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Abstract Introduction A transformation of food systems is urgently needed, given their contribution to three ongoing and interlinked global health pandemics: (1) undernutrition and food insecurity, (2) obesity and non-communicable diseases (NCDs), and (3) climate change and biodiversity loss. As policymakers make decisions that shape food systems, this study aimed to identify and prioritise policies with double- or triple-duty potential to achieve healthier and more environmentally sustainable food systems. Methods This study undertook a 4-step methodological approach, including (i) a compilation of international policy recommendations, (ii) an online survey, (iii) four regional workshops with international experts and (iv) a ranking for prioritisation. Policies were identified and prioritised based on their double- or triple-duty potential, synergies and trade-offs. Using participatory and transdisciplinary approaches, policies were identified to have double- or triple-duty potential if they were deemed effective in tackling two or three of the primary outcomes of interest: (1) undernutrition, (2) obesity/NCDs and (3) environmental degradation. Results The desk review identified 291 recommendations for governments, which were merged and classified into 46 initially proposed policies. Based on the results from the online survey, 61% of those policies were perceived to have double- or triple-duty potential. During the workshops, 4 potential synergies and 31 trade-offs of these policies were identified. The final list of 44 proposed policies for healthier and more environmentally sustainable food systems created was divided into two main policy domains: ‘food supply chains’ and ‘food environments’. The outcome with the most trade-offs identified was ‘undernutrition’, followed by ‘environmental sustainability’, and ‘obesity/NCDs’. Of the top five expert-ranked food supply chain policies, two were perceived to have triple-duty potential: (a) incentives for crop diversification; (b) support for start-ups, and small- and medium-sized enterprises. For food environments, three of the top five ranked policies had perceived triple-duty potential: (a) affordability of healthier and more sustainable diets; (b) subsidies for healthier and more sustainable foods; (c) restrictions on children's exposure to marketing through all media. Conclusion This study identified and prioritised a comprehensive list of double- and triple-duty government policies for creating healthier and more environmentally sustainable food systems. As some proposed policies may have trade-offs across outcomes, they should be carefully contextualised, designed, implemented and monitored.

Objective We performed a scoping review of the relevant literature on home‐based telehealth in rheumatology to understand its appropriate application in rheumatology practice. Methods We searched the Cochrane Library, PubMed, Web of Science, and scientific meeting abstracts to identify articles that specifically addressed telehealth suitability, barriers to telehealth, patient‐reported outcomes (PROs) collected in telehealth settings, and telehealth satisfaction. From the initial search of 4,882 studies, 23 reports were included. In addition, 10 abstracts were also eligible for analysis, resulting in a total of 33 articles: 2 randomized clinical trials, 9 prospective cohort studies, and 22 retrospective studies. Results We found that triage appointments or predictive models could be helpful in selecting patients for telehealth and that telehealth interventions were appropriate for follow‐up of patients with systemic lupus erythematosus and inflammatory arthritis, but that conducting new patient visits over telehealth was not ideal. Barriers to telehealth include patient factors (age, technology access) and need for physician/process factors (eg, physical examinations). PROs collected in regular practice can be incorporated into telehealth. Several small, single‐center studies suggest that telehealth does not lead to negative outcomes compared with in‐person visits, and overall, patients report high patient satisfaction with telehealth. In several scenarios, home‐based telehealth was equivalent to in‐person visits with regard to patient outcomes and satisfaction. Conclusion The widespread potential of telehealth to manage and deliver care for people with rheumatic disease is significant. As such, further research in the form of randomized controlled trials can help contribute to growing evidence that shapes telehealth implementation for patients with rheumatic diseases.

ABSTRACTAdvertisements promoting energy-dense, nutrient-poor food and drinks influence children’s dietary choice and preference and are pervasive in children’s environments across Aotearoa, New Zealand. Using a combination of datasets from separate studies, this research seeks to describe the extent of children’s unhealthy food/drink advertising exposure in all primary and intermediate school food zones (n = 381) in Tāmaki Makaurau, Auckland, and assess whether this exposure correlates with indicators of neighbourhood deprivation. To achieve this, we developed a simple advertising exposure score using images of advertising collected from Google Street View, and investigated its spatial correlation with indicators of neighbourhood deprivation. Outdoor advertising was present in proximity to 61.9% of the sampled schools (n = 236); of which 83.1% of adverts promoted unhealthy food and/or drinks (n = 2669). Advertising exposure increased statistically significantly with neighbourhood deprivation (p

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Abstract Background In this retrospective review, the relative importance of systemic inflammation among other causes of acute kidney injury (AKI) was investigated in 1224 consecutive colorectal surgery patients. A potential benefit from reducing excessive postoperative inflammation on AKI might then be estimated. Methods AKI was determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The entire population (mixed group), composed of patients with or without sepsis, and a subpopulation of patients without sepsis (aseptic group) were examined. Markers indicative of inflammation were procedure duration, the first postoperative white blood cell (POD # 1 WBC) for the mixed population, and the neutrophil-to-lymphocyte ratio (POD #1 NLR) for the aseptic population. Multivariable logistic regression was then performed using significant (P

Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.

Background: Digital health studies using electronic patient reported outcomes (ePROs), wearables, and clinical data to provide a more comprehensive picture of patient health. Methods: Newly initiated patients on upadacitinib or adalimumab for RA will be recruited from community settings in the Excellence NEtwork in RheumatoloGY (ENRGY) practice-based research network. Over the period of three to six months, three streams of data will be collected (1) linkable physician-derived data; (2) self-reported daily and weekly ePROs through the ArthritisPower registry app; and (3) biometric sensor data passively collected via wearable. These data will be analyzed to evaluate correlations among the three types of data and patient improvement on the newly initiated medication. Conclusions: Results from this study will provide valuable information regarding the relationships between physician data, wearable data, and ePROs in patients newly initiating an RA treatment, and demonstrate the feasibility of digital data capture for Remote Patient Monitoring of patients with rheumatic disease.

Brownfields are increasingly called upon to be transformed from potentially contaminated, often vacant properties into community assets that provide multiple benefits. Further, brownfields revitalization can provide critical opportunities and, particularly, nature-based solutions can enhance multiple ecological, human health, and economic benefits. Through a series of non-exhaustive surveys of existing examples of environmental benefits of cleanups, case study examples of brownfield cleanups achieving environmental benefits, and potential ecosystem services tools relevant to steps of a brownfields cleanup effort, we explore practical ideas for enhancing environmental benefits of brownfields cleanups by applying ecosystem services concepts. Examples of nature-based solutions, where appropriate, include the use of rain gardens, permeable pavements, green spaces, and the use of green technologies. Further, this article provides an overview of recent policy initiatives focused on nature-based solutions and enhancing ecosystem services in brownfields cleanup, revitalization, and reuse. Our goals are to increase the knowledge base on these opportunities and discuss how these concepts can be achieved through sharing success stories, making outreach materials accessible, and holding workshops to help successfully operationalize these concepts in a community’s visioning for upcoming revitalization projects.

Abstract Background Teledermatology (TD) is an evidence-based practice that may increase access to dermatologic care. We sought to use the Exploration, Preparation, Implementation, and Sustainment (EPIS) and the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to evaluate implementation of TD at Duke. Methods The EPIS and RE-AIM frameworks were deployed to design and implement a TD program that leveraged the strengths of the Duke University Health System and addressed previously reported barriers to implementation of store-and-forward and synchronous TD models. In the resultant hybrid TD model, trained primary care providers (PCPs) sent e-comm referrals with clinical and dermatoscopic images to dermatology. These e-consults were reviewed asynchronously and patients were scheduled for a synchronous video visit with dermatology within days. Dermatologists managed the patient plan. This hybrid TD model was piloted at four primary care clinics. Pertinent outcomes from a TD-adapted RE-AIM framework were tracked using electronic health record data. Patient satisfaction was assessed using a post-video visit survey (n = 18). Implementation barriers and facilitators were also collected through provider surveys (n = 24 PCPs, n = 10 dermatologists, n = 10 dermatology residents). Results At four PCP clinics throughout 9/1/2021–4/30/2022, there were 218 TD referrals. Video visits occurred on average 7.5 ± 0.5 days after referral and 18/18 patients completing the post-visit survey were satisfied. Adoption varied between clinics, with one placing 22% of all dermatology referrals as TD and another placing 2%. The primary PCP barriers to TD were time burdens, lack of fit in clinic flow, and discomfort with image taking. Top-endorsed potential facilitating interventions included allowing for rash referrals without dermoscopy and assurance for clinical evaluation within 3 days. Conclusions The use of implementation science frameworks allowed for identification of system and contextual strengths which informed the hybrid TD pilot. Barriers and facilitating interventions will provide guidance for expansion and ongoing maintenance of TD.

This article attends to the intimate contradictions that differentially shape and limit caring capacities and relations in a violent world, and the embodied ethical and political transformations at the heart of learning to care otherwise. From manifestos calling for ‘universal care’ in defiance of the state-sanctioned horrors of the pandemic era, to the abolitionist politics of care developed by BLM organizers through movement building and healing, and the proliferation of mutual-aid infrastructures to meet needs and distribute resources in the face of overwhelming crisis and neglect—these examples and so many others illustrate with undeniable clarity that radical care is finally on the agenda. In what follows, I hope to contribute to this urgent conversation by pointing to how care is shaped in fundamentally contradictory ways under conditions of entrenched structural violence, and the limitations of normative frameworks when confronting this reality. To unambiguously valorize care in ethical and political life is to risk occluding the constitutive violence of existing social structures and norms, its impact on the intimacies of caring relations, and ultimately the ways that communities mobilize alternate economies and practices of care towards healing and social change. While it is crucial to value care and work for a more caring society, I claim that efforts to transform patterns of relational harm and develop new sensibilities should also be highlighted as integral components of radical caring praxis.

Teachers’ work is influenced by their perception of their work environment, projecting this into the quality of education and product delivered to society. Therefore, this study analyzes how the work environment manifests itself in a Higher Education Institution, considering affiliation, commitment, communication, motivation, recognition, and other factors that affect the performance of a university teacher. The results show that teachers’ perceptions of their work environment are internally differentiated, with factors such as commitment, internal communication, recognition, empathy, physical integrity at work, remuneration, joint participation between work teams, and authority having negative connotations. A suggestion for improvement is executing plans designed to generate an effective organizational change in the detected weaknesses.

Objective Patients with autoimmune rheumatic diseases (ARDs) are at greater risk of COVID‐19 infection and hospitalization, increasing the stress and uncertainty already associated with unpredictable conditions. These may be heightened for patients with ARDs from underrepresented minority backgrounds. This study aimed to explore patient experiences and ARD‐related challenges during the first year of the pandemic. Methods Between December 2020 and May 2021, 60‐minute semistructured interviews were conducted with English‐ and Spanish‐speaking adults, aged 18 years or older with self‐reported diagnosis of ARD, via phone or videoconferencing using an interview guide on living with an ARD during the pandemic. Analysis combined methods of phenomenology and content analysis through three steps: 1) summarizing interviews, 2) iteratively refining units of meaning, and 3) axial and selective coding to determine cross‐cutting themes. Study procedures were conducted by a multidisciplinary team, a majority also diagnosed with ARDs. Results The research team interviewed 22 patients (39.8 ± 15.7 years old; 82.8% female; 31.8% Hispanic or Latino/a/x) with ARDs. Themes included 1) information access and understanding, 2) problem solving access to health care, 3) balancing risks, and 4) mental health implications. Within these themes, patients from underrepresented minority backgrounds faced unique challenges. Conclusion Patients with ARDs require direct and timely communication about their risk of COVID‐19 morbidity and mortality and require increased support for psychosocial and ARD‐related implications of the pandemic. Health care systems must consider ways to support patients who are balancing chronic disease management with risk reduction for contracting emerging COVID‐19 variants.

Objective The study objective was to prioritize topics for future patient‐centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. Methods A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. Results Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were “How well a vaccine works for adults with autoimmune conditions” and “How beliefs about vaccine safety affect vaccine uptake.” Conclusion A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Vitamin B12, or cobalamin, is an essential nutrient required for diverse physiological functions secondary to its role as a critical cofactor for two mammalian enzymes, methionine synthase and methylmalonyl-CoA mutase. While essential throughout all life stages, several pathways that require vitamin B12, including hematopoiesis, myelination, and DNA/histone methylation, are particularly critical during pregnancy and fetal development. This narrative review aims to describe vitamin B12 in pregnancy, with emphasis on the placenta’s role in ensuring adequate nutrition of the fetus and impacts of vitamin B12 deficiency on placental development and function. Our literature search included preclinical model systems and human cohorts and interventions. Our review identified evidence of B12 deficiency resulting in impaired placental development, greater placental inflammation, and modulation of placental docosahexaenoic acid concentration, collectively suggestive of vitamin B12 deficiency as a determinant of both maternal and fetal health outcomes. Heterogeneity in study design complicated generalization of findings. Future studies should consider selecting a B12 marker that is relatively stable across pregnancy, such as holotranscobalamin, while accounting for important confounders such as maternal folate.

BackgroundDigital health studies using electronic patient-reported outcomes (ePROs) and wearables bring new challenges, including the need for participants to consistently provide trial data. ObjectiveThis study aims to characterize the engagement, protocol adherence, and data completeness among participants with rheumatoid arthritis enrolled in the Digital Tracking of Arthritis Longitudinally (DIGITAL) study. MethodsParticipants were invited to participate in this app-based study, which included a 14-day run-in and an 84-day main study. In the run-in period, data were collected via the ArthritisPower mobile app to increase app familiarity and identify the individuals who were motivated to participate. Successful completers of the run-in period were mailed a wearable smartwatch, and automated and manual prompts were sent to participants, reminding them to complete app input or regularly wear and synchronize devices, respectively, during the main study. Study coordinators monitored participant data and contacted participants via email, SMS text messaging, and phone to resolve adherence issues per a priori rules, in which consecutive spans of missing data triggered participant contact. Adherence to data collection during the main study period was defined as providing requested data for >70% of 84 days (daily ePRO, ≥80% daily smartwatch data) or at least 9 of 12 weeks (weekly ePRO). ResultsOf the 470 participants expressing initial interest, 278 (59.1%) completed the run-in period and qualified for the main study. Over the 12-week main study period, 87.4% (243/278) of participants met the definition of adherence to protocol-specified data collection for weekly ePRO, and 57.2% (159/278) did so for daily ePRO. For smartwatch data, 81.7% (227/278) of the participants adhered to the protocol-specified data collection. In total, 52.9% (147/278) of the participants met composite adherence. ConclusionsCompared with other digital health rheumatoid arthritis studies, a short run-in period appears useful for identifying participants likely to engage in a study that collects data via a mobile app and wearables and gives participants time to acclimate to study requirements. Automated or manual prompts (ie, “It’s time to sync your smartwatch”) may be necessary to optimize adherence. Adherence varies by data collection type (eg, ePRO vs smartwatch data). International Registered Report Identifier (IRRID)RR2-10.2196/14665

Abstract Background Difficulties in cancer services access increase the burden of disease and mortality in rural areas, and telehealth can be a useful tool to address these inequalities. Objective We aimed to describe the outcomes of patients in rural and urban areas with solid tumors managed by oncologists through telemedicine. Methods We conducted a retrospective cohort study of patients with solid tumors from March to December 2020. A total of 1270 subjects with solid tumors were included, 704 living in urban areas and 566 in rural areas. Results The most frequent tumors were breast (51.8%) and prostate (12.4%). The trend of telemedicine care was similar for both populations; in-person care was more frequent in the urban population. There were no differences in referral to the emergency room, need for hospitalization, and mortality for both groups. Conclusion Telemedicine is a care modality that reduces barriers in the care of patients with solid tumors, evidencing similar outcomes regardless of living in rural or urban areas.

Abstract Background Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. Methods We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. Discussion We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Objective Uptake of treat-to-target (TTT) strategies for rheumatoid arthritis (RA) management is low. Our objective was to understand the heterogeneity in patients’ conceptualisation of RA treatment to inform interventions improving TTT uptake.Design Eligible participants recruited from an online research registry rated 56 items (on 5-point scales) reflecting concepts raised from patient interviews. Using items describing adhering to physician recommendations to create a binary criterion variable for medication adherence, we conducted a principal components analysis on the remaining items using Varimax rotation, describing how these factors predict adherence over and above demographic characteristics. We further use optimal sets in regression to identify the individual concepts that are most predictive of medication adherence.Results We found significant heterogeneity in patients’ conceptualisation of RA treatment among 621 persons with RA. A scree plot revealed a four-factor solution explained 38.4% of the variance. The four factors expected to facilitate TTT uptake were (% variance explained): (1) Access to high quality care and support (11.3%); (2) low decisional conflict related to changing disease-modifying antirheumatic drugs (DMARDs) (10.1%); (3) endorsement of a favourable DMARD risk/benefit ratio (9.9%); and (4) confidence that testing reflects disease activity (7.2%). These factors account for 13.8% of the variance in full medication adherence, fully explaining the only significant demographic predictor, age of the patient. The individual items most predictive of poor adherence centre on the lack of effective patient–physician communication, specifically insufficient access to information from rheumatologists, along with the need to seek information elsewhere.Conclusion Patients’ conceptualisation of RA treatment varies; however, almost all patients have difficulty escalating DMARDs, even with access to quality information and an understanding of the benefits of TTT. Tailored interventions are needed to address patient hesitancy to escalate DMARDs.

Small Island Developing States (SIDS) in the Pacific are heavily reliant on imported foods which are often nutritionally deficient, and typically high in salt, fat, and sugar. To curb nutrition-related non-communicable diseases, nutrition policies are needed to create food environments that promote healthy diets. However, international trade and investment agreements (TIAs) may interfere with the policy space for SIDS to regulate their food environments by requiring member states to meet trade obligations that could conflict with their nutrition policy goals. In this review, we identify real examples of where TIAs have been responsible for changes in Pacific SIDS’ nutrition policies alongside the potential for further constraints on healthy nutrition policies from Pacific Island participation in TIAs. In addition, we note the effects of regulatory chill from TIA obligations in Pacific SIDS, whereby healthy nutrition policies are not considered, developed, or implemented due to the threat of trade disputes or the complexity of TIA procedural requirements. Existing literature indicates that TIAs have shaped nutrition policies to fit within the global trade paradigm despite SIDS’ nutrition policy imperatives. More can be done locally, regionally, and internationally to increase the importance of nutrition in the trade agenda, leverage regional institutions to champion nutrition regulation and support SIDS in navigating the trade and nutrition policy environment.

Abstract Background Children’s exposure to unhealthy food and beverage marketing has a direct impact on their dietary preference for, and consumption of, unhealthy food and drinks. Most children spend time online, yet marketing restrictions for this medium have had slow uptake globally. A voluntary Children’s and Young People’s Advertising (CYPA) Code was implemented in Aotearoa, New Zealand (NZ) in 2017. This study explores the Code’s limitations in protecting children from harmful food and beverage marketing practices on digital platforms accessible to children. Methods A cross-sectional content analysis of company websites (n = 64), Facebook pages (n = 32), and YouTube channels (n = 15) of the most popular food and beverage brands was conducted between 2019 and 2021 in NZ. Brands were selected based on market share, web traffic analysis and consumer engagement (Facebook page ‘Likes’ and YouTube page views). Analysis focused on volume and type of food posts/videos, level of consumer interaction, nutritional quality of foods pictured (based on two different nutrient profile models), and use of specific persuasive marketing techniques. Results Eighty-one percent of websites (n = 52) featured marketing of unhealthy food and beverages. Thirty-five percent of websites featuring unhealthy food and beverages used promotional strategies positioning their products as ‘for kids’; a further 13% used ‘family-oriented’ messaging. Several websites featuring unhealthy products also had designated sections for children, ‘advergaming,’ or direct messaging to children. Eighty-five percent of all food and drink company Facebook posts and YouTube videos were classified as unhealthy. Twenty-eight percent of Facebook posts for unhealthy products featured persuasive promotional strategies, and 39% premium offers. Nearly 30% of YouTube videos for unhealthy food and beverages featured promotional strategies, and 13% premium offers. Ten percent of Facebook posts and 13% of YouTube videos of unhealthy food and beverages used marketing techniques specifically targeting children and young people. Conclusions The voluntary CYPA Code has been in effect since 2017, but the inherent limitations and loopholes in the Code mean companies continue to market unhealthy food and beverages in ways that appeal to children even if they have committed to the Code. Comprehensive and mandatory regulation would help protect children from exposure to harmful marketing.

Abstract Background SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. Results We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206+ regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal mucosa. Conclusions This study identifies SP140 as a druggable epigenetic therapeutic target for CD.

Abstract Background Cardiovascular disease (CVD) is the most common cause of death among people with rheumatoid arthritis (RA), with an estimated increased risk of 50–60% compared to the general population. Lipid-lowering strategies have been shown to lower CVD risk significantly in people with RA and hyperlipidemia. Thus, CVD risk assessment has an important role to play in reducing CVD among people with RA. Yet currently only 37 to 45% of this population are receiving primary lipids screening. This paper describes the CArdiovascular Risk assEssment for RA (CARE RA) intervention, which is designed to address this issue. CARE RA is a peer coach intervention, that is, an intervention in which a person with RA coaches another person with RA, which is designed to educate people with RA about the relation between RA and CVD risk and to help them obtain evidence-based CVD risk assessment and treatment. Methods This is an open-label pilot study that will test if the participants assigned to complete the CARE RA curriculum with a peer coach will receive a cardiovascular risk assessment more frequently compared to those that complete the CARE RA curriculum by themselves. The CARE RA intervention is guided by Social Cognitive Theory. Participants in the peer coach intervention arm will receive the assistance of a peer coach who will call the participants once a week for 5 weeks to go over the CARE RA curriculum and train them on how to obtain CVD risk assessment. The control arm will complete the CARE RA curriculum without any assistance. Participants will be randomized 1:1 either to the control arm or to the peer coach intervention arm. The primary outcome is a participant’s having a CVD risk assessment or initiating a statin, if indicated. Secondary outcomes include patient activation and RA medication adherence. The RE-AIM implementation framework guides the implementation and evaluation of the intervention. Discussion This pilot study will test the feasibility of the peer coach intervention in anticipation of a larger trial. CARE RA pioneers the use of peer coaches to facilitate the implementation of evidence-based treatment guidelines among people with RA. Trial registration ClinicalTrials.gov NCT04488497 . Registered on July 28, 2020.

Editorial: Feminist Encounters with Situated Knowledges of Gender and Love

A roundtable discussion featuring Serena Petrella, Associate Professor of Sociology, Gender and Women’s Studies at Brandon University, Canada; Amanda Gouws, SARChI Chair in Gender Politics at Stellenbosch University, South Africa; and Danai Mupotsa, Senior Lecturer in the Department of African Literature at the University of the Witwatersrand, South Africa. Hosted by Dr Wernmei Yong Ade (Mei), formerly from Nanyang Technical University, Singapore, now living in the US; Professor Deirdre Byrne (Deirdre), University of South Africa, and Dr Kelly Gardiner (Kelly), La Trobe University, Australia. The roundtable discussion was held online and recorded on 2 February 2023.

The lighthouse has long been a familiar setting for stories of love, conflict, and epiphany. That isolated tower on the clifftop brims with symbolic possibility and sometimes cliché, positioning it as a site of gendered love, with popular fiction titles embedding the trope of the contained world revolving, like the lit lamp, around the male authority. But the lighthouse also has an explicit historical situatedness. The nineteenth century British lighthouses, in particular, were seen as outposts of empire. They are immovable inscriptions of the outlines of islands, the edges of continents – the imprint of colonisation on country. And they are often seen as male domains. In the popular imagination, a lighthouse is much more than its function. Does recent historical fiction perpetuate or subvert what we think we know about lighthouses and the people who populated them? How does it portray the officially gendered roles and intense relationships of women characters? How might historical novels set in settler colonies recognise the specific meaning of the lighthouse as a marker of imperial authority? And how do we read the lighthouse and its place in the imagination as a geography of gender and love?

Objective Aims were to 1) to characterize patient decision‐making with treatment for axial spondyloarthritis (axSpA) and 2) to explore relationships among decision‐making, treatment satisfaction, and biologic disease modifying antirheumatic drugs (bDMARDs). Methods ArthritisPower participants with physician‐diagnosed axSpA were invited to complete an online survey about their treatment and their most recent physician visit. Analysis compared treatment decision by satisfaction and bDMARD status. Results Among the 274 participants, 87.2% were female, and the mean age was 50 years. Of participants, 79.5% had researched treatment before their most recent physician visit, and 56.9% discussed treatment change at their most recent physician visit. Of treatment‐change discussions, 69.2% of them were related to escalation, compared with deescalation (27.6%) and/or switching (39.1%). Among those participants who discussed a change, 73.7% agreed to it because they felt that their disease was not being controlled (54.9%) or felt that it could be better controlled on new treatment (20.3%). Top symptoms prompting change were back/buttock pain (63.3%), other joint pain (55.1%), and fatigue (54.1%). Among bDMARD‐treated participants (n = 128), important factors for treatment decisions were prevention of long‐term axSpA consequences (92.9%) and doctor's advice (87.5%). Among 43.4% of participants reporting treatment dissatisfaction, 37% did not discuss treatment change. Current bDMARD use was more common in satisfied (61.9%) than dissatisfied participants (26.9%). Conclusion In this cross‐sectional study of a predominantly female axSpA population, patients frequently researched treatment options and discussed escalation with their providers. Under two‐thirds of participants who were dissatisfied with treatment discussed changes at their most recent visit. Current bDMARD use was associated with higher satisfaction, and bDMARD users considered prevention of long‐term consequences and doctor's advice to be very important for decision‐making.

ObjectiveTo explore how placental pathology is currently used by clinicians and what placental information would be most useful in the immediate hours after delivery.Study designWe used a qualitative study design to conduct in-depth, semi-structured interviews with obstetric and neonatal clinicians who provide delivery or postpartum care at an academic medical center in the US (n = 19). Interviews were transcribed and analyzed using descriptive content analysis.ResultsClinicians valued placental pathology information yet cited multiple barriers that prevent the consistent use of pathology. Four main themes were identified. First, the placenta is sent to pathology for consistent reasons, however, the pathology report is accessed by clinicians inconsistently due to key barriers: difficult to find in the electronic medical record, understand, and get quickly. Second, clinicians value placental pathology for explanatory capability as well as for contributions to current and future care, particularly when there is fetal growth restriction, stillbirth, or antibiotic use. Third, a rapid placental exam (specifically including placental weight, infection, infarction, and overall assessment) would be helpful in providing clinical care. Fourth, placental pathology reports that connect clinically relevant findings (similar to radiology) and that are written with plain, standardized language and that non-pathologists can more readily understand are preferred.ConclusionPlacental pathology is important to clinicians that care for mothers and newborns (particularly those that are critically ill) after birth, yet many problems stand in the way of its usefulness. Hospital administrators, perinatal pathologists, and clinicians should work together to improve access to and contents of reports. Support for new methods to provide quick placenta information is warranted.

BackgroundAchieving healthy food systems will require regulation across the supply chain; however, binding international economic agreements may be constraining policy space for regulatory intervention in a way that limits uptake of ‘best-practice’ nutrition policy. A deeper understanding of the mechanisms through which this occurs, and under which conditions, can inform public health engagement with the economic policy sector. MethodsWe conducted a realist review of nutrition, policy and legal literature to identify mechanisms through which international trade and investment agreements (TIAs) constrain policy space for priority food environment regulations to prevent non-communicable diseases (NCDs). Recommended regulations explored include fiscal policies, product bans, nutrition labelling, advertising restrictions, nutrient composition regulations, and procurement policies. The process involved 5 steps: initial conceptual framework development; search for relevant empirical literature; study selection and appraisal; data extraction; analysis and synthesis, and framework revision. ResultsTwenty-six studies and 30 institutional records of formal trade/investment disputes or specific trade concerns (STCs) raised were included. We identified 13 cases in which TIA constraints on nutrition policy space could be observed. Significant constraints on nutrition policy space were documented with respect to fiscal policies, product bans, and labelling policies in 4 middle-income country jurisdictions, via 3 different TIAs. In 7 cases, trade-related concerns were raised but policies were ultimately preserved. Two of the included cases were ongoing at the time of analysis.TIAs constrained policy space through 1) TIA rules and principles (non- discrimination, necessity, international standards, transparency, intellectual property rights, expropriation, and fair and equitable treatment), and 2) interaction with policy design (objectives framed, products/services affected, nutrient thresholds chosen, formats, and time given to comment or implement). Contextual factors of importance included: actors/institutions, and political/regulatory context. ConclusionAvailable evidence suggests that there are potential TIA contributors to policy inertia on nutrition. Strategic policy design can avoid most substantive constraints. However, process constraints in the name of good regulatory practice (investor-state dispute settlement (ISDS), transparency, regulatory coherence, and harmonisation) pose a more serious threat of reducing government policy space to enact healthy food policies.

The Board Certified Psychiatric Pharmacist (BCPP) specialty certification was launched by the Board of Pharmacy Specialties in 1994. Candidates for the BCPP can qualify for the examination through 3 possible pathways: practice experience (4 years) in the specialty, completion of a PGY-1 residency plus an additional 2 years of practice experience, or completion of a PGY-2 specialty residency in psychiatric pharmacy. Recent fluctuations in the passing rate raised questions as to explanatory factors. This article represents the first published comprehensive study of candidate performance on the BCPP Examination. It describes a retrospective, observational study presenting (a) statistical trends of examination passing rates for biannual cohorts over the past 5 years, as well as (b) score distributions on the 3 performance domains of the certification. Pass-rate trend analyses suggest that variation in the proportion of eligibility pathway cohorts in the respective testing samples explains some of the fluctuation in passing rates. An analysis of variance of domain-level scores, using groups defined by eligibility pathway, yielded significant differences for nearly all group comparisons. Evaluation of the effect sizes suggest that the most disparate performance was observed on the core clinical domain, Patient-Centered Care. The results of this study are consistent with previously published research and will inform the upcoming role delineation study for the Psychiatric Pharmacy Certification.

Abstract Background Self-monitoring of blood glucose (SMBG) has been shown to reduce hemoglobin A1C (HbA1C). Accordingly, guidelines recommend SMBG up to 4–10 times daily for adults with type 2 diabetes (T2DM) on insulin. For persons not on insulin, recommendations are equivocal. Newer technology-enabled blood glucose monitoring (BGM) devices can facilitate remote monitoring of glycemic data. New evidence generated by remote BGM may help to guide best practices for frequency and timing of finger-stick blood glucose (FSBG) monitoring in uncontrolled T2DM patients managed in primary care settings. This study aims to evaluate the impact of SMBG utility and frequency on glycemic outcomes using a novel BGM system which auto-transfers near real-time FSBG data to a cloud-based dashboard using cellular networks. Methods Secondary analysis of the intervention arm of a comparative non-randomized trial with propensity-matched chart controls. Adults with T2DM and HbA1C > 9% receiving care in five primary care practices in a healthcare system participated in a 3-month diabetes boot camp (DBC) using telemedicine and a novel BGM to support comprehensive diabetes care management. The primary independent variable was frequency of FSBG. Secondary outcomes included frequency of FSBG by insulin status, distribution of FSBG checks by time of day, and hypoglycemia rates. Results 48,111 FSBGs were transmitted by 359 DBC completers. Participants performed 1.5 FSBG checks/day; with 1.6 checks/day for those on basal/bolus insulin. Higher FSBG frequency was associated with greater improvement in HbA1C independent of insulin treatment status (p = 0.0003). FSBG frequency was higher in patients treated with insulin (p = 0.003). FSBG checks were most common pre-breakfast and post-dinner. Hypoglycemia was rare (1.2%

Child birth via Cesarean section accounts for approximately 32% of all births each year in the United States. A variety of risk factors and complications can lead caregivers and patients to plan for a Cesarean delivery in advance before onset of labor. However, a non-trivial subset of Cesarean sections (∼25%) are unplanned and occur after an initial trial of labor is attempted. Unfortunately, patients who deliver via unplanned Cesarean sections have increased maternal morbidity and mortality rates and higher rates of neonatal intensive care admissions. In an effort to develop models aimed at improving health outcomes in labor and delivery, this work seeks to explore the use of national vital statistics data to quantify the likelihood of an unplanned Cesarean section based on 22 maternal characteristics. Machine learning techniques are used to ascertain influential features, train and evaluate models, and assess accuracy against available test data. Based on cross-validation results from a large training cohort (n = 6,530,467 births), the gradient-boosted tree algorithm was identified as the best performer and was evaluated on a large test cohort (n = 10,613,877 births) for two prediction scenarios. Area under the receiver operating characteristic curves of 0.77 or higher and recall scores of 0.78 or higher were obtained and the resulting models are well calibrated. Combined with feature importance analysis to explain why certain maternal characteristics lead to a specific prediction in individual patients, the developed analysis pipeline provides additional quantitative information to aid in the decision process on whether to plan for a Cesarean section in advance, a substantially safer option among women at a high risk of unplanned Cesarean delivery during labor.

Addressing the global challenge of malnutrition in all its forms will require policy measures to improve food environments, yet progress has been patchy and often slow, particularly for regulatory measures. International trade and investment agreements (TIAs) may limit governments' “policy space” for public health regulation. Constraints have been particularly apparent for public health measures targeting unhealthy commodities, including ultra-processed foods. Challenges and disputes regarding food environment regulation under TIAs (even if successfully defended) can entail significant drain of human and financial resources, and political capital. Lack of awareness or understanding of the implication of TIAs on policy space for regulation can contribute to regulatory chill and policy inertia. Governments lacking capacity to interpret their “legally available” policy space may want to err on the side of caution when there is perceived risk of a formal dispute—even if such threats are unfounded. This paper draws on analysis of literature, trade and investment dispute documentation, and data from inter-disciplinary expert interviews (n = 22) to present a new conceptual framework for the potential impacts of TIAs on policy space for regulating food environments. The analysis that underpins the framework focusses on the key policy domains of fiscal policies, front-of-pack nutrition labeling, restrictions on marketing to children, nutrient limits, and product bans. Analysis indicates that regulatory context and stakeholder influence, policy design, and mechanisms associated with TIA rules and provisions intersect in ways contributing to policy space outcomes. This new framework can provide a basis for rapidly assessing policy coherence between TIAs and food environment regulations in these domains. It can also be used to identify areas where further legal analysis would strengthen the development and defense of regulatory proposals. The framework may be applied to nutrition regulation more broadly, given the common themes that emerged across the different domains due to common interests of stakeholders, notably the food industry. It thus provides a basis for analyzing the political economy of regulation to address the commercial determinants of health in relation to unhealthy food and beverages.

Abstract Background Regulation of food environments is needed to address the global challenge of poor nutrition, yet policy inertia has been a problem. A common argument against regulation is potential conflict with binding commitments under international trade and investment agreements (TIAs). This study aimed to identify which actors and institutions, in different contexts, influence how TIAs are used to constrain policy space for improving food environments, and to describe their core beliefs, interests, resources and strategies, with the objective of informing strategic global action to preserve nutrition policy space. Methods We conducted a global stakeholder analysis applying the Advocacy Coalition Framework, based on existing academic literature and key informant interviews with international experts in trade and investment law and public health nutrition policy. Results We identified 12 types of actors who influence policy space in the food environment policy subsystem, relevant to TIAs. These actors hold various beliefs regarding the economic policy paradigm, the nature of obesity and dietary diseases as health problems, the role of government, and the role of industry in solving the health problem. We identified two primary competing coalitions: 1) a ‘public health nutrition’ coalition, which is overall supportive of and actively working to enact comprehensive food environment regulation; and 2) an ‘industry and economic growth’ focussed coalition, which places a higher priority on deregulation and is overall not supportive of comprehensive food environment regulation. The industry and economic growth coalition appears to be dominant, based on its relative power, resources and coordination. However, the public health nutrition coalition maintains influence through individual activism, collective lobbying and government pressure (e.g. by civil society), and expert knowledge generation. Conclusions Our analysis suggests that industry and economic growth-focussed coalitions are highly capable of leveraging networks, institutional structures and ideologies to their advantage, and are a formidable source of opposition acting to constrain nutrition policy space globally, including through TIAs. Opportunities for global public health nutrition coalitions to strengthen their influence in the support of nutrition policy space include strategic evidence generation and coalition-building through broader engagement and capacity-building.

Background We aimed to compare concerns, social distancing, health care disruptions, and telemedicine use in patients with autoimmune rheumatic disease (ARD) and non‐ARD and to evaluate factors associated with immunomodulatory medication interruptions. Methods Patients in a multistate community rheumatology practice network completed surveys from April 2020 to May 2020. Adults with common ARD (rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus) or non‐ARD (gout, osteoarthritis, osteoporosis) were evaluated. Concerns about coronavirus disease 2019 (COVID‐19), social distancing, health care disruptions, and telemedicine use were compared in patients with ARD versus non‐ARD, adjusting for demographics, rural residence, and zipcode‐based measures of socioeconomic status and COVID‐19 activity. Factors associated with medication interruptions were assessed in patients with ARD. Results Surveys were completed by 2319/36 193 (6.4%) patients with non‐ARD and 6885/64 303 (10.7%) with ARD. Concerns about COVID‐19 and social distancing behaviors were similar in both groups, although patients receiving a biologic or Janus kinase (JAK) inhibitor reported greater concerns and were more likely to avoid friends/family, stores, or leaving the house. Patients with ARD were less likely to avoid office visits (45.2% vs. 51.0%, odds ratio [OR] 0.79 [0.70‐0.89]) with similar telemedicine use. Immunomodulatory medications were stopped in 9.7% of patients with ARD, usually (86.9%) without a physician recommendation. Compared with patients with an office visit, the likelihood of stopping medication was higher for patients with a telemedicine visit (OR 1.54 [1.19‐1.99]) but highest for patients with no visits (OR 2.26 [1.79‐2.86]). Conclusion Patients with ARD and non‐ARD reported similar concerns about COVID‐19 and similar social distancing behaviors. Missed office visits were strongly associated with interruptions in immunomodulatory medication.

Abstract Background Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management. Methods Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure. Results Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1–3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient’s preferences regarding the importance of these PROs were stable over time. Conclusion The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.

Unhealthy diets and excess energy intake are the greatest contributors to disease and disability in Aotearoa. Unhealthy diets are heavily influenced by obesogenic food environments. Governments and the private sector have critical roles to play in creating healthier food environments, yet New Zealand consistently falls behind international best practice, suggesting a lack of accountability. The accountability cycle has five phases: setting the account, taking account, sharing the account, holding to account, and responding to the account. The ongoing monitoring of the healthiness of food environments is essential to identify key problems, assess the impact of policies, hold governments and food companies to their commitments, measure progress, and support future implementation. The Food Environments Dashboard Aotearoa was created to collate and translate more than a decade’s worth of food environment monitoring studies and their findings for policy-makers and public health advocacy groups to encourage policy change. Based on Australia’s Food Environments Dashboard, the key indicators from these studies have been identified and assessed against defined criteria to give a green (promotes health), amber (needs improvement) or red (unhealthy) rating. Data from studies implemented between 2014 and 2022 were reviewed and 65 key indicators were selected for ten domains: government, food composition, settings (schools, hospitals), food labelling, food affordability, food promotion, food retail, private sector, trade and investment, and equity. Most domains were assessed as red and none as green. The Dashboard contributes to sharing and holding to account by providing key indicators in an accessible format that will be regularly updated. We encourage the public health nutrition community of practice to contribute to, and utilise, the Dashboard to improve food environments for Aotearoa.

Objective This study aimed to analyze the concerns and health‐related behaviors in patients with vasculitis during the early phase of the coronavirus disease 2019 (COVID‐19) pandemic in North America. Methods Patients with vasculitis in North America were invited to complete an online survey through the Vasculitis Patient‐Powered Research Network in collaboration with the Vasculitis Foundation and the Relapsing Polychondritis Foundation. Questions focused on concerns and behaviors related to doctors’ visits, tests, medication, and telehealth use. Factors affecting their concern and health‐related behaviors were determined. Results Data from 662 patients were included: 90% of patients were White, 78% were women, 83% expressed moderate or high levels of concern about COVID‐19, and 87% reported that their vasculitis moderately or extremely affected their level of concern. Older age, female sex, lung disease, and immunosuppression were associated with greater concern. Doctors’ visits, laboratory tests, and other tests were avoided by 66%, 46%, and 40% of patients, respectively. Younger age, urban location, higher income, higher concern levels, and prednisone use (>10 mg/day) were associated with greater likelihood of avoiding visits or tests. Ten percent of patients on immunosuppressive therapy stopped their medication. Twenty‐nine percent patients on rituximab avoided an infusion. Forty‐four percent of patients had telehealth visits; more visits were reported for younger patients, for patients on glucocorticoids, and in Canada versus the United States. Conclusion During the COVID‐19 pandemic, patients with vasculitis have high levels of concern and exhibit potentially harmful health‐related behaviors. Health care use varies across different demographic groups and geographic regions. Specific strategies are warranted to facilitate engagement of these patients with the health care system during the pandemic.

Pigs provide a valuable large animal model for several diseases due to their similarity with humans in anatomy, physiology, genetics and drug metabolism. We recently generated a porcine model for TP53R167H and KRASG12D driven hepatocellular carcinoma (HCC) by autologous liver implantation. Here we describe a streamlined approach for developing genetically tailored porcine HCC cells by CRISPR/Cas9 gene editing and isolation of homogenous genetically validated cell clones. The combination of CRISPR/Cas9 editing of HCC cells described herein with the orthotopic HCC model enables development of various porcine HCC models, each with a specific mutational profile. This allows modeling the effect of different driver mutation combinations on tumor progression and in vivo testing of novel targeted therapeutic approaches in a clinically relevant large animal model.

Background . Sexual and gender minority youth (SGMY) experience health inequities compared with cisgender heterosexuals, and these inequities are heightened in areas with high structural stigma. Quantitative research shows school assets (e.g., adult support) are associated with better health for SGMY. Though some qualitative studies elucidated how school staff support SGMY, none have triangulated such strategies in a geographically and sociodemographically diverse sample of school staff and SGMY. This paper describes a multi-perspective qualitative study design and offers lessons learned from conducting such a study. Methods . Using a novel stratified sampling frame, we interviewed 60 SGMY and 29 school staff who attended/worked at high schools in U.S. states with low, medium, and high structural stigma. To ensure sociodemographic diversity, we constructed sampling quotas, and recruited SGMY using social media and staff using a multi-pronged approach. Results . The stratified sampling strategy met our goal of enrolling diverse SGMY and staff participants. SGMY participants attended schools in low ( n = 20), medium ( n = 22), and high ( n = 18) structural stigma states. We enrolled 18 cisgender girls, 18 cisgender boys, and 24 gender minority youth. Fifty-three percent of SGMY were youth of color, and 45% attended schools in rural areas. School staff participants worked at schools in low ( n = 11), medium ( n = 11), and high ( n = 7) structural stigma states. School staff participants were 55% heterosexual, 91% cisgender, and had diverse roles (e.g., teacher, principal, librarian, and nurse). Conclusions . This paper describes new methods for collecting qualitative data from diverse SGMY and school staff. Some lessons learned from this study include the importance of using trauma-informed interviewing methods, having a suicidality safety protocol, establishing a priori sampling quotas, and creating tailored social media advertisements. With these data we will explore the heterogeneity of SGMY and school staff experiences across varying structural stigma levels, yielding foundational information for future school-based interventions.

Abstract Isoleucyl‐tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine‐tRNA synthetase. Pathogenic variants in the IARS2 gene are associated with mitochondrial disease. We report a female with IARS2 compound heterozygous variants, p.Val499Glyfs*14 and p.Arg784Trp who presented with infantile spasms, Leigh disease and Wolff‐Parkinson White (WPW) pattern. This report expands the phenotypic spectrum of IARS2‐related disease.

Conjoined nerve roots are an infrequent and uncommon finding, rarely noted preoperatively. The conjoined root anomaly has potential for significant neurological injury during surgery. Preoperative recognition may avert disastrous nerve root injury but requires a high degree of clinical suspicion. We present the case of a 44-year-old patient with left L5/S1 radiculopathy caused by a herniated disc. During surgery we identified a triple conjoined nerve root anatomy. This anatomical variant, to our knowledge, has not been reported in literature. We describe the anatomical findings and surgical implications.

Abstract Background There are limited real-world data on the diagnostic experiences of patients with psoriatic arthritis (PsA), including medical care sought and potential barriers to diagnosis. We aim to describe patient experiences related to receiving a PsA diagnosis. Methods Ours was a mixed-method, 2-phase study. Phase 1 comprised concept elicitation and cognitive interviews with clinical experts and adults diagnosed with PsA to develop a cross sectional, web-based survey. US adults with a self-reported PsA diagnosis were recruited through a patient support community (CreakyJoints), an online patient research registry (ArthritisPower), and social media outreach. In Phase 2, the online survey collected data on sociodemographics, clinical symptoms, disease burden, and diagnosis history of survey respondents with PsA. Results Of the 203 respondents included, 172 (84.7%) were female, and the mean (SD) age was 51.6 (10.8) years. The time between seeking medical attention and receiving a diagnosis was

Abstract Background Few studies have investigated patients’ own treatment goals in rheumatoid arthritis (RA). The objective of this real-world, cross-sectional study of US patients with RA was to identify factors that patients believed influenced their physician’s treatment decisions. Secondary objectives included reasons patients tolerated sub-optimal disease control and their perceived barriers to treatment optimization. Methods Eligible participants were enrolled in the ArthritisPower registry, ≥ 19 years, had physician-diagnosed RA, unchanged treatment within 3 months of baseline, prior/current disease-modifying antirheumatic drug treatment (DMARDs), and computer/smartphone access. In December 2017, participants completed Patient-Reported Outcomes Measurement Information System-Computerized Adaptive Tests (PROMIS-CAT) for pain interference, fatigue, sleep disturbance, and physical function. Routine Assessment of Patient Index Data 3 (RAPID3) provided disease activity scores (0–30). Participants completed an online survey on barriers to treatment optimization, including self-perception of disease compared to RAPID3/PROMIS scores. Results A total of 249 participants met inclusion criteria and completed the survey. Mean age (SD) was 52 (11) years, and the majority were female (92%) with high RAPID3 disease activity (175/249 [70%]; median score 18). The main reason participants did not change treatment was their physician’s recommendation (66%; n = 32). Of participants with high RAPID3 disease activity, 66 (38%) were offered a treatment change; 19 (29%) of whom declined the change. Most participants who intensified treatment did so because their symptoms had remained severe or worsened (51%; n = 33); only 16 (25%) participants intensified because they had not reached a specified treatment goal. Among participants who self-reported their disease activity as “none/low” or “medium” (n = 202; 81% of cohort), most still had RAPID3 high disease activity (137/202 [68%]; score > 12). Most PROMIS scores showed moderate agreement with participants’ self-assessment of health status, in contrast to RAPID3 (weighted kappa: 0.05 [95% CI − 0.01, 0.11]). Conclusions Most participants trusted their rheumatologist’s treatment decisions and prioritized their physician’s treatment goals over their own. Patients should be encouraged to share their treatment goals/expectations with their rheumatologist, in line with the treat-to-target approach. RAPID3 may be inappropriate for setting patient-centric treatment goals given the poor agreement with self-reported disease activity; most PROMIS scores showed better alignment with patients’ own assessments.

El proceso de toma de decisiones (TD) en entornos críticos es un proceso complejo que puede ser simulado gracias a las capacidades telemáticas actuales, que permiten interactuar con grandes cantidades de datos en tiempo real. Este documento describe la arquitectura planteada desde un proceso de investigación, desarrollado del Centro de Desarrollo de Tecnología Aeroespacial de la FAC (CETAD), que permitió utilizando herramientas computarizadas, basados en conocimiento experto, crear un entorno en el que el decisor evalué sus opciones preparándose para eventos reales, simulando las características del proceso de TD en tiempo, recursos y estrategias en un entorno en tiempo real. Este documento describe el producto de una investigación que dio como resultado un sistema de simulación con una arquitectura basada que combina lógica difusa, algoritmos genéticos y árboles de decisiones con los que se puede modelar diversas entidades y su respuesta automática de acuerdo a los patrones y situaciones simuladas, en la que a través de operadores el decisor puede modificar las instrucciones para las entidades dentro de unas restricciones parametrizadas que obedecen a condiciones físicas. También basado en técnicas de inteligencia de negocios, se generan informes para evaluar las decisiones tomadas. Este tipo de tecnologías mejora la capacidad de planificación y facilitar el proceso de toma de decisiones. Este sistema permite simular cualquier despliegue de medios en el contexto de la seguridad nacional y eventos críticos. Así, se desarrolló un estudio de caso para la implementación de una simulación orientada al soporte en el escenario de un desastre natural.

Abstract The Decade on Ecosystem Restoration aims to provide the means and incentives for upscaling restoration efforts worldwide. Although ecosystem restoration is a broad, interdisciplinary concept, effective ecological restoration requires sound ecological knowledge to successfully restore biodiversity and ecosystem services in degraded landscapes. We emphasize the critical role of knowledge and data sharing to inform synthesis for the most robust restoration science possible. Such synthesis is critical for helping restoration ecologists better understand how context affects restoration outcomes, and to increase predictive capacity of restoration actions. This predictive capacity can help to provide better information for evidence‐based decision‐making, and scale‐up approaches to meet ambitious targets for restoration. We advocate for a concerted effort to collate species‐level, fine‐scale, ecological community data from restoration studies across a wide range of environmental and ecological gradients. Well‐articulated associated metadata relevant to experience and social or landscape contexts can further be used to explain outcomes. These data could be carefully curated and made openly available to the restoration community to help to maximize evidence‐based knowledge sharing, enable flexible re‐use of existing data and support predictive capacity in ecological community responses to restoration actions. We detail how integrated data, analysis and knowledge sharing via synthesis can support shared success in restoration ecology by identifying successful and unsuccessful outcomes across diverse systems and scales. We also discuss potential interdisciplinary solutions and approaches to overcome challenges associated with bringing together subfields of restoration practice. Sharing this knowledge and data openly can directly inform actions and help to improve outcomes for the Decade on Ecosystem Restoration.

The quality of sugarcane broth can be affected by soil management. In compacted soils the productivity is reduced, and the raw material is poor. This research aimed to evaluate productivity and quality of sugarcane for four soil management types: (CT) heavy harrow + light harrow; (CTI) Subsoiler + light harrow; (MT) Subsoiler and (NT) no soil movement. The variables investigated were resistance to soil penetration (SPR), the chemical raw material quality (broth) and crop yield. In crop rows, SPR did not reach severe levels up to 0.3 m for sugarcane root development. However, below this layer, MT, NT, and CTI reached SPR limiting values of 2.50, 2.35 and 1.95 MPa, respectively. In inter-crop rows, compaction was concentrated in soil surface layers (0–0.3 m). In addition, all adopted managements presented SPR above the critical value (2 MPa). The soil preparation forms qualitatively affected the sugarcane broth, showing higher fiber and protein contents in NT, MT, and CT. The PS, Brix, TRS, and Pol were not affected by soil management. Still, higher absolute values were found in the NT, indicating an increase in broth quality when applying conservation management. The highest yields were obtained by reduced tillage (MT), surpassing the lowest yield management (NT) with an increase of 10.5 Mg ha−1.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.

Background:. Perioperative hyperglycemia can have an even more detrimental effect on postoperative outcomes in patients without diabetes than in patients with diabetes, but it has not been established if the treatment of patients without diabetes is safe and effective. We hypothesized that sliding-scale insulin for severe postoperative hyperglycemia (glucose ≥180 mg/dL) could lower mean postoperative glucose levels and minimize short-term complications in patients without diabetes undergoing major joint replacement. Methods:. In a prospective study group, 1,398 consecutive patients, with and without diabetes, undergoing joint replacement were monitored and treated for hyperglycemia and were compared with 886 historical, less frequently monitored controls. The primary outcome was the mean glucose level in patients with and without diabetes within 48 hours after the surgical procedure. Two secondary outcomes could be examined only in the prospective study group, which, by design, had much more frequent glucose sampling and insulin use than the historical controls. First, the contribution of comorbidities and procedural factors to postoperative hyperglycemia in patients without diabetes was assessed with multivariable linear regression. Second, the ability of insulin treatment to reduce complications in patients without diabetes who developed hyperglycemia was evaluated. Results:. In comparison with 886 historical controls, enhanced glucose management lowered the mean glucose (and standard deviation) from 129 ± 28 mg/dL to 123 ± 23 mg/dL for patients without diabetes (p = 0.041). Multivariable linear regression revealed factors that contributed to elevated mean glucose in patients without diabetes: preoperative fasting glucose (p < 0.001), perioperative steroid use (p < 0.001), general anesthesia (p < 0.001), procedure duration (p = 0.003), and transfusion (p = 0.008). Of 968 patients without diabetes, 203 developed severe hyperglycemia. The recommended insulin coverage was given to 129 of these patients, and 74 patients did not receive it for various clinical reasons. Insulin treatment reduced the frequency of positive cultures from any site (p = 0.025) and a composite of positive cultures and readmissions (p = 0.006) in comparison with no insulin treatment. No patient without diabetes who received insulin experienced mild or severe hypoglycemia. Conclusions:. Postoperative hyperglycemia is frequent in patients without diabetes after orthopaedic surgery, but an enhanced glucose management program can lower mean postoperative glucose levels. The treatment of hyperglycemia in patients without diabetes reduced short-term complications and was associated with minimal side effects. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

AbstractLittle is known about the genetic architecture of antifungal immunity in natural populations. Using two population genetic approaches, quantitative trait locus (QTL) mapping and evolve and resequence (E&R), we explored D. melanogasterBeauveria bassianaB. bassianaB. bassiana