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A new regional coupled modelling framework is introduced – the Regional Coupled Suite (RCS). This provides a flexible research capability with which to study the interactions between atmosphere, land, ocean, and wave processes resolved at kilometre scale, and the effect of environmental feedbacks on the evolution and impacts of multi-hazard weather events. A configuration of the RCS focussed on the Indian region, termed RCS-IND1, is introduced. RCS-IND1 includes a regional configuration of the Unified Model (UM) atmosphere, directly coupled to the JULES land surface model, on a grid with horizontal spacing of 4.4 km, enabling convection to be explicitly simulated. These are coupled through OASIS3-MCT libraries to 2.2 km grid NEMO ocean and WAVEWATCH III wave model configurations. To examine a potential approach to reduce computation cost and simplify ocean initialization, the RCS includes an alternative approach to couple the atmosphere to a lower resolution Multi-Column K-Profile Parameterization (KPP) for the ocean. Through development of a flexible modelling framework, a variety of fully and partially coupled experiments can be defined, along with traceable uncoupled simulations and options to use external input forcing in place of missing coupled components. This offers a wide scope to researchers designing sensitivity and case study assessments. Case study results are presented and assessed to demonstrate the application of RCS-IND1 to simulate two tropical cyclone cases which developed in the Bay of Bengal, namely Titli in October 2018 and Fani in April 2019. Results show realistic cyclone simulations, and that coupling can improve the cyclone track and produces more realistic intensification than uncoupled simulations for Titli but prevents sufficient intensification for Fani. Atmosphere-only UM regional simulations omit the influence of frictional heating on the boundary layer to prevent cyclone over-intensification. However, it is shown that this term can improve coupled simulations, enabling a more rigorous treatment of the near-surface energy budget to be represented. For these cases, a 1D mixed layer scheme shows similar first-order SST cooling and feedback on the cyclones to a 3D ocean. Nevertheless, the 3D ocean generally shows stronger localized cooling than the 1D ocean. Coupling with the waves has limited feedback on the atmosphere for these cases. Priorities for future model development are discussed.

Arsenic contamination of soils threatens the health of millions globally through accumulation in crops. While plants detoxify arsenic via phytochelatin (PC) complexation and efflux of arsenite from roots, arsenite efflux mechanisms are not fully understood. Here, white lupin (Lupinus albus) was grown in semi-hydroponics and exudation of glutathione (GSH) derivatives and PCs in response to arsenic was scrutinised using LC-MS/MS. Inhibiting synthesis of PC precursor GSH with L-buthionine sulfoximine (BSO) or ABC transporters with vanadate drastically reduced (>22%) GSH-derivative and PC2 exudation, but not PC3 exudation. This was accompanied by arsenic hypersensitivity in plants treated with BSO and moderate sensitivity with vanadate treatment. Investigating arsenic-phytochelatin (As-PC) complexation revealed two distinct As-PC complexes, As bound to GSH and PC2 (GS-As-PC2) and As bound to PC3 (As-PC3), in exudates of As-treated lupin. Vanadate inhibited As-PC exudation, while BSO inhibited both the synthesis and exudation of As-PC complexes. These results demonstrate a role of GSH-derivatives and PC exudation in lupin arsenic tolerance and reveal As-PC exudation as a new potential mechanism contributing to active arsenic efflux in plants. Overall, this study uncovers insight into rhizosphere arsenic detoxification with potential to help mitigate pollution and reduce arsenic accumulation in crops.

This paper describes the next-generation ocean forecast model for the European north-west shelf, which will become the basis of operational forecasts in 2018. This new system will provide a step change in resolution and therefore our ability to represent small-scale processes. The new model has a resolution of 1.5 km compared with a grid spacing of 7 km in the current operational system. AMM15 (Atlantic Margin Model, 1.5 km) is introduced as a new regional configuration of NEMO v3.6. Here we describe the technical details behind this configuration, with modifications appropriate for the new high-resolution domain. Results from a 30-year non-assimilative run using the AMM15 domain demonstrate the ability of this model to represent the mean state and variability of the region.Overall, there is an improvement in the representation of the mean state across the region, suggesting similar improvements may be seen in the future operational system. However, the reduction in seasonal bias is greater off-shelf than on-shelf. In the North Sea, biases are largely unchanged. Since there has been no change to the vertical resolution or parameterization schemes, performance improvements are not expected in regions where stratification is dominated by vertical processes rather than advection. This highlights the fact that increased horizontal resolution will not lead to domain-wide improvements. Further work is needed to target bias reduction across the north-west shelf region.

It is hypothesized that more accurate prediction and warning of natural hazards, such as of the impacts of severe weather mediated through various components of the environment, require a more integrated Earth System approach to forecasting. This hypothesis can be explored using regional coupled prediction systems, in which the known interactions and feedbacks between different physical and biogeochemical components of the environment across sky, sea and land can be simulated. Such systems are becoming increasingly common research tools. This paper describes the development of the UKC2 regional coupled research system, which has been delivered under the UK Environmental Prediction Prototype project. This provides the first implementation of an atmosphere–land–ocean–wave modelling system focussed on the United Kingdom and surrounding seas at km-scale resolution. The UKC2 coupled system incorporates models of the atmosphere (Met Office Unified Model), land surface with river routing (JULES), shelf-sea ocean (NEMO) and ocean waves (WAVEWATCH III). These components are coupled, via OASIS3-MCT libraries, at unprecedentedly high resolution across the UK within a north-western European regional domain. A research framework has been established to explore the representation of feedback processes in coupled and uncoupled modes, providing a new research tool for UK environmental science. This paper documents the technical design and implementation of UKC2, along with the associated evaluation framework. An analysis of new results comparing the output of the coupled UKC2 system with relevant forced control simulations for six contrasting case studies of 5-day duration is presented. Results demonstrate that performance can be achieved with the UKC2 system that is at least comparable to its component control simulations. For some cases, improvements in air temperature, sea surface temperature, wind speed, significant wave height and mean wave period highlight the potential benefits of coupling between environmental model components. Results also illustrate that the coupling itself is not sufficient to address all known model issues. Priorities for future development of the UK Environmental Prediction framework and component systems are discussed.

Abstract The ISS rodent habitat has provided crucial insights into the impact of spaceflight on mammals, inducing symptoms characteristic of liver disease, insulin resistance, osteopenia, and myopathy. Although these physiological responses can involve the microbiome on Earth, host-microbiota interactions during spaceflight are still being elucidated. We explore murine gut microbiota and host gene expression in the colon and liver after 29 and 56 days of spaceflight using multiomics. Metagenomics revealed significant changes in 44 microbiome species, including relative reductions in bile acid and butyrate metabolising bacteria like Extibacter muris and Dysosmobacter welbionis. Functional prediction indicate over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes. Host gene expression described corresponding changes to bile acid and energy metabolism, and immune suppression. These changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and that these interactions might critically influence human health and long-duration spaceflight feasibility.

Abstract Background Development of the cow-calf bond post-partum and passive immunity of calves from spring-calving beef × beef (B×B) and beef × dairy (B×D) cow genotypes was determined using primiparous and multiparous (Experiment 1), and primiparous and second-parity (Experiment 2) animals. In Experiment 1, calves either suckled colostrum naturally (‘natural-suckling’) (n = 126), or were fed colostrum, using an oesophageal-tube (‘artificially-fed’) (n = 26), from their dam within 1-h post-partum. In Experiment 2, all calves (n = 60) were artificially-fed colostrum from their dam. Prior to colostrum suckling/feeding, colostrum was sampled for IgG analysis. The cow-calf bond was assessed using CCTV recordings during the first 4-h post-partum. Calves were blood sampled at 48-h post-partum to determine IgG and total protein (TP) concentrations, and zinc sulphate turbidity (ZST) units. Results There was no difference (P > 0.05) in cow licking behaviours and calf standing and suckling behaviours between the genotypes, except in Experiment 2 where B×D calves had more attempts to suckle before suckling occurred (P ≤ 0.05) compared to B×B calves. In Experiment 1, multiparous cows licked their calves sooner (P ≤ 0.05) and for longer (P 0.05) between the genotypes in either Experiment. In Experiment 1, colostrum IgG concentrations were greater (P ≤ 0.05) in multiparous compared to primiparous cows and their calves had superior (P ≤ 0.05) passive immunity; no effect of parity was found in Experiment 2. Passive immunity did not differ (P > 0.05) between suckled and artificially-fed calves in Experiment 1. Conclusions Cow genotype had little effect on cow-calf behaviours, but under ‘natural-suckling’ conditions primiparous cows expressed maternal inexperience and their calves were less vigorous than multiparous cows. Colostrum IgG concentration and calf passive immunity measures were unaffected by genotype, but under ‘natural-suckling’ conditions calves from primiparous cows had lower passive immunity.

This informal presentation seeks to analyze the late Brinsley Samaroo’s major work as a historian. It discusses his pioneering research and writing on labour and political struggles in Trinidad & Tobago in the last century, and his involvement in research on the indentured Indian Diaspora in that country and in the Caribbean more generally. It also notes his work as a public intellectual and cultural activist.

BACKGROUND: Burnout among clinicians is common and can undermine quality of care, patient outcomes, and workforce preservation, but sources of burnout or protective factors unique to clinicians working in safety-net settings are less well understood. Understanding these clinician experiences may inform interventions to reduce burnout. OBJECTIVE: To describe clinician perspectives on sources of burnout in a safety-net healthcare system. DESIGN: Semi-structured interviews were conducted with clinicians from multiple disciplines who provided care at a safety-net healthcare system from October 2018 to January 2019. Transcripts were analyzed using thematic analysis. PARTICIPANTS: Forty clinicians (25 female and 15 male; mean [SD] age, 41 [9.1]) participated, including physicians, social workers, advanced practice providers, nurses, psychologists, physical and occupational therapists, and other healthcare professionals. MAIN OUTCOMES AND MEASURES: Themes and subthemes that reflected clinician experiences, burnout, and workload expectations. KEY RESULTS: Five themes emerged: limited resources (entrenched social injustices, brokenness of the US healthcare system, precarious discharge options, and revolving door readmissions), barriers to building trust with patients (chasm of communication, addressing fear and mistrust, and being exposed to threats), administrative requirements (criticism hampering meaningful care, assuming extra workloads, bureaucratic burden), compassion fatigue (confronting traumatic situations, persistent worry about patient safety and welfare, witnessing mistreatment and stigmatization, overextending and overinvesting, withdrawing and shutting down, blaming self and career crisis), and advocacy as a counterbalance to burnout (solidarity when helping underserved communities, fervent advocacy, and patient gratitude). CONCLUSIONS: Among clinicians who provide care in a safety-net healthcare system, sources of burnout included limited resources, barriers to building trust with patients, administrative requirements, and compassion fatigue, but clinicians remained driven by their desire to advocate for patients. Policy-level interventions which increase funding to safety-net healthcare systems to bolster existing resources and staffing, create peer-support and wellness programs, and support advocacy efforts may mitigate burnout.

Summary: Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model. Within the selected model, we then evaluate AB0023, identifying that it does not inhibit collagen cross-linking or reduce tissue stiffness, nor does it inhibit LOXL2 catalytic activity. In contrast, it does potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases.

Background: Young people with learning disabilities use many digital technologies to undertake meaningful and social activities in their everyday lives. Understanding these digital activities is essential for supporting their digital participation. Including them in exploring their digital activities can be challenging with conventional qualitative research methods, because digital activities are a complex and abstract topic to discuss, particularly for people with learning disabilities. In this paper, we present the rationale for developing and using visual tangible artefacts (VTAs) to include young people with learning disabilities in exploring their digital activities. Methods: We devised a suite of VTAs to engage young people (aged 14-27 years) with learning disabilities in exploring their digital activities via interviews, diaries, and workshops. The VTAs comprised Talking Mats (TMs), probing with technology, digital snapshots and inspiration cards. Findings: Our significant methodological findings were that VTAs are useful for exploring digital activities with young people with learning disabilities. TMs and probing with technology can engage participants to map, recall and explain their digital activities. Digital snapshots are valuable for validating findings with participants, and inspiration cards aid perspectives about digital aims. Although communication and abstract representations can be challenging for people with learning disabilities, VTAs that combine familiar, simple, intuitive, individualised, rewarding elements and collaboration with participants proved valuable for exploring their digital activities. Conclusion: We concluded that VTAs are inclusive tools for exploring the digital activities of and with young people with learning disabilities. The VTAs allowed access to conversations, information and insights that are not obtainable otherwise. As such, the VTAs may be regarded as a new model for inclusive research in the field of disability and technology studies.

Callimico (Callimico goeldii) are members of the callitrichid family, and a species of conservation concern managed within the European Association of Zoos and Aquaria (EAZA) ex situ program. They benefit from extensive ‘Best Practice’ guidelines developed by the Callitrichid Taxon Advisory Group (TAG), but there are gaps in species-specific knowledge and captive management research. A survey was created to understand and evaluate current housing and husbandry within EAZA collections holding callimico. The questionnaire allowed collation of details including enclosure size along with prevalence of mixed species exhibits, use of UV-B lighting, enclosure complexity and enrichment routines. Responding collections represented 44% of the current callimico holders, with the results allowing comparative analysis of current practice against the guidelines and considering previous research. Significant positive differences were discovered between minimum recommended enclosure dimensions, including total enclosure volume, 32 m3 (p < 0.001, median = 100) and height, 2.5 m (p < 0.001, median = 3) versus EAZA’s minimum recommended dimensions. Encouragingly, no significant difference in complexity was found between on and off exhibit housing, but the results suggest that being housed in a mixed species exhibit offers a more complex environment for callimico (W = 405.5, p < 0.005). The responses revealed overall good practice, although a disparity was noted in the provision of UV-B lighting and the prevalence of enrichment. Observational research focusing on spatial use, preference and behavior is recommended to complement husbandry guidelines. Reference of the survey findings to welfare indicators could determine the effect of current housing and husbandry on callimico welfare.

Abstract The article describes the revolutionary new ways of communicating the written word when moving from the Medieval to Modern period in Europe, primarily the use of paper and moveable typeface printing and how these catalysed important cultural developments. A similar revolution has taken place in the last 50 years with the development of the internet. The article looks at how scientific publishing has changed with electronic publishing, including the development of Open Access. The journal Heritage Science is placed into this context. Especially important for scientific journals in an era when anyone can post anything on a webpage, is maintaining standards through high quality refereeing which distinguishes formal scientific literature from informal websites.

The integration of Quality Management System (QMS) principles into the life cycle of development, deployment, and utilization of machine learning (ML) and artificial intelligence (AI) technologies within healthcare settings holds the potential to close the AI translation gap by establishing a robust framework that accelerates the safe, ethical, and effective delivery of AI/ML in day-to-day patient care. Healthcare organizations (HCOs) can implement these principles effectively by embracing an enterprise QMS analogous to those in regulated industries. By establishing a QMS explicitly tailored to health AI technologies, HCOs can comply with evolving regulations and minimize redundancy and rework while aligning their internal governance practices with their steadfast commitment to scientific rigor and medical excellence.

Namibia, a southern African country with an Ubuntu culture that emphasizes interrelations, generally displays a low reading culture. In this study, we explored a social approach to reading to engage Namibian primary learners. Inspired by promising reading approaches, such as shared group reading enhanced by embodied actions, we created Spin Da Bottle--a multiplayer reading-action game to draw Namibian learners into reading while keeping them captivated in action. The game was co-designed with 36 learners and then evaluated by 32 learners with an adapted immersion questionnaire, post-experience survey and individual interviews. 50 learners were then observed while playing at a public event. Our findings confirm that learners are engaged and enjoy the collective embodied reading experience. We observed different group behaviours scaffolding individual readers. We contribute to the field of reading technologies a digital tool that creates a collective and embodied reading experience, and an adapted immersion instrument.

OBJECTIVES/GOALS: Healthcare sectors are rushing to develop AI models. Yet, a dearth of coordinated practices leaves many teams struggling to implement models into practice. The Enterprise AI Translation Advisory Board uses across-disciplinary team to facilitate AI translation. METHODS/STUDY POPULATION: The Mayo Clinic Enterprise AI Translation Advisory Board was established to assess AI solutions lever aging cross-disciplinary team science to accelerate AI innovation and translation. The 23-member board reflects expertise in data science, qualitative research, user experience, IT, human factors, informatics, regulatory compliance,ethics, and clinical care, with members spanning thought leadership, decision-making, and clinical practice. Taking an approach of respectful communication, transparency, scientific debate, and open discussion, the Board has consulted onover two dozen projects at various stages of the AI life cycle. RESULTS/ANTICIPATED RESULTS: Common issues identified for projects earlier in the AI life cycle, sometimes fatal but often address able once identified, include a lack of buy-in from potential product users, a lack of planningabout integration into clinical workflow, inadequately labeled data, and attempting to use machine learning when what is desired is really a causal model for intervening. Recommendations for projects later in the AI life cycle include details of a testing plan (silent evaluation, pragmatic clinical trials), advice about clinical integration, both post-hoc and on going auditing for performance disparities, and planning for regulatory clearance. DISCUSSION/SIGNIFICANCE: Advising is more valuable for projects at the ideation phase, when multi disciplinary interrogation can identify weaknesses. But at all phases, projects have gaps related to a lack of specific disciplinary expertise. A multi disciplinary cluster like the AI Translation Advisory Board seeks to address these gaps.

The prevalence of multiple age-related cardiovascular disease (CVD) risk factors is high among individuals living in low- and middle-income countries. We described receipt of healthcare services for and management of hypertension and diabetes among individuals living with these conditions using individual-level data from 55 nationally representative population-based surveys (2009-2019) with measured blood pressure (BP) and diabetes biomarker. We restricted our analysis to non-pregnant individuals aged 40-69 years and defined three mutually exclusive groups (i.e., hypertension only, diabetes only, and both hypertension-diabetes) to compare individuals living with concurrent hypertension and diabetes to individuals with each condition separately. We included 90,086 individuals who lived with hypertension only, 11,975 with diabetes only, and 16,228 with hypertension-diabetes. We estimated the percentage of individuals who were aware of their diagnosis, used pharmacological therapy, or achieved appropriate hypertension and diabetes management. A greater percentage of individuals with hypertension-diabetes were fully diagnosed (64.1% [95% CI: 61.8-66.4]) than those with hypertension only (47.4% [45.3-49.6]) or diabetes only (46.7% [44.1-49.2]). Among the hypertension-diabetes group, pharmacological treatment was higher for individual conditions (38.3% [95% CI: 34.8-41.8] using antihypertensive and 42.3% [95% CI: 39.4-45.2] using glucose-lowering medications) than for both conditions jointly (24.6% [95% CI: 22.1-27.2]).The percentage of individuals achieving appropriate management was highest in the hypertension group (17.6% [16.4-18.8]), followed by diabetes (13.3% [10.7-15.8]) and hypertension-diabetes (6.6% [5.4-7.8]) groups. Although health systems in LMICs are reaching a larger share of individuals living with both hypertension and diabetes than those living with just one of these conditions, only seven percent achieved both BP and blood glucose treatment targets. Implementation of cost-effective population-level interventions that shift clinical care paradigm from disease-specific to comprehensive CVD care are urgently needed for all three groups, especially for those with multiple CVD risk factors.

Introduction Technology-facilitated, self-directed upper limb (UL) rehabilitation, as an adjunct to conventional care, could enhance poststroke UL recovery compared with conventional care alone, without imposing additional resource burden. The proposed pilot randomised controlled trial (RCT) aims to assess whether stroke survivors will engage in self-directed UL training, explore factors associated with intervention adherence and evaluate the study design for an RCT testing the efficacy of a self-directed exer-gaming intervention for UL recovery after stroke.Methods and analysis This is a multicentre, internal pilot RCT; parallel design, with nested qualitative methods. The sample will consist of stroke survivors with UL paresis, presenting within the previous 30 days. Participants randomised to the intervention group will be trained to use an exergaming device and will be supported to adopt this as part of their self-directed rehabilitation (ie, without formal support/supervision) for a 3-month period. The primary outcome will be the Fugl Meyer Upper Extremity Assessment (FM-UE) at 6 months poststroke. Secondary outcomes are the Action Research Arm Test (ARAT), the Barthel Index and the Modified Rankin Scale. Assessment time points will be prior to randomisation (0–1 month poststroke), 3 months and 6 months poststroke. A power calculation to inform sample size required for a definitive RCT will be conducted using FM-UE data from the sample across 0–6 months time points. Semistructured qualitative interviews will examine factors associated with intervention adoption. Reflexive thematic analysis will be used to code qualitative interview data and generate key themes associated with intervention adoption.Ethics and dissemination The study protocol (V.1.9) was granted ethical approval by the Health Research Authority, Health and Care Research Wales, and the London- Harrow Research Ethics Committee (ref. 21/LO/0054) on 19 May 2021. Trial results will be submitted for publication in peer-reviewed journals, presented at national and international stroke meetings and conferences and disseminated among stakeholder communities.Trial registration number NCT04475692

BackgroundPersonalized asthma management depends on a clinician’s ability to efficiently review patient’s data and make timely clinical decisions. Unfortunately, efficient and effective review of these data is impeded by the varied format, location, and workflow of data acquisition, storage, and processing in the electronic health record. While machine learning (ML) and clinical decision support tools are well-positioned as potential solutions, the translation of such frameworks requires that barriers to implementation be addressed in the formative research stages. ObjectiveWe aimed to use a structured user-centered design approach (double-diamond design framework) to (1) qualitatively explore clinicians’ experience with the current asthma management system, (2) identify user requirements to improve algorithm explainability and Asthma Guidance and Prediction System prototype, and (3) identify potential barriers to ML-based clinical decision support system use. MethodsAt the “discovery” phase, we first shadowed to understand the practice context. Then, semistructured interviews were conducted digitally with 14 clinicians who encountered pediatric asthma patients at 2 outpatient facilities. Participants were asked about their current difficulties in gathering information for patients with pediatric asthma, their expectations of ideal workflows and tools, and suggestions on user-centered interfaces and features. At the “define” phase, a synthesis analysis was conducted to converge key results from interviewees’ insights into themes, eventually forming critical “how might we” research questions to guide model development and implementation. ResultsWe identified user requirements and potential barriers associated with three overarching themes: (1) usability and workflow aspects of the ML system, (2) user expectations and algorithm explainability, and (3) barriers to implementation in context. Even though the responsibilities and workflows vary among different roles, the core asthma-related information and functions they requested were highly cohesive, which allows for a shared information view of the tool. Clinicians hope to perceive the usability of the model with the ability to note patients’ high risks and take proactive actions to manage asthma efficiently and effectively. For optimal ML algorithm explainability, requirements included documentation to support the validity of algorithm development and output logic, and a request for increased transparency to build trust and validate how the algorithm arrived at the decision. Acceptability, adoption, and sustainability of the asthma management tool are implementation outcomes that are reliant on the proper design and training as suggested by participants. ConclusionsAs part of our comprehensive informatics-based process centered on clinical usability, we approach the problem using a theoretical framework grounded in user experience research leveraging semistructured interviews. Our focus on meeting the needs of the practice with ML technology is emphasized by a user-centered approach to clinician engagement through upstream technology design.