Are We Fulfilling the Promise of a Jesuit Education? A Group of Educators’ Reflective Examen

Higher education is often faced with external pressures that can guide the practice and offerings of colleges and universities. Graduate professional education in the health professions is especially prone to accreditation standards and its associated professional movements. At a Jesuit university, these external pressures, along with public pressure for job-ready graduates, must be intertwined with the history and the promise of a Jesuit education — that of transformation. As educators at a Jesuit university, our roles involve more than offering this kind of education. Our responsibility is to revisit what this promise means as a way of examining our practice. This article shares the reflective practice of five colleagues working in different roles at a Jesuit university seeking answers to questions of whether they are delivering on the promise of Jesuit education. The article includes a guiding set of questions, a short reflection on each author’s experience, and a review of the external and internal influences on their programs, providing a guide for a type of practice Examen that can be used by any faculty or staff member

ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.

ObjectiveWe aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations.MethodsPatients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features.ResultsA total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy.ConclusionsARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy

Chapter Globally Optimised Energy-Efficient Data Centres

A great deal of energy in Information and Communication Technology (ICT) systems can be wasted by software, regardless of how energy-efficient the underlying hardware is. To avoid such waste, programmers need to understand the energy consumption of programs during the development process rather than waiting to measure energy after deployment. Such understanding is hindered by the large conceptual gap from hardware, where energy is consumed, to high-level languages and programming abstractions. The approaches described in this chapter involve two main topics: energy modelling and energy analysis. The purpose of modelling is to attribute energy values to programming constructs, whether at the level of machine instructions, intermediate code or source code. Energy analysis involves inferring the energy consumption of a program from the program semantics along with an energy model. Finally, the chapter discusses how energy analysis and modelling techniques can be incorporated in software engineering tools, including existing compilers, to assist the energy-aware programmer to optimise the energy consumption of code

Association and Mutation Analyses of 16p11.2 Autism Candidate Genes

Background: Autism is a complex childhood neurodevelopmental disorder with a strong genetic basis. Microdeletion or duplication of a ∼500–700-kb genomic rearrangement on 16p11.2 that contains 24 genes represents the second most frequent chromosomal disorder associated with autism. The role of common and rare 16p11.2 sequence variants in autism etiology is unknown.Methodology/Principal Findings: To identify common 16p11.2 variants with a potential role in autism, we performed association studies using existing data generated from three microarray platforms: Affymetrix 5.0 (777 families), Illumina 550 K (943 families), and Affymetrix 500 K (60 families). No common variants were identified that were significantly associated with autism. To look for rare variants, we performed resequencing of coding and promoter regions for eight candidate genes selected based on their known expression patterns and functions. In total, we identified 26 novel variants in autism: 13 exonic (nine non-synonymous, three synonymous, and one untranslated region) and 13 promoter variants. We found a significant association between autism and a coding variant in the seizure-related gene SEZ6L2 (12/1106 autism vs. 3/1161 controls; p = 0.018). Sez6l2 expression in mouse embryos was restricted to the spinal cord and brain. SEZ6L2 expression in human fetal brain was highest in post-mitotic cortical layers, hippocampus, amygdala, and thalamus. Association analysis of SEZ6L2 in an independent sample set failed to replicate our initial findings.Conclusions/Significance: We have identified sequence variation in at least one candidate gene in 16p11.2 that may represent a novel genetic risk factor for autism. However, further studies are required to substantiate these preliminary findings.</p

Linkage of whole genome sequencing and administrative health data in autism: A proof of concept study

Whether genetic testing in autism can help understand longitudinal health outcomes and health service needs is unclear. The objective of this study was to determine whether carrying an autism-associated rare genetic variant is associated with differences in health system utilization by autistic children and youth. This retrospective cohort study examined 415 autistic children/youth who underwent genome sequencing and data collection through a translational neuroscience program (Province of Ontario Neurodevelopmental Disorders Network). Participant data were linked to provincial health administrative databases to identify historical health service utilization, health care costs, and complex chronic medical conditions during a 3-year period. Health administrative data were compared between participants with and without a rare genetic variant in at least 1 of 74 genes associated with autism. Participants with a rare variant impacting an autism-associated gene (n = 83, 20%) were less likely to have received psychiatric care (at least one psychiatrist visit: 19.3% vs. 34.3%, p = 0.01; outpatient mental health visit: 66% vs. 77%, p = 0.04). Health care costs were similar between groups (median: $5589 vs.$4938, p = 0.4) and genetic status was not associated with odds of being a high-cost participant (top 20%) in this cohort. There were no differences in the proportion with complex chronic medical conditions between those with and without an autism-associated genetic variant. Our study highlights the feasibility and potential value of genomic and health system data linkage to understand health service needs, disparities, and health trajectories in individuals with neurodevelopmental conditions

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Abstract Background Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. Methods We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. Results We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 × 10−03; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten “CNV positive” trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. Conclusions Our findings suggest that rare CNVs may contribute to the etiology of OCD.http://deepblue.lib.umich.edu/bitstream/2027.42/134675/1/11689_2016_Article_9170.pd

Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Globally, functional traits are weak predictors of juvenile tree growth, and we do not know why

1. Plant functional traits, in particular specific leaf area (SLA), wood density and seed mass, are often good predictors of individual tree growth rates within communities. Individuals and species with high SLA, low wood density and small seeds tend to have faster growth rates. 2. If community-level relationships between traits and growth have general predictive value, then similar relationships should also be observed in analyses that integrate across taxa, biogeographic regions and environments. Such global consistency would imply that traits could serve as valuable proxies for the complex suite of factors that determine growth rate, and, therefore, could underpin a new generation of robust dynamic vegetation models. Alternatively, growth rates may depend more strongly on the local environment or growth–trait relationships may vary along environmental gradients. 3. We tested these alternative hypotheses using data on 27 352 juvenile trees, representing 278 species from 27 sites on all forested continents, and extensive functional trait data, 38% of which were obtained at the same sites at which growth was assessed. Data on potential evapotranspiration (PET), which summarizes the joint ecological effects of temperature and precipitation, were obtained from a global data base. 4. We estimated size-standardized relative height growth rates (SGR) for all species, then related them to functional traits and PET using mixed-effect models for the fastest growing species and for all species together. 5. Both the mean and 95th percentile SGR were more strongly associated with functional traits than with PET. PET was unrelated to SGR at the global scale. SGR increased with increasing SLA and decreased with increasing wood density and seed mass, but these traits explained only 3.1% of the variation in SGR. SGR–trait relationships were consistently weak across families and biogeographic zones, and over a range of tree statures. Thus, the most widely studied functional traits in plant ecology were poor predictors of tree growth over large scales. 6. Synthesis. We conclude that these functional traits alone may be unsuitable for predicting growth of trees over broad scales. Determining the functional traits that predict vital rates under specific environmental conditions may generate more insight than a monolithic global relationship can offer

Molecular Characterization of NRXN1 Deletions from 19,263 Clinical Microarray Cases Identifies Exons Important for Neurodevelopmental Disease Expression

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P \u3c 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3\u27 end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5\u27 NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5\u27 end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61