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Abstract Introduction Engaging families in behavioral health services is a high priority for juvenile justice (JJ) systems and family advocacy groups. Family-driven care (FDC) enhances family engagement and decision-making power in youth behavioral health services, ultimately, improving youth and family mental health and substance abuse outcomes. Despite the benefits, there is limited guidance on how to integrate FDC into behavioral health care within the JJ system. Therefore, the goal of this study is to understand factors that promoted adoption of FDC the JJ context. Methods JJ staff and leadership across the state of Georgia participated in surveys and interviews to understand contextual implementation determinants related to the adoption of FDC. Between November 2021- July 2022, 140 JJ staff participated in the survey from 61 unique JJ organizations. In addition, 16 staff participated in follow-up key informant interviews to explain quantitative findings. Results Based on a mixed methods analysis, JJ agencies were more likely to implement FDC if they had the following characteristics: (1) presence of site leaders that were strongly committed to family engagement, (2) a shared understanding that family engagement was a top priority, (3) staff training related to family engagement, (4) external partnerships with organizations that serve families, (5) a workplace culture that was supportive of innovation, and (6) presence of family engagement programs that were easier (or more feasible) for staff to implement. Discussion This mixed methods study underscores the importance of strengthening these 6 inner and outer setting implementation determinants when preparing to integrate FDC into JJ systems. Findings are used to promote the adoption and delivery of this high priority intervention in a state-level JJ system.

Fire regimes are intrinsically shaped by humans, but current global fire models do not reflect the diverse objectives humans have for managing fire. With new data sources and collaboration across disciplines, an improved understanding of human influences on fire regimes is increasingly possible and essential to represent.

Abstract Background Improving family engagement in juvenile justice (JJ) system behavioral health services is a high priority for JJ systems, reform organizations, and family advocacy groups across the United States. Family-driven care (FDC) is a family engagement framework used by youth-serving systems to elevate family voice and decision-making power at all levels of the organization. Key domains of a family-driven system of care include: 1) identifying and involving families in all processes, 2) informing families with accurate, understandable, and transparent information, 3) collaborating with families to make decisions and plan treatments, 4) responding to family diversity and inclusion, 5) partnering with families to make organizational decisions and policy changes, 6) providing opportunities for family peer support, 7) providing logistical support to help families overcome barriers to participation, and 8) addressing family health and functioning. FDC enhances family participation, empowerment, and decision-making power in youth services; ultimately, improving youth and family behavioral health outcomes, enhancing family-child connectedness, and reducing youth recidivism in the JJ setting. Methods We evaluated staff-perceived adoption of the eight domains of FDC across detention and community services agencies in the state of Georgia. We collected mixed methods data involving surveys and in-depth qualitative interviews with JJ system administrators, staff, and practitioners between November 2021- July 2022. In total, 140 individuals from 61 unique JJ agencies participated in surveys; and 16 JJ key informants participated in qualitative interviews. Results FDC domains with the highest perceived adoption across agencies included identifying and involving families, informing families, collaborative decision-making and treatment planning, and family diversity and inclusion. Other domains that had mixed or lower perceived adoption included involving families in organizational feedback and policy making, family peer support, logistical support, and family health and functioning. Adoption of FDC domains differed across staff and organizational characteristics. Conclusions Findings from this mixed methods assessment will inform strategic planning for the scale-up of FDC strategies across JJ agencies in the state, and serve as a template for assessing strengths and weaknesses in the application of family engagement practices in systems nationally.

Abstract Background Variants that disrupt mRNA splicing account for a sizable fraction of the pathogenic burden in many genetic disorders, but identifying splice-disruptive variants (SDVs) beyond the essential splice site dinucleotides remains difficult. Computational predictors are often discordant, compounding the challenge of variant interpretation. Because they are primarily validated using clinical variant sets heavily biased to known canonical splice site mutations, it remains unclear how well their performance generalizes. Results We benchmark eight widely used splicing effect prediction algorithms, leveraging massively parallel splicing assays (MPSAs) as a source of experimentally determined ground-truth. MPSAs simultaneously assay many variants to nominate candidate SDVs. We compare experimentally measured splicing outcomes with bioinformatic predictions for 3,616 variants in five genes. Algorithms’ concordance with MPSA measurements, and with each other, is lower for exonic than intronic variants, underscoring the difficulty of identifying missense or synonymous SDVs. Deep learning-based predictors trained on gene model annotations achieve the best overall performance at distinguishing disruptive and neutral variants, and controlling for overall call rate genome-wide, SpliceAI and Pangolin have superior sensitivity. Finally, our results highlight two practical considerations when scoring variants genome-wide: finding an optimal score cutoff, and the substantial variability introduced by differences in gene model annotation, and we suggest strategies for optimal splice effect prediction in the face of these issues. Conclusion SpliceAI and Pangolin show the best overall performance among predictors tested, however, improvements in splice effect prediction are still needed especially within exons.

Abstract Purpose Clonal hematopoiesis (CH) describes the aging-associated expansion of mutant hematopoietic cell populations. In various cohorts, CH has been associated with increased morbidity and mortality from non-hematologic diseases such as cardiovascular disease and infections, including COVID-19. Comorbidities placing individuals at risk of complications from these disorders, such as diabetes, also increase in prevalence with age and frequently co-exist with CH. How CH interacts with other aging-associated comorbidities to impact human health remains unknown. Methods We assessed the impact of CH on the pre-existing end-organ damage and ultimate clinical outcomes among 242 patients hospitalized with COVID-19 at Michigan Medicine from March to June of 2020. In contrast to most previous studies, these patients skewed older with the majority having multiple comorbidities, which placed them at higher risk for end-organ damage and poor clinical outcomes. Results Overall CH was not significantly associated with increased COVID-19 mortality after controlling for other risk factors, although we did note a borderline-significant association specifically for non-DNMT3A CH mutations. In contrast, we observed a significant association between CH and pre-existing chronic kidney disease (CKD), which was strongest for DNMT3A mutant CH. Conclusions These data suggest that the clinical impact of CH is influenced by the specific gene(s) mutated and is further modified by other comorbidities and clinical risk factors frequently present in the elderly.

Fire has cultural and economic significance for Indigenous and rural peoples worldwide, being used to manage landscapes for activities such as hunting, gathering, cropping, and forestry, and for ceremonial and spiritual purposes. Policy interventions by state and non-state organizations, such as regulations, economic incentives, and communication campaigns, can target fire use directly, or affect it indirectly, for example, by restricting land access. Yet evidence of such impacts has not been synthesized at the global scale. We analyzed 512 examples in 68 countries to describe the range of policy interventions by state and non-state organizations that target and/or affect fire use, categorizing interventions based on the broad actor types involved, their mode of operation (e.g., regulation) and their intentionality and/or possible effects vis-a-vis fire use. Of these interventions, 74% involved only state agencies in policy design and implementations, 4% involved only non-state organizations, and 18% involved collaboration between state and/or non-state organizations and/or communities. Three hundred and nine interventions directly targeted fire use, of which 87% aimed to eliminate or constrain fire use. Two hundred and three affected fire use indirectly, of which 88% led to reductions in or constraints upon fire use. Though there is some recognition in the 21st century of a need, in certain contexts, to support local fire use, for reasons related to environmental justice, ecology, wildfire risk and climate change, the literature we reviewed points to several challenges for contemporary efforts toward this end. These include contradictions between policy interventions, mistrust between actors following histories of fire suppression, greater fuel loads increasing the risk of burning where fire has been suppressed, and the need to consider the indirect effects of other types of policy, such as those related to land tenure.

In many landscapes worldwide, fire regimes and human–fire interactions were reorganised by colonialism and continue to be shaped by neo-colonial processes. The introduction of fire suppression policies and state-centric property-rights systems across conservation areas and the intentional erasure of Indigenous governance systems and knowledge have served to decouple Indigenous fire-dependent communities from culturally mediated fire regimes and fire-adapted landscapes. This has driven a decline in anthropogenic fires while simultaneously increasing wildfire risk where Indigenous people have been excluded, resulting in widespread social–ecological vulnerabilities. Much contemporary fire research also bears colonial legacies in its epistemological traditions, in the global geographical distribution of research institutions, and the accessibility of research outputs. We report on a two-day workshop titled ‘Fire Management Across Contested Landscapes’ convened concurrently in Nairobi, Kenya, and London, UK. The workshop formed part of a series of workshops on ‘Decolonising Fire Science’ held by the Leverhulme Centre for Wildfires, Environment and Society, UK. The workshop in Nairobi invited diverse Kenyan stakeholders to engage in participatory activities that facilitate knowledge sharing, aiming to establish an inclusive working fire network. Activities included rich pictures, world café discussions, participatory art, and the co-development of a declaration to guide fire management in Kenya. Meanwhile, in London, Leverhulme Wildfires researchers explored participatory research methodologies including rich pictures and participatory video, and developed a declaration to guide more equitable research. There were opportunities throughout the workshop for participants in Nairobi and London to engage in dialogue with one another, sharing their experiences and understandings of complex fire challenges in Kenya and globally.

Abstract Background Lynch syndrome (LS) is a cancer predisposition syndrome affecting more than 1 in every 300 individuals worldwide. Clinical genetic testing for LS can be life-saving but is complicated by the heavy burden of variants of uncertain significance (VUS), especially missense changes. Result To address this challenge, we leverage a multiplexed analysis of variant effect (MAVE) map covering >94% of the 17,746 possible missense variants in the key LS gene MSH2. To establish this map’s utility in large-scale variant reclassification, we overlay it on clinical databases of >15,000 individuals with LS gene variants uncovered during clinical genetic testing. We validate these functional measurements in a cohort of individuals with paired tumor-normal test results and find that MAVE-based function scores agree with the clinical interpretation for every one of the MSH2 missense variants with an available classification. We use these scores to attempt reclassification for 682 unique missense VUS, among which 34 scored as deleterious by our function map, in line with previously published rates for other cancer predisposition genes. Combining functional data and other evidence, ten missense VUS are reclassified as pathogenic/likely pathogenic, and another 497 could be moved to benign/likely benign. Finally, we apply these functional scores to paired tumor-normal genetic tests and identify a subset of patients with biallelic somatic loss of function, reflecting a sporadic Lynch-like Syndrome with distinct implications for treatment and relatives’ risk. Conclusion This study demonstrates how high-throughput functional assays can empower scalable VUS resolution and prospectively generate strong evidence for variant classification.

Although it has long been recognised that human activities affect fire regimes, the interactions between humans and fire are complex, imperfectly understood, constantly evolving, and lacking any kind of integrative global framework. Many different approaches are used to study human-fire interactions, but in general they have arisen in different disciplinary contexts to address highly specific questions. Models of human-fire interactions range from conceptual local models to numerical global models. However, given that each type of model is highly selective about which aspects of human-fire interactions to include, the insights gained from these models are often limited and contradictory, which can make them a poor basis for developing fire-related policy and management practices. Here, we first review different approaches to modelling human-fire interactions and then discuss ways in which these different approaches could be synthesised to provide a more holistic approach to understanding human-fire interactions. We argue that the theory underpinning many types of models was developed using only limited amounts of data and that, in an increasingly data-rich world, it is important to re-examine model assumptions in a more systematic way. All of the models are designed to have practical outcomes but are necessarily simplifications of reality and as a result of differences in focus, scale and complexity, frequently yield radically different assessments of what might happen. We argue that it should be possible to combine the strengths and benefits of different types of model through enchaining the different models, for example from global down to local scales or vice versa. There are also opportunities for explicit coupling of different kinds of model, for example including agent-based representation of human actions in a global fire model. Finally, we stress the need for co-production of models to ensure that the resulting products serve the widest possible community.

This article examines the past century of fire management of the coastal pine savanna in Belize, drawing on archival evidence,interviews, and ethnographic enquiry into an international development project in Belize. It considers contemporary approaches that seek to use prescribed fire with the participation of local communities in relation to past practices. The Belizean savanna has long been shaped by human fire use. Its flora is ecologically adapted to fire. Yet fire has been repeatedly cast as a problem, from c. 1920, by British colonial and, later, USA foresters, and, most recently, by international and local non-governmental nature conservation organizations. Informed by different schools of thought, each of these organizations has designed programs of fire management aiming to reduce wildfire frequency. Yet little has changed; Belize's diverse and growing rural population has continued to use fire, and the savannas burn, year upon year. While the planned aims and methods differed, each program of fire management has, in practice, been similarly structured and constrained by its genesis within colonial or international development. Funding and leadership for fire management has been inconsistent. Each program has been shaped by a specifically Belizean ecology and politics, in excess of its definition of the fire 'problem' and 'solutions' to it. Powerful political elites and fire users in Belize have not seen clear incentives for the fire management supported by official policy. This analysis highlights that contemporary efforts to build more ecologically and environmentally just forms of fire management must be understood in the context of broader political struggles over land and resources.

Human use and management of fire in landscapes have a long history and vary globally in purpose and impact. Existing local research on how people use and manage fire is fragmented across multiple disciplines and is diverse in methods of data collection and analysis. If progress is to be made on systematic understanding of human fire use and management globally, so that it might be better represented in dynamic global vegetation models, for example, we need improved synthesis of existing local research and literature. The database of anthropogenic fire impacts (DAFI) presented here is a response to this challenge. We use a conceptual framework that accounts for categorical differences in the land system and socio-economic context of human fire to structure a meta-study for developing the database. From the data collated, we find that our defined anthropogenic fire regimes have distinct quantitative signatures and identify seven main modes of fire use that account for 93% of fire instance records. We describe the underlying rationales of these seven modes of fire use, map their spatial distribution and summarise their quantitative characteristics, providing a new understanding that could become the basis of improved representation of anthropogenic fire in global process-based models. Our analysis highlights the generally small size of human fires (60% of DAFI records for mean size of deliberately started fires are

Abstract In this paper, we define the Association of Standardized Patient Educators (ASPE) Standards of Best Practice (SOBP) for those working with human role players who interact with learners in a wide range of experiential learning and assessment contexts. These human role players are variously described by such terms as standardized/simulated patients or simulated participants (SP or SPs). ASPE is a global organization whose mission is to share advances in SP-based pedagogy, assessment, research, and scholarship as well as support the professional development of its members. The SOBP are intended to be used in conjunction with the International Nursing Association for Clinical Simulation and Learning (INACSL) Standards of Best Practice: SimulationSM, which address broader simulation practices. We begin by providing a rationale for the creation of the ASPE SOBP, noting that with the increasing use of simulation in healthcare training, it is incumbent on ASPE to establish SOBP that ensure the growth, integrity, and safe application of SP-based educational endeavors. We then describe the three and a half year process through which these standards were developed by a consensus of international experts in the field. Key terms used throughout the document are defined. Five underlying values inform the SOBP: safety, quality, professionalism, accountability, and collaboration. Finally, we describe five domains of best practice: safe work environment; case development; SP training for role portrayal, feedback, and completion of assessment instruments; program management; and professional development. Each domain is divided into principles with accompanying key practices that provide clear and practical guidelines for achieving desired outcomes and creating simulations that are safe for all stakeholders. Failure to follow the ASPE SOBP could compromise the safety of participants and the effectiveness of a simulation session. Care has been taken to make these guidelines precise yet flexible enough to address the diversity of varying contexts of SP practice. As a living document, these SOBP will be reviewed and modified periodically under the direction of the ASPE Standards of Practice Committee as SP methodology grows and adapts to evolving simulation practices.

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Evaluation of educational interventions is often focused on immediate and/or short-term metrics associated with knowledge and/or skills acquisition. We developed an educational intervention to support international medical graduates working in rural Victoria. We wanted an evaluation strategy that included participants’ reactions and considered transfer of learning to the workplace and retention of learning. However, with participants in distributed locations and limited program resources, this was likely to prove challenging. Elsewhere, we have reported the outcomes of this evaluation. In this educational development report, we describe our evaluation strategy as a case study, its underpinning theoretical framework, the strategy, and its benefits and challenges. The strategy sought to address issues of program structure, process, and outcomes. We used a modified version of Kirkpatrick’s model as a framework to map our evaluation of participants’ experiences, acquisition of knowledge and skills, and their application in the workplace. The predominant benefit was that most of the evaluation instruments allowed for personalization of the program. The baseline instruments provided a broad view of participants’ expectations, needs, and current perspective on their role. Immediate evaluation instruments allowed ongoing tailoring of the program to meet learning needs. Intermediate evaluations facilitated insight on the transfer of learning. The principal challenge related to the resource intensive nature of the evaluation strategy. A dedicated program administrator was required to manage data collection. Although resource-intensive, we recommend baseline, immediate, and intermediate data collection points, with multi-source feedback being especially illuminating. We believe our experiences may be valuable to faculty involved in program evaluations.

Liberal Learning 101 The thing I hated most about teaching Liberal Learning was the overwhelming knowledge that I had no knowledge. The newfangled academic setup (going back to the millennium [...]

for James Tate, 1943-2015 You seemed inordinately old, or drunk, at least, though in reality you were neither. We were at a conference in Miami, talking in the hotel bar [...]