Trainee Research Forum 1
Welcome to the 17th annual Trainee Research Forum. Each year we host this event to showcase unique and innovative research being conducted by trainees on the Oak Street campus. The community at BC Children’s Hospital provides trainees with a true ‘bench to bedside’ opportunity for research. We provide training opportunities for graduate students, postdoctoral fellows, clinical residents and sub-specialty fellows throughout the year, and for undergraduate and medical students through our flagship Summer Student Research Program. The diversity of the research here is remarkable, and the Trainee Research Forum provides a wonderful preview of the interdisciplinary work our trainees will pursue as they progress into their own careers as scientific and clinical investigators. We are proud of the trainees here and we are pleased to be able to help them become leaders in their respective fields. Wyeth W. Wasserman, Ph.D.
Executive Director, BC Children’s Hospital Research Institute Associate Dean, Research, Faculty of Medicine, University of British Columbia 2
2017 Trainee Research Forum Thursday, June 22 Poster Presentations 1:00 p.m Chieng Family Atrium
Showcasing the outstanding work of research trainees and clinical residents or subspecialty fellows based on the Oak Street campus and their contributions to research Each participant has been assigned to one of 7 groups and will have 5 minutes to discuss their poster and up to 5 minutes for questions
Awards Ceremony & Reception 2:45 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 trainee recipients of the 2017: • Poster Presentation Awards • Outstanding Achievement Awards • Studentships & Fellowships The ceremony will also feature a talk by Dr. Jan M. Friedman, Geoffrey L. Hammond Lectureship recipient, on his career and research highlights 3
Celebrating excellence in our talented research community 2017 Award Recipients
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Geoffrey L. Hammond Lectureship 2017 Recipient The Geoffrey L. Hammond Lectureship recognizes investigators on the Oak Street Campus who have made a significant impact on improving the health and well-being of children and/or families, served as a role model and mentor to junior researchers, trainees and students over the last 10 years, and provided leadership to the community on the Oak Street Campus. Dr. Jan M. Friedman is a clinical geneticist and Professor of Medical Genetics at UBC. He received his MD from Tulane University in New Orleans and his PhD in Genetics from the University of Washington (UW) in Seattle. He completed a pediatrics residency at the Children’s Memorial Hospital in Chicago and a clinical fellowship in medical genetics at UW. He joined UBC and the BC Provincial Medical Genetics Program in 1986 and has since held leadership positions at UBC, BC Children’s & Women’s Hospital and BC Children’s Hospital Research Institute, as well as in national and international scientific societies.
Dr. Jan M. Friedman, Investigator, BC Children’s Hospital; Professor, UBC Department of Medical Genetics
In the past decade, Dr. Friedman has been a pioneer in the development and application of cytogenetic and genomic tools to understand the genetic causes and clinical consequences and improve diagnosis of intellectual disability syndromes. He is also a recognized expert in teratology, with his focus on determining the risk for birth defects arising from maternal anti-depressant use during pregnancy, which provides critical information that is essential for the development of regulatory guidelines for these medications. He has published more than 270 peer-reviewed papers, has written six books and edited two others. Dr. Friedman is the Director of CAUSES Clinic at BC Children’s Hospital. The research clinic provides advanced DNA testing, clinical interpretation, genetic counselling, and personalized recommendations for treatment for children with complex, undiagnosed medical conditions. Dr. Friedman has supervised numerous graduate students and postdoctoral fellows, as well as mentoring many medical genetics residents and fellows. Through his mentorship, Dr. Friedman provides support, wisdom and demonstrates a rigorous approach to research. He has been, and undoubtedly will continue to be, a tremendous role model for students, junior researchers and anyone else that has the privilege of working with him. 5
Outstanding Achievement Awards: Masters Student Ms. Emma Hitchcock completed a Master of Science in Medical Genetics at UBC this past April under the supervision of Dr. William Gibson. Emma’s focus of study is families with hereditary brain aneurysms, with the goal of identifying a genetic variant that is a major risk factor for this disease. Throughout her research, Emma has been responsible for every aspect from consenting families; collecting detailed family histories, clinical information and samples for DNA extraction; and analyzing DNA sequencing results.
Ms. Emma Hitchcock Gibson Research Team This award recognizes the outstanding achievement of a masters student whose research skills and analytical capacity clearly demonstrate the individual’s potential as a productive member of the scientific community
In addition to being a skilled researcher, Emma is an exceptional student, presenter and writer. She has already written two first author papers and also written and contributed extensively to a number of successful grant applications. Emma first presented her work at the BCCHR Trainee Forum, for which she received the top poster prize in her category in both 2015 and 2016. She has also presented internationally at the European Society of Human Genetics conference in May 2016. Emma is also a tutor and mentor, tutoring first year medical students through a workshop on Prenatal Diagnosis, and meeting weekly with a Little Sister for one-on-one tutoring as part of the Big Sisters of BC Lower Mainland Study Buddy program. Emma received a Medical Genetics Teaching Award for her role as teaching assistant for “Developmental Origins of Human Disease” during the 2015 – 2016 academic year. Emma is a personable and collaborative team player in all that she does. In addition to her academic and professional achievements, she is an accomplished rower and has worked as an assistant coach and a Varsity Athletics Representative. Emma’s diverse skill sets will serve her well both in her position as Study Coordinator with Dr. Gibson’s team and her future academic and professional pursuits.
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Outstanding Achievement Awards: Doctoral Student Ms. Giulia Muraca is a PhD student in the School of Population and Public Health at UBC under the supervision of Dr. K.S. Joseph; she is expected to defend her doctoral thesis later this year. Her work focuses on the perinatal period, with an emphasis on outcome-based assessments of forceps, vacuum and cesarean delivery. Giulia authored 13 publications during her doctoral degree (six as first author), nine published, one in revision and three under review. She has also published 12 posters and abstracts and delivered 13 oral presentations nationally and internationally over the course of her doctoral studies. She recently received an award for best poster presentation from BCCHR at the Healthy Starts Theme’s inaugural Research Day in November 2016.
Ms. Giulia Muraca Joseph Research Team This award recognizes the outstanding achievement of a doctoral student whose demonstrated originality, research ability and a capacity for critical thinking identify the individual as being likely to become a contributing member in the scientific community
Giulia and her work have also been recognized by the Canadian Institutes of Health Research with a Vanier Canada Graduate Scholarship and by UBC through a Four-Year Fellowship. She has also proven herself to be a dedicated mentor, working as a graduate student mentor, senior teaching assistant and peer mentor at UBC. Her current volunteer activities include serving as a board member of the Gosena Community Effort, a registered NGO that provides bursaries to students in Namibia. Giulia’s PhD work is promising and will have a significant impact on obstetric practice with regard to reducing rates of maternal and infant complications, making deliveries safer for both mothers and babies. She has demonstrated outstanding achievements for a doctoral student and will continue to make significant contributions to research.
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Outstanding Achievement Awards: Postdoctoral Fellow Dr. Britt Drögemöller has proven to be an outstanding postdoctoral fellow as part of the Ross Lab. Her research focuses on the identification of genetic variants that place individuals at increased risk of experiencing severe adverse drug reactions. Her aim is to guide strategies to allow for the implementation of personalized treatment strategies, which provide maximum benefit and minimal harm to patients.
Dr. Britt Ingrid Drögemöller Ross Research Team This award recognizes the outstanding achievement of a postdoctoral fellow whose high academic achievements, personal leadership qualities and demonstrated research ability show promise of the individual becoming a future leader in health research
Dr. Drögemöller has published 24 peer-reviewed articles and is first author for 12 of these articles. In addition to her academic strengths, Dr. Drögemöller has proven to be a skilled communicator and has presented at several international and national conferences. She was awarded “Best Presentation” on six occasions, including “Best Overall Presentation” at the BCCHR E2i Research Day 2016. In addition to sharing her research through traditional means she has also shared her research through news articles and talks, making it accessible to the general public. Dr. Drögemöller’s accomplishments are further evidenced by the awards she has received, including 13 bursaries/ fellowships and 14 travel awards/student stipends. She was also a co-investigator for a BCCHR E2i Seed Grant. Aside from her research-related activities, Dr. Drögemöller has also proven herself to be a strong mentor and leader. She leads the monthly Canada-wide CPNDS journal club, and she is a member of the BCCHR Trainee Council. Previously, she has also served as a facilitator for the UBC Vancouver Summer Program, was a part of the team that organized the first genomics hackathon in Vancouver, and has led laboratory tours and workshops at the Gairdner High School Student Symposium and BCCHR Open House. Dr. Drögemöller has made valuable contributions to the research performed at BCCHR and has demonstrated exceptional leadership qualities. Her work has been outstanding, and she is well-positioned to continue her success as she moves forward in her career.
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Outstanding Achievement Awards: Resident Over the last three years, Dr. Alison Lee has participated in two largescale research projects. Through her involvement with these projects, she has had one first author publication and a submitted manuscript.
Dr. Alison Lee Doan Research Team This award recognizes the outstanding achievement of a resident whose scholarly activity, industry and commitment to the research endeavour are an example to other trainees and who has contributed to advances in child, youth or women’s health
Dr. Lee has presented her research at two national conferences and three international conferences. As a pediatric resident, she presented the results of her completed research project to a national pediatric emergency medicine conference – a forum normally reserved for pediatric emergency medicine sub-specialty fellows to present work-in-progress. Her presentation was well-received and was praised by national leaders in pediatric emergency research. Dr. Lee was a co-presenter at a BC provincial-wide Grand Rounds for her research in mental health in emergency departments. She received an iACT Trainee Clinical Investigator Seed Grant to help with her project, and has also subsequently received a BC Pediatric Society Travel Grant and UBC Pediatrics Research Curriculum grant. In addition, she was the recipient of the Canadian Pediatric Society Conference award for best abstract in mental health in 2016. In addition to her research, Dr. Lee is actively involved in both her residency and her community. She is the co-founder of the Learning Buddies Network, a social pediatrics program aimed at providing free private tutoring in literacy and math to kids and fostering leadership and teaching skills in young adults. Within residency, she was elected by her peers to serve as Chief Resident. She is also part of the simulation team, teaches Pediatric Advanced Life Support (PALS) within the hospital, and sits on the board of BC Pediatrics Society as a resident representative. Dr. Lee also exhibits a keen interest in global health and has had the opportunity to work in Botswana, South Africa and Jamaica during her time in residency. She will be starting her fellowship in Pediatric Emergency Medicine in July 2017 and hopes to continue broadening both her research and clinical experience. 9
Outstanding Achievement Awards: Clinical Sub-specialty Resident or Fellow Dr. Abu Raya is an exceptionally promising clinicianscientist at BC Children’s, where he has been an infectious diseases fellow for almost two years. In addition to managing a busy clinical workload he has led multiple studies and has 21 published manuscripts; he was first author for 18 of those publications.
Dr. Bahaa Abu Raya Sadarangani Research Team This award recognizes the outstanding achievement of a clinical sub-specialty resident or fellow, whose research initiatives have been pursued in a conscientious, original and competentmanner, and who has the potential for academic excellence in their future career in their chosen specialty
As part of the Vaccine Evaluation Center, Dr. Abu Raya’s research has been predominantly in the field of immunization in pregnancy to protect the newborn and infant, focusing on pertussis. The data he has generated over the last few years has contributed significantly to immunization policy-making in several countries, specifically contributing to recommendations that pregnant women be immunized with pertussis vaccines. He has continued this area of work since his move to BCCH. As a pediatric infectious disease fellow, and given his expertise in maternal immunization, Dr. Abu Raya has developed his research interests further, joining a global consortium of experts in maternal immunization led by the Vaccine Evaluation Center. He was also invited to join the “Immunization Monitoring Program Active” (IMPACT) pertussis working group and the “Progressing Immunization in Pregnancy Evaluation and Research” (PIPER) group. Dr. Abu Raya has also been involved in immunization research with global relevance, specifically relevant to HIVexposed uninfected infants, resulting in two publications in Frontiers in Immunology in 2016. In addition to these publications Dr. Abu Raya has presented his work at various local, national and international meetings, including the European Society for Paediatric Infectious Diseases Annual Meeting – the largest pediatric infectious diseases meeting in the world. Dr. Abu Raya has excelled throughout his career, with several ‘cum laude’ honors over the last 10 years. He has continued to follow this outstanding trajectory, being awarded a Thrasher Research Fund Early Career Award and one of the prestigious International Doctoral Fellowship Awards from UBC, ensuring a strong start to his PhD in July at BCCHR. 10
Graduate Studentships Michael Cuccione Childhood Cancer Foundation Graduate Studentship Lisa Decotret, Pallen Research Team. Role of protein tyrosine phosphatase alpha (PTPa) in invadopodia formation and function BC Children’s Hospital Research Institute Jan M. Friedman Graduate Studentship Kelsie Doering, Taubert Research Team. Dissecting the response to oxidative stress to find novel drug targets BC Children’s Hospital Research Institute Healthy Starts Graduate Studentship Emma Graham, Mostafavi Research Team. Integration of genetic and metabolomic data for prioritization of causal genes in neurodevelopmental disorders Michael Cuccione Childhood Cancer Foundation Graduate Studentship Matthew Gynn*, Reid Research Team. Utilization of asparaginase-expressing yeast for the treatment of leukemia BC Children’s Hospital Research Institute Graduate Studentship Christina Michalski, Lavoie Research Team. Enhancing immune defenses of premature neonates through metabolic reprogramming BC Children’s Hospital Research Institute Graduate Studentship Katherine MacDonald, Levings & Piret Research Teams. Optimization of thymus-derived regulatory T cell culture for cell-based therapy Canucks for Kids Fund Childhood Diabetes Laboratories Graduate Studentship Sarah Montgomery, Devlin & Panagiotopoulos Research Teams. Cardiovascular health of children treated with second-generation antipsychotics Michael Cuccione Childhood Cancer Foundation Graduate Studentship Foujan Pedari, Lim Research Team. CALR regulates JAK/STAT signaling in cell survival and drug resistance in pediatric acute lymphoblastic leukemia Michael Cuccione Childhood Cancer Foundation Graduate Studentship Lorenz Nierves, Lange Research Team. Discovering unique cell surface-exposed protein termini in pediatric leukemia BC Children’s Hospital Research Institute Graduate Studentship Paulina Piesik*, Dutz Research Team. Using the skin immune system to induce systemic tolerance BC Children’s Hospital Research Institute Graduate Studentship Phillip Richmond, Wasserman Research Team. Clinical grade copy number variant calling from whole genome sequencing BC Children’s Hospital Research Institute Graduate Studentship Yuanjie Zou, Luciani Research Team. Investigating the importance of lysosomal physiology and pathophysiology in diabetes and islet transplantation *Accepted external funding, declined BCCHR funding
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Postdoctoral Fellowships BC Children’s Hospital Research Institute Bertram Hoffmeister Postdoctoral Fellowship Dr. Laura Cook, Levings Research Team. Characterizing clostridium difficile toxin-specific CD4+ T cells BC Children’s Hospital Research Institute Mining for Miracles Postdoctoral Fellowship Dr. Hind Sbihi, Turvey Research Team. Targeting green spaces and transportation for childhood asthma prevention: Insights at the genetic level
Clinical & Translational Research Seed Grants Dr. Ali Eslami & Dr. Fern Jasper-Fayer, Stewart Research Team. The Influence of task load on functional networks in pediatric OCD Dr. Jayson Potts & Dr. Mohamed Elgendi, K.Lim Research Team. A Pilot Study to Determine the Optimal Finger for Hypertension and Preeclampsia Assessment Using Pulse Oximeter Collection Dr. Meghna Rajaprakash & Dr. Regula Neuenschwander, Oberlander Research Team. Child and adolescent placebo studies: Neurobiological underpinnings – genetic variants and executive functions
BC Children’s Hospital Research Insitutute training awards are funded by the BC Children’s Hospital Foundation 12
Showcasing excellence in our talented research community 2017 Poster Presentations
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Participants Session One
Masters Students
Session Two Masters Students
Name
Abstract Title
Page
Hilary Brewis
Defining the features of a functionally minimal H2A.Z histone variant in budding yeast
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Jennet Baltayeva
Diet-induced obesity may alter uterine natural killer cell biology at maternal-fetal interface
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Amanda Henderson
Programming of offspring adiposity and glucose homeostasis by maternal folate/vitamin B12 imbalance: The roles of insulin-like growth factor-1 and energy metabolism
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Ryan Kopstick
The dynamic social brain
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Jessica Luk
Aberrant functional activity in language association network is predicted from disorganization syndrome in schizophrenia
24
Lorenz Nierves
Optimizing a proteomic workflow for the isolation of cell surface proteins and termini
25
Dalal Qanaq
Associations of maternal folate and vitamin B-12 status with gestational age and birthweight
26
Victor Yuan
Placental DNA methylation ethnicity predictor
27
Name
Abstract Title
Page
Catherine Biggs
Characterization and successful treatment of a novel autosomal dominant immune dysregulatory syndrome caused by a JAK1 gain-of-function mutation
29
Giulia Del Gobbo
A method for estimating ancestry as a continuous variable for genetic or epigenetic studies
30
Kristy Dever
A broader role for FCP1 in transcription regulation
31
Peter Radonic
Determining the pediatric requirement of dietary threonine for growth and development
32
Lindsay Richter
Trends in neonatal mortality and morbidity following spontaneous and latrogenic preterm delivery: Washington State, USA, 2004-2013
33
Thyrza Toledo
Circulating DNA analysis in children with solid tumors given granulocyte colony stimulating factor
34
Samantha Schaffner
Epigenetic, transcriptional, and apoptotic responses to neonatal alcohol exposure in mice are influenced by sex and brain region
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Session Three Doctoral Students
Session Four Doctoral Students
Name
Abstract Title
Page
Hani Bagheri
Is there a mirror phenotype for 2p15p16.1 microdeletion syndrome?
37
Joshua Brown
Distinct roles of Rtt107 in checkpoint regulation and genome maintenance
38
Michelle Chakraborti
The development of social networks among families attending physical activity programs for children with neurodevelopmental disabilities: An opportunity to strengthen families and enhance childcare
39
Harpreet Chhina
Qualitative insights to health related quality of life among US and Canadian based children with lower limb deformities
40
Avery Lam
Expression and regulation of amphiregulin in human regulatory T cells
41
Christina Michalski
Cellular metabolic and translational constraints in preterm monocytes
42
Mahdis Monajemi
The role of MALT1 in macrophages
43
S.M Reza Rahavi
In vivo evaluation of localization and immune sensitivity of human neuroblastoma in xenografts
44
Name
Abstract Title
Page
Abeer Aljaadi
Prevalence of iron deficiency anemia in nonpregnant women of reproductive age living in Kuala Lumpur, Malaysia
46
Sarah Anderson
Examining conduct disorder symptoms, callousunemotional traits, and the development of substance use through adolescence and young adulthood: The moderating role of sex
47
Allison Ezzat
Is knee confidence a concern in youth & young adults 3-10 years following intra-articular knee injury?
48
Daphne McRae
Antenatal midwifery care: Reducing prevalence of small for gestational age birth and preterm birth for women with low socioeconomic position
49
Naama Rotem-Kohavi
Alterations in resting state networks following in-utero SSRI exposure in the neonatal brain – preliminary results
50
Jean Philippe Sauve
Tuft cells and their role in intestinal inflammation
51
Samantha Wilson
Utility and reproducibility of DNA methylation profiling in preeclampsia and intrauterine growth restriction placentas
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Session Five Doctoral Students
Session Six
Doctoral Students
Name
Abstract Title
Page
Kayleigh Campbell
In utero SSRI antidepressant exposure and maternal depression predict corpus callosum microstructure in term-born neonates
54
Madeleine Ennis
Dietary phenylalanine requirements for healthy pregnant women are increased in late gestation
55
Lisa Kozicky
Intravenous immunoglobulin-activated IL-10 producing macrophages may be useful to treat Inflammatory Bowel Disease
56
Rachelle Pullmer
Self-compassion in relation to depressive symptoms in adolescents: A gender comparison
57
Lakshana Sreenivasan
The role of IL6/STAT3 in chemoresistance of medulloblastoma
58
Ella Weik
Distinct attentional strategies differentially engage component processes of the attention system
59
Olivia Wong
Elucidating the consequences of the overexpression of histone variant H2A.Z in transcription
60
Name
Abstract Title
Page
Mark Bichin
Altered neural network engagement during working memory at school age in children born very preterm
62
Nicha Boonpattrawong
Maternal obesity and exercise programs cardiometabolic heatlh in offspring
63
Alyssa Kirlin
The Yaf9 YEATS domain plays a role in its association with chromatin modifying complexes
64
Chaini Konwar
Genetic and epigenetic profiling of acute chorioamnionitis associated placentas
65
Phillip Richmond
Clinical grade copy number variant calling from whole genome sequencing in the diagnosis of rare genetic disorders
66
Jonathan Simkin
Differences in colorectal cancer screening rates across income strata by rural and urban status: Results from the Canadian Community Health Survey (2013/2014)
67
Desiree Wilson
Engaging children in examining neighbourhood play-friendliness: A participatory research project using visual methods
68
Kevin Tsai
Mucus deficiency results in negative selection of developing T cells restricted to oral antigens
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Session Seven Postdoctoral Fellows & Subspecialty Residents or Fellows
Session Eight Postdoctoral Fellows & Subspecialty Residents or Fellows
Name
Abstract Title
Page
Ainsley Boudreau
Predicting use of medications for children with ADHD: The contribution of parent social cognitions
71
Fern Jaspers-Fayer
The influence of symptom provocation on executive function in pediatric obsessivecompulsive disorder
72
Alison Lee
A psychosocial assessment and management tool for youth in crisis
73
James McCammon
Management of the proximal tibiofibular joint in tibial lengthening
74
Beth Payne
Precision medicine for pregnant and recentlypregnant women receiving critical care: The CIPHER (Collaborative Integrated Pregnancy Highdependency Estimate of Risk) model
75
Ainsley Boudreau
Examining the acceptability and effectiveness of group-based comprehensive behavioural intervention for Tics in elementary-aged children
76
Robert Selles
Parent tolerance of child distress in pediatric obsessive-compulsive disorder: Correlates and relationship with group family-based cognitive behavioral therapy outcomes
77
Jon Stacey
Unplanned post-operative admission after ambulatory surgery at BCCH: An audit
77
Name
Abstract Title
Page
Emily Schaeffer
The need for further corrective surgery in Developmental Dysplasia of the Hip: Surgical decision-making and practice variability
80
Liezl du Plessis
High incidence of acute kidney injury during chemotherapy for acute myeloid leukemia
81
Jenny Fairthorne
Depressed, low SES women have high numbers of physician visits in the year before pregnancy: implications for pre-conception care
82
Devon Greyson
Childhood immunization mandates: The international landscape
83
Juliana Negreiros
Differences in OCD-affected youth’s executive functioning when using direct versus indirect measures of the same theoretical construct
84
Cheryl Peters
Systemic inflammatory response syndrome criteria and sepsis mortality in children: Time for a new definition?
85
Nicholas Williams
An objective approach to developing guidelines for resuscitation at the threshold of viability
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Room 2108 Patio Registration
Chan Centre for Family Health Education
Main Entrance
Reception
Refreshments
Session One - Masters Students #1 - 8
Session Six - Doctoral Student #38 - 44
Session Two - Masters Students #9 - 15
Session Seven - Postdoctoral Fellows, Residents & Subspecialty Residents #45 - 52
Session Three - Doctoral Students #16 - 23 Session Four - Doctoral Students #24 - 30
Session Eight - Postdoctoral Fellows, Residents & Subspecialty Residents #53 - 59
Session Five - Doctoral Students #31 - 37 18 The drawing is intended for visual reference only, it is not to scale
Session One MASTERS STUDENTS Moderator: Laura Sly Participants: Hilary Brewis Jennet Baltayeva Amanda Henderson Ryan Kopstick Jessica Luk Lorenz Nierves Dalal Qanaq Victor Yuan
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Board # 1 Hilary Brewis, Masters Student Supervisor: Michael Kobor, Healthy Starts
Defining the features of a functionally minimal H2A.Z histone variant in budding yeast Hilary T Brewis, Michael S Kobor Chromatin structure and underlying DNA accessibility can be modulated by the incorporation of a variety of different histone variants. One of the many H2A histone variants, H2A.Z is found to be enriched in the promoters of genes that flank heterochromatin domains and subtelomeric regions, and is required for correct transcriptional regulation of chromosome segregation, DNA repair, and cell differentiation. In yeast, H2A.Z is very similar to H2A, with a 60% conserved amino acid sequence and an almost identical 3D structure. Despite their similarity, the two histones have distinct functionality. While the functional differences between H2A and H2A.Z have been relatively well characterized, the distinct structural features of H2A.Z that cause these variations remain unknown. To tease apart the functional regions of H2A.Z, a library of varying H2A-H2A.Z hybrids (created by replacing regions of an H2A gene with the corresponding H2A.Z gene sequence) are being examined for their ability to perform as a wild-type H2A.Z. Hybrid function will be assessed for (i) their ability to rescue htz1Δ mutant phenotypes in various genotoxic growth assays, (ii) their interaction with the H2A.Z specific histone chaperone Chz1 and the subunits of the chromatin remodeler SWR1-C using immunoprecipitation, and (iii) the H2A.Z dependent gene expression using RT-qPCR. Preliminary results have shown that some individual regions can partially rescue the knockout phenotype, however it is still unclear if these hybrids fully imitate H2A.Z specific localization in gene promoters. Using the insights gained from this research, I will construct a H2AH2A.Z hybrid that contains the minimal amount of H2A.Z sequence necessary to functionally perform as wild-type H2A.Z. This will contribute to our understanding H2A.Z function in eukaryotes and provide insight into many biological mechanisms mediated by H2A.Z.
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Board # 2 Jennet Baltayeva, Masters Student Supervisor: Alexander Beristain, Healthy Starts
Diet-induced obesity may alter uterine natural killer cell biology at maternal-fetal interface Jennet Baltayeva, Barbara Castellana, Eunice Chin, Julian K. Christians, Alexander G. Beristain Objective: Maternal obesity is associated with multiple adverse reproductive outcomes, negatively affecting maternal and fetal health. The mechanisms that link obesity to pregnancy complications remain unclear. Proper development of the placenta and establishment of utero-placental vasculature are essential for optimal fetal growth and survival. Uterine immune cells, particularly uterine natural killer cells (uNKs), play a fundamental role in promoting these events. This work aims to develop a mouse model of obesity in pregnancy to examine the effects of obesity on uNK cell biology and placental development. Methods: A diet-induced mouse model of obesity was established by subjecting 6-week old female C57BL-6 mice to a high-fat (HFD) or control diet for 13 weeks. Following the diet, mice were mated with C57BL-6 male mice, and on days 10 (gd10) and 14 (gd14) of gestation uterine horns were extracted and decidual mononuclear cells (DMCs) were isolated. Subpopulations of tissue-resident (tr) and conventional (c) uNK cells were quantified via multicolour flow-cytometry and characterized in their expression of the cytotoxicity receptor (NCR1). RNA from gd10 uNKs was isolated for gene expression analysis. Utero-placental tissues from gd14 implantation sites will be dedicated for immunohistological analysis. Results: Phenotypic analysis of uNKs revealed that diet-induced obesity resulted in subtle alterations in sub-populations of uNK cells at gd10 in mice, characterized by increased proportions of tr-uNK cells and uNK cells expressing the NCR1. Conclusion: As tr-uNK cells produce angiogenic factors (i.e. VEGF) in early pregnancy, the cellular alterations identified in this study suggest that maternal obesity may lead to alterations in vascularization in the uterus. Further, an increase in the uNK cell NCR1 population suggests that maternal obesity may also result in alterations in uNK cell cytotoxicity/activity. Future work will examine vascular/angiogenic changes within implantation sites and global gene expression changes in uNK cells between control and HFD mice.
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Board # 3 Amanda Henderson, Masters Student Supervisor: Angela Devlin, Healthy Starts
Programming of offspring adiposity and glucose homeostasis by maternal folate/vitamin B12 imbalance: The roles of insulin-like growth factor-1 and energy metabolism Amanda M. Henderson, Rika E. Aleliunas, Nolan G. J. Chem, Daven C. Tai, Sanjoy Ghosh, Angela M. Devlin Developmental programming suggests that prenatal/early postnatal environment can impact risk for chronic diseases. Population studies suggest that maternal folate/vitamin B12 (B12) status during pregnancy may affect adiposity and insulin resistance in children. Folate is required for methyl metabolism and is metabolically linked to B12. The mechanisms underlying the relationship between maternal folate/B12 status and offspring adiposity and insulin resistance are not understood. It was reported that maternal B12 deficiency during pregnancy disrupts growth hormone (GH)/insulinlike growth factor-1 (IGF-1). The objective of this study is to determine if programming of offspring adiposity by maternal folate/B12 imbalance involves disturbances in the GH/IGF-1 axis and energy metabolism. Female mice (C57BL/6J) were fed one of 3 diets six weeks prior to breeding, through pregnancy, and lactation; control (2mg folic acid/kg diet, M-CON), supplemental FA (10mg/kg) with adequate B12 (SFA+B12), or supplemental FA without B12 (SFA-B12). One male and one female pup from each dam were weaned onto a control or a western diet (45% energy from fat). Tissue was harvested from offspring at 20 weeks post-weaning. Serum IGF-1 concentrations were quantified by ELISA. Lipid classes were quantified in liver by HPLC-ELSD. Hepatic Cpt1a and adipocyte Acaca mRNA were quantified by Real-Time PCR. Female SFA-B12 offspring fed the control diet had lower (p<0.05) serum IGF-1 concentrations than M-CON and SFA+B12 offspring. This was accompanied by higher (p<0.05) hepatic Cpt1a mRNA expression in SFA-B12 and SFA+B12 offspring than M-CON offspring. Female SFA-B12 and SFA+B12 offspring fed the western diet had lower (p<0.05) adipocyte Acaca mRNA expression than M-CON offspring. Male SFA-B12 offspring fed the control diet had higher (p<0.05) linoleic acid (C18:2n-6) and lower (p<0.05) eicosapentaenoic acid (C20:5n-3) concentrations in the liver than M-CON and SFA+B12 offspring. Male SFA-B12 offspring fed the western diet had lower (p<0.05) hepatic Cpt1a mRNA expression than M-CON and SFA+B12 offspring.
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Board # 4 Ryan Kopstick, Masters Student Supervisor: Christine Tipper, Brain, Behaviour & Development
The dynamic social brain Ryan Kopstick, Christine Tipper Introduction: There is debate over whether autism spectrum disorder (ASD)-related interpersonal difficulties are result from disruptions in non-verbal social brain processes supporting “mirroring” (understanding another’s actions through a shared neural code for observing and performing actions), or “mentalizing” (deliberate consideration of another’s state of mind, intentions, or beliefs). Methods: This study utilized high-density EEG (dEEG) to quantify dynamics in functional brain networks supporting mirroring and mentalizing processes. We collected dEEG while neurotypical adults aged 19-35 performed a dynamic social cognition task, in which 12-s video clips of social scenes depicted ordinary or peculiar actions. Peculiar actions consisted of peculiar means (how an action was performed), peculiar intentions (why an action was performed), or peculiar social interactions. A photo judgment task, shown previously to differentiate mirroring and mentalizing brain networks using fMRI, was used as a functional localizer. Results: Preliminary dEEG data revealed a sustained ERP negativity in parietal channels beginning at 700 ms following peculiar means (mirroring), a reduced P3 component amplitude at temporal channels for peculiar intentions (mentalizing), a sustained positivity in parietal channels beginning at 500 ms, and a sustained negativity in frontal channels beginning at 300 ms for social interactions. Event-related synchronizations (ERSs) in alpha- and beta-band frequency spectral power at early (200-1400 ms), middle (2100-2800 ms), and late (4200-4800 ms) time points during the epoch were larger for peculiar actions overall, but this difference was greatest at parietal channels for means, frontal and temporal channels for intentions, and parietal channels for social interactions. Social interactions also showed the opposite pattern in frontal channels, where ERSs were larger for ordinary than peculiar actions. There were also differences in the timing of ERSs, with increasing latencies for intentions, means, and social interactions (respectively) in parietal and temporal channels, and social interactions, intentions, and means (respectively) in frontal channels. Conclusion: The brain codes multiple dimensions of observed actions, and different neural networks are involved in representing means (“mirroring”), intentions (“mentalizing”), and social interactions. Ongoing analyses will localize distinct mirroring and mentalizing networks and chart their interactions during naturalistic social cognition.
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Board # 5 Jessica Luk, Masters Student Supervisor: Todd Woodward, Brain, Behaviour & Development
Aberrant functional activity in language association network is predicted from disorganization syndrome in schizophrenia Jessica Luk, Todd Woodward Advances in neuroimaging techniques are beginning to allow researchers to characterize aberrant functional networks in patients with schizophrenia. Recent work from our laboratory has characterized seven functional brain networks that are reliably elicited with cognitive demand: the i) response, ii) visual attention, iii) inner speech, iv) cognitive evaluation, v) language, vi) default mode, and vii) primary sensory networks. The language network is a necessary mediator in language association of semantic concepts. A dysfunctional language network is therefore a primary candidate associated with the pathology of schizophrenia. Recent work from our lab has implicated the language network to be involved in the presentation of schizophrenia, where lowered activity within the language network is correlated with schizophrenia. Based on legacy data from our lab of 30 patients diagnosed with schizoaffective disorder or schizophrenia, we use functional magnetic imaging constrained principal component analysis (fMRI-CPCA) to extract functionallyrelevant neural networks involved in the semantic integration task to delineate its relationship with symptomology. Briefly, fMRI-CPCA is a statistical tool combining multivariate multiple regression with principal component analysis (PCA) we use to predict coordinated activity in the output of an HDR shape. We then extrapolate how particular types of symptoms have predictive value in predicting the resulting hemodynamic response (HDR) shape as measured by fMRI. Multivariate regression analysis indicated 31.1% of variance could be predicted by symptoms, where PCA revealed three components (component 1-3) accounted for 9.4%, 7.4%, and 6.7% of total variance, respectively (p < 0.04). Specifically, the HDR shape was most correlated with disordered cognitive symptoms in schizophrenia, where the peak HDR shape is negatively correlated to inappropriate affect and disordered thought. The rise of HDR signal is negatively correlated with underactivity (motor) and inappropriate affect, and positively correlated with severity of negative symptoms flattened affect and poverty of speech. By virtue of fMRI-CPCA, we can demarcate the association of specific symptoms in schizophrenia with functional activity within the language network.
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Board # 6 Lorenz Nierves, Masters Student Supervisor: Philipp Lange, Childhood Diseases
Optimizing a proteomic workflow for the isolation of cell surface proteins and termini Lorenz A. Nierves, Chia-Wei Kuan, Philipp F. Lange Background: Recent advances in targeted immunotherapy led to renewed interest in exploring the plasma membraneâ&#x20AC;&#x2122;s (PM) proteome and how changes in this sub-proteome could be linked to many diseases. Additionally, there is strong evidence that deregulated proteases in the microenvironment play an important role in the pathogenesis of cancer. It is therefore possible that the processing of cell surface proteins is altered in cancer. We hypothesize that the altered microenvironment and presence of cancer-specific proteases in the bone marrow (BM) of Acute Lymphocytic Leukemia (ALL) lead to new and targetable cell surface protein termini that are not found on normal cells. Objective: To optimize a proteomic workflow that will enable the isolation and analysis of cell surface proteins and termini from clinical samples. Approach: To enrich for cell surface proteins and termini for LC-MS/MS analysis, we will use two complementary approaches. I) We adapt the well-established cell-surface biotinylation/streptavidin (SA) pull-out to enrich for cell surface proteins and to simulaneously label surface-exposed protein N-termini. Briefly, intact cells are incubated with biotin to label proteins localized at the plasma membrane. After, biotin-labeled proteins are enriched through the use of magnetic SA beads. II) We combine cell-surface biotinylation with Terminal Amine Isotope Labeling of Substrates (TAILS) to enrich for cell surface termini. For this approach, biotin is used to label and protect accessible cell surface termini and lysine residues. An amine reactive polymer is then used to bind and remove peptides with unprotected amine groups in the N-terminus or lysine residues. Using Jurkat cells, we are currently optimizing the workflowâ&#x20AC;&#x2122;s parameters. Once the workflow is reliably capable of enriching for cell surface proteins and termini from limited amounts of cells, we will move on to clinical samples. Currently, we have 60 clinical samples from paediatric pre-B ALL and T-ALL patients stored in the BC Childrenâ&#x20AC;&#x2122;s Hospital Biobank. Outlook: We will derive a panel of cancer-specific termini to be characterized further. We will investigate the effect of microenvironment and protease alterations on the synthesis of these cancerspecific termini in vitro by using the optimized proteomic workflow to monitor changes in the termini over time.
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Board # 7 Dalal Qanaq, Masters Student Supervisor: Yvonne Lamers, Healthy Starts
Associations of maternal folate and vitamin B-12 status with gestational age and birthweight Dalal Qanaq, Theresa Schroder, Graham Sinclair, Benjamin Jung, Andre Mattman, Hilary D Vallance, Yvonne Lamers Birthweight and gestational age have been inversely associated with chronic disease risk in later life. The water-soluble vitamins folate and vitamin B12 (B12) have interdependent roles that are essential for fetal growth. Maternal folate and B12 concentrations during pregnancy have been positively associated with birthweight and gestational age; however, the findings are inconsistent. Recently, concerns have been raised regarding a potential adverse effect of high maternal folate status on pregnancy outcomes. Objective: To evaluate the association of maternal serum folate and B12 concentrations, combined and individually, with birth outcome, including birthweight and gestational age at birth. Methods: This retrospective cohort study included 685 apparently healthy mother-newborn dyads residing in the Lower Mainland, British Columbia. Maternal serum samples were collected in the first and second trimester at 9-13 and 15-19 gestational weeks, respectively, and measured for biomarkers of folate and B12 concentration. Exclusion criteria for maternal samples were hormone use, multiple pregnancy and non-naturally conceived. Newborns with inborn errors of metabolism, receiving parenteral nutrition or transfusion were excluded. The association of folate and B12 concentration with birth outcomes was assessed using multivariate linear regression models. Results: First and second trimester median (IQR) serum folate concentrations were 66.8 (53.4; 81.6) and 69.4 (55.5; 87.5) nmol/L, respectively, and those of total B12 were 220 (161; 299) and 201 (147; 272) pmol/L, respectively. The prevalence of low birthweight (< 37 gestational weeks) were 2.63% and 9.68%, respectively. After adjustment for ethnicity, maternal age, and newborn sex, neither maternal folate nor total B12 concentrations combined, or B12 concentration individually, in either trimester were significantly associated with birthweight. However, every 10-nmol/L increase in maternal serum folate concentration in the first trimester was associated with a 13-g decrease in birthweight (P=0.04). Neither folate nor B12 concentration combined or individually, in either trimester was significantly associated with gestational age. Conclusion: Early-pregnancy serum folate and total B12 concentrations were not associated with birth outcomes in this sample. The statistically significant, yet weak inverse association between first trimester maternal folate concentration and birthweight requires further investigation to elucidate the possible adverse effect of high folate concentration. 26
Board # 8 Victor Yuan, Masters Student Supervisor: Wendy Robinson, Healthy Starts
Placental DNA methylation ethnicity predictor Victor Yuan, Ming Wan, Michael Yuen, Nivretta Thatra, Anni Zhang Background: A large component of DNA methylation (DNAm) variability is associated with ethnicity. It is important to account for ethnicity in any large-scale population epigenetic study, or else interpretation of results can be confounded with factors correlated with ethnicity. Moreover, the effect of ethnicity on prenatal health remains largely unexplored. The aim of this study was to develop a model that predicts ethnicity based on DNAm data from placental tissue. Methods: 45 non-pathology placentas (33 Caucasians, 12 Asians) were measured on the Illumina 450k array, which measures DNAm at >450,000 sites. We filtered these sites based on a standard deviation of > 0.10 and used machine learning approaches to regress a penalized logistic model on the remaining 10,775 sites to predict Asian or Caucasian ethnicity. We show the utility of the predictor by using the predictor to obtain the ethnicity of 52 placental samples with unknown ethnicity from a second publicly-available dataset (‘GSE69502’). Results: We found that support vector machines (SVM) and a penalized regression model (glmnet) were comparable in their performance with an area under the curve (AUC) = 0.978 ±0.05, and 0.977 ±0.024, respectively in building a DNAm -based ethnicity predictor. Our final model was built using the dataset with a linear combination of 11 CpGs, 6 of which were overlapping with our list of significantly differentially methylated CpGs between Asians and Caucasians using an false discovery rate (FDR) of 0.05. We found that using the predictor on the second dataset with unknown ethnicity returned primarily Caucasian predictions, which is consistent with the demographic of the population where the tissue was collected in. Conclusion: Placental tissue samples show unique DNAm signatures reflecting Caucasian or Asian ethnicity. This ethnicity predictor can be used to account for ethnicity as a covariate in large –scale population epigenetic datasets. Future work involving more datasets may improve the accuracy of this ethnicity predictor and may return insights on the relationship between ethnicity and DNA methylation.
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Session Two MASTERS STUDENTS Moderator: Kelly Brown Participants: Catherine Biggs Giulia Del Gobbo Kristy Dever Peter Radonic Lindsay Richter Thyrza Toledo Samantha Schaffner
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Board # 10 Catherine Biggs, Masters Student Supervisor: Stuart Turvey, Healthy Starts
Characterization and successful treatment of a novel autosomal dominant immune dysregulatory syndrome caused by a JAK1 gain-of-function mutation Catherine M Biggs, Kate L Del Bel, Robert J Ragotte, Felix Orben, Luigi D Notarangelo, Margaret L McKinnon, Stuart E Turvey Introduction: Janus Kinase 1 (JAK1) plays an essential, non-redundant role in the JAK/STAT signaling cascade, a key pathway in the control of hematopoiesis and immune function. Significant progress has been made in elucidating the role of JAK1, but gaps in our knowledge still persist. Loss-offunction mutations in JAK1 have been associated with atypical mycobacterial infections, while somatic gain-of-function mutations have been linked to T-cell acute lymphoblastic leukemia. Results: We describe the first known patients carrying a germ-line gain-of-function mutation in JAK1. The clinical phenotype includes severe atopic dermatitis, markedly elevated peripheral blood eosinophil counts with eosinophilic infiltration of the liver and gastrointestinal tract, hepatosplenomegaly, autoimmunity, and failure to thrive. Functional analysis established the gainof-function phenotype caused by the mutation and in vitro studies demonstrated that the enhanced signaling could be controlled by ruxolitinib, an approved JAK1/2 inhibitor. T cell phenotypic analysis revealed a decreased proportion of naĂŻve CD4+ T cells, with elevated percentages of polarized T helper subsets compared to healthy controls. The patients were treated with ruxolitinib with remarkable improvement in a variety of clinical end-points, including hematological profiles and growth parameters. Conclusions: This characterization of a human JAK1 gain-of-function mutation expands our current understanding of the role of JAK1 in eosinophil biology, hematopoiesis and immune function.
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Board # 11 Giulia Del Gobbo, Masters Student Supervisor: Wendy Robinson, Healthy Starts
A method for estimating ancestry as a continuous variable for genetic or epigenetic studies GF Del Gobbo, C Konwar, WP Robinson Genetic or epigenetic association studies can be confounded by population stratification, typically caused by differences in genetic ancestry. Accounting for such effects is important, and is commonly practiced by using self-reported race/ethnicity as a surrogate. Ancestry informative marker (AIM) panels have been developed to infer ancestry or determine population sub-structure. These panels combine SNPs with allele frequencies that vary significantly between ancestral populations. In this study, we assessed the efficacy of a published AIM panel to differentiate ancestral populations, and develop a method to describe ancestry as a continuous variable. Methods: DNA from 368 placentas were genotyped at 55 AIM SNPs using the Sequenom iPlex Gold platform. SNPs and samples with call rates <0.9 were removed, leaving 53 SNPs and 355 samples. Genotypes for 2157 individuals from African, East Asian, European, and South Asian populations from the 1000 Genomes Project (1kGP) were downloaded for 50/53 available SNPs. A multidimensional scaling (MDS) analysis was applied to the 1kGP genotypes to assess the efficacy of the AIMs to differentiate ancestral populations. A second MDS analysis was applied to the 1kGP and placental samples to extract ancestry-reflective MDS coordinates in the placentas. KolmogrovSmirnov tests were used to assess differences in coordinate distributions between groups. Results: The top 3 MDS coordinates provided the best separation of the four 1kGP superpopulations. The distributions of these 3 coordinates were significantly different between the 1kGP populations (all p<0.01). Unsupervised k-means clustering with k=4, using the 3 coordinates as inputs, predicted ancestral population groups with over 98.9% accuracy. The 3 MDS coordinates provide evidence that our Vancouver population is more admixed than the 1kGP populations. In individuals with available maternal reported ethnicity, the top 2 MDS coordinates are significantly different (p=7.772e-16) between the two major ethnicity groups, Caucasian and East Asian. Conclusions: A small panel of 50 AIMs can be effective to assess genetic ancestry. Not only can this method be of use when ethnicity information is not available, but these MDS coordinates provide a novel way to describe ancestry along a continuum rather than grouping individuals into discrete categories, which is particularly relevant when studying admixed populations.
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Board # 12 Kristy Dever, Masters Student Supervisor: Michael Kobor, Healthy Starts
A broader role for FCP1 in transcription regulation Dever Kristy, Aristizabal Maria J., Negri Gian Luca, Benschop Joris J., Holstege Frank C. P., Krogan Nevan J., Kobor Michael S. Fcp1 is a phosphatase known to play a role in transcription elongation and termination by dephosphorylating the C-terminal domain (CTD) of RNA Polymerase II (RNAPII). Despite the functional overlap, FCP1 and RNAPII mutants display different gene expression and genetic interaction profiles, suggesting that Fcp1 has functions beyond dephosphorylating the CTD of RNA Polymerase II. By exploring our genetic and gene expression profiles of FCP1 truncation mutants, we identified transcription regulatory pathways particularly sensitive to loss of Fcp1 function, namely genes regulated by the transcription factor Skn7, which is a known phosphor-protein. Here, we discuss evidence of Fcp1 regulating Skn7 protein levels. Additionally, we explored the involvement of Cdk8 in this pathway, as we previously observed that loss of CDK8 suppressed FCP1 mutant growth phenotypes. Interestingly, the genetic suppression was accompanied by a normalizing effect on Skn7 mRNA levels. Furthermore, we found that Cdk8 played a role in regulating Skn7 protein stability as well as the levels of Skn7 phosphorylation. FCP1 and CDK8 mutants were also found to affect the transcription of Skn7 dependent oxidative stress response genes, along with Skn7 enrichment at these gene promoters. Future work will focus on further characterizing the role of Fcp1 and Cdk8 play in Skn7 biology, including determining if this is through a direct role in Skn7 phosphorylation dynamics.
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Board # 13 Peter Radonic, Masters Student Supervisor: Rajavel Elango, Healthy Starts
Determining the pediatric requirement of dietary threonine for growth and development Peter Radonic, Madeleine Ennis, Abrar Turki, Betina Rasmussen, Rajavel Elango Background: Threonine, an essential amino acid, is required for protein synthesis throughout the body. As a result of its large rate of incorporation into gut mucosa, consuming adequate amounts of threonine is essential for proper digestive and immune function, as well as for preventing growth restriction. Previously we showed that requirements for lysine, another essential amino acid, increased by 20% due to gut parasitic infection and malnourishment, compared to healthy children. Objective: Our primary objective was to determine the amount of threonine that 6-10y healthy Canadian children need to satisfy requirements for protein synthesis. Using the Indicator Amino Acid Oxidation (IAAO) method, we measured the oxidation of L-[1-13C]-phenylalanine in the body through 13CO2 (F13CO2) production, in response to different test threonine intakes. Methods: 4 healthy Canadian children (2 boys: 2 girls) aged 7.5 Âą 1.3 y randomly received 6-9 test threonine intakes, each ranging from 0-50 mg/kg/d, as well as an amino acid mixture patterned after egg protein and given in sufficient quantity to have an intake of 1.5 g/kg/d of protein. The diet was adequate in carbohydrate, fats, vitamins and minerals, and provided 1.7x the resting energy requirement, as determined by indirect calorimetry. Meals were isocaloric and isonitrogenous on all study days. Breath samples were collected before and during isotopic steady state. The rate of 13C enrichment in breath samples was measured using an isotope ratio mass spectrometer. The requirement for threonine was determined using a bi-phasic linear regression crossover model to determine a breakpoint in 13CO2 production, which represents the mean threonine requirement among participants. Results: Our results indicate a requirement of 20.63 mg/kg/d of threonine for 6-10 y healthy Canadian children. Conclusions: Current recommendations for threonine are set at 19 mg/kg/d for school-aged children, based on a mathematical calculation. Our direct measurements suggest a slightly higher requirement than this. While most healthy children in developed countries will meet this need, children at risk for low protein intake due to gut infection and/or malnourishment need to be evaluated, as their requirements for this gut-specific amino acid needs may be higher.
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Board # 14 Lindsay Richter, Masters Student Supervisor: Sarka Lisonkova, Healthy Starts & Joseph Ting, Evidence to Innovation
Trends in neonatal mortality and morbidity following spontaneous and latrogenic preterm delivery: Washington State, USA, 2004-2013 Lindsay Richter, Joseph Ting, Anne Synnes, Ken Lim, Sarka Lisonkova Background: Preterm birth (less than 37 weeks) is the leading cause of neonatal mortality and morbidity. After a decade of increase, the preterm birth rate in the US has declined recently, with the largest decline at late preterm gestation (34-36 weeks). Concomitant changes in adverse neonatal outcomes are unknown. Objective: To examine temporal trends in neonatal mortality and severe morbidity among infants born preterm following i) preterm premature rupture of membranes (PPROM), ii) spontaneous labour, or iii) iatrogenic delivery. Methods: We included all singleton live births in Washington State, USA, 2004-2013 (n=737,711). Types of preterm delivery included birth following PPROM (>12 hours), iatrogenic delivery (labour induction and caesarean delivery without labour), and spontaneous labour (all other delivery). Adverse outcome included neonatal death or severe morbidity consisting of: bronchopulmonary dysplasia, intraventricular haemorrhage grade â&#x2030;Ľ3, or periventricular leukomalacia. Cochran-Armitage test was used to assess temporal trends. Logistic regression was used to adjust for temporal changes in other risk factors. Results: The overall preterm birth rate declined (7.3%-7.0%). Preterm birth declined following PPROM (1.3%-1.1%) and following spontaneous labour (3.2%-3.0%), while iatrogenic preterm birth increased (2.7%-2.9%; all p<0.01). Overall neonatal mortality/morbidity rate declined at 24-27 weeks (56.1%-47.9%) and 28-31 weeks (16.5%-11.3%; all p<0.01). Following PPROM, neonatal mortality/ morbidity rate declined only at 28-31 weeks (14.3%-7.6%; p<0.05). Following iatrogenic delivery, neonatal mortality/morbidity rate declined at 24-27 weeks (64.4%-49.3%), 28-31 weeks (19.8%13.3%), and 32-33 weeks (3.9%-1.8%; all p<0.01). There was no change in the rate of neonatal mortality/morbidity following spontaneous preterm labour. Late preterm birth rates declined significantly in all delivery categories (all p-values <0.05), yet neonatal mortality/morbidity rates remained unchanged among late preterm infants. Conclusions: Overall, neonatal morality/morbidity declined among infants born at early gestation (24-31 weeks) between 2004 and 2013. Neonatal mortality/morbidity declined significantly among infants born by iatrogenic delivery at 24-33 weeks and among those following PPROM, which was evident mostly at 28-31 weeks. The recent data on declining rates of preterm birth and improving rates of serious newborn adverse health outcomes following PPROM and iatrogenic delivery provide important information for health care providers and administrators on population needs for specialized neonatal care. 33
Board # 15 Thyrza Toledo, Masters Student Supervisor: Suzanne Vercauteren, Childhood Diseases
Circulating DNA analysis in children with solid tumors given granulocyte colony stimulating factor Thyrza Toledo, Suzanne Vercauteren Background: Solid tumor patients with chemotherapy induced neutropenia or who are preparing for stem cell harvest are administered a drug called Granulocyte-Colony Stimulating Factor (G-CSF). However, studies in mice showed that G-CSF can promote tumor growth and metastasis. We are investigating whether G-CSF stimulates tumor growth in solid tumor patients by non-invasively measuring tumor-specific circulating cell-free DNA (cfDNA) in the blood. Also, it is possible that residual tumor may still be present in the bone marrow and may be collected during stem cell harvest. If transplanted back into the patient, this could result in tumor growth and relapse. Thus, we are studying whether tumor-specific cfDNA levels in the plasma correlates with tumor-specific genomic DNA (gDNA) levels in the stem cell product on the day of stem cell harvest. These are important questions to address because this could affect the future use of G-CSF as a drug and provide a non-invasive method to assess the presence of residual tumor. Methods and Results: Total cfDNA in plasma of eleven children with solid tumors before and after G-CSF treatment was measured by qPCR. Six children [two Rhabdomyosarcoma, three Neuroblastoma (NB), one Burkittâ&#x20AC;&#x2122;s lymphoma (BL)] had higher total cfDNA levels post G-CSF while five (four NB, one BL) had lower total cfDNA levels (n=11; p=0.8026). Currently we are investigating whether the cfDNA detected is tumor specific. Also, plasma and stem cells from the day of stem cell harvest were collected from four children who had NB and bone marrow metastasis plus two additional children with Choroid Plexus Carcinoma and Glioblastoma. Tumor-specific DNA was measured by methylation specific qPCR. At the time of stem cell harvest (post G-CSF administration), we found no evidence of tumor gDNA contamination in the stem cell product of all six children. However, we found evidence of tumor cfDNA in the plasma product for the four NB cases. Conclusions: Tumor-specific cfDNA can be detected in the plasma of children with pediatric cancer at the time of stem cell harvest but its presence was not indicative of tumor contamination of the stem cell product.
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Board # 15B Samantha Schaffner, Masters Student Supervisor: Michael Kobor, Healthy Starts
Epigenetic, transcriptional, and apoptotic responses to neonatal alcohol exposure in mice are influenced by sex and brain region Schaffner, S. L., Lussier, A. A., Baker, J. A., Goldowitz, D., Hamre, K. M., Kobor, M. S. Neonatal alcohol exposure disrupts brain development, leading to lifelong physiological and behavioral deficits. Ethanol impacts the brain through altered epigenetic profiles, i.e. modifications to histone tails and DNA methylation that impact chromatin structure and transcription. While epigenetic dysregulation is correlated with ethanol exposure, the causality of molecular alterations resulting in neurodevelopmental phenotypes is poorly understood. Here, we examined histone modifications, chromatin modifying and apoptotic gene expression, and DNA methylation in a mouse model of neonatal alcohol exposure. We show that alcohol alters histone modifications and impacts gene expression in a sex-specific manner, with differential expression profiles in the cortex and cerebellum. We also suggest that promoter DNA methylation may correlate with ethanolinduced changes in transcription. C57BL/6J mice were exposed to alcohol on postnatal day 7 via 2 subcutaneous injections of 2.5 g/ kg of ethanol 2 hours apart with controls given isovolumetric saline. Brain tissue was collected and flash frozen 7 hours after injection. Histones were extracted from the tissue and changes in chromatin marks were assayed by western blot. DNA and RNA were also extracted; RNA was assessed by reverse-transcription quantitative PCR (RT-qPCR), and DNA was sodium bisulfite converted and analyzed by pyrosequencing. Our findings of differential chromatin modifier expression suggest a potential origin for altered histone modifications found in neonatal alcohol-exposed mice. In addition, the significant differences in expression found in females emphasizes the need for research, prevention, and treatment that is tailored to gender, and the role of hormonal programming in early brain development and stress response.
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Session Three DOCTORAL STUDENTS Moderator: Joseph Ting Participants: Hani Bagheri Joshua Brown Michelle Chakraborti Harpreet Chhina Avery Lam Christina Michalski Mahdis Monajemi S.M Reza Rahavi
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Board # 16 Hani Bagheri, Doctoral Student Supervisor: Evica Rajcan-Separovic, Healthy Starts
Is there a mirror phenotype for 2p15p16.1 microdeletion syndrome? Hani Bagheri, Ying Qiao, Xianghong Shan, Sally Martell, Suzanne Lewis, Cheryl Y. Gregory-Evans, Evica Rajcan-Separovic Introduction: The 2p15p16.1 microdeletion syndrome has been described in 33 cases (Bagheri et al., 2016). Its core phenotype includes intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. Patient cell line and zebrafish studies identified three candidate genes XPO1, BCL11A, and REL. Their knock-down in zebrafish caused microcephaly, dysmorphic body, hindered growth, small fins and structural brain abnormalities. It was recently suggested that 2p15p16.1 microduplication causes mirror phenotypes and macrocephaly in carriers (Loviglio et al., 2016). Our aim was to test this possibility in a larger number of patients with the duplication and by overexpression of the 3 candidate genes in zebrafish. Methods: Clinical and genomic information for patients with 2p15p16.1 microduplication was extracted from DECIPHER. Overexpression of XPO1, REL and BCL11A in zebrafish embryos was performed by human RNA injection in 1-cell stage embryos. Head size, growth and body morphology was examined at 2 days post-fertilization. Results: Twelve patients were reported in DECIPHER with 2p15p16.1 duplications and phenotypes and only 1 had macrocephaly. Patients with microcephaly were also noted in this cohort ruling out a clear association of duplication and macrocephaly. Overexpression of XPO1 and REL in zebrafish did not cause phenotypic abnormalities, while BCL11A overexpression caused a hindered body growth and dysmorphic body trunk, but comparable head structure and size to controls. Conclusion: Our studies do not support the existence of mirror phenotypes in cases with 2p15p16.1 duplication. The overexpression of BCL11A, however, may be associated with body dysmorphology but not head size anomaly.
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Board # 17 Joshua Brown, Doctoral Student Supervisor: Michael Kobor, Healthy Starts
Distinct roles of Rtt107 in checkpoint regulation and genome maintenance Joshua A. R. Brown, Michael S. Kobor Cells rely on various DNA damage response pathways to maintain viability and genome stability in the presence of constant replication stress and DNA damage. Rtt107 is a budding yeast protein that acts as a scaffold to recruit other proteins to sites of DNA damage. rtt107-ko mutant phenotypes include hyperactivation of the checkpoint kinase Rad53 and prolonged cell cycle arrest. These phenotypes have been attributed to a model for Rtt107 function, termed checkpoint dampening, in which Rtt107 prevents Rad53 hyperactivation by reducing Rad9-Dpb11 interaction. We sought to clarify the relationship between rtt107-ko mutant phenotypes and the checkpoint dampening model by using a rad9-ST462,474AA (rad9-2A) allele that specifically disrupts Rad9-Dpb11 interaction. Incorporation of the rad9-2A allele failed to rescue the Rad53 hyperactivation phenotype of the rtt107-ko mutant after MMS treatment. Our results indicate that Rad53 hyperactivation does not primarily result from Rad9-Dpb11 interaction in the rtt107-ko mutant, and may instead be the result of the higher level of DNA damage present in the rtt107-ko mutant after MMS treatment. We next investigated the reliance of the rtt107-ko mutant on DNA damage tolerance pathways for MMS resistance, a defect potentially linked to Rad53 hyperactivation. We found that this defect was also independent of Rad9-Dpb11 interaction and the checkpoint dampening model. In contrast to the other phenotypes we investigated, the spontaneous genome instability phenotype of the rtt107ko mutant was enhanced by the rad9-2A allele, indicating that Rad9-Dpb11 interaction promotes genome stability in the absence of Rtt107. These findings highlight diverse roles of Rtt107 in the DNA damage response, distinct from previously identified Rtt107 functions.
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Board # 18 Michelle Chakraborti, Doctoral Student Supervisor: Jean-Paul Collet, Brain, Behaviour & Development
The development of social networks among families attending physical activity programs for children with neurodevelopmental disabilities: An opportunity to strengthen families and enhance childcare M.Chakraborti, P. Kong, W. McKellin, A. Miller, JP Collet Introduction: The WHO framework on functioning and disability (ICF-CY) emphasizes the importance of ‘family’ as the most significant environmental factor affecting child development, especially for children and youth with neurodevelopmental disabilities (CYND). The family is responsible for ensuring continuity in care across the lifespan of the child. Family functioning however, is often destabilised by an ongoing need to adapt to the child’s needs and challenging behavior. As a result, families are under immense stress and socially isolated, which affects their mental health. This highlights the need for programs that are capable of supporting CYND, while simultaneously, strengthening families through social integration. The solution may be community based physical activity programs (PAPs) such as Special Olympics, which support CYND. Besides the benefits they provide CYNDs, PAPs have the potential to strengthen families by social networks that provide family support and enhance social integration. Objectives: This proof of concept exploratory study investigates the PAPs’ potential for social network development; the impact of PAP-related networks on families’ integration; and the importance of PAP-networks in comparison to other support networks. Method: Mixed-methods approach: prospective cohort study to collect information at baseline and after 3 months using standardized scales on social integration (SSI), quality of life (FQOL), resilience (FRAS), and empowerment (FES); structured interviews and ethnographic observation. Preliminary Results: 50 families with CYND between 2 to 24 years were recruited from 24 Special Olympics PAPs across British Columbia. A thematic analysis of the baseline interviews (n=25) illustrates that PAPs strengthen families by facilitating socialization through the formation of social networks. Emergent themes suggest these networks formed between families, in the context of PAPs, promote the sense of community, provide emotional support and exchange of information, reduce child-related stress and promote parental self-efficacy. Furthermore, 75% families ranked PAP-related networks as ‘most important support’ in comparison to other organizations such as parent support groups, as they simultaneously benefit from socialization with families while their child benefits from the activity. Conclusion: Preliminary evidence suggests PAPs represent a unique platform that can potentially strengthen both families and CYND simultaneously, enabling a continuous improvement in their health outcomes. Ultimately, strengthened families provide better care to children. 39
Board # 19 Harpreet Chhina, Doctoral Student Supervisor: Anthony Cooper, Evidence to Innovation
Qualitative insights to health related quality of life among US and Canadian based children with lower limb deformities Harpreet Chhina, Anne Klassen, Jacek Kopec, Natasha Longmire, John L. Oliffe, Anthony Cooper Aim: To understand the health related quality of life (HRQOL) of children with lower limb deformities (LLD). Methods: Children aged 8 to 18 years with LLD and/or their parent were recruited (August 201516) from BC Children’s Hospital (BCCH), Vancouver, BC and Nemours Children’s Hospital (NCH), Orlando, Florida. Individual interviews with the child and parent were conducted separately, recorded, transcribed verbatim and coded using a line-by-line approach. Analysis was guided by interpretive description comprising a constant comparison approach to identify patterns, and account for diversity to distill thematic findings. Results: 37 interviews were conducted {16 at BCCH (7 children, 9 parents), 21 at NCH (11 children, 10 parents)}. Five HRQOL themes include: physical, psychological and social function, appearance, and experience of care. In terms of physical function, children with LLD were able to participate in sports and recreational activities, however, physical limitations forced them to make adjustments or choose less demanding activities. Complex treatment procedures involving external or internal fixators and wheelchairs made activities more challenging. For psychological function, children described experiencing a range of emotions including anger, frustration, depression and helplessness. Psychological issues seemed more pronounced for adolescents with LLD. Social function was affected due to the inability to fully participate in activities with their peers. Some were hesitant to make new friends or go out with their friends. In terms of appearance, children reported feeling self-conscious of their LLD and ‘different’ from their peers. Participants were particularly selfconscious about limping, leaning and shifting. Some children reported staring, teasing and laughing from peers. In terms of the experience of care, children in Canadian centres (socialized medicine) seemed to be diagnosed and treated at an earlier age, and possibly as a result seemed to report comparatively fewer challenges. Conclusion: LLD has substantial impact on the HRQOL of children. However, these results are to be taken with a word of caution since they represent only one Canadian and US centre. Ongoing work involves interviews at other centres in Canada, Ethiopia and India. Qualitative findings will guide the development of a patient reported HRQOL questionnaire for children with LLD
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Board # 20 Avery Lam, Doctoral Student Supervisor: Megan Levings, Childhood Diseases
Expression and regulation of amphiregulin in human regulatory T cells Avery J Lam, Sabine M Ivison, Anne M Pesenacker, Guy Charron, Haiming Huang, iGenoMed Consortium, Sachdev S Sidhu, James G Pan, John D Rioux, Megan K Levings Regulatory T cells are essential for maintaining immune homeostasis and self-tolerance. Several lines of evidence suggest that adoptive transfer of Tregs can prevent, and in some cases cure, a variety of pathological conditions, from autoimmunity to transplant rejection. In addition to their effects on immune cells, there is also emerging evidence that Tregs have direct effects on tissue repair. Specifically, Tregs in mice promote tissue repair after infection or injury by producing the EGF family member amphiregulin (AREG) under the control of the alarmins IL-18 and IL-33. We investigated expression and regulation of AREG in human peripheral blood Tregs. TCR stimulation of Tregs increased AREG mRNA and protein, particularly in the HLA-DR(-) subset, but levels were lower than in conventional T cells. In contrast to reports from murine Tregs, IL-18 and IL-33 did not modulate human Treg production of AREG. Ex vivo Tregs expressed IL-18R, but expression of IL33R (ST2) was not detectable. To more accurately measure human ST2 expression, we used phage display to generate a series of anti-ST2 mAbs. Experiments in ST2-transfected HEK-293 cells and ST2-transduced T cells revealed several candidate anti-ST2 mAbs that were superior to commercially available mAbs for flow cytometric detection of human ST2. Experiments to better define the localization and biology of human ST2+ Tregs are in progress. Knowledge of whether human Tregs produce AREG is important to understand their potential to mediate tissue repair in addition to immunosuppression when used as a cell-based therapy.
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Board # 21 Christina Michalski, Doctoral Student Supervisor: Pascal Lavoie, Healthy Starts
Cellular metabolic and translational constraints in preterm monocytes Christina Michalski, Bernard Kan, Hilda HT Au, Dan Luciani, Colin Ross, Eric Jan, Pascal M. Lavoie The innate immune system is critical protecting newborns against infections before they develop an immunological memory. However, innate immune pathogen responses are broadly suppressed below 33 weeks of gestation to prevent rejection of maternal tissues. This increases the risk of sepsis when infants are born very prematurely. Recently, it has been shown that innate immune cells require a metabolic switch from oxidative phosphorylation to aerobic glycolysis, in order to supply the massive energy requirement for protein synthesis during an immune activation. This switch is regulated through the mechanistic target of rapamycin (mTOR) master immune regulator. However, the underlying mechanism(s) controlling the activity of innate immune cells in humans during ontogeny remain unclear. On the basis of preliminary observations showing discordance between the expression of immune signaling proteins and their respective transcripts, we hypothesized that the broad functional attenuation in preterm neonatal immune cells is due to a metabolic reprogramming resulting in decreased translation capacity of immune response proteins. To address this hypothesis, we combined genome-wide transcriptome analyses (Illumina HT-12 Human Bead Array) and polysome profiling (qPCR) comparing preterm, term (cord) and adult (peripheral) primary (blood) monocytes after stimulation with LPS (endotoxin). We found that LPS-stimulated (5h) preterm monocytes express a wide array of cytokine and chemokine gene transcripts, without expression of the corresponding proteins. In pathway analyses, we identify metabolic disturbances in these cells. This was confirmed by showing a reduced lactate production and reduced glycolytic capacity in these cells, as measured using real-time extracellular acidification (Agilent Seahorse Analyzer). We also found that genes encoding ribosomal subunits were severely down-regulated both before, but also after stimulation in preterm monocytes, compared to term or adult monocytes. Our preliminary data suggests that translation is substantially reduced in preterm monocytes (as demonstrated by radioactive Met/Cys pulse-labeling), and that this mechanism is mTOR-related as evidence by lack of mTOR phosphorylation in preterm monocytes. Through polysome profiling experiments we demonstrate a relationship between the developmental lack of immune signaling proteins and their degree of translation. Altogether, our data provide a novel mechanism through which immune activation is constrained during fetal life.
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Board # 22 Mahdis Monajemi, Doctoral Student Supervisor: Laura Sly, Childhood Diseases
The role of MALT1 in macrophages Mahdis Monajemi, Susan C. Menzies, Laura M. Sly MALT1 is a signalling molecule that acts as both a protein and a protease. MALT1 plays a key role in Nuclear Factor kappa B (NF-ÎşB) activation downstream of the B and T cell receptor causing lymphocyte activation and proliferation. MALT1 also plays a role in macrophage activation by acting downstream of dectin-1, dectin-2, and TLR4 signalling pathways. A key role for MALT1 in intestinal homeostasis and inflammation was recently demonstrated because patients deficient in MALT1 develop severe combined immunodeficiency accompanied by dramatic inflammation along the gastrointestinal tract. MALT1 contribution to inflammation has been attributed to B and T cells. However, the role of MALT1 in macrophage-mediated inflammation has not been investigated. Based on this, we hypothesize that Malt1 deficiency causes inflammation by increasing macrophage inflammatory responses. Our results show that Malt1 deficient murine macrophages have a lower inflammatory response than wild type macrophages. In contrast, inhibiting Malt1 activity increases inflammatory cytokine production by murine macrophages in response to stimulation. Interestingly, we found that Malt1 deficiency exacerbates mice susceptibility to DSS induced colitis same as patient deficient for Malt1. However, depletion of macrophages only modestly protects Malt1 deficient mice against DSS-induced colitis. Taken together, our studies are consistent with a model in which MALT1 activity reduces proinflammatory macrophage responses but its scaffolding function increases macrophage inflammatory responses. In future studies, we will investigate the cell-specific contribution of MALT1 deficient macrophages to inflammatory disease using mice with myeloid-specific MALT1 deficiency. These studies will provide critical information about the cell specific role of MALT1 and possible side effects of MALT1 inhibitors currently used for lymphoma treatment.
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Board # 23 S.M Reza Rahavi, Doctoral Student Supervisor: Gregor Reid, Childhood Diseases & James Lim, Childhood Diseases
In vivo evaluation of localization and immune sensitivity of human neuroblastoma in xenografts Reza Rahavi, Gregor Reid, James Lim Neuroblastoma (NB) is the most commonly occurring extra-cranial solid tumor in children and accounts for ~10% of all childhood cancers [1]. Half of NB cases occur in children under two years of age. NB is thought to originate from neural crest precursor cells of the developing sympathetic nervous system, with primary tumors localizing in the abdomen, adrenal gland or lumbar ganglia; however its metastatic spread includes such diverse tissues as the lymph nodes, bone, bone marrow, liver and skin [1]. Low and intermediate risk NB have excellent prognosis, with greater than 90% survival. However, the high-risk metastatic form that accounts for ~50% of NB has survival outcomes of less than 30% with conventional therapy [2]. Due to the heterogenous genetic landscape inherent to NB, a major focus for therapy development is aimed at harnessing the anti-tumour capabilities of the immune system, in particular that mediated by natural killer (NK) cells [2, 3]. We hypothesize that the in vivo NB tumour killing capacity of NK cells can be enhanced by cell adhesion manipulation to promote both NK cell recruitment to target tissues and formation of the cytolytic immune synapse between NK and NB cells. To enable testing of this hypothesis, I have developed a dual-reporter mouse model for human NB metastasis and NK cell targeting based on click beetle red and green bioluminescence. The development and application of this immunological tumor models will provide the foundation for the pre-clinical testing of anti-NB immune-based strategies.
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Session Four DOCTORAL STUDENTS Moderator: Rajavel Elango Participants: Abeer Aljaadi Sarah Anderson Allison Ezzat Daphne McRae Naama Rotem-Kohavi Jean Philippe Sauve Samantha Wilson
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Board # 24 Abeer Aljaadi, Doctoral Student Supervisor: Angela Devlin, Childhood Diseases & Tim Green, Healthy Starts
Prevalence of iron deficiency anemia in non-pregnant women of reproductive age living in Kuala Lumpur, Malaysia Abeer M. Aljaadi, Ru En How, Su Peng Loh, Shannon E. Hunt, Crystal D. Karakochuk, Susan I. Barr, Angela M. Devlin, Geok Lin Khor, Tim J. Green Anemia affects 1.65 billion individuals worldwide, especially young children and women of reproductive age. Anemia prevalence in pregnant women (hemoglobin <110 g/L) in Malaysia is estimated to be 38%. However, there is limited evidence on the prevalence of anemia and iron deficiency anemia (IDA) in non-pregnant Malaysian women and no studies have adjusted ferritin values for inflammation. This cross-sectional study aims to determine the prevalence of anemia and IDA in a sample of healthy non-pregnant Malay and Chinese women (19-45 years) living in Kuala Lumpur, Malaysia. Fasting blood samples were collected from women living in Kuala Lumpur, Malaysia (n=210) and, for comparison purposes, from women living in Vancouver, Canada (n=206). Malaysian participants were of Malay (n=105) and Chinese (n=105) descent; Canadian participants were of European (n=110) and Chinese (n=96) descent. Samples were analyzed for hemoglobin, plasma vitamin B12, serum retinol binding protein (RBP), serum iron biomarkers (soluble transferrin receptor [sTfR] and ferritin), and markers of inflammation (C-reactive protein [CRP] and α-1 acid glycoprotein [AGP]). Anemia (hemoglobin <120 g/L) prevalence was higher in Malaysian women compared to Canadian women (18% and 7%, respectively; p=0.001). In Malaysia, 11% (n=24) of women had IDA (based on hemoglobin <120 g/L and either inflammation-adjusted ferritin <15 μg/L or sTfR >8.3 mg/L), compared to 3% (n=6) of Canadian women. No significant ethnic differences were found among women in anemia or IDA prevalence. Depleted iron stores (inflammation-adjusted ferritin <15 μg/L) were found in 21% of Malaysian women and in 15% of Canadian women. The prevalence of acute (CRP >5 mg/L) and chronic (AGP >1 g/L) inflammation was 7% and <1%, respectively, in Malaysian participants, compared to 4% and <1% in Canadian participants. Adjustment for inflammation (using AGP and CRP biomarkers) did not change the prevalence of IDA in Malaysian or Canadian women. There was no biochemical evidence of vitamin A deficiency (RBP <0.7 μmol/L) and <1% of women had vitamin B12 deficiency (B12 <148 pmol/L) in both populations. These findings suggest that over half the anemia in Malaysian non-pregnant women is attributed to iron deficiency. Further research is required to investigate the prevalence of IDA in a nationally representative sample.
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Board # 25 Sarah Anderson, Doctoral Student Supervisor: Robert McMahon, Brain, Behaviour & Development
Examining conduct disorder symptoms, callous-unemotional traits, and the development of substance use through adolescence and young adulthood: The moderating role of sex Sarah L. Anderson, Yao Zheng, Robert J. McMahon Conduct disorder (CD) symptoms are among the best predictors of adolescent substance use. A subset of youth with CD also display callous-unemotional (CU) traits (e.g., lack of empathy, egocentricity, lack of guilt). However, little research has explored how CU traits may predict substance use or how sex may moderate outcomes. A community sample of youth (N = 753, 42% female, 46% African American) from the Fast Track project was followed annually from grade 7 to 2 years post-high school to examine the role of CU traits, CD symptoms, and their interaction with sex in predicting past month cigarette use and past year alcohol misuse. Latent growth curve models were used to examine systematic developmental change of substance use through adolescence and young adulthood. Neither CD symptoms nor CU traits were uniquely associated with the linear slope of cigarette use (B = 0.33 and -0.03, ns, respectively) or alcohol misuse (B = -0.10 and -0.09, ns, respectively). The interaction of sex and CD symptoms (but not the interaction of sex and CU traits) significantly predicted the linear slopes of cigarette use (B = -0.32) and alcohol misuse (B = -0.10). Further analyses showed that, among those without any CD symptoms, sex predicted the linear slope of cigarette use (B = 0.28), but not the linear slope of alcohol misuse (B = -0.01, ns). The change of the odds of boys using cigarettes in the past month relative to no use was 1.14 times of that of girls for every 1-year increase. However, among those with CD symptoms, sex did not predict the linear slope of cigarette use (B = 0.13, ns) or alcohol misuse (B = 0.04, ns). These results indicate that sex may play an important role in identifying youth at risk for increasing their use of cigarettes in non-clinical samples (i.e., those without CD symptoms) but not in samples of youth with CD symptoms. This study provides further validation that males are at heightened risk to increase their use of cigarettes throughout adolescence and young adulthood. Overall, these results highlight the important role of targeted substance use prevention programs for adolescents and young adults, particularly among males, given the varied health risks associated with cigarette use.
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Board # 26 Allison Ezzat, Doctoral Student Supervisor: Mariana Brussoni, Evidence to Innovation
Is knee confidence a concern in youth & young adults 3-10 years following intra-articular knee injury? AM. Ezzat, JL. Whittaker, C. Toomey, PK. Doyle-Baker, M. Brussoni, CA. Emery Background: In people with knee osteoarthritis, low knee confidence has been associated with fear of movement, increased pain, and decreased strength. Little is known about knee confidence in young adults with a history of knee joint injury that are at high risk of post-traumatic osteoarthritis (PTOA). The association between knee confidence and other modifiable PTOA risk factors has not been examined. Objectives: To examine knee confidence in youth and young adults with previous intra-articular knee injury compared to matched uninjured controls, adjusting for body composition and PA participation. Methods: This historical cohort study included 200 youth and young adults; 100 who sustained a sport-related intra-articular knee injury 3-10 years previously and 100 uninjured controls. Knee confidence was based on a question from the Knee Osteoarthritis and Outcome Score: â&#x20AC;&#x153;How much are you troubled by lack of confidence in your knee?â&#x20AC;? Body composition was assessed by fat mass index (total fat relative to height2; FMI; kg/m2). PA participation was obtained via the modified Godin-Shepard Leisure Time Questionnaire (total minutes/week). Study groups were compared using descriptive statistics (mean within-pair difference; 95% confidence interval [95%CI]). Multivariable conditional logistic regression (odds ratio; 95% CI) examined the association between injury group and knee confidence adjusting for FMI (kg/m2) and PA participation (min). Results: Among the injured participants, 49% (95%CI; 39, 59) were bothered by lack of knee confidence (37%=mildly, 7%=moderately, 4%=severely, and 1%=extremely), compared to 12% (95%CI; 5.5, 18.5) of controls (11%=mildly, 1% moderately.) Injured participants had higher FMI compared to controls [mean within pair difference=1.05 kg/m2 (95% CI; 0.53, 1.57)], however total PA/week did not differ [mean within pair difference = -6.4 min (95% CI; -28.9, 16.2)]. In the final multivariable model, the odds of low knee confidence in the injured participants was 7.5-fold that in the uninjured controls [OR=7.5 (95%CI=2.7, 21.1)]. Conclusions: Knee confidence is a concern for youth and young adults after knee injury and may be important when evaluating PTOA risk. Additional research should evaluate the association of knee confidence and objectively measured PA and other clinical outcomes will inform a more comprehensive understanding of risk factors for PTOA.
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Board # 27 Daphne McRae, Doctoral Student Supervisor: Patricia Janssen, Healthy Starts & Nazeem Muhajarine
Antenatal midwifery care: Reducing prevalence of small for gestational age birth and preterm birth for women with low socioeconomic position Daphne McRae, Nazeem Muhajarine, Saraswathi Vedam, Maureen Mayhew, Deborah Mpofu, Ulrich Teucher, Patricia Janssen Background: For women of low socioeconomic position, antenatal midwifery care has been shown to improve infant birth outcomes in some North American studies, though conclusions based on the literature have been limited by methodological weaknesses within studies, small sample sizes, diverging results, and few recent studies. Purpose: To determine among women with low socioeconomic position, if antenatal midwifery vs. obstetrician or general practitioner care significantly reduced the odds of small-for-gestational-age birth and/or preterm birth. Methods: Eligibility for this population-level, retrospective cohort study was based on low to moderate risk pregnancy, to residents of British Columbia, who had singleton births (2005- 2012), no more than two provider-types involved in care, and received Medical Services Plan premium subsidy assistance (n=57,872). Administrative maternity and billing data were merged with neighbourhood and community-level health equity data from four provincial sources. Logistic regression models were used to control for confounding. Results: Odds of small-for-gestational-age birth were reduced for midwives’ vs. obstetricians’ patients (adjusted OR 0.60, 95% CI: 0.51-0.70), and vs. general practitioners’ patients (AOR 0.73, 95% CI: 0.63-0.84). Likelihood of preterm birth was reduced for midwives’ vs. obstetricians’ patients (AOR 0.53, 95% CI: 0.45-0.62), and vs. general practitioners’ patients (AOR 0.74, 95% CI: 0.630.86). In sub-group analyses, odds of small-for-gestational-age birth were even further reduced for midwifery vs. obstetrician patients who were substance using (AOR 0.30, 95% CI: 0.13-0.68). Women with both a mental health diagnosis and substance use during pregnancy had even lower odds of small-for-gestational-age birth if in the care of a midwife vs. an obstetrician (AOR 0.19, 95% CI: 0.05-0.72). Substance using midwifery patients were also less likely to have preterm birth (AOR 0.25, 95% CI: 0.12-0.52), vs. obstetrician patients. Conclusions: For women with low socioeconomic position, antenatal midwifery care reduced the likelihood of small-for-gestational-age birth and preterm birth compared to obstetrician or general practitioner care. These associations were stronger among midwifery vs. obstetrician patients with low socioeconomic position and other socially complex conditions.
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Board # 28 Naama Rotem-Kohavi, Doctoral Student Supervisor: Tim Oberlander & Naznin Virji-Babul, Brain, Behaviour & Development
Alterations in resting state networks following in-utero SSRI exposure in the neonatal brain â&#x20AC;&#x201C; preliminary results Naama Rotem-Kohavi, Lynne Williams, Naznin Virji-Babul, Angela Martina Muller, Bruce Bjornson, Ursula Brain, Janet Werker, Steven Miller, Ruth Grunau, Tim F Oberlander Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used to treat depression during pregnancy. SSRIs inhibit the serotonin (5HT) transporter, freely cross the placenta and have shown to alter 5HT signaling in the fetal brain. Both prenatal maternal mood disturbances and in-utero SSRIs can alter infant behavior and have been shown to shift language auditory perception development. Advances in resting state-(rs)fMRI research has identified resting state networks (RSNs) in newborns. These RSNs have functional relevance as auditory and visual networks, providing an opportunity to examine the effect of early experiences on neurodevelopment. Therefore, our aim was to study the effect of in-utero SSRIs on neonatal RSN development, accounting for prenatal maternal mood symptoms. Non-exposed (n=26) and SSRI-exposed (n=15) 6-day-old neonates underwent (rs)fMRI scan. Maternal prenatal appraisal of stressors was assessed at third trimester using the pregnancy experience scale (PES). Independent component analysis (ICA) was used to extract RSNs. We found that SSRI-exposed neonates had higher levels of blood oxygenation level dependent (BOLD) signal in auditory RSN compared with non-exposed neonates, in the regions of the caudate and frontal inferior triangularis (adjusted for age at MRI scan and maternal appraisal of negative stressors, P<0.02 corrected for multiple comparisons). These results suggest an effect of in-utero SSRI exposure on the functional connectivity of the neonatal auditory network, even when accounting for maternal appraisal of negative stressors. These findings might provide some insight into the functional origins of previously observed shifts in auditory language perception development.
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Board # 29 Jean Philippe Sauve, Doctoral Student Supervisor: Laura Sly, Childhood Diseases
Tuft cells and their role in intestinal inflammation Jean Philippe Sauvé, Roger Jen, Keith McLarren, Hayley Brugger, Eyler Ngoh, Theodore Steiner, Laura Sly Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by intestinal inflammation. Intestinal epithelial cells play a critical role in mucosal homeostasis and dysregulation of pro-inflammatory epithelial cell function could lead to the intestinal inflammation that characterizes IBD. However, we do not know the events that initiate inflammation or the cell types involved. One type of cell that may play a role is the tuft cell. Tuft cells are the only epithelial cells in the uninflamed intestine that express COX-1 and COX-2, the rate-limiting enzymes required for production of prostaglandins, like pro-inflammatory PGE2. In our research investigating the lipid phosphatase SHIP, we discovered that tuft cells express SHIP. SHIP deficiency leads to increased PI3-kinase activity in cells resulting in increased cell proliferation, reduced apoptosis, and increased cell activation. SHIP expression is currently believed to be restricted to hematopoietic cells. However, using bone marrow transplantation, we found that tuft cells were not radiosensitive, suggesting that they are not bone-marrow derived and are not hematopoietic in origin. In addition, SHIP deficient mice develop spontaneous Crohn’s disease-like intestinal inflammation. Onset of inflammation coincides with the developmental appearance of tuft cells. In wild type mice, tuft cells are found in the lung and ileum, both locations where SHIP deficient mice develop spontaneous inflammation, and we found that tuft cell numbers were increased 6-fold in the inflamed ileum of SHIP deficient mice. Based on this, we hypothesized that SHIP deficient tuft cells may initiate inflammation in the SHIP deficient mouse. We found that SHIP deficient mice had more COX-1 positive cells in the ileum and more COX activity, PGD2 and PGE2 in full thickness ileal tissue homogenates, compared to their wild type littermates. Finally, prophylactic inhibition of COX activity with piroxicam, reduced the development of intestinal inflammation in SHIP deficient mice whereas therapeutic treatment had no effect. This suggests that tuft cells may be critical in the initiation of spontaneous intestinal inflammation in SHIP deficient mice.
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Board # 30 Samantha Wilson, Doctoral Student Supervisor: Wendy Robinson, Healthy Starts
Utility and reproducibility of DNA methylation profiling in preeclampsia and intrauterine growth restriction placentas SL Wilson, K Leavey, B Cox, WP Robinson Introduction: Preeclampsia (PE), proteinuric gestational hypertension, can be divided into early-onset PE (EOPE; associated with inadequate placentation; diagnosis <34 weeks) and late-onset PE (LOPE; associated with inherent maternal factors). Intrauterine growth restriction (IUGR), pathologically poor fetal growth, often co-occurs with PE. However, the relationship between EOPE, LOPE, and IUGR remains unclear. Our objective was to use placental DNA methylation (DNAm) profiling to investigate the etiology of EOPE, LOPE and IUGR, and their relationship to one another. Methods: Placental samples from a discovery cohort (43 controls, 22 EOPE, 18 LOPE, 11 IUGR) and a validation cohort (15 controls, 22 EOPE, 11 LOPE) were evaluated using the Illumina HumanMethylation450 array, which measures DNAm at >480,000 CpG sites across the genome. To minimize gestational age (GA) effects, EOPE samples were compared to pre-term control samples (GA <37 weeks), while LOPE and IUGR were compared to term controls (GA >37 weeks). Linear regression was used to identify differentially methylated (DM) sites (FDR<0.05, â&#x2C6;&#x2020;β>0.1). Results: A total of 1703 sites were DM in EOPE compared to pre-term controls, while 5 sites were DM in LOPE and 0 sites were DM in IUGR compared to term controls. Of the 1703 sites associated with EOPE, 599 were validated in an independent cohort. These 599 sites clustered samples from both cohorts into 3 distinct methylation clusters. Interestingly, LOPE samples that had a clinical indication of a more EOPE-like phenotype (ex. PE diagnosed earlier (34.0-35.9 weeks) and/or co-occurring IUGR), indicating a more placental-mediated phenotype, clustered with the EOPE methylation cluster. Conclusions: Numerous changes in DNAm are observed in EOPE but not LOPE or IUGR, although some LOPE appeared to have an EOPE-like DNAm profile. This study suggests that DNAm may provide an independent source for refining clinical diagnoses for research purposes.
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Session Five DOCTORAL STUDENTS Moderator: Francis Lynn Participants: Kayleigh Campbell Madeleine Ennis Lisa Kozicky Rachelle Pullmer Lakshana Sreenivasan Ella Weik Olivia Wong
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Board # 31 Kayleigh Campbell, Doctoral Student Supervisor: Tim Oberlander, Brain, Behaviour & Development
In utero SSRI antidepressant exposure and maternal depression predict corpus callosum microstructure in term-born neonates Kayleigh S.J. Campbell, Lynne J. Williams, Daniel H.C. Kim, Ursula Brain, Bruce H. Bjornson, Ruth E. Grunau, Dan W. Rurak, Steven P. Miller, Tim F. Oberlander Background: Antenatal maternal mood disturbances and use of selective serotonin reuptake inhibitor (SSRI) antidepressants are common. SSRIs are diffusible across the placenta and have been associated with altered neonatal behaviour, raising key questions regarding their influence on early neurodevelopment. Cerebral white matter (WM) undergoes rapid and complex maturation in the third-trimester, and the neurotransmitter serotonin (5-HT) has critical roles in neuronal proliferation, synaptogenesis, and myelination in the developing brain. Given that early maturational processes may be sensitive to altered 5-HT signaling, we hypothesized that WM microstructure would be altered in term-born neonates following in utero SSRI antidepressant exposure. Objective: To investigate the effects of in utero SSRI antidepressant exposure on early corpus callosum microstructural development in term-born neonates. Methods: MR imaging was undertaken on SSRI-exposed (n=18) and non-exposed (n=32) termborn neonates at postnatal day-6. Cerebral WM was examined with diffusion tensor imaging (DTI), which yields measures of fractional anisotropy (FA) as an index of WM microstructural maturity. A region-of-interest (ROI) approach was used to investigate the effects of SSRI exposure on FA in the corpus callosum (CC). ROIs were placed in the genu, body and splenium of the CC, and mean FA was extracted. With multiple linear regression, FA was predicted using SSRI-exposure status, CC region, infant weight at the MRI scan (adjusted for birth gestational age), and mean maternal mood measures obtained in the third-trimester with the Hamilton Rating Scales for Depression (HAM-D). Results: Analysis with multiple linear regression found SSRI-exposure, prenatal maternal HAM-D score, CC region, and adjusted infant MRI weight had a significant effect on FA (adjusted R2=0.20; p<0.001). Importantly, a significant interaction was observed between SSRI-exposure status and prenatal maternal depression (HAM-D) when predicting FA in the genu (SSRI-Exposed: t=-2.57, p=0.02; Non-Exposed: t=-2.37, p=0.01). Post hoc analysis found that adjusted FA in the genu is significantly higher in SSRI-exposed neonates (n=18; t=-6.13, p<0.001), but significantly lower in neonates exposed to prenatal maternal depression alone (n=15; t=7.06, p<0.001). Conclusions: Neonate callosal microstructure is predicted by in utero SSRI-exposure and prenatal maternal depression, suggesting that early maturational processes in the CC may be sensitive to altered 5-HT signaling in utero. There are exposure-dependent effects on early development in the genu: SSRI-exposure may advance microstructural maturity, while exposure to maternal depressed mood may delay maturity. 54
Board # 32 Madeleine Ennis, Doctoral Student Supervisor: Rajavel Elango, Healthy Starts
Dietary phenylalanine requirements for healthy pregnant women are increased in late gestation Madeleine Ennis, Betina Rasmussen, Christopher Tomlinson, Glenda Courtney-Martin, Paul Pencharz, Rajavel Elango Background: Phenylalanine (PHE), an essential amino acid, is required for protein synthesis and integral for proper fetal development. Via the conditionally essential amino acid tyrosine (TYR), PHE is the precursor for neurotransmitters dopamine, norepinephrine and epinephrine. Currently the dietary requirements for PHE during pregnancy are unknown. Objectives: Our objective was to determine PHE requirements (in the presence of excess TYR) during late stages of gestation (33-39 wks) in healthy women using two different methods: Indicator Amino Acid Oxidation (IAAO, using L-[1-13C]leucine) and Direct Amino Acid Oxidation (DAAO, using L-[113C]Phenylalanine). Methods: 10 healthy pregnant women (age=32 Âą4y, gestational age=34Âą3wks) were studied at a range of PHE intakes (2.5 to 30.5 mg/kg/d in the IAAO study; and 5.5 to 25.5 mg/kg/d in the DAAO study). On each study day, test intakes were provided as 8 isocaloric and isonitrogenous meals. The meals supplied 1.5g /kg/d protein and 1.7 X the measured resting energy expenditure calories. Protein was provided as a crystalline amino acid mix based on egg protein composition. On each study day breath samples were collected at baseline and during isotopic steady state, and 13C enrichment was measured using an Isotope Ratio Mass Spectrometer. PHE requirement was determined using a two-phase linear regression crossover model to identify a breakpoint in 13CO2 production (which represents the mean PHE requirement) in response to different PHE intakes. Results: Preliminary analysis suggests that the requirement for PHE is 15.1 mg/kg/d based on IAAO and 15.6 mg/kg/d based on DAAO technique. Conclusions: Previously the PHE requirement (with excess TYR) in healthy adult males was shown to be 9.1 mg/kg/day using the DAAO method. When compared to the requirement of adult men, these results indicate that there is an increased requirement (~66% higher) for dietary PHE during late stages of pregnancy. The similarities in the requirement estimates derived from the two different carbon oxidation methods suggest reliability of our estimates. These results are also similar to our earlier study on lysine, another essential amino acid, where we showed higher requirements during late gestation. The PHE requirement during early stages of pregnancy remains to be determined.
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Board # 33 Lisa Kozicky, Doctoral Student Supervisor: Laura Sly, Childhood Diseases
Intravenous immunoglobulin-activated IL-10 producing macrophages may be useful to treat Inflammatory Bowel Disease Lisa Kozicky, Susan Menzies, Naomi Hotte, Karen L. Madsen, Laura M. Sly Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease characterized by inflammation along the intestinal tract. Current treatment for IBD relies on non-specific immune suppression. However, up to 40% of people are predicted to become refractory to all available therapies so development of new therapeutic strategies to treat people with IBD is urgently needed. Macrophages initiate the innate immune response and contribute to the inflammation that characterizes IBD, but they also play an equally important role in turning off the inflammatory response. We have reported that macrophages stimulated with Intravenous Immunoglobulin (IVIg), pooled polyclonal IgGs isolated from the blood of more than 1000 donors, produce high levels of the anti-inflammatory cytokine, IL-10, in response to the inflammatory stimulus, lipopolysaccharide (LPS). To determine whether IVIg-activated macrophages can be used to treat intestinal inflammation, we adoptively transferred (IVIg+LPS)-activated macrophages into mice or treated mice with IVIg during DSS-induced intestinal inflammation. Adoptive transfer of (IVIg+LPS)-activated macrophages or IVIg treatment reduced clinical disease activity during DSS colitis, including weight loss, rectal bleeding, and stool consistency. Histological evidence of inflammation was reduced in mice, including loss of tissue architecture, immune cell infiltration, muscle thickening, ulceration, and edema. Colons were longer in the (IVIg+LPS)-activated macrophages or IVIg treated mice, which also indicates reduced inflammation. IVIg treatment during DSS colitis increased IL-10 and decreased pro-inflammatory cytokines in excised colon cultures. Mice with a deficiency in the IL-10 receptor demonstrated that IL-10 signaling was required for the anti-inflammatory effect of IVIg treatment. Moreover, adoptive transfer of Il10+/+ (IVIg+LPS)-activated macrophages reduced inflammation, whereas Il10-/- (IVIg+LPS)-activated macrophages did not, suggesting that macrophage IL-10 production is required to reduce inflammation. In conclusion, IVIg activated macrophages have potent anti-inflammatory activity that can be used to reduce intestinal inflammation in vivo. Adoptive transfer of in vitro-derived (IVIg+LPS)-activated macrophages or activating macrophages with IVIg in situ may provide novel effective therapies to treat intestinal inflammation in people with IBD.
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Board # 34 Rachelle Pullmer, Doctoral Student Supervisor: Shannon Zaitsoff
Self-compassion in relation to depressive symptoms in adolescents: A gender comparison Rachelle Pullmer, Jennifer S. Coelho, Sarah L. Anderson, Shannon Zaitsoff Accumulating evidence indicates that self-compassion may have widespread implications for numerous mental health problems, with recent research highlighting the protective role of selfcompassion in relation to depressive symptoms in adolescents. Given the higher prevalence of depressive symptomatology among females, it is imperative to examine whether the role of selfcompassion differs between female and male adolescents. Therefore, the purpose of this study was to examine whether the strength of the association between self-compassion and depressive symptoms and the role of hypothesized mediating variables (i.e., rumination, emotion regulation, and social comparison) differs according to gender, and to elucidate whether gender differences in levels of self-compassion exist in adolescence. A community sample of high school students (n = 310; Mage = 16.53; SD = 1.20) completed the Self-Compassion Scale (SCS), Rosenberg Self-Esteem Scale, Ruminative Responses Scale, Difficulties in Emotion Regulation Scale - Short Form, IowaNetherlands Comparison Orientation Measure, and the Center for Epidemiologic Studies Depression Scale. Preliminary analyses indicate that when controlling for self-esteem, the relation between self-compassion and depressive symptoms was stronger for females (n = 179) than for males (n = 131). While rumination and emotion regulation mediated the relation between self-compassion and depressive symptoms in males, only rumination mediated the relation between these variables in females. Social comparison did not mediate the relation between self-compassion and depressive symptoms in males or females. Males had higher SCS total scores and lower SCS subscale scores on self-judgment, over-identification and isolation in suffering. Altogether, these results provide support for the strong relation between self-compassion and depressive symptoms, yet point to gender differences that may have important implications for the development of interventions to increase self-compassion in adolescents.
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Board # 35 Lakshana Sreenivasan, Doctoral Student Supervisor: Chinten James Lim, Childhood Diseases
The role of IL6/STAT3 in chemoresistance of medulloblastoma Lakshana Sreenivasan, Hui Wang, Shyong-Quin Yap, Chi-Chao Liu, Pascal Leclair, Chinten James Lim Medulloblastoma (MB) is a high-grade paediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. Chemotherapy is one of the principal modes of treatment for cancer, but its effectiveness is often limited by drug resistance. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) proteins are often implicated in promoting tumourigenesis in most cancers. In this study, we have evaluated the role of STAT3 (a nuclear transcription factor) and IL-6 (a pleiotropic cytokine and upstream regulator of JAK/ STAT3 pathway) in a tumour microenvironment mediated drug resistance in human MBs. We have established that STAT3 is not constitutively activated in Med8A (Group 3 MB cell line) but can be rapidly activated by tyrosine phosphorylation (pSTAT3) when treated with Interleukin-6 (IL-6) alone. Several stable chemo-resistant variants of parental Med8A-S were made by gradual drug (vincristine) selection. The drug resistant variants, Med8A-R exhibited increased pSTAT3 levels upon treatment with IL-6 in a dose-dependent manner. Conditioned media from IL-6 stimulated cells is sufficient to induce increased and prolonged pSTAT3 activity. Conditioning of Med8A-S to IL-6 (Med8A IL6+ cells) resulted in significant increase in basal and stimulated pSTAT3 levels concomitant with increased IL-6 receptor expression. Drug resistance profiling of Med8A IL-6 + cells showed increased resistance to drug compared to Med8A-S and Med8A-R cell lines. Autocrine IL-6 production could be a major promoter of positive feedback loop of the JAK/STAT3 pathway and drug resistance in MBs, subsequently contributing to cellular growth and transformation. CRISPRCas9 disruption of STAT3 expression in Med8A-S and Med8A-R also led to increased susceptibility to the drug, which further suggests a prominent role of STAT3 in drug resistance. The IL-6/STAT3 is an interdependent pathway that contributes to drug resistance between the MB cells and their tumour microenvironment.
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Board # 36 Ella Weik, Doctoral Student Supervisor: Christine Tipper, Brain, Behaviour & Development
Distinct attentional strategies differentially engage component processes of the attention system Weik, E., Tipper, C. M. Introduction: Effective spatial orienting of attention can be achieved by selecting relevant locations (facilitation) or ignoring irrelevant ones (inhibition). While both processes are evident when behavioral responses are averaged across trials and participants, it remains unclear how they interact within an individual. We hypothesize that individuals may adopt a particular attentional strategy predominated by either facilitation or inhibition and that utilizing these distinct strategies will result in distinct patterns of activity in brain networks that comprise the attention system. Methods: Fifteen participants were recorded with 128 dense-array electroencephalography (dEEG) while performing a target discrimination task within a classic predictive cueing procedure using centrally presented directional (valid, invalid arrowheads) or spatially neutral cues. Targets were horizontal or vertical rectangles. ERPs were created lateral occipital and midline parietal. Results: We computed an individual strategy score, based on the ratio between facilitation and inhibition scores (defined for each trial: RT minus mean RT of neutrally cued trials devided by standard deviation of neutrally cued trials). A median split was used to identify two groups of participants who tended to be either “Facilitators” (n=9) or “Inhibitors” (n=6). As a preliminary analysis, ERPs for valid, invalid and neutral targets were calculated separately for each group. Facilitators show greater sensory gain than Inhibitors (as indicated by the difference in P1 amplitude between valid and neutral targets). An attention-related N1 effect (greater N1 component amplitude for valid relative to invalid and neutral targets) was observed for both groups. Overall, P3 component amplitudes at midline parietal electrodes were the same for Facilitators and Inhibitors, but Facilitators showed a larger P3 for invalid targets relative to valid and neutral targets. Conclusions: Our preliminary results suggest that both facilitators and inhibitors attention-related benefits for the early visual processing of a validly cued stimulus. However, during a later processing stage facilitators and inhibitors use different attentional strategies regarding the cues. Facilitators tend to utilize attentional processes that highlight information at cued locations, whereas Inhibitors tend to utilize attentional processes that suppress information at locations not predicted by a spatial cue.
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Board # 37 Olivia Wong, Doctoral Student Supervisor: Michael Kobor, Healthy Starts
Elucidating the consequences of the overexpression of histone variant H2A.Z in transcription Olivia Wong, Michael S. Kobor In eukaryotes, chromatin remodeling is essential for nuclear processes. Multiple mechanisms can alter chromatin structure locally, thus changing the accessibility of DNA to DNA binding proteins. One mechanism is the exchange of the histone variant H2A.Z and the canonical histone H2A at specific genomic locations. In yeast, this process is catalyzed by the chromatin remodeling complex SWR1-C. H2A.Z is highly conserved across eukaryotes and is essential for viability in many eukaryotic organisms including mammals. In addition to being involved in various cellular processes, the overexpression of H2A.Z is linked to disease progression in many cancers including breast cancer. H2A.Z is typically found at the nucleosomes flanking transcription start sites of many gene promoters where H2A.Z occupancy is thought to be significant in fine-tuning the transcription of such genes. As previously shown, H2A.Z occupancy at the promoters of inducible genes, including GAL1 or heat shock sensitive genes, is anti-correlated to transcriptional output. However, despite the anti-correlation between H2A.Z occupancy and transcription, only a modest number of genes are differentially expressed in H2A.Z or SWR1-C subunit knockout mutants. Interestingly, the overexpression of H2A.Z resulted in defects in basal growth in comparison to wild-type cells. Moreover, cells overexpressing H2A.Z have a more severe basal growth defect than H2A.Z knockout cells, suggesting that overcompensation of H2A.Z levels may have deleterious effects on the cell. To probe at the roles and H2A.Z in transcription, we will examine the effects of H2A.Z overexpression on gene expression. In particular, we will examine the transcriptional output, including sense and antisense transcription, and H2A.Z occupancy at respective genomic locations.
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Session Six DOCTORAL STUDENTS Moderator: Matthias Gรถrges Participants: Mark Bichin Nicha Boonpattrawong Alyssa Kirlin Chaini Konwar Phillip Richmond Jonathan Simkin Desiree Wilson Kevin Tsai
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Board # 38 Mark Bichin, Doctoral Student Supervisor: Ruth Grunau, Brain, Behaviour & Development
Altered neural network engagement during working memory at school age in children born very preterm M. Bichin, C. Chau, S. Doesburg, A. Herdman, U. Ribary, R.E. Grunau Background: Children born very preterm display poorer working memory (WM) than those born full term (FT). Using magnetoencephalography (MEG) we found altered WM task-associated regional oscillatory synchrony in 8 year old children born very preterm. Relationships between WM taskassociated whole-brain network organization and cognitive performance in children born very preterm remain unknown. Objective: To identify neural networks used in WM task performance by 8 yr. old children born at different degrees of prematurity compared to FT, and examine if relationships between functional engagement of those networks and cognitive performance differs in these children. Design/Methods: Children N = 109 (29 extremely low gestational age ([ELGA; born 24-28 weeks GA], 40 very low gestational age [VLGA 29-32 weeks], and 40 full term [FT â&#x2030;Ľ37 weeks]) were imaged using MEG at age 8 yrs during a visuospatial WM task. Cognitive assessment (WISC-IV) was conducted. Exclusions: major brain injury and/or sensory, motor or cognitive impairment. Analysis of MEG sensor-spaced time/frequency measurements of oscillatory power in the standard frequency bands during 3 periods (encoding, retention, retrieval) of the WM task were performed. Constrained principle component analysis (CPCA) was used to isolate differences in functional neural network engagement between ELGA, VLGA, FT groups over these periods. Results: Multiple CPCA network components were identified during each period accounting for 18% of total variance overall. Groups differed most during retention (p < .001), with ELGA & VLGA groups show greater neural engagement than FT during this period. There was an interaction between group, period and FSIQ; ELGA children with higher IQ had greater neural engagement during retrieval, wheras VLGA children with higher IQ had greater neural engagement during encoding. Neural engagement in the FT group was not associated with IQ during WM performance. Conclusions: During working memory, children born very preterm differ in recruitment and utilization of neural networks compared to children born full-term, with retention requiring the greatest shift in neural resources for children born very preterm. The relationship of IQ to different task periods for ELGA and VLGA children may reflect compensation or greater cognitive resource load required to perform executive functions.
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Board # 39 Nicha Boonpattrawong, Doctoral Student Supervisor: Angela Devlin, Healthy Starts
Maternal obesity and exercise programs cardiometabolic heatlh in offspring Nicha P. Boonpattrawong, Daven C. Tai, Rika E. Aleliunas, Elianne O. Abramovich, Angela M. Devlin The theory of developmental programming suggests that fetal and early postnatal environment can influence risk for chronic diseases, such as cardiovascular disease (CVD), later in life. Approximately 50% of women of childbearing age are overweight (BMI 25-29.9 kg/m2) or obese (BMI â&#x2030;Ľ 30 kg/ m2) in Canada. Several rodent studies have reported that offspring from obese dams have greater adiposity, insulin resistance, and vascular endothelial dysfunction â&#x20AC;&#x201C; an early indicator of CVD. Vascular endothelial dysfunction is characterized by decreased bioavailability of nitric oxide. Exercise been shown to increase availability of nitric oxide should improve vascular endothelial function and improves insulin sensitivity. We hypothesize that maternal exercise will mitigate the adverse effects of maternal obesity during pregnancy on vascular dysfunction and insulin resistance in offspring. Female (C57BL/6) mice were fed from weaning a control diet (10% kcal fat) or western diet (45% kcal fat) to induce excess adiposity. At 13 weeks of age, female mice were put into cages with or without access to a running wheel for voluntary exercise throughout breeding, pregnancy and lactation. Male offspring were weaned onto a control or western diet. At 13 weeks post weaning, glucose homeostasis was assessed by intraperitoneal glucose (IPGTT) and insulin tolerance test (IPITT). Vascular endothelial function (ex vivo) was assessed in aortic rings by isometric force measurement for vasoconstriction and vasodilatation. Gene expression in skeletal muscle was quantified by RealTime PCR. At 13 weeks on the post weaning diet, western-fed offspring from western diet-fed dams without exercise (MWS) had greater glucose intolerance (IPGTT AUC; p<0.05) than those from exercised dams (MWE). Vascular function assessments showed that MWE offspring had greater sensitivity (EC50; p<0.05) and greater maximum percent vasodilatation (p<0.05) induced by acetylcholine than MWS offspring. No significant difference was observed in SNP-induced vasodilatation. Western diet-fed offspring from exercised dams had higher Ppargc1a (p=0.077) and Slc2a4 (p=0.039) mRNA expression in skeletal muscle than those from sedentary dams. Offspring from obese dams that exercise during pregnancy have improved glucose tolerance and vascular function in adulthood. The findings suggest that maternal exercise during pregnancy improves cardiometabolic health of the offspring.
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Board # 40 Alyssa Kirlin, Doctoral Student Supervisor: Michael Kobor, Healthy Starts
The Yaf9 YEATS domain plays a role in its association with chromatin modifying complexes Alyssa C. Kirlin, Michael S. Kobor Chromatin must be modified to alter access to the underlying DNA sequence and allow for gene regulation. There are many protein complexes that mediate this process using different mechanisms, such as histone post-translational modification, histone variant incorporation, and ATP-dependent nucleosome remodeling. The YEATS domain is a recurrent protein module in these complexes and likely plays a role in complex localization by interacting with acetylated lysines in histone tails. Saccharomyces cerevisiae has three YEATS family members: Yaf9, Taf14 and Sas5. At least nine protein complexes contain one of these proteins, suggesting roles for a YEATS domain in histone acetylation, H2A.Z incorporation, chromatin remodeling and transcription. In order to identify shared and unique functions in these family members, we constructed a set of hybrid proteins in which the YEATS domains were swapped in all combinations and tested them for their ability to function in place of the wild type proteins. The hybrid YEATS proteins complemented the impaired growth and drug sensitivity phenotypes of taf14Δ strains. This complementation was not reciprocal, as the growth phenotypes of yaf9Δ were not rescued by the hybrid constructs. Further analysis of the Yaf9-derived proteins showed that they fail to incorporate into NuA4, and have diminished association with SWR1-C, despite the presence of the putative coiled-coil domain thought to mediate Yaf9’s incorporation. These hybrids also fail to co-purify with Swc4, a known interaction partner of Yaf9, suggesting the YEATS domain may play a role in this interaction. This is in contrast to Taf14, whose C-terminus appears to be solely responsible for it’s assembly into various chromatin modifying complexes. Work is now being done to identify the region of the Yaf9 YEATS domain that contributes to these protein-protein interactions.
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Board # 41 Chaini Konwar, Doctoral Student Supervisor: Wendy Robinson, Healthy Starts
Genetic and epigenetic profiling of acute chorioamnionitis associated placentas Konwar C, Price EM, Del Gobbo GF, Wilson SL, Terry J, Robinson WP Objectives: Acute chorioamnionitis (CA) is a histologic lesion reported in >40% of spontaneous preterm deliveries and is characterized by neutrophil infiltration into chorioamniotic membranes. Extraembryonic tissues from acute CA-affected pregnancies may exhibit unique genetic and DNA methylation (DNAm) signatures, reflecting heritable predisposition, increased number of immune cell types, and/or altered gene expression of immune cell types in response to inflammation. Methods: DNA was extracted from whole chorionic villi from 32 acute CA cases and 145 controls (33 preterm, 112 term). These samples were genotyped at 50 ancestry informative markers (AIMs) and 16 single nucleotide polymorphisms (SNPs) in 13 candidate innate immune system genes using the Sequenom iPLEX Gold Assay. A subset of these villous samples (22 cases, 22 preterm controls) and matched fetal membranes (amnion, chorion; 18 cases, 14 preterm controls) were further profiled at >850,000 DNAm sites using the Illumina EPIC array. Results: Differences in fetal genotype frequencies were associated with acute CA status at two SNPs (rs1554973 TLR4, rs1800450 MBL2; OR: 2.1, p <0.05), after adjusting for ethnicity using AIMs. We next assessed DNAm in the 13 candidate genes chosen for the SNP study and no difference was noted between cases and controls. However, using an epigenome-wide approach in villi we identified 66 differentially methylated sites associated with acute CA (FDR <0.15, DNAm difference >0.05). At the same thresholds, 13/66 (~20%) villi sites were also differentially methylated in chorion, but none were in amnion. Conclusion: Acute CA associated placentas showed altered DNAm signatures that were not observed in the absence of inflammation. The lack of an overlap in amnion may reflect reduced infiltration of maternal inflammatory cells into the amnion, normally only present in advanced CA. This study lays the groundwork for development of clinically useful biomarkers for acute CA using candidate SNP and genome-wide DNAm.
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Board # 42 Phillip Richmond, Doctoral Student Supervisor: Wyeth Wasserman, Evidence to Innovation
Clinical grade copy number variant calling from whole genome sequencing in the diagnosis of rare genetic disorders Phillip Richmond, Allison Matthews, Patrice Eydoux, Clara van Karnebeek, Wyeth Wasserman Over 500,000 children across Canada are affected by a rare genetic disorder, and with over 7,000 different disorders identified, the diagnostic process of finding the pathogenic variants in the genome is often burdensome. Pathogenic variants can manifest in different forms including single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs), and complex structural variants (SVs). Chromosomal microarrays (CMAs) are considered the gold standard in CNV detection for rare genetic disorders, but can only detect large CNVs. If the pathogenic variant is not a large CNV, then further tests such as exome sequencing or targeted gene approaches are used. In contrast, whole genome sequencing (WGS) can capture the entire spectrum of genetic variants, reducing the number of tests and decreasing the time required for diagnosis. However, before WGS can be adopted into the clinical setting, a systematic evaluation needs to be performed to assess the sensitivity of CNV calling from WGS data. Previous analyses comparing WGS and CMA in their CNV calling capacity report a 50-60% recovery of CMA variants using WGS, which hinders the adoption of WGS into the clinical setting. The lack of sensitivity from these analyses could be due to the use of alternative DNA sequencing technologies or limitations of the algorithmic approaches to CNV calling in WGS data. To investigate this, we are using matched CMA and WGS on a cohort of patients to compare the set of CNVs identified from multiple analysis pipelines, and explore the discordance between the resulting sets of variants. We also leverage the set of loci used in the CMA probe set to interrogate the allelic balance at those sites in the WGS data, which provides insight into the development of alternative methods detecting large CNVs with WGS.
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Board # 43 Jonathan Simkin, Doctoral Student Supervisor: Gina Ogilvie, Healthy Starts & Catherine Elliott
Differences in colorectal cancer screening rates across income strata by rural and urban status: Results from the Canadian Community Health Survey (2013/2014) Simkin J, Ogilvie G, Elliott C Background: Canadian colorectal cancer screening rates differ across income strata. In the United States, disparities across income strata worsen in rural regions. In Canada, differences in screening across income strata have not been explored by rural/urban status. Objectives: To estimate up-to-date colorectal cancer (UTD-CRC) screening rates by income among rural and urban Canadians and highlight important differences. Methods: Data from the Canadian Community Health Survey (2013/2014) was used to calculate the prevalence of UTD-CRC screening by income quintiles for Canadians aged 50-74 years. UTD-CRC screening was defined as fecal occult blood testing within 2 years or colonoscopy/sigmoidoscopy within 10 years before the survey. Rural/urban health regions were defined per Statistics Canada guidelines. Weighted proportions of UTD-CRC screening were calculated and logistic regression was used to assess the effect of income by rural/urban status. Results: Preliminary findings show the prevalence of UTD-CRC screening among Canadians was 51.9%. UTD-CRC screening rates by income ranged from 50.0% (Q1-low) to 60.6% (Q5-high) among urban and 47.2% (Q1-low) to 52.3% (Q5-high) among rural Canadians. UTD-CRC screening rates were highest in Manitoba (65.7%). Provincially, females generally had higher rates of UTD-CRC screening than males. Higher income was associated with increased odds of UTD-CRC screening compared to the lowest income quintile (ORQ5=1.55, 95% CI 1.27-1.88). The effect of income did not differ significantly between rural and urban strata. Higher education (ORpost-secondary=1.29, 95% CI 1.12-1.48) and increasing age (OR70-74=2.78, 95% CI 2.30-3.37) were associated with an increased odds of UTD-CRC screening. The effect of income differed significantly across provinces. Income disparities were largest in Manitoba (ORQ5=1.91, 95% CI 1.13-3.25). Conclusions: Half of Canadians report UTD-CRC screening but across rural and urban populations higher income was associated with higher UTD-CRC screening rates. Implications to inform future policy or practice initiatives? CRC screening participation is increasing but disparities persist. Efforts are needed to understand and address inequities, particularly among low income populations.
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Board # 44 Desiree Wilson, Doctoral Student Supervisor: Ian Pike & Mariana Brussoni, Evidence to Innovation
Engaging children in examining neighbourhood play-friendliness: A participatory research project using visual methods Desiree Wilson, Ian Pike What places and things in your neighbourhood are ‘friendly’ and ‘not friendly’ for play? In response to this question, over fifty children (ages 10-13) shared their experiences of playing outside through photographs and narratives during a participatory research project using visual methods (informed by Photovoice and Participatory Photo Mapping). This project was part of a larger study aimed at better understanding and advancing a municipal Child and Youth Friendly Community Strategy, designed with the goal of making the city better for young people across nine domains, including ‘playing’ and ‘engaging’. In this participatory project, the methods and procedures were defined in collaboration with partners and participants, including representatives from the City and School District as well as a leadership group of 12 children from the study. Over a period of three months, children participated in 10 sessions related to child-friendly communities, children’s rights, play, photography, community mapping and municipal decision-making. As part of these sessions, the children went on neighbourhood walks and took photographs of the places and things that were relevant to their experiences of outdoor play. The children then developed narratives for their photographs and shared thoughts, experiences and stories related to the images in focus groups. From this, a photo exhibit was co-created (by the children, their teachers and a student researcher) to display at the local City Hall and School District office. To complement this, children from the leadership group made presentations to City Council and the School Board, focusing particularly on safety issues (e.g., hazardous playground equipment, walking routes, street lights) and importance of engaging young people when planning and designing community spaces. This participatory research project was designed to support attempts to better understand children’s perceptions of, and relationships to, the local neighbourhood environments in which they play. It was intended to illuminate some of the complex issues involved in striving for urban environments that are play-friendly and child-friendly. While the photographs and narratives are grounded in a particular local context and are most applicable within that setting, insights from the project could have applications for other efforts to facilitate children’s play and create cities that are better for young people. In this poster/visual display we present selected photographs and narratives from the photo exhibit along with reflections and questions from the children’s discussions. The display is organized into some preliminary themes (e.g., moving around the neighbourhood, risk taking, relationships with nature). 68
Board # 44A Kevin Tsai, Doctoral Student Supervisor: Ian Pike & Mariana Brussoni, Evidence to Innovation
Mucus deficiency results in negative selection of developing T cells restricted to oral antigens Kevin Tsai, Yu-Hsuan Huang, Caixia Ma, Bruce A. Vallance, John J. Priatel A thin layer of mucus functions to segregate contents of the intestinal lumen from the intestinal epithelium. MUC2 is the primary constituent of intestinal mucin and plays critical roles in the maintenance of immune cell homeostasis and protection against bacterial infection. Here, we investigate whether intestinal mucus is essential for maintaining T cell tolerance towards intestinal luminal antigens and preventing disease caused by constitutive T cell activation. To test this hypothesis, wild type and MUC2-deficient (Muc2-/-) mice were gavaged with the model antigen ovalbumin (OVA) and the elicited OVA-specific T cell responses monitored at various time points post-treatment. Significantly, the oral administration of OVA resulted in antigen being rapidly disseminated in the blood and lymphoid tissues of Muc2-/- but not wild type mice. Given the systemic spread of antigen in Muc2-/- mice, we next sought to investigate whether the selection of developing T cells in the thymus of Muc2-/- mice is impacted by dietary antigens. Remarkably, we found that gavage of Muc2-/- mice lead to presentation of OVA by thymic dendritic cells and the deletion of OVA-specific thymocytes whereas T cell development in wild type mice appeared unaffected. Importantly, our findings demonstrate that a leaky gut may result in intestinal luminal antigens shaping the T cell repertoire of developing thymocytes. Further, these results yield important insights into how T cell tolerance against intestinal luminal antigens is established and may lead to novel treatment strategies against allergies and autoimmune diseases.
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Session Seven POSTDOCTORAL FELLOWS & SUBSPECIALTY RESIDENTS OR FELLOWS Moderator: Kishore Mulpuri Participants: Ainsley Boudreau Fern Jaspers-Fayer Alison Lee James McCammon Beth Payne Ainsley Boudreau Robert Selles Jon Stacey
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Board # 45 Ainsley Boudreau, Postdoctoral Fellow Supervisor: Janet Mah, Brain, Behaviour & Development
Predicting use of medications for children with ADHD: The contribution of parent social cognitions Ainsley Boudreau, Janet Mah Stimulant medication is a well-established treatment for ADHD (Pelham & Fabiano, 2008), although many children who could benefit from pharmacological intervention do not receive it. Given the role families play in the decision to access interventions for their child with ADHD, it is imperative that we understand the factors that contribute to the uptake and continuation of pharmacological interventions (Bekle, 2004). Our goal is to explore how well parental social cognitions, guided by the Theory of Reasoned Action (i.e., TRA; attitudes and norms), predict initiation and/or continued use of stimulant medication for children with ADHD; no previous study has explored this model in predicting medication use in a clinical sample. Sixty-nine parents of children presenting to a tertiary ADHD clinic for the first time completed questionnaires, and their clinician documented their medication usage. Results showed that, when controlling for medication status at baseline, both of the components of the TRA predicted medication status after an initial visit. Logistic regressions indicated that parents were more likely to enroll in or continue stimulant medication if they had lower stigma related to ADHD (Wald = 6.87, P <0.01), a higher opinion of ADHD medications (Wald = 4.60, P < 0.05) and a greater knowledge of ADHD (Wald = 4.86, P < 0.05); this model classifies 72.5% of the patients who will start or continue stimulant medications. Findings suggest that the parentsâ&#x20AC;&#x2122; knowledge about ADHD, opinion about treatment and ADHD-related stigma are key factors to target in order to increase the uptake and continued use of evidence-based pharmacological interventions for children with ADHD.
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Board # 46 Fern Jaspers-Fayer, Postdoctoral Fellow Supervisor: Evelyn Stewart, Brain, Behaviour & Development
The influence of symptom provocation on executive function in pediatric obsessive-compulsive disorder Fern Jaspers-Fayer, Sarah Yao Lin, Ryan Lim, Laura Belschner, Elaine Chan, Juliana Negreiros, Donna Lang, Manraj K.M. Heran, S. Evelyn Stewart Pediatric obsessive-compulsive disorder (OCD) is a common and debilitating neuropsychiatric illness, characterized by intrusive thoughts and repetitive behaviors. Previous behavioral studies have shown OCD is associated with executive function impairments on planning tasks, particularly during high task-load trials. Although clinicians working with OCD-affected youth often report that symptom provocation can negatively influence executive function, this detrimental interaction has almost never been tested in the lab. Methods: OCD-affected youth (n = 27; age = 15.07, SD = 2.65; 44% male) were recruited through the BC Childrenâ&#x20AC;&#x2122;s Hospital Provincial OCD Program (BCCH-POP), and compared to a group of healthy control participants (n = 26; age = 14.58, SD =2.87; 42% male) recruited through community advertisements. Groups were then compared on a standard planning task, the Tower of London (ToL), before and after OCD symptom provocation. Results: Before OCD symptom provocation there were no significant differences in response time (RT) between groups on low or high task load trials [t(51) = 1.402, p = 0.167 and t(51) = 1.443, p = 0.155, respectively]. After OCD symptom provocation, groups exhibited a significant difference during high task load trials, t(51) = 2.09, p = 0.042, but continued to perform at par with the healthy controls during low task load trials, t(51) = 1.222, p = 0.227. There were no significant differences between groups in accuracy, F(51) = 1.440, p = 0.236. Discussion: This is the first study to report that symptom provocation can directly impact executive function in pediatric OCD. Work completed by functional magnetic resonance imaging (fMRI) researchers suggests that OCD is underpinned by a dysfunctional cortico-striato-thalamico-cortico (CSTC) network with poorly interfacing affective (e.g., ventromedial) and cognitive (e.g., dorsolateral) loops, but this has never been tested directly. Future work should determine if this paradigm can be used to elucidate the CSTC.
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Board # 47 Alison Lee, Subspecialty Resident or Fellow Supervisor: Quynh Doan, Evidence to Innovation
A psychosocial assessment and management tool for youth in crisis Alison Lee, Mariana Deevska, Karly Stillwell, Tyler Black, Garth Meckler, Ali Eslami, David Park, Quynh Doan Background: Mental health-related pediatric emergency department (PED) visits have been on the rise, necessitating a standardized emergency psychosocial assessment and management tool to assist front-line clinicians who may not be mental health specialists. Objective: To evaluate HEARTSMAP, an emergency psychosocial assessment and management tool, on its inter-rater reliability and predictive validity in identifying youth who require psychiatric assessment and management beyond what can be provided in the PED. Design/Methods: HEARTSMAP guides the psychosocial assessment of youth with emergency mental health complaints. Using the assessed acuity and severity of concerns in ten psychosocial areas, it triggers level-specific mental health service recommendations. We conducted the study in two phases on youth <17 years of age with a mental health-related PED visit. First using extracted information from a retrospective cohort (104 randomly selected cases seen during the fall and winter of 2013-14), we applied the HEARTSMAP tool to clinical presentation information to assess the youth’s psychosocial status. Evaluators were blinded to the final PED dispositions. From this cohort, we evaluated the inter-rater agreement in triggered referral recommendations using Cohen’s Kappa statistics, and the tools sensitivity and specificity for identifying youth who required psychiatric consultation and hospitalization. In phase 2, we used HEARTSMAP to prospectively assess a convenient sample of 70 youth with mental health complaints in the PED (fall and winter of 2014-15) to further evaluate the tool’s test characteristics. Results: There was substantial agreement (κ=0.69) for cases requiring emergent psychiatric consultation and moderate agreement for cases requiring community urgent and non-urgent mental health follow-up (κ=0.4 each). HEARTSMAP’s sensitivity was 76% (95%CI: 63%, 90%) using retrospective cases and 100% (95%CI: 75%, 100%) when prospectively applied. Respective specificities were 65% (95%CI: 55%, 71%) and 33% (95%CI: 20%, 48%). Conclusion: HEARTSMAP has strong reliability, and when applied prospectively is highly sensitive in identifying patients requiring emergent psychiatric assessment and hospitalization.
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Board # 48 James McCammon, Subspecialty Resident or Fellow Supervisor: Anthony Cooper, Evidence to Innovation
Management of the proximal tibiofibular joint in tibial lengthening James McCammon, Anthony Cooper Background: The anatomy of the proximal tibiofibular joint (PTFJ) makes it inherently stable. Lengthening procedures of the tibia cause increased soft tissue tension which can affect the stability of both the distal and proximal tibiofibular joints. The purpose of this study was to review the management options of the PTFJ in tibial lengthening procedures and to document if changes in this joint correlate to clinical exam. Methods: After ethics board approval and retrospective review was conducted for 14 pediatric patients meeting inclusion criteria who underwent tibial lengthening in the last 5 years. Demographic, radiographic, surgical factors and complications were recorded and compared. Results: A total of 14 patients met criteria for inclusion. Etiology included fibular hemimelia (4), hemihypertrophy (4), post-traumatic deformities (2), blounts (1), unknown (1), posteriomedial bowing (1), compartment syndrome (1) and post-infectious (1). Mean follow-up since frame removal was 10.3 months (2.7-20.6).A cannulated screw was used to fix the distal tibiofibular joint in 10 of 14 cases and a solid cortical screw in 3 cases. No fixation was used proximally in any cases. The average mean external fixation index was 46.7 (30.7-62.8). All patients showed a decrease in the distal tibiofibular index with the average changing preoperatively from 8.2 (-4.0-18.35) mm to 6.7 (2.2-11.9) mm postoperatively. The fibula to tibia ratio average decreased from 0.99 (0.93-1.05) preoperatively to 0.95 (0.87-1.00) postoperatively. All patients showed an increase in proximal fibular migration (PFM) with an average increased distance of 9.66 (1.40-19.15) mm. The tibiofibular distraction difference ranged from -1.4-23.6 mm with an average of 14.2 mm. The average number of days in the TSF was 243.21 (184-332). The average regenerate length gained was 54.3 (37.9-77.0) mm, representing an average increase of 17.2(9.8-30.9) % in the length of the tibia. The fibula increased an average of 40.97(14.3-62.1) mm, representing a 13.1 (3.6-22.9) % increase. The mean mechanical axis deviation was -1.1 (-86.9-26.5) varus preoperatively which increased to 9.7 (-73.7-44.1) valgus postoperatively. The average change in MAD was 10.9 degrees of valgus. Pin site infections were documented in 9 of 14. There were no documented peroneal nerve palsies. There were no cases of postoperative knee pain or instability. There was one regenerate fracture. Three patients went on to have 8-plate application for genu valgum; two of the three had fibular hemimelia. There were two cases of failure of the distal cannulated screw. Conclusions: Fixation of the proximal tibiofibular joint was not necessary in 14 patients with a mean tibial lengthening of 17.2%. Isolated fixation of the distal tibiofibular joint did result in proximal fibular migration in all cases but this was not found to be clinically significant.
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Board # 49 Beth Payne, Postdoctoral Fellow Supervisor: Mark Ansermino, Healthy Starts
Precision medicine for pregnant and recently-pregnant women receiving critical care: The CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) model Beth A Payne, Helen M Ryan, U Vivian Ukah, Laura A Magee, Jeffrey Bone, Alice Aarvold, J Mark Ansermino, Zulfiqar A Bhutta, Mary Bowen, J Guilherme Cecatti, Cynthia Chazotte, Tim Crozier, Anne-CornĂŠlie JM de Pont, Oktay Demirkiran, Tao Duan, Marlot Kallen Most women who die during or soon after pregnancy die in an intensive care unit (ICU). Existing critical care outcome prediction models (i.e. APACHE) tend to overestimate maternal mortality risk. In order to more accurately guide clinical decision making for these women, we developed and internally validated a pregnancy-specific outcome prediction tool (Collaborative Integrated Pregnancy High-dependency Estimate of Risk [CIPHER]). The data for this study were derived from a cohort of 876 women admitted during or within 42 days of pregnancy to an ICU at 14 collaborating sites, defined using a 12-year (2000-12, inclusive) retrospective chart review. The primary outcome for the study was death (61 (7.0%)) or organ support for greater than 7 days (71 (8.1%)). Selection of candidate predictors used a combination of prior evidence of effect, clinical opinion and data completeness in the cohort. Logistic regression after multiple imputation of missing data was used to estimate model parameters. The final CIPHER model includes: maternal age, surgical status within 24hrs before ICU admission, Glasgow Coma Scale, creatinine, bilirubin, aPTT and white blood cell count. Discrimination of the model was excellent (AUCROC 0.84 (95% CI 0.80 â&#x20AC;&#x201C; 0.87) with good calibration and minimal evidence of overfitting. The CIPHER model, once externally validated, could be used to support shared decision making regarding treatment plans for pregnant or recently pregnant women admitted to ICU by providing each woman a precise estimate of risk.
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Board # 50 Ainsley Boudreau, Postdoctoral Fellow Supervisor: Tara Jukes & Melanie McConnell, Brain, Behaviour & Development
Examining the acceptability and effectiveness of group-based comprehensive behavioural intervention for Tics in elementaryaged children Ainsley Boudreau, Melanie McConnell, Tara Jukes Comprehensive Behavioral Intervention for Tics (CBIT) is as an evidence-based treatment for decreasing tic frequency, severity, and related impairment (Woods et al., 2008). Despite promising advances in the treatment of tic disorders, most children in need of intervention have not received CBIT (Woods et al., 2010). The research to date has focused on individually administered CBIT, despite the potential benefits of group treatment (e.g., more children treated, fewer clinicians needed, vicarious learning, de-stigmatization; Sobell et al., 2009). The present study attempted to address this service-delivery gap by evaluating the acceptability and effectiveness of an 8-session group-based CBIT (i.e., “Tic Busters”). Outcomes for children with tics were assessed before and following group (child/parent questionnaires and clinician rated Yale Global Tic Severity Scale). Preliminary results from the first 13 participants revealed that children who participated in the Tic Busters group had significantly fewer tics (M= 5.9, SE= 0.5 vs M= 4.4, SE= 0.6), less frequently occurring tics (M= 6.2, SE= 0.6 vs M= 4.4, SE= 0.5) and less severe tics (M= 28.3, SE= 2.2 vs M= 17.6, SE= 2.5; t(12)= 4.35, p< .01) overall, following treatment. Tic-related impairment was also significantly lower (M= 27.5, SE= 3.5 vs M= 11.7, SE= 3.7) following treatment, t(11)= 3.98, p< .01. Parents were also satisfied with the group (M = 4.95; range = 4.75 – 5.0). Our findings suggest that CBIT may be an acceptable, effective and cost-effective method for addressing the service delivery gap for children with tics.
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Board # 51 Robert Selles, Postdoctoral Fellow Supervisor: Evelyn Stewart, Brain, Behaviour & Development
Parent tolerance of child distress in pediatric obsessivecompulsive disorder: Correlates and relationship with group family-based cognitive behavioral therapy outcomes Robert Selles, Laura Belschner, Sarah Lin, Katherine McKenney, Annie Simpson, Noel Gregorowski, Evelyn Stewart Background: Preliminary evidence suggests parents’ difficulty in tolerating their child’s distress may impact the outcome of cognitive behavioral therapy for pediatric obsessive-compulsive disorder (OCD). Methods: Cross-sectional outcomes on parents of 84 youth (7-18 years old) with OCD and pre-post group, family-based cognitive-behavior therapy (GF-CBT) outcomes on parents of 51 youth were examined. The primary outcome measure was the Parent Tolerance of Child Distress scale (PT-OCD). Results: At evaluation, parents demonstrated moderate tolerance. Parent tolerance significantly correlated with OCD-related family impairment for both mothers and fathers. In addition, mothers’ tolerance was related to their ratings of parental efficacy while fathers’ ratings were associated with their ratings of the child’s coercive/disruptive behavior. Over treatment, mothers demonstrated a small improvement in overall PT-OCD score while fathers demonstrated a medium-large improvement in overall PT-OCD score. In regards to the impact of baseline PT-OCD on treatment outcome, lower initial scores for fathers was associated with larger improvements in overall severity and family functioning, while mothers’ initial scores were not associated with outcomes. Improving PT-OCD was associated with improvements in family functioning for both mothers and fathers while fathers’ improvements in PT-OCD also correlated with greater improvements in overall severity. Conclusions: The findings are the first to examine a self-report rating of parent distress tolerance in youth with OCD. The findings support the relationship between parent-tolerance and family impairment as well as the relationship of parent-tolerance and the impact of treatment.
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Board # 52 Jon Stacey, Subspecialty Resident or Fellow Supervisor: Simon Whyte, Evidence to Innovation
Unplanned post-operative admission after ambulatory surgery at BCCH: An audit Jonathan Stacey, Simon Whyte Rates of unplanned admission after ambulatory surgery in adults have been used as surrogate markers of patient safety, quality of care and resourse allocation. There is little in the contemporary pediatric literature addressing this topic. This retrospective audit of all unplanned admissions after ambulatory surgery at BC Childrenâ&#x20AC;&#x2122;s Hospital from Match 2015 to October 2016 sought to provide a descriptive study of such unplanned admissions, identify commonalities of patient, anesthetic and surgical factors, and provide direction for future studies. After exclusions, the overall rate of unplanned admission was 1.1%. 9% of admissions were associated with unanticipated intra-operative events. Admission appeared independent of time of completion of surgery. The rate of anesthesia-related admissions was 0.3%, and two major groups were identified; younger children with identifiable risk factors with post-operative airway or respiratory concerns, and older teens undergoing orthopedic procedures experiencing post-operative pain crises. The rate of surgical-related admissions was 0.72%. The majority of children admitted overnight for observation were discharged without incident the next morning. In conclusion, the rate of unplanned admission after ambulatory surgery at BCCH was comparable to other published data. The rate of anesthesia-related admission compares favorably with other studies. The reasons for this may warrant further investigation.
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Session Eight
POSTDOCTORAL FELLOWS & SUBSPECIALTY RESIDENTS OR FELLOWS Moderator: Manish Sadarangani Participants: Emily Schaeffer Liezl du Plessis Jenny Fairthorne Devon Greyson Juliana Negreiros Cheryl Peters Nicholas Williams
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Board # 53 Emily Schaeffer, Postdoctoral Fellow Supervisor: Kishore Mulpuri, Evidence to Innovation
The need for further corrective surgery in Developmental Dysplasia of the Hip: Surgical decision-making and practice variability Emily K Schaeffer, Wudbhav N Sankar, Nicholas MP Clarke, Alaric Aroojis, Charles T Price, Kishore Mulpuri, IHDI Study Group Background: Many studies on Developmental Dysplasia of the Hip (DDH) use the need for further corrective surgery (FCS) after primary treatment as an outcome representing treatment failure. However, the decision to proceed with, and timing of, FCS can be dependent upon surgeon preference Objectives: The objective of this study was to capture variability in surgical decision-making regarding need for FCS after primary treatment for DDH. Methods: Twenty patients previously treated for DDH were selected from the records of two pediatric orthopaedic surgeons practicing at tertiary care hospitals. Demographic information, diagnosis, initial treatment(s) and serial radiographs were compiled and sent to international pediatric orthopaedic surgeons. For each case, surgeons were asked whether a surgical intervention would be necessary based on radiographs and radiographic measures, and if so, what intervention should be performed. Questions about reason for non-intervention and advanced imaging were also posed. Mean age of patients at time of query was 4.1 years (range 2.0-8.3). Results: There were 16 survey respondents. Surgeons unanimously agreed in favour of intervention in 3/20 cases. Average standardized consensus (0 to 1) was 0.52, 95% CI [0.34-0.70]. When respondents felt an intervention was necessary, there was considerable variation in procedure choice. Most frequent procedures were pelvic osteotomy (41%), combined pelvic and femoral osteotomy (24%) and femoral osteotomy alone (11%). Consensus did not correlate with patient age or length of follow-up since index procedure. When “no intervention” was selected, “Likely to improve on own” was the most frequent reason (51%), then “Possible future intervention” (40%) and “Definite future intervention” (8%). Conclusion: Surgical decision-making for FCS is widely variable between surgeons. Provided the same series of radiographs and radiographic measures, surgeons unanimously agreed on intervention necessity in 15% of cases, and reached majority consensus in only 60% of cases. There was further variation in procedure choice and intervention timing. This survey demonstrates the inherent variability in management of residual dysplasia between pediatric orthopaedic surgeons and highlights the importance of caution when interpreting studies using FCS as a surrogate outcome measure. This knowledge will aid in the identification of objective outcomes and provide a basis for consensus discussion.
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Board # 54 Liezl du Plessis, Subspecialty Resident or Fellow Supervisor: Cherry Mammen & Rod Rassekh, Evidence to Innovation
High incidence of acute kidney injury during chemotherapy for acute myeloid leukemia Liezl du Plessis, Jim Potts, Rod Rassekh, Cherry Mammen Background: Childhood acute myeloid leukemia (AML) is rare with an incidence of 7.6 cases per million children. Our local physicians became concerned about a high incidence of acute kidney injury (AKI) in our AML population. The Medical Research Council (MRC) chemotherapy backbone for AML is not considered nephrotoxic. The epidemiology of AKI in childhood AML has not been extensively studied. Hospitalized children with AKI have higher mortality and an increased risk to develop chronic kidney disease (CKD) in survivors. Objectives: To determine the incidence of AKI during chemotherapy for childhood AML and identifying risk factors associated with these episodes. Method: A retrospective cohort study of 53 children, newly diagnosed with de-novo AML receiving chemotherapy from May 2005 to April 2016. All available serum creatinine (SCr) levels were reviewed during therapy-related hospitalizations, to identify AKI in individual patients. Kidney Disease: Improving Global Outcomes (KDIGO) criteria was use to define AKI. Urine output was not assessed as an AKI indicator. Severe AKI was defined as AKI stages 2 or 3. We explored risk factors for AKI within cycle 1 and with the combination of chemotherapy cycles. Results: Median age was 9.1 years (interquartile range [IQR], 2.3-13.5). AKI developed in 34 patients (64%) with multiple AKI episodes in 10 patients (46 total episodes). Severe AKI occurred in 23 patients (43.4%) with 24 total episodes. Severe sepsis was identified 15 patients (28.3%). In cycle 1, univariate analysis identified severe sepsis as a risk factor for severe AKI (P=.003). With the combination of chemotherapy cycles, older age (â&#x2030;Ľ10years) was identified on multivariate analysis, as an independent risk factor for severe AKI (odds ratio: 22.2; 95% confidence interval 3-162, P=.002). Conclusion: There was a high incidence of AKI in our AML cohort. During chemotherapy, older age (â&#x2030;Ľ10years) was an independent risk factor for severe AKI. Severe sepsis was common and associated with severe AKI in cycle 1. Survivors of childhood AML should be monitored for long term kidney health. Further prospective, multi-center AKI studies are needed in this susceptible population
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Board # 55 Jenny Fairthorne, Postdoctoral Fellow Supervisor: Tim Oberlander, Brain, Behaviour & Development
Depressed, low SES women have high numbers of physician visits in the year before pregnancy: implications for pre-conception care Jenny Fairthorne, Gillian E Hanley, Tim F Oberlander There is a higher prevalence of depression in women of low socio-economic status (SES). Due to the negative effects on the fetus of maternal depression, particularly in combination with low SES, it is important to address depression prior to pregnancy. Hence, during the year before pregnancy, by SES, we estimated the odds of a physician visit associated with a diagnosis of depression and the odds of greater numbers of physician visits in women by depressive status. We used population-based registry data of women with a live birth in British Columbia (BC) from 1999-2009 and estimated family SES decile using tax-file data. Mixed Effects Logistic Regression, adjusting for maternal age and parity, and STATA14 were used for analyses. Non-depressed and disadvantaged women from Decile-1 and Decile-2 were about 30% more likely to have more than 20 physician visits [aOR=1.35(95% CI: (1.16, 1.57); aOR=1.29(95% CI: (1.11, 1.49)]. Similarly, depressed and disadvantaged women from Decile-1 and Decile-2 were more likely to have more than 20 physician visits [aOR=1.49(95% CI: (1.14, 1.96); aOR=1.25(95% CI: (0.95, 1.64)]. Screening for depression in pregnancy is routine in BC. However, physicians should carefully assess and then refer affected women, particularly those of lower SES, who indicate their intention to become pregnant and again early in pregnancy. In such ways, the adverse effects of prenatal depression, and the interactive effects with low SES, on the subsequent child might be reduced.
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Board # 56 Devon Greyson, Postdoctoral Fellow Supervisor: Julie Bettinger, Healthy Starts
Childhood immunization mandates: The international landscape Devon Greyson, Karina Spoyalo, Julie Bettinger Introduction: Motivated by concerns regarding inadequate vaccination coverage and the potential for vaccine preventable disease outbreaks, governments internationally have been discussing, implementing, and tightening policies requiring documentation of immunization for school enrolment. In 2015, the Canadian Medical Association passed a resolution recommending that all provinces require vaccine records for school enrolment; however the question of how best to legislate this remains unclear. Objective: This poster presents an overview of school or childcare based immunization policies in Canada and international comparator countries, to identify commonalities and differences among policies. Methods: An environmental scan was conducted in the spring of 2017 to identify mandatory documentation and immunization policies in Canada and OECD comparator countries. Policy attributes were abstracted using a common rubric in order to compare across jurisdictions. Results: In Canada, New Brunswick and Ontario require immunization for school and childcare, unless exempt for medical, religious, or conscientious reasons. However, enforcement of the New Brunswick policy is more open to interpretation than that in Ontario. All fifty states in the USA require immunization as well; however, among the states there is a wide range of detail on exemptions, conditional enrollment policies, exclusion criteria, and penalties. Australia’s national “No Jab No Pay” policy denies financial benefits to unvaccinated families and allows only medical exemptions. Additionally, three of six Australian states have “No Jab No Play” policies, which require immunization records for childcare. New Zealand has no mandated immunization policy. Among European comparators, mandates are rare, present only in France and some regions of Italy. Meanwhile, Germany, the UK, Sweden, and the Netherlands have strong recommendations but no requirements. Likewise, Japan’s policy is voluntary; however are immunizations split into “scheduled and covered” and “elective and not covered.” Conclusion: Among comparator countries, there is wide variation in childhood immunization policy, and no international standard has emerged. Discrepancies among policies may serve to increase confusion and hesitancy regarding the importance of immunization.
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Board # 57 Juliana Negreiros, Postdoctoral Fellow Supervisor: Evelyn Stewart, Brain, Behaviour & Development
Differences in OCD-affected youth’s executive functioning when using direct versus indirect measures of the same theoretical construct Juliana Negreiros, Laura Belschner, Sarah Lin, Fern Jaspers–Fayer, S. Evelyn Stewart Background: There is increasing interest in determining whether executive dysfunction is a common characteristic present in pediatric OCD. While most research has assessed executive function (EF) via standardized testing, very few have used questionnaires of parent report of child’s behaviour. This is of concern as inconsistencies between test performance and real-life behaviours have been documented in the literature. Objective: This study examined EF deficits in OCD-affected youth in comparison to healthy controls (HC), using direct (standardized testing) and indirect (questionnaire) instruments. Methods: Sixty-six OCD-affected youth (CY-BOCS = 16.6/40, 39% male, mean age = 13.7 years) and 47 HCs (34% male, mean age = 13.2 years) were assessed for EF via standardized testing (CANTAB) and a questionnaire that examined parents’ perception of their youth’s daily behaviour (BRIEF). To investigate group differences, independent t-tests were conducted in the areas of response inhibition, set shifting, planning, and working memory. Bonferroni correction was performed (p<0.006), and effect size was reported. Direct and indirect measures were then correlated to determine if they tapped into the same theoretical constructs. Results: Findings indicated that only the standardized planning test showed significant group differences (p=0.002; d=0.60). In contrast, all of the BRIEF subscales showed significant differences between groups, where the OCD group demonstrated deficits (p<0.001; d=0.93-1.56). No significant relationships between the same theoretical constructs were found for either group, although the study was well powered. Discussion: In comparison to HCs, OCD-affected youth exhibited planning deficits during standardized testing, but no other EF deficits. In comparison, when assessed using an indirect EF measure, the OCD group presented with significant difficulty in daily behaviour. Such discrepant findings between direct and indirect EF measures suggest that indirect EF instruments may be superior in discriminating EF deficits between OCD and HC groups. Furthermore, there were no correlations between the CANTAB tests and the corresponding BRIEF subscales, which suggest that the instruments may measure different theoretical constructs or that the direct measure may lack ecological validity. Thus, assessing EF through indirect measures might provide additional and meaningful information about executive dysfunction in real-life situations of OCD-affected youth. 84
Board # 58 Cheryl Peters, Subspecialty Resident or Fellow Supervisor: Tex Kissoon, Healthy Starts & Matthias Görges, Evidence to Innovation
Systemic inflammatory response syndrome criteria and sepsis mortality in children: Time for a new definition? Srinivas Murthy, Niranjan Kissoon, Rollin Brant, Matthias Görges Rationale: Systemic inflammatory response syndrome (SIRS) criteria for defining sepsis has poor specificity and fails to predict mortality accurately in one in eight adults. However, it is still being used in children. Objectives: To evaluate the SIRS criteria and the quick Sepsis-related Organ Failure Assessment (qSOFA) in identifying children with infections at risk of increased mortality. Methods: Data from the Virtual Pediatric Systems Pediatric Intensive Care Unit (PICU) database were queried for children who were admitted with infections between 2009 and 2014; multiple imputation was used for missing elements. Observed mortality, including age-group effects, was analyzed for SIRS-positive patients and qSOFA-positive patients. Measurements and Main Results: Data from 101,115 patients, admitted to participating PICUs with an infection-related diagnosis, revealed an overall mortality of 3.90%. Mortality increased strongly once 3 SIRS criteria were met, with imputed risks of 2.17, 2.09, 2.77, 4.38, and 8.47% for 0 to 4 SIRS criteria respectively. The consensus definition for sepsis (2 or more SIRS criteria, including abnormal leukocyte count or temperature) missed 1 in 5 deaths, including 30% of children <2 years old, and 48% of neonates <1 week old. The qSOFA criteria showed similar results but improved predictive capability, particularly in those <1 week of age (missing only 15%). The area under the ROC curve was 63.2 (95% CI 62.2−64.3) for SIRS criteria and 64.2 (95% CI 63.1−65.3) for qSOFA criteria. Conclusions: Both SIRS and qSOFA criteria were overall poor predictors of mortality, especially in younger children. Re-defining sepsis in children is worth pursuing.
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Board # 59 Nicholas Williams, Subspecialty Resident or Fellow Supervisor: Susan Albersheim, Healthy Starts & Anne Synnes, Brain, Behaviour & Development
An objective approach to developing guidelines for resuscitation at the threshold of viability Nicholas Williams, Susan Albersheim, Anne Synnes Background: Threshold of viability (TOV) guidelines that identify limits for administering and withholding resuscitation for extremely preterm deliveries are typically based on changing gestational age specific outcomes. Furthermore these guidelines are often made without a priori criteria. Decision-making (DM) outside of these thresholds is generally made by informed parents. Objective: To define, a priori, the threshold criteria for TOV guidelines. Design/Methods: After definitions of survival, severe neurodevelopmental impairment (sNDI) or any NDI were provided, a multiple-choice survey of 8 questions was given to perinatal health care professionals (HCPs) to elicit the probability of survival/NDI at which respondents would always resuscitate, recommend resuscitation, not recommend resuscitation or never resuscitate. As sNDI represents the worst developmental outcome, this definition was used for questions regarding withholding resuscitation. Agreement by > 80 % of respondents was used to define threshold criteria. Results: 92 HCPs responded to the survey. Clear consensus was demonstrated for resuscitating and not resuscitating when survival rates were >90% and <1% respectively. No clear agreement was reached regarding the relevance of NDI, as approximately 50% of responders felt this outcome was irrelevant for DM, however, there would have to be a >90% chance of sNDI before HCPs would not offer resuscitation. Resuscitation would not be recommended at <5% chance of survival but would be recommended if the chance of survival was >50%. Conclusions: Our results show that objective, a priori criteria for defining TOV guidelines can be developed. These initial results will form the basis for a Delphi process to obtain more rigorous consensus. Such criteria can then be applied to local outcomes and adapted to multiple risk factors and changes over time, thus enabling avoidance of subjective â&#x20AC;&#x153;gestational ageismâ&#x20AC;?.
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The Research Education Office, at the BC Children’s Hospital Research Institute, supports the development of an enriched, multidisciplinary learning environment for researchers onsite How do we support the research community? • Offer a curriculum for graduate students and postdoctoral fellows to help build analytical capacity and enchance career development skills • Coordinate training resources and professional development opportunities for clinical researchers • Bridge the gap between basic science and clinical research with unique networking and funding opportunities
• Provide a foundation for investigators to produce skilled and confident graduates • Introduce undergraduate and medical students to research across disciplines, maximizing the connections with peers and mentors • Lead the development of outreach programs, engaging high school students and the public with world-class researchers and clinicians
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Dedication to Research Education
High school students participated in programs intended to broaden their knowledge of research this year
Trainees in 2016 - 2017
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785 Alumni trainees
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Hours of professional development and research skills trainining offered in 2016 - 2017
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