Taking On Tobacco: A Discussion with Dr. Andrew Pipe About His Career and The Ottawa Model for Smoking Cessation

 Dr. Andrew Pipe is chief of the division of Prevention and Rehabilitation at the University of Ottawa Heart Institute and Professor in the Faculty of Medicine at the University of Ottawa. He completed his medical training at Queen’s University, and interned at The Ottawa Hospital, beginning a career path which combined his interests in sports medicine, health promotion, and advocacy. He has been a physician for athletes at the international level, served on several sporting and anti-doping organizations, and is recognized as a leading expert on cardiovascular disease prevention, physical activity, and smoking cessation.   Dr Andrew Pipe est professeur à la Faculté de médecine à l’Université d’Ottawa et il est également responsable de la division de prévention et de réhabilitation à l’Institut de cardiologie de l’Université d’Ottawa. Dr Pipe a terminé son éducation à l’Université de Queen’s et son entrainement à l’Hôpital d’Ottawa où il a commencé sa carrière dans un domaine incluant la médecine sportive, la promotion de la santé et la défense des droits. Il a été médecin pour les athlètes au niveau international et il est reconnu comme un expert sur la prévention de maladies cardiovasculaires, sur l’activité physique, et sur la cessation du tabagisme

Parr sampling data

This is field-recorded data of the sex, maturity and measurements of 100 parr. Some parr were too small and could not be sexed in the field. Sampling occurred via electrofishing in collaboration with the Department of Fisheries and Oceans, St. John's, Newfoundland

Data from: Mature male parr contribution to the effective size of an anadromous Atlantic salmon (Salmo salar) population over 30 years

We describe temporal changes in the genetic composition of a small anadromous Atlantic salmon (Salmo salar) population from South Newfoundland, an area where salmon populations are considered threatened (COSEWIC 2010). We examined the genetic variability (13 microsatellite loci) in 869 out-migrating smolt and post-spawning kelt samples, collected from 1985 to 2011 for a total of 22 annual collections and a 30 year span of assigned cohorts. We estimated the annual effective number of breeders (Nb) and the generational effective population size (Ne) through genetic methods and demographically using the adult sex ratio. Comparisons between genetic and demographic estimates show that the adult spawners inadequately explain the observed Ne estimates, suggesting that mature male parr are significantly increasing Nb and Ne over the study period. Spawning as parr appears to be a viable and important strategy in the near absence of adult males

Ecological and Microsatellite data

This tab-delimited file contains all the allele scores for 869 samples across 13 microsatellites, along with the relevant demographic data

Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature

We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ

Early infantile epileptic encephalopathy due to biallelic pathogenic variants inPIGQ: Report of seven new subjects and review of the literature

We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelicPIGQvariants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtypePIGQcDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum ofPIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants inPIGQ

PLPHP deficiency:clinical, genetic, biochemical, and mechanistic insights

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery