Dire wolves were the last of an ancient New World canid lineage.

Dire wolves are considered to be one of the most common and widespread large carnivores in Pleistocene America1, yet relatively little is known about their evolution or extinction. Here, to reconstruct the evolutionary history of dire wolves, we sequenced five genomes from sub-fossil remains dating from 13,000 to more than 50,000 years ago. Our results indicate that although they were similar morphologically to the extant grey wolf, dire wolves were a highly divergent lineage that split from living canids around 5.7 million years ago. In contrast to numerous examples of hybridization across Canidae2,3, there is no evidence for gene flow between dire wolves and either North American grey wolves or coyotes. This suggests that dire wolves evolved in isolation from the Pleistocene ancestors of these species. Our results also support an early New World origin of dire wolves, while the ancestors of grey wolves, coyotes and dholes evolved in Eurasia and colonized North America only relatively recently.

Dynamically regulated transcription factors are encoded by highly unstable mRNAs in the Drosophila larval brain.

The level of each RNA species depends on the balance between its rates of production and decay. Although previous studies have measured RNA decay across the genome in tissue culture and single-celled organisms, few experiments have been performed in intact complex tissues and organs. It is therefore unclear whether the determinants of RNA decay found in cultured cells are preserved in an intact tissue, and whether they differ between neighboring cell types and are regulated during development. To address these questions, we measured RNA synthesis and decay rates genome wide via metabolic labeling of whole cultured Drosophila larval brains using 4-thiouridine. Our analysis revealed that decay rates span a range of more than 100-fold, and that RNA stability is linked to gene function, with mRNAs encoding transcription factors being much less stable than mRNAs involved in core metabolic functions. Surprisingly, among transcription factor mRNAs there was a clear demarcation between more widely used transcription factors and those that are expressed only transiently during development. mRNAs encoding transient transcription factors are among the least stable in the brain. These mRNAs are characterized by epigenetic silencing in most cell types, as shown by their enrichment with the histone modification H3K27me3. Our data suggest the presence of an mRNA destabilizing mechanism targeted to these transiently expressed transcription factors to allow their levels to be regulated rapidly with high precision. Our study also demonstrates a general method for measuring mRNA transcription and decay rates in intact organs or tissues, offering insights into the role of mRNA stability in the regulation of complex developmental programs.

Prevalence of menthol cigarette use among adults who smoke from the United States by census division and demographic subgroup, 2002-2020: findings from the International Tobacco Control (ITC) project.

BACKGROUND: Targeted marketing of menthol cigarettes in the US influences disparities in the prevalence of menthol smoking. There has been no analysis of sub-national data documenting differences in use across demographic subgroups. This study estimated trends in the prevalence of menthol use among adults who smoke in the nine US census divisions by sex, age, and race/ethnicity from 2002 to 2020. METHODS: Data from 12 waves of the US ITC Survey were used to estimate the prevalence of menthol cigarette use across census divisions and demographic subgroups using multilevel regression and post-stratification (n = 12,020). Multilevel logistic regression was used to predict the prevalence of menthol cigarette use in 72 cross-classified groups of adults who smoke defined by sex, age, race/ethnicity, and socioeconomic status; division-level effects were fit with a random intercept. Predicted prevalence was weighted by the total number of adults who smoke in each cross-classified group and aggregated to divisions within demographic subgroup. Estimates were validated against the Tobacco Use Supplement to the Current Population Survey (TUS-CPS). RESULTS: Overall modeled prevalence of menthol cigarette use was similar to TUS-CPS estimates. Prevalence among adults who smoke increased in each division from 2002 to 2020. By 2020, prevalence was highest in the Middle (46.3%) and South Atlantic (42.7%) and lowest in the Pacific (25.9%) and Mountain (24.2%) divisions. Prevalence was higher among adults aged 18-29 (vs. 50+) and females (vs. males). Prevalence among non-Hispanic Black people exceeded 80% in the Middle Atlantic, East North Central, West North Central, and South Atlantic in all years and varied most among Hispanic people in 2020 (Pacific: 26.5%, New England: 55.1%). CONCLUSIONS: Significant geographic variation in the prevalence of menthol cigarette use among adults who smoke suggests the proposed US Food and Drug Administration (FDA) menthol cigarette ban will exert differential public health benefits and challenges across geographic and demographic subgroups.

School Nurses' Experiences of Organizational Support During the COVID-19 Pandemic.

School nurses encountered many workplace struggles while providing care during the COVID-19 pandemic. Several struggles involved organizational support, including having sufficient time, resources, compensation, and school leadership support. The purpose of this mixed methods study was to explore the experiences of school nurses working during the COVID-19 pandemic as they related to sufficient time to complete COVID-related activities, sufficient COVID-19 resources, compensation, and perceived organizational (school leadership) support. We obtained data from 1,564 National Association of School Nurses members regarding respondent characteristics, school characteristics, measures of organizational support, and qualitative perceived organizational support using a 17-question survey. Perceptions of having sufficient time to complete COVID-related tasks and infringement of these tasks on routine activities were worse for those with greater years of experience and education. Compensation for additional COVID-related work was more favorable for LPNs. School leaders should be aware of their role in bolstering organizational support and its impact.

Escherichia coli SymE is a DNA-binding protein that can condense the nucleoid.

Type I toxin-antitoxin (TA) systems typically consist of a protein toxin that imbeds in the inner membrane where it can oligomerize and form pores that change membrane permeability, and an RNA antitoxin that interacts directly with toxin mRNA to inhibit its translation. In Escherichia coli, symE/symR is annotated as a type I TA system with a non-canonical toxin. SymE was initially suggested to be an endoribonuclease, but has predicted structural similarity to DNA binding proteins. To better understand SymE function, we used RNA-seq to examine cells ectopically producing it. Although SymE drives major changes in gene expression, we do not find strong evidence of endoribonucleolytic activity. Instead, our biochemical and cell biological studies indicate that SymE binds DNA. We demonstrate that the toxicity of symE overexpression likely stems from its ability to drive severe nucleoid condensation, which disrupts DNA and RNA synthesis and leads to DNA damage, similar to the effects of overproducing the nucleoid-associated protein H-NS. Collectively, our results suggest that SymE represents a new class of nucleoid-associated proteins that is widely distributed in bacteria.

Examining the Effectiveness of the 2012 Canadian Graphic Warning Label Policy Change by Sex, Income, and Education.

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 (ß = 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.

Evaluating the impact of plain packaging among Canadian smokers: findings from the 2018 and 2020 ITC Smoking and Vaping Surveys.

BACKGROUND: In February 2020, Canada implemented plain packaging without any changes to the size and content of health warning labels (HWLs), which were last updated in 2012 (pictorial HWLs on 75% of the pack front and back). This pre-post evaluation study assessed the impact of plain packaging in Canada on: (1) pack appeal; (2) HWL effectiveness; and (3) support for plain packaging. Additionally, a quasi-experimental design was used to assess the Canadian results relative to two comparator countries: Australia, where plain packaging (with new larger HWLs) was implemented in 2012, and the United States (USA), where plain packaging has not been implemented and the same text warnings have appeared on cigarette packs since 1985. METHODS: Data are from adult smokers who participated in the 2018 and/or 2020 International Tobacco Control Smoking and Vaping Surveys in Canada (n=4600), Australia (n=1834) and the USA (n=3046). Online surveys were conducted before (February to July 2018) and after (February to June 2020) the implementation of plain packaging in Canada. Adjusted regression analyses were conducted on weighted data. RESULTS: Plain packaging was associated with a significant increase in the percentage of Canadian smokers who did not like the look of their cigarette pack (2018: 28.6% vs 2020: 44.7%, p<0.001), whereas no change in pack appeal was observed among smokers in Australia and the USA over the same period. Plain packaging was not associated with changes in HWL effectiveness in Canada. Support for plain packaging increased significantly among Canadian smokers (2018: 25.6% vs 2020: 33.7%, p<0.001). CONCLUSIONS: Plain packaging in Canada substantially reduced pack appeal and increased support for the policy among adult smokers; however, there was no increase in the effectiveness of Canada's 8-year-old HWLs. The impact of plain packaging on health warning effectiveness may depend on the design of the warnings and length of time since implementation.

Impact of Canada's menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre-post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA.

INTRODUCTION: Between 2015 and 2018, Canada banned menthol cigarettes. This study pooled data from two pre-post cohort studies (the Ontario Menthol Ban Study, and the International Tobacco Control Policy Evaluation (ITC) Canada Survey, conducted in seven provinces) to derive more precise estimates of the impact of Canada's menthol ban on quitting and to apply these estimates to project the impact of a menthol ban in the USA. METHODS: Weighted multivariable logistic analyses compared post-ban quit success of menthol smokers with non-menthol smokers (for daily smokers and for all (daily + non-daily) smokers), controlling for sex, age, ethnicity, education, baseline smoking status, baseline cigarettes per day and study regions. Projections to the USA were created by multiplying the effect size of the Canadian menthol ban on quitting (percentage of increased quitting among menthol smokers) by the number of menthol smokers overall and among African Americans, from the 2019 National Survey on Drug Use and Health. RESULTS: After the menthol cigarette ban, menthol smokers were more likely than non-menthol smokers to have quit smoking among daily smokers (difference=8.0%; 95% CI: 2.4% to 13.7%,p=0.005) and all (daily+non-daily) smokers (difference=7.3%; 95% CI: 2.1% to 12.5%,p=0.006). The projected number of smokers who would quit after a US menthol ban would be 789 724 daily smokers (including 199 732 African Americans) and 1 337 988 daily+non-daily smokers (including 381 272 African Americans). CONCLUSIONS: This pooled analysis of Canada's menthol cigarette ban provides the foundation for estimating the impact of menthol bans in the USA and other countries. Projections suggest that a US menthol cigarette ban would have a substantial impact on increasing quitting.

AMPREDICT PROsthetics-Predicting Prosthesis Mobility to Aid in Prosthetic Prescription and Rehabilitation Planning.

OBJECTIVE: To develop and validate a patient-specific multivariable prediction model that uses variables readily available in the electronic medical record to predict 12-month mobility at the time of initial post-amputation prosthetic prescription. The prediction model is designed for patients who have undergone their initial transtibial (TT) or transfemoral (TF) amputation because of complications of diabetes and/or peripheral artery disease. DESIGN: Multi-methodology cohort study that identified patients retrospectively through a large Veteran's Affairs (VA) dataset then prospectively collected their patient-reported mobility. SETTING: The VA Corporate Data Warehouse, the National Prosthetics Patient Database, participant mailings, and phone calls. PARTICIPANTS: Three-hundred fifty-seven veterans who underwent an incident dysvascular TT or TF amputation and received a qualifying lower limb prosthesis between March 1, 2018, and November 30, 2020 (N=357). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Amputee Single Item Mobility Measure (AMPSIMM) was divided into a 4-category outcome to predict wheelchair mobility (0-2), and household (3), basic community (4), or advanced community ambulation (5-6). RESULTS: Multinomial logistic lasso regression, a machine learning methodology designed to select variables that most contribute to prediction while controlling for overfitting, led to a final model including 23 predictors of the 4-category AMPSIMM outcome that effectively discriminates household ambulation from basic community ambulation and from advanced community ambulation-levels of key clinical importance when estimating future prosthetic demands. The overall model performance was modest as it did not discriminate wheelchair from household mobility as effectively. CONCLUSIONS: The AMPREDICT PROsthetics model can assist providers in estimating individual patients' future mobility at the time of prosthetic prescription, thereby aiding in the formulation of appropriate mobility goals, as well as facilitating the prescription of a prosthetic device that is most appropriate for anticipated functional goals.

Increased prevalence of loneliness and associated risk factors during the COVID-19 pandemic: findings from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: Older adults have been disproportionately impacted by COVID-19 and related preventative measures undertaken during the pandemic. Given clear evidence of the relationship between loneliness and health outcomes, it is imperative to better understand if, and how, loneliness has changed for older adults during the COVID-19 pandemic, and whom it has impacted most. METHOD: We used "pre-pandemic" data collected between 2015-2018 (n = 44,817) and "during pandemic" data collected between Sept 29-Dec 29, 2020 (n = 24,114) from community-living older adults participating in the Canadian Longitudinal Study on Aging. Loneliness was measured using the 3-item UCLA Loneliness Scale. Weighted generalized estimating equations estimated the prevalence of loneliness pre-pandemic and during the pandemic. Lagged logistic regression models examined individual-level factors associated with loneliness during the pandemic. RESULTS: We found the adjusted prevalence of loneliness increased to 50.5% (95% CI: 48.0%-53.1%) during the pandemic compared to 30.75% (95% CI: 28.72%-32.85%) pre-pandemic. Loneliness increased more for women (22.3% vs. 17.0%), those in urban areas (20.8% vs. 14.6%), and less for those 75 years and older (16.1% vs. 19.8% or more in all other age groups). Loneliness during the pandemic was strongly associated with pre-pandemic loneliness (aOR 4.87; 95% CI 4.49-5.28) and individual level sociodemographic factors [age < 55 vs. 75 + (aOR 1.41; CI 1.23-1.63), women (aOR 1.34; CI 1.25-1.43), and no post-secondary education vs. post-secondary education (aOR 0.73; CI 0.61-0.86)], living conditions [living alone (aOR 1.39; CI 1.27-1.52) and urban living (aOR 1.18; CI 1.07-1.30)], health status [depression (aOR 2.08; CI 1.88-2.30) and having two, or ≥ three chronic conditions (aOR 1.16; CI 1.03-1.31 and aOR 1.34; CI 1.20-1.50)], health behaviours [regular drinker vs. non-drinker (aOR 1.15; CI 1.04-1.28)], and pandemic-related factors [essential worker (aOR 0.77; CI 0.69-0.87), and spending less time alone than usual on weekdays (aOR 1.32; CI 1.19-1.46) and weekends (aOR 1.27; CI 1.14-1.41) compared to spending the same amount of time alone]. CONCLUSIONS: As has been noted for various other outcomes, the pandemic did not impact all subgroups of the population in the same way with respect to loneliness. Our results suggest that public health measures aimed at reducing loneliness during a pandemic should incorporate multifactor interventions fostering positive health behaviours and consider targeting those at high risk for loneliness.

Feasibility Assessment of a School Nurse-Led Approach Using Chronic Absenteeism to Establish the School-Based Active Surveillance Process.

This article shares what was learned from the feasibility assessment of a nurse-led school-based active surveillance (SBAS) pilot to track chronic absenteeism using myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an exemplar. This pilot encompassed a 3-year period with training and feedback from school nurses (SNs) on data collection and ME/CFS. SNs found that the SBAS process helped them effectively identifying undiagnosed conditions. The assessment revealed the importance of focusing outreach efforts and establishing relationships with the school leadership in developing health policies and programs in the school setting. The pilot data were used to develop a manual to guide SNs for the SBAS process. This can be viewed as a model for SNs in establishing a surveillance to identify and track conditions like ME/CFS. With overlapping symptoms of Long COVID to ME/CFS, this assessment may provide insights for additional efforts to understand the impact of Long COVID on students' education.

Prenatal cannabis use and its impact on offspring neuro-behavioural outcomes: A systematic review.

Introduction: Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods: MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results: Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = -0.27 (95% CI = -0.60 to 0.07)], global intelligence quotient [-0.16 (-0.42 to 0.10)], reading [-0.05 (-0.29 to 0.20)], written comprehension [-0.09 (-0.40 to 0.22)], spelling [-0.04 (-0.26 to 0.17)], and mathematics [-0.01 (-0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions: The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes.

Factors Associated With Willingness to Receive a COVID-19 Vaccine Among 23,819 Adults Aged 50 Years or Older: An Analysis of the Canadian Longitudinal Study on Aging.

Identifying persons who are least willing to receive a coronavirus disease 2019 (COVID-19) vaccine is critical for increasing uptake via targeted outreach. We conducted a survey of 23,819 Canadian Longitudinal Study on Aging participants from September 29 to December 29, 2020, to assess factors associated with COVID-19 vaccination willingness and reasons for willingness or lack thereof. Among adults aged 50-96 years, 84.1% (95% confidence interval (CI): 83.7, 84.6) were very or somewhat willing to receive a COVID-19 vaccine; 15.9% (95% CI: 15.4, 16.3) were uncertain or very or somewhat unwilling. Based on logistic regression, those who were younger, female, had lower education and income, were non-White, and lived in a rural area were less willing to receive a COVID-19 vaccine. After controlling for these factors, recent receipt of influenza vaccine (adjusted odds ratio = 14.3, 95% CI: 12.5, 16.2) or planning to receive influenza vaccine (adjusted odds ratio = 10.5, 95% CI: 9.5, 11.6), as compared with no receipt or planning, was most strongly associated with COVID-19 vaccination willingness. Willingness was also associated with believing one had never been infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and experiencing negative pandemic consequences. Safety concerns were most common among those unwilling. Our comprehensive assessment of COVID-19 vaccination willingness among older adults in Canada, a prioritized group for vaccination due to their risk of severe COVID-19 outcomes, provides a road map for conducting outreach to increase uptake, which is urgently needed.

Ribo-Pop: simple, cost-effective, and widely applicable ribosomal RNA depletion.

The measurement of RNA abundance derived from massively parallel sequencing experiments is an essential technique. Methods that reduce ribosomal RNA levels are usually required prior to sequencing library construction because ribosomal RNA typically comprises the vast majority of a total RNA sample. For some experiments, ribosomal RNA depletion is favored over poly(A) selection because it offers a more inclusive representation of the transcriptome. However, methods to deplete ribosomal RNA are generally proprietary, complex, inefficient, applicable to only specific species, or compatible with only a narrow range of RNA input levels. Here, we describe Ribo-Pop (ribosomal RNA depletion for popular use), a simple workflow and antisense oligo design strategy that we demonstrate works over a wide input range and can be easily adapted to any organism with a sequenced genome. We provide a computational pipeline for probe selection, a streamlined 20-min protocol, and ready-to-use oligo sequences for several organisms. We anticipate that our simple and generalizable "open source" design strategy would enable virtually any laboratory to pursue full transcriptome sequencing in their organism of interest with minimal time and resource investment.

Cognitive Function Is Associated With Multiple Indices of Adiposity in the Canadian Longitudinal Study on Aging: A Cross-Sectional Analysis.

OBJECTIVE: Prior studies have suggested reciprocal relationships between cognitive function and adiposity, but this has not been investigated with population representative data sets. The purpose of this study was to examine the association between cognitive function and adiposity in a large population-based sample of middle-aged and older adults. It was hypothesized that better scores on tests of cognitive function would be associated with lower adiposity, and this association would be primarily mediated through life-style behavior and physical health status. METHODS: Using baseline data from the Canadian Longitudinal Study on Aging ( N = 30,097), we tested our hypotheses using three indicators of cognitive function (animal fluency, Stroop interference, and reaction time) and four indicators of adiposity (body mass index, total fat mass, waist circumference, and waist-hip ratio). Hierarchical multivariable linear regression modeling was conducted followed by tests for moderation by socioeconomic status and mediation through diet, physical activity, hypertension, and diabetes status. RESULTS: All measures of cognitive indicators were significantly associated with adiposity after adjusting for confounders. In general, superior performance on animal fluency, Stroop, and reaction time tasks were associated with lower adiposity by most metrics. Stroop interference was associated with lower adiposity across all metrics, including body mass index ( b = - 0.04, 95 % confidence interval [CI] = - 0.06 to - 0.01), total fat mass ( b = 19.35, 95 % CI = 8.57 to 30.12), waist circumference ( b = 33.83, 95 % CI = 10.08 to 57.58), and waist-hip ratio ( b = 0.13, 95 % CI = 0.01 to 0.24). These associations were more substantial for moderate- and high-income subpopulations. Mediation analyses suggested that the aforementioned effects were mediated through life-style behavior (e.g., diet and physical activity) and physical health conditions (e.g., diabetes and hypertension). CONCLUSIONS: Reliable associations exist between cognitive function and adiposity in middle-aged and older adults. The associations seem to be mediated through life-style behavior and physical health conditions.

The Differential Impact of the 2000 Canadian Graphic Warning Label Policy on Smoking Prevalence by Sex and Education: A Difference-in-Difference-in-Difference Model.

INTRODUCTION: Using a quasiexperimental design, we compared the impact of the 2000 Canadian introduction of graphic warning labels (GWLs) on differences in smoking prevalence by sex and education, to the United States, where no GWLs were introduced. METHODS: We pooled 1999-2004 data from the Canadian Tobacco Use Monitoring Survey and the U.S. Behavioral Risk Factor Surveillance System. We used a difference-in-difference (DD) model to assess the impact of Canadian policy introduction on smoking prevalence, and a difference-in-difference-in-difference (DDD) model to examine differences in the policy impact by sex and education, comparing Canada (the treatment group) with the United States (the control group). RESULTS: From 1999 to 2004, smoking prevalence decreased from 23.7% to 18.6% in Canada, and from 21.7% to 20.0% in the United States. Results from the DD regression models showed that Canadian respondents reported lower odds of being a current smoker compared to the U.S. respondents following the 2000 introduction of GWLs (OR = 0.84, 95% CI = 0.74-0.94). The DDD model showed that the impact of the Canadian GWLs versus the United States did not differ by sex or education. CONCLUSIONS: The 2000 Canadian GWL policy reduced smoking prevalence overall, with similar reductions for males and females and across education levels. The impact of the Canadian GWLs in reducing smoking prevalence did not reduce differences by sex or education. Although beneficial for all smokers, GWLs may not serve to decrease existing disparities, especially those by socioeconomic status. IMPLICATIONS: Existing evidence shows that GWL implementation is associated with reductions in smoking prevalence. But there is limited evidence from past evaluation studies on whether the impact of GWLs on smoking prevalence differs by sociodemographic subgroup. Our findings confirm existing studies that the 2000 implementation of GWLs in Canada was significantly associated with an overall reduction in smoking prevalence in Canada compared to the United States. However, our study improves existing evidence by showing that the impact of the Canadian GWLs on smoking prevalence did not differ by sex or education, and thus did not reduce existing smoking disparities by educational levels.

Increasing Cannabis Use Is Associated With Poorer Cigarette Smoking Cessation Outcomes: Findings From the ITC Four Country Smoking and Vaping Surveys, 2016-2018.

INTRODUCTION: Concurrent use of tobacco and cannabis may impede successful cigarette smoking cessation. This study examined whether changes in cannabis use frequency were associated with smoking cessation. AIMS AND METHODS: Nationally representative samples of adult cigarette smokers from Canada (n = 1455), the United States (n = 892), England (n = 1416), and Australia (n = 717) were surveyed in 2016 and 2018. In each year, smokers reported how often they used cannabis in the previous 12 months. Reports were compared to determine whether cannabis use increased, remained unchanged, or decreased. Smoking cessation outcomes, measured in 2018, were (1) any attempt to quit in the previous year, (2) currently quit, and (3) currently quit for at least 6 months. Weighted multivariable logistic regression estimated the association between changes in cannabis use and cessation outcomes. RESULTS: Cigarette smokers who increased their frequency of cannabis use were significantly less likely to be currently quit than noncannabis-using smokers (adjusted odds ratio (aOR) = 0.52, 95% CI = 0.31% to 0.86%); they were also less likely to have quit for at least 6 months (aOR = 0.30; 95% CI = 0.15% to 0.62%). CONCLUSIONS: Smokers who increase their frequency of cannabis use have poorer smoking cessation outcomes compared to noncannabis-using smokers. It will be important to monitor the impact of cannabis legalization on patterns of cannabis use, and whether this influences cigarette smoking cessation rates. IMPLICATIONS: Cigarette smokers who start using cannabis may be less likely to quit cigarettes compared with smokers who do not use cannabis at all. If smokers who also use cannabis are more likely to continue smoking, it is important to monitor these trends and understand the impact, if any, on smoking cessation in jurisdictions that have legalized cannabis for nonmedical use.

Isolated CNS Relapse in 2 High-Risk B-cell Acute Lymphoblastic Leukemia Patients Following SARS-CoV-2 Infection.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy with a highly favorable overall prognosis. Central nervous system (CNS) relapse of B-ALL is relatively rare and is associated with inferior survival outcomes. We present two patients with B-ALL who developed isolated CNS relapse following confirmed infection with severe acute respiratory syndrome coronavirus 2. In addition to individual and disease factors, we posit that delays in therapy together with immune system modulation because of severe acute respiratory syndrome coronavirus 2 may account for these 2 cases of CNS relapsed B-ALL. We report on this clinical observation to raise awareness of this potential association.

The Journey: Parental Expectations and Perceptions of Therapy Services for Children With Down Syndrome.

PURPOSE: The researchers sought to identify and describe parents' expectations and perceptions of therapy services received by their children with Down syndrome. METHODS: This study used a qualitative descriptive approach conducted in 2 phases: individual semi-structured parent interviews followed by focus groups. Analysis of interview transcripts served as the basis for development of codes, categories, and themes describing parents' beliefs, values, and opinions of their children's therapy. RESULTS: Within the metaphor of The Journey, 3 major themes emerged: Where are we going? Who's driving the car? What I really need for this trip. CONCLUSIONS: Parents value the principles of family-centered care and want a partnership with therapists in caring for their children. Therapists can help parents of children with Down syndrome navigate their children's therapy services by establishing a relationship of trust and by communicating with respect, understanding, and compassion.

The combined effect of behavioural risk factors on disability in aging adults from the Canadian Longitudinal Study on Aging (CLSA).

The objective of this study was to explore how behavioural risk factors (smoking, physical activity, and nutrition) cluster together and assess how clusters of behavioural risk factors are associated with functional disability by age and sex at the individual and population level. We used currently available baseline cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The CLSA is a national, population-based longitudinal study established to understand and examine health of an aging population. This study included 51,338 Canadian men and women aged 45 to 85 years residing in the community in 10 Canadian provinces. Behavioural risk factors included smoking, physical activity, and nutrition. The main outcome used in the study was functional disability, which was assessed using a questionnaire adapted from the Older Americans Resources and Services Multidimensional Assessment Questionnaire. In this analyses of unique combinations of the risk factors of smoking, physical activity, and nutritional risk, the magnitude of the association of the behavioural risk factors with functional disability was dependent on which risk factors were included and differed by age and sex strata. Of the risk factors, physical activity accounted for between 70% to 90% of the total population level risk in individuals with all three risk factors, suggesting it is a key driver of the population burden of disability. Together, these results show that considering unique clusters of risk factors, as well as age and sex, is essential for tailoring public health strategies to reduce the burden of disability among aging populations.