecca Lim Evelyne Piret Kathryn Reilly Amir Wachtel Watch Presentations Online: Thursday, July 30 | 10:45 am www.bcchr.ca/posterday

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Session #4 | Poster #20 Risa Fox, Undergraduate Student, University of British Columbia Supervisor: Janice Eng

Effects of epidural stimulation to restore meaningful function after spinal cord injury: A systematic review Risa Fox, Janice Eng, Matthew Queree

Introduction: Epidural spinal cord stimulation is a neuromodulation technique that can evoke sensorimotor responses below the level of lesion in spinal cord injury. However, due to the invasive nature of this procedure and the low number of SCI research participants, there have yet to be many studies examining the effects of epidural stimulation on spinal cord injury populations. This review aims to assess the efficacy of epidural stimulation in restoring meaningful function after SCI, particularly in the areas of bladder, circulatory, motor, respiratory, spasticity, and spinal cord vulnerability.

Methods: A search for relevant studies was conducted electronically through the following databases: EMBASE, MEDLINE, CINAHL, and PsycINFO. The search was carried out from June 2019 to July 2020, identifying studies published between 1980-2020 that investigated the use of epidural stimulation following SCI. The search terms used were a combination of terms used to describe “epidural stimulation” and “spinal cord injury”. Studies were excluded if: (1) analyzed non-human subjects (2) were not published in English (3) were conference abstracts or scoping reviews (4) were published before 1980 (5) had a N < 2. The data extracted included: population characteristics, study design, characteristics of the intervention, outcome measures, and relevant results.

Results: The search initially resulted in 2928 papers, of which 17 studies and 4 systematic reviews were included in the systematic review. The total SCI sample size comprised of 126 persons. All studies applied stimulation from the lower cervical to upper thoracic levels, most commonly in a 16-electrode array. Epidural stimulation was reported to provide positive effects in treating bladder, circulatory, motor, respiratory, spasticity, pain, and spinal cord vulnerability, with minimal adverse effects.

Conclusions: Epidural stimulation has been reported to improve outcomes in some participants’ function in bladder, movement, spasticity, and pain. However, more research should be conducted to further evaluate the efficacy of this treatment, particularly in areas not related to motor function, to further understand its applicability in a clinical setting.

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Session #4 | Poster #21 Gurman Khera, Undergraduate Student, University of British Columbia Supervisor: Kevan Jacobson, Childhood Diseases

Infliximab Dose Optimization During Maintenance Therapy In Children With Inflammatory Bowel Disease Gurman Khera, Felipe Briglia, Sally Lawrence, Alice Foster, Evelyn Briglia, Kevan Jacobson

Background: Inflammatory bowel disease (IBD) activity has been monitored based on symptoms and disease activity indices. Recently a “treat to target” strategy was reported to be associated with better outcomes. Optimizing biologic therapy based on Therapeutic Drug Monitoring (TDM) is becoming standard of care for management of IBD patients.

However, there are limited data on serum infliximab (IFX) trough levels in Pediatric IBD patients on maintenance therapy.

Aims: Evaluate the impact of IFX dose optimization during maintenance therapy (after dose #4) in children.

Methods: A chart review was performed. Demographics, CRP, ESR, albumin, PUCAI/PCDAI were recorded along with low baseline IFX trough levels (< 5 μg/mL) and trough levels following dose adjustments. Trough level requests were determined by clinical and/or biochemical loss of response. Comparisons were made between pre- and post- dose adjustment data. Analysis included t-test and x2 and a p<0.05 was considered significant.

Results: 151 patients who received their first IFX infusion between Nov/08 and Jan/18 were reviewed. 51 patients (40 Crohn Disease (CD) and 11 Ulcerative Colitis (UC)) met the inclusion criteria. Median age at diagnosis was 10.6 years; Paris classification CD: A1b (75%) L3 (55%) L2 (37.5%) L1 (5%) L4a (17.5%) L4b (12.5%) and B1 (92.5%), UC: E4 (63.6%) E3 (18.2%) and E2 (18.2%). Perianal disease in 37.5% of CD patients. Concomitant therapy in 78.5% of patients (Methotrexate 41.2%, Azathioprine 37.3%). The median number of IFX doses at baseline was 17, median dose (mg/kg) 8.5 with a dosing interval of 8 weeks. Baseline trough level was 1.9. Request for IFX trough level was based on clinical (29.4%), biochemical (33.3%), and both clinical and biochemical findings (37.3%). 98% of patients had dose adjustments with a 5.8-fold increase in trough levels, 21% incremental increase in remission rates, and 10% reduction in disease activity.

Conclusions: Optimizing IFX therapy through TDM during maintenance is beneficial for children with IBD. A higher rate of remission was achieved following dose adjustments in patients with low trough levels.

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Session #4 | Poster #22 Salina Kung, Medical Student, University of British Columbia Supervisor: Vilte Barakauskas, Healthy Starts

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

Pregnancy and Pediatric Reference Intervals for Safe Medicine (P2RISM) Salina Kung, Yasmin Derayat, Ann Tran, Alastair Williams, Karla Muyzer, Catherine Leung, Michelle Dittrick, Ashton Ellis, Wee-Shian Chan, Kate Chipperfield, Vilte Barakauskas

Background: Laboratory tests guide decisions about maternity care during and after pregnancy. Comparing results with a range of values called the reference interval (RI) derived from a healthy population enables the interpretation of test results. RIs have been developed for non-pregnant populations but are not appropriate for interpreting maternal and neonatal blood tests in the early postpartum period due to considerable physiological changes occurring after delivery.

A pilot postpartum RI study at BC Women’s Hospital (P2RISM) is being conducted to establish and confirm RIs for mothers and newborn babies by collecting and analyzing blood samples. Evaluation of the study process will inform the development of a sustainable and patient-centered recruitment process.

Objectives: This project is an extension of the P2RISM study and aims to identify the challenges and facilitators related to the recruitment of mothers and newborn babies to the study from the perspectives of the participants, researchers and healthcare staff.

Methods: Mothers with a low-risk, singleton pregnancy delivering at BC Women’s Hospital were invited to participate in the P2RISM study and complete an online survey about their reasons for accepting or declining study participation.

Phlebotomists will be invited to complete an online questionnaire about the study blood collection process. Researchers, hospital staff and healthcare providers involved with P2RISM will be invited to a phone interview to explore factors affecting recruitment efforts.

Preliminary Results: 73 mothers have been recruited to date and 68 mothers completed a survey about their reasons for participating. The majority of consented mothers participated to “help healthcare move forward” (89.7%). Following study completion, 41 mothers completed a follow-up survey. 34 out of 41 mothers suggested ways to improve participation in future RI studies, including communicating the importance of the study (50%) and reducing hospital visits (50%). Out of 111 mothers who declined study participation, 41 completed a decline survey. A commonly reported reason for declining study participation was being “too tired, busy or overwhelmed” (43.9%).

Significance: The results will inform the development of a recruitment process that will improve the experience and engagement of mothers, newborn babies, researchers and healthcare staff in RI studies. Results will be summarized in an engagement plan developed in collaboration with patient partners.

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Session #4 | Poster #23 Rebecca Lim, Undergraduate Student, University of British Columbia Supervisor: Julie Bettinger, Healthy Starts

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

Knowledge and attitudes of children and adolescents towards vaccines: A systematic review Rebecca Lim, Hana Mijovic, Julie Bettinger

Background: Vaccinations have resulted in the eradication of diseases that were once thought to be incurable, such as smallpox. Despite this, many individuals doubt the benefits of vaccines. An individual’s knowledge and attitudes towards vaccinations are shaped by a variety of information sources, including healthcare professionals and the media. In the early stages of a child’s life, parents make decisions on behalf of their children regarding their vaccinations. Literature reviews have been performed to determine parents’ and caretakers’ attitudes towards vaccines. However, although they will eventually have to make their own decisions regarding vaccinations, little is known about children’s and adolescents’ attitudes towards vaccinations. Thus, this systematic review of qualitative studies will contribute to a better understanding of what is currently known about the beliefs and attitudes that children and adolescents have towards vaccines.

Aim: Describe children and adolescents’ knowledge and attitudes towards vaccines.

Methods: MEDLINE, EMBASE, and CINAHL were searched for relevant literature. Any qualitative or mixed-method study that reported on the knowledge and attitudes of children and adolescents (aged 5-18) towards vaccines were included.

Articles were screened by abstract and title, then fully assessed for eligibility, by two reviewers. Discrepancies were resolved through discussion with the help of a third reviewer. Studies meeting the inclusion criteria were included in the final systematic review. Data will be extracted from the published literature and recorded on a standardized form.

Next steps: Currently, we are in the title and abstract screening stage. This study will determine gaps in knowledge regarding children’s and adolescents’ vaccine knowledge and attitudes.

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Session #4 | Poster #24 Evelyne Piret, Undergraduate Student, McGill University Supervisors: Gina Ogilvie & Beth Payne, Healthy Starts

Acceptability and side effects of thermal ablation for the treatment of cervical precancerous lesions in low- and middle-income countries: a systematic review Carolyn Nakisige, Evelyne Piret, Beth Payne, Gina Ogilvie

Background: Cervical cancer disproportionately affects women in low- and middle- income countries (LMICs) who represent 91% of deaths due to a lack of widespread prevention programs. In 2019, the World Health Organization (WHO) recommended thermal ablation for the treatment of cervical precancerous lesions in LMIC settings based on early evidence of effectiveness, simplicity of use, and reduced cost compared to other treatment options. There is now ongoing debate about how to best implement this treatment in HPV or VIA based screening programs so that unnecessary harms due to overtreatment are minimized. In order to inform the debate, we are conducting a systematic review to summarize the type and severity of side effects caused by thermal ablation for the treatment of women with cervical precancerous lesions in LMICs. Methods: A search strategy was developed to identify articles including populations of women who received treatment by thermal ablation for precancerous lesions on their cervix. A search in OVID Medline, EMBASE, CINAHL, and CAB Global Health from database inception to July 2020 yielded 1336 results. Articles will be included if they report any side effects from thermal ablation conducted in LMICs. Additional outcomes related to acceptability will be collected, such as willingness to follow-up or receive repeat treatment. Results will be supplemented with reference lists from relevant literature and LMIC regional databases. Full articles will be assessed for quality (Downs and Black, 1998) and data will be extracted on reported side effects.

Significance: We hypothesize that thermal ablation will be associated with an acceptable proportion of minor side effects such as cramping, bleeding, and discharge for women in LMICs. This will add to the debate over the riskbenefit of overtreating women through widespread prevention programs using thermal ablation. Ultimately, we aim to support efforts to establish effective prevention programs within lower resource contexts to advance the WHOâ&#x20AC;&#x2122;s goal of eliminating cervical cancer as a public health problem.

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Session #4 | Poster #25 Kathryn Reilly, Undergraduate Student, Quinnipiac University Supervisor: Lise Leveille, Evidence to Innovation

Quadriceps realignment and rectus femoris re-routing: description of a novel procedure for proximal extensor mechanism realignment in skeletally immature patients Lise Leveille, Kathryn Reilly

Background: Habitual patella dislocation is a rare condition in children in which the patella dislocates with each flexion and extension cycle of the knee. The surgical treatment is controversial and frequently complicated by the presence of open growth plates. This study describes a novel surgical technique involving realignment of the proximal extensor mechanism for the treatment of habitual patella dislocation.

Purpose: The aim of this study is to observe the efficacy of this novel technique in a series of patients.

Methods: We retrospectively reviewed records of patients who underwent the quadriceps realignment with rectus femoris rerouting procedure for patella dislocation at BC Childrenâ&#x20AC;&#x2122;s Hospital between 2001 and 2020. The procedure included a lateral retinacular release, proximal mobilization and release of the rectus femoris tendon, release of the remainder of the quadriceps mechanism from the patella, rerouting of the rectus femoris tendon under and through the vastus medialis (VMO), followed by VMO advancement, and vastus intermedius and lateralis imbrication and repair.

Outcome measures collected include knee range of motion, activity level, pain history, recurrent patella instability and need for revision surgical procedures.

Results: The study included 17 girls and 7 boys, for a total of 24 patients and 29 knees. The average age at surgery was 10 years 2 months, and the age range was 5 years 8 months to 15 years 5 months. The follow up duration ranged from 2 months to 11 years with an average of 3 years 3 months. At final follow up two patients experienced some pain with intense activity, and two patients experienced pain as a result of an inciting event. Four patients experienced some subluxation postoperatively. One patient with dislocations secondary to Kabuki syndrome received a revision surgical procedure. Complications included 4 patients requiring additional operations for wound dehiscence. Eleven patients had full return to activity.

Conclusion: Quadriceps realignment with rectus femoris rerouting is a good surgical option in skeletally immature patients with habitual patella dislocation. There is a low rate of complications and recurrence of instability. Most patients were able to return to unrestricted activity.

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Session #4 | Poster #26 Amir Wachtel, Medical Student, Queen’s University Supervisor: Jugpal Arneja, Evidence to Innovation

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

Predicting Unplanned Hospital Readmissions at BC Children’s Hospital Amir Wachtel, Boris Kuzeljevic, Rebecca Courtemanche, Marija Bucevska, Jugpal Arneja, Douglas Courtemanche

Background: When a patient is discharged from the hospital and then is unexpectedly readmitted within 30 days, this event is defined as an unplanned hospital readmission (UHR). Approximately 20-40% of UHRs may be preventable.

Patients with UHRs are at a higher risk of adverse health outcomes and UHRs cost roughly $1.8 billion annually. Thus, anticipating their occurrence using risk-prediction models may improve patient care and decrease cost.

The predictive factors used in UHR risk-prediction models for the adult population do not aptly apply to pediatrics.

Predictive factors for pediatric unplanned readmissions may differ based on country/healthcare system, may be institution specific, and may be specific to the time period studied. There are few predictive models for pediatric unplanned readmissions and the ones that have been created have only achieved moderate predictive abilities and only include a single time period.

Purpose: This study aims to identify the significant risk factors associated with unplanned readmissions at BC Children’s Hospital (BCCH) and to compare them with those identified at other institutions. The identified BCCH-specific risk factors will be used to create a risk-predictive model for pediatric UHRs. Finally, UHR rates and their associated risk factors at BCCH will be analyzed over a 10-year time period.

Methods: A retrospective cohort study will be performed using an electronic inpatient dataset extracted from the BCCH discharge abstract database (DAD), with the primary outcome variable being the 30-day unplanned hospital readmission.

All admissions between April and March of 2007-2009 and 2017-2019 will be examined. Twenty-one covariables will be extracted from the DAD to assess their associations with UHRs. Data analysis will be performed to describe the study population and derive and validate a risk-predictive model for UHRs. Significance: Knowing the significant risk factors associated with pediatric UHRs, could allow for future quality improvement trials to decrease their occurrence. This, in turn, could decrease the negative health outcomes associated with unplanned readmissions and decrease the financial burden they place on the Canadian healthcare system.

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Session #5 BASIC SCIENCE

Moderator: Dr. Alejandra Wiedeman Participants: Sanjit Bains Gurmaan Gill Frances Scheepers Miranda Tsuyuki Lily Yip Watch Presentations Online: Thursday, July 30 | 1:00 pm www.bcchr.ca/posterday

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Session #5 | Poster #27 Sanjit Bains, Undergraduate Student, University of British Columbia Supervisors: Michael Kobor & Samantha Schaffner, Healthy Starts

Congratulations to Sanjit on receiving a UBC Genome Science & Technology Summer Scholarship

Chronic Stress Interacts with Alpha Synuclein Overexpression to Alter Epigenetic Regulation in Parkinson’s Model Mice Sanjit Bains, Samantha Schaffner, Thomas Hentrich, Zinah Wassouf, Julia Schulze-Hentrich, Michael Kobor

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting mainly older adults and involving loss of motor control. The PD brain is identified by accumulations of the alpha synuclein protein (SNCA) and damage of dopaminergic neurons, cells specializing in movement. Familial PD etiology often includes dysregulation of SNCA through point mutations or overexpression; however, its cause is not fully understood because a genetic mutation does not necessitate PD diagnosis. Epigenetic dysregulations have been discovered in PD patients, presenting an emerging interest in how SNCA aggregates impact regulation of neuronal genes. The epigenome is modulated by both genotype and the environment, making it ideal to assess the interplay of both genetic risk factors like SNCA overexpression and environmental factors, which have been shown to affect PD risk.

Methods: In this study, our goal was to investigate which molecular pathways undergo epigenetic perturbations when SNCA overexpressing mice are exposed to chronic stress. To do this, we assessed genome wide DNAm and DNAhm patterns in the hippocampus of wild type and SNCA overexpressing mice randomly assigned to chronic stress and standard environment (n=4 per group) by reduced representation bisulfite sequencing (RRBS).

Results: We found that SNCA overexpression in standard environment was associated with differential DNAm and DNAhm in neurotransmission related genes. Interestingly, SNCA overexpression in the chronic stress environment induced additional changes not associated with the transgene in standard environment, classified as “reactive sites” with differential DNAm and DNAhm in some neurological development and regulation genes. Sites associated with SNCA overexpression regardless of environment, characterized as “pan-genotype sites”, had changes in DNAhm in a few intergenic sites and DNAm at various genes.

Conclusions: These results suggest that SNCA overexpression induces stress-dependent epigenetic disturbances in neuronal health pathways. This may help in understanding why PD susceptibility varies across individuals and suggests the importance of considering lifestyle interventions of stress reduction for PD prevention, especially for those with genetic risk for SNCA overexpression. These insights could be further supported by integrating the DNAm and DNAhm patterns with differential gene expression, which is a future aim as expression data is also available for these samples.

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Session #5 | Poster #28 Gurmaan Gill, Undergraduate Student, University of British Columbia Supervisor: Philipp Lange, Childhood Diseases

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

How Degradomics Studies Contribute to Our Understanding of Cell Death Mechanisms Gurmaan Gill, Philipp Lange, Aleksandra Pawlowska, Anuli Uzozie, Amanda Lorentzian

Background: Inducing cell death mechanisms is one of the main ways in which several diseases can be treated, including cancer. However, there are still large gaps in our understanding of programmed cell death mechanisms. Recently, degradomics studies have made large strides in filling these gaps by helping identify the proteoforms created from protease cleavage during cell death. Thus, the aim of the study is to assess the role degradomics has played in our understanding of cell death mechanisms.

Search Methods: We conducted a literature review on PubMed using the search terms (Degradomics) AND (Apoptosis), (Degradomics) AND (Necroptosis), and (Degradomics) AND (Autophagy). We also checked the references in each relevant study for additional studies. The N-termini associated with cell death mechanisms in N-terminomics studies were then extracted from these studies. To determine if apoptotic proteases have a different activity profile than non-apoptotic proteases, these N-termini were compared to the N-termini identified in a study investigating non-apoptotic HeLa cells.

Results: We included 10 studies that identified N-termini associated with apoptosis. Of the 3 studies that identified the most N-termini, there were 273 N-termini in common. Furthermore, we included data from Degrabase, which is a database that compiled 8258 peptides produced from apoptosis in 44 experiments. 605 of these peptides overlap with the peptides found in non-apoptotic HeLa cells. Degradomics studies in autophagy have identified several hundred autophagosome protein candidates. Further research looked at the roles of cytochalasin D, p62, PARK7, and LC3C in the autophagy mechanism. Degradomics research in necroptosis is lacking. The next step is to connect the N-termini identified in these studies to proteins involved in these cell death mechanisms.

Clinical Significance: Since one of the hallmarks of cancer is the evasion of cell death mechanisms, many therapies look to restore those mechanisms. While most therapies looked at inducing apoptosis, there has been little research looking into inducing necroptosis or autophagy as an alternative. Furthermore, little is known about anastasis, which is the process of a cell recovering from cell death. Degradomics can play a large role in learning more about cell death mechanisms and developing possible therapies.

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Session #5 | Poster #29 Frances Scheepers, Undergraduate Student, McMaster University Supervisor: Lise Leveille, Evidence to Innovation

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

Split Tibialis Posterior Tendon Transfer (SPOTT) for Equinovarus Foot in Cerebral Palsy Frances Scheepers, Lise Leveille, Timothy Bhatnagar

Background: Equinovarus foot deformity is commonly seen in children with cerebral palsy. This deformity results from muscle weakness creating an imbalance of forces across the ankle, presenting as hindfoot inversion and equinus with forefoot supination. The split tendon transfer of the posterior tibialis (SPOTT) is a surgical correction, where the split tendon is transferred posterior to the fibula with insertion on the peroneus brevis tendon. An alternate routing of the split tendon transfer through the interosseous membrane has also been described. This variation has a theoretical benefit of improving ankle functionality.

Purpose: The purpose of this study is to 1. report instrumented gait analysis outcomes for ambulatory patients who underwent a SPOTT procedure; 2. determine if surgical routing (posterior to the fibula (Posterior group)) or through the interosseous membrane (IO group) impacts post-operative foot and ankle kinematics and kinetics.

Methods: A retrospective review was performed of all patients undergoing a SPOTT procedure for spastic equinovarus foot deformity with pre- and post-operative gait lab data. Patient demographics, tendon transfer technique, concurrent procedures, perioperative course, and complications were collected.

Results: 47 patients met inclusion criteria. 22 patients were in the IO group and 25 in the posterior group. The average patient age was 12.3 years for the IO group and 10.1 years for the posterior group. Preliminary data is available for pain and Gillette Gait Index (GGI) before and after the surgery. Of the patients in the IO group 22.2% reported pain after the surgery, compared to 30.8% in the posterior group. The mean pre- and post-operative GGI for patients undergoing an IO SPOTT procedure was 71.7 (S.D. 13.7) and 88.9 (S.D. 15.0), respectively, compared to 73.9 (S.D. 17.1) and 82.2 (S.D. 12.5), respectively, for a posterior SPOTT procedure.

Conclusion: Based on our preliminary analysis, both the IO group and posterior group showed a similar improvement in post-operative GGI. A similarly low percentage of patients reported post-operative pain. The SPOTT technique is a beneficial procedure with low a low rate of complications regardless of the surgical technique used.

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Session #5 | Poster #30 Miranda Tsuyuki, Undergraduate Student, University of British Columbia Supervisor: Joanne Matsubara

Congratulations to Miranda on receiving a UBC Faculty of Medicine Summer Studentship: Florence & George Heighway Endowment Fund in partnership with Vancouver Coastal Health Research Institute

Granzyme B Promotes Early Stages of AMD in Bruch’s Membrane and RPE in Mouse Models Miranda Tsuyuki, Jacob Ng, Joanne A. Matsubara

Background: Age-related Macular Degeneration (AMD), a retinal disease, is the leading cause of blindness in North America. With inflammasome activity suggested to be a mechanism for AMD, we investigated Granzyme B (GzmB), a serine protease, found in tissues during aging, chronic inflammation and in the abnormal degradation of the extracellular matrix (ECM) which normally provides structural and biochemical support to surrounding cells. While GzmB has been shown to cleave cell-cell adhesion and basement membrane proteins, there is little information of its effects in the eye.

Purpose: This study attempts to resolve the role of GzmB, a novel protease, in reorganizing Bruch’s Membrane (BM) underneath the retinal pigmented epithelium (RPE) and the breakdown of the blood-retinal barrier in genetically modified mice.

Methods: C57Bl6/J (WT) and knock-out (KO) mice models of Apolipoprotein-E (ApoE), GzmB and a combined ApoE+GzmB double KO (on C57Bl6/J background) were kept on high-fat diets for 9 months, sacrificed, and had eyes processed for immunofluorescence (IF) in paraffin sections. Samples (3 per group) were imaged using Z-stack confocal microscopy at four different areas of the RPE. Image processing by ZEN Blue followed by densitometric analysis was performed to quantify levels of GzmB in BM and RPE. Results: GzmB immunolabeling was present in the BM of outer retina of WT and ApoE-KO, a model for accelerated aging. As expected, GzmB IF was significantly lower in GzmB-KO and DKO groups. When imaged at a higher power, the fluorescence was shown to be present in the space between RPE cells but further investigation will need to be undertaken in order to elucidate the exact location of the GzmB in the extracellular space.

Conclusion: GzmB is a novel serine protease that is present in the outer retina of the ApoE-KO, known to have early pathological features associated with AMD, such as a thickened BM and increased lipid-associated deposits between RPE and BM. In addition, GzmB levels are heightened and promote cleavage of ECM, remodeling of BM and the disruption of the blood-retinal barrier function in the RPE monolayer. These data suggest that inhibitors of extracellular GzmB activity may improve changes in the outer retina during the early stages of AMD. Follow-up studies are being conducted to elucidate GzmB’s exact location within the retina using double-staining for cell junction proteins.

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Session #5 | Poster #31 Lily Yip, Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development

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

Functional connectivity of the brain: fMRI analysis of two language tasks Lily Yip, Todd Woodward

Purpose: Some of the hallmark features of schizophrenia are speech disturbances and impaired language processing, which often manifests as the inability to organize and express thoughts coherently. Previous research showed that there were differences in neural activity when assessing word meanings between controls and schizophrenia patients, with hyperactivity in some regions, and hypoactivity in others. Both the semantic association (relating the meaning of two words) and lexical decision (real words or not) tasks are widely accepted as valid tools to investigate linguistic processes.

Merging the data of these two experiments allow for the detection of a possible language-processing network.

Goal: To explore the functional networks underlying linguistic processing.

Methods: In the semantic association (SA) experiment, participants matched word pairs that varied in semantic distance (close vs. distant). In the lexical decision task (LDT), participants determined whether a series of four-letter sequences were real English words. Using fMRI-CPCA (fMRI constrained principal analysis), we can identify a finer representation of the functional brain networks involved in language retrieval.

Anticipated Outcomes: Analysis of the SA and LDT data would provide insight into the functional brain networks involved in these tasks. Past studies involving controlled semantic association showed reduced coordinated activity in the fusiform gyrus and the inferior prefrontal cortex in schizophrenia patients. As schizophrenia patients often experience impaired language processing, we also expect some of these left-dominant regions to be involved in the language processing network.

Implications: Through first identifying functional brain networks involved in linguistic processes in the general population, these findings provide a basis for comparison to the altered functional brain networks observed in schizophrenia patients. This will help to enhance the understanding of language impairment in schizophrenia on a neural level, thereby influencing interventions and treatment methods for this psychiatric disorder.

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Session #6

CLINICAL, POPULATION HEALTH & HEALTH SERVICES Moderator: Dr. Matthew Smyth Participants: Umara Hansen Angella Lee Johnson Liu Victoria McCann Scout McWilliams Mikayla Shymka Sydney Sparanese Watch Presentations Online: Thursday, July 30 | 1:00 pm www.bcchr.ca/posterday

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Session #6 | Poster #32 Umara Hansen, Undergraduate Student, University of Ottawa Supervisor: Evelyn Stewart, Brain, Behaviour & Development

Assessing the utility and consistency of teacher rating scales relative to clinician ratings in pediatric obsessive-compulsive disorder Umara Hansen, Zainab Naqqash, John Best, S. Evelyn Stewart

Background: Obsessive-Compulsive Disorder (OCD) is a complex disorder which often develops in children between ages 7-12 that causes repetitive and provoking thoughts and/or urges followed by specific behaviors which act to relieve the distress. Previous research has highlighted OCD-related difficulties in school functioning such as lack of concentration, limited academic performance, and inhibition in social situations. While there exists a large number of teacher rating scales to assess mental illness symptomatology in children, few studies have focused specifically on comparing a variety of teacher rating scales, within the same population, to identify which scale is most useful in evaluating youth OCD symptoms in a school setting.

Objective: This study aims to investigate the extent to which teacher and clinician-reported ratings align in an OCD subspecialty program participant group.

Methods: Study participants include individuals consenting to a study of Neurocognition in Pediatric OCD in addition to those consenting to the BCCH OCD program registry. Teacher-reported measures include: Teacher Report Form (TRF), Conners’ Rating Scale, Child Obsessive-Compulsive Impact Scale Revised (COIS-R), and Behavior Rating Inventory of Executive Functioning (BRIEF). Clinician ratings will include the Children’s Yale-Brown OC Scale (CY-BOCS), a gold-standard measure of pediatric OCD severity. They will also include psychiatric comorbidities, based upon diagnostic interview.

A partial correlation analysis, accounting for child age and sex, will be conducted between the CY-BOCS, and all four teacher ratings. A further partial correlation analysis, also accounting for child age and sex, will be done within the COIS-R scale in order to evaluate the correlation between the COIS-R teacher’s report, the COIS-R self-report and the COIS-R parent report to ensure that there is consistency amongst all three scales.

Implication: Overall, these findings will help inform how OCD symptoms might manifest in the classroom, as viewed from the perspective of the child’s teacher. Gaining further insight into which teacher rating scales most closely associates with child’s OCD symptoms may allow for earlier detection; generally, implementation of the most accurate scale will grant clinicians a better understanding of the impact of OCD on daily school functioning.

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Session #6 | Poster #33 Angella Lee, Undergraduate Student, Cornell University Supervisor: Yvonne Lamers, Healthy Starts

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

Investigating the differences in maternal dietary intake for women of different BMI statuses 1.5 years after delivery Angella Lee, Yvonne Lamers

Background: Weight gain and weight retention are both common for women post-pregnancy, but both are unfortunately associated with negative health outcomes in later life. The impacts of physiological, psychological, and dietary factors on such weight gain and retention remain unclear, especially after the defined post-partum period.

Objective: To determine whether there is a relationship between dietary intake and BMI status in women at 1.5 years after delivery.

Methods: Data was collected from 85 women with toddlers aged 1.5 years as part of a six-month study clinical study in Vancouver, B.C., Canada. Their dietary intake for the last year was assessed using the Canadian Diet History Questionnaire II (C-DHQ II), which was created by the National Cancer Institute. Demographic information, including height and weight, was collected using a separate General Information Questionnaire. The women were split into three groups (normal weight, overweight, obese) according to their BMI and their nutrient intake was analyzed using one-way ANOVA and Kruskal-Wallis tests performed in RStudio.

Results: The women involved in the study were recruited by convenience sampling. On average, they were 33 years old, with a total household income of between $70 000 and $80 000 per year and a bachelor’s degree. Examination of the energy-adjusted intakes of 22 different micro- and macronutrients, both with and without the inclusion of supplements, revealed that only the dietary intake of sodium differed significantly (95% CI: 31.435, 493.64) between the overweight and obese groups (α = 0.05).

Conclusion: This study suggests that there are few differences in nutrient intake between women of different BMI statuses at 1.5 years post-pregnancy, but this study is limited in the number and power. Further studies should account for changes in BMI before and after pregnancy, as well as explore the physiological and psychological factors that may lead to post-pregnancy weight gain and weight retention.

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Session #6 | Poster #34 Johnson Liu, Undergraduate Student, University of British Columbia Supervisor: Janice Eng

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

Does accelerometer measurement of upper extremity use capture changes following stroke? A systematic review Johnson Liu, Chieh-ling Yang, Janice J Eng

Background: Approximately 85% of individuals with stroke will display upper extremity (UE) paresis at 6 months poststroke. Evidence continues to support the need for intensity and repetition of motor skills to promote neuroplasticity and motor learning, therefore accelerometers have been commonly adopted as a method to assess UE function by quantifying real-world activity given its objectivity. Accelerometer measurements have been shown to be reliable and valid, however, it is necessary that outcome measures are able to detect changes in UE function in response to an intervention or over a natural recovery process. Currently, no review has summarized the evidence for its responsiveness, the ability for an instrument to accurately detect change when it has occurred.

Objective: The purpose of the review is to critically examine evidence on the responsiveness of accelerometers as an outcome measure, specifically in context of the UE functional recovery following stroke.

Methods: A systematic literature review was performed to identify articles that provide responsiveness data for three types of change (observed, important, detectable) using accelerometer measurements to quantify UE functional activity in people with stroke. 6 databases MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Central, Ei Compendex) were searched from database inception to June 2020 using a strategy developed between the authors and a librarian from the University of British Columbia. Additionally, systematic reviews identified during screening were hand searched for relevant literature. Articles will be assessed for risk of bias using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The methodological quality and screening of studies included will be examined independently by two reviewers. A third reviewer will be consulted should there be any disagreements that cannot be resolved through consensus. Data will be extracted using a form developed by the research team. The review will be registered on PROSPERO. Preliminary Results: This review included 15 studies (14 through screening, 1 through handsearching).

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Session #6 | Poster #35 Victoria McCann, Medical Student, Queen’s University Supervisor: Simon Whyte, Evidence to Innovation

Congratulations to Victoria on receiving a BC Children’s Hospital Research Institute Evidence to Innovation Summer Studentship

Genetic Differences in Pharmacodynamic Safety Endpoints with Propofol Anaesthesia in Children Victoria McCann, Simon Whyte, Bruce Carleton, Matthias Görges, Andrew Poznikoff

Background: Propofol is an extensively used intravenous sedative and general anesthetic. For many reasons, propofol is an ideal anesthetic; however, it also has a narrow therapeutic window. There is only a small difference in the dose required to produce loss of consciousness (LOC) and the dose required to produce potentially life-threatening effects such as loss of protective airway reflexes and cessation of spontaneous breathing. Furthermore, there is substantial variation between individuals in the doses required to achieve these endpoints.

Objectives: Primary: 1. To describe and quantify doses of propofol required to produce loss of consciousness and apnea in children of differing ages, sex and self-identified countries of origin 2. To identify genomic associations that may explain variability and generate hypotheses for further study 3. To identify genomic ancestry and examine how pharmacogene allele variants that may explain the findings of (1) above are distributed across genomic ancestries Secondary: 1. To examine the correlation between self-identified countries of family origin and genomic ancestry Methods: The study is a prospective, non-randomized, single-cohort study of two pharmacodynamic endpoints (loss of consciousness and apnea) in children aged 3-18 requiring propofol anesthesia with subsequent genome-wide association study (GWAS) and principal component analysis (PCA) to examine pharmacogenomic explanations for pharmacodynamic variability. Average propofol doses at which LOC and apnea occur will be stratified prospectively by age and sex, and retrospectively by genetic ancestry.

Implications: The potential benefit of this work would be to produce more tailored propofol dosing recommendations for children, as well as an associated increase in safety of administration. Anesthesiologists at BC Children’s Hospital routinely use intravenous induction of sedation and general anesthesia with propofol. Refining the dosing recommendations to account to pharmacogenomic variability will make procedural sedation safer for children.

Experienced propofol users already adjust for age and body weight, therefore this study may enable further refinements according to sex as well as ancestry.

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Session #6 | Poster #36 Scout McWilliams, Medical Student, National University of Ireland, Galway Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

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

Sleep an Outcome Measure in Interventional ADHD Randomized Controlled Trials (RCTs): Scoping Review Methodology Scout McWilliams, Ted Zhou, Helen Brown, Sylvia Stockler, Osman Ipsiroglu

Introduction: Emerging literature is demonstrating the intrinsic role of sleep in ADHD, a common disorder affecting approximately 7.5% of children and adolescents worldwide. This interconnection was recently strengthened with the description of ADHD sleep phenotypes and ADHD-related sleep disorders. In this context, we will investigate sleep as an outcome measure in interventional ADHD RCTs. The research questions are (1) which tools are used to measure sleep, and (2) the validity of the chosen tools. In contrast to previous literature reviews conducted by our lab, where the searches were framed and conducted by a librarian, we have decided to develop the methodology ourselves in collaboration with a librarian.

Methods: Due to its exploratory nature, we will conduct a scoping review that follows the methodological framework outlined by Arksey and Oâ&#x20AC;&#x2122;Malley. We have organized the work into the following phases: (1) protocol & search strategy development; (2) identifying studies; (3) data collection & analyses. Research questions and search terms were identified through structured discussions and trial searches.

Results: Search terms were divided into three categories: ADHD, sleep, and RCT. Although ADHD is a standardized diagnosis, the nuances of writing ADHD revealed varying results, which were encompassed by using adjacency functions (e.g. attention deficit adj2 disorder). The initial keywords for sleep were expansive, but as many hits did not meet the inclusion criteria, we agreed on the keywords: sleep* (truncation), fatigue, insomnia, somnolence. Subject headings were adapted for each database based on the keywords. Finally, we selected validated RCT filters from the Cochrane Handbook. Databases were chosen based on their relevance to the field and inclusion of studies from diverse geographical locations: CINAHL, Embase, Medline, and PsycINFO. Accurate search terms and precise RCT filters decreased the number of results by 339 in Medline. The final search (all databases) yielded 2265 results. The developed protocol was registered with Open Science Framework.

Conclusions: We accomplished Phase 1 and started Phase 2. Focussing on methodology enabled the development of a comprehensive search strategy for reviewing sleep as an outcome measure in interventional ADHD RCTs and a standard operating procedure for future literature searches in our lab.

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Session #6 | Poster #37 Mikayla Shymka, Undergraduate Student, Dalhousie University Supervisor: Kevin Harris, Evidence to Innovation

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

Assessing the Utility of 3D Cardiac Models in Medical Education Mikayla Shymka, Caroline Illmann, Saketh Vijayashankar, Martin Hosking, Kevin Harris

Background: Congenital Heart Disease (CHD) is the most common congenital malformation in newborns, occurring in approximately 1% of live births each year. CHD is characterized by the malformation of the heart and surrounding blood vessels. The two-dimensional (2D) images used to represent the complex three-dimensional (3D) anatomy can make it difficult for students to conceptualize the relationships between the cardiac structures in CHD and effected physiology.

Recently, 3D printing has been introduced into the medical field, especially in surgical specialties. 3D cardiac models have shown utility in preoperative planning, patient and family discussions, and medical trainee education. The use of cardiac models may improve understanding and student satisfaction; however, previous findings have been inconclusive, or reliant on subjective parameters. Additionally, knowledge retention has not yet been measured. Further study is required to establish the impact of 3D cardiac models on learnersâ&#x20AC;&#x2122; objective knowledge acquisition and retention when incorporated into medical education.

Objective: This study aims to determine whether the use of 3D models improves 10-day knowledge retention compared to conventional teaching methods through an objective knowledge assessment. We will also investigate whether students report increased satisfaction and improved understanding of CHD when the 3D models are provided.

Methods: The study includes third- and fourth-year medical students on clinical rotation in the Childrenâ&#x20AC;&#x2122;s Heart Centre.

The students are group randomized to attend a didactic teaching session, with or without 3D printed cardiac models.

The workshops are 1-hour sessions, taught by a qualified clinician focusing on tetralogy of Fallot and d-transposition of the great arteries. Students will complete an objective knowledge assessment pre-, post-, and 10-days post-workshop to measure knowledge acquisition and retention following the session. Students will also complete a survey following the workshop to evaluate demographics and self-reported satisfaction.

Impact: The findings of this study will contribute to the ongoing process of determining the utility of 3D cardiac models in medical education. This study will generate novel data on knowledge retention, addressing a current gap in the literature.

It will also add objective data about the benefit of cardiac models to student understanding.

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Session #6 | Poster #38 Sydney Sparanese, Medical Student, University of British Columbia Supervisor: Quynh Doan, Evidence to Innovation

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

Using MyHEARTSMAP to measure the association between psychosocial factors and persistent post-concussive symptoms in children Sydney Sparanese, Takuro Ishikawa, Quynh Doan

Background: Mild traumatic brain injury (mTBI) is a major public health burden, accounting for 2.87 million emergency department (ED) visits in the US in 2014. Moreover, 20-30% of children will experience persistent post-concussive symptoms (PPCS) at 3 months post-injury. The etiology of PPCS is multi-factorial, but there is no consensus on the effects of non-injury factors on PPCS. Objective: To estimate the association between psychosocial factors and PPCS, we will use the self-reported MyHEARTSMAP domain scores (social, psychiatric, functional and youth health) and the Health and Behavior Inventory (HBI), Post-concussion Symptom Interview (PCS-I) scores.

Methods: Children age 8 to 17 years seeking care for mTBI or orthopedic injuries (OI) as controls, were recruited in the ED as part of a national, prospective, longitudinal cohort study, Advancing Concussion Assessment in Pediatrics (A-CAP). We approached participants for this study at a scheduled A-CAP study follow-up visit, where MyHEARTSMAP, PCS-I symptoms scores (participant self-reported for both), and HBI (proxy-reported by accompanying guardian) were completed.

In addition to descriptive statistics, psychosocial and PPCS severity distributions, we will report correlational analysis to identify independent variables associated with greater counts and severity of PPCS at 6-months post-injury. We will later use multiple linear regressions to examine the association between severity of psychosocial issues and PPCS burden.

Results: We approached 153 families and enrolled 122 (79.7%) participants to this study; 70 with mTBI and 52 with OI. Participants were on average 12.6 years old and 44.3% were females. Prevalence of moderate or severe psychosocial concerns by domains among participants with mTBI and OI controls were respectively: social 2.9% & 2.0%, function 2.9% & 2.0%, youth health 2.9% & 0%, and psychiatry 7.4% and 10.0%. Correlational analyses and modelling is ongoing to identify psychosocial variables that correlate with greater symptom burden.

Potential Outcomes: This data has the potential to inform management recommendations such that patients could be more appropriately triaged for their risk of a complicated recovery following concussion. This could allow physicians to individualize their care for patients who would potentially benefit from closer follow-up.

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Session #7

CLINICAL, POPULATION HEALTH & HEALTH SERVICES Moderator: Dr. Matthew Smyth Participants: Sara (Seungwon) Choi Parnian Hosseini Gita Manhas Lulu Pei Stephanie Quon Sarah Wissmann Sandy Wu Donna Seraj & Harman Grewal Watch Presentations Online: Thursday, July 30 | 2:30 pm www.bcchr.ca/posterday

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Session #7 | Poster #39 Sara (Seungwon) Choi, Medical Student, University of British Columbia Supervisor: Hannah Piper, Healthy Starts

Congratulations to Sara (Seungwon) on receiving a BC Children’s Hospital Research Institute Healthy Starts Summer Studentship

Using urine sodium to creatinine ratio as a marker of total body sodium to improve growth in babies with short bowel syndrome Sara Choi, Hannah Piper

Background: Short bowel syndrome (SBS) in babies occurs after intestinal loss such that the remaining small bowel cannot support normal growth. SBS affects approximately 35 of every 100,000 live births in North America, with the incidence being ten times higher in premature infants. Babies with SBS typically lose significant fluid volume and electrolytes in their stool. Previous studies have outlined the importance of routinely monitoring total body sodium as it correlates with weight gain and growth. Currently at BC Women’s Neonatal Intensive Care Unit (NICU) urine sodium (UNa) is used as a non-invasive surrogate for total body sodium, to guide replacement in babies with SBS. However, UNa can be misleading if used in isolation as it does not account for urine output. The urine sodium to urine creatinine ratio (UNa:UCr) may offer a more accurate measure of total sodium status as it reflects renal function. Thus far there are no publications validating the use of UNa:Cr in babies with SBS. The purpose of this study is to correlate UNa with UNa:UCr, and patient growth to establish guidelines for the routine use of UNa:UCr to guide sodium supplementation in infants with SBS. Methods: We conducted a retrospective chart review of 54 infants with SBS cared for in the BC Women’s NICU between January 2018-May 2020 and who were followed by the neonatal intestinal rehabilitation program (neoCHIRP). Collected data included: etiology of SBS and intestinal anatomy, nutritional status, weekly growth anthropometrics (including weight, length and head circumference), weekly serum and urine electrolyte values, and daily sodium intake. Statistical analysis will be performed to determine the correlation between UNa and UNa:UCr and determine how each variable relates to growth. Stepwise logistic regression analysis will be performed to model the correlation between UNa:Cr, UNa, and weight gain. Excel and GraphPad Prism will be used for statistical analysis.

Implications: By completing this study, we will have a better understanding of utilizing UNa:UCr in the clinical setting to guide sodium supplementation in babies with SBS. It may offer a more accurate marker of total body sodium and optimize healthy growth in this population.

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Session #7 | Poster #40 Parnian Hosseini, Medical Student, University of British Columbia Supervisor: Mark Ansermino, Healthy Starts

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

Review on the Implementation of Patient Tracking Systems in Healthcare Parnian Hosseini, Dustin Dunsmuir, Mark Ansermino

Background: The introduction and development of real-time location systems (RTLS) have led to the integration of these systems within the healthcare setting for various uses such as tracking assets and patients, and identification and verification of patients and medication. However, despite the apparent benefits, RTLS implementation has been slow and limited. A scoping review of the literature was performed to identify successes and failures of RTLS implementation for patient tracking in clinical settings. Additionally, we aimed to identify cases of RTLS implementation in low- and middleincome countries.

Methods: A comprehensive search of PUBMED and IEEE Explore with combinations of search terms “Real Time Location System”, ”RFID”, “BLE”, “WLAN”, “IR”, “Patient Track*”, and “Patient Identification System” yielded 584 results. After abstract screening, 65 full-text articles were reviewed, and 24 articles were ultimately included in the study. Studies were included if they focused on RTLS implementation for patient tracking using active tracking systems - not requiring input from a patient or staff.

Results: The article included in this review consisted of 7 qualitative studies or reviews of RTLS implementation and challenges, 7 computer simulation studies on the feasibility and benefits of RTLS, 1 qualitative survey study on nurse satisfaction with an RTLS, and 9 case reports of RTLS implementation in various settings. Studies implementing tracking systems reported positive outcomes, including decreased patient wait-times (7), increased efficiency in workflow (6), increased accuracy of data in systems (2), decreased length of stay (2), increased patient satisfaction (1), and increased staff safety (1) . Studies additionally reported lack of accuracy (6), challenges in system setup and data monitoring (3), lack of standard for RTLS and different technologies available (3), security and privacy issues (3), and cost concerns (2) as barriers to implementation of these systems.

Furthermore, studies on RTLS were focused in higher income countries, predominately the USA (14), Taiwan (2), Canada (2), and Germany (2). No studies reporting RTLS implementation in low- or middle-income countries were found.

Conclusion: Despite the conceived and demonstrated benefits of the use of RTLS in healthcare, the technology reviewed requires further development prior to widespread adoption. Additionally, the implementation of systems has been focused on high resource settings. This review will be used to inform a pilot study of a low-cost Bluetooth-low Energy tracking system in Kenya and Uganda where implementation will have more pronounced challenges, including technological barriers.

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Session #7 | Poster #41 Gita Manhas, Undergraduate Student, University of British Columbia Supervisor: Janice Eng

Investigating the relationship between step counts, standing time, and functional outcomes during stroke rehabilitation Gita Manhas, Janice Eng

Background: Research indicates that stroke is the leading cause of neurologic disability in older adults, with one in five Canadians over the age of 55 experiencing the effects of a stroke. A high proportion of individuals recovering from a stroke experience residual movement impairment; most commonly, limited walking ability. While the greatest opportunity for neurologic and functional recovery after stroke is during the first six weeks of physical therapy rehabilitation, it can be challenging to safely mobilize a patient during this time given reductions in muscle strength, balance, and aerobic fitness.

Purpose: This study investigated the physical activity and upright mobility patterns of adults recovering from stroke during their inpatient rehabilitation physiotherapy sessions. Specifically, this study provided insight into how mobility patterns during physical therapy relate to recovery of walking ability.

Methods: This study used data previously collected from a clinical trial investigating the efficacy of an exoskeleton-based physical therapy program during stroke inpatient rehabilitation. Thirty-six adults with subacute stroke, recruited from three Canadian rehabilitation hospitals, were randomized to receive either an exoskeleton-based gait rehabilitation program or usual physiotherapy care. Participants were monitored twice weekly during physiotherapy sessions until discharge; mobility data was collected using the activPAL3 micro (PAL Technologies, Glasgow, UK), an activity tracker measuring step counts and time spent in sedentary and upright (standing, walking) postures. Demographic and stroke details were recorded at enrolment while functional outcome data was collected at baseline and post-intervention.

Pearson correlation and linear regression were used to determine relationships between mobility patterns and functional outcome.

Results: Average step counts in therapy was significantly and moderately correlated with initial (Berg Balance Scale, r=0.39, p=0.006) and post-intervention (BBS, r=0.42, p=0.01) balance function, as well as post-intervention walking ability (Functional Ambulation Capacity, r=0.45, p=0.009). Average upright time in therapy was only significantly correlated with average step counts (r=0.8, p<0.001). Taking into account initial walking ability, average step count in therapy remained a predictor of post-intervention walking (p=0.008) and balance (p=0.02) ability.

Significance: This study highlighted the efficacy of current physiotherapy practices in achieving physical activity recommendations, and whether or not this allowed individuals suffering a stroke to make meaningful advances in walking ability. Overall, this research provides a framework with which to approach stroke inpatient physical therapy in the future.

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Session #7 | Poster #42 Lulu Pei, Graduate Student, University of British Columbia Supervisor: Crystal Karakochuk, Healthy Starts

Baseline iron biomarkers as predictors of a hemoglobin response to 12 weeks of daily iron supplementation in Cambodian women Lulu Pei, Crystal Karakochuk

Background: Anemia, defined as a low hemoglobin concentration, has serious consequences for women such as an increased risk of poor birth outcomes. The WHO recommends iron supplementation for all women in countries where population-level rates of anemia prevalence are high (>40%). However, anemia is not always due to iron deficiency; thus, hemoglobin concentration alone is not an ideal biomarker to determine if iron supplementation is warranted. There is a need to identify which hematological biomarkers can best predict a response to iron supplementation in order to inform WHO policy.

Objective: Our aim was to investigate the predictive power of several biomarkers of iron status towards a 12-week hemoglobin response to iron supplementation among women, using classification models and receiver operating characteristic (ROC) curve analysis.

Methods: Data used in this analysis were obtained from a previously conducted randomized controlled trial of daily oral iron supplementation with 60 mg ferrous sulphate in non-pregnant Cambodian women of reproductive age. Baseline hemoglobin, inflammation-adjusted ferritin, soluble transferrin receptor, hepcidin, and transferrin saturation were evaluated for their predictive power on a 12-week hemoglobin response to iron supplementation. ROC curves from fitted logistic regression models for each biomarker were used to make discrimination comparisons, and variable selection methods were used to construct a multi-biomarker prognostic model.

Results: Overall, out of the 381 participants receiving iron supplements, only 25% experienced a 12-week hemoglobin response of â&#x2030;Ľ10 g/L. Additionally, despite the high anemia prevalence in this cohort (>60%), only 22% had low iron stores. ROC curve analysis using area under the curve (AUC) as a measure of model discrimination ability indicated that baseline hemoglobin (AUC=0.81), inflammation-adjusted ferritin (AUC=0.83), and hepcidin (AUC=0.82) serve as the best univariate predictors for a hemoglobin response. Applying variable selection methods in developing a multivariate prognostic model yielded the selection of baseline hemoglobin, ferritin, and hepcidin (AUC=0.86) as the best combined set of biomarkers for the prediction of a hemoglobin response.

Conclusion: Measurement of baseline hemoglobin, inflammation-adjusted ferritin, or hepcidin were the best individual biomarkers for identifying women most likely to respond to 12 weeks of iron supplementation among non-pregnant Cambodian women of reproductive age. Conjunctional measurement of all three biomarkers provided an even greater predictive power. Discrepancy between the prevalence of anemia and iron status indices highlights the need for more targeted guidelines for iron supplementation.

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Session #7 | Poster #43 Stephanie Quon, Undergraduate Student, University of British Columbia Supervisor: Guy Dumont, Healthy Starts

Congratulations to Stephanie on receiving a Natural Sciences and Engineering Research Council of Canada Undergraduate Student Research Award, BC Childrenâ&#x20AC;&#x2122;s Hospital Research Institute Summer Studentship & UBC Faculty of Medicine Summer Studentship

Smartphone Video-Based Respiratory Rate Tracking for Infants Stephanie Quon, Soodeh Ahani, Liisa Holsti, Pascal Lavoie, Guy Dumont

Background: Each year, about four million infants worldwide die of severe illnesses in their first month. Chances of survival greatly increase if critical conditions are promptly treated. However, recognizing early warning signs can be difficult, especially in low-resource settings lacking monitoring technology. Therefore, we need accessible, reliable, and low-cost devices that can help identify sick infants.

Objective: The objective of this project was to develop a computer algorithm that automatically measures respiratory rate from videos of infants captured using a smartphone. This algorithm was designed to work from videos containing motion artifacts and taken in varied lighting conditions.

Methods: In a study, 59 videos were captured from infants <3 months of age at Kamuzu Central Hospital in Malawi, East Africa. To facilitate respiratory rate tracking, 5 small (<0.5 cm) yellow stickers were applied on the infantâ&#x20AC;&#x2122;s forehead (x1), chest (x2), abdomen (x2). The algorithm, implemented in MATLAB, used a combination of signal processing, computer vision, and machine learning techniques to extract respiratory rate. This algorithm was trained to automatically identify stickers with >15,000 labelled images. Accuracy was determined by comparing algorithm output values to visually determined respiratory rate.

Results: The algorithm succeeded in video stabilization, automatically tracking sticker positions, and accurately determining respiratory rate from vertical and horizontal sticker movement.

Conclusion: The preliminary results from this algorithm show we have a feasible method of accurately measuring respiratory rate under real-life video acquisition conditions in low-resource settings. To formally determine the accuracy of the algorithm, it will be tested on additional videos. The algorithm will also be extended to recognize abnormal breathing patterns, such as paradoxical breathing and apnea.

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Session #7 | Poster #44 Sarah Wissmann, Undergraduate Student, University of British Columbia Supervisor: Lydia Bajno

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

Access to diagnostic ultrasound in infants with developmental dysplasia of the hip: A road too far?

Sarah Wissmann, Lydia Bajno, Heather Bray, Jim Potts

Background: Developmental hip dysplasia (DDH) occurs in about 1 in 1000 newborns and ranges in severity from mild acetabular dysplasia to hip dislocation. Untreated DDH is associated with significant morbidity including early osteoarthritis and hip replacement. Females, breech position during pregnancy, or a family history of the disease increase the risk of DDH. A screening ultrasound is carried out at 6-8 weeks of age if a baby has an abnormal clinical exam or risk factor. This ultrasound is read by a radiologist to determine if the hip joints are forming normally. If a baby is found to have DDH, a harness, cast, or surgery may be used to realign the femoral head in the acetabulum.

Purpose: Despite DDH being relatively straightforward to diagnose, children are travelling significant distances to BC Children’s Hospital (BCCH) for screening ultrasounds. The aim of the project is to locate existing ultrasound resources in BC and the Yukon to determine why patients are not accessing ultrasounds in their community. This will help identify ways of increasing local access to DDH screening and reduce travel costs for families.

Methods: Our study is divided into three phases: • Phase 1: Picture Archive and Communication System (PACS) and Powerchart will be used to access patient records for infants who came to BCCH for a hip ultrasound related to DDH between January 1, 2018 and December 31, 2019. Postal codes will be used to determine travel distances.

• Phase 2: Ultrasound managers and lead technologists in hospitals and ultrasound clinics in BC and the Yukon will be contacted to identify what resources are available for DDH-screening.

• Phase 3: An economic analysis of travel costs will be estimated for patients coming to BCCH and educators travelling to local communities to teach DDH screening in other parts of BC and the Yukon.

Expected outcomes: We anticipate a number of people are travelling to BCCH unnecessarily. This may be due to a lack of knowledge and resources in some communities. Offering education can address this problem and alleviate the costburden placed on families who have to travel.

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Session #7 | Poster #45 Sandy Wu, Medical Student, University of British Columbia Supervisor: Paul Yong, Healthy Starts

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

Pathways for patient-centered diagnosis and management of endometriosis-associated deep dyspareunia: A pilot randomized trial Natasha Orr, Kate Wahl, Sandy Wu, Arianne Albert, Lori Brotto, Ryan Flannigan, Paul Yong

Background: Endometriosis is characterized by the abnormal growth of endometrial tissue outside of the uterus. This condition affects approximately 1 in 10 females, and can cause various types of pain, including deep dyspareunia, defined as deep pelvic pain with vaginal penetration. People with endometriosis and dyspareunia have been shown to have significantly reduced sexual quality of life, lower self-esteem, and impaired sexual function. For a subset of patients, conventional treatment for their endometriosis does not improve deep dyspareunia. Additionally, deep dyspareunia can be difficult to evaluate because a standard pelvic exam may not reflect â&#x20AC;&#x153;real lifeâ&#x20AC;? experiences, and questionnaire-based assessments could be limited by recall bias.

Purpose: The aim of this pilot study is to evaluate the acceptability and effectiveness of two tools that may help address the management of dyspareunia: 1) A phallus length reducer (PLR, brand name: Ohnut), consisting of 4 interconnected silicone rings worn externally over the penetrating object to reduce pain with deep penetration by allowing adjustable limitation of penetration depth, and 2) A vaginal insert for at home self-assessment of the extent and severity of deep dyspareunia.

Methods: The PLR and vaginal insert will be evaluated in a pilot randomized controlled trial. 40 patient participants and their partners will be randomized to the intervention (6 weeks of PLR use) or control group and all patient participants will self-assess their deep dyspareunia using the vaginal insert. The primary outcome will be the reduction in deep dyspareunia with PLR use compared to the control. Secondary outcomes include acceptability of the PLR for patients and their partners, changes in sexual function due to the PLR, acceptability of the vaginal insert, and correlation of pain ratings from the vaginal insert self-assessment to physical exam findings.

Significance: We hypothesize that two tools may help address these concerns with respect to deep dyspareunia. The phallus length reducer could reduce pain with deep penetration. This is a relatively inexpensive tool that is publicly available for purchase. The vaginal insert could be used to self-assess pain in a safe, comfortable space (e.g., at home).

This method for assessing pain may allow patients more control over the process and provide a more ecologically valid measure of their dyspareunia. Data from this pilot study will be used to design and power a future clinical trial.

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Session #7 | Poster #46 Donna Seraj & Harman Grewal, Undergraduate Students, University of British Columbia Supervisor: Lisa Jacques

Reduction of Mucosal Barrier Injuries in Pediatric Oncology/ Hematology/BMT Patients Donna Seraj, Harman Grewal, Lisa Jacques

Background: Mucosal Barrier Injuries (MBIs) are characterized by acute inflammation and ulceration of oral mucosal membranes in patients undergoing cancer treatment. They can lead to further complications such as bloodstream infections, which increase length of stay and interventions required. Additionally, MBIs cause significant pain and discomfort, thereby compromising nutrition and oral hygiene. Literature suggests implementing an oral care regimen and using ongoing patient education to reduce the incidence of bloodstream infections, and MBIs. However, BC Childrenâ&#x20AC;&#x2122;s Hospital does not have a formal oral care protocol or mucositis grading scale in place.

Objective: Evaluate, develop, and implement resources to support oral care education and maintenance in the pediatric oncology population at BC Childrenâ&#x20AC;&#x2122;s Hospital; with the aim of reducing the bloodstream infection rate related to mucosal barrier injuries from 3.95/1000 line days to 1.5/1000 line days.

Methods: Our target population is pediatric oncology/hematology/BMT inpatients at BC Childrenâ&#x20AC;&#x2122;s Hospital. Weekly RN chart audits were performed from December 2019 to March 2020 to record documentation of oral care, mobilization, and bathing prior to any intervention. Patient-family interviews were conducted to gauge education received on the importance of oral care for prevention of MBIs. We designed educational resources for nurses to utilize in patient oral care education. An oral care algorithm was further developed to standardize assessment and the creation of personalized oral care plans for patients.

Expected Outcomes: This project will: 1) reinforce adherence to individualized oral care plans, including explicit documentation, to reduce the bloodstream infection rate related to MBIs in pediatric oncology patients, 2) educate and engage staff, patients, and families at BCCH in infection control and oral care quality improvement projects, and 3) inform the ongoing development and assessment of oral care resources and protocols in order to establish a standard of care.

Future Steps: A clinical oral care protocol to be implemented site-wide will be finalized and reviewed. We will also be developing a mucositis grading scale based on a preliminary literature search. This work will guide the introduction of various mucositis prevention and management strategies, including cryotherapy, salt and baking soda oral rinses, chlorhexidine oral rinses, and oral glutamine.

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