The Canadian Institutes of Health Research (CIHR, French: Instituts de recherche en santé du Canada, IRSC) is the major federal agency responsible for funding health and medical research in Canada. It is the successor to the Medical Research Council of Canada. It aims to create new health knowledge and to translate that knowledge from the research setting into real world applications.CIHR supports more than 13,000 researchers and trainees through grants, fellowships, scholarships, and other funding, as part of the federal government's investment in health research. The peer review process is a vital part of CIHR. Review by panels of peers from the research community ensures that proposals approved for funding by CIHR meet internationally accepted standards of scientific excellence.CIHR combined with the Social Sciences and Humanities Research Council and the Natural Sciences and Engineering Research Council forms the major source of federal government funding to post-secondary research, and are collectively referred to as the "Tri-Council" or "Tri-Agency".
Comprehensive genomic testing in routine cancer care pathways has created the need to interpret the consequences of somatic (acquired) genomic variants beyond the currently well-characterised driver variants in cancer gene hotspots. While several guidelines have been published to determine the oncogenicity of somatic cancer gene variants, they lack a comprehensive and flexible approach that encompasses all available lines of evidence. Individual UK laboratories have developed local approaches to standardise somatic variant interpretation, often based on different sets of published guidelines, but a comprehensive national standardised framework is lacking. The absence of standardisation in approaches to somatic variant interpretation highlights a significant gap in the field of genomic medicine within the UK healthcare system. Key stakeholders from across the UK cancer genomics diagnostic community formed the UK Somatic Variant Interpretation Group (SVIG-UK) in September 2018 to develop a consensus approach for interpretation of somatic variants identified through genomic testing in patients with solid tumours and haematological malignancies. SVIG-UK scientists conducted a review of existing somatic variant interpretation classification systems and although they mostly agreed on evidence sources for variant interpretation, differences were identified in how the evidence should be used, weighted and combined. The SVIG-UK team subsequently developed a single, standardised UK-wide approach to somatic variant interpretation which encompassed both solid tumour and haematological cancer genomic testing. This framework was shared with stakeholders across the UK alongside variants for preliminary testing. Outcomes were then reviewed and following engagement sessions across the community, the variant interpretation recommendations were updated and ratified by the UK Association of Clinical Genomics Sciences. We present herein the SVIG-UK framework and recommendations, which provide a standardised, comprehensive and flexible approach for classifying the oncogenicity of somatic variants in cancer genes.
OBJECTIVE:To determine if newborns receiving morphine or methadone as the primary pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS) tolerate and receive fewer days of opioid using an accelerated wean protocol (15% decrements) compared with using a slower wean protocol (10% decrements). STUDY DESIGN:Newborns ≥36 weeks of gestation receiving morphine or methadone for NOWS were enrolled in a pragmatic blinded, randomized multicenter trial. Newborns underwent protocol-driven weaning with decreasing opioid doses of either 15% or 10% decrements. Weaning was encouraged every 24 hours, and if signs of NOWS worsened, the preceding dose was resumed. To maintain blinding, the last 3 dose levels of the 15% decrements were placebo. The primary outcome was the number of days of opioid treatment from the first weaning dose to cessation of opioids. RESULTS:Slow enrollment prompted early trial closure; 189 newborns were randomized, 98 (51.9%) to 15% decrements (mean ± SD, 38.8 ± 1.2 weeks gestation, 59.8% male) and 91 (48.1%) to 10% decrements (38.8 ± 1.3 weeks gestation, 61.5% male). Morphine was used most commonly. Intention-to-treat analysis included all but 4 infants withdrawn in the 15% decrement group. The durations of opioid treatment during weaning were 8.2 (7.2, 9.5) (adjusted mean [95% CI]) and 11.2 (9.7, 12.9) days for 15% and 10% decrement groups, respectively (P < .001). Adverse events were few in both groups. CONCLUSION:Pharmacologic treatment of NOWS using an accelerated wean protocol (15% decrements) was well tolerated with fewer days of opioid treatment compared with 10% decrements. TRIAL REGISTRATION:ClinicalTrials.gov number: NCT04214834.
Although autonomy-relevant parenting practices (solicitation, rule-setting, and psychological control) have been linked to adolescent disclosure, little is known about how these practices operate across cultural contexts. Existing studies often examined these practices in isolation or relied on cross-sectional designs, limiting understanding of their unique relations over time. This study examined these associations longitudinally across eight countries differing in average individualism and collectivism, focusing on the mediating role of adolescents’ perceptions of parental warmth, neglect, and overcontrol. Participants were 1,215 adolescents (50.3% girls) assessed at ages 13, 15, and 16. Perceived psychological control predicted greater perceived neglect and overcontrol, and perceived overcontrol, in turn, significantly predicted lower disclosure; this indirect effect was significant. Neither solicitation nor rule-setting predicted disclosure over time. However, when focusing only on voluntary disclosure (excluding secrecy items), solicitation predicted greater disclosure. Findings highlight the differential impact of parenting practices on disclosure over time, with psychological control as a risk factor and solicitation potentially facilitating disclosure depending on its measurement.
In this commentary, I discuss the history and legacy of Marc Lalonde’s ground-breaking report on health promotion and critically assess how far we have come in building a society that produces health, not sickness. In doing so, I will share the arc that I see between the Lalonde Report and our new Strategic Initiative at CIHR’s Institute of Population and Population Health (IPPH), Moving Upstream, which focuses on the structural determinants of health. I propose that Moving Upstream can help us move the needle on equitable health promotion research, policy, and practice in Canada, thus building on the foundation created by Lalonde. Dans ce commentaire, j'aborde l'histoire et l'héritage du rapport de Marc Lalonde sur la promotion de la santé, et j'évalue de manière critique les progrès accomplis dans l'édification d'une société axée sur la santé, et non sur la maladie. Ce faisant, je présenterai le lien que je vois entre le rapport Lalonde et notre nouvelle initiative stratégique à l'Institut de la santé et des populations (ISPP) des IRSC, «Agir en Amont», qui développe la recherche sur les déterminants structurels de la santé. Je propose que «Agir en Amont» puisse nous aider à faire progresser la recherche, les politiques et les pratiques en matière de promotion de la santé au Canada, en nous appuyant sur les bases posées par Lalonde.
Most neurons are embedded in multiple circuits, with signaling to distinct postsynaptic partners playing functionally different roles. The function of specific connections can be interrogated using synaptically localized optogenetic effectors; however, these tools are often experimentally difficult to validate or produce paradoxical outcomes. We have developed a system for photoablation of synaptic connections originating from genetically defined neurons based on presynaptic localization of the fluorogen-activating protein dL5** that acts as a photosensitizer when bound to a cell-permeable fluorogen dye. Using the well-mapped zebrafish escape circuit as a readout, we first show that cytoplasmically expressed dL5** enables efficient spatially targeted neuronal ablation using near-infrared light. We then demonstrate that spatially patterned illumination of presynaptically localized dL5** (syp-dL5) can effectively disconnect neurons from selected downstream partners, suppressing postsynaptic responses and producing precise behavioral deficits. This technique should be applicable to almost any genetically tractable neuronal circuit, enabling refined manipulation of functional connectivity within the nervous system.
