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We also conducted Bayesian multi-trait analysis using the estimated vegetative indices as secondary traits. Three vegetative indices (Datt3, REP_Li, and Vogelmann2) had high genetic correlations (rA) with powdery mildew visual ratings with average rA values of 0.76, 0.71, and 0.71, respectively. Increasing training population sizes by incorporating individuals with only vegetative index information yielded substantial increases in predictive ability. These results strongly indicate the use of vegetative indices as secondary traits for indirect selection. Overall, combining spectrometry and genome-wide prediction improved selection accuracy and response to selection for powdery mildew resistance, demonstrating the power of an integrated phenomics-genomics approach in strawberry breeding.
Cefotaxime is frequently used in critically ill children, however pharmacokinetic (PK) studies to support adequate dosing in this patient population are limited.
To characterize cefotaxime PK in critically ill children and evaluate exposures achieved by current and alternative dosing regimens.
Children (0-18 years) admitted to the paediatric ICU, receiving intravenous cefotaxime (100-150 mg/kg/day, interval 6-8 h) were included (Clinicaltrials.gov NCT03248349). Total plasma cefotaxime concentrations were measured on multiple study days. Population-PK analysis was performed using nonlinear mixed effects modelling (NONMEM™). Dose evaluations were performed using typical patients across the paediatric age range and target attainment was determined for MICs of 0.5, 2 and 4 mg/L.
479 cefotaxime plasma concentrations from 52 children (median age 1.6, range 0.03-17.7 years) were used to describe cefotaxime PK. We describe a two-compartment structural model with interindividual variability, including bodyweight as covariate for volume of distribution and clearance. Model predicted exposure for 150 mg/kg/day (current dose) showed trough concentrations <0.5 mg/L in patients >4 years of age. The maximum cefotaxime doses (200 mg/kg/day, interval 6 h) proved adequate for MICs ≤0.5 mg/L across the whole age range. Similar daily doses with increased frequency (interval 4 h) covered MICs up to 2 mg/L, while a loading dose followed by continuous infusion regimens are needed to adequately treat MICs of 4 mg/L.
Higher cefotaxime doses are required for adequate exposure for most pathogens in critically ill children. A higher dose frequency or continuous infusion is advisable to improve target attainment for intermediately susceptible pathogens.
Higher cefotaxime doses are required for adequate exposure for most pathogens in critically ill children. A higher dose frequency or continuous infusion is advisable to improve target attainment for intermediately susceptible pathogens.
Colorectal cancer is a leading cancer incidence and cause of death worldwide and in Vietnam. Although screening is considered an effective measure to prevent and control colorectal cancer, there is no such effort in Vietnam.
Between 01 January 2018 and 31 October 2019, a population-based colorectal cancer screening program was conducted in Hanoi, Vietnam. A health advocacy campaign and follow-up phone calls were used to enroll residents aged ≥40years old to complete an immunochemical-fecal occult blood testing. Positive immunochemical-fecal occult blood testing was followed by a colonoscopy. We also conducted a systematic review of the colorectal cancer screening programs in the Asia-Pacific region that used similar approach by searching Ovid Medline and PubMed databases.
During study period, 103 542 individuals among 672 742 eligible residents attended the screening of whom 81.5% participants finished immunochemical-fecal occult blood testing test and the positive rate was 6.1%. The coverage rate for isources.With the advances in sequencing technologies, a huge amount of biological data is extracted nowadays. Analyzing this amount of data is beyond the ability of human beings, creating a splendid opportunity for machine learning methods to grow. The methods, however, are practical only when the sequences are converted into feature vectors. Many tools target this task including iLearnPlus, a Python-based tool which supports a rich set of features. In this paper, we propose a holistic tool that extracts features from biological sequences (i.e. DNA, RNA and Protein). These features are the inputs to machine learning models that predict properties, structures or functions of the input sequences. Our tool not only supports all features in iLearnPlus but also 30 additional features which exist in the literature. Moreover, our tool is based on R language which makes an alternative for bioinformaticians to transform sequences into feature vectors. We have compared the conversion time of our tool with that of iLearnPlus we transform the sequences much faster. We convert small nucleotides by a median of 2.8X faster, while we outperform iLearnPlus by a median of 6.3X for large sequences. Finally, in amino acids, our tool achieves a median speedup of 23.9X.Research has demonstrated that antibiotic prescribing and use are social processes. Despite the availability of guidelines and policies for optimized use, many challenges remain. Whilst much of the research in antimicrobial resistance is focused on new drugs, the socio-cultural and socio-economic drivers for infections and antibiotic use are also important considerations. Context-specific solutions that are co-developed with end users are needed if we are to optimize the use of existing and new antibiotics. The threat of antimicrobial resistance is not subject to geographical boundaries, and to truly be effective, interventions need to have the potential to be scaled to different settings. The inequities in funding, knowledge generation, ownership and transfer between the global North and South must be acknowledged and eradicated. Striking a balance in funding and equity requires in-country capacity building for (i) delivering sustainable research; (ii) assuring equitable representation in research outputs; and (iii) supporting career progression of researchers through further funding, to support the generation of locally owned knowledge that contributes to optimized healthcare systems and translation into clinical practice.
The American Academy of Pediatrics strongly recommends that children age 2 and under should have little to no digital media exposure. However, most children are exposed to regular screen time at home. This may also be true for hospitalized children. Through education and access to alternatives, we aimed to reduce screen exposure in our children's hospital for children 2 and under.
Between January 2020 and May 2021, we designed and implemented a quality improvement intervention to educate staff and caregivers on the American Academy of Pediatrics screen time recommendations and offer alternatives for hospitalized children. Our primary aim was to decrease screen time exposure for children age 2 and under by 50% within 12 months of project initiation. Balancing measures included staff perception of workload when using screens and perceived parental acceptance of screens being turned off.
During baseline data collection period, screens were on for an average of 63% of the audits. Following interventions, the average was reduced to 40%. The outcome measure met special cause with 8 consecutive points below the center line. There was a significant increase in staff who reported offering screen alternatives after intervention. Staff perception of workload and perceived parental acceptance was unchanged.
Through implementation of this quality improvement initiative, we reduced screen time by approximately 37% without impacting staff workload. Most importantly, we were able to educate staff and model best practices for caregivers, which may carry into the home, leading to a reduction of screen time and improved health overall.
Through implementation of this quality improvement initiative, we reduced screen time by approximately 37% without impacting staff workload. Most importantly, we were able to educate staff and model best practices for caregivers, which may carry into the home, leading to a reduction of screen time and improved health overall.Area 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes visual information for action. The signals that area 5 ultimately conveys to motor cortex, the main area providing output to the spinal cord, are unknown. We analyzed area 5 neuronal activity during vision-independent locomotion on a flat surface and vision-dependent locomotion on a horizontal ladder in cats focusing on corticocortical neurons (CCs) projecting to motor cortex from the upper and deeper cortical layers and compared it to that of neighboring unidentified neurons (noIDs). We found that upon transition from vision-independent to vision-dependent locomotion, the low discharge of CCs in layer V doubled and the proportion of cells with 2 bursts per stride tended to increase. In layer V, the group of 2-bursters developed 2 activity peaks that coincided with peaks of gaze shifts along the surface away from the animal, described previously. One-bursters and either subpopulation in supragranular layers did not transmit any clear unified stride-related signal to the motor cortex. Most CC group activities did not mirror those of their noID counterparts. CCs with receptive fields on the shoulder, elbow, or wrist/paw discharged in opposite phases with the respective groups of pyramidal tract neurons of motor cortex, the cortico-spinal cells.In plant cells, linkage between the cytoskeleton, plasma membrane, and cell wall is crucial for maintaining cell shape. In highly polarized pollen tubes, this coordination is especially important to allow rapid tip growth and successful fertilization. Varoglutamstat mouse Class I formins contain cytoplasmic actin-nucleating formin homology domains as well as a proline-rich extracellular domain and are candidate coordination factors. Here, using Arabidopsis, we investigated the functional significance of the extracellular domain of two pollen-expressed class I formins AtFH3, which does not have a polar localization, and AtFH5, which is limited to the growing tip region. We show that the extracellular domain of both is necessary for their function, and identify distinct O-glycans attached to these sequences, AtFH5 being hydroxyproline-arabinosylated and AtFH3 carrying arabinogalactan chains. Loss of hydroxyproline arabinosylation altered the plasma membrane localization of AtFH5 and disrupted actin cytoskeleton organization. Moreover, we show that O-glycans differentially affect lateral mobility in the plasma membrane. Together, our results support a model of protein sub-functionalization in which AtFH5 and AtFH3, restricted to specific plasma membrane domains by their extracellular domains and the glycans attached to them, organize distinct subarrays of actin during pollen tube elongation.
To investigate whether deiodinase inhibitor iopanoic acid (IOP) has chondroprotective properties, a mechanically stress induced model of human aged explants was used to test both repeated dosing and slow-released IOP.
Human osteochondral explants subjected to injurious mechanical stress (65%MS) were treated with IOP or IOP incapsulated in Poly lactic-co-glycolic acid (PLGA)-polyethylene glycol (PEG) nanoparticles (NP) (PLGA-PEG NPs (NP(IOP)). Changes to cartilage integrity and signalling was determined by Mankin scoring of histology, sulphated glycosaminoglycan (sGAG) release and expression levels of catabolic, anabolic and hypertrophic markers. Subsequently, on a subgroup of samples, RNA-sequencing was performed on 65%MS (n = 14) and 65%MS+IOP (n = 7) treated cartilage to identify IOPs mode of action.
Damage of injurious mechanical stress was confirmed by increased cartilage surface damage in the Mankin score, increased sGAG release, consistent upregulation of catabolic markers and downregulation of anabolic markers.
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