1,362 research outputs found

    Planetary nebulae detected in the Spitzer Space Telescope GLIMPSE 3D Legacy Survey

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    Due to interstellar extinction, optical census of Galactic planetary nebulae (PNs) is highly incomplete, and some compact H ii regions might have been mis-classified as PNs. The problem is particularly severe in the Galactic plane where the extinction in the optical is significant and hampers the detections of PNs. Unlike optical observations, infrared (IR) observations are hardly affected by interstellar extinction, and provide a good opportunity to study highly obscured PNs. In this study, we use the data from the Spitzer Legacy Infrared Mid-Plane Survey Extraordinaire 3D (GLIMPSE 3D) to investigate the mid-infrared (MIR) properties of PNs and PN candidates. © 2012 International Astronomical Union.published_or_final_versionThe IAU Symposium No. 283: 'Planetary Nebulae: an Eye to the Future', Puerto de la Cruz, Tenerife, Spain, 25-29 July 2011. In International Astronomical Union Proceedings, 2011, v. 7 n. S283, p. 528-52

    Estimates of global consumption of child-appropriate antibiotic formulations

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    Global sales of oral antibiotics formulated for children.

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    Objective: To investigate international consumption patterns of child-appropriate oral formulations of antibiotics by formulation type, with a focus on dispersible tablets, using data from a global sales database. Method: Antibiotic sales data for 2015 covering 74 countries and regional country groups were obtained from the MIDAS® pharmaceutical sales database, which includes samples of pharmacy wholesalers and retailers. The focus was on sales of child-appropriate oral formulations of Access antibiotics in the 2017 World Health Organization's WHO Model list of essential medicines for children. Sales volumes are expressed using a standard unit (i.e. one tablet, capsule, ampoule or vial or 5 mL of liquid). Sales were analysed by antibiotic, WHO region and antibiotic formulation. Findings: Globally, 17.7 billion standard units of child-appropriate oral antibiotic formulations were sold in 2015, representing 24% of total antibiotic sales of 74.4 billion units (both oral and parenteral) in the database. The top five child-appropriate Access antibiotics by sales volume were amoxicillin, amoxicillin with clavulanic acid, trimethoprim-sulfamethoxazole, cefalexin and ampicillin. The proportion of the top five sold for use as a syrup varied between 42% and 99%. Dispersible tablets represented only 22% of all child-appropriate oral formulation sales and made up only 15% of sales of 10 selected Access antibiotics on the model list for children. Conclusion: Globally most child-appropriate oral antibiotics were not sold as dispersible tablets in 2015, as recommended by WHO. There is a clear need for novel solid forms of antibiotics suitable for use in children

    Collapse of stamps for soft lithography due to interfacial adhesion

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    Collapse of elastomeric elements used for pattern transfer in soft lithography is studied through experimental measurements and theoretical modehng. The objective is to identify the driving force for such collapse. Two potential driving forces, the self-weight of the stamp and the interfacial adhesion, are investigated. An idealized configuration of periodic rectangular grooves and flat punches is considered. Experimental observations demonstrate that groove collapse occurs regardless of whether the gravitational force promotes or suppresses such collapse, indicating that self-weight is not the driving force. On the other hand, model predictions based on the postulation that interfacial adhesion is the driving force exhibit excellent agreement with the experimentally measured collapse behavior. The interfacial adhesion energy is also evaluated by matching an adhesion parameter in the model with the experimental data.open546

    Variation in target attainment of β-lactam antibiotic dosing between international pediatric formularies

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    As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. β-lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dose recommendations from the major paediatric reference sources and tries to answer the question: does β-lactam dose heterogeneity matter? Does it impact on pharmacodynamic (PD) target attainment? For three important severe clinical infections - pneumonia, sepsis and meningitis - pharmacokinetic (PK) models were identified for common β-lactam antibiotics. Real-world demographics were derived from three multi-center point prevalence surveys. Simulation results were compared with minimum inhibitory concentration (MIC) distributions, to inform appropriateness of recommended doses in targeted and empiric treatment. Whilst cephalosporin dose regimens are largely adequate for target attainment, they also pose most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin and meropenem doses as potentially requiring review/optimisation in order to preserve the use of these agents in future

    Zebrafish globin switching occures in two developmental stages and is controlled by the LCR

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    Globin gene switching is a complex, highly regulated process allowing expression of distinct globin genes at specific developmental stages. Here, for the first time, we have characterized all of the zebrafish globins based on the completed genomic sequence. Two distinct chromosomal loci, termed major (chromosome 3) and minor (chromosome 12), harbor the globin genes containing α/β pairs in a 5'-3' to 3'-5' orientation. Both these loci share synteny with the mammalian α-globin locus. Zebrafish globin expression was assayed during development and demonstrated two globin switches, similar to human development. A conserved regulatory element, the locus control region (LCR), was revealed by analyzing DNase I hypersensitive sites, H3K4 trimethylation marks and GATA1 binding sites. Surprisingly, the position of these sites with relation to the globin genes is evolutionarily conserved, despite a lack of overall sequence conservation. Motifs within the zebrafish LCR include CACCC, GATA, and NFE2 sites, suggesting functional interactions with known transcription factors but not the same LCR architecture. Functional homology to the mammalian α-LCR MCS-R2 region was confirmed by robust and specific reporter expression in erythrocytes of transgenic zebrafish. Our studies provide a comprehensive characterization of the zebrafish globin loci and clarify the regulation of globin switching

    GAPPS (Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies) a critical appraisal system for antimicrobial PKPD studies - development and application in pediatric antibiotic studies

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    Introduction: There are limited data on optimal dosing of antibiotics in different age groups for neonates and children. Clinicians usually consult pediatric formularies or online databases for dose selection, but these have variable recommendations, are usually based on expert opinion and are not graded based on the existing pharmacokinetic-pharmacodynamic (PKPD) studies. We describe here a potential new tool that could be used to grade the strength of evidence emanating from PKPD studies. Areas covered: A scoring system was developed (GAPPS tool) to quantify the strength of each PK assessment and rate the studies quality in already published articles. GAPPS was evaluated by applying it to pediatric PKPD studies of antibiotics from the 2019 Essential Medicines List for children (EMLC), identified through a search of PubMed. Expert opinion: Evidence for most antibiotic dose selection decisions was generally weak, coming from individual PK studies and lacked PKPD modeling and simulations. However, the quality of evidence appears to have improved over the last two decades. Incorporating a formal grading system, such as GAPPS, into formulary development will provide a transparent tool to support decision-making in clinical practice and guideline development, and guide PKPD authors on study designs most likely to influence guidelines
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