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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.

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.

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.

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.

The next generation of space-based networks for communications, sensing, and navigation will contain optical clocks embedded within satellites. To fully realize the capabilities of such clocks, high-precision clock synchronization across the networks will be necessary. Current experiments have shown the potential for classical frequency combs to synchronize remote optical clocks over free space. However, these classical combs are restricted in precision to the standard quantum limit. Quantum frequency combs, however, which exhibit quantum properties such as squeezing and entanglement, provide pathways for going beyond the standard quantum limit. Here, we present our perspective on the prospects for practical clock synchronization in space using both classical and quantum frequency combs. We detail the current outcomes achievable with a classical frequency comb approach to synchronization, before quantifying the potential outcomes offered by quantum frequency combs. Challenges to be overcome in deploying frequency combs in space are presented, and the implications of almost-perfect synchronization for future space-based applications and experiments are discussed.

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.

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.

Abstract This study investigates the effects of including patients’ clinical information on the performance of deep learning (DL) classifiers for disease location in chest X-ray images. Although current classifiers achieve high performance using chest X-ray images alone, consultations with practicing radiologists indicate that clinical data is highly informative and essential for interpreting medical images and making proper diagnoses. In this work, we propose a novel architecture consisting of two fusion methods that enable the model to simultaneously process patients’ clinical data (structured data) and chest X-rays (image data). Since these data modalities are in different dimensional spaces, we propose a spatial arrangement strategy, spatialization, to facilitate the multimodal learning process in a Mask R-CNN model. We performed an extensive experimental evaluation using MIMIC-Eye, a dataset comprising different modalities: MIMIC-CXR (chest X-ray images), MIMIC IV-ED (patients’ clinical data), and REFLACX (annotations of disease locations in chest X-rays). Results show that incorporating patients’ clinical data in a DL model together with the proposed fusion methods improves the disease localization in chest X-rays by 12% in terms of Average Precision compared to a standard Mask R-CNN using chest X-rays alone. Further ablation studies also emphasize the importance of multimodal DL architectures and the incorporation of patients’ clinical data in disease localization. In the interest of fostering scientific reproducibility, the architecture proposed within this investigation has been made publicly accessible( https://github.com/ChihchengHsieh/multimodal-abnormalities-detection ).

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.

Current food production and consumption practices are impacting both human and planetary health. Though these challenges are multifaceted, shifting to healthy dietary choices from sustainable food systems is one solution. Food-based labelling is a common public-health strategy aimed at influencing consumption practices, primarily displaying front-of-pack nutrition labelling to encourage healthier choices. Due to the dual impact of food on human and planetary health there is a growing need to additionally include environmental impact information. However, this potentially conflicting information could overwhelm consumers, necessitating a simplified approach that combines both nutritive and environmental values. Previous work has identified existing models, termed sustainable food profiling models, for labelling of individual food products based on their environmental impacts and nutritive value. Foods are rarely eaten in isolation and are often consumed as composite meals, which aggregate to diets. Therefore, it is important to identify indices that exist to assess or rank meals and diets according to their nutritional and environmental impacts. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 01 May 2024 (PROSPERO registration ID = CRD42024537149). In the present protocol the methodology to identify and review existing food-based indices for the assessment of nutritive value and environmental impact of meals and diets and their intended public health purpose is described. Our primary research questions are: (i) what food-based indices assessing nutritive value and environmental impact exist for classification or ranking of meals or diets? and (ii) what are the methods used to create, and the key characteristics of, these indices?. The results are expected to increase understanding of, and highlight the variation in, the creation of combined measures for the assessment of nutritive value and environmental impact for meals and diets. Additionally, findings can be used to inform researchers, business, and policy actors on future approaches for labelling foods, meals, or diets in a way that supports healthy and sustainable meal choices and diets.

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.

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

Land restoration requires innovative approaches to prevent ongoing degradation and increase the functionality of land use. While land restoration has been studied extensively from the perspective of ecologists and local communities it is a topic that remains at the periphery of the financial economics literature, despite the global financial system’s centrality to the problem. This paper reviews the literature on financial instruments that are designed for land-based ecological restoration, extracts key learnings from this literature and deploys a functional perspective to better understand how financial instruments that aim to scale up land restoration activities can be mainstreamed within the global financial system. This paper presents a framework that promotes public channels to best direct public and private capital towards land restoration projects. Matching the supply of capital with a pipeline of spatially explicit and sometimes unique restoration solutions requires an architecture that can implement this coordination and aggregation function. This has the potential to mitigate transaction costs and improve transparency issues associated with monitoring and reporting. This framework is illustrated for an actual land restoration program underway in Europe.

Background: The use of regional anesthesia in shoulder arthroscopy improves perioperative pain control, thereby reducing the need for opioids and their recognized side effects. Occasionally one type of block is not suitable for a patient’s anatomy or comorbidities or requires a specially trained anesthetist to safely perform. The primary aim of this study is to compare the efficacy of 3 different nerve blocks for pain management in patients undergoing shoulder arthroscopy. Methods: A 3-arm, blinded, randomized controlled trial in patients undergoing elective, unilateral shoulder arthroscopic procedures between August 2018 and November 2020 was conducted at a single center. One hundred and thirty participants were randomized into 1 of 3 regional anesthesia techniques. The first group received an ultrasound-guided interscalene block performed by an anesthetist (US + ISB). The second group received an ultrasound-guided suprascapular nerve block and an axillary nerve block by an anesthetist (US + SSANB). The final group received a suprascapular nerve block without ultrasound and an axillary nerve block under arthroscopic guidance by an orthopedic surgeon (A + SSANB). Intraoperative pain response, analgesia requirements, and side effects were recorded. Visual analogue pain scores and opioid doses were recorded in the Post Anaesthesia Care Unit (PACU) and daily for 8 days following the procedure. Results: Twelve patients withdrew from the study after randomization, leaving 39 participants in US + ISB, 40 in US + SSANB, and 39 in A + SSANB. The US + ISB group required significantly lower intraoperative opioid doses than US + SSANB and A + SSANB (P