Patient and Physician Factors Associated with First Diagnosis of Non-affective Psychotic Disorder in Primary Care

Primary care physicians play a central role in pathways to care for first-episode psychosis, and their increased involvement in early detection could improve service-related outcomes. The aim of this study was to estimate the proportion of psychosis first diagnosed in primary care, and identify associated patient and physician factors. We used linked health administrative data to construct a retrospective cohort of people aged 14-35 years with a first diagnosis of non-affective psychosis in Ontario, Canada between 2005-2015. We restricted the sample to patients with help-seeking contacts for mental health reasons in primary care in the six months prior to first diagnosis of psychotic disorder. We used modified Poisson regression models to examine patient and physician factors associated with a first diagnosis of psychosis in primary care. Among people with early psychosis (n = 39,449), 63% had help-seeking contacts in primary care within six months prior to first diagnosis. Of those patients, 47% were diagnosed in primary care and 53% in secondary/tertiary care. Patients factors associated with lower likelihood of diagnosis in primary care included male sex, younger age, immigrant status, and comorbid psychosocial conditions. Physician factors associated with lower likelihood of diagnosis in primary care included solo practice model, urban practice setting, international medical education, and longer time since graduation. Our findings indicate that primary care is an important contact for help-seeking and diagnosis for a large proportion of people with early psychosis. For physicians less likely to diagnose psychosis in primary care, targeted resources and interventions could be provided to support them in caring for patients with early psychosis

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

Variable Stars in Leo A: RR Lyraes, Short-period Cepheids, and Implications on Stellar Content

We present the results of a search for short-period variable stars in Leo A. We have found 92 candidate variables, including eight candidate RR Lyrae stars. From the RR Lyraes, we measure a distance modulus of (m-M)_0 = 24.51 +/- 0.12, or 0.80 +/- 0.04 Mpc. This discovery of RR Lyraes confirms, for the first time, the presence of an ancient (> ~11 Gyr) population in Leo A accounting for at least 0.1% of the galaxy's V luminosity. We have also discovered a halo of old (> ~2 Gyr) stars surrounding Leo A, with a scale length roughly 50% larger than that of the dominant young population. We also report the discovery of a large population of Cepheids in Leo A. The median absolute magnitude of our Cepheid sample is M_V = -1.1, fainter than 96% of SMC and 99% of LMC Cepheids. Their periods are also unusual, with three Cepheids that are deduced to be pulsating in the fundamental mode having periods of under 1 day. Upon examination, these characteristics of the Leo A Cepheid population appear to be a natural extension of the classical Cepheid period-luminosity relations to low metallicity, rather than being indicative of a large population of ``anomalous'' Cepheids. We demonstrate that the periods and luminosities are consistent with the expected values of low-metallicity blue helium-burning stars (BHeBs), which populate the instability strip at lower luminosities than do higher-metallicity BHeBs.Comment: 46 pages, 12 figures Accepted by A

Rare Variant Enrichment analysis Supports

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, onl

Rare Variant Enrichment Analysis Supports GREB1L as a Contributory Driver Gene in the Etiology of Mayer-Rokitansky-Küster-Hauser Syndrome

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was used to further reproduce GREB1L findings in diverse genetic backgrounds. Proband and OMIM phenotypes annotated using the Human Phenotype Ontology were analyzed to quantitatively delineate the phenotypic spectrum associated with GREB1L variant alleles found in our MRKH cohort and those previously published. This study reports 18 novel GREB1L variant alleles, 16 within a multiethnic MRKH cohort and two within a congenital scoliosis cohort. Cohort-wide analyses for a burden of rare variants within a single gene identified likely damaging variants in GREB1L (MIM: 617782), a known disease gene for renal hypoplasia and uterine abnormalities (MIM: 617805), in 16 of 590 MRKH probands. GREB1L variant alleles, including a CNV null allele, were found in 8 MRKH type 1 probands and 8 MRKH type II probands. This study used quantitative phenotypic analyses in a worldwide multiethnic cohort to identify and strengthen the association of GREB1L to isolated uterine agenesis (MRKH type I) and syndromic MRKH type II

Oligosaccharyltransferase Inhibition Induces Senescence in RTK-Driven Tumor Cells

Asparagine (N)-linked glycosylation is a protein modification critical for glycoprotein folding, stability, and cellular localization. To identify small molecules that inhibit new targets in this biosynthetic pathway, we initiated a cell-based high throughput screen and lead compound optimization campaign that delivered a cell permeable inhibitor (NGI-1). NGI-1 targets the oligosaccharyltransferase (OST), a hetero-oligomeric enzyme that exists in multiple isoforms and transfers oligosaccharides to recipient proteins. In non-small cell lung cancer cells NGI-1 blocks cell surface localization and signaling of the EGFR glycoprotein, but selectively arrests proliferation in only those cell lines that are dependent on EGFR (or FGFR) for survival. In these cell lines OST inhibition causes cell cycle arrest accompanied by induction of p21, autofluorescence, and changes in cell morphology; all hallmarks of senescence. These results identify OST inhibition as a potential therapeutic approach for treating receptor tyrosine kinase-dependent tumors and provides a chemical probe for reversibly regulating N-linked glycosylation in mammalian cells

Tackling health inequalities: moving theory to action

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement

Hexaploid oat ( L., 2 = 6 = 42) is a member of the Poaceae family and has a large genome (∼12.5 Gb) containing 21 chromosome pairs from three ancestral genomes. Physical rearrangements among parental genomes have hindered the development of linkage maps in this species. The objective of this work was to develop a single high-density consensus linkage map that is representative of the majority of commonly grown oat varieties. Data from a cDNA-derived single-nucleotide polymorphism (SNP) array and genotyping-by-sequencing (GBS) were collected from the progeny of 12 biparental recombinant inbred line populations derived from 19 parents representing oat germplasm cultivated primarily in North America. Linkage groups from all mapping populations were compared to identify 21 clusters of conserved collinearity. Linkage groups within each cluster were then merged into 21 consensus chromosomes, generating a framework consensus map of 7202 markers spanning 2843 cM. An additional 9678 markers were placed on this map with a lower degree of certainty. Assignment to physical chromosomes with high confidence was made for nine chromosomes. Comparison of homeologous regions among oat chromosomes and matches to orthologous regions of rice ( L.) reveal that the hexaploid oat genome has been highly rearranged relative to its ancestral diploid genomes as a result of frequent translocations among chromosomes. Heterogeneous chromosome rearrangements among populations were also evident, probably accounting for the failure of some linkage groups to match the consensus. This work contributes to a further understanding of the organization and evolution of hexaploid grass genomes

Resilient Pedagogy: Practical Teaching Strategies to Overcome Distance, Disruption, and Distraction

Resilient Pedagogy offers a comprehensive collection on the topics and issues surrounding resilient pedagogy framed in the context of the COVID-19 pandemic and the social justice movements that have swept the globe. As a collection, Resilient Pedagogy is a multi-disciplinary and multi-perspective response to actions taken in different classrooms, across different institution types, and from individuals in different institutional roles with the purpose of allowing readers to explore the topics to improve their own teaching practice and support their own students through distance, disruption, and distraction