Molecules targeting a novel homotrimer cavity of Spike protein attenuate replication of SARS-CoV-2.

The SARS-CoV-2 Spike glycoprotein (S) utilizes a unique trimeric conformation to interact with the ACE2 receptor on host cells, making it a prime target for inhibitors that block viral entry. We have previously identified a novel proteinaceous cavity within the Spike protein homotrimer that could serve as a binding site for small molecules. However, it is not known whether these molecules would inhibit, stimulate, or have no effect on viral replication. To address this, we employed structural-based screening to identify small molecules that dock into the trimer cavity and assessed their impact on viral replication. Our findings show that a cohort of identified small molecules binding to the Spike trimer cavity effectively reduces the replication of various SARS-CoV-2 variants. These molecules exhibited inhibitory effects on B.1 (European original, D614G, EDB2) and B.1.617.2 (δ) variants, while showing moderate activity against the B.1.1.7 (α) variant. We further categorized these molecules into distinct groups based on their structural similarities. Our experiments demonstrated a dose-dependent viral replication inhibitory activity of these compounds, with some, like BCC0040453 exhibiting no adverse effects on cell viability even at high concentrations. Further investigation revealed that pre-incubating virions with compounds like BCC0031216 at different temperatures significantly inhibited viral replication, suggesting their specificity towards the S protein. Overall, our study highlights the inhibitory impact of a diverse set of chemical molecules on the biological activity of the Spike protein. These findings provide valuable insights into the role of the trimer cavity in the viral replication cycle and aid drug discovery programs aimed at targeting the coronavirus family.

Equity and modeling in sustainability science: Examples and opportunities throughout the process.

Equity is core to sustainability, but current interventions to enhance sustainability often fall short in adequately addressing this linkage. Models are important tools for informing action, and their development and use present opportunities to center equity in process and outcomes. This Perspective highlights progress in integrating equity into systems modeling in sustainability science, as well as key challenges, tensions, and future directions. We present a conceptual framework for equity in systems modeling, focused on its distributional, procedural, and recognitional dimensions. We discuss examples of how modelers engage with these different dimensions throughout the modeling process and from across a range of modeling approaches and topics, including water resources, energy systems, air quality, and conservation. Synthesizing across these examples, we identify significant advances in enhancing procedural and recognitional equity by reframing models as tools to explore pluralism in worldviews and knowledge systems; enabling models to better represent distributional inequity through new computational techniques and data sources; investigating the dynamics that can drive inequities by linking different modeling approaches; and developing more nuanced metrics for assessing equity outcomes. We also identify important future directions, such as an increased focus on using models to identify pathways to transform underlying conditions that lead to inequities and move toward desired futures. By looking at examples across the diverse fields within sustainability science, we argue that there are valuable opportunities for mutual learning on how to use models more effectively as tools to support sustainable and equitable futures.

Access to episodic primary care: a cross-sectional comparison of walk-in clinics and urgent primary care centers in British Columbia.

AIM: This study aimed to identify publicly reported access characteristics for episodic primary care in BC and provided a clinic-level comparison between walk-in clinics and UPCCs. BACKGROUND: Walk-in clinics are non-hospital-based primary care facilities that are designed to operate without appointments and provide increased healthcare access with extended hours. Urgent and Primary Care Centres (UPCCs) were introduced to British Columbia (BC) in 2018 as an additional primary care resource that provided urgent, but not emergent care during extended hours. METHODS: This cross-sectional study used publicly available data from all walk-in clinics and UPCCs in BC. A structured data collection form was used to record access characteristics from clinic websites, including business hours, weekend availability, attachment to a longitudinal family practice, and provision of virtual services. FINDINGS: In total, 268 clinics were included in the analysis (243 walk-in clinics, 25 UPCCs). Of those, 225 walk-in clinics (92.6%) and two UPCCs (8.0%) were attached to a longitudinal family practice. Only 153 (63%) walk-in clinics offered weekend services, compared to 24 (96%) of UPCCs. Walk-in clinics offered the majority (8,968.6/ 78.4%) of their service hours between 08:00 and 17:00, Monday to Friday. UPCCs offered the majority (889.3/ 53.7%) of their service hours after 17:00. CONCLUSION: Most walk-in clinics were associated with a longitudinal family practice and provided the majority of clinic services during typical business hours. More research that includes patient characteristics and care outcomes, analyzed at the clinic level, may be useful to support the optimization of episodic primary healthcare delivery.

Differential RNA editing landscapes in host cell versus the SARS-CoV-2 genome.

The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA editing pathways playing a role in viral evolution, here, we use an in vitro human cell infection model to assess RNA mutation types in two SARS-CoV-2 strains representing the original and the alpha variants. The variants showed both different cellular responses and mutation patterns with alpha showing higher mutation frequency with most substitutions observed being C-U, indicating an important role for apolipoprotein B mRNA editing catalytic polypeptide-like editing. Knockdown of select APOBEC3s through RNAi increased virus production in the original virus, but not in alpha. Overall, these data suggest a deaminase-independent anti-viral function of APOBECs in SARS-CoV-2 while the C-U editing itself might function to enhance genetic diversity enabling evolutionary adaptation.

One for all-human kidney Caki-1 cells are highly susceptible to infection with corona- and other respiratory viruses.

In vitro investigations of host-virus interactions are reliant on suitable cell and tissue culture models. Results are only as good as the model they are generated in. However, choosing cell models for in vitro work often depends on availability and previous use alone. Despite the vast increase in coronavirus research over the past few years, scientists are still heavily reliant on: non-human, highly heterogeneous or not fully differentiated, or naturally unsusceptible cells requiring overexpression of receptors and other accessory factors. Complex primary or stem cell models are highly representative of human tissues but are expensive and time-consuming to develop and maintain with limited suitability for high-throughput experiments.Using tissue-specific expression patterns, we identified human kidney cells as an ideal target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and broader coronavirus infection. We show the use of the well-characterized human kidney cell line Caki-1 for infection with three human coronaviruses (hCoVs): Betacoronaviruses SARS-CoV-2 and Middle Eastern respiratory syndrome coronavirus and Alphacoronavirus hCoV 229E. Caki-1 cells show equal or superior susceptibility to all three coronaviruses when compared to other commonly used cell lines for the cultivation of the respective virus. Antibody staining against SARS-CoV-2 N protein shows comparable replication rates. A panel of 26 custom antibodies shows the location of SARS-CoV-2 proteins during replication using immunocytochemistry. In addition, Caki-1 cells were found to be susceptible to two other human respiratory viruses, influenza A virus and respiratory syncytial virus, making them an ideal model for cross-comparison for a broad range of respiratory viruses. IMPORTANCE Cell lines remain the backbone of virus research, but results are only as good as their originating model. Despite increased research into human coronaviruses following the COVID-19 pandemic, researchers continue to rely on suboptimal cell line models of: non-human origin, incomplete differentiation, or lacking active interferon responses. We identified the human kidney Caki-1 cell line as a potential target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This cell line could be shown to be infectable with a wide range of coronaviruses including common cold virus hCoV-229E, epidemic virus MERS-CoV, and SARS-CoV-2 as well as other important respiratory viruses influenza A virus and respiratory syncytial virus. We could show the localization of 26 SARS-CoV-2 proteins in Caki-1 cells during natural replication and the cells are competent of forming a cellular immune response. Together, this makes Caki-1 cells a unique tool for cross-virus comparison in one cell line.

Climate oscillation impacts on water supply augmentation planning.

Climate oscillations ranging from years to decades drive precipitation variability in many river basins globally. As a result, many regions will require new water infrastructure investments to maintain reliable water supply. However, current adaptation approaches focus on long-term trends, preparing for average climate conditions at mid- or end-of-century. The impact of climate oscillations, which bring prolonged and variable but temporary dry periods, on water supply augmentation needs is unknown. Current approaches for theory development in nature-society systems are limited in their ability to realistically capture the impacts of climate oscillations on water supply. Here, we develop an approach to build middle-range theory on how common climate oscillations affect low-cost, reliable water supply augmentation strategies. We extract contrasting climate oscillation patterns across sub-Saharan Africa and study their impacts on a generic water supply system. Our approach integrates climate model projections, nonstationary signal processing, stochastic weather generation, and reinforcement learning-based advances in stochastic dynamic control. We find that longer climate oscillations often require greater water supply augmentation capacity but benefit more from dynamic approaches. Therefore, in settings with the adaptive capacity to revisit planning decisions frequently, longer climate oscillations do not require greater capacity. By building theory on the relationship between climate oscillations and least-cost reliable water supply augmentation, our findings can help planners target scarce resources and guide water technology and policy innovation. This approach can be used to support climate adaptation planning across large spatial scales in sectors impacted by climate variability.

Effectiveness of training before unsedated MRI scans in young children: a randomized control trial.

BACKGROUND: Young children requiring clinical magnetic resonance imaging (MRI) may be given general anesthesia. General anesthesia has potential side effects, is costly, and introduces logistical challenges. Thus, methods that allow children to undergo awake MRI scans are desirable. OBJECTIVES: To compare the effectiveness of mock scanner training with a child life specialist, play-based training with a child life specialist, and home book and video preparation by parents to allow non-sedated clinical MRI scanning in children aged 3-7 years. MATERIALS AND METHODS: Children (3-7 years, n=122) undergoing clinical MRI scans at the Alberta Children's Hospital were invited to participate and randomized to one of three groups: home-based preparation materials, training with a child life specialist (no mock MRI), or training in a mock MRI with a child life specialist. Training occurred a few days prior to their MRI. Self- and parent-reported functioning (PedsQL VAS) were assessed pre/post-training (for the two training groups) and pre/post-MRI. Scan success was determined by a pediatric radiologist. RESULTS: Overall, 91% (111/122) of children successfully completed an awake MRI. There were no significant differences between the mock scanner (89%, 32/36), child life (88%, 34/39), and at-home (96%, 45/47) groups (P=0.34). Total functioning scores were similar across groups; however, the mock scanner group had significantly lower self-reported fear (F=3.2, P=0.04), parent-reported sadness (F=3.3, P=0.04), and worry (F=3.5, P=0.03) prior to MRI. Children with unsuccessful scans were younger (4.5 vs. 5.7 years, P<0.001). CONCLUSIONS: Most young children can tolerate awake MRI scans and do not need to be routinely anesthetized. All preparation methods tested, including at-home materials, were effective.

Primary and Community Care Mapping: Helping Communities Collaboratively Plan Health Services in a Patient-Centred Manner.

Primary care, a core feature of sustainable, high-quality healthcare systems, is undergoing significant system changes across Canada. Complex system change often fails without active implementation support. Primary and Community Care (PACC) Mapping is a rapid co-design method that helps community stakeholders engage in planning at various stages of their change. PACC Mapping has been used in multiple provinces for a range of areas, from maternity care to vaccine planning. This paper outlines the PACC Mapping approach, early experiences and scaling through training facilitators.

Pregnancy, obstetrical and neonatal outcomes in women exposed to physician-related occupational hazards: a scoping review.

OBJECTIVE: Evidence is needed to guide organisational decision making about workplace accommodations for pregnant physicians. Our objective was to characterise the strengths and limitations of current research examining the association between physician-related occupational hazards with pregnancy, obstetrical and neonatal outcomes. DESIGN: Scoping review. DATA SOURCES: MEDLINE/PubMed, EMBASE, CINAHL/ EBSCO, SciVerse Scopus and Web of Science/Knowledge were searched from inception to 2 April 2020. A grey literature search was performed on 5 April 2020. The references of all included articles were hand searched for additional citations. ELIGIBILITY CRITERIA: English language citations that studied employed pregnant people and any 'physician-related occupational hazards', meaning any relevant physical, infectious, chemical or psychological hazard, were included. Outcomes included any pregnancy, obstetrical or neonatal complication. DATA EXTRACTION AND SYNTHESIS: Physician-related occupational hazards included physician work, healthcare work, long work hours, 'demanding' work, disordered sleep, night shifts and exposure to radiation, chemotherapy, anaesthetic gases or infectious disease. Data were extracted independently in duplicate and reconciled through discussion. RESULTS: Of the 316 included citations, 189 were original research studies. Most were retrospective, observational and included women in any occupation rather than healthcare workers. Methods for exposure and outcome ascertainment varied across studies and most studies had a high risk of bias in data ascertainment. Most exposures and outcomes were defined categorically and results from different studies could not be combined in a meta-analysis due to heterogeneity in how these categories were defined. Overall, some data suggested that healthcare workers may have an increased risk of miscarriage compared with other employed women. Long work hours may be associated with miscarriage and preterm birth. CONCLUSIONS: There are important limitations in the current evidence examining physician-related occupational hazards and adverse pregnancy, obstetrical and neonatal outcomes. It is not clear how the medical workplace should be accommodated to improve outcomes for pregnant physicians. High-quality studies are needed and likely feasible.

Finding Primary Care-Repurposing Physician Registration Data to Generate a Regionally Accurate List of Primary Care Clinics: Development and Validation of an Open-Source Algorithm.

BACKGROUND: Some Canadians have limited access to longitudinal primary care, despite its known advantages for population health. Current initiatives to transform primary care aim to increase access to team-based primary care clinics. However, many regions lack a reliable method to enumerate clinics, limiting estimates of clinical capacity and ongoing access gaps. A region-based complete clinic list is needed to effectively describe clinic characteristics and to compare primary care outcomes at the clinic level. OBJECTIVE: The objective of this study is to show how publicly available data sources, including the provincial physician license registry, can be used to generate a verifiable, region-wide list of primary care clinics in British Columbia, Canada, using a process named the Clinic List Algorithm (CLA). METHODS: The CLA has 10 steps: (1) collect data sets, (2) develop clinic inclusion and exclusion criteria, (3) process data sets, (4) consolidate data sets, (5) transform from list of physicians to initial list of clinics, (6) add additional metadata, (7) create working lists, (8) verify working lists, (9) consolidate working lists, and (10) adjust processing steps based on learnings. RESULTS: The College of Physicians and Surgeons of British Columbia Registry contained 13,726 physicians, at 2915 unique addresses, 6942 (50.58%) of whom were family physicians (FPs) licensed to practice in British Columbia. The CLA identified 1239 addresses where primary care was delivered by 4262 (61.39%) FPs. Of the included addresses, 84.50% (n=1047) were in urban locations, and there was a median of 2 (IQR 2-4, range 1-23) FPs at each unique address. CONCLUSIONS: The CLA provides a region-wide description of primary care clinics that improves on simple counts of primary care providers or self-report lists. It identifies the number and location of primary care clinics and excludes primary care providers who are likely not providing community-based primary care. Such information may be useful for estimates of capacity of primary care, as well as for policy planning and research in regions engaged in primary care evaluation or transformation.

Direct Lysis RT-qPCR of SARS-CoV-2 in Cell Culture Supernatant Allows for Fast and Accurate Quantification.

Studying the entire virus replication cycle of SARS-CoV-2 is essential to identify the host factors involved and treatments to combat infection. Quantification of released virions often requires lengthy procedures, whereas quantification of viral RNA in supernatant is faster and applicable to clinical isolates. Viral RNA purification is expensive in terms of time and resources, and is often unsuitable for high-throughput screening. Direct lysis protocols were explored for patient swab samples, but the lack of virus inactivation, cost, sensitivity, and accuracy is hampering their application and usefulness for in vitro studies. Here, we show a highly sensitive, accurate, fast, and cheap direct lysis RT-qPCR method for quantification of SARS-CoV-2 in culture supernatant. This method inactivates the virus and permits detection limits of 0.043 TCID50 virus and <1.89 copy RNA template per reaction. Comparing direct lysis with RNA extraction, a mean difference of +0.69 ± 0.56 cycles was observed. Application of the method to established qPCR methods for RSV (-ve RNA), IAV (segmented -ve RNA), and BHV (dsDNA) showed wider applicability to other enveloped viruses, whereby IAV showed poorer sensitivity. This shows that accurate quantification of SARS-CoV-2 and other enveloped viruses can be achieved using direct lysis protocols, facilitating a wide range of high- and low-throughput applications.

Paving the Way for Electronic Patient-Centered Measurement in Team-Based Primary Care: Integrated Knowledge Translation Approach.

BACKGROUND: Patient-centered measurement (PCM) aims to improve the overall quality of care through the collection and sharing of patient values, outcomes, and perspectives. However, the use of PCM in care team decisions remains limited. Integrated knowledge translation (IKT) offers a collaborative, adaptive approach to explore best practices for incorporating PCM into primary care practices by involving knowledge users, including patients and providers, in the exploratory process. OBJECTIVE: This study aims to test the feasibility of using patient-generated data in team-based care; describe the use of these data for team-based mental health care; and summarize patient and provider care experiences with PCM. METHODS: We conducted a multi-method exploratory study in a rural team-based primary care clinic using IKT to co-design, implement, and evaluate the use of PCM in team-based mental health care. Care pathways, workflows, and quality improvement activities were adjusted iteratively to improve integration efforts. Patient and provider experiences were evaluated using individual interviews relating to the use of PCM and patient portals in practice. All meeting notes, interview summaries, and emails were analyzed to create a narrative evaluation. RESULTS: During co-design, a care workflow was developed to incorporate electronically collected patient-generated data from the patient portal into the electronic medical record, and customized educational tools and resources were added. During implementation, care pathways and patient workflows for PCM were developed. Patients found portal use easy, educational, and validating, but data entries were not used during care visits. Providers saw the portal as extra work, and the lack of portal and electronic medical record integration was a major barrier. The IKT approach was invaluable for addressing workflow changes and understanding the ongoing barriers to PCM use and quality improvement. CONCLUSIONS: Although the culture toward using PCM is changing, the use of PCM during care has not been successful. Patients felt validated and supported through portal use and could be empowered to bring these data to their visits. Training, modeling, and adaptable PCM methods are required before PCM can be integrated into routine care.

Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions.

BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock.

Youth, Caregiver, and Provider Perception of the Transition from Pediatric to Adult Care for Youth with Chronic Diseases.

OBJECTIVE: Youth with chronic diseases are required to transition from pediatric to adult care across the world at variable ages in their adolescent years. The aim of this study is to examine perspectives of young patients, caregivers, and physicians in the transition process. METHODS: This 3-phase mixed methods research study gathered data using an iterative approach with the collaboration of youth coresearchers. Physician opinions were gathered through a survey. Further data were collected through 15 semistructured, standardized interviews of adolescent medicine physicians. Perspectives of adolescents and young adult (AYA) patients and their caregivers were gathered independently using a 20-item survey. Quantitative data were analyzed with descriptive statistics and sorted by theme. RESULTS: In phase 1, respondents rated current transition processes as an average 5.19/10 on a 10-point Likert scale (1 = poor and 10 = excellent) with no participants rating 9 or 10 of 10. The top barrier identified was a lack of communication between pediatric and adult doctors (71.0%). The top ranked strategy for improvement was to provide formal transition guidelines (69.8%). In phase 2, specific concerns include lack of insurance coverage, lack of physicians available to take on youth transitioning to adult care who are also knowledgeable regarding pediatric conditions, and lack of funding or staff support for transition clinics. In phase 3, most of the youth surveyed (52%) reported that their physicians have not involved them in conversations about transitioning. AYA patients prefer the point of transfer to occur with other life transitions such as graduation, and caregivers prefer transfer to happen during times of stability where their children can dedicate adequate time to their health. CONCLUSION: Fulfilling youth desire for increased patient autonomy and ownership can help overcome their poor perception of the transition process. Increased physician training in adolescent health and improvements in post-transition community plans may be beneficial to prevent loss to follow-up among young patients across medical disciplines. Successful transition into adult care requires a unique process for each youth and requires adequate preparation from the pediatric front, empowerment of young patients and their families, and continuity of care by adult providers.

A head mounted augmented reality design practice for maintenance assembly: Toward meeting perceptual and cognitive needs of AR users.

Head Mounted Display (HMD) based Augmented Reality (AR) is being increasingly used in manufacturing and maintenance. However, limited research has been done to understand user interaction with AR interfaces, which may lead to poor usability, risk of occupational hazards, and low acceptance of AR systems. This paper uses a theoretically-driven approach to interaction design to investigate the impact of different AR modalities in terms of information mode (i.e. video vs. 3D animation) and interaction modality (i.e. hand-gesture vs. voice command) on user performance, workload, eye gaze behaviours, and usability during a maintenance assembly task. The results show that different information modes have distinct impacts compared to paper-based maintenance, in particular, 3D animation led to a 14% improvement over the video instructions in task completion time. Moreover, insights from eye gaze behaviours such as number of fixations and transition between Areas of Interest (AOIs) revealed the differences in attention switching and task comprehension difficulty with the choice of AR modalities. While, subjective user perceptions highlight some ergonomic issues such as misguidance and overreliance, which must be considered and addressed from the joint cognitive systems' (JCSs) perspective and in line with the predictions derived from the Multiple Resources Model.

Medicinal cannabis in children and adolescents with autism spectrum disorder: A scoping review.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition estimated to affect 1 in 66 children in Canada and 1 in 270 individuals worldwide. As effective therapies for the management of ASD core and associated symptoms are limited, parents are increasingly turning to clinicians for advice regarding the use of medicinal cannabis to manage behavioural disturbances. OBJECTIVE: The objective of this scoping review was to identify and map symptoms, outcomes and adverse events related to medicinal cannabis treatment for ASD-related behaviours. METHODS: Ovid MEDLINE, Embase, CINAHL, PsycInfo, Web of Science Core Collection, Google Scholar and grey literature sources were searched up to 5 January 2020 for studies. Included studies met the following criteria: (1) investigate the use of medicinal cannabis, (2) at least 50% participants had ASD, (3) at least 50% of the study population was 0-18 years old and (4) any study design (published or unpublished). RESULTS: We identified eight completed and five ongoing studies meeting the inclusion criteria. All studies reported substantial behaviour and symptom improvement on medicinal cannabis, with 61% to 93% of subjects showing benefit. In the three studies reporting on concomitant psychotropic medication usage and with cannabis use, up to 80% of participants observed a reduction in concurrent medication use. Adverse events related to cannabis use were reported in up to 27% of participants related, and two participants had psychotic events. CONCLUSIONS: Early reports regarding medicinal cannabis in paediatric ASD symptom management are presented as positive; the evidence, however, is limited to very few retrospective cohort and observational studies. Evidence of safety and efficacy from prospective clinical trials is needed.

Advancing digital patient-centered measurement methods for team-based care.

Objectives: To conceptualize new methods for integrating patient-centered measurement into team-based care. Methods: A standalone portal was introduced into a rural clinic to support conceptualization of new methods for integration of patient-centered measurement in team-based care. The portal housed mental health-related online resources, three patient-reported measures and a self-action plan. Six providers and four patients used the portal for four months. Our data collection techniques included clinic discussions, one-on-one interviews, workflow diagrams and data generated through the portal. Analysis was supported through coding interview transcripts, looking across multiple sources of research data and research team discussions. Results: Our research team conceptualized five team-based patient-centered measurement methods through this study. Patient-centered measurement Team Mapping offfers a technique to provide greater clarity of care-team roles and responsibilities in data collected through patient-centered measurement. Longitudinal Care Alignment can guide the care-team on incorporating patient-centered measurement into ongoing provider-patient interactions. Digital Tool Exploration can be used to evaluate a team's readiness toward digital tool adoption, and the impact of these tools. Team-based quality improvement serves as a framework for engaging teams in patient-centered quality improvement. Shared learning is a method that promotes patientprovider interactions that validate patient's perspectives of their care. Conclusion: The portal illuminated new methods for the integration of patient-centered measurement in team-based care. The first three proposed patient-centered measurement methods provides ways to assess how a clinic can incorporate patient-centered measurement methods into team-based care. The latter two methods focus on the aim of patient-generated data in which patient's values and perspectives are represented and quality of patient-centered care can be evaluated. Further testing is needed to assess the utility of these patient-centered measurement methods across different clinical settings and domains.

Team-based care Evaluation and Adoption Model (TEAM) Framework: Supporting the comprehensive evaluation of primary care transformation over time.

OBJECTIVE: To introduce the new Team-based care Evaluation and Adoption Model (TEAM) Framework. QUALITY OF EVIDENCE: The initial TEAM Framework was derived from a series of reviews and consultations with academic and clinical experts. In a parallel process, team-based primary and community care evaluation in Canada was assessed through a structured review of academic literature, followed by a review of policy literature of existing primary care evaluation frameworks. MAIN MESSAGE: The review of academic articles alongside an analysis of policy documents and existing evaluation frameworks in primary care resulted in the development of the 10-dimension TEAM Framework. CONCLUSION: Primary care transformation requires evaluation over time. The TEAM Framework provides a comprehensive framework for assessing evidence needed to support short- and long-term actionable improvements for team-based primary and community care in Canada. This framework will inform the development of an evaluation tool kit for primary care teams.

The era of virtual care: Perspectives of youth on virtual appointments in COVID-19 and beyond.

In response to COVID-19, paediatric providers have shifted to providing outpatient health care appointments through telehealth. Youth perspectives on changes to health care access during the pandemic are important to consider when optimizing care for paediatric patients. Youth who contributed to this commentary reported that major benefits of virtual care included time savings, ease of access, continuity of care, and ability to participate in health appointments from the comfort of one's own home without a risk of COVID-19 exposure. These youth also recognized limitations to virtual care, including the inability to complete laboratory or imaging tests, and the lack of physical examination capabilities. Additionally, they stressed the importance of visual components of virtual appointments and health care providers needing to consider privacy restrictions youth may have. Overall, our cohort of youth feel positive about virtual care and hope care providers can work with youth individually to determine the best solution for them.

Joint inference of CFC lifetimes and banks suggests previously unidentified emissions.

Chlorofluorocarbons (CFCs) are harmful ozone depleting substances and greenhouse gases. CFC production was phased-out under the Montreal Protocol, however recent studies suggest new and unexpected emissions of CFC-11. Quantifying CFC emissions requires accurate estimates of both atmospheric lifetimes and ongoing emissions from old equipment (i.e. 'banks'). In a Bayesian framework we simultaneously infer lifetimes, banks and emissions of CFC-11, 12 and 113 using available constraints. We find lifetimes of all three gases are likely shorter than currently recommended values, suggesting that best estimates of inferred emissions are larger than recent evaluations. Our analysis indicates that bank emissions are decreasing faster than total emissions, and we estimate new, unexpected emissions during 2014-2016 were 23.2, 18.3, and 7.8 Gg/yr for CFC-11, 12 and 113, respectively. While recent studies have focused on unexpected CFC-11 emissions, our results call for further investigation of potential sources of emissions of CFC-12 and CFC-113, along with CFC-11.