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Perspectives on Indigenous cultural competency and safety in Canadian hospital emergency departments: a scoping review

Sherpa Romeo green journal. Permission to deposit author manuscriptBackground: Emergency departments are primary health care entry points for Indigenous persons in Canada. They are also among the settings where Indigenous patients report access barriers and discriminatory treatment. Cultural competency and cultural safety have been proposed as approaches to improving emergency care. Aim:To identify and elaborate upon barriers and facilitators of cultural competency and safety in Canadian Emergency Departments. Methods: We conducted a scoping review to search published and grey literature to identify and extract data on definitions, measures, facilitators and barriers of cultura lcompetency and safety. Results: Six articles met inclusion criteria. Studies presented perspectives from patients, care providers, health care organizations, and Indigenous knowledge holders. Key themes emerged across studies and stakeholders. These include: Interpersonal relationships between patients and care providers; cultural competency training; Emergency Department capacity; and racism and discrimination. Conclusion: We recommend that Emergency Department cultural competency and safety initiatives i) be built up on post-colonial understanding and partnerships with local Indigenous communities ii) provide practitioners with competencie sin relationship-building and self-awareness iii) orient ED resources and services to meet the needs of patients with limited access to non-emergency health care and iv) aim to prevent discrimination.Ye

CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the {\beta}-globin locus

The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the 3-dimensional folding of a 1 Mbp region of human chromosome 11 containing the {\beta}-globin genes by integrating looping interactions of the insulator protein CTCF determined comprehensively by chromosome conformation capture (3C) into a polymer model of chromatin. We find that CTCF-mediated cell type specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the {\beta}-globin locus control region (LCR) and genes. In these cells, the modeled {\beta}-globin domain folds into a globule with the LCR and the active globin genes on the periphery. By contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact positioning of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.Comment: Full article, including Supp. Mat., is available at Nucleic Acids Research, doi: 10.1093/nar/gks53

PATH-38. ROSETTE-FORMING GLIONEURONAL TUMOR IS DEFINED BY FGFR1 ACTIVATING ALTERATIONS WITH FREQUENT ACCOMPANYING PI3K AND MAPK PATHWAY MUTATIONS

Abstract BACKGROUND Rosette-forming glioneuronal tumor (RGNT) is an uncommon CNS tumor originally described in the fourth ventricle characterized by a low-grade glial neoplasm admixed with a rosette-forming neurocytic component. METHODS We reviewed clinicopathologic features of 42 patients with RGNT. Targeted next-generation sequencing was performed, and genome-wide methylation profiling is underway. RESULTS The 20 male and 22 female patients had a mean age of 25 years (range 3–47) at time of diagnosis. Tumors were located within or adjacent to the lateral ventricle (n=16), fourth ventricle (15), third ventricle (9), and spinal cord (2). All 31 tumors assessed to date contained FGFR1 activating alterations, either in-frame gene fusion, kinase domain tandem duplication, or hotspot missense mutation in the kinase domain (p.N546 or p.K656). While 7 of these 31 tumors harbored FGFR1 alterations as the solitary pathogenic event, 24 contained additional pathogenic alterations within PI3-kinase or MAP kinase pathway genes: 5 with additional PIK3CA and NF1 mutations, 4 with PIK3CA mutation, 3 with PIK3R1 mutation (one of which also contained focal RAF1 amplification), 5 with PTPN11 mutation (one with additional PIK3R1 mutation), and 2 with NF1 deletion. The other 5 cases demonstrated anaplastic features including hypercellularity and increased mitotic activity. Among these anaplastic cases, 3 harbored inactivating ATRX mutations and two harbored CDKN2A homozygous deletion, in addition to the FGFR1 alterations plus other PI3-kinase and MAP kinase gene mutations seen in those RGNT without anaplasia. CONCLUSION Independent of ventricular location, RGNT is defined by FGFR1 activating mutations or rearrangements, which are frequently accompanied by mutations involving PIK3CA, PIK3R1, PTPN11, NF1, and KRAS. Whereas pilocytic astrocytoma and ganglioglioma are characterized by solitary activating MAP kinase pathway alterations (e.g. BRAF fusion or mutation), RGNT are genetically more complex with dual PI3K-Akt-mTOR and Ras-Raf-MAPK pathway activation. Rare anaplastic examples may show additional ATRX and/or CDKN2A inactivation

Association of pregnancy complications/risk factors with the development of future long-term health conditions in women : overarching protocol for umbrella reviews

Acknowledgments Patient representatives and MuM-PreDiCT team. Funding This work was funded by the Strategic Priority Fund 'Tackling multimorbidity at scale' programme (grant number-MR/W014432/1) delivered by the Medical Research Council and the National Institute for Health and Care Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council.Peer reviewedPublisher PD

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

The Suspected CANcer (SCAN) pathway::protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer

Introduction Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of ‘low-risk but not no-risk’ cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England’s cancer survival rates through establishing effective routes to early diagnosis. Methods and analysis To evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys. Ethics and dissemination The Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences