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Abstract Since dietary intake is challenging to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, 24-hour recalls, and diet records) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors, which can lead to inaccuracies in the calculation of nutrient profiles. Currently, few computational methods exist to address this problem. In the present study, we introduce a deep-learning approach—Microbiome-based nutrient profile corrector (METRIC), which leverages gut microbial compositions to correct random errors in self-reported dietary assessments using 24-hour recalls or diet records. We demonstrate the excellent performance of METRIC in minimizing the simulated random errors, particularly for nutrients metabolized by gut bacteria in both synthetic and three real-world datasets. Additionally, we find that METRIC can still correct the random errors well even without including gut microbial compositions. Further research is warranted to examine the utility of METRIC to correct actual measurement errors in self-reported dietary assessment instruments.

Abstract Background Perioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias. Objective We aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant. Methods This single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes. Results Twenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05). Conclusion and Relevance Both AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications.

Abstract Background To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. Results Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. Conclusion For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies.

Abstract The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare (

Electrosynthesis is a technique that is attracting increased attention and has many appealing features, particularly its potential greenness. At the same time, electrosynthesis requires a solvent and a supporting electrolyte in order for current to pass through the reaction. These are effectively consumable reagents unless a convenient means of recycling can be developed. As part of our interest in unusual solvents and electrochemistry, we explored the application of simple, inexpensive, and recyclable deep eutectic solvents to the allylation of carbonyls. While several sets of conditions were developed, the goal of avoiding stoichiometric amounts of metal has proven elusive. Still, a deep eutectic solvent can be used to plate out and thus recover the metal used, offering an interesting new option for electrochemical allylations.

Abstract Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients’ samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

Abstract Background Several recent global events may have impacted adolescent sleep and exacerbated pre-existing disparities by social positions (i.e., social roles, identity or sociodemographic factors, and/or group memberships that are associated with power and oppression due to the structures and processes in a given society at given time). Current understanding of sleep among adolescents is critical to inform interventions for a more equitable future, given the short and long-term consequences of inadequate sleep on health and well-being. This study aimed to provide contemporary evidence on sleep disparities by key social positions among adolescents in Canada. Methods Cross-sectional analyses were conducted using self-reported data collected during 2020–2021 (the first full school year after the COVID-19 pandemic onset) from 52,138 students (mean [SD] age = 14.9 [1.5]) attending 133 Canadian secondary schools. Multiple regression models were used to test whether sleep quality (how well students slept during past week), duration (weekday, weekend, weighted daily average), and guideline adherence (8–10 h/day) differed by sex and gender, race and ethnicity, and socioeconomic status (SES). Results Females reported a mean [95% CI] difference of -1.7 [-3.7, 0.4] min/day less sleep on weekdays than males, but 7.1 [4.5, 9.6] min/day more sleep on weekends, resulting in no difference in average daily sleep between males and females. Females were less likely to report good quality sleep compared to males (AOR = 0.57 [0.54, 0.60]). SES followed a generally monotonic trend where higher scores were associated with more sleep on weekdays (Δhighest: lowest = -28.6 [-39.5, -17.6]) and weekends (Δhighest: lowest = -17.5 [-3.8, -31.2]) and greater likelihood of higher sleep quality (AORhighest: lowest = 3.04 [2.35, 3.92]). Relative to White adolescents, weekday and average daily sleep duration were lower among all other racial identities; mean differences ranged from ∼ 5–15 min/day, with Black students reporting the least sleep. Conclusions Differences in sleep duration and quality were most profound among adolescents from the lowest and highest SES. Racial disparities were more evident on weekdays. Compensatory weekend sleep appears more pronounced in females than males. Addressing sleep inequities is critical, as a robust predictor of multiple health outcomes.

The aryl diester compound, 2-methyl-1,4-phenylene bis(3,5-dibromobenzoate), C21H12Br4O4, was synthesized by esterification of methyl hydroquinone with 3,5-dibromobenzoic acid. A crystalline sample was obtained by cooling a sample of the melt (m.p. = 502 K/DSC) to room temperature. The molecular structure consists of a central benzene ring with anti-3,5-dibromobenzoate groups symmetrically attached at the 1 and 4 positions and a methyl group attached at the 2 position of the central ring. In the crystal structure (space group P\overline{1}), molecules of the title aryl diester are located on inversion centers imposing disorder of the methyl group and H atom across the central benzene ring. The crystal structure is consolidated by a network of C—H...Br hydrogen bonds in addition to weaker and offset π–π interactions involving the central benzene rings as well as the rings of the attached 3,5-dibromobenzoate groups.

Abstract Neurodevelopmental disorders are rapidly increasing in prevalence and have been linked to various environmental risk factors. Mounting evidence suggests a potential role of vitamin D in child neurodevelopment, though the causal mechanisms remain largely unknown. Here, we investigate how vitamin D deficiency affects children’s communication development, particularly in relation to Autism Spectrum Disorder (ASD). We do so by developing an integrative network approach that combines metabolomic profiles, clinical traits, and neurodevelopmental data from a pediatric cohort. Our results show that low levels of vitamin D are associated with changes in the metabolic networks of tryptophan, linoleic, and fatty acid metabolism. These changes correlate with distinct ASD-related phenotypes, including delayed communication skills and respiratory dysfunctions. Additionally, our analysis suggests the kynurenine and serotonin sub-pathways may mediate the effect of vitamin D on early life communication development. Altogether, our findings provide metabolome-wide insights into the potential of vitamin D as a therapeutic option for ASD and other communication disorders.

Abstract The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human intestinal epithelial cells (IECs). Here, we present two reporters and a complete platform for analyzing cell cycle phases in live primary human IECs. We interrogate the transcriptional identity of IECs grown on soft collagen, develop two fluorescent cell cycle reporter IEC lines, design and 3D print a collagen press to make chamber slides for optimal imaging while supporting primary human IEC growth, live image cell cycle dynamics, then assemble a computational pipeline building upon free-to-use programs for semi-automated analysis of cell cycle phases. The PIP-FUCCI construct allows for assigning cell cycle phase from a single image of living cells, and our PIP-H2A construct allows for semi-automated direct quantification of cell cycle phase lengths using our publicly available computational pipeline. Treating PIP-FUCCI IECs with oligomycin demonstrates that inhibiting mitochondrial respiration lengthens G1 phase, and PIP-H2A cells allow us to measure that oligomycin differentially lengthens S and G2/M phases across heterogeneous IECs. These platforms provide opportunities for future studies on pharmaceutical effects on the intestinal epithelium, cell cycle regulation, and more.

Abstract Background E-cigarette use represents a contemporary mode of nicotine product use that may be changing the risk profile of participating adolescents. Understanding differences in sociodemographic characteristics of adolescents engaging in contemporary e-cigarette use and traditional cigarette use is important for effectively developing and targeting public health intervention programs. The objective of this study was to identify and compare sociodemographic risk profiles for exclusive e-cigarette use and dual-product use among a large sample of Canadian youth. Methods A survey of 46,666 secondary school students in the 2021-22 wave of the COMPASS study measured frequency of past month e-cigarette and cigarette use as well as age, sex, gender, racial or ethnic background, spending money, relative family affluence, and having one’s own bedroom. Rates of cigarette-only, e-cigarette-only, and dual product use were calculated, and separate classification trees were run using the CART algorithm to identify sociodemographic risk profiles for weekly dual-product use and weekly e-cigarette-only use. Results Over 13% of adolescents used only e-cigarettes at least weekly, 3% engaged in weekly dual e-cigarette and cigarette use, and less than 0.5% used only cigarettes. Available spending money was a common predictor of dual-product and e-cigarette-only use. Gender diverse youth and youth with lower perceived family affluence were at higher risk for dual-product use, while white and multiethnic adolescents were at greater risk of e-cigarette-only use. Two high-risk profiles were identified for e-cigarette-only use and four high-risk profiles were identified for dual product use. Conclusions This study used a novel modelling approach (CART) to identify combinations of sociodemographic characteristics that profile high-risk groups for exclusive e-cigarette and dual-product use. Unique risk profiles were identified, suggesting that e-cigarettes are attracting new demographics of adolescents who have not previously been considered as high-risk for traditional cigarette use.

Summary: Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival. Methods: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation. Findings: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70–0.76) included whole-body maximum standardised uptake value (SUVmax), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65–0.72) included SUVmax, time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68–0.77) included SUVmax, lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUVmax. Interpretation: These models of outcomes with 177Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design. Funding: Novartis.

ABSTRACT Optimal egg size theory implies that female organisms balance between fecundity and individual offspring investment according to their environment. Past interspecific studies suggest that fishes in large marine systems generally produce smaller eggs than those in small freshwater systems. We tested whether intraspecific egg size variation reflected a similar pattern by comparing egg size among yellow perch (Perca flavescens) populations inhabiting a range of system sizes. In 2018, 2019, and 2023, we collected yellow perch egg samples from 12 locations in systems ranging in surface area from 37 to 5,390,492 ha. First, we found that egg diameter significantly increased with maternal total length in five of eight individually tested populations. After accounting for these maternal effects, we found a significant interaction, where females inhabiting larger lakes, such as the main basins of Lakes Erie and Michigan, produced smaller eggs than those in smaller inland lakes, and the greatest differences were demonstrated among females of greater total length. This egg size variation in the largest females is consistent with interspecific egg size comparisons between marine and freshwater fishes. However, by examining a single species across vastly different environments, we were able to support theoretical expectations that maternal investment in offspring should vary with environmental conditions controlling early‐life resource acquisition and competition.

IntroductionMultifarious selective pressures can interact to affect species’ life history evolution, with predation and thermal exposure as selective pressures for nesting birds. Gray Vireos (Vireo vicinior) seemingly nest on the periphery of their nesting substrate because of lower predation rates, thereby increasing exposure to weather. We explored how nest placement and vegetation structure can be used to account for the increased weather exposure that Gray Vireos experience when nesting on the periphery of the nesting substrate to avoid predation.MethodsFor each Gray Vireo nest, we placed temperature and light data loggers at three locations: at the nest site, at the opposite orientation of the nest within the nesting tree, and at the same orientation of the nest but in an adjacent tree. To measure nest orientation, we recorded the inverse compass azimuth (+/−1°) from the nest toward the trunk of the nesting tree, while accounting for declination. Nest temperatures and light exposure were compared across various dimensions of nest placement.ResultsThe orientation of nests was cooler than the opposite orientation in the mornings and in the late afternoons. When nests were placed in hotter orientations (e.g., south- or west-facing), nests surrounded by more foliage or placed closer to the interior of trees could compensate for the increased exposure.DiscussionOur findings suggest Gray Vireos accounted for the increased thermal exposure that comes from predator avoidance by using secondary dimensions of nest placement. Specifically, nests could be placed in orientations with cooler temperatures or in hotter orientations with greater shade potential. These results highlight how the interactive selection pressures of predation risk and microclimate can be tiered and shape life-history characteristics of birds.

Accuracy-optimized convolutional neural networks (CNNs) have emerged as highly effective models at predicting neural responses in brain areas along the primate ventral stream, but it is largely unknown whether they effectively model neurons in the complementary primate dorsal stream. We explored how well CNNs model the optic flow tuning properties of neurons in dorsal area MSTd and we compared our results with the Non-Negative Matrix Factorization (NNMF) model, which successfully models many tuning properties of MSTd neurons. To better understand the role of computational properties in the NNMF model that give rise to optic flow tuning that resembles that of MSTd neurons, we created additional CNN model variants that implement key NNMF constraints – non-negative weights and sparse coding of optic flow. While the CNNs and NNMF models both accurately estimate the observer's self-motion from purely translational or rotational optic flow, NNMF and the CNNs with nonnegative weights yield substantially less accurate estimates than the other CNNs when tested on more complex optic flow that combines observer translation and rotation. Despite its poor accuracy, NNMF gives rise to tuning properties that align more closely with those observed in primate MSTd than any of the accuracy-optimized CNNs. This work offers a step toward a deeper understanding of the computational properties and constraints that describe the optic flow tuning of primate area MSTd.

Aims: Previous research has reported racial disparities in out-of-hospital cardiac arrest (OHCA) interventions, including bystander CPR and AED use. However, studies on other prehospital interventions are limited. The primary objective of this study was to investigate race/ethnic disparities in out-of-hospital cardiac arrest (OHCA) interventions: EMS response times, medication administration, and decisions for intra-arrest transport. The secondary objective was to evaluate differences in the provision of Bystander CPR (CPR) and application of AED. Methods: We retrospectively analyzed data from the Salt Lake City Fire Department (2010–2023). We included adults 18 years or older with EMS-treated OHCA. Race/ethnicity was categorized as White people, Asian people, Black people, Hispanic people, and others. We employed multivariable regression analysis to evaluate the association between race/ethnicity and the outcomes of interest. Results: Unadjusted analyses revealed no significant differences across ethnic groups in EMS response, medication administration, bystander CPR, or intra-arrest transport decisions. However, significant ethnic disparities were observed in Automated External Defibrillator (AED) utilization, Black people having the lowest rate (6.5%) and Asian people the highest (21.8%). The adjusted analysis found no significant association between race/ethnicity and all OHCA intervention measures, nor between race/ethnicity and survival outcomes. Conclusions: Our multivariable analysis found no statistically significant association between race/ethnicity and EMS response time, epinephrine administration, antiarrhythmic medication use, bystander CPR, AED intervention, or intra-arrest transport. These results imply regional variations in ethnic disparities in OHCA may not be consistent across all areas, warranting further research into disparities in other regions and additional influential factors like neighborhood conditions and socioeconomic status.

Abstract Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

IntroductionResearch characterizing substance use disparities between gender minority youth (GMY) and non-GMY (i.e. girls and boys) is limited. The aim of this study was to examine the differences in substance use behaviours among gender identity (GI) groups and identify associated risk and protective factors. MethodsCross-sectional data from Canadian secondary school students (n = 42 107) that participated in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study were used. Hierarchal logistic regression models estimated current substance use (cigarettes, e-cigarettes, binge drinking, cannabis and nonmedical prescription opioids [NMPOs]). Predictor variables included sociodemographics, other substances, mental health outcomes, school connectedness, bullying and happy home life. Interaction terms were used to test mental health measures as moderators in the association between GI and substance use. ResultsCompared to non-GMY, GMY reported a higher prevalence for all substance use outcomes. In the adjusted analyses, GMY had higher odds of cigarette, cannabis and NMPO use and lower odds for e-cigarette use relative to non-GMY. The likelihood of using any given substance was higher among individuals who were involved with other substances. School connectedness and happy home life had a protective effect for all substances except binge drinking. Bullying victimization was associated with greater odds of cigarette, e-cigarette use and NMPOs. Significant interactions between GI and all mental health measures were detected. ConclusionFindings highlight the importance of collecting a GI measure in youth population surveys and prioritizing GMY in substance use–related prevention, treatment and harm reduction programs. Future studies should investigate the effects of GI status on substance use onset and progression among Canadian adolescents over time.

IntroductionLes travaux de recherche caractérisant les disparités en matière de consommation de substances entre les jeunes faisant partie de minorités de genre et les jeunes ne faisant pas partie de minorités de genre, c’est-à-dire les filles et les garçons, sont limités. L’objectif de cette étude était d’explorer les différences dans les comportements liés à la consommation de substances entre groupes d’identité de genre et de déterminer les facteurs de risque et les facteurs de protection correspondants. MéthodologieNous avons utilisé les données transversales associées aux élèves canadiens du secondaire (n = 42 107) qui avaient participé à l’année 8 (2019-2020) ou à l’année 9 (2020-2021) de l’étude COMPASS. Des modèles de régression logistique hiérarchiques nous ont permis d’estimer la consommation de substances (cigarettes, cigarettes électroniques, consommation excessive d’alcool, cannabis et opioïdes à des fins non médicales). Les variables prédictives comprenaient les caractéristiques sociodémographiques, la consommation d’autres substances, les résultats en matière de santé mentale, les liens avec l’école, l’intimidation et une vie familiale heureuse. Nous avons utilisé des termes d’interaction pour tester les mesures de la santé mentale en tant que modérateurs de l’association entre l’identité de genre et la consommation de substances. RésultatsComparativement aux jeunes ne faisant pas partie de minorités de genre, les jeunes faisant partie de minorités de genre avaient une prévalence plus élevée pour tous les résultats liés à la consommation de substances. Dans les analyses ajustées, les jeunes faisant partie de minorités de genre avaient une probabilité plus élevée de fumer des cigarettes, de consommer du cannabis et d’utiliser des opioïdes à des fins non médicales et une probabilité plus faible d’utiliser des cigarettes électroniques par rapport aux autres jeunes. La probabilité de consommer une substance donnée était plus élevée chez ceux qui consommaient d’autres substances. La connexion à l’école et une vie familiale heureuse avaient un effet protecteur contre toutes les substances, sauf la consommation excessive d’alcool. La victimisation par intimidation était associée à une plus grande probabilité d’usage de cigarettes, de cigarettes électroniques et d’opioïdes à des fins non médicales. Nous avons observé des interactions statistiquement significatives entre l’identité de genre et l’ensemble des mesures de la santé mentale. ConclusionNos constatations soulignent l’importance de recueillir une mesure de l’identité de genre dans les enquêtes sur les jeunes et de prioriser les jeunes faisant partie de minorités de genre dans les programmes de prévention, de traitement et de réduction des méfaits liés à la consommation de substances. Les études ultérieures devraient porter sur les effets de l’identité de genre sur le début et l’évolution de la consommation de substances chez les adolescents canadiens au fil du temps.

Abstract The prevalence of alcohol‐use disorders is higher amongst adults experiencing homelessness (AEH) compared with domiciled adults. Greater exposure to heavy drinkers increases personal risk for heavy alcohol use. AEH spend substantial periods of time at shelters and report greater pressure to use alcohol when near shelter locations, as well as greater negative affect when near a shelter. It is unclear if the relationship between affect and (1) interacting with people and (2) being near someone AEH drank alcohol with before differs when AEH are at a shelter versus not. AEH reporting alcohol misuse (n = 72, Mage = 47, 85% male, 68% non‐White) completed five daily smartphone‐based ecological momentary assessments over 28 days. Generalized multilevel modeling revealed that when AEH were interacting with someone they drank with before, they had significantly lower positive affect when at a shelter (b = −0.17, p = 0.05) versus when not (b = 0.00, p = 0.99). AEH are likely to interact with previous drinking partners while at shelters. It may be important to deliver real‐time treatment messages targeting affect in these moments, as well as deliver alcohol reduction/abstinence messages.

Background: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. Objective: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. Methods: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). Results: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. Conclusions: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. Trial registration: ClinicalTrials.gov Identifier NCT03887715.

Abstract The molecular characteristics of metastatic upper tract urothelial carcinoma (UTUC) are not well understood, and there is a lack of knowledge regarding the genomic and transcriptomic differences between primary and metastatic UTUC. To address these gaps, we integrate whole-exome sequencing, RNA sequencing, and Imaging Mass Cytometry using lanthanide metal-conjugated antibodies of 44 tumor samples from 28 patients with high-grade primary and metastatic UTUC. We perform a spatially-resolved single-cell analysis of cancer, immune, and stromal cells to understand the evolution of primary to metastatic UTUC. We discover that actionable genomic alterations are frequently discordant between primary and metastatic UTUC tumors in the same patient. In contrast, molecular subtype membership and immune depletion signature are stable across primary and matched metastatic UTUC. Molecular and immune subtypes are consistent between bulk RNA-sequencing and mass cytometry of protein markers from 340,798 single cells. Molecular subtypes at the single-cell level are highly conserved between primary and metastatic UTUC tumors within the same patient.

Abstract Background Physical activity behaviours are known to be highly correlated. Adolescents who participate in one type of physical activity (e.g., physical education) have a greater likelihood of participating in other physical activities (e.g., organized sports); however, little research has examined participation rates in various physical activity behaviours concurrently. This study identified longitudinal physical activity profiles among secondary school aged youth in Ontario, Canada. Methods We used data from the COMPASS Study, a school-based prospective cohort study of adolescents in Canada. Using a repeated measures latent class analysis, Ontario students who participated in grade 9 PE in 2015-16 were analysed through to 2018-19 (n = 1,917). Latent classes were defined by: PE participation, guideline adherence (≥ 60 min/day of moderate to vigorous activity over the last 7 days), and sport participation (varsity, community, and/or intramural). Multinomial logistic regression models were used to examine associations between latent class membership and student characteristics. Results Three distinct latent classes were identified for females and four were identified for males. These classes were: (1) Guidelines (high probability of guideline adherence; females: 44%; males: 16%), (2) PE & Sports (high probability of PE and sport participation; females: 33%; males: 43%), (3) Guidelines & Sports (high probability of guideline adherence and sport participation; females: 23%; males: 23%;), and (4) Inactive (low probability of all physical activity indicators; males: 18%). Strength training, sleep, and English grade were associated with class membership among females. Ethno-racial identity, weekly spending money, strength training, and English and math grades were associated with class membership among males. Conclusions Findings suggest that latent physical activity profiles differ by sex. Guideline adherence was the most common class among females, indicating high levels of independent physical activity, whereas PE & Sport participation was the most common class among males, indicating greater tendency towards organized activities. Additionally, a substantial number of male students were not engaging in any physical activity. Participation in both PE and sports did not necessarily lead to meeting physical activity guidelines, highlighting that these activities alone may not be providing sufficient levels of physical activity that align with current recommendations for Canadian youth.

IntroductionThe COVID-19 pandemic intensified the impact of risk factors for adolescent mental health, including financial worry. Social support has shown to protect from negative mental health during times of stress. We examined the effect of financial worry on changes in anxiety and depression symptoms among Canadian adolescents prior to and during the pandemic, and assessed whether social support from family and friends moderated any changes. MethodsWe analyzed 2-year linked data from the 2018/19 (pre-pandemic) and 2020/21 (during-pandemic) waves of the COMPASS study, with reports from 12 995 Canadian secondary school students. A series of multilevel linear regressions were conducted to examine the main hypotheses under study. ResultsStudents scored an average (SD) of 7.2 (5.8) on the anxiety (GAD-7) and 10.0 (6.5) on the depression (CESD-10) scales; 16.1% reported they experienced financial worry during the pandemic. Financial worry was a strong and significant predictor of increased anxiety scores (+1.7 score between those reporting “true/mostly true” versus “false/mostly false”) during the pandemic, but not for depression scores. Low family and friend support were associated with anxiety, and low family support was associated with depression. No significant interactions were detected between social support and financial worry. ConclusionPandemic-related financial worry was significantly associated with anxiety in our large sample of Canadian adolescents. Clinical and public health initiatives should be aware of adolescents’ financial worry and its associations with anxiety during times of crisis.

IntroductionLa pandémie de COVID-19 a intensifié les effets des facteurs de risque associés à la santé mentale des adolescents, en particulier les préoccupations financières. Par ailleurs, on sait que le soutien social offre une protection contre les problèmes de santé mentale pendant les périodes de stress. C’est dans ce cadre que nous avons exploré l’effet des préoccupations financières sur les variations des symptômes d’anxiété et de dépression chez les adolescents canadiens avant et pendant la pandémie, pour déterminer si le soutien social apporté par la famille et les amis modérait ces variations. MéthodologieNous avons analysé des données couplées sur deux ans provenant des vagues 2018-2019 (avant la pandémie) et 2020-2021 (pendant la pandémie) de l’étude COMPASS pour 12 995 élèves canadiens du secondaire. Nous avons réalisé une série de régressions linéaires multiniveaux pour explorer les principales hypothèses à l’étude. RésultatsLes élèves ont obtenu un score moyen de 7,2 (écart-type : 5,8) pour l’anxiété (échelle GAD-7) et de 10,0 (6,5) pour la dépression (échelle CESD-10), et 16,1 % des élèves ont déclaré avoir eu des préoccupations financières pendant la pandémie. Les préoccupations financières ont constitué un facteur de prédiction important et statistiquement significatif de scores d’anxiété plus élevés (+1,7 entre ceux qui ont répondu « vrai/le plus souvent vrai » et ceux qui ont répondu « faux/le plus souvent faux ») pendant la pandémie, mais non en ce qui concerne les scores de dépression. Il existe un lien entre un faible soutien de la part de la famille et des amis et l’anxiété ainsi qu’entre un faible soutien de la part de la famille et la dépression. Aucune interaction importante n’a été observée entre le soutien social et les préoccupations financières. ConclusionLes préoccupations financières liées à la pandémie ont été fortement associées à l’anxiété dans notre large échantillon d’adolescents canadiens. Les initiatives cliniques et sanitaires doivent tenir compte des préoccupations financières des adolescents et de leurs liens avec l’anxiété en période de crise.

Abstract There are known individual differences in both the ability to learn the layout of novel environments and the flexibility of strategies for navigating known environments. However, it is unclear how navigational abilities are impacted by high-stress scenarios. Here we used immersive virtual reality (VR) to develop a novel behavioral paradigm to examine navigation under dynamically changing situations. We recruited 48 participants (24 female; ages 17–32) to navigate a virtual maze (7.5 m × 7.5 m). Participants learned the maze by moving along a fixed path past the maze’s landmarks (paintings). Subsequently, participants experienced either a non-stress condition, or a high-stress condition tasking them with navigating the maze. In the high-stress condition, their initial path was blocked, the environment was darkened, threatening music was played, fog obstructed more distal views of the environment, and participants were given a time limit of 20 s with a countdown timer displayed at the top of their screen. On trials where the path was blocked, we found self-reported stress levels and distance traveled increased while trial completion rate decreased (as compared to non-stressed control trials). On unblocked stress trials, participants were less likely to take a shortcut and consequently navigated less efficiently compared to control trials. Participants with more trait spatial anxiety reported more stress and navigated less efficiently. Overall, our results suggest that navigational abilities change considerably under high-stress conditions.

Abstract All-polymer solar cells (all-PSCs) offer improved morphological and mechanical stability compared with those containing small-molecule-acceptors (SMAs). They can be processed with a broader range of conditions, making them desirable for printing techniques. In this study, we report a high-performance polymer acceptor design based on bithiazole linker (PY-BTz) that are on par with SMAs. We demonstrate that bithiazole induces a more coplanar and ordered conformation compared to bithiophene due to the synergistic effect of non-covalent backbone planarization and reduced steric encumbrances. As a result, PY-BTz shows a significantly higher efficiency of 16.4% in comparison to the polymer acceptors based on commonly used thiophene-based linkers (i.e., PY-2T, 9.8%). Detailed analyses reveal that this improvement is associated with enhanced conjugation along the backbone and closer interchain π-stacking, resulting in higher charge mobilities, suppressed charge recombination, and reduced energetic disorder. Remarkably, an efficiency of 14.7% is realized for all-PSCs that are solution-sheared in ambient conditions, which is among the highest for devices prepared under conditions relevant to scalable printing techniques. This work uncovers a strategy for promoting backbone conjugation and planarization in emerging polymer acceptors that can lead to superior all-PSCs.

Abstract Background Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. Methods We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). Results We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. Conclusions miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.

Background: Determining when to recommend a change in treatment regimen due to insufficient improvement is a common challenge in therapeutics. Methods: In a sample of 7215 patients with major depressive disorder treated with transcranial magnetic stimulation (TMS) and with PHQ-9 scores before, during and after the course, 3 groups were identified based on number of acute course sessions: exactly 36 sessions (N = 3591), more than 36 sessions (N = 975), and less than 36 sessions (N = 2649). Two techniques were used to determine thresholds for percentage change in PHQ-9 scores at assessments after 10, 20, and 30 sessions that optimized prediction of endpoint response status: the Youden index and fixing the false positive rate at 10%. Positive and negative predictive values were calculated to assess the accuracy of identifying final nonresponders and responders, respectively. Results: There was greater accuracy in predicting final response than nonresponse, especially in the groups that had at least 36 sessions. Substantial proportions of patients with low levels of early improvement were classified as responders at the end of treatment. Limitations: The findings should be validated with clinician ratings using a more comprehensive depression severity scale. Conclusions: Manifesting clinical improvement early in the TMS course is strongly predictive of final status as a responder, while lack of early improvement is a relatively poor indicator of final nonresponse status. The predictive value of lack of early symptomatic improvement is too low to make reliable recommendations regarding changes in treatment regimen.

Background: Medical mistrust may worsen communication between ICU surrogate decision-makers and intensivists. The prevalence of and risk factors for medical mistrust among surrogate decision-makers are not known. Research Question: What are the potential sociodemographic risk factors for high medical mistrust among surrogate decision-makers of critically ill patients at high risk of death? Study Design and Methods: In this pilot cross-sectional study conducted at a single academic medical center between August 2022 and August 2023, adult patients admitted to the medical ICU and their surrogate decision-makers were enrolled. All patients were incapacitated at enrollment with Sequential Organ Failure Assessment scores of ≥ 7 or required mechanical ventilation with vasopressor infusion. Surrogate decision-maker sociodemographic characteristics were age, race, sex, education, relationship to the patient, employment, prior exposure to a loved one transitioning to hospice or comfort-focused care, and religiousness. The primary outcome was surrogate decision-maker medical mistrust, measured using the Medical Mistrust Multiformat Scale. Multiple linear regression was used to determine sociodemographic characteristics associated with higher medical mistrust. Results: Thirty-one patients and their surrogate decision-makers were enrolled during the study period, surpassing our goal of 30 pairs and indicating recruitment feasibility. Mean ± SD surrogate age was 53.8 ± 14.5 years, 24 surrogates were female, and mean medical mistrust score was 17.1 ± 5.4. Race was associated with medical mistrust, with Black participants showing higher medical mistrust compared with White participants (β =10.21; 95% CI, 3.40-17.02; P = .010). Religiousness was associated with lower medical mistrust (β = –2.94; 95% CI, –4.43 to –1.41; P = .003). Prior exposure to hospice or comfort-focused care was associated with higher medical mistrust (β = 7.06; 95% CI, 1.21-12.91; P = .025). Interpretation: We found that recruiting ICU surrogates and measuring medical mistrust within 48 h of ICU admission was feasible. Several surrogate sociodemographic characteristics were associated with changes in medical mistrust. These preliminary findings will inform the design of future studies.

Aim: Cardiac arrest afflicts over 600,000 people annually in the United States. Rates of survival from cardiac arrest have remained stagnant for decades. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is most commonly used in the management of severe hemorrhagic shock, primarily for non-compressible thoracoabdominal trauma. A growing body of evidence suggests it may serve a role in augmenting cardiac and cerebral perfusion in non-traumatic, refractory cardiac arrest. Typically, REBOA is deployed by interventional radiologists under real-time fluoroscopy. Limited data exist to demonstrate the feasibility or logistics of successful REBOA deployment in emergency departments by emergency medicine physicians. Methods: We describe an emergency medicine-driven training program and treatment protocol developed to deploy REBOA in the emergency department for patients experiencing refractory out-of-hospital cardiac arrest and deemed ineligible for ECPR. We detail the training, certification processes, and clinical outcomes from our first eight cases. Results: Five emergency medicine physicians underwent training for REBOA placement through a didactic curriculum and hands-on training with mannequin and live tissue porcine models. Since protocol implementation, eight patients have undergone REBOA catheterization by emergency medicine physicians: 5 males and 3 females, age range 25–79. The first pass success was 8/8 (100 %), and all 3 commercially available catheters in the United States were successfully used. ROSC was achieved in 3/8 (37.5 %) patients, although no patients survived to hospital discharge. No REBOA catheter-associated complications were identified. Conclusions: This series demonstrates feasibility of emergency physician placed REBOA for non-traumatic, refractory cardiac arrest a novel resuscitative technique. Through a combination of focused education, innovative technology use, robust large animal model-based training, and strategic procedural integration, we showcase the potential for emergency departments to spearhead the adoption of this potentially life-saving intervention.

AbstractIntroduction Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, nonspecific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study’s aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense’s N-TidalTM capnometer.Method For COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1–4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity.Results The best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value (PPV) of 0.834. Evaluating performance on all test capnograms that were confidently ruled in or out yielded PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, sensitivity of 0.958, specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1.Conclusion The N-TidalTM device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care as a rapid rule-in or rule-out test. N-TidalTM also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.

Assessments of lake ecosystem health, based on indicators of physical–chemical water quality, ecological conditions, and human health risks, are needed to apprise the public and facilitate lake management. While unrefereed lake water quality reports exist, this is the first peer-reviewed study to report data processing and analysis methods and results for current state and recent trends in multiple environmental indicators in monitored lakes across Aotearoa New Zealand. Lake grading based on national criteria indicated that many lakes are failing to achieve statutory bottom lines for phytoplankton chlorophyll a, total nitrogen, and total phosphorus concentrations. In contrast, most monitored lakes had high grades for two human health risk indicators, E. coli and cyanobacteria concentrations, and for potential toxicity of ammonia for biological communities. We included 166 lakes and considered indicator state and trends for two lake classifications based on geomorphology and land cover. Elevated scores for an indicator of trophic state (the trophic level index; TLI) in most shoreline, riverine, peat, landslide, dam, and aeolian lakes indicated eutrophic conditions or worse. Lower TLI scores were indicative of oligotrophic conditions in most glacial lakes. Nutrient, E. coli and suspended sediment concentrations and TLI scores were positively correlated, and Secchi depths negatively correlated, with high-intensity agricultural land cover. Ten-year trend analyses indicated that lakes with increasing Secchi disk depth, chlorophyll a, dissolved reactive phosphorus, E. coli, ammoniacal nitrogen, TLI, total nitrogen, and total suspended solids trends outnumbered those with decreasing trends. Twenty-year trend analyses indicated that the numbers of lakes with increasing and decreasing trends in most of the indicators we assessed were comparable, but lakes with increasing 20-year trends in total nitrogen outnumbered those with decreasing trends, and lakes with decreasing 20-year trends in ammoniacal nitrogen, dissolved reactive phosphorus, total phosphorus, and nitrate nitrogen outnumbered those with increasing trends. This study presents clear data processing steps and trend analysis methods as applied to a nationwide dataset for Aotearoa New Zealand, while acknowledging data limitations. For example, the choice of trend periods is challenging and can greatly affect conclusions. The results of this empirical study and the collective results of preceding studies of lake ecosystem health indicate that eutrophication poses a threat to the ecological health of many if not most lakes in Aotearoa New Zealand. Recommendations include monitoring network expansion especially for the indicators bottom dissolved oxygen and cyanobacteria (toxic and total cyanobacteria biovolumes) and judicious selection of trend periods in lake-specific trend analyses to determine causes for increasing or decreasing trends in environmental indicators.

Abstract Background Asthma is routinely treated with inhaled corticosteroids (ICS). Asthma patients on ICS are at increased risk of adrenal suppression, a potentially serious effect of long‐term glucocorticoid exposure; however, this relationship is poorly understood. Therefore, this study aims to identify metabolite biomarkers related to adrenal suppression in asthma patients taking ICS. Methods A total of 571 urine metabolites from 200 children with asthma on ICS in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) cohort were profiled. Samples were grouped by peak plasma cortisol measurement as adrenal sufficient (>350 nmol/L) or insufficient (≤350 nmol/L) (outcome). Regression and discriminant‐based statistical models combined with network analyses were utilized to assess relationships between metabolites and the outcome. Finally, prioritized metabolites were validated using data from an ancillary study of the Childhood Asthma Management (CAMP) cohort with similar characteristics to PASS. Results Ninety metabolites were significantly associated with adrenal suppression, of which 57 also could discriminate adrenal status. While 26 metabolites (primarily steroids) were present at lower levels in the adrenal insufficient patients, 14 were significantly elevated in this group; the top metabolite, mannitol/sorbitol, was previously associated with asthma exacerbations. Network analyses identified unique clusters of metabolites related to steroids, fatty acid oxidation, and nucleoside metabolism, respectively. Four metabolites including urocanic acid, acetylcarnitine, uracil, and sorbitol were validated in CAMP cohort for adrenal suppression. Conclusions Urinary metabolites differ among asthma patients on ICS, by adrenal status. While steroid metabolites were reduced in patients with poor adrenal function, our findings also implicate previously unreported metabolites involved in amino acid, lipid, and nucleoside metabolism.

Abstract Understanding how changing seasonal precipitation will affect ecosystems and water resources can benefit from understanding how precipitation from different seasons contributes to runoff versus evapotranspiration (ET). We use stable‐isotope data from 23 National Ecological Observatory Network watersheds to quantify the fractions of winter and summer precipitation that supply ET, and the fractions of ET supplied by summer versus winter precipitation. Across 20 watersheds, 34%–101% of summer precipitation supplied ET, with 8%–105% of ET supplied by summer precipitation; these end‐member‐splitting solutions were poorly constrained in the other three watersheds. These precipitation partitioning fractions were significantly correlated with many topographic, climatic, and vegetation metrics. This first empirical study of seasonal precipitation partitioning fractions across diverse ecoregions demonstrates that they can be well‐constrained in many locations using existing public data sets, and that partitioning‐fraction variations are largely explained by climate variations.

Introduction & Background Epochs of hyperglycaemia and hypoglycaemia may each increase risk of common chronic diseases and impair both cognitive and physical function even in people without diabetes. Older people may have greater frequency of adverse glycaemic excursions, partly due to disordered autonomic function and sleep quality. Data for older, non-diabetic people are however scant. Objectives & Approach 1) To describe blood glucose variability (completed) and 2) its socio-demographic and lifestyle correlates in a predominantly non-diabetic cohort of older adults (planned). Participants were recruited during 2021-2023 from an English birth cohort (the 1946 National Survey for Health and Development Study). They wore a continuous glucose monitor (Freestyle libre Abbott), which measured circulating glucose four times/hour, for seven days. Summary statistics and time outside range (4.4-7.8mmol/L) were calculated. Further information on glycaemic excursions and day-to-day variability will be gleaned using the R “iglu” package. For all CGM summary and excursion measures, future analyses will investigate: associations with HbA1c, socio-demographics, body composition, physical activity, diet and alcohol use. Results will be stratified by sleep/ wake time periods estimated from simultaneous actigraphy (Philips Actiwatch Spectrum Plus). Sensitivity analyses will exclude people taking hypo/ hyperglycaemic medications and those with diabetes. Relevance to Digital Footprints Derived summary measures can be used by future studies to give insights into glycaemic variability as a population-level risk factor. This work will bring together multiple data sources, i.e. from CGM, actigraphy and baseline cohort data. Results Participants were aged 75-76 years, 45% female and 10% had diagnosed diabetes; median (IQR) BMI was 26.8 (24.6-29.2) kg/m2. CGM data from 308 participants was collected, for a median (IQR) of 6.9 (6.7-7.6) days. Average glucose over the recording period was 5.7mmol/L (5.3-6.2mmol/L), standard deviation was 1.0mmol/L (0.8-1.3mmol/L), time outside range was 12.8% (6.2-24.7%) and 16% of participants spent ≥1 hour/day above and ≥1 hour/day below range. Conclusions & Implications CGM was feasible for this cohort of older adults, and demonstrated high levels of time outside range for a predominantly non-diabetic group. Future analysis will determine whether enhanced characterisation of glycaemic variability is a potentially more accurate tool for predicting future disease risk than isolated glucose measurements.

Intravenous self-administration in rats is used widely to study the reinforcing effects of drugs and serves as the gold standard for assessing their use and misuse potential. One challenge that researchers often encounter when scaling up experiments is balancing the cost, time investment to construct, and robustness of each implanted catheter. These catheters include multiple components such as surgical meshing and a variety of entry ports designed to facilitate the connection of the rat to a catheter port tethering system. Other considerations include maintaining the catheters free of blockage during the extent of the drug self-administration experiment. These large-scale studies provide ample opportunity for the catheter system to fail. The failure and replacement of commercially purchased catheters leads to ballooning expenses, and the failure of in-lab manufactured catheters requires the manufacture of reserves, also increasing costs, as these handmade products are inherently more variable. We have developed a catheter system that combines a commercially available implantable back-mounted entry connector system with inexpensive medical items such as surgical mesh, sutures, and an air-tight back flow prevention system to bolster the overall success of self-administration experiments. • Method to bolster commercially available jugular catheter components for long-lasting self-administration experiments. • Reduces the overall cost per unit of self-administration experiments. • Easily assembled by laboratory students and staff.

Classroom videos are a common source of data for educational researchers studying classroom interactions as well as a resource for teacher education and professional development. Over the last several decades emerging technologies have been applied to classroom videos to record, transcribe, and analyze classroom interactions. With the rise of machine learning, we report on the development and validation of neural networks to classify instructional activities using video signals, without analyzing speech or audio features, from a large corpus of nearly 250 h of classroom videos from elementary mathematics and English language arts instruction. Results indicated that the neural networks performed fairly-well in detecting instructional activities, at diverse levels of complexity, as compared to human raters. For instance, one neural network achieved over 80% accuracy in detecting four common activity types: whole class activity, small group activity, individual activity, and transition. An issue that was not addressed in this study was whether the fine-grained and agnostic instructional activities detected by the neural networks could scale up to supply information about features of instructional quality. Future applications of these neural networks may enable more efficient cataloguing and analysis of classroom videos at scale and the generation of fine-grained data about the classroom environment to inform potential implications for teaching and learning.

Abstract Background To assess whether changes in breakfast and water consumption during the first full school year after the emergence of the COVID-19 pandemic varied based on sex/gender, race/ethnicity, and socioeconomic status among Canadian adolescents. Methods Prospective annual survey data collected pre- (October 2019-March 2020) and post-COVID-19 onset (November 2020-June 2021) the Cannabis, Obesity, Mental health, Physical activity, Alcohol, Smoking, and Sedentary behaviour (COMPASS) study. The sample consisted of 8,128 students; mean (SD) age = 14.2 (1.3) years from a convenience sample of 41 Canadian secondary schools. At both timepoints self-reported breakfast and water consumption were dichotomized as daily or not. Multivariable logistic generalized estimating equations with school clustering were used to estimate differences in maintenance/adoption of daily consumption post-COVID-19 based on demographic factors, while controlling for pre-COVID-19 behaviour. Results Adjusted odds ratios (AOR) with 95% confidence intervals are reported. Females (AOR = 0.71 [0.63, 0.79]) and lower socioeconomic status individuals (AORLowest:Highest=0.41 [0.16, 1.00]) were less likely to maintain/adopt daily breakfast consumption than male and higher socioeconomic status peers in the 2020–2021 school year. Black identifying individuals were less likely than all other racial/ethnic identities to maintain/adopt plain water consumption every day of the week (AOR = 0.33 [0.15, 0.75], p

Abstract Variational autoencoder architectures have the potential to develop reduced-order models for chaotic fluid flows. We propose a method for learning compact and near-orthogonal reduced-order models using a combination of a β-variational autoencoder and a transformer, tested on numerical data from a two-dimensional viscous flow in both periodic and chaotic regimes. The β-variational autoencoder is trained to learn a compact latent representation of the flow velocity, and the transformer is trained to predict the temporal dynamics in latent-space. Using the β-variational autoencoder to learn disentangled representations in latent-space, we obtain a more interpretable flow model with features that resemble those observed in the proper orthogonal decomposition, but with a more efficient representation. Using Poincaré maps, the results show that our method can capture the underlying dynamics of the flow outperforming other prediction models. The proposed method has potential applications in other fields such as weather forecasting, structural dynamics or biomedical engineering.

Abstract The computation of a similarity measure for genomic data is a standard tool in computational genetics. The principal components of such matrices are routinely used to correct for biases due to confounding by population stratification, for instance in linear regressions. However, the calculation of both a similarity matrix and its singular value decomposition (SVD) are computationally intensive. The contribution of this article is threefold. First, we demonstrate that the calculation of three matrices (called the covariance matrix, the weighted Jaccard matrix, and the genomic relationship matrix) can be reformulated in a unified way which allows for the application of a randomized SVD algorithm, which is faster than the traditional computation. The fast SVD algorithm we present is adapted from an existing randomized SVD algorithm and ensures that all computations are carried out in sparse matrix algebra. The algorithm only assumes that row-wise and column-wise subtraction and multiplication of a vector with a sparse matrix is available, an operation that is efficiently implemented in common sparse matrix packages. An exception is the so-called Jaccard matrix, which does not have a structure applicable for the fast SVD algorithm. Second, an approximate Jaccard matrix is introduced to which the fast SVD computation is applicable. Third, we establish guaranteed theoretical bounds on the accuracy (in $$L_2$$ L 2 norm and angle) between the principal components of the Jaccard matrix and the ones of our proposed approximation, thus putting the proposed Jaccard approximation on a solid mathematical foundation, and derive the theoretical runtime of our algorithm. We illustrate that the approximation error is low in practice and empirically verify the theoretical runtime scalings on both simulated data and data of the 1000 Genome Project.

IntroductionLes produits de tabac chauffé sont de nouveaux produits du tabac susceptibles d’attirer les jeunes. Cette étude visait à explorer, dans quatre provinces canadiennes, si la proximité et la densité des détaillants de produits de tabac chauffé autour des écoles secondaires étaient associées à une utilisation de ces produits chez les adolescents. MéthodologieUne recherche menée en ligne entre novembre 2020 et mars 2021 a permis de repérer les détaillants qui vendaient des dispositifs IQOS et des bâtonnets HEETS (conçus pour les dispositifs IQOS) dans des zones tampons circulaires de 500 m, 1 000 m et 1 500 m autour de 120 écoles secondaires ayant participé à l’étude COMPASS 2020-2021. Les données sur la proximité et la densité des détaillants ont été liées à des données transversales sur les élèves (N = 40 636), et des modèles de régression multiniveaux ont été utilisés pour explorer l’association entre, d’une part, la proximité et la densité des détaillants de produits de tabac chauffé et, d’autre part, l’utilisation de produits de tabac chauffé, après ajustement pour les covariables pertinentes. RésultatsSi seulement 10,0 % des écoles étaient situées à moins de 1 000 m d’au moins un détaillant vendant des dispositifs IQOS, 65,0 % d’entre elles étaient situées à proximité d’au moins un détaillant vendant des bâtonnets HEETS. L’école fréquentée par l’élève était responsable de 23,7 % de la variabilité de la probabilité d’utilisation de produits de tabac chauffé. Toutefois, la proximité et la densité des détaillants de produits de tabac chauffé autour des écoles n’ont présenté aucune association significative avec la probabilité d’utilisation de ces produits chez les élèves. ConclusionBien que l’école fréquentée par l’élève soit responsable d’une part importante de la variabilité de l’utilisation de produits de tabac chauffé, ces résultats laissent penser que les élèves pourraient obtenir des produits de tabac chauffé par des sources autres que les commerces de détail. Il faut continuer de surveiller la situation, car l’utilisation des produits de tabac chauffé chez les adolescents est susceptible d’évoluer.

IntroductionHeated tobacco products (HTPs) are novel tobacco products that may appeal to youth. This study explored whether HTP retailer proximity and density to secondary schools were associated with youth use of HTPs in four Canadian provinces. MethodsAn online search between November 2020 and March 2021 identified retailers selling IQOS devices and HEETS (tobacco sticks used in IQOS) within 500 m, 1000 m and 1500 m radius circular buffer zones around high schools (N = 120) participating in the COMPASS study in 2020–2021. Retailer proximity/density data were linked to crosssectional student-level data (N = 40 636 students), and multilevel regression models examined the association between HTP retailer proximity and density and current HTP use, controlling for relevant covariates. ResultsWhile only 10.0% of schools had at least one retailer selling IQOS devices within 1000 m of the school, 65.0% of schools had at least one retailer selling HEETS. The school a student attended accounted for 23.7% of the variability in the likelihood of currently using an HTP. However, HTP retailer proximity to and density around schools were not significantly associated with the likelihood of students currently using HTPs. ConclusionWhile the school a student attended accounted for a significant amount of variability in HTP use, these findings suggest that students may be obtaining HTPs through other, non-retail sources. Continued monitoring is warranted as HTP use among youth may change.

Abstract Background Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. Methods Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort’s distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial’s intervention was targeted (national). Results Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p

Abstract Background Very little research has examined how perceptions of cannabis access among underage youth in Canada have changed since cannabis was legalized and since the onset of the COVID-19 pandemic. As such, this paper examines the effect of the early and ongoing stages of the COVID-19 pandemic period on youth perceptions of cannabis access over time since the onset of the Cannabis Act in 2018 in a large sample of Canadian youth. Methods Using data from the COMPASS study (T1:2018/19, T2:2019/20, T3:2020/21), we used both repeat cross-sectional data [T1 (n = 38,890), T2 (n = 24,109), and T3 (n = 22,795)] to examine overall trends in perceptions of cannabis access, and sequential cohort longitudinal data [n = 4,677 students linked from T1 to T3] to examine the differential changes in perceptions of cannabis access among students over time. Results In the cross-sectional sample, the frequency of students reporting that cannabis was easy to access decreased by 26.7% from T1 (51.0%) to T3 (37.4%), although respondents who have used cannabis were more likely to report access was easy. In the longitudinal sample, perceptions of cannabis access being easy increased over time, especially among cannabis users. Perceived ease of access appears to have been slightly impeded during the initial pandemic period but rebounded during the ongoing pandemic period. Conclusions While the prevalence of youth reporting that cannabis is easy to access has declined since legalization and throughout the early and ongoing pandemic periods, a substantial number of underage youth continue to report that cannabis is easy to access. This suggest that there is an ongoing need for continued cannabis control efforts to address this issue.

Abstract Introduction Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab. Methods Aptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways. Results Over two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E−05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E−05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E−07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E−06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E−06, FDR-corrected: 0.0006) with worse response. Protein–protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab. Conclusions This study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection.

Background Public health surveillance involves the collection, analysis and dissemination of data to improve population health. The main sources of data for public health decision-making are surveys, typically comprised of self-report which may be subject to biases, costs and delays. To complement subjective data, objective measures from sensors could potentially be used. Specifically, advancements in personal mobile and wearable technologies enable the collection of real-time and continuous health data. Objective In this context, the goal of this work is to apply a mobile health platform (MHP) that extracts health data from the Apple Health repository to collect data in daily-life scenarios and use it for the prediction of stress, a major public health issue. Methods A pilot study was conducted with 45 participants over 2 weeks, using the MHP to collect stress-related data from Apple Health and perceived stress self-reports. Apple, Withings and Empatica devices were distributed to participants and collected a wide range of data, including heart rate, sleep, blood pressure, temperature, and weight. These were used to train random forests and support vector machines. The SMOTE technique was used to handle imbalanced datasets. Results Accuracy and f1-macro scores were in line with state-of-the-art models for stress prediction above 60% for the majority of analyses and samples analysed. Apple Watch sleep features were particularly good predictors, with most models with these data achieving results around 70%. Conclusions A system such as the MHP could be used for public health data collection, complementing traditional self-reporting methods when possible. The data collected with the system was promising for monitoring and predicting stress in a population.

Abstract Predator non‐consumptive effects (NCE) can alter prey foraging time and habitat use, potentially reducing fitness. Prey can mitigate NCEs by increasing vigilance, chewing‐vigilance synchronization, and spatiotemporal avoidance of predators. We quantified the relationship between Mexican wolf (Canis lupus baileyi) predation risk and elk (Cervus canadensis) behavior. We conducted behavioral observations on adult female elk and developed predation risk indices using GPS collar data from Mexican wolves, locations of elk killed by wolves, and landscape covariates. We compared a priori models to determine the best predictors of adult female behavior and multitasking. Metrics that quantified both spatial and temporal predation risk were the most predictive. Vigilance was positively associated with increased predation risk. The effect of predation risk on foraging and resting differed across diurnal periods. During midday when wolf activity was lower, the probability of foraging increased while resting decreased in high‐risk areas. During crepuscular periods when elk and wolves were most active, increased predation risk was associated with increased vigilance and slight decreases in foraging. Our results suggest elk are temporally avoiding predation risk from Mexican wolves by trading resting for foraging, a trade‐off often not evaluated in behavioral studies. Probability of multitasking depended on canopy openness and an interaction between maternal period and predation risk; multitasking decreased prior to parturition and increased post parturition in high‐risk areas. Openness was inversely related to multitasking. These results suggest adult female elk are altering the type of vigilance used depending on resource availability/quality, current energetic needs, and predation risk. Our results highlight potentially important, but often‐excluded behaviors and trade‐offs prey species may use to reduce the indirect effects of predation and contribute additional context to our understanding of predator–prey dynamics.