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Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression., (© 2024. The Author(s).)

Forests harbor extensive biodiversity and act as a strong global carbon and nitrogen sink. Although enhancing tree diversity has been shown to mitigate climate change by sequestering more carbon and nitrogen in biomass and soils in manipulative experiments, it is still unknown how varying environmental gradients, such as gradients in resource availability, mediate the effects of tree diversity on carbon and nitrogen accrual in natural forests. Here, we use Canada's National Forest Inventory data to explore how the relationships between tree diversity and the accumulation of carbon and nitrogen in tree biomass and soils vary with resource availability and environmental stressors in natural forests. We find that the positive relationship between tree functional diversity (rather than species richness) and the accumulation of carbon in tree biomass strengthens with increasing light and soil nutrient availability. Moreover, the positive relationship between tree functional diversity and the accumulation of carbon and nitrogen in both organic and mineral soil horizons is more pronounced at sites with greater water and nutrient availabilities. Our results highlight that conserving and promoting functionally diverse forests in resource-rich environments could play a greater role than in resource-poor environments in enhancing carbon and nitrogen sequestration in Canada's forests., (© 2024. The Author(s).)

Objective: Multimorbidity is recognized as a serious health condition faced by a majority of older adults. Research investigating adaptive responses to multimorbidity, termed multimorbidity resilience, has been growing. This paper examines protective and risk factors, with a focus on health behaviours, socio-economic resources, and social support using an established measure of resilience (Connor-Davidson Resilience Scale) among older adults, focusing on older persons with two or more concurrent chronic conditions., Methods: Using Baseline (2011-2015), Follow-up One (2015-2018), and Follow-up Two (2018-2021) data from the Comprehensive Cohort of the Canadian Longitudinal Study on Aging, we tested hypotheses using 13,064 participants aged 65 years and older, who completed all waves and reported two or more of 27 chronic conditions, for the full sample of multimorbid individuals and three multimorbidity clusters: Cardiovascular/Metabolic, Musculoskeletal, and Mental Health. Associations between protective and risk factors and resilience were examined using linear regression to model the Connor-Davidson resilience scale, adjusting for illness context and social determinants of health., Results: Among all multimorbid individuals, the strongest associations with resilience were found for higher self-rated health, greater sleep satisfaction, better appetite, higher household income, more relatives and friends, being overweight (compared to normal weight), fewer housing problems, and fewer skipped meals. Weaker associations were found for non-smokers, less alcohol consumption, less pain, sedentary behaviour, being non-married (compared to married), and among Canadian born (compared to foreign). The analyses for the three multimorbidity clusters were largely replicated for the three multimorbidity clusters, but with some nuances depending on the cluster., Discussion: This research provides confirmatory evidence for several protective and risk factors affecting the ability to cope and recover from multimorbidity adversity among older adults. There are consistent patterns for the multimorbidity disease clusters, but some distinct relationships arise that are worthy of attention. The implications of the findings for modifiable health behaviours and socio-economic factors are discussed for their public health and clinical relevance., (© 2024. The Author(s).)

Objectives: This study aims to assess the current state of advanced pediatric emergency medicine (PEM) point-of-care ultrasound (POCUS) training in North America, including trends in dedicated PEM POCUS fellowships and alternative advanced POCUS training pathways, to better guide future educational efforts within the field., Methods: We identified and surveyed 22 PEM POCUS fellowship directors across the United States and Canada regarding PEM POCUS fellowship application trends, potential barriers to pursuing additional POCUS training, and novel training models that meet the needs of the PEM POCUS workforce., Results: The past 5 years have seen a growth in both PEM POCUS fellowship program number and trainee positions available, with a general impression by fellowship directors of a high demand for faculty who have these training credentials. However, there was a discordant drop in fellowship applicants and corresponding match rate in 2022, the cause of which is not clear. A number of programs are offering alternative advanced training options including combined PEM/POCUS fellowships and POCUS tracks within PEM fellowship., Conclusion: As POCUS use within PEM evolves, a growing number of advanced training options are being developed. Understanding the motivations and barriers for pursuing advanced POCUS training can help to shape these options going forward, to ensure the experience incorporated within each model meets the needs of trainees, the needs of PEM divisions, and the future needs of our field., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Unnecessary diagnostic tests and treatments in children cared for in emergency departments (EDs) do not benefit patients, increase costs, and may result in harm. To address this low-value care, a taskforce of pediatric emergency medicine (PEM) physicians was formed to create the first PEM Choosing Wisely recommendations. Using a systematic, iterative process, the taskforce collected suggested items from an interprofessional group of 33 ED clinicians from 6 academic pediatric EDs. An initial review of 219 suggested items yielded 72 unique items. Taskforce members independently scored each item for its extent of overuse, strength of evidence, and potential for harm. The 25 highest-rated items were sent in an electronic survey to all 89 members of the American Academy of Pediatrics PEM Committee on Quality Transformation (AAP COQT) to select their top ten recommendations. The AAP COQT survey had a 63% response rate. The five most selected items were circulated to over 100 stakeholder and specialty groups (within the AAP, CW Canada, and CW USA organizations) for review, iterative feedback, and approval. The final 5 items were simultaneously published by Choosing Wisely United States and Choosing Wisely Canada on December 1, 2022. All recommendations focused on decreasing diagnostic testing related to respiratory conditions, medical clearance for psychiatric conditions, seizures, constipation, and viral respiratory tract infections. A multinational PEM taskforce developed the first Choosing Wisely recommendation list for pediatric patients in the ED setting. Future activities will include dissemination efforts and interventions to improve the quality and value of care specific to recommendations., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Placement of a ventricular assist device (VAD) improves outcomes in children with advanced heart failure, but adverse events remain important consequences. Preoperative mechanical ventilation (MV) increases mortality, but it is unknown what impact prolonged postoperative MV has., Design: Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Cardiac Critical Care Consortium (PC 4 ) registries were used to identify and link children with initial VAD placement admitted to the cardiac ICU (CICU) from August 2014 to July 2020. Demographics, cardiac diagnosis, preoperative and postoperative CICU courses, and outcomes were compiled. Univariable and multivariable statistics assessed association of patient factors with prolonged postoperative MV. Multivariable logistic regression sought independent associations with outcomes., Setting: Thirty-five pediatric CICUs across the United States and Canada., Patients: Children on VADs included in both registries., Interventions: None., Measurements and Main Results: Two hundred forty-eight ACTION subjects were linked to a matching patient in PC 4 . Median (interquartile) age 7.7 years (1.5-15.5 yr), weight 21.3 kg (9.1-58 kg), and 56% male. Primary diagnosis was congenital heart disease (CHD) in 35%. Pre-VAD explanatory variables independently associated with prolonged postoperative MV included: age (incidence rate ratio [IRR], 0.95; 95% CI, 0.93-0.96; p < 0.01); preoperative MV within 48 hours (IRR, 2.76; 95% CI, 1.59-4.79; p < 0.01), 2-7 days (IRR, 1.82; 95% CI, 1.15-2.89; p = 0.011), and greater than 7 days before VAD implant (IRR, 2.35; 95% CI, 1.62-3.4; p < 0.01); and CHD (IRR, 1.96; 95% CI, 1.48-2.59; p < 0.01). Each additional day of postoperative MV was associated with greater odds of mortality (odds ratio [OR], 1.09 per day; p < 0.01) in the full cohort. We identified an associated greater odds of mortality in the 102 patients with intracorporeal devices (OR, 1.24; 95% CI, 1.04-1.48; p = 0.014), but not paracorporeal devices (77 patients; OR, 1.04; 95% CI, 0.99-1.09; p = 0.115)., Conclusions: Prolonged MV after VAD placement is associated with greater odds of mortality in intracorporeal devices, which may indicate inadequacy of cardiopulmonary support in this group. This linkage provides a platform for future analyses in this population., Competing Interests: Drs. Rosenthal and Lorts received funding from Abiomed. Dr. Rosenthal disclosed that he is Chair of Data and Safety Monitoring Board for Berlin Heart Active Driver Study. Dr. Lorts received funding from Abbott, Medtronic, Syncardia, and Bayer; her institution received funding from Berlin Heart. Dr. Zafar received funding from TransMedics. Dr. Zhang disclosed work for hire. Dr. VanderPluym received funding from Merck and AstraZeneca. Dr. Schumacher disclosed that his institution houses the Pediatric Cardiac Critical Care Consortium (PC 4 ) data coordinating center, which is partially funded by the PC 4 consortium and that he is the director of the data coordinating center and task force leader for an Advanced Cardiac Therapies Improving Outcomes Network workgroup; he disclosed off-label use of ventricular assist devices. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Chronic stress is an important risk factor in the development of obesity. While research suggests chronic stress is linked to excess weight gain in children, the biological or behavioral mechanisms are poorly understood., Objective: The objectives of the Family Stress Study are to examine behavioral and biological pathways through which chronic stress exposure (including stress from COVID-19) may be associated with adiposity in young children, and to determine if factors such as child sex, caregiver-child relationship quality, caregiver education, and caregiver self-regulation moderate the association between chronic stress and child adiposity., Methods: The Family Stress Study is a prospective cohort study of families recruited from 2 Canadian sites: the University of Guelph in Guelph, Ontario, and McMaster University in Hamilton, Ontario. Participants will be observed for 2 years and were eligible to participate if they had at least one child (aged 2-6 years) and no plans to move from the area within the next 3 years. Study questionnaires and measures were completed remotely at baseline and will be assessed using the same methods at 1- and 2-year follow-ups. At each time point, caregivers measure and report their child's height, weight, and waist circumference, collect a hair sample for cortisol analysis, and fit their child with an activity monitor to assess the child's physical activity and sleep. Caregivers also complete a web-based health and behaviors survey with questions about family demographics, family stress, their own weight-related behaviors, and their child's mental health, as well as a 1-day dietary assessment for their child., Results: Enrollment for this study was completed in December 2021. The final second-year follow-up was completed in April 2024. This study's sample includes 359 families (359 children, 359 female caregivers, and 179 male caregivers). The children's mean (SD) age is 3.9 years (1.2 years) and 51% (n=182) are female. Approximately 74% (n=263) of children and 80% (n=431) of caregivers identify as White. Approximately 34% (n=184) of caregivers have a college diploma or less and nearly 93% (n=499) are married or cohabiting with a partner. Nearly half (n=172, 47%) of the families have an annual household income ≥CAD $100,000 (an average exchange rate of 1 CAD=0.737626 USD applies). Data cleaning and analysis are ongoing as of manuscript publication., Conclusions: Despite public health restrictions from COVID-19, the Family Stress Study was successful in recruiting and using remote data collection to successfully engage families in this study. The results from this study will help identify the direction and relative contributions of the biological and behavioral pathways linking chronic stress and adiposity. These findings will aid in the development of effective interventions designed to modify these pathways and reduce obesity risk in children., Trial Registration: ClinicalTrials.gov NCT05534711; https://clinicaltrials.gov/study/NCT05534711., International Registered Report Identifier (irrid): DERR1-10.2196/48549., (©Shannon M Pare, Elizabeth Gunn, Katherine M Morrison, Alison L Miller, Alison M Duncan, Andrea C Buchholz, David W L Ma, Paul F Tremblay, Lori Ann Vallis, Nicola J Mercer, Jess Haines. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 20.06.2024.)

Background: Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk., Methods: We collected serum samples from 289 adult female participants in a 2018-2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography-tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics., Results: 17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among "White" participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than "White". Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status., Conclusions: We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS., (© 2024. Crown.)

Rapid climate change is altering Arctic ecosystems at unprecedented rates. These changes in the physical environment may open new corridors for species range expansions, with substantial implications for subsistence-dependent communities and sensitive ecosystems. Over the past 20 years, rising incidental harvest of Pacific salmon by subsistence fishers has been monitored across a widening range spanning multiple land claim jurisdictions in Arctic Canada. In this study, we connect Indigenous and scientific knowledges to explore potential oceanographic mechanisms facilitating this ongoing northward expansion of Pacific salmon into the western Canadian Arctic. A regression analysis was used to reveal and characterize a two-part mechanism related to thermal and sea-ice conditions in the Chukchi and Beaufort seas that explains nearly all of the variation in the relative abundance of salmon observed within this region. The results indicate that warmer late-spring temperatures in a Chukchi Sea watch-zone and persistent, suitable summer thermal conditions in a Beaufort Sea watch-zone together create a range-expansion corridor and are associated with higher salmon occurrences in subsistence harvests. Furthermore, there is a body of knowledge to suggest that these conditions, and consequently the presence and abundance of Pacific salmon, will become more persistent in the coming decades. Our collaborative approach positions us to document, explore, and explain mechanisms driving changes in fish biodiversity that have the potential to, or are already affecting, Indigenous rights-holders in a rapidly warming Arctic., (Global Change Biology© 2024 His Majesty the King in Right of Canada and The Author(s). Global Change Biology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Fisheries and Oceans Canada.)

Objectives: We aimed to define and map subcompetencies required for pediatric cardiac critical care (PCCC) fellowship education and training under the auspices of the Pediatric Cardiac Intensive Care Society (PCICS). We used the 2022 frameworks for PCCC fellowship learning objectives by Tabbutt et al and for entrustable professional activities (EPAs) by Werho et al and integrated new subcompetencies to the EPAs. This complementary update serves to provide a foundation for standardized trainee assessment tools for PCCC., Design: A volunteer panel of ten PCICS members who are fellowship education program directors in cardiac critical care used a modified Delphi method to develop the update and additions to the EPA-based curriculum. In this process, the experts rated information independently, and repetitively after feedback, before reaching consensus. The agreed new EPAs were later reviewed and unanimously accepted by all PCICS program directors in PCCC in the United States and Canada and were endorsed by the PCICS in 2023., Procedure and Main Results: The procedure for defining new subcompetencies to the established EPAs comprised six consecutive steps: 1) literature search; 2) selection of key subcompetencies and curricular components; 3) written questionnaire; 4) consensus meeting and critical evaluation; 5) approval by curriculum developers; and 6) PCICS presentation and endorsement. Overall, 110 subcompetencies from six core-competency domains were mapped to nine EPAs with defined levels of entrustment and examples of simple and complex cases. To facilitate clarity and develop a future assessment tool, three EPAs were subcategorized with subcompetencies mapped to the appropriate subcategory. The latter covering common procedures in the cardiac ICU., Conclusions: This represents the 2023 update to the PCCC fellowship education and training EPAs with the defining and mapping of 110 subcompetencies to the nine established 2022 EPAs. This goal of this update is to serve as the next step in the integration of EPAs into a standardized competency-based assessment framework for trainees in PCCC., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: We previously described derivation and validation of the emergency department trigger tool (EDTT) for adverse event (AE) detection. As the first step in our multicenter study of the tool, we validated our computerized screen for triggers against manual review, establishing our use of this automated process for selecting records to review for AEs., Methods: This is a retrospective observational study of visits to three urban, academic EDs over 18 months by patients ≥ 18 years old. We reviewed 912 records: 852 with at least one of 34 triggers found by the query and 60 records with none. Two first-level reviewers per site each manually screened for triggers. After completion, computerized query results were revealed, and reviewers could revise their findings. Second-level reviewers arbitrated discrepancies. We compare automated versus manual screening by positive and negative predictive values (PPVs, NPVs), present population trigger frequencies, proportions of records triggered, and how often manual ratings were changed to conform with the query., Results: Trigger frequencies ranged from common (>25%) to rare (1/1000) were comparable at U.S. sites and slightly lower at the Canadian site. Proportions of triggered records ranged from 31% to 49.4%. Overall query PPV was 95.4%; NPV was 99.2%. PPVs for individual trigger queries exceeded 90% for 28-31 triggers/site and NPVs were >90% for all but three triggers at one site. Inter-rater reliability was excellent, with disagreement on manual screening results less than 5% of the time. Overall, reviewers amended their findings 1.5% of the time when discordant with query findings, more often when the query was positive than when negative (47% vs. 23%)., Conclusions: The EDTT trigger query performed very well compared to manual review. With some expected variability, trigger frequencies were similar across sites and proportions of triggered records ranged 31%-49%. This demonstrates the feasibility and generalizability of implementing the EDTT query, providing a solid foundation for testing the triggers' utility in detecting AEs., (© 2024 Society for Academic Emergency Medicine.)

Competing Interests: Competing interests: None declared.

Background: Leading digit bias is a heuristic whereby humans overemphasize the left-most digit when evaluating numbers (e.g., 9.99 vs. 10.00). The bias might affect the interpretation of hemoglobin results and influence red cell transfusion in hospitalized patients., Study Design and Methods: Adults who received a red cell transfusion while registered at the University Health Network (Toronto, Canada) between January 1, 2016 and January 1, 2022 (n = 6 years) were included. The primary analysis excluded apheresis, red cell disorders, radiology suites, and operating rooms. The primary comparison was a regression discontinuity analysis of transfusion occurrence above and below the hemoglobin threshold of 79 g/L (local units). Additional analyses tested other leading digit and control thresholds (71, 81, and 91 g/L). Secondary analyses explored temporal covariates and clinical subgroups., Results: A total of 211,872 red cell transfusions were identified over the study period (median pre-transfusion hemoglobin 76 g/L; interquartile range = 69-92 g/L), with 107,790 inpatient transfusions in the primary analysis. The 79 g/L threshold showed 815 fewer red cell units above the threshold (95% confidence interval [CI]: -1215 to -415). The 69 g/L threshold showed 2813 fewer transfused units (95% CI: -4407 to -1220), and 89 g/L showed 40 fewer units (95% CI: -408 to 328). The effect was accentuated during daytime, weekday, and May-June months, persisted in analyses including all transfusions, and was absent at control thresholds., Conclusion: Leading digit bias might have a modest influence on the decision to transfuse red cells. The findings may inform practice guidelines and quasi-experimental study design in transfusion research., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Purpose: This article is prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee and provides educators recommendations for optimizing inclusive education for our students with disabilities. Medical educators are increasingly encountering students with disabilities and have the responsibility of ensuring requirements are met., Method: Medical education committee members from the US and Canada reviewed the literature on disabilities in medical student education to identify best practices and key discussion points. An iterative review process was used to determine the contents of an informative paper., Results: Medical schools are required to develop technical standards for admission, retention, and graduation of their students to practice medicine safely and effectively with reasonable accommodation. A review of the literature and obstetrics and gynecology expert opinion formed a practical list of accommodation strategies and administrative steps to assist educators and students., Conclusion: Medical schools must support the inclusion of students with disabilities. We recommend a collaborative approach to the interactive process of determining reasonable and effective accommodations that includes the students, a disability resource professional and faculty as needed. Recruiting and supporting medical students with a disability strengthens the diversity commitment and creates a more inclusive workforce.

Objectives: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps., Design: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS., Setting: British Columbia, Ontario and Quebec, Canada., Participants: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers., Results: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV., Conclusions: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the swift governments' response to the COVID-19 pandemic, there remains a paucity of literature assessing the degree to which; priority setting (PS) was included in the pandemic plans and the pandemic plans were publicly accessible. This paper reflects on the methods employed in a global comparative analysis of the degree to which countries integrated PS into their COVID-19 pandemic plans based on Kapiriri & Martin's framework. We also assessed if the accessibility of the plans was related to the country's transparency index., Methods: Through a three stage search strategy, we accessed and reviewed 86 national COVID-19 pandemic plans (and 11 Canadian provinces and territories). Secondary analysis assessed any alignment between the readily accessible plans and the country's transparency index., Results and Conclusion: 71 national plans were readily accessible while 43 were not. There were no systematic differences between the countries whose plans were readily available and those whose plans were 'missing'. However, most of the countries with 'missing' plans tended to have a low transparency index. The framework was adapted to the pandemic context by adding a parameter on the need to plan for continuity of priority routine services. While document review may be the most feasible and appropriate approach to conducting policy analysis during health emergencies, interviews and follow up document review would assess policy implementation., Competing Interests: Declaration of competing interest We declare no conflict., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6 , and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1 ), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample., Methods: A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n  = 91), while responders continued ESC (i.e., ESC-Only, n  = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models., Results: In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F (2,54) = 8.00, p  < 0.001, q  = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF ( r  = -0.42, p  = 0.004, q  = 0.034) and SS ( r  = -0.43, p  = 0.003, q  = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction ( r  = -0.39, p  = 0.009, q  = 0.052)., Conclusions: CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation., Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy., Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium., Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508)., Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage., Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52])., Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

This perspective identifies harmful phrasing and frames in current clinician and researcher work relating to immigrant health and provides equity-centered alternatives. Recommendations are organized within two broad categories, one focused on shifting terminology toward more humanizing language and the second focused on changing frames around immigration discourse. With regards to shifting terminology, this includes: 1) avoiding language that conflates immigrants with criminality (i.e., "illegal"); 2) using person-first language (i.e., "person applying for asylum" or "detained person" rather than "asylum-seeker" or "detainee"); 3) avoiding comparisons to "native" populations to mean non-foreign-born populations, as this contributes to the erasure of Native Americans and indigenous people; 4) avoiding hyperbolic and stigmatizing "crisis" language about immigrants; and 5) understanding inherent limitations of terms like "refugee," "asylum seeker," "undocumented" that are legal not clinical terms. With regards to challenging dominant frames, recommendations include: 6) avoiding problematization of certain borders compared to others (i.e., U.S.-Mexico versus U.S.- Canada border) that contributes to selectively subjecting people to heightened surveillance; 7) recognizing the heterogeneity among immigrants, such as varying reasons for migration along a continuum of agency, ranging from voluntary to involuntary; 8) avoiding setting up a refugee vs. migrant dichotomy, such that only the former is worthy of sympathy; and 9) representing mistrust among immigrants as justified, instead shifting focus to clinicians, researchers, and healthcare systems who must build or rebuild trustworthiness. Ensuring inclusive and humanizing language use and frames is one critical dimension of striving for immigrant health equity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Woolly mammoths in mainland Alaska overlapped with the region's first people for at least a millennium. However, it is unclear how mammoths used the space shared with people. Here, we use detailed isotopic analyses of a female mammoth tusk found in a 14,000-year-old archaeological site to show that she moved ~1000 kilometers from northwestern Canada to inhabit an area with the highest density of early archaeological sites in interior Alaska until her death. DNA from the tusk and other local contemporaneous archaeological mammoth remains revealed that multiple mammoth herds congregated in this region. Early Alaskans seem to have structured their settlements partly based on mammoth prevalence and made use of mammoths for raw materials and likely food.

Background: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the postoperative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology to tailor each patient's therapeutic needs. To date, there is no validated French-Canadian questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in Canadian French., Methods: A 3-phased approach was used. Phase 1: The NDII was translated from English to Canadian French using a "forward and backward" translational technique following international guidelines. Phase 2: A cognitive debriefing session was held with 10 Canadian French-speaking otolaryngology patients to evaluate understandability and acceptability. Phase 3: The final version was administered prospectively to 30 patients with prior history of ND and 30 control patients. These patients were asked to complete the questionnaire 2 weeks after their first response. Test-retest reliability was calculated with Spearman's correlation. Internal consistency was elicited using Cronbach's alpha., Results: NDII was successfully translated and validated to Canadian French. Cronbach's alpha revealed high internal consistency (0.92, lower 95% confidence limit 0.89). The correlation for test-retest validity were strong or very strong (0.61-0.91)., Conclusion: NDII is an internationally recognized QoL tool for the identification of ND-related impairments. This validated Canadian French version will allow clinicians to adequately assess the surgery-related QoL effect of neck surgery in the French-speaking population, while allowing French institutions to conduct and/or participate in multisite clinical trials requiring the NDII as an outcome measure., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT)., Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID)., Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late)., Results: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001)., Conclusion: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID., (Copyright © 2023. Published by Elsevier Inc.)

Background: HIV prevalence data among transgender (trans) people are not routinely collected in national estimates, including Canada, contributing to gender-based inequities. We examined HIV prevalence and associated factors among trans women in clinical care in two large Canadian cities., Methods: Retrospective chart data of trans women aged 16+ were collected from six family medicine and/or HIV clinics in Montreal and Toronto, Canada, 2018-2019. Multinomial logistic regression was used to analyze factors associated with documented HIV positive or missing HIV status relative to documented HIV negative status., Results: Among 1,059 patients, 7.5% were HIV positive, 54.4% HIV negative, and 38.1% missing HIV data. Findings showed lower odds of being HIV positive for those <30 years or 30-50 years (vs. >50 years); higher odds were seen for those: of Black race/ethnicity (vs. white), landed immigrant or refugee (vs. Canadian citizen), receiving social assistance (vs. not), and whom ever having used recreational drugs., Conclusions: Albeit high, the prevalence of HIV was lower than expected based on global estimates. Missing HIV status data suggest gaps in testing. Findings highlight socioeconomic and clinical realities among trans women in Canada and inform future HIV prevention and support., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Mostafa Shokoohi is now an employee at Eversana. The remaining authors have no conflicts of interest to disclose.

Objectives: The public health impact of nicotine vaping products (NVPs) is subject to complex transitions between NVP and cigarette use. To circumvent the data limitations and parameter instability challenges in modeling transitions, we indirectly estimate NVPs' impact on smoking prevalence and resulting smoking-attributable deaths using the SimSmoke simulation model., Methods: Canada SimSmoke uses age- and sex-specific data on Canadian population, smoking prevalence and tobacco control policies. The model incorporates the impact of cigarette-oriented policies on smoking prevalence but not the explicit contribution of NVPs. The model was calibrated from 1999 to 2012, thereby projecting smoking prevalence before NVPs were widely used in Canada. The NVP impact on smoking prevalence is inferred by comparing projected 2012-2020 smoking trends absent NVPs to corresponding trends from two Canadian national surveys. We further distinguish impacts before and after NVPs became regulated in 2018 and more available., Results: Comparing 2012-2020 survey data of post-NVP to SimSmoke projected smoking prevalence trends, one survey indicated an NVP-related relative reduction of 15% (15%) for males (females) age 15+, but 32% (52%) for those ages 15-24. The other survey indicated a 14% (19%) NVP-related smoking reduction for ages 18+, but 42% (53%) for persons ages 18-24. Much of the gain occurred since Canada relaxed NVP restrictions. NVP-related 2012-2020 smoking reductions yielded 100,000 smoking-attributable deaths averted from 2012 to 2060., Conclusion: Smoking prevalence in Canada, especially among younger adults, declined more rapidly once NVPs became readily available. The emergence of NVPs into the Canadian marketplace has not slowed the decline in smoking., (© 2023. The Author(s).)

Naturalistic psychedelic use among Canadians is common. However, interactions about psychedelic use between patients and clinicians in Canada remain unclear. Via an anonymous survey, we assessed health outcomes and integration of psychedelic use with health care providers (HCP) among Canadian adults reporting past use of a psychedelic. The survey included 2,384 participants, and most (81.2%) never discussed psychedelic use with their HCP. While 33.7% used psychedelics to self-treat a health condition, only 4.4% used psychedelics with a therapist and 3.6% in a clinical setting. Overall, 44.8% ( n  = 806) of participants were aware of substance testing services, but only 42.4% ever used them. Multivariate regressions revealed that therapeutic motivation, higher likelihood of seeking therapist guidance, and non-binary gender identification were significantly associated with higher odds of discussing psychedelics with one's primary HCP. Having used a greater number of psychedelics, lower age, non-female gender, higher education, and a therapeutic motivation were significantly associated with higher odds of awareness of substance testing. We conclude that naturalistic psychedelic use in Canada often includes therapeutic goals but is poorly connected to conventional healthcare, and substance testing is uncommon. Relevant training and education for HCPs is needed, along with more visible options for substance testing.

Background: Preventing transmission is crucial for reducing infections with multidrug-resistant organisms (MDROs) in nursing homes. To identify resident characteristics associated with MDRO spread, we investigated associations between patient characteristics and contamination of their proximate room surfaces with vancomycin-resistant enterococci (VRE)., Methods: In this retrospective observational study, we used demographic and clinical data (including data on comorbidities, physical independence, catheter use within the past 30 days, and antibiotic exposure within the past 30 days) and surveillance cultures of patient body sites and room surfaces at enrolment and during weekly follow-up visits within the first month, and monthly thereafter (up to 6 months), in six US nursing homes collected in a previous clinical trial (September, 2016, to August, 2018). We did 16S rRNA gene sequencing on perirectal surveillance swabs to investigate the association between the gut microbiota and the culture status of participants and their rooms., Findings: We included 245 participants (mean age 72·5 years [SD 13·6]; 111 [45%] were men, 134 [55%] were women, 132 [54%] were non-Hispanic white, and 112 [46%] were African American). We collected 2802 participant samples and 5592 environmental samples. At baseline, VRE colonisation was present in 49 (20%) participants, with environmental surfaces being contaminated in 36 (73%) of these patients. Hand contamination among VRE-colonised participants was more common in those with environmental contamination compared with those without (50 [51%] of 99 vs seven [13%] of 55; p<0·0001). We found a correlation between hand contamination and both groin and perirectal colonisation and contamination of various high-touch room surfaces (Cohen's κ 0·43). We found participant microbiota composition to be associated with antibiotic receipt within the past 30 days (high-risk antibiotics p=0·011 and low-risk antibiotics p=0·0004) and participant VRE colonisation status, but not environmental contamination among VRE-colonised participants (participant only vs uncolonised p=0·071, both participant and environment vs uncolonised p=0·025, and participant only vs participant and environment p=0·29). Multivariable analysis to identify independent factors associated with VRE-colonised participants contaminating their environment identified antibiotic exposure (adjusted odds ratio 2·75 [95% CI 1·22-6·16]) and male sex (2·75 [1·24-6·08]) as being associated with increased risk of environmental contamination, and physical dependence as being associated with a reduced risk of environmental contamination (0·91 [0·83-0·99])., Interpretation: Our data support antibiotic use and interaction with proximal surfaces by physically independent nursing home residents as under-appreciated drivers of environmental contamination among VRE-colonised residents. Integrating resident hand-hygiene education and antimicrobial stewardship will strengthen efforts to reduce MDROs in nursing homes., Funding: US Centers for Disease Control and Prevention, National Institute of Health, Canadian Institutes of Health Research, and University of Michigan., Competing Interests: Declaration of interests KR is supported in part by an investigator-initiated grant from Merck & Co and has consulted for Seres Therapeutics and Summit Therapeutics. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Rising atmospheric vapour pressure deficit (VPD) associated with climate change affects boreal forest growth via stomatal closure and soil dryness. However, the relationship between VPD and forest growth depends on the climatic context. Here we assess Canadian boreal forest responses to VPD changes from 1951-2018 using a well-replicated tree-growth increment network with approximately 5,000 species-site combinations. Of the 3,559 successful growth models, we observed a relationship between growth and concurrent summer VPD in one-third of the species-site combinations, and between growth and prior summer VPD in almost half of those combinations. The relationship between previous year VPD and current year growth was almost exclusively negative, while current year VPD also tended to reduce growth. Tree species, age, annual temperature, and soil moisture primarily determined tree VPD responses. Younger trees and species like white spruce and Douglas fir exhibited higher VPD sensitivity, as did areas with high annual temperature and low soil moisture. Since 1951, summer VPD increases in Canada have paralleled tree growth decreases, particularly in spruce species. Accelerating atmospheric dryness in the decades ahead will impair carbon storage and societal-economic services., (© 2023. Crown.)

Introduction: As interest in medicine grows, admissions committees must review an increasingly competitive pool of medical school and residency candidates. Nearly all admissions committees have moved towards a holistic review, which considers an applicant's experiences and attributes in addition to academic metrics. As such, identifying nonacademic predictors of success in medicine is necessary. Parallels between skills necessary to succeed in athletics and in medicine have been drawn, including teamwork, discipline and resiliency. This systematic review synthesises the current literature to evaluate the relationship between participation in athletics and performance in medicine., Methods: The authors searched five databases to conduct a systematic review following PRISMA guidelines. Included studies assessed medical students, residents or attending physicians in the United States or Canada and used prior athletic participation as a predictor or explanatory variable. The review examined associations between prior athletic participation and outcomes in medical school, residency and/or as an attending physician., Results: Eighteen studies evaluating medical students (78%), residents (28%) or attending physicians (6%) met inclusion criteria for this systematic review. Twelve (67%) studies specifically assessed participants based on skill level, and five (28%) studies specifically assessed participants based on type of athletic participation (team versus individual). Sixteen studies (89%) found that former athletes performed significantly better than their counterparts (p < 0.05). These studies found significant associations between prior athletic participation and better outcomes in multiple performance indicators, including exam scores, faculty ratings, surgical errors and burnout., Conclusions: Current literature, although limited, suggests that prior participation in athletics may be a predictor of success in medical school and residency. This was demonstrated through objective scoring methods, such as USMLE, and subjective outcomes, such as faculty ratings and burnout. Specifically, multiple studies indicate that former athletes demonstrated increased surgical skill proficiency and decreased burnout as medical students and residents., (© 2023 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Significance: This study examines the differential effects of Canadian point-of-sale (POS) tobacco display bans across provinces on quit attempts and smoking cessation, by sex, education and income., Methods: We analysed survey data from five waves (waves 4-8) of the International Tobacco Control Canada Survey, a population-based, longitudinal survey, where provinces implemented display bans between 2004 and 2010. Primary outcomes were quit attempts and successful cessation. We used generalised estimating equation Poisson regression models to estimate associations between living in a province with or without a POS ban (with a 24-month threshold) and smoking outcomes. We tested whether these associations varied by sex, education and income by including interaction terms., Results: Across survey waves, the percentage of participants in provinces with POS bans established for more than 24 months increased from 5.0% to 95.8%. There was no association between POS bans and quit attempts for provinces with bans in place for 0-24 months or more than 24 months, respectively (adjusted relative risk (aRR)=0.99, 95% CI: 0.89 to 1.10; 1.03, 95% CI: 0.88 to 1.20). However, we found a differential impact of POS bans on quit attempts by sex, whereby bans were more effective for women than men for bans of 0-24 months. Participants living in a province with a POS ban for at least 24 months had a higher chance of successful cessation (aRR=1.49; 95% CI: 1.08 to 2.05) compared with those in a province without a ban. We found no differences in the association between POS bans and quit attempts or cessation by education or income, and no differences by sex for cessation., Conclusion: POS bans are associated with increased smoking cessation overall and more quit attempts among women than men., Competing Interests: Competing interests: GF and JT have been expert witnesses/consultants for governments defending their country’s policies/regulations in litigation., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prediction of treatment outcomes is a key step in improving the treatment of major depressive disorder (MDD). The Canadian Biomarker Integration Network in Depression (CAN-BIND) aims to predict antidepressant treatment outcomes through analyses of clinical assessment, neuroimaging, and blood biomarkers., Methods: In the CAN-BIND-1 dataset of 192 adults with MDD and outcomes of treatment with escitalopram, we applied machine learning models in a nested cross-validation framework. Across 210 analyses, we examined combinations of predictive variables from three modalities, measured at baseline and after 2 weeks of treatment, and five machine learning methods with and without feature selection. To optimize the predictors-to-observations ratio, we followed a tiered approach with 134 and 1152 variables in tier 1 and tier 2 respectively., Results: A combination of baseline tier 1 clinical, neuroimaging, and molecular variables predicted response with a mean balanced accuracy of 0.57 (best model mean 0.62) compared to 0.54 (best model mean 0.61) in single modality models. Adding week 2 predictors improved the prediction of response to a mean balanced accuracy of 0.59 (best model mean 0.66). Adding tier 2 features did not improve prediction., Conclusions: A combination of clinical, neuroimaging, and molecular data improves the prediction of treatment outcomes over single modality measurement. The addition of measurements from the early stages of treatment adds precision. Present results are limited by lack of external validation. To achieve clinically meaningful prediction, the multimodal measurement should be scaled up to larger samples and the robustness of prediction tested in an external validation dataset.

Since their introduction to North America in the 1980s, research to develop effective control tools for invasive mussels (Dreissena polymorpha and D. rostriformis bugensis) has been ongoing across various research institutions using a range of testing methods. Inconsistencies in experimental methods and reporting present challenges for comparing data, repeating experiments, and applying results. The Invasive Mussel Collaborative established the Toxicity Testing Work Group (TTWG) in 2019 to identify "best practices" and guide development of a standard framework for dreissenid mussel toxicity testing protocols. We reviewed the literature related to laboratory-based dreissenid mussel toxicity tests and determined the degree to which standard guidelines have been used and their applicability to dreissenid mussel testing. We extracted detailed methodology from 99 studies from the peer-reviewed and gray literature and conducted a separate analysis for studies using presettlement and postsettlement mussels. We identified specific components of methods and approaches that could be refined or standardized for dreissenid mussels. These components included species identification, collection methods, size/age class distinction, maintenance practices, testing criteria, sample size, response measures, reporting parameters, exposure methods, and mortality criteria. We consulted experts in the field of aquatic toxicology and dreissenid mussel biology on our proposed. The final recommendations contained in the present review are based on published standard guidelines, methods reported in the published and gray literature, and the expertise of TTWG members and an external panel. In addition, our review identifies research needs for dreissenid mussel testing including improved methods for early-life stage testing, comparative data on life stages and between dreissenid mussel species, inclusion of a reference toxicant, and additional testing of nontarget species (i.e., other aquatic organisms). Environ Toxicol Chem 2023;42:1649-1666. © 2023 His Majesty the King in Right of Canada. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2023 His Majesty the King in Right of Canada. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: We conducted a national survey to assess the experiences of stigma and harassment among physicians and nurse practitioners providing abortions and abortion service administrators in Canada., Study Design: We conducted an exploratory, cross-sectional, national, anonymized, online survey between July and December 2020. Subsections of the survey explored stigma and harassment experienced by respondents, including the 35-item Revised Abortion Providers Stigma Scale and open-ended responses. We analyzed the quantitative data to generate descriptive statistics and employed a reflexive thematic analysis to interpret open-ended responses., Results: Three hundred fifty-four participants started the stigma and harassment section of the survey. Among low-volume clinicians (<30 abortions/year, 60%, n = 180) 8% reported harassment; 21% among higher volume clinicians (≥30 abortions/year, 40%, n = 119) and 47% among administrators (n = 39), most commonly picketing. The mean stigma score was 67.8 (standard deviation 17.2; maximum score 175). Our qualitative analysis identified five themes characterizing perceptions of stigma and harassment: concerns related to harassment from picketing, protestors, and the public; wanting protestor "bubble zones"; aiming to be anonymous to avoid being a target; not providing an abortion service; but also witnessing a safe and positive practice environment., Conclusions: Being a low-volume clinician compared to higher volume clinician and administrator appears to be associated with less harassment. Clinicians providing abortion care in Canada reported mid-range abortion-related stigma scores, and expressed strong concerns that stigma interfered with their abortion provision. Our results indicate that further de-stigmatization and protection of abortion providers in Canada is needed through policy and practice interventions including bubble zones., Implications: While Canadian abortion care clinicians and administrators reported relatively low incidence of harassment, our results indicate that they are concerned about stigma and harassment. However, as this was an exploratory survey, these data may not be representative of all Canadian abortion providers. Our data identify a need to support abortion clinicians and to bolster protections for dedicated abortion services., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Variation in priorities during pandemic planning among the federal, provincial and territorial jurisdictions are thought to have impacted Canada's ability to effectively control the spread of the COVID-19 virus, and protect the most vulnerable. The potential influence of diverse and divergent political, cultural, and behavioural factors, regarding inclusion of priority setting (PS) in pandemic preparedness planning across the country is not well understood. This study aimed to examine how the Canadian federal, provincial and territorial COVID-19 pandemic preparedness planning documents integrated PS., Methods: A documentary analysis of the federal, eight provincial, three territorial COVID-19 preparedness and response plans. We assessed the degree to which the documented PS processes fulfilled established quality requirements of effective PS using the Kapiriri & Martin framework., Results: While the federal plan included most of the parameters of effective PS, the provinces and territories reflected few. The lack of obligation for the provinces and territories to emulate the federal plan is one of the possible reasons for the varying inclusion of these parameters. The parameters included did not vary systematically with the jurisdiction's context., Conclusion: Provinces could consider using the framework of the federal plan and the WHO guidelines to guide future pandemic planning. Regular evaluation of the instituted PS would provide a mechanism through which lessons can be harnessed and improvement strategies developed. Future studies should describe and evaluate what PS mechanisms were implemented., Competing Interests: Declaration of Competing Interest The authors declare no conflict to declare, (Copyright © 2023. Published by Elsevier B.V.)

The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15-1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

It is commonly expected that exotic plants experience reduced herbivory, but experimental evidence for such enemy release is still controversial. One reason for conflicting results might be that community context has rarely been accounted for, although the surrounding plant diversity may moderate enemy release. Here, we tested the effects of focal tree origin and surrounding tree diversity on herbivore abundance and leaf damage in a cross-Atlantic tree-diversity experiment in Canada and Germany. We evaluated six European tree species paired with six North American congeners in both their native and exotic range, expecting lower herbivory for the exotic tree species in each pair at each site. Such reciprocal experiments have long been called for, but have not been realized thus far. In addition to a thorough evaluation of overall enemy release effects, we tested whether enemy release effects changed with the surrounding tree diversity. Herbivore abundance was indeed consistently lower on exotics across all six tree genera (12 comparisons). This effect of exotic status was independent of the continent, phylogenetic relatedness, and surrounding tree diversity. In contrast, leaf damage associated with generalist leaf chewers was consistently higher on North American tree species. Interestingly, several species of European weevils were the most abundant leaf chewers on both continents and the dominant herbivores at the Canadian site. Thus, most observed leaf damage is likely to reflect the effect of generalist herbivores that feed heavily on plant species with which they have not evolved. At the German site, sap suckers were the dominant herbivores and showed a pattern consistent with enemy release. Taken together, the consistently lower herbivory on exotics on both continents is not purely a pattern of enemy release in the strictest sense, but to some degree additionally reflects the susceptibility of native plants to invasive herbivores. In conclusion, our cross-Atlantic study is consistent with the idea that nonnative trees have generally reduced herbivory, regardless of tree community diversity and species identity, but for different reasons depending on the dominant herbivore guild., (© 2023 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Purpose: Residency programs in oral maxillofacial surgery (OMS) have the lowest percentage (2020: 18.4%) of female graduates among all dental specialty programs. When considering this underrepresentation of female OMS residents, prior studies have not examined how OMS role models might shape dental students' interest in OMS careers. The objectives were to assess female versus male students' OMS-related career motivation, their experiences/attitudes toward three groups of OMS role models (i.e., OMS residents, faculty, and practitioners), and relationships between role model-related experiences/attitudes and career motivation., Methods: 363 female and 335 male students from 14 United States and two Canadian dental schools participated in this cross-sectional study by responding to an online survey., Results: 13.8% of female and 26% of male respondents (p < 0.001) were much/very much interested in OMS careers. More male than female students had shadowed an OMS in an office setting (43.4% vs. 35.1%; p < 0.05). The groups did not differ in their motivation to learn more and earlier about OMS nor in the quantity of OMS-related experiences prior to and during dental school. However, male students were more satisfied with the quality of these experiences (5-point scale with 5 = most positive: Means: 3.76 vs. 3.53; p < 0.05), were more comfortable approaching/working with OMS instructors (3.51 vs. 3.19; p < 0.01) and reported to have learned more from residents (3.52 vs. 3.31; p < 0.05) and faculty (3.75 vs. 3.45; p < 0.01) than female students. Female students agreed less that OMS residents, faculty, and practitioners encouraged students to pursue OMS (3.27 vs. 3.44; p < 0.01 / 3.46 vs. 3.63; p < 0.01 / 3.45 vs. 3.61; p < 0.01). Role model-related experiences and attitudes correlated with an interest in an OMS career., Conclusions: The two groups do not differ in the quantity of most OMS experiences before and during dental school and their motivation to learn more and earlier about OMS. However, female students' less positive OMS-related educational experiences and less positive attitudes toward role models correlate with a lower interest in OMS careers., (© 2023 The Authors. Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Background: Potential bidirectional drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are of concern for trans women with HIV and their healthcare providers. This study aimed to characterize patterns of FHT and ART among trans women with HIV and to compare serum hormone levels to trans women without HIV., Methods: Charts of trans women were reviewed at seven HIV primary care or endocrinology clinics in Toronto and Montreal from 2018 to 2019. ART regimens, FHT use, serum estradiol, and serum testosterone levels were compared on the basis of HIV status (positive, negative, missing/unknown)., Results: Of 1495 trans women, there were 86 trans women with HIV, of whom 79 (91.8%) were on ART. ART regimens were most commonly integrase inhibitor-based (67.4%), many boosted with ritonavir or cobicistat (45.3%). Fewer (71.8%) trans women with HIV were prescribed FHT, compared to those without HIV (88.4%) and those with missing/unknown status (90.2%, p < 0.001). Among trans women on FHT with recorded serum estradiol ( n = 1153), there was no statistical difference in serum estradiol between those with HIV (median: 203 pmol/L, IQR: 95.5, 417.5) and those with negative (200 mol/L [113, 407]) or missing/unknown HIV status (227 pmol/L [127.5, 384.5) ( p = 0.633). Serum testosterone concentrations were also similar between groups., Conclusions: In this cohort, trans women with HIV were prescribed FHT less often than trans women with negative or unknown HIV status. There was no difference in serum estradiol or testosterone levels of trans women on FHT regardless of HIV status, providing reassurance regarding potential drug-drug interactions between FHT and ART.

Objective: To assess the regulations on Cannabis advertising across U.S. states for variation and compare with Canadian federal policies, for the purpose of identifying opportunities to protect the public, especially the youth and other vulnerable populations, from health risks. Methods: We reviewed Health Canada's Cannabis Act and Cannabis Regulations to identify prohibited marketing and advertising activities for cannabis products. The Canadian guidelines (where cannabis is legal for both medical and nonmedical use) were compared with regulations in the 36 U.S. states where cannabis is legalized for medical and/or adult (e.g., recreational) use. Results: Cannabis advertising regulations vary greatly and have little consistency across the U.S. states. Most states do not address many of the cannabis advertising activities that are prohibited in Canada. Among the 31 states that do allow some form of cannabis advertising, 74% explicitly prohibit targeting or appealing to minors and 68% prohibit making false or misleading claims. There are 11 illegal advertising tactics in Canada, such as glamorization and testimonials, that were not specifically discussed in any of the U.S. state policies. Conclusion: The lack of consistent marketing guidelines could expose youth and vulnerable populations to cannabis advertisements; more widespread or federal guidance is needed.

Background: Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders., Objective: The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder., Methods: We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations., Results: Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results., Conclusion: The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.

The latter half of the twentieth century witnessed the emergence of the hospice movement as a response to the increasing medicalization of death and the associated suffering. Palliative care, a term coined by the Canadian urologic surgeon Balfour Mount, represents an expansion of hospice philosophy upstream within the health care system extending to the care of hospitalized patients with life-threatening illnesses. This article offers a brief history of the development of surgical palliative care, i.e., palliative care directed specifically toward relief of suffering associated with serious surgical illnesses and culminating in the formation of the Surgical Palliative Care Society.

Context: Certified athletic therapists in Ireland and Canada serve essential concussion assessment and management roles, but their health care practices and concussion knowledge have not been established., Objective: To examine Irish and Canadian athletic therapist cohorts' (1) concussion knowledge, (2) current concussion assessment and management techniques across all job settings, and (3) the association of concussion assessment and management practices with years of clinical experience and highest degree attained., Design: Cross-sectional cohort study., Setting: Online survey., Patients or Other Participants: Licensed Irish (49.7%, n = 91/183) and Canadian (10.1%, n = 211/2090) athletic therapists., Main Outcome Measure(s): Athletic therapists completed an online survey assessing their demographics, concussion knowledge (symptom recognition, patient-clinician scenarios), frequency of concussions assessed annually, and assessment and return-to-play (RTP) measures using a modified, previously validated survey. Symptom recognition consisted of 20 (8 true, 12 false) items on recognition of signs and symptoms that were scored as total correct. Descriptive statistics and odds ratios were used to examine survey responses where appropriate., Results: Irish (86.8%, n = 46/53) and Canadian (93.4%, n = 155/166) athletic therapists indicated RTP guidelines were the most common method for determining RTP. Symptom recognition scores were 72.8% ± 17.0% among Irish and 76.6% ± 17.0% among Canadian athletic therapists. Irish (91.2%, n = 52/57) and Canadian (90.4%, n = 161/178) athletic therapists reported standardized sideline assessments as the most used concussion assessment method. Irish and Canadian athletic therapists' use of 2-domain (Irish: 38.6% [n = 22/57]; Canadian: 73.6% [n = 131/178]) and 3-domain (Irish: 3.5% [n = 2/57]; Canadian: 19.7% [n = 35/178]) minimum assessments (ie, symptoms, balance, or neurocognitive) was not associated with education or clinical experience (P ≥ .07), except for Canadian athletic therapists with master's degrees having greater odds of completing 2-domain assessments at initial evaluation than those with bachelor's degrees (odds ratio = 1.80; 95% CI = 1.41, 1.95)., Conclusions: Irish and Canadian athletic therapists demonstrated similar concussion knowledge; however, most did not fully adhere to international consensus guidelines for concussion assessment as evidenced by low 2- and 3-domain assessment use. Athletic therapists should aim to implement multidimensional concussion assessments to ensure optimal health care practices and patient safety., (© by the National Athletic Trainers' Association, Inc.)

Introduction: We examined the differential impact of the 2012 Canadian GWL policy changes on key indicators of warning label impact and quit intentions using national cohorts of Canadian and U.S. adults who smoke., Aims and Methods: We used data from all waves of the International Tobacco Control surveys (2002-2020) in Canada and the United States. Our key measures were quit intentions and an index of warning label effectiveness (salience, cognitive and behavioral reactions). We estimated overall policy impact by comparing Canada (treatment group) with the United States (control group) using controlled interrupted time series (CITS) regression models, with interactions to examine whether policy impact varied by sex, education, and income., Results: The CITS model showed a statistically significant increase in the warning label effectiveness in Canada post-policy, compared to the United States (β = 0.84, 95% CI 0.35,1.33). Similarly, the odds of quit intentions were relatively higher among adults who smoked in Canada compared to the United States (OR = 1.89, 95% CI 1.51,2.36) post-policy. The three-way interaction model showed that these associations were greater among adults from low socioeconomic status (SES) groups than in high SES groups., Conclusions: The 2012 change in the Canadian GWL policy was associated with stronger cognitive and behavioral responses to GWLs and higher odds of quit intentions among adults who smoked in Canada when compared to the United States, specifically among individuals from low SES groups, suggesting a positive equity impact. Our findings affirm the need for countries to implement or enhance GWLs, in line with the WHO Framework Convention on Tobacco Control (FCTC)., Implications: The evidence on the potential health equity benefit of GWL policies is mixed. To further understand the influence of GWL policies on tobacco use disparities, more systematic research using pre/post-policy designs with control groups is needed. Using a CITS model, we aimed to strengthen the available evidence on the causal influence of this tobacco control approach. Our findings show that the 2012 GWL policy change had a greater impact on adults who smoked from low SES groups than it did on adults who smoked from high SES groups, indicating a potentially positive equity impact and confirming the need for countries to implement or maximize the size of GWLs, as recommended by the WHO FCTC., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Major depressive disorder (MDD) is associated with various cognitive impairments, including response inhibition. Deficits in response inhibition may also underlie poor antidepressant treatment response. Recent studies revealed that the neurobiological correlates of response inhibition can predict response to pharmacological treatments. However, the generalizability of this finding to first-line nonpharmacological treatments, particularly cognitive behavioral therapy, remains to be investigated., Methods: Data from two independent treatment protocols were combined, one in which 65 patients with MDD underwent treatment with escitalopram, and the other in which 41 patients with MDD underwent a course of cognitive behavioral therapy. A total of 25 healthy control subjects were also recruited. Neural correlates of response inhibition were captured by participants completing a Go/NoGo task during electroencephalography recording. Response inhibition-related measures of interest included the amplitudes of the N2 and P3 event-related potentials., Results: Pretreatment P3 amplitude, which has been linked to both the motor and cognitive aspects of response inhibition, was a significant predictor of change in depressive symptoms following escitalopram and cognitive behavioral therapy treatment. A greater pretreatment P3 amplitude was associated with a greater reduction in depressive severity. In addition, the pretreatment P3 amplitude was found to be significantly greater at baseline in remitters than in nonremitters and healthy control subjects., Conclusions: The integrity of response inhibition may be critical for a successful course of pharmacological or psychological treatment for MDD. Electrophysiological correlates of response inhibition may have utility as a general prognostic marker of treatment response in MDD. Future studies may investigate the benefit of preceding first-line treatments with interventions that improve response inhibition in MDD., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder., Methods: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria., Results: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient., Conclusions: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

Understanding boreal/hemi-boreal forest growth sensitivity to seasonal variations in temperature and water availability provides important basis for projecting the potential impacts of climate change on the productivity of these ecosystems. Our best available information currently comes from a limited number of field experiments and terrestrial biosphere model (TBM) simulations of varying predictive accuracy. Here, we assessed the sensitivity of annual boreal/hemi-boreal forest growth in Canada to yearly fluctuations in seasonal climate variables using a large tree-ring dataset and compared this to the climate sensitivity of annual net primary productivity (NPP) estimates obtained from fourteen TBMs. We found that boreal/hemi-boreal forest growth sensitivity to fluctuations in seasonal temperature and precipitation variables changed along a southwestern to northeastern gradient, with growth limited almost entirely by temperature in the northeast and west and by water availability in the southwest. We also found a lag in growth climate sensitivity, with growth largely determined by the climate during the summer prior to ring formation. Analyses of NPP sensitivity to the same climate variables produced a similar southwest to northeast gradient in growth climate sensitivity for NPP estimates from all but three TBMs. However, analyses of growth from tree-ring data and analyses of NPP from TBMs produced contrasting evidence concerning the key climate variables limiting growth. While analyses of NPP primarily indicated a positive relationship between growth and seasonal temperature, tree-ring analyses indicated negative growth relationships to temperature. Also, the positive effect of precipitation on NPP derived from most TBMs was weaker than the positive effect of precipitation on tree-ring based growth: temperature had a more important limiting effect on NPP than tree-ring data indicated. These mismatches regarding the key climate variables limiting growth suggested that characterization of tree growth in TBMs might need revision, particularly regarding the effects of stomatal conductance and carbohydrate reserve dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia., Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds., Results: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms., Conclusions: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia., Competing Interests: Declaration of Competing Interest FA reports grants/contracts from BMS, Celgene, Novartis and Sandoz; consulting fees from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and Sanofi-Aventis. LC reports grants/contracts from NIH/NIAMS; participation on a data safety monitoring/advisory board for NIH/NIAMS; a leadership/fiduciary role with American College of Rheumatology. MAF reports expert testimony for the plaintiff and the defendant; leadership/fiduciary role with Health Canada, Australian Centre for Cannabinoid Clinical and Research Excellence, Arthritis Foundation US, Canadian Rheumatology Association, American College of Rheumatology abstract committee. EK reports royalties/licenses for studentlitteratur and liber; consulting fees from Eli Lilly; leadership/fiduciary role with IASP Terminology Task Force and IASP ICD-11 Task Force. SR reports grants/contracts from General Nursing Council Trust, Haywood Foundation and CRN. JAPS reports grants/contracts from Pfizer; payment/honoraria from Eli Lilly and Amgen; participation on a data safety monitoring/advisory board for Eli Lilly and Abbvie; and owner of MyFibromyalgia.org. AT reports consulting fees from Pfizer. RG reports leadership/fiduciary roles with International Myopain Society. DW reports grants/contracts from Versus Arthritis Foundation and Michigan Medicine Dan Barry., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The fungal kingdom represents an extraordinary diversity of organisms with profound impacts across animal, plant, and ecosystem health. Fungi simultaneously support life, by forming beneficial symbioses with plants and producing life-saving medicines, and bring death, by causing devastating diseases in humans, plants, and animals. With climate change, increased antimicrobial resistance, global trade, environmental degradation, and novel viruses altering the impact of fungi on health and disease, developing new approaches is now more crucial than ever to combat the threats posed by fungi and to harness their extraordinary potential for applications in human health, food supply, and environmental remediation. To address this aim, the Canadian Institute for Advanced Research (CIFAR) and the Burroughs Wellcome Fund convened a workshop to unite leading experts on fungal biology from academia and industry to strategize innovative solutions to global challenges and fungal threats. This report provides recommendations to accelerate fungal research and highlights the major research advances and ideas discussed at the meeting pertaining to 5 major topics: (1) Connections between fungi and climate change and ways to avert climate catastrophe; (2) Fungal threats to humans and ways to mitigate them; (3) Fungal threats to agriculture and food security and approaches to ensure a robust global food supply; (4) Fungal threats to animals and approaches to avoid species collapse and extinction; and (5) Opportunities presented by the fungal kingdom, including novel medicines and enzymes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Introduction: An increasing number of studies are examining the link between the endocannabinoidome and major depressive disorder (MDD). We conducted an exploratory analysis of this system to identify potential markers of treatment outcomes., Methods: The dataset of the Canadian Biomarker Integration Network in Depression-1 study, consisting of 180 patients with MDD treated for eight weeks with escitalopram followed by eight weeks with escitalopram alone or augmented with aripiprazole was analyzed. Association between response Montgomery-Asberg Depression Rating Scale (MADRS; score reduction≥50%) or remission (MADRS score≤10) at weeks 8 and 16 and single nucleotide polymorphisms (SNPs), methylation, and mRNA levels of 33 endocannabinoid markers were examined. A standard genome-wide association studies protocol was used for identifying SNPs, and logistic regression was used to assess methylation and mRNA levels., Results: Lower methylation of CpG islands of the diacylglycerol lipase alpha gene ( DAGLA ) was associated with non-remission at week 16 ( DAGLA ; OR=0.337, p<0.003, q=0.050). Methylation of DAGLA was correlated with improvement in Clinical Global Impression (p=0.026), Quick Inventory of Depressive Symptomatology (p=0.010), and Snaith-Hamilton Pleasure scales (p=0.028). We did not find any association between SNPs or mRNA levels and treatment outcomes., Discussion: Methylation of DAGLA is a promising candidate as a marker of treatment outcomes for MDD and needs to be explored further., Competing Interests: There was no role of the following granting agencies/sponsors in the design, collection of data, analysis, interpretation of data, writing of this paper, and decision to submit the paper for publication. Muhammad I. Husain receives research support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, CAMH Foundation, the PSI Foundation, and the University of Toronto. He has provided consultancy to Mindset Pharma, PsychEd Therapeutics, and Wake Network. He holds stock/stock options in Mindset Pharma. Raymond W. Lam has received honoraria for ad hoc speaking or advising/consulting or received research funds from: Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, Sanofi, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. Claudio N. Soares received/has pending grants that include Canadian Institutes for Health Research, Ontario Brain Institute, Ontario Research Fund, and Eisai. He also receives consulting feed or honorarium from Lundbeck, Otsuka, Pfizer, Bayer, and Eisai. Sagar V. Parikh reports research support in the past three years from Takeda, Sage, Janssen, Merck, the Ontario Brain Institute, and the Canadian Institutes for Health Research; honoraria from Aifred, Assurex, Janssen, Lundbeck, Mensante, Neonmind, Otsuka, and Sage; and shares in Neonmind and Mensante. Roumen Milev has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Neonmind, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. Jane A. Foster receives consulting and speaking fees from Takeda Canada and RBH. Faranak Farzan received funding from CIHR, NSER, and Michael Smith Foundation for Health Research. Benoit H. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute, the US National Institute of Health, Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study funded by Brain Canada). He has been an unpaid consultant to Myriad Neuroscience. Sidney Kennedy received grants/has pending grants, including Abbott, Allergan, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, and Xian-Janssen. He also receives consulting fees or honorarium from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen. He has stock/stock options from Field Trip Health. Stefan Kloiber’s work has been supported by the Academic Scholar Award and the Labatt Family Innovation Fund in Brain Health, Department of Psychiatry, University of Toronto. DJM’s research work is supported by the Canadian Institutes of Health Research, the Ontario Brain Foundation, the Alternate Funding Plan of Ontario, and the Centre for Addiction and Mental Health Foundation. GZ’s work has been supported by the Academic Scholar Award and the Labatt Family Innovation Fund in Brain Health, Department of Psychiatry, University of Toronto, in addition to the Brain & Behavior Research Foundation, International Obsessive-Compulsive Disorder Foundation, and the Physicians’ Services Incorporated Foundation in Ontario, Canada. SK has received an honorarium for past consultation from EmpowerPharm. All other authors declare no conflict of interest. Helena K. Kim, Gwyneth Zai, Daniel J. Müller, Benicio N. Frey, Gustavo Turecki, and Shreejoy J. Tripathy have no conflicts to disclose., (Thieme. All rights reserved.)