The rheology of interactions between leukocytes, platelets and the vessel wall in thrombo-inflammation.

Leukocytes and platelets must adhere to the wall of blood vessels to carry out their protective functions in inflammation and haemostasis. Recruitment is critically dependent on rheological variables (wall shear rate and stress, red cell aggregation and haematocrit) which affect delivery to the vessel wall as well as velocities and forces experienced there. Leukocyte recruitment is efficient only up to wall shear rates of about 300 s-1 and usually restricted to low-shear post-capillary venules in inflammation. Being smaller, platelets experience lower velocities and shear forces adjacent to the wall and can adhere at much higher shear rates for haemostasis in arteries. In addition, we found quite different effects of variations in haematocrit or red cell aggregation on attachment of neutrophils or platelets, which also assist their separate recruitment in venules or arteries. However, it has become increasingly evident that inflammatory and thrombotic responses may occur together, with platelets promoting the adhesion and activation of neutrophils and monocytes. Indeed, it is 30 years since we demonstrated that platelets could cause neutrophils to aggregate in suspension and, when attached to a surface, could support selectin-mediated rolling of all leukocytes. Thrombin-activated platelets could further induce neutrophil activation and immobilisation. In some conditions, platelets could bind to intact endothelial monolayers and capture neutrophils or monocytes. Subsequently, we found that extracellular vesicles released by activated platelets (PEV) fulfilled similar functions when deposited on surfaces or bound to endothelial cells. In murine models, platelets or PEV could act as bridges for monocytes in inflamed vessels. Thus, leukocytes and platelets are rheologically adapted for their separate functions, while novel thrombo-inflammatory pathways using platelets or PEV may underlie pathogenic leukocyte recruitment.

Using process-oriented model output to enhance machine learning-based soil organic carbon prediction in space and time.

Monitoring and modelling soil organic carbon (SOC) in space and time can help us to better understand soil carbon dynamics and is of key importance to support climate change research and policy. Although machine learning (ML) has attracted a lot of attention in the digital soil mapping (DSM) community for its powerful ability to learn from data and predict soil properties, such as SOC, it is better at capturing soil spatial variation than soil temporal dynamics. By contrast, process-oriented (PO) models benefit from mechanistic knowledge to express physiochemical and biological processes that govern SOC temporal changes. Therefore, integrating PO and ML models seems a promising means to represent physically plausible SOC dynamics while retaining the spatial prediction accuracy of ML models. In this study, a hybrid modelling framework was developed and tested for predicting topsoil SOC stock in space and time for a regional cropland area located in eastern China. In essence, the hybrid model uses predictions of the PO model in unsampled years as additional training data of the ML model, with a weighting parameter assigned to balance the importance of SOC values from the PO model and real measurements. The results indicated that temporal trends of SOC stock modelled by PO and ML models were largely different, while they were notably similar between the PO and hybrid models. Cross-validation showed that the hybrid model had the best performance (RMSE = 0.29 kg m-2), with a 19 % improvement compared with the ML model. We conclude that the proposed hybrid framework not only enhances space-time soil carbon mapping in terms of prediction accuracy and physical plausibility, it also provides insights for soil management and policy decisions in the face of future climate change and intensified human activities.

Optimizing the detection of emerging infections using mobility-based spatial sampling.

Background: Timely and precise detection of emerging infections is crucial for effective outbreak management and disease control. Human mobility significantly influences infection risks and transmission dynamics, and spatial sampling is a valuable tool for pinpointing potential infections in specific areas. This study explored spatial sampling methods, informed by various mobility patterns, to optimize the allocation of testing resources for detecting emerging infections. Methods: Mobility patterns, derived from clustering point-of-interest data and travel data, were integrated into four spatial sampling approaches to detect emerging infections at the community level. To evaluate the effectiveness of the proposed mobility-based spatial sampling, we conducted analyses using actual and simulated outbreaks under different scenarios of transmissibility, intervention timing, and population density in cities. Results: By leveraging inter-community movement data and initial case locations, the proposed case flow intensity (CFI) and case transmission intensity (CTI)-informed sampling approaches could considerably reduce the number of tests required for both actual and simulated outbreaks. Nonetheless, the prompt use of CFI and CTI within communities is imperative for effective detection, particularly for highly contagious infections in densely populated areas. Conclusions: The mobility-based spatial sampling approach can substantially improve the efficiency of community-level testing for detecting emerging infections. It achieves this by reducing the number of individuals screened while maintaining a high accuracy rate of infection identification. It represents a cost-effective solution to optimize the deployment of testing resources, when necessary, to contain emerging infectious diseases in diverse settings.

Identification of the first homozygous intragenic deletion in the YY1AP1 gene in a consanguineous family: New insights into the phenotypic variability associated with Grange syndrome.

Grange syndrome (GRNG-MIM#135580) is a rare recessive disorder associating variable features including diffuse vascular stenosis, brachysyndactyly, osteopenia with increased bone fragility, cardiac malformations, and variable developmental delay. Since its first description in 1998, only 15 individuals from 10 families have been reported, carrying homozygous or compound heterozygous frameshift or nonsense variants in YY1AP1. In a patient with cutaneous and bone syndactyly and a hemorrhagic stroke at the age of 16 months, consistent with a clinical diagnosis of GRNG, we performed exome sequencing after negative array-CGH and congenital limb malformation panel results. Copy number variant analysis from exome data identified a homozygous intragenic out-of-frame deletion of 1.84 kb encompassing exons seven and eight of YY1AP1, confirming a molecular diagnosis of GRNG. Genetic counseling led to the identification of additional family members compatible with GRNG. Here, we provide new insights into the phenotypic variability associated with GRNG and highlight the utility of the detection of small copy number variants to identify the molecular causes of heterogeneous malformative genetic disorders.

Neutralizing RGMa with Elezanumab Promotes Cerebroprotection and Recovery in Rabbit Middle Cerebral Artery Occlusion.

Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity in several preclinical models of neurodegeneration and injury including multiple sclerosis, AIS, and SCI. Given the limitations of current treatments for AIS due to narrow time windows to intervention (TTI), and restrictive patient selection criteria, there is significant unmet need for therapeutic agents that enable tissue survival and repair following acute ischemic damage for a broader population of stroke patients. In this preclinical study, we evaluated whether elezanumab, a human anti-RGMa monoclonal antibody, could improve neuromotor function and modulate neuroinflammatory cell activation following AIS with delayed intervention times up to 24 h using a rabbit embolic permanent middle cerebral artery occlusion model (pMCAO). In two replicate 28-day pMCAO studies, weekly intravenous infusions of elezanumab, over a range of doses and TTIs of 6 and 24 h after stroke, significantly improved neuromotor function in both pMCAO studies when first administered 6 h after stroke. All elezanumab treatment groups, including the 24 h TTI group, had significantly less neuroinflammation as assessed by microglial and astrocyte activation. The novel mechanism of action and potential for expanding TTI in human AIS make elezanumab distinct from current acute reperfusion therapies, and support evaluation in clinical trials of acute CNS damage to determine optimal dose and TTI in humans. A: Ramified/resting astrocytes and microglia in a normal, uninjured rabbit brain. B: Rabbit pMCAO brain illustrating lesion on right side of brain (red), surrounded by penumbra (pink) during acute phase post stroke, with minimal injury to left brain hemisphere. Penumbra characterized by activated astrocytes and microglia (region in crosshair within circle), with upregulation of free and bound RGMa. C: Elezanumab binds to both free and bound RGMa, preventing full activation of astrocytes and microglia. D: Elezanumab is efficacious in rabbit pMCAO with a 4 × larger TTI window vs. tPA (6 vs. 1.5 h, respectively). In human AIS, tPA is approved for a TTI of 3-4.5 h. Elezanumab is currently being evaluated in a clinical Ph2 study of AIS to determine the optimal dose and TTI (NCT04309474).

Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

BACKGROUND: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers. METHODS: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed. RESULTS: The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID. CONCLUSION: This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.

Strengthening Biorisk Management Capacities in Burkina Faso: Contribution of the Global Health Security Agenda.

The Global Health Security Agenda and the International Health Regulations (2005) recommend that countries strengthen the capacity of their national laboratory systems to comply with the International Health Regulations. To efficiently and effectively direct these efforts, the US Centers for Disease Control and Prevention-in collaboration with the Ministry of Health Directorate of Laboratories, the African Society for Laboratory Medicine, and Integrated Quality Laboratory Service-assessed Burkina Faso's national laboratory system using the World Health Organization Laboratory Assessment Tool. Based on gaps observed in biorisk management, the Biosafety and Biosecurity Laboratory Assessment Tool (BSS LAT) was developed to assess 10 public laboratories handling dangerous pathogens. This tool uses a specific scoring matrix with quantitative output. Composite assessment scores for the 9 primary modules (capacity areas) were reported, with the highest scores reported in cleaning, disinfection, sterilization, waste management (42%), and good laboratory practices (40%), and the lowest scores in biosecurity/biosafety (33%), documents/regulations (18%), emergency management (16%), and risk management (5%). To address challenges identified in the assessments, a set of activities was planned with a focus on biorisk management. Results from an evaluation conducted 1 year later, using the BSS LAT, showed an increase in the average score of all indicators from 25% to 45% and an increase in the biorisk management module score from 5% to 35%. This evaluation process was a decisive step toward strengthening the capacity of the laboratory system in Burkina Faso. Global Health Security Agenda investments and activities have made a lasting impact on improving biosafety and biosecurity in public health laboratories. To ensure sustainability, a strong laboratory quality management program based on a mentorship system is greatly needed.

High-responsivity operation of quantum cascade detectors at 9 µm.

Quantum cascade detectors (QCDs) are devices operating at zero external bias with a low dark-current. They show linear detection and high saturation intensities, making them suitable candidates for heterodyne detection in long-wave infrared (LWIR) free space optical communication systems. We present an approach to mitigate the performance limitation at long wavelengths, by a comparison of similar single and multi-period QCDs for optimizing their responsivity and noise behaviour. Our InGaAs/InAlAs/InP ridge QCDs are designed for operation at λ = 9.124 µm. Optical waveguide simulations support the accurate optical characterization. A detailed device analysis reveals room-temperature responsivities of 111 mA/W for the 15-period and 411 mA/W for the single-period device.

Roles of temporal proximity between sound edges in the perceptual organization of veridical and illusory auditory events.

The gap transfer illusion is an auditory illusion in which a temporal gap in a long glide is perceived as if it had transferred to a physically continuous shorter glide. The illusion typically occurs when the long and the shorter glide cross each other at their temporal midpoints, where the long glide is physically divided by the gap. The occurrence of the gap transfer illusion was investigated in stimuli in which the duration and the slope of the long glide were 5000 ms and ∼0.8 oct/s. The shorter glide was given different frequency ranges and different temporal ranges, and thus its time-frequency slope was also varied. The overlap configuration of these crossing glides was varied as well. As control stimuli, we used stimuli in which a continuous long glide crossed a shorter glide with a gap, i.e., the opposite configuration of the gap-transfer stimuli as above, as well as stimuli in which both crossing glides were continuous. The perception of two crossing tones tended to be facilitated when the glides differed in duration and/or slope. When the glides were relatively similar in duration and slope, however, bouncing percepts appeared more often. Similarity between the crossing tones thus promoted auditory bouncing, while dissimilarity between them facilitated the crossing percept. If the crossing percept dominated in gap-transfer stimuli, the gap transfer illusion took place in a typical manner, but the illusory transfer of the gap could occur even when the crossing percept was not dominant. When the shorter glide was as short as 500 ms, the crossing percept and the gap transfer illusion were robust. The mechanism of the illusion was examined in terms of factors that can influence the perceptual integration of auditory stimulus edges, i.e., onsets and offsets, of physically different sounds. Much like the perceptual construction of speech units, we suggest that the auditory system utilizes a rough time window of several hundreds of milliseconds to construct an initial skeleton percept of auditory events. The present data indicated the importance of the temporal proximity, rather than the frequency proximity, between sound edges in the illusory tone construction.

Chronic myocardial and coronary arterial effects of intracoronary supersaturated oxygen therapy in swine with normal and ischemic-reperfused myocardium.

The study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760-1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.

How Pause Duration Influences Impressions of English Speech: Comparison Between Native and Non-native Speakers.

The purpose of this study was to investigate how the subjective impression of English speech would change when pause duration at punctuation marks was varied. Two listening experiments were performed in which written English speech segments were rated on a variety of evaluation items by both native-English speakers and non-native speakers (native-Chinese speakers and native-Japanese speakers). The ratings were then subjected to factor analysis. In the first experiment, the pauses in three segments were made into the same durations, from 0.075 to 4.8 s. Participants rated the segments on 23 evaluation items on a rating scale from 1 to 10. A varimax rotation after PCA (principal component analysis) led to two factors that were related to speech style. These two factors could be interpreted as representing speech naturalness and speech rate. Speech segments with a pause duration of 0.6 s received the highest naturalness evaluation, while perceived speech rate decreased as the physical pause duration increased, without any changes in utterance segments. In the second experiment, a full-factorial design of pause durations (0.15, 0.3, 0.6, 1.2, and 2.4 s) within and between sentences, i.e., for commas and for periods, was implemented in two speech segments. The original speech segments and speech segments without any pauses were also included as control conditions. From ratings on 12 evaluation items, similar to Experiment 1, two factors representing speech naturalness and speech rate were obtained. The results showed again that the perceived speech rate decreased with an increase only in pause duration. As for speech naturalness, the highest evaluations occurred when pause durations were 0.6 s within sentences, and either 0.6 or 1.2 s between sentences. This recommends fixing all pause durations to 0.6 s as a practical way to train non-native speakers to make their spoken English appear more natural.

The common limitations in auditory temporal processing for Mandarin Chinese and Japanese.

The present investigation focused on how temporal degradation affected intelligibility in two types of languages, i.e., a tonal language (Mandarin Chinese) and a non-tonal language (Japanese). The temporal resolution of common daily-life sentences spoken by native speakers was systematically degraded with mosaicking (mosaicising), in which the power of original speech in each of regularly spaced time-frequency unit was averaged and temporal fine structure was removed. The results showed very similar patterns of variations in intelligibility for these two languages over a wide range of temporal resolution, implying that temporal degradation crucially affected speech cues other than tonal cues in degraded speech without temporal fine structure. Specifically, the intelligibility of both languages maintained a ceiling up to about the 40-ms segment duration, then the performance gradually declined with increasing segment duration, and reached a floor at about the 150-ms segment duration or longer. The same limitations for the ceiling performance up to 40 ms appeared for the other method of degradation, i.e., local time-reversal, implying that a common temporal processing mechanism was related to the limitations. The general tendency fitted to a dual time-window model of speech processing, in which a short (~ 20-30 ms) and a long (~ 200 ms) time-window run in parallel.

Galectin-9 mediates neutrophil capture and adhesion in a CD44 and ß2 integrin-dependent manner.

Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of ß2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings.

Water budgeting in conservation agriculture-based sub-surface drip irrigation in tropical maize using HYDRUS-2D in South Asia.

In water scarce regions of South Asia, diversification of rice with maize is being advocated towards sustainability of cereal-based cropping systems. Adoption of innovative agronomic management practices, i.e., conservation agriculture (CA) and sub-surface drip irrigation (SSDI) are considered as key strategies for much needed interventions to address the challenges of water scarcity under projected climate change. Benefits from CA and SSDI concerning water economy are well-established, however, information about their complementarity and water budgeting in cereal-based systems are lacking. A field study was conducted with process-based model (HYDRUS-2D) to understand water transport, root water uptake and components of soil water balance in maize grown in rotation with wheat after five years of continuous adoption of conservation agriculture. In this study, altogether eight treatments comprising of 6 CA+ treatments (CA coupled with SSDI); permanent beds using sub-surface drip (PB-SSD) with (WR) and without (WOR) crop residue at different N rates, 0, 120 and 150 kg N ha-1 were compared with CA (PB using furrow irrigation-FI with crop residue-120 kg N ha-1) and conventional tillage practices (CT) (CT using FI without crop residue-120 kg N ha-1). Results showed that the model could simulate the daily changes in profile soil water content with reasonable accuracy in all the treatments. Simulated soil water balance indicated higher cumulative root water uptake (CRWU), lower cumulative evaporation (CE) and higher soil water retention in CA+ (PB-SSD+ crop residue at 150 and 120 kg N ha-1) than CA and CT plots. Hydrus-2D model efficiency > 0, RMSE between 0.009-0.026 and R2 value between 0.80-0.92 at P < 0.01 indicates that the model is performing efficiently. The mean evaporation from CA+ treatments was 10 and 36% less than CA and CT treatments, respectively. On average, CRWU under CA+ treatments were 14-48% higher than FI treatments. The mean cumulative deep drainage in CA+ plots was 80-100 mm less than CA and CT plots. In CA+ based plots significantly higher biomass production and radiation use efficiency were observed with reduced water use than CA and CT. Therefore, the study justifies the water-saving nature of CA+, while maintaining higher productivity and meeting the transpiration demand of crops and halting unnecessary evaporation and deep drainage losses.

Differences in Three Vection Indices (Latency, Duration, and Magnitude) Induced by "Camera-Moving" and "Object-Moving" in a Virtual Computer Graphics World, Despite Similarity in the Retinal Images.

To create a self-motion (vection) situation in three-dimensional computer graphics (CG), there are mainly two ways: moving a camera toward an object ("camera moving") or by moving the object and its surrounding environment toward the camera ("object moving"). As both methods vary considerably in the amount of computer calculations involved in generating CG, knowing how each method affects self-motion perception should be important to CG-creators and psychologists. Here, we simulated self-motion in a virtual three-dimensional CG-world, without stereoscopic disparity, which correctly reflected the lighting and glare. Self-motion was induced by "camera moving" or by "object moving," which in the present experiments was done by moving a tunnel surrounding the camera toward the camera. This produced two retinal images that were virtually identical in Experiment 1 and very similar in Experiments 2 and 3. The stimuli were presented on a large plasma display to 15 naive participants and induced substantial vection. Three experiments comparing vection strength between the two methods found weak but significant differences. The results suggest that when creating CG visual experiences, "camera-moving" induces stronger vection.

The role of valve stiffness in the insurgence of deep vein thrombosis.

Deep vein thrombosis is a life-threatening development of blood clots in deep veins. Immobility and blood flow stagnancy are typical risk factors indicating that fluid dynamics play an important role in the initiation of venous clots. However, the roles of physical parameters of the valves and flow conditions in deep vein thrombosis initiation have not been fully understood. Here, we describe a microfluidics in vitro method that enabled us to explore the role of valve elasticity using in situ fabrication and characterisation. In our experimental model the stiffness of each valve leaflet can be controlled independently, and various flow conditions were tested. The resulting complex flow patterns were detected using ghost particle velocimetry and linked to localised thrombus formation using whole blood and an aqueous suspension of polystyrene particles. In particular, valves with leaflets of similar stiffness had clot formation on the valve tips whereas valves with leaflets of different stiffness had clot formation in the valve pocket.

Agricultural labor, COVID-19, and potential implications for food security and air quality in the breadbasket of India.

To contain the COVID-19 pandemic, India imposed a national lockdown at the end of March 2020, a decision that resulted in a massive reverse migration as many workers across economic sectors returned to their home regions. Migrants provide the foundations of the agricultural workforce in the 'breadbasket' states of Punjab and Haryana in Northwest India.There are mounting concerns that near and potentially longer-term reductions in labor availability may jeopardize agricultural production and consequently national food security. The timing of rice transplanting at the beginning of the summer monsoon season has a cascading influence on productivity of the entire rice-wheat cropping system. To assess the potential for COVID-related reductions in the agriculture workforce to disrupt production of the dominant rice-wheat cropping pattern in these states, we use a spatial ex ante modelling framework to evaluate four scenarios representing a range of plausible labor constraints on the timing of rice transplanting. Averaged over both states, results suggest that rice productivity losses under all delay scenarios would be low as compare to those for wheat, with total system productivity loss estimates ranging from 9%, to 21%, equivalent to economic losses of USD $674 m to $1.48 billion. Late rice transplanting and harvesting can also aggravate winter air pollution with concomitant health risks. Technological options such as direct seeded rice, staggered nursery transplanting, and crop diversification away from rice can help address these challenges but require new approaches to policy and incentives for change.

Optimization of rain gauge sampling density for river discharge prediction using Bayesian calibration.

River discharges are often predicted based on a calibrated rainfall-runoff model. The major sources of uncertainty, namely input, parameter and model structural uncertainty must all be taken into account to obtain realistic estimates of the accuracy of discharge predictions. Over the past years, Bayesian calibration has emerged as a suitable method for quantifying uncertainty in model parameters and model structure, where the latter is usually modelled by an additive or multiplicative stochastic term. Recently, much work has also been done to include input uncertainty in the Bayesian framework. However, the use of geostatistical methods for characterizing the prior distribution of the catchment rainfall is underexplored, particularly in combination with assessments of the influence of increasing or decreasing rain gauge network density on discharge prediction accuracy. In this article we integrate geostatistics and Bayesian calibration to analyze the effect of rain gauge density on river discharge prediction accuracy. We calibrated the HBV hydrological model while accounting for input, initial state, model parameter and model structural uncertainty, and also taking uncertainties in the discharge measurements into account. Results for the Thur basin in Switzerland showed that model parameter uncertainty was the main contributor to the joint posterior uncertainty. We also showed that a low rain gauge density is enough for the Bayesian calibration, and that increasing the number of rain gauges improved model prediction until reaching a density of one gauge per 340 km2. While the optimal rain gauge density is case-study specific, we make recommendations on how to handle input uncertainty in Bayesian calibration for river discharge prediction and present the methodology that may be used to carry out such experiments.

Indian agriculture, air pollution, and public health in the age of COVID.

Emerging evidence supports the intuitive link between chronic health conditions associated with air pollution and the vulnerability of individuals and communities to COVID-19. Poor air quality already imposes a highly significant public health burden in Northwest India, with pollution levels spiking to hazardous levels in November and early December when rice crop residues are burned. The urgency of curtailing the COVID-19 pandemic and mitigating a potential resurgence later in the year provides even more justification for accelerating efforts to dramatically reduce open agricultural burning in India.

Impact of Coronary Atherosclerosis on Bioresorbable Vascular Scaffold Resorption and Vessel Wall Integration.

The integration of the Absorb bioresorbable vascular scaffold (BVS) into the arterial wall has never been tested in an in vivo model of atherosclerosis. This study aimed to compare the long-term (up to 4 years) vascular healing responses of BVS to an everolimus-eluting metallic stent in the familial hypercholesterolemic swine model of atherosclerosis. The multimodality imaging and histology approaches indicate that the resorption and vascular integration profile of BVS is not affected by the presence of atherosclerosis. BVS demonstrated comparable long-term vascular healing and anti-restenotic efficacy to everolimus-eluting metallic stent but resulted in lower late lumen loss at 4 years.