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Significance: As the field of artificial intelligence evolves rapidly, these hallmarks are intended to capture fundamental, complementary concepts necessary for the progress and timely adoption of predictive modeling in precision oncology. Through these hallmarks, we hope to establish standards and guidelines that enable the symbiotic development of artificial intelligence and precision oncology., (©2024 American Association for Cancer Research.)

Myosin II is a molecular motor that converts chemical energy derived from ATP hydrolysis into mechanical work. Myosin II isoforms are responsible for muscle contraction and a range of cell functions relying on the development of force and motion. When the motor attaches to actin, ATP is hydrolyzed and inorganic phosphate (P i ) and ADP are released from its active site. These reactions are coordinated with changes in the structure of myosin, promoting the so-called "power stroke" that causes the sliding of actin filaments. The general features of the myosin-actin interactions are well accepted, but there are critical issues that remain poorly understood, mostly due to technological limitations. In recent years, there has been a significant advance in structural, biochemical, and mechanical methods that have advanced the field considerably. New modeling approaches have also allowed researchers to understand actomyosin interactions at different levels of analysis. This paper reviews recent studies looking into the interaction between myosin II and actin filaments, which leads to power stroke and force generation. It reviews studies conducted with single myosin molecules, myosins working in filaments, muscle sarcomeres, myofibrils, and fibers. It also reviews the mathematical models that have been used to understand the mechanics of myosin II in approaches focusing on single molecules to ensembles. Finally, it includes brief sections on translational aspects, how changes in the myosin motor by mutations and/or posttranslational modifications may cause detrimental effects in diseases and aging, among other conditions, and how myosin II has become an emerging drug target.

Though the Explicit Discrimination Scale (EDS) has been subjected to extensive psychometric evaluation in Brazil, the instrument has yet to be comprehensively assessed among working-age adult respondents in the country. This study aimed to fill this knowledge gap. Data from around 1200 diverse members of a cohort investigation were used to examine: (1) the positioning of respondents along the continuum of the EDS latent trait; (2) how well the corresponding items represent the EDS construct map; and (3) the extent to which the EDS items follow their expected levels of intensity. We assessed these properties with Loevinger's H, Guttman errors, and Item Response Theory parameters. Findings suggest that two abridged versions of the instrument-but especially the eight-item EDS-may adequately arrange respondents along the latent trait continuum. Analyses also revealed that scale items are reasonably spread over the construct map, with some discrepancy between the expected levels of intensity and their empirical positioning in the corresponding plot. The shortened versions of EDS have good psychometric properties among Brazilian working-age adult respondents. In addition to examining the invariance of the EDS across multiple groups, future psychometric evaluations should assess the external validity of the scale., (© 2024 The Author(s). Journal of Community Psychology published by Wiley Periodicals LLC.)

Strontium isotope ( 87 Sr/ 86 Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving 87 Sr/ 86 Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the 87 Sr/ 86 Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression. We demonstrate the efficacy of this Sr isoscape, in combination with other lines of evidence, to trace the African roots of individuals from historic slavery contexts, particularly those with highly radiogenic 87 Sr/ 86 Sr ratios uncommon in the African Diaspora. Our study provides an extensive African 87 Sr/ 86 Sr dataset which includes scientifically marginalized regions of Africa, with significant implications for the archaeology of the transatlantic slave trade, wildlife ecology, conservation, and forensics., Competing Interests: Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)

Young people aged 18-29 are considered "adult" within the Australian HIV health service context. However, evidence increasingly defines this age group as distinct from the broader adult population such that the needs of young people living with HIV may be overlooked in the context of HIV service design and delivery. This analysis draws on the Young + Positive study, a national study in Australia that documented the perspectives of young people (aged 18-29) living with HIV. Data were collected via survey (n = 60) and interview (n = 25) methods between 2018 and 2019. The data were analysed using descriptive statistics and thematic analysis, exploring the inner- and outer-world factors influencing participant engagement with HIV care and support. Using the multi-dimensional framework by Harms [2021. Understanding human development (3rd ed.). Oxford University Press], we found that both inner- and outer-world factors influenced participants' ability and motivations to engage with specialist HIV treatment and support. Inner-world factors included psychological outlook, and perceptions of HIV and HIV services. Outer-world factors included workforce competencies of service providers, physical space of the service and hours of service operation. These research findings confirm that opportunities exist to better meet the treatment and care needs of young people living with HIV.

Introduction: The main strategy to achieve equal provision of oral care in Sweden has been to offer partial subsidies for the adult population. However, their effects on unmet oral care needs (UOCNs) have not been extensively assessed., Objective: This study used an intersectionality framework to examine 1) the overall frequency of UOCNs, 2) single-indicator inequities, and 3) intersectional inequities in total UOCNs and financial-related UOCNs (FUOCNs) in Sweden before and after implementation of a partial subsidization reform in 2008., Methods: Data from 12 national surveys conducted over 2004 to 2018 were divided into 3 periods: prereform (2004 to 2007), early postreform (2008 to 2011), and late postreform (2012 to 2018). The analytic sample consisted of 98,177 respondents aged 24 to 84 y. Changes in the prevalence of UOCNs were estimated by inferential statistics. Single-indicator and intersectional inequities were examined by intersectional analysis of individual heterogeneity and discriminatory accuracy, across 48 strata defined by gender, age, educational level, income, and immigrant status., Results: The prevalence of total UOCNs and FUOCNs decreased significantly early after the reform, followed by a slight rebound. Relative inequities increased by education, income, and immigrant status after the reform and decreased for age. The discriminatory accuracy for both types of UOCNs was moderate and improved marginally but significantly with the inclusion of the intersectional strata. Most intersectional strata showed greater FUOCN inequities after the reform., Conclusions: Contrary to expected, larger inequities in FUOCNs were identified in most intersectional strata after the reform. The moderate discriminatory accuracy suggested that Sweden could benefit from future strategies to foster equity that are universal but proportionately more intense among the intersectional strata with greater inequities (proportionate universalism)., Knowledge Transference Statement: This analysis highlighted the benefit of adopting the principle of proportionate universalism as a strategy to reduce unmet oral care needs in Sweden. This would mean implementing universal strategies and specific support measures for the most vulnerable social groups as a future oral care policy change in Sweden., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Victims of sexual homicide may be deceived by perpetrators who use a friendly approach to gain access to them, making it difficult for the victim to assess the danger posed by the stranger. When investigating sexual homicides committed by strangers, investigators often lack direct information, including how the perpetrator gained access to the victim. To identify potential predictors of the approach method used in sexual homicides, this study analyzed the preferences and behaviors of sexual murderers who target strangers based on their approach method. The results of the logistic regression analysis showed that in comparison to offenders using "blitz" or "surprise" attacks, those using a deceptive "con" approach tended to have more male victims, exploit vulnerability, and exhibit post-crime organization by relocating the victim's body and successfully disposing of the weapon used in the crime. Their crimes also more frequently involved oral sex and had lower rates of victim beating. This study discusses the investigative implications of these findings., (© 2024 The Author(s). Behavioral Sciences & the Law published by John Wiley & Sons Ltd.)

This study explores the health-related quality of life (HRQoL) experienced by patients with Long COVD-19 using data from British Columbia's post-COVID-19 Recovery Clinics. A retrospective cohort of 3463 patients was analyzed to assess HRQoL through the EQ-5D-5L questionnaire which includes five dimensions (mobility, self-care, usual activities, physical health, and mental health) administered to patients; responses were analyzed using the Visual Analogue Score (VAS). Notably, 95% of participants reported HRQoL scores below 90, with 50% scoring under 60, indicating significant impacts on their well-being. The analysis revealed that HRQoL is significantly influenced by various social determinants of health (SDoH), including age, sex, employment status, and ethnicity, each showing distinct correlations with HRQoL dimensions and overall VAS scores. Specifically, older age was associated with decreased mobility and increased pain/discomfort but less anxiety and depression, highlighting varying impacts across the age spectrum. The study highlights the multifaceted impacts of Long COVID on the lives of patients and underscores the necessity of targeted strategies to improve HRQoL among diverse groups, considering specific SDoH. Such a comprehensive approach could lead to more equitable health outcomes and support the development of tailored public health policies aimed at the recovery and rehabilitation of Long COVID sufferers., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics declaration: This study has received approval from the Research Ethics Board at the Simon Fraser University (#30001542) and adheres to all relevant guidelines and regulations for research involving de-identified health data (e.g. CHREB, Tri-Council Policy Statement on the Ethical Conduct for Research Involving Humans [TCPS2]). Consent to participate/consent to publish: Not applicable. According to the Freedom of Information and Protection of Privacy Act—British Columbia Law (RSBC 1996, c 165, “ https://canlii.ca/t/566l3 ” retrieved on 2024-07-22), aggregated data from medical records can be used for research purposes at health organizations; therefore, informed consent is not required., (© 2024. The Author(s).)

An affective variant of the Stop-Signal task was used to study the interaction between emotion and response inhibition (RI) in healthy young participants. The task involved the covert presentation of emotional faces as go stimuli, as well as a manipulation of motivation and affect by inducing a negative mood through the assignment of unfair punishment. In the literature on emotion and RI, there are contrasting findings reflecting the variability in the method used to calculate the RI latency, namely the Stop-Signal Reaction Time (SSRT). In fact, previous studies found both facilitatory and detrimental effects of affective manipulations over RI. However, they did not use the most robust SSRT estimation approach, namely the integration, casting some doubts on the reliability of the inferences. For these reasons, the present research draws attention on how the effect of the emotional manipulation may be due to a biased SSRT estimation. Specifically, the focus of our study was on how the effect of emotion on the SSRT may vary according to different estimation procedures, the mean and two variants of the integration method. We predicted that the effect of the emotional manipulation in the SST would depend on the SSRT estimation method employed. Indeed, a significant effect of emotion was only found when SSRT was estimated with the mean method. We conclude that the mean method should be avoided in the study of emotion and RI because it overestimates SSRT. Rather, the integration approach should be used for future research in this field, while also factoring in information about the participants' strategy in emotional contexts that require greater effortful control and offer a challenge to self-regulation both in health and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Coccaro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pandemics like COVID-19 have a huge impact on human society and the global economy. Vaccines are effective in the fight against these pandemics but often in limited supplies, particularly in the early stages. Thus, it is imperative to distribute such crucial public goods efficiently. Identifying and vaccinating key spreaders (i.e., influential nodes) is an effective approach to break down the virus transmission network, thereby inhibiting the spread of the virus. Previous methods for identifying influential nodes in networks lack consistency in terms of effectiveness and precision. Their applicability also depends on the unique characteristics of each network. Furthermore, most of them rank nodes by their individual influence in the network without considering mutual effects among them. However, in many practical settings like vaccine distribution, the challenge is how to select a group of influential nodes. This task is more complex due to the interactions and collective influence of these nodes together. This paper introduces a new framework integrating Graph Neural Network (GNN) and Deep Reinforcement Learning (DRL) for vaccination distribution. This approach combines network structural learning with strategic decision-making. It aims to efficiently disrupt the network structure and stop disease spread through targeting and removing influential nodes. This method is particularly effective in complex environments, where traditional strategies might not be efficient or scalable. Its effectiveness is tested across various network types including both synthetic and real-world datasets, demonstrting a potential for real-world applications in fields like epidemiology and cybersecurity. This interdisciplinary approach shows the capabilities of deep learning in understanding and manipulating complex network systems., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

AgeTech refers to a growing sector that is advancing the use of technologies, such as information and communication technologies (ICTs), mobile technologies, robotics, wearables and smart home systems to enhance the lives of older adults. Although AgeTech can be seen as an opportunity for empowering older people and enhance their overall quality of life, crucial ethical issues have to be addressed. The articles in this topical collection focus on these and other ethical questions, particularly in respect to key emerging technologies of AI and robotics. The overall aim is to explore the multifaceted ethical landscape of emerging AgeTech and to provide frameworks and strategies for ethically-appropriate technologies that support the health, well-being, and quality of life of older adults., (© 2024. The Author(s).)

The logistic regression model for a binary outcome with a continuous covariate can be expressed equivalently as a two-sample density ratio model for the covariate. Utilizing this equivalence, we study a change-point logistic regression model within the corresponding density ratio modeling framework. We investigate estimation and inference methods for the density ratio model and develop maximal score-type tests to detect the presence of a change point. In contrast to existing work, the density ratio modeling framework facilitates the development of a natural Kolmogorov-Smirnov type test to assess the validity of the logistic model assumptions. A simulation study is conducted to evaluate the finite-sample performance of the proposed tests and estimation methods. We illustrate the proposed approach using a mother-to-child HIV-1 transmission data set and an oral cancer data set., (© 2024 Wiley‐VCH GmbH.)

Background: Neonatal sepsis is a deadly disease with non-specific clinical signs, delaying diagnosis and treatment. There remains a need for early biomarkers to facilitate timely intervention. Our objective was to identify neonatal sepsis gene expression biomarkers that could predict sepsis at birth, prior to clinical presentation., Methods: Among 720 initially healthy full-term neonates in two hospitals (The Gambia, West Africa), we identified 21 newborns who were later hospitalized for sepsis in the first 28 days of life, split into early-onset sepsis (EOS, onset ≤7 days of life) and late-onset sepsis (LOS, onset 8-28 days of life), 12 neonates later hospitalized for localized infection without evidence of systemic involvement, and 33 matched control neonates who remained healthy. RNA-seq was performed on peripheral blood collected at birth when all neonates were healthy and also within the first week of life to identify differentially expressed genes (DEGs). Machine learning methods (sPLS-DA, LASSO) identified genes expressed at birth that predicted onset of neonatal sepsis at a later time., Findings: Neonates who later developed EOS already had ∼1000 DEGs at birth when compared to control neonates or those who later developed a localized infection or LOS. Based on these DEGs, a 4-gene signature (HSPH1, BORA, NCAPG2, PRIM1) for predicting EOS at birth was developed (training AUC = 0.94, sensitivity = 0.93, specificity = 0.92) and validated in an external cohort (validation AUC = 0.72, sensitivity = 0.83, and specificity = 0.83). Additionally, during the first week of life, EOS disrupted expression of >1800 genes including those influencing immune and metabolic transitions observed in healthy controls., Interpretation: Despite appearing healthy at birth, neonates who later developed EOS already had distinct whole blood gene expression changes at birth, which enabled the development of a 4-gene predictive signature for EOS. This could facilitate early recognition and treatment of neonatal sepsis, potentially mitigating its long-term sequelae., Funding: CIHR and NIH/NIAID., Competing Interests: Declaration of interests AA provided legal consultation for MCIC Vermont Inc and received honorarium for lecture on neonatal sepsis from the University of Rome. BK participated in a Data Safety Monitoring Board for Johnson & Johnson. JDA received travel funding from the American Society for Histocompatibility and Immunogenetics, World Vaccine Congress, and International Network of Special Immunization Services. OAO received travel funding from the American Academy of Pediatrics. OL is a named inventor on patents held by Boston Children's Hospital relating to small molecule adjuvants (e.g., Novel imidazopyrimidine compounds and uses thereof; EP3709998A1) and to human in vitro systems that model responses to immunomodulators and vaccines (e.g., Tissue constructs and uses thereof; US20150152385A1), has served as a consultant to Glaxo Smith Kline and Hillevax, and is co-founder of and advisor to Ovax, Inc. REWH has a contract from Sepset Biosciences for development of diagnostic assays for adult sepsis (indirect relationship to this work) and is CEO of Asep Medical and Sepset BioSciences that are commercially developing adult sepsis diagnostics, although the signatures described here have not been filed for patent protection. All other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We describe a case of severe accidental hypothermia of a kayaker with preserved consciousness and shivering despite a rectal temperature of 22.9°C following a 50-min immersion in 3°C water with an estimated core temperature cooling rate of 10.6°C/h. Based on survival at sea prediction curves and cooling rates from physiology studies, cold water (eg, 0-5°C) immersion is expected to drop core temperature by 2 to 4°C/h. Furthermore, accidental hypothermia classification systems predict that severely hypothermic patients are usually unconscious and not shivering. The patient in this report rewarmed rapidly at 3.6°C/h with only minimally invasive measures and was discharged fully neurologically intact. In 41 similar cases of survival in moderate to severe hypothermia with core temperatures <32°C due to cold water immersion, cold air exposure, or avalanche burial, mean cooling rates were 4.3±3.3°C/h (range 0.4-10.6°C/h). Including the current patient, shivering was reported in only four cases. We found several other cases of rewarming from moderate to severe hypothermia with only minimally invasive measures. The current and summarized cases lead us to conclude that patients may be at risk of severe hypothermia in <60 min of cold water immersion and that it is possible for severely hypothermic patients to have preserved consciousness, close to normal vital signs, and shivering. Minimally invasive or noninvasive rewarming of patients with severe hypothermia is also possible, especially in those who continue to shiver. Hypothermia management should not necessarily be guided by classification systems or core temperature alone but rather by a careful consideration of the entire clinical picture.

Introduction: Early adolescents who are new to Canada experience dual challenges of navigating developmental changes and multiple cultures. This study examined how changes in early adolescents' emotional health from ages 9 to 12 differed by immigration background, and to what extent peer belonging and supportive school climate protected or promoted their emotional health., Methods: This study drew upon linked self-report and administrative data. Across 10 school districts in British Columbia, Canada, N = 4479 non-immigrant, immigrant, and refugee adolescents reported on their peer belonging, school climate, and emotional health (life satisfaction, optimism, self-esteem, sadness, worries) in Grades 4 and 7, using the Middle Years Development Instrument. Immigration background including immigration class (economic, family, refugee) and generation status (first, second) were obtained from linked Immigration, Refugees, and Citizenship Canada data. Multi-level modeling assessed the effect of time (grade level), immigration group, and changes in peer belonging and school climate on changes in self-reported emotional health. Analyses were adjusted for gender, English first language, and low family income., Results: Immigrant and refugee adolescents reported worse emotional health in Grade 4 compared to non-immigrants. Non-immigrant and immigrant adolescents reported declines in emotional health from Grades 4 to 7. In contrast, first-generation refugee adolescents reported significant improvements in life satisfaction, and first- and second-generation refugees reported improvements in worries over this period. Perceived improvements in peer belonging and school climate were associated with positive changes in emotional health for all adolescents., Conclusions: Changes in adolescents' emotional health from Grades 4 to 7 differed between immigrants, refugees, and non-immigrants. Immigrants and refugees who enter adolescence with lower emotional health than their non-immigrant peers may particularly benefit from culturally responsive school and community-based interventions., (© 2024 The Author(s). Journal of Adolescence published by John Wiley & Sons Ltd on behalf of Foundation for Professionals in Services to Adolescents.)

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disease that is primarily diagnosed and managed by rheumatologists; however, it is often primary care providers who first encounter RA-related symptoms. This study developed and validated a case definition for RA using national surveillance data in primary care settings., Methods: This cross-sectional validation study used structured electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Based on the reference set generated by EMR reviews by five experts, three machine learning steps: 'bag-of-words' approach to feature generation, feature reduction using a feature importance measure coupled with recursive feature elimination and clustering, and classification using tree-based methods (Decision Tree, Random Forest, and Extreme Gradient Boosting). The three tree-based algorithms were compared to identify the procedure that generated the optimal evaluation metrics. Nested cross-validation was used to allow evaluation and comparison and tuning of models simultaneously., Results: Of 1.3 million patients from seven Canadian provinces, 5,600 people aged 19 + were randomly selected. The optimal algorithm for selecting RA cases was generated by the XGBoost classification method. Based on feature importance scores for features in the XGBoost output, a human-readable case definition was created, where RA cases are identified when there are at least 2 occurrences of text "rheumatoid" in any billing, encounter diagnosis, or health condition table of the patient chart. The final case definition had sensitivity of 81.6% (95% CI, 75.6-86.4), specificity of 98.0% (95% CI, 97.4-98.5), positive predicted value of 76.3% (95% CI, 70.1-81.5), and negative predicted value of 98.6% (95% CI, 98.0-98.6)., Conclusion: A case definition for RA in using primary care EMR data was developed based off the XGBoost algorithm. With high validity metrics, this case definition is expected to be a reliable tool for future epidemiological research and surveillance investigating the management of RA in CPCSSN dataset., Competing Interests: Declarations. Ethics approval and consent to participate: This study has received approval from the Health Research Ethics Board at the University of Alberta (Pro00107346) and the University of Calgary (REB21-0723) and adheres to all relevant guidelines and regulations for research involving de-identified health data (e.g. CHREB, Tri-Council Policy Statement on the Ethical Conduct for Research Involving Humans [TCPS2]). The CPCSSN database has received ethics approval, including waivers of individual patient informed consent for their de-identified data to be used for surveillance and research, from each contributing network’s local Research Ethics Board (Queen’s University, Memorial University of Newfoundland, University of Ottawa, University of Calgary, Dalhouse University, University of Toronto, Western University, Bruyère Research Institute, University of British Columbia, University of Alberta, and University of Manitoba). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Individual variability in clinical response to dopaminergic replacement therapy (DRT) is a key barrier to efficacious treatment for patients with Parkinson's disease (PD). A better understanding of the neurobiological sources of such inter-individual differences is necessary to inform future clinical interventions and motivate translational research. One potential source of this variability is an unintended secondary activation of extra-nigrostriatal dopamine systems by DRT, particularly in the neocortex. In this study, we use magnetoencephalography data collected from patients with PD before and after DRT to map their individual cortical neurophysiological responses to dopaminergic pharmacotherapy. By combining these DRT response maps with normative atlases of cortical dopamine receptor and transporter densities, we link the variable enhancement of rhythmic beta activity by DRT to dopamine-rich cortical regions. Importantly, patients who exhibited a larger dopaminergic beta cortical enhancement showed a smaller clinical improvement from DRT, indicating a potential source of individual variability in medication response for patients with PD. We conclude that these findings inform our understanding of the dopaminergic basis of neurophysiological variability often seen in patients with PD, and indicate that our methodological approach may be useful for data-driven contextualization of medication effects on cortical neurophysiology in future research and clinical applications.

Theory and evidence from developed economies suggests that innovation activities benefit from agglomeration economies associated with urban economic density. However, despite the fact that eighteen of the world's top twenty cities are in developing countries, we do not know whether agglomeration affects innovation in the same way in developing countries. We propose that, while there are still agglomeration benefits, the development path followed by cities in developing countries also creates significant agglomeration costs and these act to limit innovation. We build a unique database to measure consistently both urban economic density and innovation across a large number of developing countries. Based on geospatial information, we combine data on nightlights at the city level to proxy urban density with information on innovation activity at the firm level. We find that in developing countries, as urban economic density increases, innovation first increases and then begins to decrease beyond a certain point, with the decline being most prominent in the largest cities. That is, the largest cities in developing countries are not able to act as sustainable sources of innovation. Cities in developing countries therefore display different patterns of agglomeration from those documented in the literature focused on developed countries. Our analysis explores the relationship between UN Sustainable Development Goal (SDG) 9 which fosters innovation, and SDG 11 which promotes sustainable and resilient cities. Our results suggest the importance of addressing urban agglomeration costs as a means to facilitate innovative activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Estrin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Identifying individuals with tuberculosis (TB) with a high risk of onward transmission can guide disease prevention and public health strategies. Here, we train classification models to predict the first sampled isolates in Mycobacterium tuberculosis transmission clusters from demographic and disease data. We find that supervised learning, in particular balanced random forests, can be used to develop predictive models to identify people with TB that are more likely associated with TB cluster growth, with good model performance and AUCs of ≥ 0.75. We also identified the most important patient and disease characteristics in the best performing classification model, including host demographics, site of infection, TB lineage, and age at diagnosis. This framework can be used to develop predictive tools for the early assessment of potential cluster growth to prioritise individuals for enhanced follow-up with the aim of reducing transmission chains., Competing Interests: Competing interests The authors declare no competing interests. Ethics declarations Ethics were obtained from the University of British Columbia (certificate H12-00910) and informed consent for participation in the study was not required, as determined by institutional REB review., (© 2024. The Author(s).)

Survivors of adverse childhood experience are at elevated risk for psychological distress. In recent years, renewed interest in psychedelic medicine has highlighted the therapeutic potential of psilocybin for those who have experienced childhood adversity. However, recreational psilocybin use remains illegal and access to approved therapies is difficult. Such use provides an opportunity to explore the therapeutic potential of psilocybin for psychological distress among people with adverse childhood experiences. Therefore, we conducted an online survey to assess interest in, acceptability of, and experiences with psilocybin. We further explored whether the association between Adverse Childhood Experiences Questionnaire (ACEQ) scores and psychological distress was lower among those who had used psilocybin in the past three months. Results showed high levels of interest in and acceptability of psilocybin that did not differ across ACEQ scores. Results also showed that the effect of adverse childhood experiences on psychological distress was lower for people who had recently used psilocybin ( p  = .019). Taken together, these findings suggest that psilocybin therapy may be potentially acceptable and may feasibly help in supporting survivors of adverse childhood experiences with particularly strong benefits to those with more severe childhood adversity.

Background and Aims: Guidelines now recommend inpatient continuous glucose monitor (CGM) use with confirmatory blood glucose measurements. However, the Food and Drug Administration has not yet officially approved CGM for inpatient use in large part because its accuracy has not been established in this setting. We tested the accuracy of the Dexcom G6 (G6) in 28 adults on an insulin infusion in a medical-surgical intensive care unit with 1064 matched CGM and arterial point-of-care pairs. Methods: The participants were on average 57.29 (SD 2.39) years, of whom 13 had a prior diagnosis of diabetes and 14 were admitted for a surgical diagnosis. The first 19 participants received the G6 without calibration and had a mean absolute relative difference (MARD) of 13.19% (IQR 5.11, 19.03) across 659 matched pairs, which just meets the critical care expert recommendation of MARD <14%. We then aimed to improve accuracy for the subsequent 9 participants using a calibration protocol. Results: The MARD for calibrated participants was 9.65% (3.03, 13.33), significantly lower than for uncalibrated participants ( P < 0.001). Calibration also demonstrated excellent safety with 100% of values within the Clarke Error Grid zones A and B compared with 99.07% without calibration. Our protocol achieved the lowest MARD and safest CEG profile in the critical care setting and well exceeds the critical care expert recommendations. Our large sample of heterogenous critically ill patients also reached comparable accuracy to the MARD of 9% for G6 in outpatients. We believe our calibration protocol will allow G6 to be used with sufficient accuracy in inpatients.

Pediatric skulls change rapidly in size and shape during development, especially for children up to 8 years of age. This project was developed to address the gap in understanding of the three-dimensional growth parameters of the human skull during this period and the impact these growth patterns have on fontanelle closure and suture formation. This study offers novel data on the dynamic changes in the anatomy of the skull with the intention of providing better guidance for pediatric surgical care. Craniometric landmarks defined on three-dimensional computed tomography reconstructions were used to map skull development in children aged 0 to 8 years old. A total of 364 datasets were analyzed and statistically representative 3D skulls with anatomical craniometric features such as head shape, bone size, suture and fontanelle closure time were generated for 17 age groups spanning birth to 8 years of age to provide a comprehensive neuroanatomical understanding of how the pediatric skull changes over time. This study indicates that the cranial bones follow a non-linear growth pattern, with the occipital and frontal bones driving the directionality of fontanelle closure and delivers a 3D visualization of the developmental characteristics of the skull providing a landmark resource for understanding the growth dynamics of the human skull. While clinical measurements remain valid approaches for the planning of surgical interventions, these 3D models may provide a more accurate planning paradigm., (© 2024. The Author(s).)

Background Aims: Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies., Methods: A steering committee of 22 international experts, including stakeholders from different MSC research fields, participated in the three Delphi rounds. For the first round, to obtain a broad perspective, additional investigators recommended by the steering committee were invited to participate. The first two rounds consisted of online surveys, whereas the third round took the form of a virtual meeting. Participants were asked to rate a series of potential defining characteristics of MSCs and items for reporting guidelines. Consensus was defined as at least 80% of the participants rating the item in the same category of importance., Results: Eighty-seven international participants participated in the first round survey (spring 2023), 17 participants participated in the second online survey (fall 2023) and 15 participants participated in the final virtual consensus meeting (January 2024). For the MSC definition, 20 items were considered and nine reached consensus. Items included terminology (one item), cell marker expression (five items), tissue origin (one item), stemness (one item) and description of critical quality attributes (one item). For the reporting guidelines, with the 28 initial items and the additional items suggested during round 1, a total of 33 items to report were included. This included items on MSC intervention group and control (e.g., MSC product, dose and administration), MSC characteristics (e.g., MSC provenance, "fitness," viability and immune compatibility) and MSC culture conditions (e.g., oxygen environment, culture medium and use of serum)., Conclusions: By applying a Delphi method to establish a consensus definition for MSCs and reporting guidelines for MSC-based clinical trials, this work represents a significant advance in improving transparency and reproducibility in the conduct and reporting of MSC research., Competing Interests: Declaration of competing interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. All rights reserved.)

The global population is aging rapidly, and a research question of critical importance is why some older adults suffer tremendous cognitive decline while others are mostly spared. Past aging research has shown that older adults with spared cognitive ability have better local short-range information processing while global long-range processing is less efficient. We took this research a step further to investigate whether the underlying structural connections, measured in vivo using diffusion magnetic resonance imaging (dMRI), show a similar shift to support cognitive ability. We analyzed the structural connectivity streamline probability (representing the probability of connection between regions) and nodal efficiency and local efficiency regional graph theory metrics to determine whether age and cognitive ability are related to structural network differences. We found that the relationship between structural connectivity and cognitive ability with age was nuanced, with some differences with age that were associated with poorer cognitive outcomes, but other reorganizations that were associated with spared cognitive ability. These positive changes included strengthened local intrahemispheric connectivity and increased nodal efficiency of the ventral occipital-temporal stream, nucleus accumbens, and hippocampus for older adults, and widespread local efficiency primarily for middle-aged individuals., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)

Purpose: The COVID-19 pandemic magnified pre-existing socioeconomic, operational, and structural challenges in long-term care across the world. In Canada, the long-term care sector's dependence on caregivers as a supplement to care workers became apparent once restrictive visitation policies were employed. We conducted a scoping review to better understand the associations between caregiving and resident, formal and informal caregiver health in long-term care before and during the COVID-19 pandemic., Methods: A literature search was performed using MEDLINE, AgeLine, Google Advanced, ArXiv, PROSPERO, and OSF. Pairs of independent reviewers screened titles and abstracts followed by a review of full texts. Studies were included if they reported biological, psychological, or social health outcomes associated with caregiving (or lack thereof)., Results: After screening and reviewing 252 records identified by the search strategy, a total of 20 full-text records were eligible and included in this review. According to our results, research on caregiving increased during the pandemic, and researchers noted restrictive visitation policies had an adverse impact on health outcomes for residents and formal and informal caregivers. In comparison, caregiving in long-term care prior to the pandemic, and once visitation policies became less restrictive, led to mostly beneficial health outcomes., Conclusion: Caregiver interventions, for the most part, appear to promote better health outcomes for long-term care residents and formal and informal caregivers. Suggestions to better support caregiving in long-term care settings are offered., Competing Interests: Declarations. Conflicts of interest: There are no conflicts of interest to report. Ethical approval: Not required. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

The COVID-19 pandemic has killed millions across the world in only two years. Government health restrictions aimed at preventing transmission have impacted typical mourning practices such as funeral gatherings and in-person grief support services. This research examines the potential impacts that the pandemic may have had on people's ability to grieve. We employed a mixed methods study design to ask those who have lost a loved one during this time to reflect on their mourning practices with an anonymous survey. Our results present themes of complicated grief, the uncertainty of who to blame for frustrations, and common needs requested by the bereaved to help them mourn during these unprecedented times. These findings may help inform grief support and bereavement services during current and future mass death and pandemic health concerns., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The purpose of this study was to compare the frequency and duration of on-side and off-side strokes and stroke transitions between male and female canoe slalom athletes during international competitions. We analysed 33 International Canoe Federation World Cup, World Championship and European Canoe Association Championship canoe slalom race videos, from 2018 to 2020, frame-by-frame. We recorded drive durations and transition durations for each race run. We also recorded the frequency of different stroke types and transition types used in each run. Stroke timing parameters differed between female and male athletes. We found that female athletes performed a significantly greater proportion of switch transitions and on-side strokes. Male athletes performed a significantly greater proportion of cross transitions and off-side strokes. Male athletes performed significantly faster cross transitions. On-on and off-off transition durations were significantly faster than cross transitions, and cross transitions were significantly faster than switch transitions. Females had a significantly longer drive duration and lower stroke frequency compared to males. Overall, stroke and drive durations of on-side strokes and off-side strokes were not significantly different. This study identifies stroke technique differences between male and female canoe slalom athletes which can be used as a basis for future research and training.

This cross-sectional study evaluated the configural and metric structures of the Intersectional Discrimination Index (InDI), an instrument that measures anticipated (InDI-A), dat-to-day (InDI-D), and major (InDI-M) discrimination. Data from a broader study, focused on the impacts of discrimination on the mental health of women living in Brazil, were used. Approximately 1,000 women, selected according to a convenience sampling scheme, answered the InDI and questions about sociodemographic characteristics in an electronic form that was administered in 2021. Exploratory factor analyses and exploratory structural equation modeling were applied to the first half of the sample; for the second, confirmatory factor analysis was conducted. Taken together, the findings suggest that each of the three measures is one-dimensional. However, unlike the study that originally proposed the InDI for use in Canada and the United States, we observed the presence of residual correlations in the three subscales evaluated, all of which were suggestive of content redundancy between specific pairs of items. The three measures showed moderate to strong factor loadings and acceptable fit to the data. InDI exhibited reasonable internal validity, potentially becoming a valuable instrument for investigating the health effects of intersectional discrimination in Brazil. Future studies should evaluate the consistency of these findings, examine the scalar structure of the instrument, and analyze its invariance among different marginalized groups.

Aim: To explore the views of tobacco-smoking chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) patients on telehealth-based cessation programs and the role of e-cigarettes as an aid to quit smoking., Background: Tobacco smoking accelerates the progression of COPD. Traditional smoking cessation programs often do not entirely address the unique needs of COPD patients, leading to suboptimal effectiveness for this population. This research is aimed at describing the attitudes and preferences of COPD and ACO patients toward innovative, telehealth-based smoking cessation strategies and the potential application of e-cigarettes as a quitting aid., Methods: A qualitative exploratory approach was adopted in this study, employing both focus groups and individual interviews with English-speaking adults with diagnosed COPD or ACO. Participants included both current smokers (≥ 5 cigarettes/day) and recent ex-smokers (who quit < 12 months ago). Data were systematically coded with iterative reliability checks and subjected to thematic analysis to extract key themes., Findings: A total of 24 individuals participated in this study. The emergent themes were the perceived structure and elements of a successful smoking cessation program, the possible integration of telehealth with digital technologies, and the strategic use of e-cigarettes for smoking reduction or cessation. The participants stressed the importance of both social and professional support in facilitating smoking cessation, expressing a high value for insights provided by ex-smokers serving as mentors. A preference was observed for group settings; however, the need for individualized plans was also highlighted, considering the diverse motivations individuals had to quit smoking. The participants perceived online program delivery as potentially beneficial as it could provide immediate access to support during cravings or withdrawals and was accessible to remote users. Opinions on e-cigarettes were mixed; some participants saw them as a less harmful alternative to conventional smoking, while others were skeptical of their efficacy and safety and called for further research.

Attending to the behaviors of eyewitnesses at police lineups could help to determine whether an eyewitness identification is accurate or mistaken. Eyewitness identification decision processes were explored using augmented reality holograms. Children (n = 143; Mage = 10.79, SD = 1.12 years) and adults (n = 152; Mage = 22.12, SD = 7.47 years) viewed staged crime videos and made identification decisions from sequential lineups. The lineups were presented in augmented reality. Children were less accurate than adults on the lineup task. For adults, fast response times and high post-identification confidence ratings were both reflective of identification accuracy. Fast response times were also reflective of accuracy for children; however, children's confidence ratings did not reflect the likely accuracy of their identifications. A new additional measure, the witness' proximity to the augmented reality lineup, revealed that children who made mistaken identifications moved closer to the lineup than children who correctly identified the person from the crime video. Adults who moved any distance towards the lineup were less accurate than adults who did not move at all, but beyond that, adults' proximity to the lineup was not reflective of accuracy. The findings give further evidence that behavioral indicators of deliberation and information-seeking by eyewitnesses are signals of low lineup identification reliability. The findings also suggest that when assessing the reliability of children's lineup identifications, behavioral measures are more useful than metacognitive reports., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Price, Fitzgerald. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We hypothesized that increased cardiorespiratory fitness (CRF) slows down a person's aging, particularly in individuals with chronic airflow limitation (CAL). Participants aged ≥40 years ( n  = 78) had baseline blood DNA methylation profiled and underwent cardiopulmonary cycle exercise testing at baseline and at three years. Epigenetic clocks were calculated and tested for their association with CRF using linear regression. Differentially methylated genes associated with CRF were identified using a robust linear model. Higher CRF at baseline was associated with lower age acceleration in the epigenetic clocks DNAmAgeSkinBlood ( p = 0.016 ), DNAmGrimAge ( p = 0.012 ), and DNAmGrimAge2 ( p = 0.011 ). These effects were consistent in individuals with CAL (DNAmGrimAge p = 0.009 and DNAmGrimAge2 p = 0.007 ). CRF at three years was associated with baseline DNAmGrimAge ( p = 0.015 ) and DNAmGrimAge2 ( p = 0.011 ). Differentially methylated genes associated with CRF enriched multiple aging-related pathways, including cellular senescence. Enhancing CRF may be one intervention that can slow biological aging and improve health outcomes in chronic respiratory diseases., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: The onset of the COVID-19 pandemic drove a rapid and widespread shift to virtual care, followed by a gradual return to in-person visits. Virtual visits may offer more convenient access to care for some, but others may experience challenges accessing care virtually, and some medical needs must be met in-person. Experiences of the shift to virtual care and benefits of in-person care may vary by immigration experience (immigration status and duration), official language level, and age. We examined use of virtual care and return to in-person visits in the Canadian province of British Columbia (BC), comparing patterns by age and across immigration groups, including length of time in Canada and language level (official languages English and French) at time of arrival., Methods: We used linked administrative health and immigration data to examine total primary care visits (virtual or in-person) and return to in-person visits during the COVID-19 pandemic (2019/20-2021/2) in BC. We examined the proportion of people with any primary care visits and with any in-person visits within each year as measures of access to primary care. We estimated the odds of any primary care visits and any in-person visits by immigration group and official language level assessed prior to arrival: non-immigrants, long-term immigrants, recent immigrants (< 5 years) with high assessed official language level and recent immigrants (< 5 years) with low assessed official language level (assessed prior to arrival), stratified by age., Results: In general, changes in access to primary care (odds of any visits and odds of any in-person visits) were similar across immigration groups over the study period. However, we observed substantial disparities in access to primary care by immigration group among people aged 60 + , particularly in recent immigrants with low official language level (0.42, 0.40-0.45). These disparities grew wider over the course of the pandemic., Conclusion: Though among younger adults changes in access to primary care between 2019-2021 were similar across immigration groups, we observed significant and growing inequities among older adults, with particularly limited access among adults who immigrated recently and with low assessed official language level. Targeted interventions to ensure acceptable, accessible care for older immigrants are needed., (© 2024. The Author(s).)

Importance: Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice., Objective: To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada., Design, Setting, and Participants: For this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024., Main Outcomes and Measures: Outcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty., Results: In the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population., Conclusions and Relevance: In this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.

Older adults have difficulty maintaining balance when faced with postural disturbances, a task that is influenced by the stiffness of the triceps surae and Achilles tendon. Age-related changes in Achilles tendon stiffness have been reported at matched levels of effort, but measures typically have not been made at matched loads, which is important due to age-dependent changes in strength. Moreover, there has been limited investigation into age-dependent changes in muscle stiffness. Here, we investigate how age alters muscle and tendon stiffness and their influence on ankle stiffness. We hypothesized that age-related changes in muscle and tendon contribute to reduced ankle stiffness in older adults and evaluated this hypothesis when either load or effort were matched. We used B-mode ultrasound with joint-level perturbations to quantify ankle, muscle, and tendon stiffness across a range of loads and efforts in seventeen healthy younger and older adults. At matched loads relevant to standing and the stance phase of walking, there was no significant difference in ankle, muscle, or tendon stiffness between groups (all p > 0.13). However, at matched effort, older adults exhibited a significant decrease in ankle (27%; p = 0.008), muscle (37%; p = 0.02), and tendon stiffness (22%; p = 0.03) at 30% of maximum effort. This is consistent with our finding that older adults were 36% weaker than younger adults in plantarflexion (p = 0.004). Together, these results indicate that, at the loads tested in this study, there are no age-dependent changes in the mechanical properties of muscle or tendon, only differences in strength that result in altered ankle, muscle, and tendon stiffness at matched levels of effort., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: Governance models are a defining characteristic of health-care systems, yet little research is available about the governance of health-care delivered in correctional facilities. This study aims to explore the perspectives of correctional services leaders in British Columbia, Canada, on the motivations for transferring responsibility for health-care services in provincial correctional facilities to the Ministry of Health, as well as key lessons learned., Design/methodology/approach: Eight correctional services leaders participated in one-on-one interviews between September 2019 and February 2020. The authors used inductive thematic analysis to explore key themes. To triangulate early effects of the transfer identified by participants the authors used complaints data from Prisoners' Legal Services to examine changes over time., Findings: The authors identified four major themes related to the rationale for this transfer: 1) quality and equivalence of care, 2) integration and throughcare, 3) values and expertise and 4) funding and resources. Facilitators included changes in the external environment, having the right people in the right places, a strong sense of alignment and shared goals and a changing culture in corrections. Participants also highlighted challenges, including ongoing human resourcing issues, having to navigate and define shared responsibilities and adapting a large bureaucracy to the environment in corrections. Consistent with outcomes described by participants, data showed that a lower proportion of complaints received after the transfer were related to health-care., Originality/value: The perspectives of correctional leaders on the transfer of governance for health-care services in custody to the community health-care system provide novel insights into the processes and potential of this change., (© Katherine E. McLeod, Amanda Butler, Ruth Elwood Martin and Jane A. Buxton.)