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.

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.

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.

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.

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.

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.

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.

The Gender of COVID-19 Experts in Newspaper Articles: a Descriptive Cross-Sectional Study.

BACKGROUND: Pre-existing gender-based disparities in academia may have worsened during the COVID-19 pandemic. Being cited as an expert source in newspaper articles about COVID-19 may increase an individual's research or leadership profile. In addition, visibility in a newspaper article is an important component of representation in academia. OBJECTIVE: To determine whether women were underrepresented as COVID-19 expert sources in print newspapers in the USA. DESIGN: We undertook a cross-sectional study of English-language newspaper articles that addressed the COVID-19 pandemic and that were published in the top 10 most widely read newspapers in the USA between April 1 and April 15, 2020. MAIN MEASURES: We extracted the names of all people cited as expert sources and categorized the gender of each expert source based on pronoun usage within the article or on a business, university, or organization website. The professional role of each expert was assigned based on their description in the article. KEY RESULTS: Of 2297 expert sources identified, 35.9% (95% confidence interval [CI] 33.9-37.8%; n = 824) were women and 63.7% were men (95% CI 61.8-65.7%; n = 1464). This result was similar when considering unique experts in each newspaper and for all included newspapers; of the 1738 unique experts per newspaper, 34.6% were women (95% CI 32.3-36.8%; n = 601), and of the 1593 unique experts in all newspapers, 36.5% were women (95% CI 34.1-38.9%; n = 581). Of articles with multiple experts referenced (n = 374), 102 cited only men experts (27.3%) and 44 cited only women experts (11.8%). Women were underrepresented as experts as Healthcare Workers and Professionals, Non-STEM Experts, Public Health Leaders, and STEM Scientists. There were no differences in the proportion of women experts between newspapers or between different regions of the USA. CONCLUSIONS: Altogether, our findings support that men academics outnumber women as COVID-19 experts in newspaper articles.

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.

Role of the novel endoribonuclease SLFN14 and its disease-causing mutations in ribosomal degradation.

Platelets are anucleate and mostly ribosome-free cells within the bloodstream, derived from megakaryocytes within bone marrow and crucial for cessation of bleeding at sites of injury. Inherited thrombocytopenias are a group of disorders characterized by a low platelet count and are frequently associated with excessive bleeding. SLFN14 is one of the most recently discovered genes linked to inherited thrombocytopenia where several heterozygous missense mutations in SLFN14 were identified to cause defective megakaryocyte maturation and platelet dysfunction. Yet, SLFN14 was recently described as a ribosome-associated protein resulting in rRNA and ribosome-bound mRNA degradation in rabbit reticulocytes. To unveil the cellular function of SLFN14 and the link between SLFN14 and thrombocytopenia, we examined SLFN14 (WT/mutants) in in vitro models. Here, we show that all SLFN14 variants colocalize with ribosomes and mediate rRNA endonucleolytic degradation. Compared to SLFN14 WT, expression of mutants is dramatically reduced as a result of post-translational degradation due to partial misfolding of the protein. Moreover, all SLFN14 variants tend to form oligomers. These findings could explain the dominant negative effect of heterozygous mutation on SLFN14 expression in patients' platelets. Overall, we suggest that SLFN14 could be involved in ribosome degradation during platelet formation and maturation.

Dual Arm Co-Manipulation Architecture with Enhanced Human-Robot Communication for Large Part Manipulation.

The emergence of collaborative robotics has had a great impact on the development of robotic solutions for cooperative tasks nowadays carried out by humans, especially in industrial environments where robots can act as assistants to operators. Even so, the coordinated manipulation of large parts between robots and humans gives rise to many technical challenges, ranging from the coordination of both robotic arms to the human-robot information exchange. This paper presents a novel architecture for the execution of trajectory driven collaborative tasks, combining impedance control and trajectory coordination in the control loop, as well as adding mechanisms to provide effective robot-to-human feedback for a successful and satisfactory task completion. The obtained results demonstrate the validity of the proposed architecture as well as its suitability for the implementation of collaborative robotic systems.

Team Mapping: A Novel Method to Help Community Primary Healthcare Practices Transition to Team-Based Care.

The team mapping method engages participants in rapid, facilitated co-creation workshops to help groups explore how to work together in a primary care team. It uses patient personas (local evidence-based simulated cases) to explore team structure through paper prototyping circles of care (the persona's healthcare system). Roles and tasks are collectively defined through the discussion. Team mapping builds on three foundational methods and, through a three-stage process, facilitates the formation and strengthening of new and existing relationships, fostering team development through the process. This paper describes team mapping, outlines when it can be applied and highlights the benefits for teams.

Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction.

In addition to mutations in ITG2B or ITGB3 genes that cause defective αIIbß3 expression and/or function in Glanzmann's thrombasthenia patients, platelet dysfunction can be a result of genetic variability in proteins that mediate inside-out activation of αIIbß3 The RASGRP2 gene is strongly expressed in platelets and neutrophils, where its encoded protein CalDAG-GEFI facilitates the activation of Rap1 and subsequent activation of integrins. We used next-generation sequencing (NGS) and whole-exome sequencing (WES) to identify 2 novel function-disrupting mutations in RASGRP2 that account for bleeding diathesis and platelet dysfunction in 2 unrelated families. By using a panel of 71 genes, we identified a homozygous change (c.1142C>T) in exon 10 of RASGRP2 in a 9-year-old child of Chinese origin (family 1). This variant led to a p.Ser381Phe substitution in the CDC25 catalytic domain of CalDAG-GEFI. In 2 Spanish siblings from family 2, WES identified a nonsense homozygous variation (c.337C>T) (p.Arg113X) in exon 5 of RASGRP2 CalDAG-GEFI expression was markedly reduced in platelets from all patients, and by using a novel in vitro assay, we found that the nucleotide exchange activity was dramatically reduced in CalDAG-GEFI p.Ser381Phe. Platelets from homozygous patients exhibited agonist-specific defects in αIIbß3 integrin activation and aggregation. In contrast, α- and δ-granule secretion, platelet spreading, and clot retraction were not markedly affected. Integrin activation in the patients' neutrophils was also impaired. These patients are the first cases of a CalDAG-GEFI deficiency due to homozygous RASGRP2 mutations that are linked to defects in both leukocyte and platelet integrin activation.

Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) measurements.

INTRODUCTION AND HYPOTHESIS: The relationship between pelvic floor muscles and measurements of urethral function is not well studied. It is not known whether adjusting for clinical, demographic and urodynamic parameters would improve the association between MUCP and ALPP. Our hypothesis was that pelvic floor muscle strength (PFMS) influences the relationship between MUCP and ALPP. METHODS: This was a retrospective study of women who underwent a complex urodynamic study with evaluation of MUCP and ALPP using ICD-9 codes with documentation of PFMS. RESULTS: Urodynamic stress incontinence was confirmed in 478 patients, of whom 323 had MUCP recorded and 263 had both MUCP and ALPP recorded. Women with higher PFMS had a higher MUCP. In regression analysis ALPP at 150 mL and MUCP were weakly associated (coefficient 0.43, 95% CI 0.08-0.78; p = 0.02), whereas ALPP at capacity and MUCP were moderately associated (coefficient 0.60, 95% CI 0.25-0.95; p < 0.001). CONCLUSIONS: This study showed that MUCP and ALPP at 150 mL were weakly associated and that this improved to a moderate association for ALPP at capacity. MUCP increased with increasing PFMS among women with stress urinary incontinence and decreased with increasing age. There was no evidence that ALPP was associated with PFMS or age. The relationship between MUCP and ALPP was unchanged when accounting for covariates of PFMS (age, parity, BMI, prior procedure, urethral mobility, bladder capacity, stage of cystocele, or stage of uterine or apical prolapse).

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia.

Inherited thrombocytopenia: novel insights into megakaryocyte maturation, proplatelet formation and platelet lifespan.

The study of patients with inherited bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets and their precursor, the megakaryocyte. The normal range of platelet counts in the bloodstream ranges from 150 000 to 400 000 platelets per microliter and is normally maintained within a narrow range for each individual. This requires a constant balance between thrombopoiesis, which is primarily controlled by the cytokine thrombopoietin (TPO), and platelet senescence and consumption. Thrombocytopenia can be defined as a platelet count of less than 150 000 per microliter and can be acquired or inherited. Heritable forms of thrombocytopenia are caused by mutations in genes involved in megakaryocyte differentiation, platelet production and platelet removal. In this review, we will discuss the main causative genes known for inherited thrombocytopenia and highlight their diverse functions and whether these give clues on the processes of platelet production, platelet function and platelet lifespan. Additionally, we will highlight the recent advances in novel genes identified for inherited thrombocytopenia and their suggested function.

"That was the Last Time I Saw my House": The Importance of Place Attachment among Children and Youth in Disaster Contexts.

Place attachment is important for children and youth's disaster preparedness, experiences, recovery, and resilience, but most of the literature on place and disasters has focused on adults. Drawing on the community disaster risk reduction, recovery, and resilience literature as well as the literature on normative place attachment, children and youth's place-relevant disaster experiences are examined. Prior to a disaster, place attachments are postulated to enhance children and youth's disaster preparedness contributions and reinforce their pre-disaster resilience. During a disaster, damage of, and displacement from, places of importance can create significant emotional distress among children and youth. Following a disaster, pre-existing as well as new place ties can aid in their recovery and bolster their resilience moving forward. This framework enriches current theories of disaster recovery, resilience, and place attachment, and sets an agenda for future research.

The impact of chronic endurance and resistance training upon the right ventricular phenotype in male athletes.

OBJECTIVES: The traditional view of differential left ventricular adaptation to training type has been questioned. Right ventricular (RV) data in athletes are emerging but whether training type mediates this is not clear. The primary aim of this study was to evaluate the RV phenotype in endurance- vs. resistance-trained male athletes. Secondary aims included comparison of RV function in all groups using myocardial speckle tracking, and the impact of allometric scaling on RV data interpretation. METHODS: A prospective cross-sectional design assessed RV structure and function in 19 endurance-trained (ET), 21 resistance-trained (RT) and 21 sedentary control subjects (CT). Standard 2D tissue Doppler imaging and speckle tracking echocardiography assessed RV structure and function. Indexing of RV structural parameters to body surface area (BSA) was undertaken using allometric scaling. RESULTS: A higher absolute RV diastolic area was observed in ET (mean ± SD: 27 ± 4 cm(2)) compared to CT (22 ± 4 cm(2); P < 0.05) that was maintained after scaling. Whilst absolute RV longitudinal dimension was greater in ET (88 ± 9 mm) than CT (81 ± 10 mm; P < 0.05), this difference was removed after scaling. Wall thickness was not different between ET and RT and there were no between group differences in global or regional RV function. CONCLUSION: We present some evidence of RV adaptation to chronic ET in male athletes but limited structural characteristics of an athletic heart were observed in RT. Global and regional RV functions were comparable between groups. Allometric scaling altered data interpretation in some variables.