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This study describes the process of co-developing an operational climate forecast service for the viticulture sector. Weather and climate conditions affect grapevine development in cultivars: anticipating the atmospheric variables in the coming weeks and months is thus relevant for effectively managing vineyards, as impacts will be felt in wine production, biodiversity, and a wide range of related aspects. The operational service was co-developed with two types of users: impact modellers, who are the intermediary users incorporating climate forecast outputs in phenological and disease models, and end-users from the wine sector with vineyards in various European locations. For the operational service, sub-seasonal and seasonal climate forecasts were tailored considering their needs. The initial steps of the co-production process identified relevant decisions for which the service was essential and co-defined effective ways to deliver the climate information. Afterwards the climate forecasts outputs were integrated with impact model data. Substantial efforts were directed at the harmonisation of climate services information with the decision-making system of end-users. Because end-users need to navigate, comprehend, and select from various alternative options amidst uncertainty, significant emphasis has been placed on crafting the visual representation of the climate service, incorporating interactive elements, and cognitive considerations, thereby enhancing the overall user experience. Practical implications: Weather and climate conditions affect the development of cultivars: phenological stages, disease risk, or wine quality. This study presents the co-production process for deploying a climate service for vineyard management. The service consists of the near-real-time operational provision of sub-seasonal and seasonal climate forecasts. This service aims to help vineyard managers make decisions by anticipating the climate conditions up to three months in advance for a set of essential climate variables. The service includes the requirements of a set of intermediary users, which are disease risk and phenology researchers who feed their impact models with the provided climate forecasts. To our knowledge, it is the first time that sub-seasonal and seasonal climate forecasts have been integrated into an operational service for vineyard management.The service was developed during the VitiGEOSS project, the primary outcome of which is the VitiGEOSS platform: a single entry-point solution for wine producers aiming to boost vineyard sustainability. Three pilot plots are used for the service development: the Douro region in Portugal, the Catalonia region in Spain, and the Campania region in Italy. The co-production is seen as an iterative, interactive and collaborative process that brings together a plurality of knowledge sources to mutually define problems and develop usable products to address these problems. The process can be divided into three phases: initial co-exploration, co-design and co-development.The co-exploration phase consisted of conducting a benchmark analysis, identifying available services to viticulture and highlighting the gap that the newly developed solution could fill in. In the co-design phase, more intense engagement methods were implemented to communicate the capabilities of climate forecasts and design the product’s visualisation. Finally, the co-evaluation consisted of an ad hoc and ongoing process during the recurring meetings and a final workshop conducted with direct and potential users to obtain feedback on using the platform and potential further developments.As a result, the operational post-processing workflow of the sub-seasonal and seasonal state-of-the-art model outputs was adapted to include users’ requirements. The workflow includes the downscaling of model outputs to increase their spatial resolution, the storage of sub-seasonal climate forecasts at daily frequencies to feed phenological impact models, the provision of past climate simulations to train the impact models, the bias-adjust of climate forecasts to reduce systematic model errors, the assessment of the climate forecasts to aware users on their quality and the deployment of a server to allow access to impact modellers.The variables provided are mean, minimum and maximum temperature, accumulated precipitation and solar radiation. The final co-designed product consists of a graphic of bars. The user can select the location and variable, and the forecasts for the next four weeks or the next three months are displayed for the sub-seasonal and seasonal climate forecasts, respectively. For each week or month, three bars show the tercile probabilities of above-normal, normal or below-normal conditions for the time of the year. The limits of the tercile categories are also displayed, which helps to understand the averaged values of the variable in the selected region and the time of the year calculated with information from the past. The probabilities of extremes, i.e. exceeding (non-exceeding) the percentile 90th (10th), are displayed as extra bars for each week and month in case the prediction is skilful and they are greater than 40%.Last but not least, the results of the skill assessment are shown. This skill assessment consists of calculating a metric for each location, initialisation date and forecast time. When this metric, known as skill score, is positive (negative), the climate model forecast is better (worse) than the climatology (the climatology is a naive forecast which considers all categories equiprobable by definition). If the skill is negative, which means there is no proof of the added value of using the numerical model prediction, the bars are blurred, and the user can still be informed of the tercile category limits.The service has been provided for almost two consecutive years. During this period, we have confirmed the value of some key recommendations from literature when co-producing a climate service. Especially relevant is the need to invest time and resources to conduct a good co-production process by repeating the iterative process. We also tested the idea of providing information in the format of seasonal climate forecast outlooks to end-users before the service was operational. In this way, the climate service process would be ‘slowed down’, by which the use of climate data is incorporated more slowly and allows for place-based knowledge from the resource managers to be included too.One of the most challenging questions is the communication of the probabilistic forecasts product and their quality. The probabilistic nature of climate forecasts is sometimes understood by novice users as the incapacity to provide a deterministic forecast. Similarly, negative skill leads users to interpret the forecast fails. Overall, the perception of the service quality can be low. To avoid this perception, the co-producing process is essential to engage with users and redefine the service if possible.In this work, we have tried different ways to overcome low-quality perception. The users requested access to the climate forecasts for their vineyard plots. For that reason, the downscaling technique was applied to increase the spatial resolution, and the bar plots were designed to show the forecast for a specific location. However, to improve the perception of the forecast quality, the forecast can be contextualised by providing the forecast in the format of a map of the surrounding areas.Despite all these limitations, end-users reported on the extreme importance of climate information. Furthermore, end-users can benefit from getting the climate services integrated with the impact models to take maximum advantage of all services and make timely decisions, but also receiving this information in a clear, parsimonious and direct format that is intuitive and can be easily incorporated into the decision-making processes is key for the sustainability of their farm fields.After the operational provision of the climate forecast service, some implications of our findings have been detected: ● Combined downscaling and contextualisation. Downscaling techniques help to provide more accurate information at the location scale. Nevertheless, the spatial visualization over large regions may help to contextualize the climate forecasts, and that is also beneficial for end-user interpretation of the climate-related information. ● Skill. Efforts to provide more skilful climate forecasts are required, as well as alternative information to be used in situations where skill is lacking (e.g.: past climate information). The skill assessment is crucial to inform users about forecast reliability and accuracy. It enhances user understanding and trust in the service by generating realistic expectations. ● Operationalisation. Reducing the time for data processing or increasing the computational resources will allow the provision of climate forecasts that are closer to the date of production. Users will benefit from earlier access to the information than the current time-lapse. ● Co-production. The co-production process ensures the service is designed based on user needs and feedback which is more likely to be adopted and effectively utilized by users. This process never ends, so, it needs to be applied if future developments or requests are included in the current service. ● Support for sustainability. End-users benefit from the integration of the climate forecast along with phenological and disease risk services. Further explorations to include more climate variables in the service and in the impact models will be beneficial for end-users. For instance, the probabilities of extreme events help vineyard managers prepare for potential adverse conditions, while, safeguarding vineyards against weather impacts through proactive measures. ● Capacity building. By training users about the nature of climate forecasts, they can enhance the preparedness and resilience response to varying climate conditions. New information and products could be co-explored to co-evaluate their utility and usefulness.

Mounier-Kuhn syndrome is a rare airway disease characterized by tracheal and bronchial dilatation, primarily affecting middle-aged men. We present a case of Mounier-Kuhn syndrome in a 40-year-old man with a history of recurrent respiratory infections since adolescence. The diagnostic journey involved a multidisciplinary approach incorporating clinical evaluation, radiological imaging, and bronchoscopy. Computed tomography findings, including maximum intensity projection reconstructions and 3D rendering, facilitated the diagnosis by revealing significant airway dilation and associated abnormalities. Treatment primarily focused on supportive measures, including antibiotic therapy and respiratory physiotherapy.This case underscores the importance of considering Mounier-Kuhn syndrome in patients with recurrent respiratory infections and highlights the role of advanced imaging techniques in diagnosis.

Abstract Introduction Accurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate – leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports. Methods Radiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone. Results The dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing. Conclusion ClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE.

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As ASEAN countries, including Vietnam, approach the living standards of developed countries, their copper demand is set to rise. This study investigates Vietnam’s copper stock and flow from 1995 to 2050, employing dynamic material flow analysis and five socioeconomic pathway scenarios (SSPs). Based on this, the secondary copper reserves of Vietnam were assessed. The results showed that the domestic copper demand is expected to grow to 526–1062 kt, resulting in a rapid increase in scrap generation. In 2022, Vietnam’s secondary copper reserves stood at 2.2 Mt and are projected to reach 6.8–8.6 Mt by 2050 under the SSP2 scenario. This corresponds to 3.6–4.6 times the 1.8 Mt primary copper reserve of Vietnam. However, these primary and secondary reserves cannot meet the cumulated demand by 2050. On the other hand, a large amount of copper, 8.9 Mt to 10 Mt, will become difficult-to-recover resources, such as waste in landfill sites, dissipated materials, or mixed metal loss. To promote the sustainable use of copper in Vietnam, we recommend increased geological expedition and mining investment, and improved waste management systems related to secondary resources.

The articulation of time-space dimensions is a theme both for theorists of various disciplines and for those who deal with the problems of the exegesis of texts. The globalization process makes us perceive a hybrid present and permeable spaces, both with cultural consequences in relation to the process of attribution of meaning. This is the very broad outline in which I read the texts of D. Greig presented here, texts that, in the crisis of traditional historicism, address the theme in an unusual way: the relationship between history and memory has changed the nature of historical writing, accentuating the function of cultural memory (mnemo-history), with individual and collective past inevitably as its objects.

Introduction: As the COVID-19 pandemic has demonstrated, the complexity of factors involved in the emergence of health threats requires a holistic One Health (OH) approach to enhance the effectiveness of prevention, preparedness, and response (PPR) strategies. Therefore, we conducted a scoping review to explore how the OH approach has been adopted in the context of PPR strategies to health threats, and the challenges and benefits deriving from its integration. Methods: We defined the research questions and a strategy to guide the peer-reviewed and grey literature search to identify relevant articles and documents (identification). We assessed them for eligibility according to predefined criteria (screening) and finally included the ones that answered the research questions (inclusion). We performed a descriptive and thematic analysis of the results. Results: A total of 138 records were included in the review (57 from the peer-reviewed literature and 81 from the grey literature). The OH approach was mainly adopted in prevention strategies, particularly within the governance area. Human and animal health were the most integrated disciplines in the OH approach, while environmental and social sciences were the less integrated. The most targeted threats were antimicrobial resistance and zoonoses, with the African region being the most represented. Conducive factors for the adoption of OH PPR strategies were identified in resolutions and guidance emanating from international organisations. Discussion: The global governance of OH should utilise conducive factors, such as international resolutions and guidance, to enhance the adoption of multisectoral and multi-actor PPR strategies, that focus on national and international priorities and neglected threats, such as environmental hazards and pandemic risk. Integrated frameworks and metrics for the implementation and evaluation of OH PPR strategies need to be consolidated to contribute to the growing body of evidence supporting the adoption of the OH approach.

Due to several factors, such as environmental and climate changes, the risk of health threats originating at the human–animal–environment interface, including vector-borne diseases (VBDs) and zoonoses, is increasing. Low-resource settings struggle to counter these multidimensional risks due to their already-strained health systems and are therefore disproportionally affected by the impact caused by these changes. Systemic approaches like One Health (OH) are sought to strengthen prevention and preparedness strategies by addressing the drivers of potential threats with a multidisciplinary and multisectoral approach, considering the whole system at the human–animal–environment interface. The integration of OH in national plans can be challenging due to the lack of effective coordination and collaboration among different sectors. To support the process of knowledge coproduction about the level of OH integration in prevention and preparedness strategies against health threats in Armenia, a situation analysis was performed on Crimean–Congo hemorrhagic fever/virus and anthrax (identified by local stakeholders as priorities to be addressed with the OH approach), and actions to strengthen the national OH system were identified with the support of a OH conceptual framework. The study highlighted that multidisciplinary and multisectoral efforts towards prevention and preparedness against VBDs and zoonoses threats need to be strengthened in Armenia, and priority actions to integrate the OH approach were identified.

Omecamtiv mecarbil (OM) is a small molecule that has been shown to improve the function of the slow human ventricular myosin (MyHC) motor through a complex perturbation of the thin/thick filament regulatory state of the sarcomere mediated by binding to myosin allosteric sites coupled to inorganic phosphate (Pi) release. Here, myofibrils from samples of human left ventricle (β-slow MyHC-7) and left atrium (α-fast MyHC-6) from healthy donors were used to study the differential effects of μmolar [OM] on isometric force in relaxing conditions (pCa 9.0) and at maximal (pCa 4.5) or half-maximal (pCa 5.75) calcium activation, both under control conditions (15 °C; equimolar DMSO; contaminant inorganic phosphate [Pi] ~170 μM) and in the presence of 5 mM [Pi]. The activation state and OM concentration within the contractile lattice were rapidly altered by fast solution switching, demonstrating that the effect of OM was rapid and fully reversible with dose-dependent and myosin isoform-dependent features. In MyHC-7 ventricular myofibrils, OM increased submaximal and maximal Ca2+-activated isometric force with a complex dose-dependent effect peaking (40% increase) at 0.5 μM, whereas in MyHC-6 atrial myofibrils, it had no effect or—at concentrations above 5 µM—decreased the maximum Ca2+-activated force. In both ventricular and atrial myofibrils, OM strongly depressed the kinetics of force development and relaxation up to 90% at 10 μM [OM] and reduced the inhibition of force by inorganic phosphate. Interestingly, in the ventricle, but not in the atrium, OM induced a large dose-dependent Ca2+-independent force development and an increase in basal ATPase that were abolished by the presence of millimolar inorganic phosphate, consistent with the hypothesis that the widely reported Ca2+-sensitising effect of OM may be coupled to a change in the state of the thick filaments that resembles the on–off regulation of thin filaments by Ca2+. The complexity of this scenario may help to understand the disappointing results of clinical trials testing OM as inotropic support in systolic heart failure compared with currently available inotropic drugs that alter the calcium signalling cascade. [ABSTRACT FROM AUTHOR]

ABSTRACT P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findings and discovered a role for intestinal HNF4α in P-gp regulation. These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp expression and highlight unappreciated connections between multiple pathways linked to colonic health. IMPORTANCE Preventing aberrant inflammation is essential to maintaining homeostasis in the mammalian intestine. Although P-glycoprotein (P-gp) expression in the intestine is critical for protecting the intestinal epithelium from toxins and damage due to neutrophil infiltration, its regulation in the intestine is poorly understood. Findings presented in our current study have now uncovered a sophisticated and heretofore unappreciated intracellular signaling network or “reactome” directed by intestinal microbial metabolites that orchestrate regulation of P-gp. Not only do we confirm the role of histone deacetylases (HDAC) inhibition and nuclear receptor activation in P-gp induction by butyrate and bile acids, but we also discovered new signaling pathways and transcription factors that are uniquely activated in response to the combination of microbial metabolites. Such findings shed new light into a multi-tiered network that maintains P-gp expression in the intestine in the context of the fluctuating commensal microbiome, to sustain a homeostatic tone in the absence of infection or insult.