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Background: Recent studies have reported increased prevalence for autism spectrum disorders in a number of geographical locations. Our objective was to determine the incidence and 1-year cohort prevalence for autism spectrum disorders in children less than 15 years of age and living in the Avalon Peninsula at the time of diagnosis. Methods: Retrospective and prospective data were obtained from the Janeway Children’s Health and Rehabilitation Centre (St. John’s), including the identification and specific diagnosis for all children assessed for autism spectrum disorder from 2006 to 2010. Additional clinic data were reviewed to update the data until the end of 2013. Results: From 2006 to 2010, 272 children had a diagnosis of autism spectrum disorder, averaging 54 new cases per year. The incidence of new cases increased from 10.1 to 16.7 cases per 10 000 per year from 2006 to 2010. At the end of 2013, the prevalence among children born in 2006 was 1 case of autism spectrum disorder per 46 children or 215.77 per 10 000. Interpretation: We found higher rates of autism spectrum disorder than previously reported for this population. The prevalence in this region is also high when compared with other global populations. The high rate of diagnosis supports the need for a provincial autism spectrum disorder registry and further research on autism spectrum disorder within this population.

Problem Giving and receiving honest and helpful feedback for leadership development is a common challenge in all types of organizations but particularly in academic medicine. Approach At Memorial University of Newfoundland, in 2014, a consensus emerged to develop a new method for evaluating the leadership performance of the discipline chairs, dean, and vice dean, and to provide these leaders with the evaluation results to help them improve their performance. The leaders responsible for developing and implementing this method (called the Memorial Method) decided to use a survey to obtain faculty members' perceptions about their leader's performance. Beginning in October 2014, a portion of several regular meetings of the discipline chairs with the dean and vice dean was used to develop the survey, by first discussing the broad dimensions of leadership performance, then discussing these dimensions in more detail and drafting specific questions. The resulting survey included 44 quantitative questions addressing eight leadership dimensions. In March-April 2015, the survey was administered electronically to full-time faculty members on a confidential basis. The results were compiled and reported to each discipline chair and to the dean and vice dean. Outcomes In total, 144/249 faculty responded to the survey (response rate: 58%). For the various dimensions, individual chairs' mean scores ranged from 2.82 to 4.70, and overall mean scores ranged from 3.57 to 4.24. Psychometric properties of the survey suggested it was both reliable and valid. Next steps The survey will be repeated, this time with part-time as well as full-time faculty included.

Background Recurrent microdeletions and microduplications of ∼555 kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioural features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited. Methods We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion positive 26-month-old female who has developmental delay (DD) and autistic features. Results Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. The mother of proband 3 has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (non-dysmorphic ASD female with a duplication) has two apparently healthy duplication positive relatives. Probands 1 and 2 have deletion negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence. Conclusions The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with non-specific major or minor dysmorphism. There are deletion positive ASD probands with a less severe phenotype than deletion negative ASD siblings underscoring the significant phenotypic heterogeneity.

Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 unbalanced CNVs in 44% of ASD families not present in 500 controls (and re-examined in another 1152 controls). Karyotyping detected additional balanced changes. Although most variants were inherited, we found a total of 27 cases with de novo alterations, and in three (11%) of these individuals, two or more new variants were observed. De novo CNVs were found in approximately 7% and approximately 2% of idiopathic families having one child, or two or more ASD siblings, respectively. We also detected 13 loci with recurrent/overlapping CNV in unrelated cases, and at these sites, deletions and duplications affecting the same gene(s) in different individuals and sometimes in asymptomatic carriers were also found. Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility. Our most compelling result discovered CNV at 16p11.2 (p = 0.002) (with characteristics of a genomic disorder) at approximately 1% frequency. Some of the ASD regions were also common to mental retardation loci. Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup.

Importance The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. Objective To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. Design, Setting, and Participants The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). Exposures All probands underwent CMA, with WES performed for 95 proband-parent trios. Main Outcomes and Measures The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Results Of 258 probands, 24 (9.3%, 95% CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95% CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. For CMA, the proportion of children with a positive test result was 7 of 168 (4.2%, 95% CI, 1.7%-8.4%) in the essential group, 4 of 37 (10.8%, 95% CI, 3.0%-25.4%) in the equivocal group, and 13 of 53 (24.5%, 95% CI, 13.8%-38.3%) in the complex group ( P P = .02). Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95% CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined molecular diagnostic yield was 6.3% (95% CI, 1.7%-15.2%) in the essential group (4/64 children), 28.6% (95% CI, 3.7%-71.0%) in the equivocal group (2/7 children), and 37.5% (95% CI, 18.8%-59.4%) in the complex group (9/24 children; 3-group comparison, P = .001). The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). Conclusions and Relevance Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.

Two patients with homocystinuria are discussed. Both patients presented with behavioural abnormalities and deficits in attention - symptoms that are frequently encountered in paediatric office practice. In both cases, the diagnosis of homocystinuria was not made at initial presentation. Subtle but definite phenotypic features eventually provided the first indication of homocystinuria between the ages of five to seven years. Laboratory screening confirmed homocystine in the urine, and elevated methionine and homocysteine plasma levels in both patients. Patients with inborn errors of metabolism such as homocystinuria are treated first by family physicians and paediatricians. Without a high index of suspicion, physicians can easily overlook a diagnosis of homocystinuria. The management of patients with homocystinuria continues to pose a challenge to physicians and care givers.

The rate of nitrogen formation during the thermal decomposition of azobenzene in static and stirred-flow systems was measured over the temperature range of 368.9 °C to 437.4 °C. The first order rate constant was found to be given by the expression[Formula: see text]A consideration of the equilibrium constant between cis-azobenzene and trans-azobenzenc, and the rate of attainment of equilibrium, leads to the conclusion that a small concentration of cis-azobenzene is always present, at equilibrium with the trans isomer. Since the cis isomer is likely to be more reactive than the trans isomer the rate constant cannot be ascribed to the trans isomer alone. No effect of variation of surface-to-volume ratio could be detected. Some preliminary experiments in which toluene and ethylene were employed as additives indicated that these did not affect the rate of formation of nitrogen. Nevertheless, because of a certain amount of scatter in the results, a small effect could not be excluded. There were at least nine products, in addition to nitrogen.