Digital Commons Network^™

Antiinflammatory Therapy With Canakinumab For Atherosclerotic Disease, P. M. Ridker, B. M. Everett, T. Thuren, J. G. Macfadyen, W. H. Chang, C. Ballantyne, F. Fonseca, J. Nicolau, W. Koenig, S. D. Anker, J. J.P. Kastelein, J. H. Cornel, P. Pais, D. Pella, J. Genest, R. Cifkova, A. Lorenzatti, T. Forster, Z. Kobalava, L. Vida-Simiti, M. Flather, H. Shimokawa, H. Ogawa, M. Dellborg, P. R.F. Rossi, R. P.T. Troquay, P. Libby, R. J. Glynn, H. Krum

Paediatrics Publications

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: …

Global, Regional, And National Comparative Risk Assessment Of 84 Behavioural, Environmental And Occupational, And Metabolic Risks Or Clusters Of Risks, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016, Gbd 2016 Risk Factors Collaborators

Paediatrics Publications

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context.

METHODS: We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and …

Global, Regional, And National Incidence, Prevalence, And Years Lived With Disability For 328 Diseases And Injuries For 195 Countries, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016, Gbd 2016 Disease And Injury Incidence And Prevalence Collaborators

Paediatrics Publications

BACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between …

Global, Regional, And National Disability-Adjusted Life-Years (Dalys) For 333 Diseases And Injuries And Healthy Life Expectancy (Hale) For 195 Countries And Territories, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016, Gbd 2016 Dalys And Hale Collaborators

Paediatrics Publications

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI).

METHODS: We used results from the Global …

Insulin-Like Growth Factor Binding Protein-6 Alters Skeletal Muscle Differentiation Of Human Mesenchymal Stem Cells, Doaa Aboalola, Victor K. M. Han

Paediatrics Publications

Insulin-like growth factor binding protein-6 (IGFBP-6), the main regulator of insulin-like growth factor-2 (IGF-2), is a component of the stem cell niche in developing muscle cells. However, its role in muscle development has not been clearly defined. In this study, we investigated the role of IGFBP-6 in muscle commitment and differentiation of human mesenchymal stem cells derived from the placenta. We showed that placental mesenchymal stem cells (PMSCs) have the ability to differentiate into muscle cells when exposed to a specific culture medium by expressing muscle markers Pax3/7, MyoD, myogenin, and myosin heavy chain in a stage-dependent manner with the …

Is A Motivational Interviewing Based Lifestyle Intervention For Obese Pregnant Women Across Europe Implemented As Planned? Process Evaluation Of The Dali Study, Judith G.M. Jelsma, David Simmons, Nina Gobat, Stephen Rollnick, Kinga Blumska, Goele Jans, Sander Galjaard, Gernot Desoye

Paediatrics Publications

Background: Process evaluation is an essential part of designing and assessing complex interventions. The vitamin D and lifestyle intervention study (DALI) study is testing different strategies to prevent development of gestational diabetes mellitus among European obese pregnant women with a body mass index ≥29kg/m2. The intervention includes guidance on physical activity and/or healthy eating by a lifestyle coach trained in motivational interviewing (MI). The aim of this study was to assess the process elements: reach, dose delivered, fidelity and satisfaction and to investigate whether these process elements were associated with changes in gestational weight gain (GWG). Methods: Data on reach, …

Impact Of The Supporting Physical Activity In The Childcare Environment (Space) Intervention On Preschoolers' Physical Activity Levels And Sedentary Time: A Single-Blind Cluster Randomized Controlled Trial, Patricia Tucker, Leigh M. Vanderloo, Andrew M. Johnson, Shauna M. Burke, Jennifer D. Irwin, Anca Gaston, Molly Driediger, Brian W. Timmons

Paediatrics Publications

Background: Physical activity levels among preschoolers in childcare are low and sedentary time high. The Supporting Physical Activity in the Childcare Environment (SPACE) intervention had three components: 1. portable play equipment; 2. staff training; and, 3. modified outdoor playtime (i.e., shorter, more frequent periods). This study aimed to examine the effectiveness of the SPACE intervention on preschoolers' physical activity levels and sedentary time during childcare hours (compared to standard care). Methods: Via a single-blind cluster randomized controlled trial, 338 preschoolers (39.86±7.33months; 52% boys) from 22 centre-based childcare facilities (11 experimental, 11 control) were enrolled. Preschoolers wore an Actical™ accelerometer for …

The Mediating Effect Of Depressive Symptoms On The Relationship Between Bullying Victimization And Non-Suicidal Self-Injury Among Adolescents: Findings From Community And Inpatient Mental Health Settings In Ontario, Canada, Philip Baiden, Shannon L. Stewart, Barbara Fallon

Paediatrics Publications

Although bullying victimization has been linked to a number of behavioral and emotional problems among adolescents, few studies have investigate the mechanism through which bullying victimization affect non-suicidal self-injury. The objectives of this study were to examine the effect of bullying victimization on non-suicidal self-injury and the mediating effect of depressive symptoms on the relationship between bullying victimization and non-suicidal self-injury among adolescents. Data for this study came from the interRAI Child and Youth Mental Health dataset. A total of 1650 adolescents aged 12–18 years (M =14.56; SD =1.79; 54.2% males) were analyzed. Binary logistic and Poisson regression models were …

The Relationship Between Paediatric Practitioners And ‘Industry’, Susan Albersheim, Kevin Coughlin

Paediatrics Publications

Paediatric practitioners interact with industry representatives for many purposes but most often to receive information on new and existing products. While practitioners believe they are immune to the marketing influences exerted by these representatives, research has demonstrated otherwise. The literature suggests that the public is aware of such influences and that most people feel industry influence on practitioners is inappropriate. National guidelines go some way toward regulating practitioner–industry interactions, although they are not always clear or sufficient. The present practice point explores the context for these relationships, raises some ethical issues specific to paediatric practitioners and provides recommendations for maintaining …

Activating Transcription Factor 3 Promotes Loss Of The Acinar Cell Phenotype In Response To Cerulein-Induced Pancreatitis In Mice, Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin

Paediatrics Publications

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. …

Therapeutic And Prognostic Implications Of Braf V600e In Pediatric Low-Grade Gliomas., Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara Mckeown, Jim Loukides, Ofelia Cruz, Carmen De Torres, Cheng-Ying Ho, Roger J Packer, Ruth Tatevossian, Ibrahim Qaddoumi, Julie H Harreld, James D Dalton, Jean Mulcahy-Levy, Nicholas Foreman, Matthias A Karajannis, Shiyang Wang, Matija Snuderl, Amulya Nageswara Rao, Caterina Giannini, Mark Kieran, Keith L Ligon, Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Sabine Mueller, Theodore Nicolaides, Karen Silva, Romain Perbet, Alexandre Vasiljevic, Cécile Faure Conter, Didier Frappaz, Sarah Leary, Courtney Crane, Aden Chan, Ho-Keung Ng, Zhi-Feng Shi, Ying Mao, Elizabeth Finch, David Eisenstat, Bev Wilson, Anne Sophie Carret, Peter Hauser, David Sumerauer, Lenka Krskova, Valerie Larouche, Adam Fleming, Shayna Zelcer, Nada Jabado, James T Rutka, Peter Dirks, Michael D Taylor, Shiyi Chen, Ute Bartels, Annie Huang, David W Ellison, Eric Bouffet, Cynthia Hawkins, Uri Tabori

Paediatrics Publications

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown.

Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180).

Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a …

Regulation Of Osteogenic Differentiation Of Placental-Derived Mesenchymal Stem Cells By Insulin-Like Growth Factors And Low Oxygen Tension, Amer Youssef, Victor K. M. Han

Paediatrics Publications

Placental mesenchymal stem cells (PMSCs) are multipotent cells that can differentiate in vitro to multiple lineages, including bone. Insulin-like growth factors (IGFs, IGF-1 and IGF-2) participate in maintaining growth, survival, and differentiation of many stem cells, including osteoprogenitors. Low oxygen tension (PO2) can maintain stem cell multipotency and impede osteogenic differentiation. In this study, we investigated whether PMSC osteogenic differentiation is influenced by low PO2 and by IGFs. Our results indicated that low PO2 decreased osteogenic markers RUNX2 and OPN; however, re-exposure to higher oxygen tension (room air) restored differentiation. IGFs, especially IGF-1, triggered an earlier expression of RUNX2 and …

The Effectiveness Of The Anti-Cd11d Treatment Is Reduced In Rat Models Of Spinal Cord Injury That Produce Significant Levels Of Intraspinal Hemorrhage, N. M. Geremia, T. Hryciw, F. Bao, F. Streijger, E. Okon, J. H.T. Lee, L. C. Weaver, G. A. Dekaban, B. K. Kwon, A. Brown

Paediatrics Publications

We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not …

Brief Report: Deficiency Of Complement 1r Subcomponent In Early-Onset Systemic Lupus Erythematosus: The Role Of Disease-Modifying Alleles In A Monogenic Disease, Erkan Demirkaya, Qing Zhou, Carolyne K. Smith, Michael J. Ombrello, Natalie Deuitch, Wanxia L. Tsai, Patrycja Hoffmann, Elaine F. Remmers, Masaki Takeuchi, Yong Hwan Park, Jae Jin Chae, Kenan Barut, Dogan Simsek, Amra Adrovic, Sezgin Sahin, Salim Caliskan, Settara C. Chandrasekharappa, Sarfaraz A. Hasni, Amanda K. Ombrello, Massimo Gadina, Daniel L. Kastner, Mariana J. Kaplan, Ozgur Kasapcopur, Ivona Aksentijevich

Paediatrics Publications

Objective: To identify a genetic cause of early-onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of the disease. Methods: We performed whole-exome sequencing and single-nucleotide polymorphism array genotyping in family members with and without SLE. Protein and gene expression, cytokine profile, neutrophil extracellular trap (NET) formation, and presence of low-density granulocytes were evaluated in patient primary cells and serum samples. Results: We identified a novel, homozygous, loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Using the Sanger method of DNA sequencing in 14 family members, we confirmed the presence of the mutation …

Strategies To Reduce Line Infections In A Small Child With Homozygous Familial Hypercholesterolaemia Who Cannot Yet Receive Ldl Apheresis, Misan Lee, Janet Barr, Stewart Kribs, Guido Filler

Paediatrics Publications

Patients with homozygous familial hypercholesterolaemia are optimally treated with low-density lipoprotein apheresis. Young patients who do not meet a weight threshold (25 kg) receive regular plasmapheresis. This approach may remove excessive immunoglobulins and vascular access set-up can be challenging. We report the case of a 4 year-old child who exhibited repeated septic infections (5 in 6 months) and had recurrent access issues before two interventions were implemented: (1) the percutaneous central venous line was modified to two implanted paediatric ports, and (2) the patient started receiving two bags of Octaplasma at the end of each plasmapheresis treatment to account for …

Growth And Weight Gain In Children With Juvenile Idiopathic Arthritis: Results From The Reacch-Out Cohort., Jaime Guzman, Tristan Kerr, Leanne M Ward, Jinhui Ma, Kiem Oen, Alan M Rosenberg, Brian M Feldman, Gilles Boire, Kristin Houghton, Paul Dancey, Rosie Scuccimarri, Alessandra Bruns, Adam M Huber, Karen Watanabe Duffy, Natalie J Shiff, Roberta A Berard, Deborah M Levy, Elizabeth Stringer, Kimberly Morishita, Nicole Johnson, David A Cabral, Maggie Larché, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne E Ramsey, Johannes Roth, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Shirley M L Tse, Roxana Bolaria, Katherine Gross, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Jean Dorval, Claire Leblanc, Claire St Cyr, Michele Gibbon, Rae S M Yeung, Ciarán M Duffy, Lori B Tucker

Paediatrics Publications

BACKGROUND: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.

METHODS: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth.

RESULTS: One thousand one hundred forty seven children …

A Reporter Mouse Model For In Vivo Tracing And In Vitro Molecular Studies Of Melanocytic Lineage Cells And Their Diseases, Melissa Crawford, Valerie Leclerc, Lina Dagnino

Paediatrics Publications

Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, and melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. …

Voluntary Running Exercise Protects Against Sepsis-Induced Early Inflammatory And Pro-Coagulant Responses In Aged Mice, Karel Tyml, Scott Swarbreck, Cynthia Pape, Dan Secor, James Koropatnick, Qingping Feng, Ruud A.W. Veldhuizen, Sean E. Gill

Paediatrics Publications

Background: Despite many animal studies and clinical trials, mortality in sepsis remains high. This may be due to the fact that most experimental studies of sepsis employ young animals, whereas the majority of septic patients are elderly (60 - 70 years). The objective of the present study was to examine the sepsis-induced inflammatory and pro-coagulant responses in aged mice. Since running exercise protects against a variety of diseases, we also examined the effect of voluntary running on septic responses in aged mice. Methods: Male C57BL/6 mice were housed in our institute from 2-3 to 22 months (an age mimicking that …

Heterozygous De Novo Ubtf Gain-Of-Function Variant Is Associated With Neurodegeneration In Childhood., Simon Edvardson, Claudia M Nicolae, Pankaj B Agrawal, Cyril Mignot, Katelyn Payne, Asuri Narayan Prasad, Chitra Prasad, Laurie Sadler, Caroline Nava, Thomas E Mullen, Amber Begtrup, Berivan Baskin, Zöe Powis, Avraham Shaag, Boris Keren, George-Lucian Moldovan, Orly Elpeleg

Paediatrics Publications

Ribosomal RNA (rRNA) is transcribed from rDNA by RNA polymerase I (Pol I) to produce the 45S precursor of the 28S, 5.8S, and 18S rRNA components of the ribosome. Two transcription factors have been defined for Pol I in mammals, the selectivity factor SL1, and the upstream binding transcription factor (UBF), which interacts with the upstream control element to facilitate the assembly of the transcription initiation complex including SL1 and Pol I. In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, we identified a heterozygous variant, c.628G>A in UBTF, encoding p.Glu210Lys in UBF, which …

Disruption Of Cdk-Resistant Chromatin Association By Prb Causes Dna Damage, Mitotic Errors, And Reduces Condensin Ii Recruitment, Charles A. Ishak, Courtney H. Coschi, Michael V. Roes, Frederick A. Dick

Paediatrics Publications

Organization of chromatin structure is indispensible to the maintenance of genome integrity. The retinoblastoma tumor suppressor protein (pRB) mediates both transcriptional repression and chromatin organization, but the independent contributions of these functions have been difficult to study. Here, we utilize a synthetic Rb1 mutant allele (F832A) that maintains pRB association at cell cycle gene promoters, but disrupts a cyclin-dependent kinase (CDK)-resistant interaction with E2F1 to reduce occupancy of pRB on intergenic chromatin. Reduced pRB chromatin association increases spontaneous γH2AX deposition and aneuploidy. Our data indicates that the CDK-resistant pRB-E2F1 scaffold recruits Condensin II to major satellite repeats to stabilize chromatin …

Choosing Wisely Canada: The Canadian College Of Medical Geneticists’ (Ccmg) List Of Five Items Physicians And Patients Should Question, Elaine Goh, Andrea Guerin, Joanna Lazier, Sharan Goobie, Tanya N. Nelson, Ron Agatep, Victoria Mok Siu, Yaren Y. Niederhoffer, Julie Richer

Paediatrics Publications

No abstract provided.

Nonsymbolic And Symbolic Magnitude Comparison Skills As Longitudinal Predictors Of Mathematical Achievement, Iro Xenidou-Dervou, Dylan Molenaar, Daniel Ansari, Menno Van Der Schoot, Ernest C.D.M. Van Lieshout

Paediatrics Publications

What developmental roles do nonsymbolic (e.g., dot arrays) and symbolic (i.e., Arabic numerals) magnitude comparison skills play in children's mathematics? We assessed a large sample in kindergarten, grade 1 and 2 on two well-known nonsymbolic and symbolic magnitude comparison measures. We also assessed children's initial IQ and developing Working Memory (WM) capacities. Results demonstrated that symbolic and nonsymbolic comparison had different developmental trajectories; the first underwent larger developmental improvements. Both skills were longitudinal predictors of children's future mathematical achievement above and beyond IQ and WM. Nonsymbolic comparison was moderately predictive only in kindergarten. Symbolic comparison, however, was a robust and …

The Economic Impact Of Workplace Wellness Programmes In Canada, J. C. Jacobs, E. Yaquian, S. M. Burke, M. Rouse, G. Zaric

Paediatrics Publications

Background The economic benefits of workplace wellness programmes (WWPs) are commonly cited as a reason for employers to implement such programmes; however, there is limited evidence outside of the US context exploring their economic impact. US evidence is less relevant in countries such as Canada with universal publicly funded health systems because of the lower potential employer savings from WWPs. Aims To conduct a systematic review of the Canadian literature investigating the economic impact of WWPs from an employer perspective. The quality of that evidence was also assessed. Methods We reviewed literature which included analyses of four economic outcomes: return …

Lessons From A Child, Paul Atkison

Paediatrics Publications

No abstract provided.

Brain Biomarkers And Pre-Injury Cognition Are Associated With Long-Term Cognitive Outcome In Children With Traumatic Brain Injury, Amy A Wilkinson, Maureen Dennis, Nevena Simic, Margot J Taylor, Benjamin R Morgan, Helena Frndova, Karen Choong, Craig Campbell, Douglas Fraser, Vicki Anderson, Anne-Marie Guerguerian, Russell Schachar, Jamie Hutchison

Paediatrics Publications

BACKGROUND: Children with traumatic brain injury (TBI) are frequently at risk of long-term impairments of attention and executive functioning but these problems are difficult to predict. Although deficits have been reported to vary with injury severity, age at injury and sex, prognostication of outcome remains imperfect at a patient-specific level. The objective of this proof of principle study was to evaluate a variety of patient variables, along with six brain-specific and inflammatory serum protein biomarkers, as predictors of long-term cognitive outcome following paediatric TBI.

METHOD: Outcome was assessed in 23 patients via parent-rated questionnaires related to attention deficit hyperactivity disorder …

The Effect Of Age On The Personality And Cognitive Characteristics Of Three Distinct Risky Driving Offender Groups, Thomas G. Brown, Marie Claude Ouimet, Manal Eldeb, Jacques Tremblay, Evelyn Vingilis, Louise Nadeau, Jens Pruessner, Antoine Bechara

Paediatrics Publications

Background We previously reported that in traffic offenders aged 19–39 years, different risky driving profiles were associated with unique personality, cognitive, and neurobiological characteristics. However, many of these characteristics evolve significantly with age. Secondary analysis on these data explored whether the characteristics associated with different risky driving profiles were influenced by driver age. Methods Data (N = 138) on three driving groups (i.e., alcohol impaired [DWI], reckless [SPEED], and impaired and reckless [MIXED]), and a low-risk control group [CTL] were stratified by age (younger: 19–28; older: 29–39). Younger and older drivers of each risky driving group were compared to their …

Comparing Very Low Birth Weight Versus Very Low Gestation Cohort Methods For Outcome Analysis Of High Risk Preterm Infants, Louise I.M. Koller-Smith, Prakesh S. Shah, Xiang Y. Ye, Gunnar Sjörs, Yueping A. Wang, Sharon S.W. Chow, Brian A. Darlow, Shoo K. Lee, Stellan Håkanson, Kei Lui, Peter Marshall, Paul Craven, Karen Simmer, Jacqueline Stack, David Knight, Andrew Watkins, Andrew Ramsden, Kenneth Tan, Kaye Bawden, Lyn Downe, Vjay Singde, Michael Stewart, Andrew Berry, Rod Hunt, Charles Kilburn, Peter Dargaville, Mary Paradisis, Nick Evans, Shelley Reid

Paediatrics Publications

Background: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. Method: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. Results: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and ≥32 weeks, AUC 0.50-0.65; ≥1500 g and <32 weeks, AUC 0.60-0.62). Conclusion: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking.

Maternal Nutrient Restriction In Guinea Pigs Leads To Fetal Growth Restriction With Evidence For Chronic Hypoxia, Alexander A. Elias, Yohei Maki, Brad Matushewski, Karen Nygard, Timothy R.H. Regnault, Bryan S. Richardson

Paediatrics Publications

BackgroundWe determined whether maternal nutrient restriction (MNR) in Guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).ResultsFGR-MNR fetuses were 36% smaller with asymmetrical growth restriction …

The Role Of Adverse Childhood Experiences As Determinants Of Non-Suicidal Self-Injury Among Children And Adolescents Referred To Community And Inpatient Mental Health Settings, Philip Baiden, Shannon L. Stewart, Barbara Fallon

Paediatrics Publications

The objectives of this study were to examine the prevalence of, and determine the effect of adverse childhood experiences on non-suicidal self-injury among children and adolescents referred to community and inpatient mental health settings. Data for this study were obtained from the interRAI Child and Youth Mental Health dataset. A total of 2038 children and adolescents aged 8–18 years (M = 12.49; SD = 2.88, 61.1% males) were analyzed. Binary logistic regression was fitted to identify predictors of non-suicidal self-injury as a function of adverse childhood experiences, depression, and social support while simultaneously controlling for age, gender, type of patient, …

An Increase In Immature Β-Cells Lacking Glut2 Precedes The Expansion Of Β-Cell Mass In The Pregnant Mouse, Christine A. Beamish, Linhao Zhang, Sandra K. Szlapinski, Brenda J. Strutt, David J. Hill

Paediatrics Publications

A compensatory increase in β-cell mass occurs during pregnancy to counter the associated insulin resistance, and a failure in adaptation is thought to contribute to gestational diabetes. Insulin-expressing but glucose-transporter-2-low (Ins+Glut2LO) progenitor cells are present in mouse and human pancreas, being predominantly located in extra-islet β-cell clusters, and contribute to the regeneration of the endocrine pancreas following induced ablation. We therefore sought to investigate the contribution of Ins+Glut2LO cells to β-cell mass expansion during pregnancy. Female C57Bl/6 mice were time mated and pancreata were collected at gestational days (GD) 6, 9, 12, 15, and 18, and postpartum D7 (n = …