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Washington is one of nine states that requires teaching about Indigenous peoples in public schools. The framework of cultural humility was used to investigate preservice teachers' knowledge and views about Indigenous culture. Eleven elementary preservice teachers were interviewed during their last year in a teacher preparation program. Interviews were conducted to uncover preservice teachers' prior experiences, current understanding, and approaches to teaching Indigenous culture in their future classrooms. Results show the challenges associated with operationalizing cultural humility and highlight the need to adapt the framework specifically to preservice teachers. One defining commonality of preservice teachers who displayed cultural humility was inquiring mindsets that lead to supportive and meaningful relationships that foster understanding of Indigenous culture. [ABSTRACT FROM AUTHOR]

Regression analyses based on transformations of cumulative incidence functions are often adopted when modeling and testing for treatment effects in clinical trial settings involving competing and semi‐competing risks. Common frameworks include the Fine–Gray model and models based on direct binomial regression. Using large sample theory we derive the limiting values of treatment effect estimators based on such models when the data are generated according to multiplicative intensity‐based models, and show that the estimand is sensitive to several process features. The rejection rates of hypothesis tests based on cumulative incidence function regression models are also examined for null hypotheses of different types, based on which a robustness property is established. In such settings supportive secondary analyses of treatment effects are essential to ensure a full understanding of the nature of treatment effects. An application to a palliative study of individuals with breast cancer metastatic to bone is provided for illustration. [ABSTRACT FROM AUTHOR]

Background: As the world's population ages, there is a growing concern with frailty, marked by reduced strength and greater vulnerability to stress. Overcoming obstacles like reluctance towards screening methods in this process is crucial for identifying and addressing frailty at an early stage. Understanding older people's perspectives can help adapt screening procedures in primary healthcare settings. Methods: A citizens' jury, comprising 14 purposively selected members reflecting community diversity, was conducted in South Australia to explore older adults' opinions on how and when frailty screenings occur within primary care settings. Participants engaged in discussions and deliberations informed by expert testimonies and evidence-based resources. This deliberative inclusive research method supported jurors to understand the evidence and contribute informed insights into health policy. Results: The jury systematically addressed several key concerns, including the major issues surrounding frailty screening, its benefits and potential harms, and measures to prevent screening bias and misdiagnosis. The outcome was 17 recommendations within the themes of screening age and frequency, consent, access and setting, communication and public awareness, and resources and cost. Conclusions: The study highlights the value of including older adults in the decision-making about health interventions aimed at them. The method proved effective in capturing a spectrum of community values and preferences, offering actionable recommendations for refining health screening policies to better address the needs and expectations of older adults. [ABSTRACT FROM AUTHOR]

PURPOSE: Somatic chromosomal alterations, particularly monosomy 3 and 8q gains, have been associated with metastatic risk in uveal melanoma (UM). Whole genome-scale evaluation of detectable alterations in cell-free DNA (cfDNA) in UM could provide valuable prognostic information. Our pilot study evaluates the correlation between genomic information using ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA in UM and associated clinical outcomes. MATERIALS AND METHODS: ULP-WGS of cfDNA was performed on 29 plasma samples from 16 patients, 14 metastatic UM (mUM) and two non-metastatic, including pre- and post-treatment mUM samples from 10 patients treated with immunotherapy and one with liver-directed therapy. We estimated tumor fraction (TFx) and detected copy-number alterations (CNAs) using ichorCNA. Presence of 8q amplification was further analyzed using the likelihood ratio test (LRT). RESULTS: Eleven patients with mUM (17 samples) of 14 had detectable circulating tumor DNA (ctDNA). 8q gain was detected in all 17, whereas monosomy 3 was detectable in 10 of 17 samples. TFx generally correlated with disease status, showing an increase at the time of disease progression (PD). 8q gain detection sensitivity appeared greater with the LRT than with ichorCNA at lower TFxs. The only patient with mUM with partial response on treatment had a high pretreatment TFx and undetectable on-treatment ctDNA, correlating with her profound response and durable survival. CONCLUSION: ctDNA can be detected in mUM using ULP-WGS, and the TFx correlates with DS. 8q gain was consistently detectable in mUM, in line with previous studies indicating 8q gains early in primary UM and higher amplification with PD. Our work suggests that detection of CNAs by ULP-WGS, particularly focusing on 8q gain, could be a valuable blood biomarker to monitor PD in UM. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC), a rare and highly aggressive malignancy, is characterized by an exceptionally poor prognosis, where the majority of patients present with extensive local invasion and/or distant metastases. 20–30% of ATCs harbor the BRAF‐V600E mutation. Neoadjuvant BRAF‐targeted therapy may have the potential to downstage and facilitate surgical resection for patients with locally advanced and unresectable primary tumors with BRAF mutation and may convey a survival advantage in those with metastatic disease. There is emerging evidence to support the use of other targeted agents, including multikinase inhibitors, as well as the incorporation of immunotherapy into the treatment regimen. Rapid molecular and pathological diagnosis and expert multidisciplinary discussion at specialized treatment centers are critical to expedite investigations and initiate treatment for this complex and rapidly progressive disease. [ABSTRACT FROM AUTHOR]

Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression profiles in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions. Genes with distinct promoter-isoform usage across brain regions were strongly enriched for neuropsychiatric disease risk variants. Moreover, we built enhancer-promoter interactions at promoter-isoform resolution across different brain regions and highlighted the contribution of brain region-specific and promoter-isoform-specific regulation to neuropsychiatric disorders. Including promoter-isoform resolution uncovers additional distal elements implicated in the heritability of diseases, thereby increasing the power to fine-map risk genes. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and underscore the importance of considering isoform information in gene regulation. Brain gene regulation is key for neuropsychiatric disorders. Here, the authors show that profiling gene expression and chromatin states in 25 brain regions enables enhancer-promoter mapping at isoform resolution, improving genetic fine-mapping. [ABSTRACT FROM AUTHOR]

Zymoseptoria tritici is an ascomycete fungus and the causal agent of Septoria tritici leaf blotch (STB) in wheat. Z. tritici secretes an array of effector proteins that are likely to facilitate host infection, colonisation and pycnidia production. In this study we demonstrate a role for Zt-11 as a Z. tritici effector during disease progression. Zt-11 is upregulated during the transition of the pathogen from the biotrophic to necrotrophic phase of wheat infection. Deletion of Zt-11 delayed disease development in wheat, reducing the number and size of pycnidia, as well as the number of macropycnidiospores produced by Z. tritici. This delayed disease development by the ΔZt-11 mutants was accompanied by a lower induction of PR genes in wheat, when compared to infection with wildtype Z. tritici. Overall, these data suggest that Zt-11 plays a role in Z. tritici aggressiveness and STB disease progression possibly via a salicylic acid associated pathway. [ABSTRACT FROM AUTHOR]

The complexities inherent in drug development are multi-faceted and often hamper accuracy, speed and efficiency, thereby limiting success. This review explores how recent developments in machine learning (ML) are significantly impacting target-based drug discovery, particularly in small-molecule approaches. The Simplified Molecular Input Line Entry System (SMILES), which translates a chemical compound's three-dimensional structure into a string of symbols, is now widely used in drug design, mining, and repurposing. Utilizing ML and natural language processing techniques, SMILES has revolutionized lead identification, high-throughput screening and virtual screening. ML models enhance the accuracy of predicting binding affinity and selectivity, reducing the need for extensive experimental screening. Additionally, deep learning, with its strengths in analyzing spatial and sequential data through convolutional neural networks (CNNs) and recurrent neural networks (RNNs), shows promise for virtual screening, target identification, and de novo drug design. Fragment-based approaches also benefit from ML algorithms and techniques like generative adversarial networks (GANs), which predict fragment properties and binding affinities, aiding in hit selection and design optimization. Structure-based drug design, which relies on high-resolution protein structures, leverages ML models for accurate predictions of binding interactions. While challenges such as interpretability and data quality remain, ML's transformative impact accelerates target-based drug discovery, increasing efficiency and innovation. Its potential to deliver new and improved treatments for various diseases is significant. [ABSTRACT FROM AUTHOR]

Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results. In the meta-analysis, we identify 41 loci that have not been associated with LDH in prior studies on top of the 23 known risk loci. We detect LDH-associated loci in the vicinity of genes related to inflammation, disc-related structures, and synaptic transmission. Overall, our research contributes to a deeper understanding of the genetic factors behind LDH, potentially paving the way for the development of new therapeutics, prevention methods, and treatments for symptomatic LDH in the future. A genome-wide association study suggests 41 previously unreported loci on top of the 23 known loci that influence the disease risk for lumbar disc herniations. Many of these loci harbour genes implicated in disc structure and inflammation, as well as genes related to the nervous system and nerve function. [ABSTRACT FROM AUTHOR]

Data assimilation combines prior (or background) information with observations to estimate the initial state of a dynamical system over a given time-window. A common application is in numerical weather prediction where a previous forecast and atmospheric observations are used to obtain the initial conditions for a numerical weather forecast. In four-dimensional variational data assimilation (4D-Var), the problem is formulated as a nonlinear least-squares problem, usually solved using a variant of the classical Gauss-Newton (GN) method. However, we show that GN may not converge if poorly initialized. In particular, we show that this may occur when there is greater uncertainty in the background information compared to the observations, or when a long time-window is used in 4D-Var allowing more observations. The difficulties GN encounters may lead to inaccurate initial state conditions for subsequent forecasts. To overcome this, we apply two convergent GN variants (line search and regularization) to the long time-window 4D-Var problem and investigate the cases where they locate a more accurate estimate compared to GN within a given budget of computational time and cost. We show that these methods are able to improve the estimate of the initial state, which may lead to a more accurate forecast. Highlights Poor initialization of Gauss-Newton method may result in failure to converge. Safeguarded Gauss-Newton improves initial state estimate within limited time/cost. Results using twin experiments with long time-window and chaotic Lorenz models. Apply state of the art least-squares convergence theory to data assimilation. Improvements to initial state estimate may lead to a more accurate forecast. [ABSTRACT FROM AUTHOR]

Low Earth Orbit (LEO) has emerged as a unique environment for evaluating altered stem cell properties in microgravity. LEO has become increasingly accessible for research and development due to progress in private spaceflight. Axiom Mission 2 (Ax-2) was launched as the second all-private astronaut mission to the International Space Station (ISS). Frozen human induced pluripotent stem cells (hiPSCs) expressing green fluorescent protein (GFP) under the SOX2 promoter, as well as fibroblasts differentiated from SOX2-GFP hiPSCs, were sent to the ISS. Astronauts then thawed and seeded both cell types into commercially available 96-well plates, which provided surface tension that reduced fluid movement out of individual wells and showed that hiPSCs or hiPSC-derived fibroblasts could survive either in suspension or attached to a Matrigel substrate. Furthermore, both cell types could be transfected with red fluorescent protein (RFP)-expressing plasmid. We demonstrate that hiPSCs and hiPSC-fibroblasts can be thawed in microgravity in off-the-shelf, commercially-available cell culture hardware, can associate into 3D spheroids or grow adherently in Matrigel, and can be transfected with DNA. This lays the groundwork for future biomanufacturing experiments in space. [ABSTRACT FROM AUTHOR]

Resting state correlations between blood oxygenation level dependent (BOLD) MRI signals from voxels in white matter (WM) are demonstrably anisotropic, so that functional correlation tensors (FCT) may be used to quantify the underlying microstructure of BOLD effects in WM tracts. However, the overall spatial distribution of FCTs and their metrics in specific populations has not yet been established, and the factors that affect their precise arrangements remain unclear. Changes in WM occur with normal aging, and these may be expected to affect FCTs. We hypothesized that FCTs exhibit a characteristic spatial pattern and may show systematic changes with aging or other factors. Here we report our analyses of the FCT characteristics of fMRI images of a large cohort of 461 cognitively normal subjects (190 females, 271 males) sourced from the Open Access Series of Imaging Studies (OASIS), with age distributions of 42 y/o – 95 y/o. Group averages and statistics of FCT indices, including axial functional correlations, radial functional correlations, mean functional correlations and fractional anisotropy, were quantified in WM bundles defined by the JHU ICBM-DTI-81 WM atlas. In addition, their variations with normal aging were examined. The results revealed a dimorphic distribution of changes in FCT metrics with age, with decreases of the functional correlations in some regions and increases in others. Supplementary analysis revealed that females exhibited significant age effects on a greater number of WM areas, but the interaction between age and sex was not significant. The findings demonstrate the reproducibility of the spatial distribution of FCT metrics and reveal subtle regional changes with age. [ABSTRACT FROM AUTHOR]

Clinical trials with random assignment of treatment provide evidence about causal effects of an experimental treatment compared to standard care. However, when disease processes involve multiple types of possibly semi-competing events, specification of target estimands and causal inferences can be challenging. Intercurrent events such as study withdrawal, the introduction of rescue medication, and death further complicate matters. There has been much discussion about these issues in recent years, but guidance remains ambiguous. Some recommended approaches are formulated in terms of hypothetical settings that have little bearing in the real world. We discuss issues in formulating estimands, beginning with intercurrent events in the context of a linear model and then move on to more complex disease history processes amenable to multistate modeling. We elucidate the meaning of estimands implicit in some recommended approaches for dealing with intercurrent events and highlight the disconnect between estimands formulated in terms of potential outcomes and the real world. [ABSTRACT FROM AUTHOR]

Summary: This Good Practice Paper provides recommendations for the use of advanced imaging for earlier diagnosis and morbidity prevention in multiple myeloma. It describes how advanced imaging contributes to optimal healthcare resource utilisation by in newly diagnosed and relapsed myeloma, and provides a perspective on future directions of myeloma imaging, including machine learning assisted reporting. [ABSTRACT FROM AUTHOR]

Little is known about the role of subjective sexual arousal within romantic relationships. The current paper addresses this limitation using a prospective study design that investigates the direct associations between subjective sexual arousal induced by a romantic partner (partner arousal) and arousal induced by pornography (porn arousal) on changes in relational outcomes. A total of 309 participants who were in a current romantic relationship completed measures of partner and porn arousal as well as relational outcomes (i.e., sexual satisfaction and relationship quality and stability) at baseline (T1) and completed a second assessment of relational outcomes 2 months later (T2). Partner arousal was found to have no significant associations with changes in relational outcomes; however, porn arousal was associated with significant declines in sexual satisfaction and relationship quality and stability over a 2-month period. This paper is the first to examine how feeling sexually aroused by porn may impact relational outcomes for those in romantic relationships. [ABSTRACT FROM AUTHOR]

We utilize duoethnography to help readers better understand the constitutive nature of disability in the contexts of chronic illness and mental health. By doing so, we articulate the concept of socio-emotional disablism, which expands structural and psycho-emotional theories of disablism to account for the ways socio-material interactions trigger emotion-work—the communicative labor and fatigue that accompanies negotiating our own emotions as well as the emotions of others in disabling contexts—thus limiting relational and ideological engagement with disability. We conclude by discussing what the concept of socio-emotional disablism teaches us about how to build more inclusive social futures through deeper interpersonal engagement and more sustainable public health practices. Points of interest: As non-apparent impairments, Crohn's Disease and OCD carry unique stigmas. The unique stigmas associated with Crohn's Disease and OCD can impact social perceptions and interactions in ways that complicate our understanding of how disablism manifests. The authors propose the concept of socio-emotional disablism to account for ableist microaggressions in the context of non-apparent impairment and the structural reconfigurations prompted by COVID-19. This study reveals how communicating experiences of disability across differences can lead to deeper understandings of disablism, which can inform more sustainable practices of inclusivity. [ABSTRACT FROM AUTHOR]

A rich literature uses law and social science methods to better understand household financial distress and overindebtedness both inside and outside of bankruptcy. This scholarship contributes to several ongoing scholarly conversations, such as those on income and wealth disparities across race and class, how people live in circumstances of financial precarity, why people turn to the legal system to solve their problems, and how to improve access to justice so people can get the help they need. We first review the current literature about who files bankruptcy, the contributors to people's need to file bankruptcy, what happens to them in bankruptcy court, and what happens after their bankruptcy cases conclude. We then outline a research agenda of low-hanging fruit that will contribute to broader sociological and sociolegal research agendas, including economic mobility, aging, gender studies, health studies, family studies, social psychology, and policy work. [ABSTRACT FROM AUTHOR]

Presumptive drug screening enables timely procurement of search and arrest warrants and represents a crucial first step in crime scene analysis. Screening also reduces the burden on forensic laboratories which often face insurmountable backlogs. In most scenarios, on-site presumptive drug screening relies on chemical field tests for initial identification. However, even when used appropriately, these test kits remain limited to subjective colorimetric analysis, produce false positive or negative results with excessive sample quantities, and are known to cross-react with numerous innocuous substances. Previous efforts to develop microfluidic devices that incorporate these chromogenic indicator reagents address only a few of the many challenges associated with these kits. This is especially true for samples where the drug of interest is present as a lacing agent. This work describes the development of a centrifugal microfluidic device capable of integrating facile sample preparation, by way of a 3D printed snap-on cartridge amenable to microwave assisted extraction, followed by chromatographic separation and chromogenic detection on-disc. As cannabis is among the most widely used controlled substance worldwide, and displays strong interference with these indicator reagents, mock samples of laced marijuana are used for a proof-of-concept demonstration. Post extraction, the microdevice completes high throughput metering just prior to simultaneous reaction with four of the most commonly employed microchemical tests, followed by objective image analysis in CIELAB (a device-independent color model). Separation and recovery of a representative controlled substance with 93% efficiency is achieved. Correct identification, according to hierarchical cluster analysis, of three illicit drugs (e.g., heroin, phencyclidine, and cocaine) in artificially laced samples is also demonstrated on-disc. The cost effective microdevice is capable of complete automation post-extraction, with a total analysis time (including extraction) of <8 min. Finally, sample consumption is minimized, thereby preventing the complete destruction of forensic evidence. [ABSTRACT FROM AUTHOR]

Heteroplasmic mitochondrial DNA (mtDNA) variants accumulate as humans age, particularly in the stem-cell compartments, and are an important contributor to age-related disease. Mitochondrial dysfunction has been observed in osteoporosis and somatic mtDNA pathogenic variants have been observed in animal models of osteoporosis. However, this has never been assessed in the relevant human tissue. Mesenchymal stem cells (MSCs) are the progenitors to many cells of the musculoskeletal system and are critical to skeletal tissues and bone vitality. Investigating mtDNA in MSCs could provide novel insights into the role of mitochondrial dysfunction in osteoporosis. To determine if this is possible, we investigated the landscape of somatic mtDNA variation in MSCs through a combination of fluorescence-activated cell sorting and single-cell next-generation sequencing. Our data show that somatic heteroplasmic variants are present in individual patient-derived MSCs, can reach high heteroplasmic fractions and have the potential to be pathogenic. The identification of somatic heteroplasmic variants in MSCs of patients highlights the potential for mitochondrial dysfunction to contribute to the pathogenesis of osteoporosis. [ABSTRACT FROM AUTHOR]

We develop a new theory of knowledge with mathematics and a broad-based series of case studies to seek a better understanding of what constitutes knowledge in the field and its value for autonomous human–machine teams facing uncertainty in the open. Like humans, as teammates, artificial intelligence (AI) machines must be able to determine what constitutes the usable knowledge that contributes to a team's success when facing uncertainty in the field (e.g., testing "knowledge" in the field with debate; identifying new knowledge; using knowledge to innovate), its failure (e.g., troubleshooting; identifying weaknesses; discovering vulnerabilities; exploitation using deception), and feeding the results back to users and society. It matters not whether a debate is public, private, or unexpressed by an individual human or machine agent acting alone; regardless, in this exploration, we speculate that only a transparent process advances the science of autonomous human–machine teams, assists in interpretable machine learning, and allows a free people and their machines to co-evolve. The complexity of the team is taken into consideration in our search for knowledge, which can also be used as an information metric. We conclude that the structure of "knowledge", once found, is resistant to alternatives (i.e., it is ordered); that its functional utility is generalizable; and that its useful applications are multifaceted (akin to maximum entropy production). Our novel finding is the existence of Shannon holes that are gaps in knowledge, a surprising "discovery" to only find Shannon there first. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic led to a proliferation of remote-proctored (or "at-home") assessments. The lack of standardized setting, device, or in-person proctor during at-home testing makes it markedly distinct from testing at a test center. Comparability studies of at-home and test center scores are important in understanding whether these distinctions impact test scores. This study found no significant differences in at-home versus test center test scores on a large-scale admissions test using either a randomized controlled trial or an observational study after adjusting for differences in sample composition along baseline characteristics. [ABSTRACT FROM AUTHOR]

Data-driven modal analysis methods provide a powerful way to decompose data into a sum of modes. The spatiotemporal Koopman decomposition (STKD) enables the computation of modes defined by global frequencies and growth rates in various spatial dimensions and time. The method is an extension of the dynamic mode decomposition (DMD) and higher-order dynamic mode decomposition (HODMD) that represents the data as a sum of standing and traveling, possibly growing or decaying, waves. In this paper, the STKD with HODMD is applied to schlieren video highlighting second mode instability waves traveling down the length of a 3-degree half-angle cone and a 7-degree half-angle cone, both at a freestream Mach number of 6. The HODMD is able to compute dominant modes and frequencies that align with those from associated experimental measurements of unsteady pressure fluctuations, and whose mode shapes clearly show the intensifying wavepacket structure of the waves. The STKD algorithm is used to compute streamwise wavenumbers, spatial growth rates, and wave speeds. The spatial growth rates from the STKD and the magnitudes of the HODMD mode shapes are used to compute the N-factor for waves of several frequencies. Overall, the STKD with HODMD is shown to be a useful tool for extracting spatiotemporal disturbance growth from a schlieren video. [ABSTRACT FROM AUTHOR]

Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. We hypothesized that cryoablation may modify the immune microenvironment through direct modulation of the tumor, thereby generating an anti-tumor response in tumors refractory to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), subjects with unresectable melanoma progressing on ICI underwent cryoablation of an enlarging metastasis, and ICI was continued for a minimum of two additional cycles. The primary endpoints were safety, feasibility and tumor response in non-ablated lesions. From May 2018 through July 2020, 17 patients were treated on study. The study met its primary endpoints with the combination strategy found to be safe and feasible with an objective response rate of 23.5% and disease control rate of 41% (4 partial response, 3 stable disease). Our data support further study of this synergistic therapeutic approach.Most patients with metastatic melanoma still develop primary or acquired resistance to immune checkpoint inhibition (ICI). Here the authors report the results of a phase II trial of cryoablation and ICI in patients with unresectable melanoma progressing on ICI. [ABSTRACT FROM AUTHOR]

Botanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. Since physicochemical and pharmacokinetic properties dictate the in vivo exposure of botanical constituents, these parameters greatly impact the pharmacological and toxicological effects of botanicals in consumer products. This study sought to use computational (i.e., in silico) models, including quantitative structure–activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of botanical constituents. One hundred and three major constituents (e.g., withanolides, mitragynine, and yohimbine) in 13 botanicals (e.g., ashwagandha, kratom, and yohimbe) were investigated. The predicted properties included biopharmaceutical classification system (BCS) classes based on aqueous solubility and permeability, oral absorption, liver microsomal clearance, oral bioavailability, and others. Over half of these constituents fell into BCS classes I and II at dose levels no greater than 100 mg per day, indicating high permeability and absorption (%Fa > 75%) in the gastrointestinal tract. However, some constituents such as glycosides in ashwagandha and Asian ginseng showed low bioavailability after oral administration due to poor absorption (BCS classes III and IV, %Fa < 40%). These in silico results fill data gaps for botanical constituents and could guide future safety studies. For example, the predicted human plasma concentrations may help select concentrations for in vitro toxicity testing. Additionally, the in silico data could be used in tiered or batteries of assays to assess the safety of botanical products. For example, highly absorbed botanical constituents indicate potential high exposure in the body, which could lead to toxic effects. Botanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. This study used computational models, including quantitative structure–activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of 103 botanical constituents in 13 botanicals. Over half constituents had high permeability and absorption at oral doses no greater than 100 mg per day. However, most glycosides showed low bioavailability after oral administration due to low absorption. [ABSTRACT FROM AUTHOR]

Iron and zinc are important nutrients during infancy, particularly for infants exclusively fed human milk at the beginning of complementary feeding (CF) from 6–12 months. The 1stFoods Study examined the ingredients and nutrient contents of commercially-available infant and toddler foods (ITFs) that were sold in the US and contained meat. Company websites (n = 22) were used to create a database of commercial ITFs (n = 165) available for purchase in the US and contained at least one meat (e.g., beef, chicken, pork). Single ingredient and ready-to-serve meals (for ages ≤ 9 months) and ready-to-serve meals (for ages 10+ months) were categorized as infant and toddler products, respectively. For each product, the ingredient list, intended age/stage, serving size (g), energy (kcal), protein (g), iron (mg), and zinc (mg) per serving were recorded from product labels. Nutrient amount/100 g was calculated for each product and medians and inter-quartile ranges were calculated and compared (1) by intended age/stage of the product and (2) according to meat type. In general, toddler products contained more iron than infant products. Within infant products (n = 65), more iron was found in products containing beef relative to products with other meats, which were similar in iron content. Within toddler products (n = 38), more iron was found in products containing seafood, followed by beef, turkey, and pork. Slightly less iron was found in products with chicken. Zinc content was infrequently reported (n = 17 total products). Because many of the products assessed contained low amounts of iron and zinc, meeting the current infant and toddler requirements for iron and zinc during the CF period may be challenging if commercial ITFs containing meat are the primary source of these nutrients. [ABSTRACT FROM AUTHOR]

Operational data assimilation systems for coupled atmosphere–ocean prediction are usually "weakly coupled", in which there is no explicit interaction between the atmosphere and ocean within the data assimilation step. Explicitly allowing for cross‐correlations between the ocean and the atmosphere may have potential benefits in improving the consistency of atmosphere and ocean analyses, as well as allowing a better use of observations at the interface. To understand whether such correlations are significant on the time‐scales of numerical weather prediction, we investigate the atmosphere–ocean cross‐correlations of short‐term forecast errors from the Met Office coupled prediction system, considering their temporal and spatial variability. We find that significant correlations exist between atmosphere and ocean forecast errors on these time‐scales, and that these vary diurnally, from day to day, spatially and synoptically. For correlations between errors in the atmospheric wind and ocean temperature, positive correlations in the North Atlantic region are found to be synoptically dependent, with correlation structures extending into the ocean throughout the deep mixed layer, beyond a depth of 100 m. In contrast, negative correlations over the Indian Ocean are very shallow and are associated with the diurnal cycle of solar radiation. The significance and variability of cross‐correlations indicates that there should be a benefit from including them in data assimilation systems, but it will be important to allow for some flow‐dependence in the correlations. Furthermore, the differing vertical extents of the cross‐correlations in different regions implies the need for situation‐dependent localisation of ensemble correlations when including them in coupled data assimilation systems. [ABSTRACT FROM AUTHOR]

In this article, we investigate how the concept of Care Biography and related concepts are understood and operationalised and describe how it can be applied to advancing our understanding and practice of holistic and person‐centred care. Walker and Avant's eight‐step concept analysis method was conducted involving multiple database searches, with potential or actual applications of Care Biography identified based on multiple discussions among all authors. Our findings demonstrate Care Biography to be a novel overarching concept derived from the conjunction of multiple other concepts and applicable across multiple care settings. Concepts related to Care Biography exist but were more narrowly defined and mainly applied in intensive care, aged care, and palliative care settings. They are associated with the themes of Meaningfulness and Existential Coping, Empathy and Understanding, Promoting Positive Relationships, Social and Cultural Contexts, and Self‐Care, which we used to inform and refine our concept analysis of Care Biography. In Conclusion, the concept of Care Biography, can provide a deeper understanding of a person and their care needs, facilitate integrated and personalised care, empower people to be in control of their care throughout their life, and help promote ethical standards of care. [ABSTRACT FROM AUTHOR]

Introduction: Supporting the health and well‐being of older Australians necessitates the implementation of effective and sustainable community‐based interventions. Rural settings, however, pose unique challenges to intervention implementation and sustainability, with limited research exploring strategies employed to overcome these complexities. Objective: To identify enabling strategies that support the sustainable implementation of community‐based health and well‐being interventions for older adults in rural Australia. Design: A scoping review, following methods by Arksey and O'Malley and enhanced by elements of the Joanna Briggs Institute methodology for scoping reviews and Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR), was conducted. An electronic search of seven databases was completed in April 2023. A thematic analysis was applied to provide a comprehensive and contextualised understanding of the phenomenon of interest. Findings: Of 1277 records screened, 15 studies were identified and included for review. Five themes identified key enablers for rural implementation: (1) Co‐designing for the local context; (2) Embedding local champions; (3) Leveraging existing local resources; (4) Maintaining impact beyond the end of the funded period and (5) Flexibility in funding models. Discussion: The sustainable implementation of interventions requires active community involvement and consultation through all stages of program design and delivery to effectively meet the health and well‐being needs of older rural‐dwelling Australians. Conclusion: Our findings advocate for clear implementation guidelines to support the design, delivery and adaptation of community‐based programs that appropriately reflect the unique contextual needs and strengths of rural communities. [ABSTRACT FROM AUTHOR]

In this paper we present new empirical evidence on the relationship between exporting experience and the duration of exports at the firm-product-destination level. We find that the direct effect of experience on export flow survival is negative. However, when we include interactions between experience and firm export diversification measures, this effect becomes positive. This suggests that more experienced firms launch more risky export flows which increases the probability of failure of any individual product-destination pairing. [ABSTRACT FROM AUTHOR]

Biometric technology encompasses a proliferating array of data forms, applications, and stakeholders but has raised numerous social and ethical concerns. This article examines contending perceptions of biometrics by developing a three-way framework of science–society orderings, drawn from social studies of biometrics and wider science studies literature. By analysing documentary sources and participant observation data through this framework, the article identifies a series of distinct normative interpretations or imaginaries of biometrics. It is argued that these imaginaries, described, respectively, as 'public good', 'collective control', and 'societal risks', project contending normative framings of science–society relations. These imaginaries were also however found to reflexively encompass perceived challenges, giving rise to practices that I term imaginative politics. These findings raise the need for science policy studies to consider the distinction between imagining and realizing in greater depth and to consider more profoundly the politics of science–society co-production. [ABSTRACT FROM AUTHOR]

Steinkrauss and Slotnick (2024) reviewed neuroimaging studies linking the hippocampus with implicit memory. They conclude that there is no convincing evidence that the hippocampus is associated with implicit memory because prior studies are confounded by explicit memory (among other factors). Here, we ask a different yet equally important question: do reports of unconscious hippocampal activity reflect a Type-I error (i.e. a false positive)? We find that 39% of studies linking the hippocampus with implicit memory (7 of 18) do not report correcting for multiple comparisons. These results indicate that many unconscious hippocampal effects may reflect a Type-I error. [ABSTRACT FROM AUTHOR]

When we uncovered a large gender gap in political ambition in the early 2000s, our research highlighted how far the United States was from gender parity in politics. Given marked increases in women's numeric representation throughout the past two decades, many might expect the gender gap in political ambition to have begun to close. Results from our new study of potential candidates, however, reveal that the magnitude of the gender gap is just as large 20 years later, and two primary explanations persist as well. We posit that even though candidate recruitment has propelled more women into electoral politics, patterns of traditional gender socialization persist. These dynamics, coupled with negative perceptions of how female candidates are treated, continue to depress women's interest in elective office. As long as running for office is a more remote endeavor for women than men, women's full political inclusion will remain a distant goal. [ABSTRACT FROM AUTHOR]

The Early Childhood Program for Language Acquisition and Community Engagement (EC PLACE) is a program designed to support language, communication, and social development of children with significant disabilities within a public preschool setting. This article describes program design and eight effective program practices which contributed to remarkable gains in children's skills and outcomes. [ABSTRACT FROM AUTHOR]

Background: In the current era of effective adjuvant therapies and de-escalation of surgery, distinguishing which patients with high-risk stage II melanoma are at increased risk of recurrence after excision of the primary lesion is essential to determining appropriate treatment and surveillance plans. Methods: A single-center retrospective study analyzed patients with stage IIB or IIC melanoma. Demographic and tumor data were collected, and genomic analysis of formalin-fixed, paraffin-embedded tissue samples was performed via an internal next-generation sequencing (NGS) platform (SNaPshot). The end points examined were relapse-free survival (RFS), distant metastasis-free survival (DMFS), overall survival (OS), and melanoma-specific survival (MSS). Uni- and multivariable Cox regressions were performed to calculate the hazard ratios. Results: The study included 92 patients with a median age of 69 years and a male/female ratio of 2:1. A Breslow depth greater than 4 mm, a higher mitotic rate, an advanced T stage, and a KIT mutation had a negative impact on RFS. A primary lesion in the head and neck, a mitotic rate exceeding 10 mitoses per mm2, a CDH1 mutation, or a KIT mutation was significantly associated with a shorter DMFS. Overall survival was significantly lower with older age at diagnosis and a higher mitotic rate. An older age at diagnosis also had a negative impact on MSS. Conclusion: Traditional histopathologic factors and specific tumor mutations displayed a significant correlation with disease recurrence and survival for patients with high-risk stage II melanoma. This study supported the use of genomic testing of high-risk stage II melanomas for prognostic prediction and risk stratification. [ABSTRACT FROM AUTHOR]

Teaching is a skill that can and should be taught in graduate education. Fortunately, many departments offer some teacher training for their graduate students to prepare them to teach introductory and other survey courses. What is apparently still lacking is training for graduate students to teach upper-level seminar-style classes. Therefore, we designed and implemented a graduate-level seminar on teaching seminars in psychology wherein course-takers developed tangible resources (e.g., syllabi) to empower them to effectively (and autonomously) teach seminar-style courses. We believe our course provides an excellent model for departments interested in further enhancing the teacher training of their graduate students. [ABSTRACT FROM AUTHOR]

The HostSeq initiative recruited 10,059 Canadians infected with SARS-CoV-2 between March 2020 and March 2023, obtained clinical information on their disease experience and whole genome sequenced (WGS) their DNA. We analyzed the WGS data for genetic contributors to severe COVID-19 (considering 3,499 hospitalized cases and 4,975 non-hospitalized after quality control). We investigated the evidence for replication of loci reported by the International Host Genetics Initiative (HGI); analyzed the X chromosome; conducted rare variant gene-based analysis and polygenic risk score testing. Population stratification was adjusted for using meta-analysis across ancestry groups. We replicated two loci identified by the HGI for COVID-19 severity: the LZTFL1/SLC6A20 locus on chromosome 3 and the FOXP4 locus on chromosome 6 (the latter with a variant significant at P < 5E-8). We found novel significant associations with MRAS and WDR89 in gene-based analyses, and constructed a polygenic risk score that explained 1.01% of the variance in severe COVID-19. This study provides independent evidence confirming the robustness of previously identified COVID-19 severity loci by the HGI and identifies novel genes for further investigation. Author summary: Host genetics determine how human genetics contribute to the response to infectious disease. HostSeq is a Canada-wide effort to contribute to our understanding of host genetics for COVID-19. The HostSeq study involves genetic and clinical data from individuals who tested positive for SARS-CoV-2 across Canada. This work examines locations in the human genome that have been reported to be involved in severe COVID-19 worldwide and determines if we also see the involvement of those genomic locations in Canadians. This work also explores several 'genetic quantities' such as a determination of how much of COVID-19 severity is due to genetics in Canada. [ABSTRACT FROM AUTHOR]

Introduction: Clinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia's new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care. Methods and analysis: The Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level. Discussion: The EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 — retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx. [ABSTRACT FROM AUTHOR]

Suicide risk assessment and stratification are a key suicide prevention strategy in mental health care systems that treat military service members and veterans. The aim of the current mixed‐method project was to address a gap in our knowledge as to how therapists make these important clinical decisions. This manuscript reports the results of a project during which six vignettes were developed reflecting varying levels of risk according to the Rocky Mountain MIRECC Risk Stratification Table. Mental health therapists were asked to evaluate the risk level of each vignette, determine a treatment disposition, and provide justification for their ratings. The results of the study indicate that therapists can reliably evaluate risk, but that treatment planning tended to be based more on vignette‐specific factors than essential features of the risk model. The qualitative findings revealed variations in the definition and perception of foundational concepts, suggesting a need for further research and training in these domains. Overall, the results support the use of vignettes as a method to assess clinical decision‐making and provide several areas for further training and research. [ABSTRACT FROM AUTHOR]

Introduction: There has been a growing call for drug and/or alcohol dependence to be managed as a chronic condition. The Flinders Chronic Condition Management Program (Flinders Program) was implemented in a drug and alcohol service in Australia in 2019–2022 to explore the feasibility of chronic condition management in outpatient clinics. Implementation involved: adaptation of the Flinders Program; adaptation of clinical procedures; training clinicians and managers; training Flinders Program Accredited Trainers; and system integration. This study aims to explore barriers and enablers to implementation. Methods: A qualitative formative evaluation was undertaken. Data included implementation documents (n = 7), responses to open‐ended questions in post‐training surveys (n = 27), and focus groups and interviews with implementation staff, clinicians, managers and a trainer (n = 16). Data were analysed using the Consolidated Framework for Implementation Research in a 'coding reliability' approach to thematic analysis. Results: Participants responded positively to the Flinders Program's philosophy, processes, tools and training. However, barriers were identified across three Consolidated Framework for Implementation Research domains: (i) outer setting (client suitability and incompatibility with external policies and incentives); (ii) characteristics of individuals (low self‐efficacy); and (iii) inner setting (lack of system and workflow integration). Discussion and Conclusions: Executive support and systems integration are important for the implementation of the Flinders Program in drug and alcohol services. This needs to be achieved within externally mandated key performance indicators for outpatient services. Further research is needed to fully evaluate the potential of a chronic condition management framework in Australian outpatient drug and alcohol services. [ABSTRACT FROM AUTHOR]

In variational assimilation, the most probable state of a dynamical system under Gaussian assumptions for the prior and likelihood can be found by solving a least‐squares minimization problem. In recent years, we have seen the popularity of hybrid variational data assimilation methods for Numerical Weather Prediction. In these methods, the prior error covariance matrix is a weighted sum of a climatological part and a flow‐dependent ensemble part, the latter being rank deficient. The nonlinear least squares problem of variational data assimilation is solved using iterative numerical methods, and the condition number of the Hessian is a good proxy for the convergence behavior of such methods. In this article, we study the conditioning of the least squares problem in a hybrid four‐dimensional variational data assimilation (Hybrid 4D‐Var) scheme by establishing bounds on the condition number of the Hessian. In particular, we consider the effect of the ensemble component of the prior covariance on the conditioning of the system. Numerical experiments show that the bounds obtained can be useful in predicting the behavior of the true condition number and the convergence speed of an iterative algorithm [ABSTRACT FROM AUTHOR]

Introduction: Tacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD‐tac). Envarsus (LCP‐tac), an extended‐release formulation, is approved for adults but not for pediatric patients. Methods: We conducted a pilot open‐label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP‐tac versus BD‐tac. We conducted two 24‐h Pk studies: pre‐conversion (BD‐tac) and 4 weeks post‐conversion to LCP‐tac. Patients were followed for 6 months, with the option to continue LCP‐tac. Results: Five patients completed the study, with no returns to BD‐tac. Median age was 15 years (range 11–17). LCP‐tac exhibited an extended‐release profile versus the bimodal profile of BD‐tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m2, range − 1.7 to 2.3 mL/min/1.73 m2). Concentration/dose ratio was higher in LCP‐tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD‐tac: LCP‐tac). Conclusion: Our pilot study confirms the extended‐release Pk profile and improved absorption of LCP‐tac compared to BD‐tac. A larger study is needed to further evaluate the population Pk characteristics in children. [ABSTRACT FROM AUTHOR]

Aims: To map the concepts of the caring life-course theory that are used in life-course approaches from different disciplines; establish whether there is a common recognition of, or language used, to describe care in those life-course approaches; and identify the role and contribution of care to the life-course literature. Design: This discursive paper uses a narrative review process to explore points of convergence and divergence between life-course approaches and the caring life-course theory. Methods: Categories for analysis were developed deductively and inductively, focusing on the constructs of fundamental care, capacity and capability, care network, care transition, care trajectory and care biography. Results: We identified four disciplinary perspectives: (1) life-course sociology; (2) life-course epidemiology; (3) lifespan developmental psychology; and (4) life-course health development. While six core constructs of the caring life-course theory were described, either explicitly or implicitly, in existing life-course approaches, no single approach fully describes the role and contribution of care across the lifespan. Conclusion: Life-course approaches have largely neglected the contribution and role of care in informing the life-course discourse. This review highlights the significance of care beyond traditional healthcare settings and recognizes it as a fundamental human need for well-being and development, which can contribute to existing lifecourse literature. Implication for the Profession and/or Patient Care: There is a need to understand care as a complex system and embrace a whole-system, life-course approach to enable nurses and other healthcare professionals to provide high-quality, patient-centred care. Impact: Incorporating care within a life-course approach provides opportunities to integrate and deliver care centred around the person, their life transitions, trajectories and care networks, including informal carers and healthcare professionals. No Patient or Public Contribution: Patients or members of the public were not involved in this study as it is a discursive paper based on the relevant literature. [ABSTRACT FROM AUTHOR]

Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic and adipose tissue. Several cells interact locally in what is known as the degenerative niche. We analysed muscle biopsies of controls and BMD patients at early, moderate and advanced stages of progression using Hyperion imaging mass cytometry (IMC) by labelling single sections with 17 markers identifying different components of the muscle. We developed a software for analysing IMC images and studied changes in the muscle composition and spatial correlations between markers across disease progression. We found a strong correlation between collagen-I and the area of stroma, collagen-VI, adipose tissue, and M2-macrophages number. There was a negative correlation between the area of collagen-I and the number of satellite cells (SCs), fibres and blood vessels. The comparison between fibrotic and non-fibrotic areas allowed to study the disease process in detail. We found structural differences among non-fibrotic areas from control and patients, being these latter characterized by increase in CTGF and in M2-macrophages and decrease in fibers and blood vessels. IMC enables to study of changes in tissue structure along disease progression, spatio-temporal correlations and opening the door to better understand new potential pathogenic pathways in human samples. [ABSTRACT FROM AUTHOR]

In contrast to prevalent strategies which make use of β-sheet mimetics to block Aβ fibrillar growth, in this study, we designed a series of sulfonyl-γ-AApeptide helices that targeted the crucial α-helix domain of Aβ13-26 and stabilized Aβ conformation to avoid forming the neurotoxic Aβ oligomeric β-sheets. Biophysical assays such as amyloid kinetics and TEM demonstrated that the Aβ oligomerization and fibrillation could be greatly prevented and even reversed in the presence of sulfonyl-γ-AApeptides in a sequence-specific and dose-dependent manner. The studies based on circular dichroism, Two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) spectra unambiguously suggested that the sulfonyl-γ-AApeptide Ab-6 could bind to the central region of Aβ42 and induce α-helix conformation in Aβ. Additionally, Electrospray ionisation-ion mobility spectrometry–mass spectrometry (ESI-IMS-MS) was employed to rule out a colloidal mechanism of inhibitor and clearly supported the capability of Ab-6 for inhibiting the formation of Aβ aggregated forms. Furthermore, Ab-6 could rescue neuroblastoma cells by eradicating Aβ-mediated cytotoxicity even in the presence of pre-formed Aβ aggregates. The confocal microscopy demonstrated that Ab-6 could still specifically bind Aβ42 and colocalize into mitochondria in the cellular environment, suggesting the rescue of cell viability might be due to the protection of mitochondrial function otherwise impaired by Aβ42 aggregation. Taken together, our studies indicated that sulfonyl-γ-AApeptides as helical peptidomimetics could direct Aβ into the off-pathway helical secondary structure, thereby preventing the formation of Aβ oligomerization, fibrillation and rescuing Aβ induced cell cytotoxicity. [ABSTRACT FROM AUTHOR]

Background: Chronic conditions and multimorbidity, the presence of two or more chronic conditions, are increasingly common in older adults. Effective management of chronic conditions and multimorbidity in older adults requires a collaborative and person‐centred approach that considers the individual's goals, preferences and priorities. However, ensuring high‐quality personalised care for older adults with multimorbidity can be challenging due to the complexity of their care needs, limited time and a lack of patient preparation to discuss their personal goals and preferences with their healthcare team. Objective: To codesign a communication and goal‐setting tool, My Wellbeing Journal, to support personalised care planning for older adults with chronic conditions and multimorbidity. Design: We drew on an experience‐based codesign approach to develop My Wellbeing Journal. This article reports on the final end‐user feedback, which was collected via an online survey with older adults and their carers. Setting and Participants: Older adults with chronic conditions, multimorbidity and informal carers living in Australia. Personalised care planning was considered in the context of primary care. Results: A total of 88 participants completed the online survey. The survey focused on participants' feedback on the tool in terms of effectiveness, efficiency, satisfaction and errors encountered. This feedback resulted in modifications to My Wellbeing Journal, which can be used during clinical encounters to facilitate communication, goal setting and progress tracking. Discussion and Conclusions: Clinicians and carers can use the tool to guide discussions with older adults about their care planning and help them set realistic goals that are meaningful to them. The findings of this study could be used to inform the development of recommendations for healthcare providers to implement person‐centred, goal‐oriented care for older adults with chronic conditions and multimorbidity. Patient or Public Contribution: Older adults living with chronic conditions and multimorbidity and their carers have contributed to the development of a tool that has the potential to significantly enhance the experience of personalised care planning. Their direct involvement as collaborators has ensured that the tool is optimised to meet the standards of effectiveness and usability. [ABSTRACT FROM AUTHOR]