2017 Summer Student Poster Day by BC Children's Hospital Research

Summer Student Poster Day 1

Welcome to the 2017 Poster Day for the Summer Student Research Program. Each year we host this event to showcase unique and innovative research being conducted by undergraduate and medical students on the Oak Street campus over the summer. The research community at BC Children’s Hospital provides students with a true ‘bench to bedside’ opportunity for research. Since the early 1990s the Summer Student Research Program has provided 1,000+ undergraduate and medical students an opportunity to participate in research projects related to children’s and women’s health. The diversity of the research here is remarkable, it is amazing to see the activities the students are involved with, including basic science, clinical and population health research. Poster Day provides a wonderful preview of the interdisciplinary work our students will pursue as they progress into their own careers as scientific and clinical investigators. We are proud of the students here and we are pleased to be able to help them become leaders in their respective fields. Jennifer Myers

Research Education Manager, BC Children’s Hospital Research Institute

2017 Summer Student Poster Day

Thursday, July 27 Poster Presentations 10:00 a.m. Chieng Family Atrium

Showcasing the outstanding work of summer students based on the Oak Street campus and their contributions to research Each participant has been assigned to one of 6 groups and will have 5 minutes to discuss their poster and up to 5 minutes for questions

Awards Ceremony 1:00 p.m. Chan Centre for Family Health Education

Join us in celebrating the accomplishments of our colleagues and the positive impact of research taking place on the Oak Street campus The award ceremony will feature the poster presentation awards

BCCHR Studentships Congratulations to the following students who recieved studentship funding from the BC Children’s Hospital Research Insititute Joban Bal, BC Children’s Hospital Research Summer Studentship. Tipper Research Team Mackenzie Campbell, BC Children’s Hospital Research Summer Studentship. Ipsiroglu Research Team Brianna Carrels, BC Children’s Hospital Research Summer Studentship. B. Verchere Research Team Aditya Chhabra, BC Children’s Hospital Research Summer Studentship. Tibbits Research Team Panteha Eshtiaghi, BC Children’s Hospital Research Summer Studentship. Dutz Research Team Jollee Fung, Centre for International Child Health Summer Studentship. Ansermino Research Team Kira Genise, BC Children’s Hospital Research Summer Studentship. Murthy Research Team Thomas Hoang, BC Children’s Hospital Research Summer Studentship. Vallance Research Team Mehima Kang, Canucks for Kids Fund Childhood Diabetes Laboratories Summer Studentship. Panagiotopoulos Research Team Melissa Kong, Childhood Diseases Summer Studentship. Nadel Research Team I-Chih Kuo, Healthy Starts Summer Studentship. Lavoie Research Team Lara Lampe, BC Children’s Hospital Research Summer Studentship. Kobor & Sokolowski Research Teams

Adina Landsberg, Childhood Diseases Summer Studentship. Blydt-Hansen Research Teams Michelle Lee, Canucks for Kids Fund Childhood Diabetes Laboratories Summer Studentship. Taubert Research Team Tiffany Lee, BC Children’s Hospital Research Summer Studentship. Coelho Research Team Michelle Lisonek, Healthy Starts Summer Studentship. Yong Research Team Alice Liu, BC Children’s Hospital Research Summer Studentship. Chadha Research Team Cassandra McDonald, Brain, Behaviour & Development Summer Studentship. Hayden Research Team Victoria McCutcheon, BC Children’s Hospital Research Summer Studentship. Cooper Research Team Lisa Nakajima, Brain, Behaviour & Development Summer Studentship. Grunau Research Team Kyle Scoten, Community Child Health Endowment. Summer Studentship. Babul Research Team Kevin Shopsowitz, BC Children’s Hospital Research Summer Studentship. Friedman Research Team Benny Tang, BC Children’s Hospital Research Summer Studentship. Luciani Research Team Emmanuel Tse, BC Children’s Hospital Research Summer Studentship. Lewis Research Team Heidi Vieira, BC Children’s Hospital Research Summer Studentship. Lim Research Team 4

BCCHR Studentships Maleeha Virk, Michael Cuccione Childhood Cancer Research Program Summer Studentship. Maxwell Research Team Melissa Wan, Evidence to Innovation Summer Studentship. Arneja Research Team

Li Qing Wang, Healthy Starts Summer Studentship. Robinson Research Team Jovi Wong, Brain, Behaviour & Development Summer Studentship. Schrader Research Team Paul Yen, BC Children’s Hospital Research Summer Studentship. C. Verchere Research Team

External Studentships Congratulations to the following students who received external funding from national, provincial or regional funding agencies Andy Yi An, NSERC Undergraduate Student Research Award. Taubert Research Team Camron Chehroudi, UBC Faculty of Medicine Summer Studentship. Verchere Research Team Aayushi Joshi, BC Injury Research and Prevention Unit Studentship. Pike Research Team Madeline Lauener, BC Cancer Agency. Schultz Research Team Wayne Leung, Mach-Gaensslen Foundation of Canada. Ipsiroglu Research Team Jim (Zhang Hao) Li, NSERC Undergraduate Student Research Award. Gibson Research Team

Iris Liu, Rare Disease Foundation Microgrant. Duffy Research Team Claire Mockler, UBC Summer Studentship. Blydt-Hansen Research Team Navjit Moore, NSERC Undergraduate Student Research Award. Vallance Research Team Samantha Pawer, NSERC Undergraduate Student Research Award. Brown Research Team Mary Shen, NSERC Undergraduate Student Research Award. Kobor Research Team

The BC Children’s Hospital research community would like to acknowledge the following organizations for supporting training opportunities on the Oak Street Campus BC Children’s Hospital Foundation Canucks for Kids Fund Centre for International Child Health Michael Cuccione Foundation Community Child Health Endowment Research Themes: Childhood Diseases, Healthy Starts, Evidence to Innovation, Brain, Behaviour & Development 5

Showcasing excellence in our talented research community 2017 Poster Presentations

Participants Session One Basic Science

Session Two

Basic Science

Name

Abstract Title

Page

Andy Yi An

Starvation, cancer, and worms: The transcriptional regulation of EFK-1

Joban Bal

Defining sociocognitive phenotypes in autism spectrum disorder

Mackenzie Blydt-Hansen Camron Chehroudi

Exome sequencing to determine a genetic cause for familial intracranial aneurysms in a Canadian family

Beta cell specific removal of PC2 accelerates type 2 diabetes development

I-Chih Kuo

Unraveling the role of hypoxia in neonatal immune responses

Madeline Lauener

Optimization for in vitro expansion of human NK reg cells (CD56 Bright)

Jim (Zhang Hao) Li

Quantification of post-translational histone acetylation on H3K27 residues using mass spectrometry (LC-MS/MS)

Mary Shen

Exploring the relationship of Ssu72 and Cdk8 in transcription regulation

Madeleine Tan

Measuring cytokine responses to evaluate innate immune development in HIV exposed/unexposed infants

Benny Tang

The importance of autophagy and lysosomal homeostasis for pancreatic beta-cell function and survival in diabetes and islet transplantation

Name

Abstract Title

Page

Brianna Carrels Aditya Chhabra

Pancreatic prohormones as biomarkers in diabetes

24 25

Thomas Hoang

Intestinal epithelial inflammasomes: Frontline defenders against Campylobacter jejuni infection

Maya Willms

Examining the role of H2A.Z in transcription via targeted removal

Lara Lampe

Determining the effects of food deprivation on the epigenome

Daisy Li

Can lipid nanoparticle encapsulation protect against dexamethasone induced diabetes?

Shannon Tang Heidi Vieira

Neonatal compensation for an immature immune system

30 31

Maleeha Virk

Cancer cell engraftment and scattering is enabled by cell cycle progression

Li Qing Wang

HLA-KIR interaction in acute chorioamnionitis affected pregnancies

Determination of the possible role of cardiac troponin I mutations in sudden cardiac death in infants (SUDI) using genome edited human induced pluripotent stem cellsderived cardiomyocytes (hiPSC-CMs)

Evaluation of integrin Îą6 (CD49f) isoforms as potential biomarkers in breast cancer

Session Three

Basic Science

Session Four Clinical

Name

Abstract Title

Page

Panteha Eshtiaghi

Skin monitoring of diabetogenic inflammation

Yue Zhou (Joe) Huang

Does viability affect the non-specific effect of Bacillus Calmette–Guérin vaccines?

Navjit Moore

THE MINI GUT EVOLUTION: Using organoids to characterize innate signalling in intestinal epithelial cells

Samantha Pawer

Analysing functionality of long non-coding RNAs

Kwestan Safari

Impact of the Fcgamma receptor gene variants on antibody-induced anti-inflammatory macrophage activation

Stephanie Schüler

Evaluation of the Effect of a Ketamine Adjuvant Anesthetic Administration on Depth of Hypnosis Indices During Total Intravenous Anesthesia – a Comparative Study Using a Novel Case Replay System

Michelle Lee

A novel transcriptional mechanism in zinc homeostasis

Kiana Yau

The role of the Nlrp3 inflammasome in islet amyloid polypeptide (IAPP)-induced diabetes

Alexandra J. Zhou

Task-positive and task-negative functional brain networks play complementary roles in verbal fluency

Name

Abstract Title

Page

Victoria Chan

The effect of dexmedetomidine on recovery room and hospital discharge times after non-painful day case procedures in children

Tara Evans-Atkinson

Nursing support services delegated diabetes care plan assessment

Jollee Fung

Building a predictive model of severe illness in children under 5 in resource-limited settings

Kira Genise

Colonization of streptococcus pneumoniae in viral bronchiolitis

Tiffany Lee

Clinical and demographic characteristics of male adolescents with eating disorders: A retrospective review

Wayne Leung & Ishmeet Singh

The role of iron deficiency in neurodevelopmental disorders (ADHD, ASD, FASD) - A scoping review

Alice Liu

Three-dimensional facial morphology and severity of sleep disturbances in children

Victoria McCutcheon Simon Robins

Paediatric elbow fractures from a child’s viewpoint

A scoping review to examine symptoms in children with rare, progressive, life-threatening disorders

Arpreet Singh

The burden of fire-related injuries in children and youth across Canada

Paul Yen

Does tissue expansion reconstruction in the trunk of children increase the risk of scoliosis?

Session Five Clinical

Name

Abstract Title

Page

Haya Abuzuluf & Tara Bishop

Post-discharge readmission and mortality among children being repatriated to northern communities: Derivation of prediction models

Natasha Carson & Hebah Hussaina

Behavioural Observations Step 1: â&#x20AC;&#x153;Fidgety Philipâ&#x20AC;?, the Godfather of ADHD?

Khaola Safia Maher & Jecika Jeyaratnam

Behavioural Observations Step 2: Developing a Shared Annotation Language for Analysis of Video Recordings

Tisha Dasgupta

The Belly Breathing App- A smartphone biofeedback application to manage stress and anxiety in children undergoing medical procedures

Aayushi Joshi

Rising fall-related death among seniors: Cause and effect of a policy change?

Melissa Kong

Use of optimized post-contrast enhanced PET/CT to improve diagnostic accuracy, staging, and follow-up of children with cancer

Michelle Lisonek

Deep dyspareunia and central sensitization in endometriosis

Jimmy Lopez

Aortic stiffness and physical activity in children with congenital heart disease

Claire Mockler

The prognostic value of urinary chemokines at 6 months after pediatric kidney transplantation

Grace Nie

Pregnancy-specific reference intervals for laboratory biomarkers: Uses, challenges, and initiatives

Kyle Scoten

Evaluation of the Concussion Awareness Training Tool (CATT) mandate by BC Hockey

Cassie Walmsley

Developmental and obstetric predictors of psychosis

Session Six Clinical

Name

Abstract Title

Page

Mackenzie Campbell

Disruptive Daytime Behaviours & Sleep in Adolescents with Down Syndrome - An Explorative Pilot-Study Using a Participatory Research Concept

Nicole Cheung

Emergency Surgery Delays - An analysis of target time achievement and causes of delay in emergency cases at BC Childrenâ&#x20AC;&#x2122;s Hospital

Nicole Hemphill

Physical activity and health behaviours in adolescents: A one-year follow-up study

Mehima Kang

Risk of chronic kidney disease following acute kidney injury during diabetic ketoacidosis in children with type 1 diabetes

Adina Landsberg

Urinary metabolite markers of chronic kidney disease in pediatric kidney transplant recipients

Iris Liu

Understanding the journey to care for Ugandan children with rare diseases

Emmanuel Tse & Seraph Bao

Behavioural Observations Step 3: Vigilance of night-time drivers

Lisa Nakajima

Stress and cognition in early childhood in infants born very preterm

Kaitlyn Samson

Vitamin D status in children and adolescents with sickle cell disease in British Columbia

Jacob Stubbs

Working memory load increases the diagnostic utility of smooth pursuit eye movements in mTBI

Lee Vargen

Predicting the whole picture: The predictive validity of the START for a range of outcomes

Helen Wu

Evaluating the feasibility of Panda, a smartphone app designed to help parents manage their child's postoperative pain

Room 2108 Patio Registration

Chan Centre for Family Health Education Session One - Basic Science #1 - 10

Main Entrance

Reception

Refreshments

Session Five - Clinical, Population Health & Health Services #40 - 51

Session Two - Basic Science #11 - 19B

Session Six - Clinical, Population Health & Health Services

Session Three - Basic Science #20 - 28

#52 - 63

Session Four - Clinical, Population Health & Health Services #29 - 39 11 The drawing is intended for visual reference only, it is not to scale

Session One BASIC SCIENCE Moderator: Joannie Allaire Participants: Andy Yi An Joban Bal Mackenzie Blydt-Hansen Camron Chehroudi I-Chih Kuo Madeline Lauener Jim (Zhang Hao) Li Mary Shen Madeleine Tan Benny Tang

Poster Board #1 Andy Yi An, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

Starvation, cancer, and worms: The transcriptional regulation of EFK-1 Andy Yi An, Forum Bhanshali, Stefan Taubert For cells to survive nutrient deficiency, they must shut off one of the most energy-consuming cellular processes: translation. One way the cell accomplishes this is to phosphorylate and inactivate the eukaryotic elongation factor 2 (eEF2) via the eEF2 kinase (eEF2K), which stops translation to conserve energy. Tumors commonly face nutrient deficiency prior to angiogenesis, and there is evidence that over-expressing eEF2K helps early tumors survive under these conditions. Therefore, our objective is to identify the transcription factors that induce eEF2K upon starvation to better understand the process of tumor survival. To study the regulation of eEF2K in vivo, I am using the model organism Caenorhabditis elegans, a nematode worm that is a highly tractable genetic model system. C. elegans has a highly conserved ortholog of eEF2K called the elongation factor kinase 1 (EFK-1). Past experiments by Leprivier et al. (2013) have shown that efk-1 is transcriptionally upregulated during starvation, consistent with experiments done on eEF2K. However, the pathways that mediate this induction are still unknown. Therefore, to delineate efk-1 induction, a candidate screen was done using qPCR and mutant worms lacking individual transcription factors known to be involved in the starvation stress response. Specifically, efk-1 mRNA levels in wild-type and these mutant worms were compared in both fed and starved conditions. Thus, two candidate transcription factors were found that are required for efk-1 induction in starvation stress: HLH-30/TFEB and DAF-16/FOXO. To validate these screen results, I am performing western blots to determine if starvation increases the activity of EFK-1 in wild-type worms and in hlh-30 and daf-16 mutants by measuring the amount of phosphorylated eEF2. I have also generated a transgenic C. elegans strain containing the efk1p::gfp transcriptional reporter, which I will use in the future as an additional tool to screen for other regulators involved in the EFK-1 pathway. The results of these experiments will increase our understanding of EFK-1/eEF2K regulation, leading to the discovery of possible therapeutic targets for cancer.

Poster Board #2 Joban Bal, Undergraduate Student, University of British Columbia Supervisor: Christine Tipper, Brain, Behaviour & Development

Defining sociocognitive phenotypes in autism spectrum disorder Joban S Bal, Christine Tipper The prevalence of autism spectrum disorder (ASD) has increased in the recent past from 6.7 per 1000 children in 2000, to 14.7 per 1,000 children in 2010 (Luciano, 2016). A key outstanding challenge in the treatment of ASD is the profound individual variability in symptom profiles, which precludes an established, “one-size-fits-all” intervention regimen. The ongoing study presented here will utilize several novel behavioural tests and mobile, wireless EEGs to measure social and cognitive function in individuals who have ASD. We will identify distinct sociocognitive profiles that are linked to identifiable patterns of brain organization. The primary hypotheses are that 1) profiles of social, cognitive, and brain function across a range of tasks will define reliable “sociocognitive phenotypes” that will help characterize individual abilities and deficits while providing meaningful context that may aid in guiding clinical care, prognosis, and tracking, 2) sociocognitive phenotype-genotype links will provide evidence regarding pathways that connect genetic signatures to distinct patterns of brain organization that underlie specific symptoms in ASD, and 3) defining brain-based sociocognitive phenotypes will define novel, clinically effective subtypes of ASD that may yield clinical utility in terms of diagnosis, treatment, and tracking. In engaging with community programs offered at the Pacific Autism Family Center (PAFC), we have found causes for concern among families are current diagnostic techniques that primarily rely on observational assessments of behavioural symptoms which can often appear later in early childhood development. As a first step, we are developing surveys that will be given to families at the PAFC to determine their primary concerns regarding behavioural, social, and communication symptoms. We have acquired a new, lightweight, mobile EEG system, and are currently testing its efficacy in comparison with more cumbersome, lab-based high-density EEG systems. Results so far have been promising, with this user-friendly unit offering data of comparable quality. Moving forward, the mobile EEGs will be used to assess brain activity dynamics while typically-developing or ASDdiagnosed children, youth, and adults participate in social and cognitive tasks. Future directions of this work include developing novel means of quantifying disturbances of social, cognitive, and brain function. Major long-term goals will be to improve individualized diagnostic precision, and introduce quantitative cognitive neuroscientific metrics that will help track individual progress and treatment efficacy.

Poster Board #3 Mackenzie Blydt-Hansen, Undergraduate Student, Queenâ&#x20AC;&#x2122;s University Supervisor: William Gibson, Childhood Diseases

Exome sequencing to determine a genetic cause for familial intracranial aneurysms in a Canadian family Mackenzie Blydt-Hansen, Emma Hitchcock, William T Gibson Background: Intracranial aneurysms (IA) are the bulging or ballooning of blood vessels in the brain. Aneurysmal rupture is the primary cause of a type of stroke called subarachnoid hemorrhage, which has a high rate of both mortality and morbidity. About 10 â&#x20AC;&#x201C; 20% of patients with IA have a hereditary type of IA called Familial Intracranial Aneurysm (FIA). Patients with FIA are more like to get multiple aneurysms, have their aneurysms rupture, and have a poor outcome after rupture. Aim: To identify candidate variants that lead to aneurysm formation In a Canadian family with FIA using exome sequencing. Methods: Exome sequencing was performed on all four affected family members. Gemini, a bioinformatic database, was used to query the exome sequencing data for variants with read depth (>10), genotype quality (>20), population frequency (<1%), and the co-segregation with FIA in the family. Candidate variants were then selected based on gene function. The top variant was validated with Sanger sequencing in both affected and unaffected family members. Results: Only 250 variants met our filtering criteria. Our top candidate is a missense variant in SERPINA1, a gene in which other variants are known to cause alpha-1 antitrypsin deficiency, a condition that has been suggested to be a risk factor for intracranial aneurysms. Significance: Identifying new disease genes for FIA will have wide-ranging implications by contributing to the scientific understanding of this disease at a molecular level, creating a genetic test to screen other families with FIA, and also potentially being a target for future pharmaceutical development.

Poster Board #4 Camron Chehroudi, Undergraduate Student, University of British Columbia Supervisor: Bruce Verchere, Childhood Diseases

Beta cell specific removal of PC2 accelerates type 2 diabetes development Camron Chehroudi, Austin Taylor, Jaques Courtade, Yi-Chun Chen, Bruce Verchere Introduction: Islet amyloid polypeptide (IAPP) is co-secreted with insulin by pancreatic beta cells. Protein aggregates of human IAPP form amyloid plaques contributing to beta cell dysfunction in patients with type 2 diabetes. Production of mature IAPP involves several post-translational modifications from the precursor peptide proIAPP, including cleavage by prohormone convertase 2 (PC2). Impairment of this processing pathway may cause accumulation of precursor forms of IAPP, serving as a nidus for amyloid formation and beta cell dysfunction. Thus, we sought to determine the effects of a mouse tissue specific PC2 knockout on glucose homeostasis, islet amyloid formation, and proIAPP processing. Methods: C57BL/6 mice with beta cell specific inducible deletion of PC2 and expression of human IAPP (hIAPP Tg/0; Pdx1-CreER Tg/0; PC2 loxP/-) were administered tamoxifen to induce PC2 deletion at 7 weeks of age. Control groups consisted of hIAPP Tg/0; PC2 loxP/- (no cre recombinase), and hIAPP Tg/0; Pdx1-CreER Tg/0; PC2 loxP/- mice administered corn oil (tamoxifen vehicle control). Glucose tolerance was assessed by intraperitoneal glucose tolerance test at 4, 8, and 16 weeks post-tamoxifen and mice were euthanized at 20 weeks for histological analysis. Pancreas sections were examined for islet morphology by insulin and glucagon immunofluorescence staining and islet amyloid prevalence by thioflavin-S staining. Results: Beta cell deletion of PC2 in hIAPP transgenic mice impaired glucose tolerance compared to control groups with normal PC2 expression at 4, 8, and 16 weeks post-tamoxifen/corn oil administration. Over the 20 week duration of the study, 45% of mice lacking PC2 developed diabetes (fasting blood glucose > 16.9 mM) while control groups with functional PC2 expression did not develop diabetes. Histological analysis displayed no differences in the per islet area of alpha and beta cells, or the alpha:beta cell ratio, across all experimental groups. However, elevated islet amyloid prevalence was observed in PC2 deficient mice. Conclusions: These findings suggest impaired proIAPP processing by PC2 deficiency accelerates diabetes development by promoting islet amyloid formation. Understanding the mechanism of IAPPinduced islet dysfunction could lead to potential type 2 diabetes treatments. Restoration of proIAPP processing may be a possible therapeutic approach to reduce amyloid formation and improve islet function in type 2 diabetes.

Poster Board #5 I-Chih Kuo, Undergraduate Student, University of British Columbia Supervisor: Pascal Lavoie, Healthy Starts

Unraveling the role of hypoxia in neonatal immune responses I-Chih Kuo, Christina Michalski, Pascal Lavoie Hypoxia refers to an oxygen tension of 1-2% which is significantly lower than that of normoxia (1021%). With oxygen serving as the terminal electron accepter in aerobic respiration and influencing numerous physiological functions, hypoxia can be pathological and is a characteristic for sites of inflammation and tumors. Physiologically however, oxygen levels in blood and especially in tissues are lower than oxygen levels in room air. Physiological hypoxia serves a critical regulator of genes involved in inflammation and critical developmental functions. This hypoxia-induced increase in immunoreactivity is mediated through induction of hypoxia signaling pathway (HIF-1-mTOR) resulting in higher levels of circulating pro-inflammatory cytokines. Despite fetal hemoglobin having a higher oxygen affinity than adult hemoglobin, the oxygen tension in fetal blood is lower than in maternal/adult blood, suggesting a hypoxic environment that the fetus is chronically exposed to. This raises the question of how hypoxia-induced inflammation is prohibited during gestation. We hypothesize that neonatal innate immune cells are less responsive to hypoxia due to reduced HIF-1-mTOR activity. To evaluate this hypothesis, neonatal (cord) and adult (peripheral) blood mononuclear cells (BMCs) were incubated under different oxygen levels and stimulated with either LPS, LPS+ATP or Curdlan to simulate bacterial and fungal infection respectively. Supernatants were collected at the end of the incubation period to measure levels of pro-inflammatory cytokines (IL-1Î˛, IL-6 and TNF-Îą) using ELISA as a readout for immunoreactivity. Interestingly, preliminary results indicate that hypoxia increases pro-inflammatory cytokine production in adult and term BMCs to similar extent. Experiments are underway to determine the effect of re-oxygenation on pro-inflammatory cytokine levels in adults and terms as well as elucidating the molecular mechanism by assessing levels of signaling molecules within the HIF1a-mTOR axis.

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

Optimization for in vitro expansion of human NK reg cells (CD56 Bright) Madeline Lauener, Kirk Schultz, Amina Kariminia Background: Over 1200 Canadians each year receive an allogeneic blood or bone marrow transplant (BMT). In children, approximately 25% of those that receive a BMT will develop chronic graftversus-host-disease (cGvHD), a rejection of recipient tissues by the transplanted donor immune system causing major morbidity. It has been found in my teamâ&#x20AC;&#x2122;s previous research in large patient populations that the presence of bright CD56 NK cells, or NKreg cells correlate with a lack of cGvHD. Based on these observations, we hypothesized that strategies to expand this population ex vivo followed by adoptive transfer, may result in a lower rate of cGvHD. Thus we wished to identify the optimal conditions for ex vivo expansion of this population. Methods: We collected blood from healthy donors and cord blood samples. In preparation for FACS sorting, we stained the mononuclear cells using CD56 APC and CD3 FITC. Both CD56 bright and dim NKreg cell populations were isolated by cell sorting. The isolated cells were cultured in the presence of IL-2, anti CD335 and anti CD2 mAbs. To observe the phenotyping, we acquired flow cytometry data on the NKreg cell populations on day one, and after twelve days in culture, to compare the change in expression using the markers CD56, CD16, Granzyme B, Perforin, CD94, and CXCR3. Functional characteristics of the expanded NKeg cell populations were investigated based on a killing assay of effector (NK cells) vs. target (K562 cells) at various ratios. Results: CD56 bright NKreg cells were found to be propagated and expanded ex vivo. Healthy donor blood has shown to have a more successful result, however cord blood needs more optimizations. CD56 bright NKreg cells do not change their expressions, or characteristics of each marker used over a twelve-day period of culture. Our results have shown that CD56 dim NKreg cells have strong cytotoxic killing at even as low as Âź ratio of effector/target, while CD56 bright NK cells are cytotoxic at only a high ratio of 2/1. Future Directions: We will continue working on the optimization of cord blood NKreg ex vivo expansion, and cytokine productions in both subpopulations.

Poster Board #7 Jim (Zhang Hao) Li, Undergraduate Student, University of British Columbia Supervisor: William Gibson, Childhood Diseases

Quantification of post-translational histone acetylation on H3K27 residues using mass spectrometry (LC-MS/MS) Jim Z.H. Li, C.K. Wong, Charlie Kuan, William T. Gibson, Philipp F. Lange Background: Traditional antibody-based methods such as western blotting and ELISA are standard protocol for quantifying protein post-translational modifications (PTMs). However, these methods have limitations on the number of markers that can be quantified per assay. Furthermore, epitopeantibody binding can be obstructed by adjacent modifications, thereby underestimating PTMs in heavily-modified proteins. To circumvent these constraints, LC-MS/MS can be employed. In this method, after initial separation of peptide fragments by high-performance liquid chromatography, tandem mass analyzers were used to filter for the precursor ions, fragment them, and then detect the product ions. Various disorders have been linked with loss-of-function mutants in enzymes catalyzing the addition of PTMs. However, the mechanisms by which these mutants cause disease remain elusive. p300 and CBP are transcriptional co-activators that exhibit histone acetyltransferase activity. Mutations in either protein can cause Rubinstein-Taybi Syndrome in heterozygotes. Purpose: The project aims to develop a feasible workflow for PTM quantification using LC-MS/MS. In addition, we seek to optimize parameters and to reduce the number of cells required, in order to create an assay that is applicable to samples collected from limiting quantities of source material (e.g. mouse islets, needle biopsies, etc.). Through this, proof-of-principle data can be generated to show that p300/CBP knockout in mice would result in reduced acetylation of H3K27. Methods: An order of 106 mouse insulinoma cells were lysed to release nuclei, which were then incubated in acid to extract histones. Aliquots were neutralized to affix propionyl moieties to the lysine residues, followed by trypsin digestion to cleave the peptides at arginine residues. Desalting and stage-tipping were performed to prepare the samples for LC-MS/MS. Significance: Although p300/CBP mutations are implicated in rare diseases such as RubinsteinTaybi Syndrome, the mechanism behind its pathology is not well-understood. Once optimized, our procedure will be applied to p300/CBP knockouts in mice pancreatic islets. If a significant change in acetylation status is found, then subsequent investigations will target acetylation levels in human patients heterozygous for p300 mutations. A significant alteration in H3K27 PTM profiles among p300 heterozygotes (compared to healthy controls) would validate a causal relationship between p300 function and its downstream PTM products, thereby providing mechanistic insight into the pathology of p300/CBP-related diseases.

Poster Board #8 Mary Shen, Undergraduate Student, University of British Columbia Supervisor: Michael Kobor, Healthy Starts

Exploring the relationship of Ssu72 and Cdk8 in transcription regulation Mary Shen, Maria Aristizabal, Michael Kobor RNA Polymerases (RNAPs) are crucial in the fundamental process of transcription. RNAPII, is responsible for the transcription of all protein coding genes. It contains a unique C-terminal domain (CTD), which is composed of hepta-peptide repeats that are evolutionarily conserved across all eukaryotic species. The CTD can be differentially phosphorylated to facilitate various co-transcriptional activities, including RNA capping, splicing, and poly-adenylation. Fcp1 and Ssu72 are both essential CTD phosphatases that have been implicated in transcription elongation and termination by de-phosphorylating the CTD of RNAPII, thus promoting the recycling of RNAPII. Consistent with FCP1’s role, preliminary findings from our laboratory showed that FCP1 truncation mutants result in synthetic lethality when combined with a CTD mutant. Moreover, FCP1’s growth phenotype were suppressed by loss of CDK8, a gene encoding a CTD kinase and member of the Mediator complex, supporting FCP1’s intimate relationship with the RNAPII-CTD and its phosphorylation status. The aim of this project is to determine if this relationship is unique to FCP1 or if it is shared with mutants of the SSU72 gene. Similar to FCP1, I found that combining a CTD mutant with ssu72-2, a temperature sensitive allele of SSU72, also resulted in lethality and that ssu72-2 mutant growth phenotypes were also suppressed by the loss of CDK8, suggesting a shared role for FCP1 and SSU72. To study the mechanistic underpinnings of the suppression of SSU72 by CDK8, I focused on their effects on transcription termination. Much to our surprise, my results showed a strong and previously unreported role for CDK8 in transcription termination. Future work will focus on understanding how FCP1, SSU72, and CDK8 individually and collectively contribute to transcription termination.

Poster Board #9 Madeleine Tan, Undergraduate Student, New York University Supervisor: Tobias Kollmann, Healthy Starts

Measuring cytokine responses to evaluate innate immune development in HIV exposed/unexposed infants Madeleine Tan, Gemma Moncunill, Daniel He, Nelly Amenyogbe, Tobias Kollmann Pregnant women infected with HIV may transmit the infection to their child; however, HIV is not a contraindication to pregnancy. The use of antiretroviral therapy (ART) before and during pregnancy reduces the risk of HIV transmission by lowering the mother’s HIV viral burden to prevent spread to the fetus. With appropriate treatment, the risk of vertical transmission is very low. Yet, regardless of fetal infection, HIV in pregnant women may have a significant damaging effect on the development of the infant’s innate immune system. HIV disrupts the pregnant woman’s immune system, which the fetus relies upon for immune instruction. We hypothesize that prenatal exposure to HIV has a negative influence on a child’s innate immune responses and their ability to efficiently react to subsequent infections and vaccines throughout childhood. Our primary objective is to study these potential changes in immunity through pregnancy outcomes and differences in innate immunity over time. In a cohort of pregnant women in Mozambique, we collected maternal, placental, and cord blood samples at birth. From children, blood samples were collected at cross sectional visits at 1, 9, and 12 months of age. Using a multiplex cytokine assay (Luminex), we analyzed cytokine concentrations and responses from HIV exposed/uninfected (HEU) and HIV unexposed/uninfected (HUU) infants to determine the effects on the infant’s innate immune system and compare immunity across the groups.

Poster Board #10 Benny Tang, Undergraduate Student, University of British Columbia Supervisor: Dan Luciani, Childhood Diseases

The importance of autophagy and lysosomal homeostasis for pancreatic beta-cell function and survival in diabetes and islet transplantation Benny Tang, Yuanjie Zou, Mei Tang, Dan S Luciani Background: Pancreatic beta-cell stress, dysfunction, and destruction contribute to the pathogenesis of type 1 and type 2 diabetes, and diminish the success of pancreatic islet transplantation as a longterm treatment for type 1 diabetes. Autophagy is an intracellular mechanism by which dysfunctional organelles and protein aggregates get delivered into lysosomes for degradation. Recent studies have identified transcription factor EB (TFEB) as a master regulator of lysosomal biogenesis and function, and some suggest autophagy may help protect beta-cells against ER and metabolic stress in diabetes and following islet transplantation. However, the importance of autophagy under hypoxia, and the roles of TFEB in beta-cells remain unexplored. Hypothesis: Disruption of autophagy and TFEB-dependent lysosomal homeostasis promote pancreatic beta-cell failure in diabetes and islet transplantation. Methods: C57BL/6 wild-type mouse islets were cultured for up to 24 hours under hypoxia (1% O2), with or without the autophagy inhibitor chloroquine. Autophagy-related and stress-response genes were examined by quantitative real-time PCR. MIN6 cells were treated for up to 18 hours with 0.5 mM or 1.5 mM palmitic acid (PA) in 25 mM glucose medium to induce glucolipotoxicity. Levels of TFEB and cleaved caspase-3 were then examined using western blot, and cell death was tracked using fluorescence imaging of propidium iodide uptake. Results: Autophagy-related and stress-response genes were upregulated in islets under hypoxia. The levels of upregulation were reduced when the islets were treated with chloroquine. MIN6 cells demonstrate a slight increase in TFEB with 0.5 mM PA at 8 hours. At 18 hours, decreases in TFEB and increases in cleaved caspase-3 were observed with increasing PA concentration. Cell death was accelerated in 1.5 mM PA compared to control or 0.5 mM PA. Conclusions and Future Directions: Preliminary results suggest that autophagy and TFEB may facilitate adaptive stress responses of beta-cells under hypoxia and moderate glucolipotoxicity, and that prolonged glucolipotoxic stress may contribute to beta-cell failure by inducing TFEB downregulation. Future experiments include examining the activation (nuclear translocation) of TFEB under these diabetes-relevant stresses, and characterizing the effects of beta-cell specific deletion of TFEB or autophagy protein 5 (ATG5) in mice.

Session Two BASIC SCIENCE Moderator: Emily Schaeffer Participants: Brianna Carrels Aditya Chhabra Thomas Hoang Maya Willms Lara Lampe Daisy Li Shannon Tang Heidi Vieira Maleeha Virk Li Qing Wang

Poster Board #11 Brianna Carrels, Undergraduate Student, University of Victoria Supervisor: Bruce Verchere, Childhood Diseases

Pancreatic prohormones as biomarkers in diabetes Brianna B Carrels, Yi-Chun Chen, Jaques A Courtade, C Bruce Verchere In type 1 diabetes (T1D), pancreatic beta cells die and are rendered dysfunctional by autoimmune attack, leading to loss of insulin production. In addition to insulin, beta cells also secrete islet amyloid polypeptide (IAPP), which plays a role in glucose homeostasis and metabolism. The IAPP precursor, proIAPP, is processed through a series of post-translational modifications before it reaches its mature form, IAPP. Forms of proIAPP include the intact form proIAPP(1-67) as well as a partially processed intermediate, proIAPP(1-48). ProIAPP(1-48) has shown to be elevated in persons with T1D and recipients of islet transplants, suggesting problems in the processing pathway of proIAPP in these conditions. We hypothesize that impaired proIAPP processing reflects beta cell dysfunction, and that proIAPP(1-67) and proIAPP(1-48) could be used as biomarkers of beta cell stress in T1D and islet transplant recipients. To this end, the mentorâ&#x20AC;&#x2122;s laboratory treated isolate mouse islets with a chemical endoplasmic reticulum (ER) stress inducer thapsigargin, to induce a diabetic stress milieu in vitro. Western blot revealed that levels of both proIAPP(1-67) and proIAPP(1-48) are elevated in islets subject to ER stress. Using a novel ELISA developed in the Verchere laboratory enabling measurement of proIAPP(1-48) in human plasma, we measured plasma proIAPP levels collected from healthy individuals and T1D subjects. The mentorâ&#x20AC;&#x2122;s laboratory previously found that proIAPP(1-48) to mature IAPP ratios are elevated in T1D subjects. To complement measurement of proIAPP(1-48) as a biomarker of beta cell dysfunction, we are developing an additional ELISA to measure circulating proIAPP(1-67) levels. The current proIAPP(1-67) assay has a limit of detection of 0.79 pM and minimal cross-reactivity with proIAPP(1-48) and mature IAPP. Once the proIAPP(1-67) ELISA is optimized, we will measure ratios of proIAPP(1-67) to mature IAPP ratios in healthy and T1D subjects. In conclusion, we have shown that elevated proIAPP levels are indicative of beta cell dysfunction and have potential as novel biomarkers for T1D.

Poster Board #12 Aditya Chhabra, Undergraduate Student, Simon Fraser University Supervisor: Glen Tibbits, Childhood Diseases

Determination of the possible role of cardiac troponin I mutations in sudden cardiac death in infants (SUDI) using genome edited human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) Aditya Chhabra, Sanam Shafaattalab, Helen Sheng, Grace Chun, Laura Dewar, Eric Lin, Glen F Tibbits Sudden unexpected death of an infant (SUDI) is defined in the literature as the natural, non-traumatic death of an apparently healthy individual in their first years of age within 24 hours of the onset of symptoms. An unidentifiable cause of death, even after conducting a thorough autopsy alongside various other screening tests can be a very traumatic experience for the families of the victims. Genotype sequencing has recently shown a potential link between these SUDIs and inherited genes, particularly those relating to inherited arrhythmic disorders potentially highlighting the value for molecular autopsies adding to what is already being conducted. In a recent study, we examined 191 cases of children who died within the first five years of life and who were autopsy and toxicology negative. While a significant number of the mutations discovered were known to be arrhythmogenic, we found 10 identical previously unknown mutations in children who all died within the first 20 months of life. These ten deceased children were harboring a R37C mutation in the cardiac fetal paralog gene TNNI1, which encodes troponin I, a critical contractile protein expressed only in the first few years of life. To determine the arrhythmogenicity of such a mutation, we used CRISPR CAS9 to introduce a heterozygous R37C mutation in WT human induced pluripotent stem cells (hiPSCs) which were subsequently differentiated into beating cardiomyocytes (hiPSC-CM). We used monolayers of R37C+/- and R37C-/- hiPSC-CMs and optical mapping (OM) techniques to monitor voltage (Vm) and Ca2+ transients. Our preliminary data strongly suggest that R37C+/- is arrhythmogenic and is the likely cause of SUDI in these infants. The mutation appears to cause mishandling of Ca2+ and thus creates electrical anomalies which induce sudden cardiac death. In my study, I am using micro OM techniques in which the Ca2+ handling is examined using a Leica SP5 confocal microscope with a resonant scanner in single cells within the monolayer of hiPSC-CM using CAL 520, a next generation fluorescent Ca2+ indicator dye with much higher sensitivity. With this approach, we can examine events such as Ca2+ sparks and Ca2+ mini-waves which are likely the underpinnings of the arrhythmogenic events observed in R37C+/- hiPSC-CMs. Ultimately, the findings from this project will provide insight into implications of this specific gene and mutation in the pathogenesis of SUDI and will allow for the re-evaluation for the value for both molecular autopsies as well as other screening methods moving forward.

Poster Board #13 Thomas Hoang, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

Intestinal epithelial inflammasomes: Frontline defenders against Campylobacter jejuni infection Thomas Hoang, Martin Stahl, Hyungjun Yang, Leigh Knodler, Bruce Vallance

Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the developed world, commonly acquired through the consumption of contaminated water or poultry products. Following exposure, C. jejuni quickly establishes itself in the intestinal tract of its host, triggering symptoms that include cramps, fever and bloody diarrhea. Previous research has described C. jejuniâ&#x20AC;&#x2122;s ability to invade intestinal epithelial cells (IECs), an important virulence trait, in vitro. However, very little is known about the importance of cell invasion in vivo and its effect on disease progression. Our lab focuses on the importance of epithelial cell inflammasome activation in controlling C. jejuni pathogenesis. Knockout mice lacking the inflammasome components ASC, Caspase-1, Caspase-1/11 or Interleukin-18, were inoculated with Campylobacter jejuni 81-176. Colon and cecal samples were collected on days 1 and 7 post-infection and their pathogen burdens were assessed. Colonization was visualized by immunofluorescence and colonic and cecal histopathology was also observed, along with relative changes in expression of the pro-inflammatory mediators interleukin-1Î˛ and interleukin-18. Our findings indicate that although there were no significant differences in luminal colonization across knockouts, there was a drastic increase in C. jejuni present and replicating within LAMP-1 positive vesicles of Caspase-1 and Capsase-1/11 knockout IECs compared to wild type. We also observed that wild type mice produced significantly more IL-1Î˛ and IL-18 relative to the inflammasome knockouts, despite the knockouts harbouring more intracellular bacteria and exhibiting increased signs of inflammation. We propose that inflammasome-mediated cleavage of Caspase-1 and the resulting immune response are responsible for combating intracellular invasion and replication in IECs by the otherwise predominantly extracellular pathogen C. jejuni. Failure to control epithelial cell invasion leads to more severe pathology later in infection and an inability to combat C. jejuni within the epithelium. The ability to invade IECs may allow this pathogen to evade oral antibiotics and humoral immunity, thus elevating its virulence and persistence over time in the gut. These results highlight the importance of inflammasome activation within the intestinal epithelium in combating C. jejuni infection and the consequences of a failure to control cell invasion during the course of infection.

Poster Board #14 Maya Willms, Undergraduate Student, University of British Columbia Supervisor: Michael Kobor & Olivia Wong, Healthy Starts

Examining the role of H2A.Z in transcription via targeted removal Maya Willms, Olivia Wong, Michael Kobor DNA is coiled around 8 histone proteins into a structural unit called the nucleosome, which is then further compacted and packaged as chromatin in the cell nucleus. The structure of chromatin is highly dynamic and is regulated by several processes, one of which is the incorporation of the histone H2A variant, H2A.Z, into the nucleosome. H2A.Z is highly conserved across eukaryotic organisms and is essential for the viability of multicellular organisms. Studies have shown that loss of H2A.Z is associated with the dysregulation of fundamental biological processes and results in embryonic lethality in higher order eukaryotes. Furthermore, the overexpression of H2A.Z has been observed in multiple cancers, as well as the proliferation of breast cancer cells. H2A.Z is predominantly found at the nucleosomes flanking the transcription start sites. In addition, H2A.Zâ&#x20AC;&#x2122;s occupancy at the gene promoters is negatively correlated with gene expression. However, whether the removal of H2A.Z from the nucleosomes at the gene promoters is sufficient to induce transcription is unclear. As such, we utilized the Anchor Away technique to induce the removal of H2A.Z from the nucleus in Saccharomyces Cerevisiae. This technique rapidly depletes the cell nucleus of H2A.Z via tethering it to an abundant cytoplasmic protein using rapamycin dependant heterodimerization. The targeted removal of H2A.Z was optimized and fluorescence microscopy was utilized to visualize the removal of H2A.Z from the nucleus. We will use this technique to investigate the role of H2A.Z in gene transcription by assaying the expression of genes with H2A.Z at the promoters, before and after its removal from the nucleus. By investigating the active removal of H2A.Z from the nucleus and examining the effect on gene expression, we hope to further elucidate the role of H2A.Z in transcription.

Poster Board #15 Lara Lampe, Undergraduate Student, University of British Columbia Supervisor: Michael Kobor & Marla Sokolowski, Healthy Starts

Determining the effects of food deprivation on the epigenome Lara Lampe, Maria Aristizabal, Michael Kobor Across species, allelic differences in the foraging (for) gene modulate the sensitivity of an individual to its environment, presenting a unique opportunity to study how gene by environment interactions can impact the way in which information is biologically embedded and transmitted across generations. In Drosophila melanogaster, two naturally occurring alleles of the for gene (rovers and sitters) underscore differences in foraging behaviour, metabolism, stress resistance, learning, and memory in relation to food availability. At the molecular level, rover and sitter flies display distinct gene expression profiles under normal and food deprived conditions, including a differential effect on genes involved in insulin signalling and sugar metabolism. Given the regulatory effect of the epigenome on gene expression, we hypothesized that rover and sitter flies also differ at the level of histone modifications, which in turn may give them a differential ability to pass down environmental information to subsequent generations. To determine the effect of genes and the environment on shaping the epigenome, I will use western blotting to map histone modifications in rover and sitter flies, at various life stages, under normal and food deprived conditions. In addition, I will also test their effect on the phosphorylation of protein phosphatase 2A (PP2A), the only candidate substrate for PKG (a cGMP-dependent protein kinase encoded by the for gene). PP2A is an important candidate because it has been implicated in some of the same molecular pathways that for participates in, including metabolism and brain biology, thus shedding light into the pathways that for participates in to influence behaviour, metabolism, stress resistance, and memory in response to environmental cues. Overall, through this work, I hope to illuminate the molecular pathways through which gene by environment interactions are biologically embedded.

Poster Board #16 Daisy Li, Undergraduate Student, University of British Columbia Supervisor: Heather Denroche, Childhood Diseases

Can lipid nanoparticle encapsulation protect against dexamethasone induced diabetes? Daisy Li, Heather C. Denroche, Sam Chen, Chris Tam, C. Bruce Verchere Background and Objectives: Dexamethasone (dex) is an effective and widely used immunosuppressant. However, under chronic exposure, dex is known to cause insulin resistance and diabetes. In this study, we tested two lipid nanoparticle (LNP) - encapsulated prodrugs of dex â&#x20AC;&#x201C; termed LD02 and LD03 - to determine whether encapsulation can protect against dex-induced insulin resistance in mouse models. Methods: Encapsulated prodrugs LD02 and LD03 were tested in separate studies using the same experiment design. C57Bl/6J 12-week-old male mice were matched for body weight (BW) and blood glucose (BG) and assigned to five test groups (n=5), received injections 3 times per week of either PBS, free form dex (4 mg/kg), matched dose prodrug, 1/10th dose prodrug, or empty LNPs. Fasting BW and BG were measured, and fasted blood from saphenous vein was drawn for plasma insulin analysis by ELISA, weekly. Insulin tolerance tests were performed on day 28 for LD02 and day 32 for LD03 experiments. Tissues were collected on days 32 and 49, for LD02 and LD03 studies, respectively. Results: For both studies, no change in BW or BG was observed. Contrary to our hypothesis, when comparing LD02 against free dex, the matched dose group had >2-fold insulin increase and the 1/10th LD02 dose promoted similar levels of hyperinsulinemia as full dose free dex. Mice treated with the LD02 matched dose were significantly insulin resistant compared to the empty LNP controls (p=0.018). Matched dose LD03 promoted only slightly less hyperinsulinemia than free dex (p= 0.0002 free dex vs. empty LNP; p=0.0062 LD03 matched vs empty LNP on day 27) but hyperinsulinemia was not seen in the 1/10th dose. No significant change in insulin sensitivity was seen between any groups in the LD03 study. Conclusion and Future Directions: LD02 does not offer protection against dex induced insulin resistance and in fact exacerbates this effect. LD03 may protect against insulin resistance at low doses, however at 4 mg/kg, it caused a similar increase of plasma insulin as free dex. Future studies will explore the effectiveness of a lower dose LD03 as an immunosuppressant compared to free dex.

Poster Board #17 Shannon Tang, Undergraduate Student, University of British Columbia Supervisor: Pascal Lavoie, Healthy Starts

Neonatal compensation for an immature immune system S. Tang, E. Marchant, Z. Sharafianardakani, P. Lavoie Background: Neonates are highly susceptible to infection, and this is the cause of over one third of neonatal mortality worldwide. Development of the adaptive immune response relies on exposure to pathogens. Relative to adults, neonates have a significantly smaller repertoire of memory cells. It logically follows that neonates depend heavily on mucosal and innate immunity. Recent research has shown an innate-like function in undifferentiated naïve CD4+ T cells. Under the harsh stimulation of PMA and Ionomycin, these cells were observed to secrete interleukin-8 (IL-8), a neutrophil chemotactic factor. Interestingly, this response was heightened in neonates, relative to adults. Neonatal naïve T cells could be leveraging these innate-like functions to seek help from nearby innate cells, in an attempt to compensate for diminished immunological memory. Objectives: 1) To define the necessary conditions and stimulation required for IL-8 production in a physiological environment; 2) To better understand the kinetics of IL-8 production and secretion; 3) To compare the effects of neonatal and adult antigen-presenting cells (APCs) on the production of IL-8 in naïve T cells. Methods: Neonatal and adult APCs were stimulated for 24 hours with PRR ligands (LPS, Curdlan or unstimulated) in media containing Brefeldin A before being cultured with neonatal or adult naïve T cells. These cells were stimulated with either OKT3 or anti-CD3/CD28 beads. Supernatants were collected 6 and 24 hours following co-culture and cells were stained for flow cytometry. Results: We did not see an effect of neonatal APCs in the induction of IL-8 in naïve T cells, but the PRR stimulation of the APCs did lead to greater production of IL-8. The responses observed from PRR stimulation were significantly lower compared to the harsh effects of PMA/I. This suggests that the IL-8 production observed in naïve T cells may be weaker in a physiological setting, but the production of IL-8 is promising as a potential innate-like function of naïve T cells. Further research in cytokine production by naïve T cells could lead to a better understanding of the immune function of neonates and provide potential avenues for the development of vaccines.

Poster Board #18 Heidi Vieira, Undergraduate Student, University of British Columbia Supervisor: James Lim, Childhood Diseases

Evaluation of integrin α6 (CD49f) isoforms as potential biomarkers in breast cancer Heidi Vieira, Vicky Li, Karen Jung, Pascal Leclair, Christopher Maxwell, Chinten James Lim Integrin α6 (CD49f) is a cell surface receptor protein with roles in cell signalling and adhesion. Increased expression of integrin α6 in breast cancer cells has been associated with more rapid disease progression as well as reduced survival time in clinical studies. There are two splice isoforms for this integrin, α6A and α6B, which differ in both the length and composition of their cytoplasmic tail. Since the cytoplasmic domains determine the specificity of integrin-mediated signaling, α6A and α6B may have distinct roles in tumourigenicity of breast cancer cells. Previously, we showed by western blotting that α6B protein levels were elevated in cells derived from tumoursphere cultures, when compared to the same cells maintained in standard tissue culture. Mammary cancer cells cultured as tumourspheres are known to enrich for a stem-like population; thus, our finding suggests a correlation between the α6B isoform and a stem-like phenotype. As differential splicing occurs at the transcript level, we hypothesized that this difference in protein expression would correlate to a detectable difference in relative transcript abundance. We aimed to optimize RTPCR for detection of integrin α6 splice variants, in order to determine the level at which this upregulation of α6B occurs. Breast cancer cells from various cell lines were plated under tumoursphere or typical culture conditions; the RNA was then extracted and analyzed by RTPCR. Preliminary results show a tumoursphere culture-mediated increase in transcripts of both isoforms in cell lines that express low α6 protein levels under typical culture conditions. This finding suggests that regulation of α6 expression may happen at the transcript level only in cell lines with low α6 protein expression. Future directions will involve profiling of relative transcript levels across a wider panel of cell lines, and correlating this with α6A and α6B protein levels. Ultimately, RTPCR detection of integrin α6 mRNA could have potential as a prognostic tool in the diagnosis and subtyping of breast cancers.

Poster Board #19 Maleeha Virk, Medical Student, National University of Ireland Supervisor: Christopher Maxwell, Childhood Diseases

Cancer cell engraftment and scattering is enabled by cell cycle progression Maleeha Virk, Marisa Connell, Tony L.H. Chu, Zhengcheng He, Seyed M.R. Rahavi, Gregor S.D. Reid, Christopher A. Maxwell Problem: Metastasis accounts for 90% of deaths from cancer. Background: Metastasis requires carcinoma cells at the original tumour site to undergo polarity reversal from apical-basal to front-rear polarity in a process defined as epithelial-to-mesenchymal transition (EMT). This polarity reversal initiates cell scattering and is achieved through intracellular changes in centrosome position and microtubule organization. Previously, we found that cell migration was more active in S/G2-phase cells. Our goal was to determine whether cell cycle progression impacts cell scattering as well as metastasis in aggressive breast cancer cells. Methods & Results: Mouse breast cancer cells, termed 4T1-luciferase2, were synchronized in G1-phase or grown asynchronously and then transplanted in NOD-scid-gamma or BALB/c mice. Bioluminescence was used to track tumour engraftment. EMT markers were assessed via RT-PCR analysis. In parallel, we studied the process of cell scattering in mammary epithelial cell lines (mouse nMuMG-FUCCI and human MCF10A). Cells were monitored via time-lapse live cell imaging as they passed through mitosis and daughter cells scattered by detaching from one another and migrating in the opposite direction. During cell scattering, inter-nuclei distances and time were measured with respect to cell cycle phase in nMUMG-FUCCI cells. Additionally, these parameters were compared in luminal and basal forms of human MCF10A cells. Our tumour engraftment study demonstrated that cells in the asynchronous phase engrafted more efficiently than G1-phase enriched cells and expressed EMT markers, such as vimentin, Cdh1, Cdh2, Snail1 and Snail2, at elevated levels. Our live cell imaging results revealed that cell scattering was cell cycle dependent with basal cells having an increased scattering distance than luminal cells. Conclusion: The outcomes from this study illustrate the importance of cell cycle progression in breast cancer metastasis specifically during cell scattering, which predominantly occurred in G1phase and was more pronounced in basal cells.

Poster Board #19B Li Qing Wang, Undergraduate Student, University of British Columbia Supervisor: Wendy Robinson, Healthy Starts

HLA-KIR interaction in acute chorioamnionitis affected pregnancies Li Qing Wang, Chaini Konwar, Maria S PeĂąaherrera, Wendy P Robinson Introduction: Babies born before 37 weeks of gestation are classified as preterm. Spontaneous preterm birth is associated with a number of conditions including chorioamnionitis (CA), which is an inflammation of the placenta and fetal membranes. Babies born from a pregnancy affected by chorioamnionitis are at an increased risk of early life-threatening infections, long-term developmental delay and poor health outcomes. One of the plausible contributors to chorioamnionitis is an inappropriate maternal immune response to fetal cells which may be partially explained by genetic variation. During the first trimester, maternal uterine natural killer (uNK) cells constitute up to 70% of uterine lymphocytes. These cells have killer-cell immunoglobulin-like receptors (KIR) that recognize and interact with human leukocyte antigens (HLA-C) class I molecules expressed on the fetal placental cells. Previous studies suggest that certain combinations of maternal KIR â&#x20AC;&#x201C; placental HLA genotypes influence the risk of reproductive success in preeclampsia and spontaneous abortions. No studies have previously examined this interaction in chorioamnionitis affected pregnancies. Therefore, we sought to investigate this interaction in chorioamnionitis to address the gaps in our current understanding of the immunological roles of KIRs and HLAs in this type of inflammation. Method: Paired fetal placental (chorionic villi) samples and maternal decidual samples from 32 chorioamnionitis cases and 160 controls were identified for this study. DNA was already available for the samples of placental villi (which reflects the fetal genotype). Both HLA-C and KIR will be genotyped by pyrosequencing. Data analysis will be performed in R statistical environment. Preliminary work: I extracted DNA from a subset of the decidual samples and performed gel electrophoresis to assess sample quality. I designed and optimized the HLA-C genotyping assay. On a subset of the identified samples I also performed HLA-C genotyping by pyrosequencing. After completion of HLA-C genotyping, I intend to characterize the KIR maternal genotypes and examine the interaction between HLA and KIR genotypes. Significance: Currently, histologic examination of the placental is the gold standard for the diagnosis of chorioamnionitis. However, placental histological examination is only possible after delivery. By examining the KIR-HLA interaction, we may be able to identify women who are at risk for developing the inflammation associated with chorioamnionitis and better understand the underlying mechanisms.

Session Three BASIC SCIENCE Moderator: Maria Aristizabal Participants: Panteha Eshtiaghi Yue Zhou (Joe) Huang Navjit Moore Samantha Pawer Kwestan Safari Stephanie SchĂźler Michelle Lee Kiana Yau Alexandra J. Zhou

Poster Board #20 Panteha Eshtiaghi, Medical Student, University of British Columbia Supervisor: Jan Dutz, Childhood Diseases

Skin monitoring of diabetogenic inflammation Panteha Eshtiaghi, Yiqun Zhang, Jan Dutz Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic beta cells. A limitation in the development of effective therapies for T1D is lack of access to tissue that reflects the inflammatory process resulting in beta cell death. Delayed type hypersensitivity is a T-cell mediated inflammatory skin reaction that allows the monitoring of cellular immune responses to a defined antigen. By administering islet antigens into the skin of non-obese diabetic (NOD) mice, we explored the skin as a feasible site for noninvasive tracking of beta cell autoimmunity. We hypothesized that circulating diabetogenic T cells will accumulate both in the pancreas and skin-transplanted islets. The ultimate goal is to develop a skin test that can be used to mirror and follow the diabetogenic immune response within the endogenous pancreas. Method: Insulitis-free islet equivalents were isolated from NOD-severe combined immunodeficient mice and injected intradermally into syngeneic NOD, non-obese resistant (NOR), and NOD diabetic mice. Autoimmune destruction of the pancreas and skin-transplanted tissue was visualized by immunohistochemistry, and immune responses in the axillary lymph nodes (ALN) were evaluated through flow cytometry at Day 6 and Day 12 post-injection. Results: Preliminary histological analysis shows that islet-injected NOD mice exhibit reduced insulitis score compared with non-injected NOD and NOR mice. No significant infiltrating cells were observed in skin tissue samples six days post injection. Furthermore, enumeration of ALN cells revealed increased number of lymphocytes in islet-injected NOD mice compared with control. Flow cytometric analyses revealed an increase in absolute number of CD69 expressing CD4+ and CD8+ T cells, V7+ CD8+ autoreactive T cells, and CD19+ B cells in ALNs of islet-transplanted NOD mice. Future directions: Further studies will stain skin-transplanted islet equivalents 24 hours after injection to track their location in the dermis and determine whether there is a need for a cell-carrier or tissue scaffold. We will also determine if intradermally injected islet protein (GAD65) can elicit a similar inflammatory response reflecting the inflammation within the pancreas. Finally, we anticipate our results will provide a starting point to investigate the role of the skin in inducing tolerogenic responses in T1D.

Poster Board #21 Yue Zhou (Joe) Huang, Undergraduate Student, University of Western Ontario Supervisor: Tobias Kollmann, Healthy Starts

Does viability affect the non-specific effect of Bacillus Calmetteâ&#x20AC;&#x201C;GuĂŠrin vaccines? Yue Zhou Huang, Byron Brooks, Danny Harbeson, Tobias R. Kollmann The Bacillus Calmette-Guerin (BCG) vaccine contains live attenuated Mycobacterium bovis and is used primarily to build adaptive immunity against pathogenic Mycobacterium tuberculosis. Studies on the BCG vaccine have previously shown that its use at an early stage of life correlates to a general decrease in mortality, beyond that afforded by the prevention of tuberculosis alone. Of the most common causes of non-accidental neonatal mortality worldwide, infectious diseases is the most prevalent, with sepsis being a major contributor. It was hypothesized and later demonstrated in mice that the administration of the BCG vaccine reduced sepsis-induced mortality rates, suggesting that a similar phenomenon may be occurring in humans as well. The mechanism behind which BCG offers this nonspecific protection against sepsis, however, is not well understood at this time. Due to concerns about bacterial dissemination, alongside the naturally low incidences of tuberculosis in most developed nations, BCG vaccination has gradually been removed/phased out from the typical vaccination schedule of infants and children in North America. The use of an inactivated vaccine could address the potential for dissemination, though studies on the use of a non-viable M. bovis without an adjuvant as a vaccine against tuberculosis have been shown to be less effective than the live attenuated variant. In this study, we aim to determine if heat-killed BCG still offers nonspecific protection against sepsis; establishing if viability is necessary would also shed light its mechanism of action. An interventional study design will be utilized to determine the nonspecific effects of BCG vaccines in Neonatal C57BL/6 pups. The pups are vaccinated at day of life 4-5 with either heat-killed BCG or live BCG, with unvaccinated pups as controls; polymicrobial sepsis is then induced at day of life 7-8 by the administration of mouse cecal slurry into the peritoneal cavity via intraperitoneal injection. The pups are euthanized 24 hours later to determine the presence of endobacteria in their blood and organs. It has been previously shown that in this sepsis model, the bacterial load found within various organs correlates to the severity of the disease.

Poster Board #22 Navjit Moore, Undergraduate Student, University of British Columbia Supervisor: Bruce Vallance, Childhood Diseases

THE MINI GUT EVOLUTION: Using organoids to characterize innate signalling in intestinal epithelial cells Navjit Moore, Joannie Allaire, Martin Stahl, Bruce Vallance Background: Inflammatory Bowel Disease (IBD) is an autoimmune disease characterized by chronic inflammation occurring in the gastrointestinal (GI) tract. The intestinal epithelial cells (IEC) are the primary interface between the host and microbes that dwell in our GI tract. Comprised of several different IEC subtypes (enterocytes, goblet cells, Paneth cells etc.), the intestinal epithelium creates a formidable barrier to protect against GI bacteria by proliferating and producing mucus, antimicrobial factors, and cytokines. Many of these responses are triggered when IEC recognize bacterial products in order to maintain gut health and homeostasis. While many groups have studied IEC response to bacteria in vitro, they have always used transformed IEC lines representing only enterocytes. Our lab is now using cutting edge technology to grow intestinal organoids (mini-guts) comprised of primary IEC derived from mice or human gut samples. These mini-guts form 3D-structures mimicking the organization/function of in vivo guts, and include all IEC subtypes. While a striking advancement, this model needs a deeper characterization to define the IEC intrinsic innate pathways and responses elicited by bacteria. Objective: To characterize mouse intestinal organoid response to whole bacteria, bacterial products, and cytokines. Methods: Crypts from cecum and colon of wildtype C57BL/6 mice were isolated and seeded in matrigel to form intestinal organoids. They were grown in media with growth factors for 2 weeks and then either treated with the bacterial product FLIC or cytokine Il-1b for 4h, 20h, or 24h. Immunostaining was done for Ki67 protein (marker for proliferation), Muc2 protein (marker for mucus), and Nfkb protein (marker for inflammation). qPCR was used to assess the mRNA expression of the chemokine Cxcl1 and the cytokine Tnfa known to be released during an inflammatory response. Preliminary Results: Immunostaining of 4h Il-1b treated intestinal organoids showed an increased nuclear localization of Nfkb protein relative to the untreated group for both cecum and colon. qPCR analysis showed an increased expression in Cxcl1 and Tnfa in the 4h FLIC and Il-1b stimulated group relative to the untreated group for both cecum and colon. Significance: The preliminary results demonstrate that we are able to mimic a slight in vivo inflammatory response in mouse intestinal organoids. The new optimized mini-gut technique will allow us do similar analysis in human intestinal organoids and help further our understanding of the dynamic relationship between bacteria, inflammation, and epithelial cells. 37

Poster Board #23 Samantha Pawer, Undergraduate Student, University of British Columbia Supervisor: Carolyn Brown, Healthy Starts

Analysing functionality of long non-coding RNAs Samantha Pawer, Thomas Dixon-McDougall, Carolyn Brown Long non-coding RNAs (lncRNAs) are emerging as important and often poorly understood regulators. The lncRNA XIST is a cis-acting transcript that initiates mammalian female X-chromosome inactivation. We hypothesize that other lncRNAs behave similarly; however, it is challenging to evaluate the functionality of lncRNAs. For one, they lack open reading frames, causing difficulties in determining the impact of mutations. Second, transcripts from enhancers or other regulatory elements create complications in demonstrating the importance of lncRNAs. To bypass these obstacles, we are testing four different approaches aimed at truncating lncRNA transcription, before analysing the transcription of target genes. We are doing this by integrating poly(A) sites into the human genome, using XIST as our initial lncRNA gene. In our first method, we used the CRISPRassisted insertion tagging (CRISPaint) application, which simultaneously cuts our specified region of XIST, as well as pCRISPaint-TagGFP2-PuroR to be inserted into the genome. For our second approach, we integrated neomycin resistant pEGFP-N1 into XIST, and followed this with selection. Our third approach builds on the first two. By ligating the neomycin resistant gene into pCRISPaintTagGFP2-PuroR, we are generating a plasmid that will both survive selection and effectively integrate into the genome. A limitation to this method is that the transcription stop may only work if the plasmid integrates into XIST in one of the two possible orientations. Thus, the goal of our fourth approach is to design a plasmid containing antibiotic resistance, and two transcription stops in opposite orientations on either side of a guide RNA target site. This will enable the plasmid to integrate into lncRNA genes, and prevent transcription regardless of the orientation of insertion. In testing our cloning approaches, the first procedure did not survive selection, while the success of the second approach is being assessed, and the third and fourth plasmids are being prepared for HT1080 transfection. Once validated, the optimal approach can be used with lesser studied lncRNA genes, and address our hypothesis to demonstrate these lncRNAs as potential regulators of target genes.

Poster Board #24 Kwestan Safari, Undergraduate Student, Simon Fraser University Supervisor: Laura Sly, Childhood Diseases

Impact of the Fcgamma receptor gene variants on antibodyinduced anti-inflammatory macrophage activation Kwestan Safari, Laura Sly Inflammatory Bowel Disease (IBD) is a chronic immune mediated disease characterized by inflammation along the gastrointestinal tract. Antibody based biological therapies have revolutionized treatment for IBD, however, 10% of patients do not respond to biological therapies. Macrophages are key players in the immune response and contribute to inflammation in IBD. Fcgamma receptors are nonspecific antibody (IgG) receptors expressed on the surface of macrophages, which activate macrophages to produce large amounts of the anti-inflammatory cytokine, IL-10 and low levels of pro-inflammatory cytokine in response to inflammatory stimuli. Macrophages co-stimulated with the pooled polyclonal IgG antibody based drug, IVIg, and LPS (a bacterial toxin) are skewed to an anti-inflammatory, IL-10 producing phenotype. A gene variant in the FcgammaRIIA receptor predisposes individuals to develop IBD and has been linked to a failure to respond to biological therapy. The FcgammaRIIA gene variant changes the receptor from a low affinity receptor for IgG, to a high affinity receptor. Macrophages from participants with the FcgammaRIIA risk variant produce higher amounts of pro-inflammatory cytokines in response to inflammatory stimuli compared to non-risk variants, as well as are less able to limit immune responses when co-stimulated with IVIg and LPS. We hypothesize that individuals with the risk variant produce more inflammatory cytokines when stimulated with LPS, and are unable to limit inflammation when co-stimulated with IVIg and LPS because the high affinity FcgammaRIIA sequesters antibody from the FcgammaRs that mediate anti-inflammatory macrophage activation. To address our hypothesis, we will determine: the effects of siRNA knockdown of Fcgamma receptors on antibody-mediated anti-inflammatory macrophage responses and the effects of FcgammaRIIA gene variants on the Fcgamma receptors used for antibody-mediated anti-inflammatory macrophage activation. We found that FcgammaRI and FcgammaRIIB were required for antibody-mediated IL-10 production in LPS-stimulated macrophages. Subjects with the high affinity FcgammaRIIA produced more inflammatory cytokines in response to LPS, and produced less IL-10 and more pro-inflammatory cytokines in response to LPS and antibody compared to non-risk variants. This may explain why people with the risk variant are more likely to develop IBD and may have implications for why the risk variant increases the chance of failing biological therapy.

Poster Board #25 Stephanie Schüler, Undergraduate Student, Hamburg University of Applied Sciences Supervisor: Matthias Görges, Evidence to Innovation

Evaluation of the Effect of a Ketamine Adjuvant Anesthetic Administration on Depth of Hypnosis Indices During Total Intravenous Anesthesia – a Comparative Study Using a Novel Case Replay System Stephanie Schüler, Dr. Chris Petersen , Dr. Matthias Görges Background: Monitoring the brain using electroencephalography (EEG) during general anesthesia provides the anesthesiologist with valuable feedback of the patient’s level of anesthesia and reduces the risk of incorrect dosage. Ketamine is a potential adjunct to a standard anesthetic, which is suspected to significant improve post-operative pain. Yet it’s effects on processed EEG parameters are poorly understood; Ketamine in contrast to most other anesthetic agents, which predominantly depress EEG, increases high frequency power in the high beta and low gamma (24- 32 Hz) range. Objectives: The purpose of this study is to compare the effects of intraoperative EEG in the presence and absence of ketamine, on outputs generated by three depth of hypnosis (DOH) monitors. Methodology: Our team previously collected EEG data from 30 adult patients, using the NeuroSENSE (NeuroWave Systems Inc., Cleveland Heights, OH) monitoring system, whereby two thirds of the patients receiving ketamine (at two different dose levels), and one-third received a placebo. De-identified EEG data will be replayed to the following DOH monitors: NeuroSENSE, BIS (Covidien, Mansfield, MA) and M-Entropy (GE Healthcare, Buckinghamshire, UK), using an in-house developed hardware case replay system. The following data will be collected: a) DOH indices for NeuroSENSE, BIS, and M-Entropy; b) Electromyography indices (EMG) for NeuroSENSE and BIS; and c) Burst suppression ratio (BSR) for NeuroSENSE, BIS, and M-Entropy. The resulting triplets of DoH, EMG, and BSR indices will be compared visually, by plotting the three time-synchronized traces. Subsequently, they will be evaluated using Bland-Altman statistics, correlation plots and four-quadrant plots for anesthetics in each condition. Next, spectrograms of EEG will be analyzed to identify areas with high presence of activity in the gamma EEG band; here, differences in DOH and EMG will be compared using paired nonparametric statistics, such as Wilcoxon’s signed ranked test. Results: We expect results to be available by the time of the poster presentation. Based on past work, we suspect different behavior of BIS and NeuroSENSE for lighter levels of DOH. Conclusion: Replay of previously recorded EEG data provides a novel approach for the comparison of clinically used DOH devices and their limitations. Our work will expand the knowledge in this area and formulate hypotheses for future work. 40

Poster Board #26 Michelle Lee, Undergraduate Student, University of British Columbia Supervisor: Stefan Taubert, Healthy Starts

A novel transcriptional mechanism in zinc homeostasis Michelle Lee, Naomi Shomer, Jennifer Grants, Stefan Taubert Zinc is a metal essential for cellular functions: it serves as a signaling molecule and as structural cofactor in many proteins. However, high zinc levels in the cytoplasm are toxic to the cell and cause heavy metal stress. Also, deregulated zinc metabolism and mutations in zinc transporter genes are linked to an increased risk for type 2 diabetes. Therefore, mechanisms that maintain zinc homeostasis are crucial for cell function and overall health of an organism. Transcriptional regulatory mechanisms play a critical role in zinc homeostasis by controlling the levels of zinc detoxification genes. Our lab uses the worm Caenorhabditis elegans, a powerful genetic model to identify conserved regulators of zinc metabolism/uptake genes. In this worm, key players in the transcriptional regulation of zinc homeostasis include the Mediator complex subunit MDT-15 and the Transcription Factor (TF) HIZR1/NHR-33; however, whether they work together or in separate pathways is not known. To study gene regulation by zinc and related metals, I used a cadmium responsive gene 1 (cdr-1) promoter GFP reporter; this reporter accurately reflects the induction of cdr-1 by zinc and the related metal cadmium. Using this reporter, I showed that mdt-15 was required to induce this induction by zinc, resembling the previously shown requirement for mdt-15 in cadmium-driven cdr-1. Next, I tested whether MDT-15 and HIZR-1/NHR-33 work together to regulate zinc homeostasis. I used a nhr33 gain-of-function (gf) mutant, which induces zinc homeostasis genes, including cdr-1, even in the absence of zinc. In these worms and wild-type controls, I then knocked down mdt-15 by RNA interference (RNAi), and subsequently examined if the induction of zinc responsive genes in nhr33(gf) worms was mdt-15 dependent. In line with this hypothesis, I found that nhr-33(gf) worms induce zinc homeostasis genes in the absence of zinc, and this induction is abrogated when mdt-15 is knocked down. Therefore, we can conclude that nhr-33 function in a mdt-15 dependent manner to regulate zinc.

Poster Board #27 Kiana Yau, Undergraduate Student, University of British Columbia Supervisor: Bruce Verchere, Childhood Diseases

The role of the Nlrp3 inflammasome in islet amyloid polypeptide (IAPP)-induced diabetes Kiana W. Yau, Heather C. Denroche, C. Bruce Verchere Background: Islet amyloid formed by aggregates of the beta-cell derived hormone, IAPP, is thought to contribute to beta-cell dysfunction in type 2 diabetes, but the mechanism is unclear. We found that IAPP aggregates induce secretion of interleukin-1β from macrophages which impairs beta-cell function. Previous in vitro studies have shown that this process is dependent on the activation of the Nlrp3 inflammasome. Aim: We aimed to determine whether Nlrp3 deficiency attenuates islet inflammation and beta-cell dysfunction in a mouse model of islet amyloid-induced diabetes. Methods: We crossed hIAPP transgenic (hIAPPTg/0) mice (rodent IAPP cannot aggregate) with global Nlrp3 knockout mice to generate hIAPPTg/0 mice and hIAPP0/0 littermate controls with (Nlpr3+/-) and without (Nlrp3-/-) functional Nlrp3. Male and female mice were fed high fat diet (45% kcal, HFD) at 10 weeks of age and had blood glucose and body weight monitored biweekly. Plasma samples were collected for quantification of insulin levels. Glucose and insulin tolerance tests will be performed at various time-points throughout the study. Results: ANOVA analysis up to 17 weeks of age (7 weeks of HFD) shows that genotype has a significant effect on blood glucose levels in male mice (p=0.0004). hIAPPTg/0; Nlrp3+/- males were significantly hyperglycemic relative to hIAPP0/0; Nlrp3+/- mice at 7 weeks of HFD (20.9±3.3 mmol/L for hIAPPTg/0; Nlrp3+/- and 11.1±1.1 mmol/L for hIAPP0/0; Nlrp3+/-; p<0.0001). Relative to hIAPPTg/0; Nlrp3+/- males, hyperglycemia was attenuated in hIAPPTg/0; Nlrp3-/- males (p=0.008). There was no significance in blood glucose levels at time points prior to 7 weeks of HFD. No differences in glycemia were observed in female mice of any genotype. High fat diet induced body weight increase in both males and females, but there were no significant differences between genotypes. Conclusions: Similar to its known contribution to hIAPP-induced inflammation in vitro, our data indicate that the Nlrp3 inflammasome mediates hIAPP-induced hyperglycemia in vivo, which may bring important implications for understanding and treating type 2 diabetes. We will continue to monitor the mice biweekly and assess beta-cell function and islet inflammation via glucose and insulin tolerance tests, plasma insulin, pro-insulin, and cytokines levels, and pancreas histology.

Poster Board #28 Alexandra J. Zhou, Undergraduate Student, University of California Supervisor: Todd Woodward, Brain, Behaviour & Development

Task-positive and task-negative functional brain networks play complementary roles in verbal fluency Alexandra J. Zhou, Paul Allen, Ryan Lim, Todd S. Woodward Overview: Verbal fluency involves generating words that begin with a particular letter, with the stipulation that no word can be repeated, and it involves both linguistic processes, and cognitive demand (the latter being increased after the most salient words for each letter are exhausted). We used multivariate methods to identify networks preferentially involved in linguistic and demand processes during verbal fluency. Methods: Twenty-six healthy participants generated non-repeating words based on the letters presented while in the MRI scanner. There were eight blocks of alternating easy and hard conditions, and in each block, a letter is presented on a screen eight times for four seconds each. Easy condition refers to the letters that are associated with more common words (e.g. C, S, and L) while the hard condition includes letters that are associated with less common words (e.g. F, I, and O). The trials were also studied in a linear fashion to note changes in network activity as trials progressed over the block. Data were analyzed using constrained principal component analysis for fMRI data (fMRICPCA). Results: Two functional brain networks were derived. One of the observed networks is a tasknegative network, which reduced activity on trials, and the other was a task-positive network (language and inner speech regions), which increased activity on trials. As the level of linguistic requirements increased (i.e., the more difficult letters), only the task positive network increased activation. In contrast, as the trials became later in the block, only the task negative network changed, increasing suppression strongly starting at trial 4 and remaining suppressed until the last trial (8). Conclusions and Significance: Based on the results obtained in this study, we can conclude that the task negative network is not simply a reciprocal mirror of the task-positive (language/inner speech) network, but unlike the language/inner speech network it is (1) sensitive to demand processes; and (2) not sensitive to linguistic demands. Future investigations can use this task as a tool to separately investigate disorders of language and cognitive demand such as autism and schizophrenia.

Session Four CLINICAL Moderator: Jim Potts Participants: Victoria Chan Tara Evans-Atkinson Jollee Fung Kira Genise Tiffany Lee Wayne Leung & Ishmeet Singh Alice Liu Victoria McCutcheon Simon Robins Arpreet Singh Paul Yen

Poster Board #29 Victoria Chan, Medical Student, Western University Supervisor: Stephan Malherbe, Evidence to Innovation

The effect of dexmedetomidine on recovery room and hospital discharge times after non-painful day case procedures in children Victoria Chan, Muizz Wahid, Andrew Poznikoff, Matthias Gรถrges, Norbert Froese, Simon Whyte, Stephan Malherbe Background: Dexmedetomidine is an alpha-2 adrenoceptor agonist used as a sedative drug in anesthesia and intensive care practice. Its benefits over other sedatives include minimal respiratory depression, reduced emergence delirium, and lower post-operative opioid requirements, all of which are of particular value in the pediatric population. One potential disadvantage of dexmedetomidine is its 2- to 3-hour half-life, which renders it a moderately long-acting drug that can lead to prolonged sedation. This may delay discharge from the hospital; however, more investigation is needed. Aim: We hypothesize that the use of dexmedetomidine prolongs discharge times in cases where little or no post-operative pain is expected. Our objectives include determining the associations between a) intra-operative dexmedetomidine administration and lengths of stay in the postanesthesia care unit (PACU) and b) the surgical day care unit (SDCU), and c) between the total cumulative dose and length of stay. Methods: With REB approval, a retrospective chart review of children who underwent day surgery at BCCH is currently ongoing. Data to be collected include types and dosages of peri-operative medications; entry and exit times from the procedure room, PACU, and SDCU; and whether the patient was admitted to hospital. We are including patients who underwent outpatient MRI examinations, gastrointestinal endoscopy procedures, and strabismus repair. Results: Interim analysis of 158 cases (54 endoscopies, 53 MRIs, and 51 strabismus surgeries), in which dexmedetomidine was administered in 50 cases, revealed that intra-operative dexmedetomidine administration in the endoscopy subgroup was associated with a median increase of 10 minutes (95% CI 3-18) of additional PACU stay compared to no administration (p=0.007), while the other subgroups showed no statistically significant difference. Preliminary data currently suggests decreasing PACU lengths of stay with increasing doses of dexmedetomidine, an effect which was not statistically significant. SDCU data has yet to be analyzed. Discussion: Interim results are interesting as our hypothesis appears to hold true in one of the three subgroups. Further chart review will be needed to elucidate the effect of dexmedetomidine on discharge times in this population, particularly to allow for logistic regression modeling to evaluate potential confounding variables, such as age, anesthesiologist, weight, etc.

Poster Board #30 Tara Evans-Atkinson, Medical Student, University of Toronto Supervisor: Brenden Hursh, Childhood Diseases

Nursing support services delegated diabetes care plan assessment Tara Evans-Atkinson, Brenden Hursh, Alex Fung, Alda Antunes Silvestre, Tamara Crozier In British Columbia, students in kindergarten through to grade 12 with type 1 diabetes mellitus can be supported through the Nursing Support Services (NSS) program. The NSS program assists students who are unable to carry out their own blood glucose monitoring and/or administer their own insulin within the school setting (the “Delegated Diabetes Care Plan”). The most recent version of the Delegated Diabetes Care Plan was implemented in 2014; before this care plan was in effect, insulin administration was not administered by school staff, but supported solely by parents/ caregivers. The aim of this study was to collect survey data to review, assess, and to make changes to the current Delegated Diabetes Care Plan so as to accommodate the needs of families, best clinical practices, and new medical technologies. It is imperative to understand the safety, quality and effectiveness of this care program in order to ensure all children in the province are receiving optimal care. We hypothesized that most parents and/or guardians are satisfied overall with the safety and care that the Delegated Diabetes Care Plan provides for their child; however, we believe families will want to be more involved in the development of the care plans, and will want them to be easier to understand. The study is currently underway, with a cross-sectional survey to be offered to all families with children receiving care from a Delegated Diabetes Care Plan in school. Families will be mailed an introductory letter containing a link and participant code that can be entered into a computer to complete the survey online. Families will have the option of completing the survey either online (via REDCap) or via a hardcopy version. There will not be any personal identifiers in the survey. Survey questions will address participant demographics, the family’s understanding of the care plan, and the family’s opinion on the effectiveness and safety of the care plan. By conducting this study, we hope to better understand if the care plans in place are providing safe, consistent and supportive care, and if they are a useful and engaging tool to use by all who require them.

Poster Board #31 Jollee Fung, Medical Student, University of British Columbia Supervisor: Mark Ansermino, Healthy Starts

Building a predictive model of severe illness in children under 5 in resource-limited settings Jollee Fung, Niranjan Kissoon, Matthew Wiens, Mike English, Samuel Akech, Dustin Dunsmuir, Mark Ansermino United Nationsâ&#x20AC;&#x2122; Sustainable Development Goal 3 aims to reduce neonatal mortality to 12 per 1,000 live births and under-5 mortality to 25 per 1,000 live births by 2030. With diarrhea, malaria, and pneumonia being the major causes for mortality in children in resource-limited settings, it is imperative to detect the earliest signs of infection that may be predictive of the childâ&#x20AC;&#x2122;s potential deterioration to severe sepsis. Danger signs such as those from the Emergency Triage Assessment and Treatment by the World Health Organization and other triage systems have been developed as an attempt to systematically identify the sick child. Here we hypothesize that we can combine existing literature and guidelines on danger signs with pulse oximetry technology to build a datadriven predictive model of severe illness in young children. To ensure that we capture all possible danger signs and predictors of severe illness in young children, a literature search was conducted using the Ovid MEDLINE database. A master list of predictor variables was generated and is undergoing a modified Del-phi process whereby the list is sent to a group of experts including pediatricians, critical care physicians, and infectious disease specialists to gather their consensus on which variables should be collected. The final list of variables will be incorporated into a mobile application that also uses portable Bluetooth-enabled pulse oximeter to generate indicators such as oxygen saturation, respiration rate, and heart rate variability. The tool will be available on an open-access network such that collaborators can adopt the tool and begin gathering data to refine the prediction model. Data analysis for the model will focus on determining which set of clinical predictors can be prognostic of a sick childâ&#x20AC;&#x2122;s deterioration to severe sepsis. The goal is to be able to identify a sick child at the earliest time point such that resources can be allocated to those who need it most in an already constrained setting.

Poster Board #32 Kira Genise, Medical Student, University of Ottawa Supervisor: Srinivas Murthy, Healthy Starts

Colonization of streptococcus pneumoniae in viral bronchiolitis Kira Genise, Srinivas Murthy Background: Viral bronchiolitis is one of the most prevalent causes of illness requiring hospitalization among children worldwide and the most common reason for admission to the pediatric intensive care unit at BC Childrenâ&#x20AC;&#x2122;s Hospital. It has been hypothesized that co-infection with bacteria results in more severe clinical outcomes. However, the effects of bacterial colonization, affecting upwards of 15% of healthy children, on critically ill patients with bronchiolitis have yet to be proven. Current clinical management consists primarily of supportive therapies with the role of antibiotics remaining controversial. Methods and Results: A retrospective chart review of children admitted to the BC Childrenâ&#x20AC;&#x2122;s Hospital PICU from 2014-2017 with a diagnostic code of bronchiolitis was performed. Patients with pathogen testing complete (n=92) were assessed for severity of illness on presentation as per standardized pediatric illness scores and clinical outcomes were evaluated based on duration of PICU stay, hospital stay, intubation and non-invasive ventilation. A comparison between children with detected Streptococcus pneumoniae (n=22) and those without (n=70) revealed no significant (p=0.20) differences in severity of illness on presentation as per PRISM III scores. Unexpectedly, preliminary analysis reveals that patients colonized with S. pneumoniae had significantly shorter PICU stays (p=0.002), hospital stays (p=0.0001) and duration of non-invasive ventilation (p=0.002). Further analysis reveals this disparity cannot be attributed to the prescription of antibiotics and additional exploration is necessary to determine the significance of these findings. Conclusions: The results of this study will provide insight into the clinical management of children with viral bronchiolitis colonized by S. pneumoniae. Initial assessments do not suggest colonization is associated with increased severity of presenting illness or negative clinical outcomes. Further analysis and prospective studies are necessary to draw definitive conclusions.

Poster Board #33 Tiffany Lee, Medical Student, University of British Columbia Supervisor: Jennifer Coelho, Brain, Behaviour & Development

Clinical and demographic characteristics of male adolescents with eating disorders: A retrospective review Tiffany Lee, Priscilla Karnabi, Alex Burns, Pei-Yoong Lam Background: Feeding and eating disorders are characterized by disturbed eating or eating-related behaviours that significantly impact physical health and/or psychosocial functioning. Previous epidemiologic research on eating disorders suggests a lifetime prevalence of eating disorders (anorexia, bulimia, and subthreshold anorexia) in male adolescents that is approximately 1/3 that of female adolescents. While a significant minority of males are affected by eating pathology, few studies describing the clinical presentation of males with eating disorders have been published. Objective: To examine the clinical and demographic characteristics of male adolescents with eating disorders who received treatment at BC Children’s Hospital or the Looking Glass Residence (a residential treatment facility for youth suffering from eating disorders) over a 12-year period. Methods: A retrospective chart review was conducted on males who were admitted to the Provincial Specialized Eating Disorders Program at BC Children’s Hospital or the Looking Glass Residence from January 1, 2003 – July 3, 2015. Data from patients’ first admission were extracted from medical records and variables included demographic data, clinical characteristics and medical characteristics. Preliminary Results: Of the 70 male adolescents included in this review, 95.7%, (n=67) received treatment from the Provincial Specialized Eating Disorders Program at BC Children’s Hospital and 4.3% (n=3) received treatment from the Looking Glass Residence. The average age of patients at admission was 14.78 years (SD=2.86). The most prevalent feeding/eating disorder diagnosis was Anorexia Nervosa, with 47.1% (n=33) of the sample receiving this diagnosis at admission. 34.3% (n=24) of patients were diagnosed with Eating Disorder Not Otherwise Specified, representing a significant proportion. Inpatient treatment was recommended for 35.7% (n=25) of the sample and outpatient treatment was recommended for 24.3% (n=17). The remainder of patients received treatment recommendations specific to their particular case. Further analysis is in progress. Next Steps: Completing analysis of identified variables will develop a more comprehensive picture of the clinical characteristics of male adolescents with eating disorders. Future directions involve comparing the clinical features of males with those of females to inform individualized and improved treatment practices.

Poster Board #34 Wayne Leung, Medical Student, University of British Columbia Ishmeet Singh, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

The role of iron deficiency in neurodevelopmental disorders (ADHD, ASD, FASD) - A scoping review Ishmeet Singh, Wayne Leung, Sylvia Stockler, Osman Ipsiroglu Introduction: Iron deficiency (ID) is the most common nutritional deficiency worldwide. While several neurodevelopmental co-morbidities are associated with ID, their interactions with iron are complex and have not been explored systematically. This scoping review investigates the relationship between ID and the most frequent neurodevelopmental conditions, such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and fetal alcohol spectrum disorder (FASD), in children and adults. Methods: Literature search was conducted using MEDLINE, CINAHL, PsychINFO, and EMBASE databases, with search terms “iron deficiency anemia” AND “ADHD” OR “ASD” OR “FASD”. Results: Thirty seven articles matched the search criteria, with primary focus on ADHD in 29 articles: 5/6 case reports, 2/5 case series, 9/11 cross-sectional studies, 8/9 case-control studies, 1/2 controlled clinical trial, 1/1 RCT and 3/3 systematic reviews; the remaining articles were focused on children with ASD, while none were on FASD. Twenty three articles (5/5 case reports, 2/2 case series, 6/8 case controls, 5/9 cross sectional studies, 1/1 RCT, 1/1 controlled clinical trials, 3/3 systematic reviews) out of 29 articles investigating ADHD found an association between iron deficiency and ADHD, while 5 articles (1/1 case reports, 3/3 case series, 1/2 cross sectional studies, 0/1 case controls, and 0/1 controlled clinical trials) out of 8 articles investigating ASD found an association between iron deficiency and ASD. All studies used serum ferritin as an indicator for iron status Conclusions: Despite the lack of studies showing high level evidence, most of the studies analysed here indicate an association between ID and ADHD. The limited number of studies performed in individuals with ASD and FASD does not allow any conclusions. The clinical takeaway is that patients with ADHD should be screened for ID, and patients should be reassessed after their ID is corrected. More high level clinical trials are required to conclusively determine whether iron supplementation can resolve ADHD symptoms.

Poster Board #35 Alice Liu, Medical Student, University of British Columbia Supervisor: Neil Chadha, Evidence to Innovation

Three-dimensional facial morphology and severity of sleep disturbances in children Alice Liu, Julie Pauwels, Benjamin Pliska, Neil K. Chadha Background: Sleep disturbances, such as obstructive sleep apnea, are a common problem faced by many Canadians. While factors such as obesity are well known to contribute to these disturbances in middle-aged adults, previous studies have shown that facial shape can also influence these disturbances in both adult and children. Historically, craniofacial anthropometry was measured via calipers, metric tape, or radiographic imaging. Traditional lateral and frontal two-dimensional photographs have also been used. However, limitations exist for accurately recording three-dimensional geometry on a 2D plane. The newest advancement in technological imaging, stereophotogrammetry, has made obtaining 3D images much more practical. A composite 3D image is created without the need of post-capture alteration. This method works particularly well in the pediatric population as as it non-invasive and the images are not affected by childrenâ&#x20AC;&#x2122;s erratic movements. Objective: To determine if there is a correlation between the three-dimensional facial morphometric parameters of children aged 2-17 years old and their reported sleep disturbances as measured by the Pediatric Sleep Questionnaire. Methods: This is a prospective cross-sectional study. Approximately 200 patients will be recruited from the Otolaryngology clinic at BC Childrenâ&#x20AC;&#x2122;s Hospital. Stereophotogrammetric surface images will be acquired using the 3dMD face system. After images are taken, participants will be asked to complete the Pediatric Sleep Questionnaire (PSQ) to assess sleep disturbances. At a later date, the 3D images of patient faces will be analyzed and 3D coordinates derived from the identified soft tissue landmarks. Linear and angular measurements between landmarks will be calculated to create a midface projection and width to height ratio. A stepwise multiple logistic regression analysis will be performed to look for any significant association between the measurements and PSQ. Age, sex, and ethnicity of participant will also be analyzed. Future Direction: This study is currently in patient recruitment and preliminary findings will be presented. By researching a possible marker of sleep disturbances at a young age, this study may help inform best practice guidelines. The results have the potential to be incorporated into how sleep disturbances in pediatric patients are clinically approached.

Poster Board #36 Victoria McCutcheon, Medical Student, University of British Columbia Supervisor: Anthony Cooper, Evidence to Innovation

Paediatric elbow fractures from a childâ&#x20AC;&#x2122;s viewpoint Victoria McCutcheon, Harpreet Chhina, Ian Pike, Mariana Brussoni, Damian Duffy, Anthony Cooper Almost every child falls while playing, but not all sustain fractures. Supracondylar humerus (SCH) fractures - fractures just above the elbow â&#x20AC;&#x201C; are the most common injuries sustained by young children following a fall, and the commonest fracture requiring a hospital visit. With increasing severity of injury, treatment options become more invasive and the potential for long lasting complications increases. The mildest form requires a period of immobilization in a cast while moderate fractures require conscious sedation and manipulation of the fracture fragments to realign them. The most severe form requires surgery to realign and pin the fracture. A small group of these patients sustain long lasting damage to either the nerves or blood vessels. To address the problems associated with severe fractures, this project is a new collaboration between the Department of Orthopaedics, the BC Injury Research and Prevention Unit, and the Office for Paediatric Surgical Evaluation and Innovation, aiming to examine all aspects of this category of elbow fracture. We will employ a mixed methods approach to better understand the mechanisms of injury and child-related factors that influence injury, especially for severe cases. This is a crucial step in identifying best practices and informing supportive policy to prevent injuries in children. We will conduct photo-elicitation interviews with children aged 6-12 years, using the photographs these children have taken of their injury location. Describing their injury and recovery in this way has been shown to elicit greater range, depth, and value of information from young populations. We will then incorporate demographic patient data, clinical data including type of treatment, complications, and outcome, and measurements of the equipment involved in the injury in order to gain a measurable view of the patient population and support an enriched view of injury. Spatial analysis of injury locations will also be completed with comparison to socioeconomic and geographical factors with the aim of influencing injury prevention strategies and neighbourhood planning and safety.

Poster Board #37 Simon Robins, Graduate Student, University of British Columbia Supervisor: Harold Siden, Brain, Behaviour & Development

A scoping review to examine symptoms in children with rare, progressive, life-threatening disorders Simon Robins, Hal Siden, Marie-Claude GrĂŠgoire, Tammie Dewan, Anne-Mette Hermansen, Colleen Pawliuk, Helen Brown, Charlotte Beck, Rose Steele Background and Objectives: This poster will present the results from an ongoing scoping review which examines Q3 conditions in children with rare, progressive, life-threatening disorders. Q3 conditions are progressive, incurable metabolic, neurological, or chromosomal childhood conditions. With no existing curative treatments, children with these conditions face an unknown lifespan and endure uncomfortable and unstable symptoms. With regard to symptoms, there is a critical need to provide evidence from which clinicians can base care, and to identify directions for future research programs. Our objective has been to evaluate the level of the research evidence to identify what is known and unknown about the assessment and management of symptoms in Q3 conditions. We expect to complete this study by the end of 2017. Methods: Our initial pilot study identified 10 symptoms as disruptive to a childâ&#x20AC;&#x2122;s health: behaviour problems; bowel incontinence; breathing difficulties; constipation; feeding difficulties; sleep disturbance; temperature regulation; tone and motor problems; urinary incontinence; and vomiting. Pain and seizures were excluded because of the wealth of existing information. Our search strategy combined these symptoms with 180 Q3 conditions that were identified through our pilot study and three literature sources. We searched MEDLINE, Embase, and CINAHL and conducted an extensive search of the grey literature to locate unpublished studies. Results: We will demonstrate the successful strategy using a PRISMA chart. We will show the scope of knowledge and identify gaps in order to better understand mechanisms, assessments, and treatment of symptoms in Q3 conditions. We will also present our preliminary findings in terms of the number of articles we found (based on our search criteria), and the preliminary data we are currently extracting through REDCap on the mechanisms, assessments, and treatments used for symptoms in Q3 conditions. Conclusions: Current knowledge regarding symptoms is needed in this complex population and high-value research opportunities need to be identified. We will provide information for clinical use and guidance for conducting effective searches related to multiple diseases and conditions.

Poster Board #38 Arpreet Singh, Graduate Student, Simon Fraser University Supervisor: Ian Pike, Evidence to Innovation

The burden of fire-related injuries in children and youth across Canada Arpreet Singh, Fahra Rajabali, Jennifer Smith, Ian Pike Background: Residential fires are a leading cause of unintentional injuries in Canada. Injuries caused by fires are horrifying and painful, with severe burns resulting in disfigurement, and possible loss of life. It is vital to understand the burden of residential fire injuries in children and youth in British Columbia (BC) and across Canada to better target fire prevention strategies. Methods: Data from National Firefighters Information Database from 2005 to 2014 were analyzed for BC, Alberta, Saskatchewan, Manitoba, Ontario and New Brunswick. The frequency and proportion of fire-related injuries within BC was compared for different age groups, provinces, and locations of origin of residential fires. Results: In BC, children under the age of 10 were 2.75 times more likely to die in a fire than children over the age of 10 (26.7% vs 9.7%). However, children over the age of 10 were 1.4 times more likely to suffer minor (75.95% vs 66.45%) and 2.13 times more likely to suffer serious fire-related injuries (14.6 vs 6.85). Compared to BC, children and youth under the age of 19 years were 1.15 times more likely to sustain minor injuries in Alberta (81.43% vs 71.05%), 2.41 times more likely to sustain serious injury in Ontario (25.88% vs 10.73%), and 3.41 times more likely to die from residential fires in Manitoba (62.05% vs 18.2%). Children and youth were 1.31 times more likely to sustain minor injuries as compared to older adults ages 55+ years (70.8% vs 53.9%) and 2.97 times less likely to die in a residential fire (11.9% vs 35.3%). The three most common locations of origin for residential fires are the kitchen (33%), bedroom (17%) and living room (15%). Conclusion: The burden of residential fire injuries in children and youth in BC remain high despite ongoing efforts to reduce preventable fires, thus preventable injuries. All provinces, including Manitoba which shows the highest rate of deaths, continue to show high rates of fire-related injuries. Further research needs to focus on the distribution of fire incidence in different socioeconomic status groups, cause of residential fires, and the use of residential fire protection features.

Poster Board #39 Paul Yen, Medical Student, University of British Columbia Supervisor: Cynthia Verchere, Evidence to Innovation

Does tissue expansion reconstruction in the trunk of children increase the risk of scoliosis? Paul Yen, Marija Bucevska, Christopher Reilly, Cynthia Verchere Tissue expansion (TE) may be used to grow additional tissue for the reconstruction of large defects, by inserting unfilled silicone balloons (tissue expanders) subcutaneously and then facilitating the gradual inflation of the implant with saline solution over 10-12 weeks. Human skin increases in surface area when stretched in a controlled fashion. Afterwards, the additional skin created may be used to replace adjacent skin lost due to trauma, extensive wounds, removal of large birthmarks, burn scars, etc. The literature describes many possible complications of TE: infection, skin necrosis, pain, hematoma, scarring, dehiscence, exposure of the expander, and others. In our clinical practice, we recently saw two patients who had undergone skin TE on the trunk in early childhood, and presented with scoliosis later. Scoliosis, or abnormal lateral spinal curvature, has a prevalence of 0.47â&#x20AC;&#x201C;5.2% in the general population. We aim to investigate a potential relationship between scoliosis and TE. We hypothesize that truncal tissue expanders and subsequent flap surgery in pediatric patients, may affect the tension, muscle balance, and alignment of the spine and trunk in such a way as to increase the risk of scoliosis. This study is designed as a combined retrospective review and prospective evaluation. The health records of patients who underwent truncal TE at BC Childrenâ&#x20AC;&#x2122;s Hospital from 1997-2017 were retrospectively reviewed; data relevant to TE were collected and analyzed. All patients identified from the retrospective review were invited for the prospective evaluation, which will begin with radiological (EOS) imaging of the spine. The diagnosis of scoliosis typically requires a Cobb angle, a gold standard indicator of lateral spinal curvature, of at least 10 degrees. If necessary, a confirmatory clinical examination will be conducted by an orthopaedic surgeon in order to establish the presence or absence of scoliosis. We are currently working on scheduling patients for the prospective evaluation. The knowledge gained from this study will guide surgeons in minimizing the risk of scoliosis in children from TE by optimizing the location of TE placement and flap reconstruction. Moreover, health care providers will be able to help families make more informed decisions regarding TE treatment.

Session Five CLINICAL

Moderator: Rebecca Ronsley Participants: Haya Abuzuluf & Tara Bishop Natasha Carson & Hebah Hussaina Khaola Safia Maher & Jecika Jeyaratnam Tisha Dasgupta Aayushi Joshi Melissa Kong Michelle Lisonek Jimmy Lopez Claire Mockler Grace Nie Kyle Scoten Cassie Walmsley

Poster Board #40 Haya Abuzuluf, Undergraduate Student, University of British Columbia Tara Bishop, Undergraduate Student, Queenâ&#x20AC;&#x2122;s University Supervisor: David Goldfarb, Healthy Starts

Post-discharge readmission and mortality among children being repatriated to northern communities: Derivation of prediction models Haya Abuzuluf, Tara Bishop, Theresa McElroy, Tahir Chaudhry, Manish Sadarangani, Matthew O. Wiens, Niranjan Kissoon, David M. Goldfarb Background: Acute infectious diseases are a leading cause of pediatric admissions in northern remote regions of Canada. Affected children are transported for treatment to southern facilities, and then discharged to their communities where follow-up is challenging and readmissions are particularly burdensome to families and the healthcare system. Post-discharge readmissions are relatively common in northern remote regions, occurring in up to 1 in 5 children. Currently, there are no reported rates of post-discharge readmission/mortality in northern BC, and no evidence-based tools to help healthcare workers identify children at highest risk of readmission. The identification of predictors for readmission and the derivation of prediction models are important steps in the aim of providing â&#x20AC;&#x153;smart dischargesâ&#x20AC;? for potentially vulnerable patients. Current Objective: To present preliminary descriptive data from initial chart reviews of infectious disease admissions to BCCH from northern rural regions of BC and Yukon. Methods: This is a retrospective cohort study involving patients admitted to BCCH or University Hospital of Northern BC with an acute infectious disease between 2000-2015 (estimated n=750). Cases were identified using Infectious Disease related ICD-10 codes of children from rural regions of northern BC and Yukon. Chart reviews are currently underway; up-to-date data will be presented. Candidate predictor variables (including clinical, laboratory, and socio-demographic factors) based on a modified Delphi process will be analyzed, and 6-month readmission/mortality statistics will be collected through PopData BC. Results: Preliminary data have been retrieved and analyzed for 94 patients; 66% were male, with median age of 5 years (IQR 1-13 years). Notable patient admission statistics included: 45% were of Aboriginal identity, and 67% had comorbidity (such as asthma, cancer, and/or developmental disability). Common admission diagnoses included: lower respiratory tract infection (24%), sepsis (11%), and/or a UTI (10%). E. coli (21%) was the leading bacterial infection, while RSV (11%) was the most common viral infection. Conclusions: Our findings include a high proportion of patients with comorbidity and Aboriginal patients, suggesting a possibility of higher risk for readmission. Further analysis linking these admissions to any subsequent readmission in the following 6-months will allow the identification of readily obtainable predictors which can help guide resources towards the most vulnerable children. 57

Poster Board #41 Natasha Carson, Undergraduate Student, University of British Columbia Hebah Hussaina, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Behavioural Observations Step 1: “Fidgety Philip”, the Godfather of ADHD? Emmanuel Tse, Natasha Carson, Hebah Hussaina, Mackenzie Campbell, Seraph Bao, Khaola Safia Maher, Jecika Jeyaratnam, Nadia Beyzaei, Karen Spruyt, Gerhard Kloesch, Osman Ipsiroglu Introduction: Psychiatrist Heinrich Hoffmann’s “Die Geschichte vom Zappelphilipp” (1845) is a story depicting a boy, Philip, displaying fidgety behaviours. Over time, paediatricians/psychiatrists identified the symptoms “Fidgety Philip” (FP) presented as characteristics of ADHD. Our goal was to develop a learning tool to teach how to annotate behavioural observations. The first step in this endeavour was to analyze FP cartoons with the goal of training research assistants (RAs) and developing a shared annotation language. Methods: (A) Using a REDCap survey structure, seven RAs without formal training analyzed three FP cartoons separately, for 8.5 minutes each. The survey comprised of (i) describing the scene; (ii) ranking the importance of features; (iii) predicting what happens next; and (iv) determining/ explaining prediction accuracy. The first and second cartoons were reversed to avoid assumptions based on the ongoing sequence. (B) Qualitative information was analyzed and negotiation points were noted. (C) Quantitatively, individual results were combined to determine totals/means of observations. (D) Previously designed pictograms were used to agree on main features in each cartoon. Results: Qualitative information was divided into (i) descriptions; and (ii) interpretations. The total number of descriptions (168) was greater than the total number of interpretations (106). In the first cartoon, the total number of descriptions and interpretations were similar: 48 descriptions versus 43 interpretations. The following two cartoons yielded more descriptions than interpretations: 58 versus 39 in the second cartoon, and 62 versus 24 in the third. This, supported by calculations of means, demonstrated a trend towards a higher ratio of descriptions to interpretations with the sequence. The accuracy of prediction (based on five RAs) between the first and second images was 0%, and 40% between the second and third. Conclusion: Descriptions, interpretations, and predictions are formed by the “Gestalt”-perception of each individual. The reduction of interpretations can be attributed to the learning experience that occurred between the first and last cartoon; relevant, neutral descriptions became the focus, while subjective interpretations decreased. To increase the descriptive quality of annotations, pictograms may serve as a neutral language that can be applied to the characterization of movements associated with so-called disruptive behaviours. 58

Poster Board #41B Khaola Safia Maher, Undergraduate Student, University of British Columbia Jecika Jeyaratnam, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Behavioural Observations Step 2: Developing a Shared Annotation Language for Analysis of Video Recordings Mackenzie Campbell, Jecika Jeyaratnam, Khaola Safia Maher, Emmanuel Tse, Seraph Bao, Natasha Carson, Hebah Hussaina, Nadia Beyzaei, Mai Berger, Yi Jui Lee, Karen Spruyt, HF Machiel Van der Loos, Gerhard Kloesch, Osman Ipsiroglu Introduction: Individuals with mental health and/or neurodevelopmental conditions often display disruptive behaviours characterized as hyperkinesia, hypermotor-restlessness, and hyper/hypoarousability, all grouped as “H-behaviours”. In 2017, the Video-Working-Group of the International Paediatric Sleep Association developed a standardized framework for analyzing video recordings of H-behaviours. As a first step before assessing the suggested framework’s feasibility and reliability, we investigated Suggested Clinical Immobilization Test (SCIT) snapshots. Our goal was to develop a shared annotation language among research assistants (RAs) that could later be applied in the annotation of video recordings. Methods: Seven RAs without previous formal training in assessing H-behaviours analyzed video recordings of five adult volunteers undergoing a SCIT; a REDCap survey structure was used for data gathering. (A) RAs reviewed 24 SCIT snapshots and made qualitative free-hand observations (e.g. of body movements, facial expressions, etc.). (B) Two days later, the same 24 SCIT snapshots were reviewed in a randomized order. (C) A and B were repeated using prepared pictograms instead of free-hand observations. (D) The categorization of observations in 12 SCIT snapshots was further analyzed. (E) Interobserver variability was assessed. Results: Observations were categorized as (i) descriptive; or (ii) interpretive (predictions or statements influenced by viewer’s “Gestalt”-perception). Median number of descriptions and interpretations per SCIT snapshot for free-hand observations were 6 and 1, respectively. Interobserver consistency was 61.9% for descriptions and 36.6% for interpretations in free-hand observations. After grouping all movement-related pictograms, median number of descriptions and interpretations per SCIT snapshot were 2 and 1, respectively. Conclusion: This exercise provided an introduction to structured behavioural observations of H-behaviours during SCITs. Free-hand observations yielded higher interobserver consistency in descriptions than interpretations. Unexpectedly, we found that the proportion of interpretations increased when annotating using pictograms. This learning experience emphasizes the importance of developing and optimizing neutral descriptors (i.e. pictograms) of body movements and behaviour patterns.

Poster Board #42 Tisha Dasgupta, Undergraduate Student, University of British Columbia Supervisor: Theresa Newlove, Healthy Starts

The Belly Breathing App- A smartphone biofeedback application to manage stress and anxiety in children undergoing medical procedures Tisha Dasgupta, Nicole Cheung, Iris Liu, Christian Petersen, Theresa Newlove Background: Psychological well-being in children, at the hospital, is highly correlated with better health outcomes and a positive outlook towards future hospital visits. Therefore, it is important to manage stress and anxiety among children undergoing medical procedures, in order to maintain their psychological well-being. Belly Breathing is a type of deep diaphragmatic breathing that produces a relaxed state. It emphasizes the connection between the body and mind, and is a popular coping strategy. Aim: To evaluate the efficacy of a smartphone biofeedback application in managing anxiety and pain perception in children having their blood drawn at BC Childrenâ&#x20AC;&#x2122;s Hospital. Methods: Children in the BCCH blood lab who met the inclusion criteria of the study were recruited and consent was obtained. Randomized controlled trials were conducted with three patient groupsone experimental and two controls. Patients in the experimental group were taught how to belly breathe using the app and allowed to play the biofeedback game before and during the procedure. The two control groups were belly breathing without using the app, and standard of care without any intervention. A self-reported measurement of anxiety and pain perception was recorded. The application also collected PPG signals throughout, as measured by a non-invasive pulse oximeter, to evaluate belly breathing compliance by monitoring heart rate. Respiratory induced sinus arrhythmia was used as a biofeedback trigger. Results: The study is currently in Phase III of patient recruitment. Preliminary analysis of the PPG recordings showed mixed responses to the belly breathing protocol. Some subjects exhibited a strong baseline modulation while others exhibited strong amplitude modulation. Overall all subjects experienced a significant sinus arrhythmia modulation and showed a positive effect during the protocol when compared to controls. The interface of the application which features customizable animated avatars has been found to be appealing and engaging to young children. Summary and Future Directions: A smartphone biofeedback app that combines animated gaming with teaching children to belly breathe has been developed. It facilitates childrenâ&#x20AC;&#x2122;s engagement and has showed positive effect in sinus arrhythmia modulation. The researchers hope to be able to make the application available through global app stores, enabling children to effectively manage their stress and anxiety during medical procedures and other stressful situations.

Poster Board #43 Aayushi Joshi, Undergraduate Student, Western University Supervisor: Ian Pike, Evidence to Innovation

Rising fall-related death among seniors: Cause and effect of a policy change? Aayushi Joshi, Fahra Rajabali, Kate Turcotte, Ian Pike To classify deaths more accurately and consistently, the BC Coroners Service implemented a policy change in 2010 to support the identification of individuals whose death was related to a previous fall. Elderly patients hospitalized from a fall-related injury may experience failing health, eventually succumbing to conditions such as pneumonia. Prior to 2010, these deaths were classified as ‘natural’ with pneumonia as the cause of death; however, following the policy change they were classified as ‘accidental’ with fall as the underlying cause of death. The aim of this study was to investigate how change in practice influences the observed time trends and whether these time trends are artifacts of inconsistent reporting or indicate a true increase in fallrelated deaths. Analysis of BC Vital Statistics mortality data from 2001-2015 for cases with ICD-10 fall codes W00-W19 showed that fall-related mortality rates among seniors aged 90+ increased after 2010, peaked in 2012 at approximately 856 per 100,000 deaths, and decreased from 2012-2014. No significant difference in fall mortality rates for specified fall sub-causes between 2007-2009 and 2012-2014 was found, suggesting that mortality rates post-2012 were approaching rates prior to the 2010 policy change. Specifically, deaths among older adults aged 85 and over appear to have driven these trends. Although there were no subsequent policy updates after 2010, time trends suggest that there may be an unofficial reversion to previous reporting practice causing the observed peak in fall mortality rates to be an artifact of reporting practice. Further, 69.8% of falls were classified as ‘unspecified’, indicating a lack of documentation of the fall event. This study demonstrates how changes in policy and practice have a significant impact on data. As such, further emphasis should be placed on accurately identifying not only the underlying cause of death, but the mechanism of death as well, as this information is necessary for the development of targeted injury prevention initiatives. In accordance with current literature, there is a need for quality assurance measures and educational interventions to appropriately train coroners and medical examiners so as to increase the accuracy of mortality data.

Poster Board #44 Melissa Kong, Undergraduate Student, University of British Columbia Supervisor: Helen Nadel, Childhood Diseases

Use of optimized post-contrast enhanced PET/CT to improve diagnostic accuracy, staging, and follow-up of children with cancer MC Kong, JE Potts, HR Nadel Background: Cancer is the leading cause of death by disease among children past infancy in North America. New advances in the diagnosis, staging and treatment of these pediatric cancers will help to reduce the mortality rate and improve morbidity in these children. Compared to other imaging modalities, PET/CT can improve accuracy of staging and follow-up of disease by detecting and localizing malignancy through high-quality images. Most malignant tumors have high metabolic activity that can be localized in the body by injection of radioactive tracers and imaged using PET/ CT. This is the largest retrospective single-institutional study investigating the use of optimized PET/ CT in children with solid tumors as the primary staging modality. Objective: The purpose of our study was to conduct a comprehensive retrospective review and analysis of the effectiveness of optimized, post-contrast enhanced, whole-body PET/CT use in British Columbia and to determine its association with pathological correlates. Methods: PET/CT scans of patients under 18 years of age with solid tumors were included in this study. A total of 1,700 scans were reviewed. Data collection included demographic information, PET/ CT imaging findings, pathology, type and number of imaging modalities used, use of intravenouslyinjected contrast, and area of scan coverage (vertex-to-toes vs. eyes-to-thighs). Results: PET/CT scans were performed on patients with lymphoma (40%), sarcoma (32%), carcinoma (5%), neuroblastoma (5%), germ cell tumor (3%), Wilmsâ&#x20AC;&#x2122; tumor (1%), or other cancers (14%). Metastases at diagnosis were detected on 34% of initial staging PET/CT scans. In PET/CT scans that detected possible metastases, almost one-third of scans detected spread of cancer above the eyes (7%) or below the thighs (24%). Conclusion: Optimized, post-contrast enhanced, whole-body PET/CT is effective in detecting distant metastases and unsuspected disease in children with solid tumor cancers. In addition, performing PET/CT scans with this method may save children unnecessary imaging studies and radiation exposure.

Poster Board #45 Michelle Lisonek, Undergraduate Student, University of British Columbia Supervisor: Paul Yong, Healthy Starts

Deep dyspareunia and central sensitization in endometriosis Natasha Orr, Michelle Lisonek, Heather Noga, Catherine Allaire, Christina Williams, Mohamed Bedaiwy, Kelly Smith, Paul Yong Background: Endometriosis is a reproductive disease that affects about 10% of women and is characterized by presence of ectopic endometrial cells. Endometriosis can cause many types of sexual and non-sexual pain, including deep dyspareunia (DD) (pain with deep penetration during sexual intercourse). Central sensitization refers to sensitization of the central nervous system neurons, especially the dorsal horn neurons, which results in hyperalgesia (increased response to pain) and allodynia (pain with innocuous stimulus). Central sensitization is associated with psychological comorbidities, and multiple tender sites on examination (e.g. bladder and pelvic floor musculature). Central sensitization can also be assessed by quantitative sensory testing, such as by identification of decreased pain-pressure threshold (PPT) at healthy unaffected areas. We hypothesize that DD in endometriosis is associated with central sensitization. Objective: Aim 1: To identify which psychological variables are associated with bladder and/or pelvic floor tenderness in women with endometriosis. Aim 2: To determine whether DD is associated with decreased PPT at healthy unaffected body areas in women with endometriosis. Methods: Aim 1: Analysis of data from a prospective patient registry of women at the BC Women’s Centre for Pelvic Pain and Endometriosis. Aim 2: Prospective recruitment of controls and cases from the patient registry, in order to measure PPT through an Electronic Thimble Algometer. Results: Aim 1: In women with Stage I/II endometriosis, depression and catastrophizing were significant predictors of bladder/pelvic floor tenderness (OR=2.228, CI: 1.285 – 3.864, p=0.004 and OR=2.132, CI: 1.171 – 3.882, p=0.013, respectively). For Stage III/IV endometriosis, anxiety was a significant predictor of bladder/pelvic floor tenderness (OR=3.406, CI: 1.615 – 7.182, p=0.001). Aim 2: The average PPT for the analyzed control participants’ deltoid muscle was 10.084±4.4997 N and the first dorsal interosseous muscle was 9.1825±5.017 N. Conclusion: Psychological factors may play a key role in the tenderness of the bladder and pelvic floor in women with endometriosis-associated deep dyspareunia. Pain-pressure thresholds from controls will be used for comparison to thresholds from women with endometriosis-associated deep dyspareunia 63

Poster Board #46 Jimmy Lopez, Undergraduate Student, University of British Columbia Supervisor: Kevin Harris, Evidence to Innovation

Aortic stiffness and physical activity in children with congenital heart disease Jimmy Lopez, Christine Voss, Nicole Hemphill, Stephanie Duncombe, Kevin Harris Background: Aortic stiffness serves as an important marker of vascular dysfunction and is a strong indicator of early cardiovascular events. Pulse-wave-velocity is used as an indirect method of determining aortic stiffness through a series of validated calculations. From previous studies, children with congenital heart diseases (CHD) have significantly elevated aortic pulse-wave-velocity when compared to the healthy group, however pulse-wave-velocity between CHDs were relatively similar. Physical activity is known to be a modifier of arterial stiffness; however, it is unknown whether it plays a mediating role in children with CHD. Recent studies conducted at our research lab have noted no differences in objectively-measured moderate-to-vigorous physical activity levels in children with CHD and healthy children. Currently, there is no information on the association between physical activity and aortic stiffness in children with CHD. Objective: The primary objective is to assess the association between aortic stiffness and physical activity in children with CHD. Methods: Eligible participants (9-16yrs) born with CHD (Fontan, Tetralogy of Fallot, Coarctation of the Aorta, Transposition of the Great Arteries) will be recruited from the Childrenâ&#x20AC;&#x2122;s Heart Centre at BC Childrenâ&#x20AC;&#x2122;s Hospital. Echocardiography will be performed in order to determine aortic pulse-wave velocity. In addition, participants will be fitted with an accelerometer positioned over the right hip (Actigraph LLC) and will be asked to wear this device for 7 consecutive days to track moderate-tovigorous physical activity levels. During clinic visits, participants also complete a validated self-report physical activity questionnaire (PAQ; scored 1-5, 1=low, 5= high), which provides further insight into their activity levels. Expected outcomes: This study will provide foundation evidence about the association between aortic stiffness and physical activity in children with CHD. This knowledge will inform interventional studies and physical activity guidelines to optimize long-term cardiovascular health in these children.

Poster Board #47 Claire Mockler, Undergraduate Student, McGill University Supervisor: Tom Blydt-Hansen, Childhood Diseases

The prognostic value of urinary chemokines at 6 months after pediatric kidney transplantation Claire Mockler, Atul Sharma, Ang Gao, Ian W. Gibson, Alexander Wong, Julie Ho, Tom D. Blydt-Hansen Introduction: Pediatric kidney transplantation is lifesaving, but long-term survival is still limited by alloimmune inflammation and injury. Early inflammation may not be detectable with creatinine monitoring. Chemokines associated with alloimmune inflammation may identify patients at increased risk and offer the possibility of prognostic testing early post-transplant. Methods: We conducted a single centre prospective cohort study of pediatric kidney transplant recipients (<18 years). Urine supernatants were collected at 6 months post-transplant, and CXCL10 and CCL2 were measured by ELISA. Urinary chemokine CXCL10 and CCL2 levels were evaluated for association with acute histology at time of biopsy (Banff i+t score), change in allograft function at 6, 12, 24, and 36 months post-transplaMnt, and allograft survival. Results: Thirty-eight patients with a mean age of 12.44 Âą 6 years and a minimum follow-up of one year post-transplant were included. At the 6-month time point, urinary CCL2 was associated with delayed allograft function (r -0.47, p<0.01). Urinary CXCL10 was associated with delayed allograft function (r -0.69, p<0.01), Banff i+t score (r 0.47, p<0.01), Banff ci+ct score (r -0.38; p=0.03) and rejection episode 6-12 months post-transplant (r 0.41; p=0.02). Urinary CCL2 was associated with change in eGFR until 6 months (r -0.43; p<0.01) and a trend was observed from 6-12 months (r -0.29; p=0.08), but not at 24 and 36 months. Urinary CXCL10 showed no association with early changes in eGFR, but was associated with change in eGFR at 36 months (r -0.49; p<0.01) and a trend was observed at 24 months (r -0.313; p=0.08). CXCL10 was associated with reduced allograft survival (HR=1.05; p=0.01), but CCL2 was not. CCL2 and CXCL10 were correlated with one another (r 0.54; p<0.01). Conclusion: Urinary chemokines CCL2 and CXCL10 measured at 6 months post-transplant provide differing prognostic information. CCL2 is associated with prior decline in function, whereas higher levels of CXCL10 are associated with subsequent episodes of rejection, functional decline over 3 years, and allograft loss.

Poster Board #48 Grace Nie, Undergraduate Student, University of British Columbia Supervisor: Vilte Barakauskas, Healthy Starts

Pregnancy-specific reference intervals for laboratory biomarkers: Uses, challenges, and initiatives Grace Nie, Benjamin Jung, Vilte Barakauskas Reference intervals used in clinical lab medicine provide a basis of comparison to detect abnormal pathology. Reference intervals represent lab test values of a representative, healthy reference population. Due to the metabolic demands of the fetus, a pregnant woman experiences physiological changes that can invalidate the use of reference intervals established in non-pregnant populations. It is necessary to establish pregnancy-specific reference intervals to distinguish pathological change from normal pregnancy-related changes and to inform prepartum and postpartum management. Many labs incorrectly employ reference intervals derived from nonpregnant populations, pregnant populations with different ethnic backgrounds, or labs using outdated analytical methods. Even reference interval studies performed using modern analytical methods and a comparable reference population often do not meet current International Federation of Clinical Chemistry (IFCC) recommendations for RI determination with regard to sufficient sample size or appropriate statistical analysis. The purpose of our review is to summarize the current gaps in obtaining pregnancy-specific reference intervals based on IFCC recommendations. Underrepresented gestational ages associated with dynamic physiological changes are emphasized. We present and discuss published values of several commonly ordered laboratory-tests used in the diagnosis of disorders and the optimization of pharmacotherapy. Our compiled values reveal conflicting intervals due to heterogeneous study designs or study populations. We describe the potential confounding effect of using a nonhomogenous population. To explain why there are gaps in pregnancy reference intervals, we consider the limitations of conducting a de novo prospective study and the unique challenges around studying the pregnant population. To address the gaps, we outline the upcoming Pregnancy Reference Intervals for Safe Medicine (PRISM) initiative to update values for our local population.

Poster Board #49 Kyle Scoten, Undergraduate Student, Queenâ&#x20AC;&#x2122;s University Supervisor: Shelina Babul, Evidence to Innovation

Evaluation of the Concussion Awareness Training Tool (CATT) mandate by BC Hockey Kyle Scoten, Kate Turcotte, Fahra Rajabali, Shelina Babul Introduction: Concussions in youth sports have become a prevalent issue in recent years. In Canada between 2004 and 2014, hockey, football, and soccer have all shown a >40% increase in rates of reported head injury in children and youth. Consequently, there is a need for a valid and standardized protocol for the recognition, treatment, and management of sport-related concussion to be widely adopted by those in the sporting community. The Concussion Awareness Training Tool (CATT), developed in 2014, is an accessible online educational tool that provides training courses on the recognition, treatment, and management of concussion. Other features of the CATT include regularly updated resources and current evidencebased information on concussion. In June 2016, the CATT was mandated by BC Hockey as a training tool to be completed by all on-ice officials (approximately 15,000) prior to their participation in the 2016-2017 season. Objectives: To assess the effectiveness of the CATT as an educational tool for BC Hockey on-ice officials. To examine the level of support in mandating the CATT course for parents of BC Hockey players. To optimize the CATT website using participant feedback. Methods: A survey was developed to solicit feedback on the CATT as a mandated concussion resource for BC Hockey officials, and distributed by BC Hockey to all on-ice officials. Quantitative and qualitative analysis were performed on the data. Results: The survey had a >10% response rate (n=1,735). The CATT training led to a significant increase in self-reported concussion knowledge amongst BC Hockey on-ice officials (p<0.001). Mandating the CATT training for parents was supported by 68.4% of respondents; with female officials being significantly more in favour of training parents compared to male officials (p<0.02). Preliminary qualitative analysis suggests that more information is needed in assessing players who have sustained a potential concussion-causing hit, but have not sustained a concussion. Conclusions: Comparing participant-reported knowledge before and after completing the CATT training course, we found that the CATT successfully increased the level of concussion-related knowledge amongst BC Hockey officials. Preliminary analysis suggests that mandating the CATT for parents of BC Hockey players should be strongly considered.

Poster Board #51 Cassie Walmsley, Undergraduate Student, McGill University Supervisor: Donna Lang, Brain, Behaviour & Development

Developmental and obstetric predictors of psychosis Cassie Walmsley, Melissa Woodward, William G Honer, Geoffrey N Smith, Allen E Thornton, Randall F White, Donna J Lang Background: Schizophrenia is a complex disorder of unknown etiology. A genetic contribution is well-documented, however the role of environmental interactions is still disputed in schizophrenia. Numerous studies have found an increased risk of schizophrenia among individuals exposed to obstetric complications (OCs), but this association remains controversial. Additionally, previous studies have shown a relationship between OCs and a greater risk of cardiovascular and metabolic compromise later in life, and these cardio-metabolic deficits are more common in patients with psychosis compared to the general population. The links between these early risks and later clinical outcomes have not yet been fully defined. Objective: Our aim is to determine the prevalence, rate, and types of obstetric stressors and early life events that may have contributed to the emergence of psychosis and related metabolic disorders in patients with schizophrenia spectrum disorders. Methods: Primary data will be based on maternal interviews. 300 mothers of offspring between the ages of 16 and 45 who have been diagnosed with a schizophrenia spectrum disorder will be administered the McNeil-SjĂśstrom Scale for Obstetric Complications (MSSOC), the Maternal Premorbid Adjustment Scale (M-PAS), and the Offspring Developmental Health Survey (ODHS). Data on frequency and severity of OCs and ratings of early developmental event markers will be compared to published general population rates and will undergo descriptive statistics, chi-square test, regression analysis, and ANOVA. We expect to see increased rates of OCs in patients with schizophrenia compared to the general population. We also expect increased severity of OCs to be associated with higher current severity of psychiatric illness, and a higher rate of metabolic disorder compared to patients whose mothers had no history of OCs. Conclusions and Future Directions: Data collection and analysis is ongoing. The results of this study will contribute to the understanding of OCsâ&#x20AC;&#x2122; etiological role in schizophrenia. This would enable adult interventions to be better targeted, and more importantly, would provide insight into potential early preventative interventions.

Session Six CLINICAL

Moderator: Caroline Lamarche Participants: Mackenzie Campbell Nicole Cheung Nicole Hemphill Mehima Kang Adina Landsberg Iris Liu Emmanuel Tse & Seraph Bao Lisa Nakajima Kaitlyn Samson Jacob Stubbs Lee Vargen Helen Wu

Poster Board #52 Mackenzie Campbell, Undergraduate Student, Queen’s University Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Disruptive Daytime Behaviours & Sleep in Adolescents with Down Syndrome - An Explorative Pilot-Study Using a Participatory Research Concept Mackenzie Campbell, Melvin Chan, Nadia Beyzaei, Mai Berger, Susan Fawcett, Sylvia Stockler, Osman Ipsiroglu Introduction: Disruptive daytime behaviours (DDBs) exhibited by adolescents with Down syndrome (DS) are often associated with underlying intellectual disability. Sleep problems may aggravate DDBs and negatively affect overall wellbeing. We investigated the relationship between sleep and DDBs in five adolescents who had not been previously assessed for sleep disorders. Our goal was to develop the methodology for an observation-based, naturalistic study applying a participatory approach by including families and teachers. Methods: A peer group of five adolescents with DS, sleep disturbances, and DDBs, attending the DS Research Foundation (DSRF) Summer School, and their families participated; two research assistants (RAs) recorded observations in the classroom utilizing the “concept of empathy”. (A) Intake interviews with parents focused on sleep problems and DDBs. (B) Recording behaviours: (i) one day of pre-recording to become familiar with participants; (ii) one week of in-class partial interval recording of DDBs; (iii) two-week sleep diary and log addressing sleep patterns and disruptions, observed daytime behaviours, and mood, completed daily by families. (C) Exit interviews debriefed families on individual findings and reviewed familial sleep problems; an abbreviated version of the Suggested Clinical Immobilization Test was applied. (D) Findings were exchanged with the professional team of the DSRF Summer School. Results: DDBs were characterized as follows: (i) “challenging”, if there was an obvious explanatory model (e.g. frustration); (ii) “goofy” (e.g. class-clown behaviours); and (iii) “unspecified”, if there was no explanatory model (e.g. shutting down). Families agreed with this classification approach, though not all professionals did. In 4/5 participants, amount of exercise affected sleep quality; 4/5 exhibited “goofy” behaviours with peers; 4/5 came from families with symptoms of restless legs syndrome (RLS). Remarkably, 5/5 presented insomnia patterns that warranted further RLS and difficulty breathing investigations. For all participants, play therapy was recommended to manage unaddressed emotions. Conclusion: Parents and the study team developed a shared language regarding DDBs and possible aggravating factors for further exploration. Unexpectedly, we observed insomnia patterns likely triggered by familial RLS in all participants. Finally, application of the “concept of empathy” resulted in recommending play therapy for unaddressed emotional wellbeing.

Poster Board #53 Nicole Cheung, Undergraduate Student, University of British Columbia Supervisor: Sonia Butterworth, Evidence to Innovation

Emergency Surgery Delays - An analysis of target time achievement and causes of delay in emergency cases at BC Childrenâ&#x20AC;&#x2122;s Hospital Nicole Cheung, Tisha Dasgupta, Sonia Butterworth Introduction: A recent study conducted in Ottawa with an adult population showed that patients who were delayed in entering the operating room had a higher mortality rate. The purpose of this study was to analyze surgical target time achievement and reasons for delay in emergent and urgent cases performed at BC Childrenâ&#x20AC;&#x2122;s Hospital (BCCH), and to determine if delays are associated with increased risk of morbidity and mortality. Methods: This study evaluates all emergent cases at BCCH including classes 1 (target < 1 hour), 2A (< 6 hours), 2B (< 24 hours) and 3 (< 72 hours). A retrospective chart review was carried out to determine risk of mortality using ASA class, SNAPPE II score, and PRISM II score. Information on surgery times were obtained from booking forms and patient charts. The data collected from these forms include: OR booking times, in-room times, incision times and priority classifications. Surgeons and anesthetists were contacted by email to determine the cause for delay in each of the delayed cases. Data collection is ongoing. Results: Preliminary results indicate that the most urgent cases (class 1) have the greatest likelihood of experiencing delays. Data collected suggests that lack of an available OR is the most common reason for delay (40%). Between May 21st and July 16th of 2017 42.1% of class 1 cases were delayed, while classes 2A, 2B, and 3 cases had a delay occurrence of 10.8%, 13.1%, and 10%, respectively. Overall between May 21st and July 16th, 15.5% of all emergent cases at BCCH were delayed. Mean times to the OR from booking were 72 min, 4.9 h, 14.5 h, and 35.5 h for class 1, 2A, 2B and 3 cases, respectively. We have also observed an increase in target time achievement in class 1 and 2A cases by 4.9% and 6.7%, respectively, since the project start date. Since no new policies have been implemented, this improvement is likely due to the Hawthorne Effect. Conclusion: For emergency surgeries, the most urgent cases have the greatest likelihood of experiencing delays. The most common cause for delay is a lack of available OR. Further data collection on all emergent and urgent cases performed at BCCH and chart review will allow us to determine delay outcomes for high and low risk patients, and how delay contributes to morbidity and mortality.

Poster Board #54 Nicole Hemphill, Undergraduate Student, University of British Columbia Supervisor: Kevin Harris, Christine Voss, Evidence to Innovation

Physical activity and health behaviours in adolescents: A one-year follow-up study Nicole Hemphill, Christine Voss, Jimmy Lopez, Stephanie Duncombe, Kevin Harris Background: Physical activity and heart healthy lifestyle choices are important for general health. However, only 1/5 Canadian youth are in ideal cardiovascular health as measured by the CANHEART index, and many do not meet guidelines for physical activity. This study will build on previous baseline findings and investigate trends in physical activity and cardiovascular health behaviours over time. Objective: To explore interactions between health-related behaviours and physical activity in adolescents over time. Methods: 13-19 year-old patients presenting to the Childrenâ&#x20AC;&#x2122;s Heart Centre for evaluation or routine follow-up were invited to participate. Adolescents completed questionnaires during their clinic visits. Participants self-reported heart-health-related lifestyle behaviours (fruit and vegetable consumption, smoking, BMI status and daily physical activity) via CANHEART index (4=ideal, 0=poor). Physical activity was assessed via a validated questionnaire (Physical Activity Questionnaire for Adolescents â&#x20AC;&#x201C; PAQ-A; scored 1=low, 5=high). Medical charts were reviewed for pertinent information. Approximately 12 months after baseline, participants were invited by email to complete the survey again. Differences between time points were assessed by Wilcoxon matched-pairs signed-ranks test (Stata v. 14.2; p<0.05). Results: To date, 29/89 contacted adolescents have completed follow-up questionnaires (responders: median age (baseline) 15.5 years (IQR: 14.9-17.0), median BMI (baseline) 20.3 (IQR: 18.4-21.9), median BMI (follow-up) 20.3 (IQR: 19.2-21.8), 28% female, 38% with congenital heart disease). CANHEART scores could only be computed for 19 participants at follow-up due to missing data, largely because participants opted not to self-report weight. Median CANHEART scores were 3 (IQR: 2-4) at baseline, and 3 (IQR: 2-3) at follow-up, which was not significantly different (n=19, z=0.799, p=0.424). Median PAQ-A scores were significantly higher at baseline (2.19, IQR: 1.70-3.43) compared with follow-up (2.16, IQR: 1.59-2.90; n=28, z=2.505, p=0.012). Conclusions: These results indicate that physical activity declines significantly in adolescents over just one year, but other health behaviours remain relatively stable. Further Directions: Follow up questionnaires will continue to be sent to participants at 12 month intervals for 5 years following their initial responses, or until they are no longer adolescents.

Poster Board #55 Mehima Kang, Undergraduate Student, Queen’s University Supervisor: Constadina Panagiotopoulos, Childhood Diseases

Risk of chronic kidney disease following acute kidney injury during diabetic ketoacidosis in children with type 1 diabetes Mehima Kang, Rebecca Ronsley, Cherry Mammen, Constadina Panagiotopoulos Background: A recent study demonstrated that 64% of children hospitalized for diabetic ketoacidosis (DKA) presented with acute kidney injury (AKI). In other pediatric populations, AKI has been shown to confer an increased risk for chronic kidney disease (CKD). Objective: To compare the risk of developing CKD in children with type 1 diabetes (T1D) three to five years following hospitalization for DKA, in those with or without a history of an AKI. Methods: This is an ambispective cohort study of T1D patients presenting to the BCCH Diabetes clinic from 11/2016 to 07/2017 (N=230). Data from past DKA admissions and current clinic visits were collected from patient records. An expected baseline creatinine (EBC) was calculated using the subject’s height and estimated GFR of 120mL/min/1.73m2. AKI, during DKA, was defined as a serum creatinine value >1.5 times the EBC. Presence of albuminuria, using ACR values, was also identified as a risk factor for CKD. eGFR was evaluated at the current clinic visit as CKD <60mL/min/1.73m2, mildly decreased as 60-90mL/min/1.73m2 and hyperfiltration as >150mL/min/1.73m2. Subjects were compared between the following groups: those without an episode of DKA, those with an episode of DKA without AKI and those with an episode of DKA and AKI. Results: Of the 200 subjects, 59.0%(N=115) had DKA, of which 56.8%(N=54) had AKI. In this subset 15.4%(N=2) had mildly decreased eGFR. Of those without AKI during DKA, 10.5%(N=2) had mildly decreased eGFR, and 10.5%(N=2) had hyperfiltration. 84.6%(N=11) of those with AKI during DKA retained normal kidney function; whereas 79%(N=15) of subjects without AKI during DKA had normal kidney function. The mean length of follow up was 3.9±3.3 years. No subjects currently meet criteria for CKD. Cumulatively, two subjects with past DKAs were referred to nephrology. Of those without DKA(N=80), 20% have mildly decreased eGFR(N=6) and 80%(N=24) have normal kidney function. Of 45 subjects with ACRs, 20%(N=9) showed presence of albuminuria. Conclusions: This is the first study to report CKD in children following an episode of DKA and AKI. Knowledge translation initiatives are urgently needed to develop protocols for renal impairment identification and to ensure timely management in children with T1D.

Poster Board #56 Adina Landsberg, Undergraduate Student, McMaster University Supervisor: Tom Blydt-Hansen, Childhood Diseases

Urinary metabolite markers of chronic kidney disease in pediatric kidney transplant recipients Adina Landsberg, Atul Sharma, Ian W. Gibson, David S. Wishart, Tom D. Blydt-Hansen Background: Kidney transplantation is life-saving, but various post-transplant injury processes cumulatively manifest as allograft chronic kidney disease (CKD). Early CKD progression is not well identified by glomerular filtration rate (GFR) monitoring, but is characterized on kidney biopsies by interstitial fibrosis and tubular atrophy (IFTA) and glomerulosclerosis (GS). In an effort to avoid need for invasive kidney biopsies, the objective of this study is to identify urinary metabolite signatures associated with IFTA and GS to non-invasively stage CKD progression in pediatric kidney transplant recipients. Methods: Urine samples (n=396) were obtained at the time of kidney biopsy from a prospective, observational cohort of 60 renal transplant patients. Samples were excluded for classifier development if obtained <1 month post-transplant, or the patient had acute kidney injury or rejection (TCMR or ABMR). Urine was assayed for 133 metabolites by quantitative mass spectrometry, and biopsy samples were graded according to the Banff criteria of IFTA (ci, ct) and percent GS (%GS) was quantified. Partial least squares analysis was used to identify metabolite profiles, expressed as a discriminant score (ds). Regression analysis was used to identify important clinical features. Results: Urine samples (n=174) from 51 patients with a mean of 28.9Âą30.3 months post-transplant were divided into training/validation sets (75:25%). Metabolite ds for IFTA stage and %GS were identified on the training sets (AUC=0.9; 95% CI=0.84-0.96 and AUC=0.82; 95% CI=0.74-0.91), with similar accuracy on the validation sets (AUC=0.71; 95% CI=0.51-0.9 and AUC=0.81; 95% CI=0.630.98). In the regression analysis (including ds), months post-transplant was associated with IFTA severity (0.01/mo, p=0.006) and %GS (0.15/mo, p<0.001). GS was also influenced by proteinuria (9.22, p=0.014), age at transplant (-0.86/yr, p=0.005) and estimated GFR (-0.17, p<0.005). Addition of clinical variables improved performance of the %GS classifier (AUC=0.9; 95% CI=0.85-0.96) but not the IFTA stage classifier (AUC=0.82; 95% CI=0.71-0.92). Conclusions: These findings, which identify urine metabolite classifiers for IFTA and GS, may provide a non-invasive tool to stage histopathological damage that is not clinically evident. Independent validation is required to verify the accuracy and improve the classifiers for eventual implementation into clinical practice.

Poster Board #57 Iris Liu, Undergraduate Student, University of British Columbia Supervisor: Damian Duffy, Evidence to Innovation

Understanding the journey to care for Ugandan children with rare diseases Iris Liu, Arlene Muzira, Bababunmi Fashola, John Sekabira, Monica Langer, Eleanor Reimer, Damian Duffy, Geoffrey Blair Background: Rare diseases by definition affect only a minor subset of the patient population. However, when taken as a collective, rare diseases represent a global health concern with an expansive reach that affects approximately 350 million people worldwide with 50% being pediatric patients. Rare diseases are defined by prevalence thresholds within the specific geographical context. In Africa, the prevalence threshold required to classify a disease as rare is not defined. In this study, the list of rare diseases included was compiled by surgeons experienced in pediatric surgery in Uganda. Objective: To understand the journey to care of children with rare surgical diseases who live in rural settings where pediatric surgical specialists are not close at hand. Methods: This study was completed at two Ugandan hospitals: Mulago National Referral Hospital in Kampala and Soroti Regional Referral Hospital in Soroti. Data was collected from April to June and May to June 2017 respectively. There are two arms of the study: the first being a patient questionnaire and the second being a focus group discussion. The patient questionnaire was adapted from the EurordisCare2 survey developed by the European Organization for Rare Diseases (EURORDIS) that was used as a tool for analyzing delays in diagnosis of rare diseases. The focus group was comprised of health care professionals who have had experience treating and/or managing pediatric patients diagnosed with rare diseases. The focus group engaged in discussions concerning current and best practices of referral and care for pediatric patients with rare diseases. The rare diseases considered are as follows: sacrococcygeal teratoma, childhood tumours/cancer, imperforate anus, Hirschsprungâ&#x20AC;&#x2122;s disease, omphalocele, gastroschisis, intestinal atresia, congenital diaphragm hernia, conjoined twins. Preliminary Results: A total of 74 patient families and 24 health care professionals participated in the study. The most common combinations of medical examinations done prior to final diagnosis were examination by doctor, biological tests and radiological tests or examination by doctor only. The majority of diagnoses were confirmed by radiological tests (55.9%) and clinical tests (35.5%). Both hospitals in study are government hospitals and therefore should offer tests, treatments and medication free of charge for patients. However, due to a lack of resources, 71% of the respondents (n=62) reported paying for the aforementioned medical tests and 54.8% of these respondents (n=62) paid by means of income or via a family member. The median cost of these tests amounted to approximately $10.75 Canadian. 75

Poster Board #59 Lisa Nakajima, Undergraduate Student, McGill University Supervisor: Ruth Grunau, Brain, Behaviour & Development

Stress and cognition in early childhood in infants born very preterm Lisa Nakajima, Cecil MY Chau, Joanne Weinberg, Steven Miller, Ruth E Grunau Introduction: Children born very preterm are exposed to pain and stressful procedures in the neonatal intensive care unit (NICU) during a sensitive period of hypothalamic-pituitary-adrenal (HPA) axis programming, which may contribute to poorer cognitive performance. Previously, we found that infants born at extremely low gestational age (ELGA, 24-28 weeks GA) have altered cortisol levels compared to very low gestational age (VLGA, 29-32 weeks GA) and full-terms (38-41 weeks). Our goal is to examine whether: 1) cortisol pattern seen previously at 18 months can be replicated in an independent cohort; 2) cortisol levels during cognitive assessment at 18 months are related to cognition. Methods: In a prospective longitudinal cohort study, N=153 children had complete data at 18 months corrected age: 74 ELGA, 48 VLGA and 31 full-term, after excluding feeding and medications that affect cortisol. Child saliva samples (assayed for cortisol) were collected at 3 timepoints in the morning: before cognitive assessment (pretest), mid-test (post1), end (post2). Cortisol values were winsorized for outliers, log transformed, and adjusted for time of day and time since waking. Cognitive ability was measured with the Bayley Scales of Infant & Toddler Developmentâ&#x20AC;&#x201C;III Cognitive Composite score. General estimating equation modeling was used to examine cortisol across timepoints by group, and Pearson correlations to examine cortisol levels in relation to cognition. Results: Group interacted with timepoint (p=.003) such that cortisol levels of ELGA > VLGA > Fullterm for pretest and post1; post2 n.s. Among the children born ELGA, lower cortisol at the end of the session was related to better cognition (p=.031), VLGA n.s., and full-term, lower pretest cortisol was related to better cognition albeit within the normal range (p=.047). Conclusion: We confirmed differences in cortisol among ELGA, VLGA and full-terms found in a previous independent cohort at 18 months, indicating altered programming of the HPA-axis long after NICU discharge. Our findings suggest that sustained high cortisol levels are related to delayed cognition in ELGA children. Next steps are to examine neonatal factors in relation to cortisol, and whether the trajectory of cortisol levels through early childhood is related to cognitive function at school entry.

Poster Board #58 Emmanuel Tse, Undergraduate Student, University of Toronto Seraph Bao, Undergraduate Student, University of British Columbia Supervisor: Osman Ipsiroglu, Brain, Behaviour & Development

Behavioural Observations Step 3: Vigilance of Night-Time Drivers Emmanuel Tse, Seraph Bao, Mackenzie Campbell, Natasha Carson, Hebah Hussaina, Khaola Safia Maher, Jecika Jeyaratnam, Nadia Beyzaei, Manuel Kemethofer, Marion Seidenberger, Karen Spruyt, Suzanne Lewis, Osman Ipsiroglu, Gerhard Kloesch Introduction: Changes in vigilance experienced throughout the day depend on the quality of night-time sleep, and are characteristic features of individuals experiencing fatigue. To standardize vigilance assessments, we reviewed videos of night-time drivers with a structured rating system and investigated how untrained research assistants (RAs) rate vigilance. Methods: Night-time driving videos of 60 adult volunteers recorded between 2 and 4 AM were provided by the Institute for Sleep-Wake-Research (ISWF, Vienna) and the Austrian Automobile Club (OEAMTC). After 30 and 90 minutes of driving, two 4.5-minute videos from 14 out of 60 participants were analyzed. (A) RAs rated participants using the Karolinska Sleepiness Scale (KSS); these values were compared with drivers’ self-ratings. (B) Open-ended and pictogram-based behavioural descriptions of participants were made. (C) For each participant, RAs predicted which video was recorded earlier. (D) Four videos were reviewed with a Delphi consensus process, determining to what extent prepared pictograms could support analyses. Results: (A) KSS participant and observer median ratings for the earlier (participants: 3.0, observers: 4.25) and later recordings (participants: 6.5, observers: 6.1) were comparable, but not significant (Chi-square: earlier p=0.6; later p=0.4). (B) Descriptions were separated into (i) task-oriented (i.e. driving); (ii) non-task oriented (i.e. non-driving); and (iii) posture-oriented (e.g. stretching) behaviours. Open-ended descriptions: task-oriented (earlier: 42%, later: 36.6%); non-task oriented (earlier: 49.5%, later: 54.8%); and posture-oriented (earlier: 8.7%, later: 8.6%) behaviours. Pictogram-based descriptions: task-oriented (earlier: 39.2% to later: 31.3%); non-task oriented (earlier: 47.2% to later: 54.5%); and posture-oriented (earlier: 13.6%, later: 14.2%). (C) In 42% of cases, RAs correctly predicted which of the two videos were recorded earlier (Kappa < 0.0). (D) Discussions identified missing icons (e.g. self-stimulation) to inform future design. Conclusion: Non-task oriented behaviours increased, task-oriented behaviours decreased, and posture-oriented behaviours remained unchanged for both open-ended and pictogram-based descriptions. RA observations corresponded to participant KSS self-ratings. Personal “Gestalt”based understanding and in-depth analysis of movement patterns supported vigilance assessment, however, earlier videos were not accurately distinguished. Posture-oriented behaviours increased in pictogram-based descriptions. Additional pictogram development may support establishment of “benchmark” behavioural patterns of vigilance. 77

Poster Board #60 Kaitlyn Samson, Undergraduate Student, University of British Columbia Supervisor: Crystal Karakochuk, Healthy Starts

Vitamin D status in children and adolescents with sickle cell disease in British Columbia Kaitlyn Samson, Heather McCartney, Suzanne Vercauteren, John Wu, Crystal Karakochuk Background: Sickle cell disease (SCD) is an inherited disorder caused by a mutation (rs334) in the HBB gene encoding hemoglobin. Polymerization causes sickle-shaped erythrocytes, resulting in anemia, increased erythropoiesis and RBC turnover, and other complications. Individuals with SCD are at risk of vitamin D deficiency due to increased erythropoiesis, inadequate dietary intakes, and lower UV production by skin (as SCD is common in individuals of African-origin). Objective: We aimed to assess serum 25-hydroxyvitamin D (25OHD) concentration (as a biomarker of vitamin D status), estimate deficiency prevalence, and investigate factors associated with 25OHD in children and adolescents with SCD attending BC Children’s Hospital in Vancouver. Methods: We conducted a retrospective chart review of SCD clinic patients (2-19 y) over a 5-year period (2012-2017). Data was available for n=45 patients with n=142 25OHD measurements assessed using an immunoassay. Other relevant data were recorded (including age, season of blood collection, prescribed supplements). Linear regression was used to determine associations between 25OHD concentration and numerous predictor variables. Results: Overall, mean ± SD 25OHD concentration was 79.1 ± 35.9 nmol/L; prevalence of vitamin D deficiency (<50 nmol/L) and insufficiency (<75 nmol/L) was 29% and 50%, respectively. The majority of individuals (n=38/45; 84%) were prescribed vitamin D supplements (between 500-1,000 IU/d). Mean 25OHD concentrations measured during the months of Jul-Sep were significantly higher (38 [95% CI: 11-65] nmol/L higher, P=0.007), as compared to Jan-Mar. The prevalence of vitamin D deficiency varied by season of blood collection (36% Jan-Mar, 25% in Apr-Jun, 20% in Jul-Sep, and 0% in Oct-Dec). Conclusions: In a population of predominantly vitamin D-supplemented children and adolescents with SCD, the prevalence of vitamin D deficiency fluctuated from 0-36% depending on season of blood collection. Season of blood collection should be considered when measuring and interpreting 25OHD concentrations and comparing values over time.

Poster Board #61 Jacob Stubbs, Undergraduate Student, University of British Columbia Supervisor: William Panenka, Brain, Behaviour & Development

Working memory load increases the diagnostic utility of smooth pursuit eye movements in mTBI Jacob L. Stubbs, Sherryse L. Corrow, Benjamin Kiang, Jeffrey Corrow, Hadley Pearce, Jason J. Barton, William J. Panenka Introduction: Despite some promising eye movement research, no objective diagnostic paradigm has been developed to diagnose mTBI. We hypothesized that combining a working memory (WM) task and smooth pursuit eye movement would provide a higher degree of diagnostic discrimination between patients and controls than either alone. Methods: 16 mTBI patients and 15 control participants followed a target on a circular trajectory, and two levels of additional WM load were added in some trials. Eye movement was tracked using infrared video-oculography. Results: Significant differences were found in smooth pursuit between mTBI participants and healthy controls across all levels of WM load. Low WM load significantly improves the tracking of mTBI patients (p < 0.01). High WM load has no effect on mTBI pursuit but significantly improves pursuit in controls (p < 0.01). A receiver operator characteristic shows an area under the curve of 0.78 for baseline pursuit, 0.70 for 1-back pursuit, and 0.90 for 2-back pursuit pursuit. Conclusion: The preliminary results indicate that pursuit with a high amount of additional WM load is a more sensitive diagnostic paradigm of mTBI than eye tracking alone.

Poster Board #62 Lee Vargen, Undergraduate Student, Simon Fraser University Supervisor: Tonia Nicholls, Brain, Behaviour & Development

Predicting the whole picture: The predictive validity of the START for a range of outcomes Lee M. Vargen, Duncan Greig, Tonia L. Nicholls The Short-Term Assessment of Risk and Treatability (START; Webster et al., 2004) is a structured professional judgment tool designed to aid in the assessment of the short-term risk for adverse outcomes in a forensic mental health context. The START is unique relative to other risk assessment tools in its incorporation of both risk and protective factors, as well as its focus on predicting a range of adverse outcomes beyond just violence and aggression (Nicholls et al., 2016). Prior research has demonstrated that the START has good predictive validity for both aggression and self-harm, however far less research has examined the measure’s predictive validity for the wider range of adverse outcomes it was designed to assess (O’Shea & Dickens, 2014). Furthermore, the research that does examine these other outcomes offers mixed support for the START’s ability to predict these other outcomes (O’Shea & Dickens, 2014). Given the considerable range of adverse outcomes that forensic mental health populations are at risk for experiencing (e.g. self-harm and suicide, substance abuse, self-neglect, victimization, and unauthorized leave), it is necessary to evaluate tools such as the START to assess their utility in informing decision-making related to the care of forensic patients. The current research was conducted with a sample of adult male inpatients in a forensic psychiatric hospital. We first examined both the nature and frequency of adverse events in this sample, including self-harm, suicidal behaviour, substance abuse, self-neglect, victimization, and unauthorized leave. Second, we examined the association between START scores and the occurrence of the aforementioned adverse outcomes in order to test the tool’s predictive validity.

Poster Board #63 Helen Wu, Undergraduate Student, McGill University Supervisor: Mark Ansermino, Healthy Starts

Evaluating the feasibility of Panda, a smartphone app designed to help parents manage their child’s post-operative pain Mark Ansermino, Dustin Dunsmuir , Terri Sun, Matthias Gorges Background: In light of growing trends towards outpatient or ambulatory surgical procedures, the tasks of managing post-operative pain and administrating medications have shifted from health care providers to caregivers at home. Studies, including a recent audit of adenotonsillecotmies performed at the BC Children’s Hospital (BCCH), have shown that pain in children after outpatient surgeries is poorly managed at home. This audit revealed that 92% of parents reported their child’s pain as moderate or severe within 48 hours after surgery and 38% of children having not received all prescribed doses of the analgesics. With motivation from this data, the Paediatric Anaesthesia Research Team here at the BCCH developed a smartphone app called Panda to help parents manage their child’s pain and keep track of medications being administered. Panda features digitized versions of the Faces Pain Scale Revised (S-FPS), Color Analogue Scale (CAS) and Simplified Concrete Ordinal Scale (S-COS) that parents can use to assess their child’s pain. The app also sets up a schedule of alerts that remind users when medications are due and features a calendar where all medications and pain checks done with a child throughout their recovery can be viewed. Objectives: The objective of this study is to evaluate the feasibility of Panda at home. Methods: Recruitment of 30 families for the study is taking place in the Surgical Day Care Unit at the BCCH. The Panda app is installed and set up on the parent’s mobile device before discharge from the hospital following ambulatory surgery and they are asked to use it as much as possible during their child’s recovery. Compliance and user satisfaction is evaluated through a post-study interview on the phone, an online questionnaire, and device-recorded audit logs of functions to identify any barriers hindering effective home-use of Panda. Three cycles are to be performed, recruiting n=10 families per iteration, for a total of n=30. Improvements to the application from each round’s feedback will be implemented between each cycle prior to initiation of the next iteration. Results: The study is still underway as we prepare for the third round of recruitment in August.

The Research Education Office, at the BC Children’s Hospital Research Institute, supports the development of an enriched, multidisciplinary learning environment for researchers onsite How do we support the research community? • Offer a curriculum for graduate students and postdoctoral fellows to help build analytical capacity and enchance career development skills • Coordinate training resources and professional development opportunities for clinical researchers • Bridge the gap between basic science and clinical research with unique networking and funding opportunities

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

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

Trainees in 2016 - 2017

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Budget for training and awards in 2017 - 2018

785 Alumni trainees

106

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

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