A comprehensive study of the electronic structure, thermodynamic and electrical transport properties reveals the existence of inhomogeneous superconductivity due to structural disorder in Ca3Rh4Sn13 ...doped with La (Ca3−xLaxRh4Sn13) or Ce (Ca3−xCexRh4Sn13) with superconducting critical temperatures T c higher than those (Tc) observed in the parent compounds. The T − x diagrams and the entropy S(x)T isotherms document well the relation between the degree of atomic disorder and separation of the high-temperature T c and Tc-bulk phases. In these dirty superconductors, with the mean free path much smaller than the coherence length, the Werthamer-Helfand-Hohenber theoretical model does not fit well the Hc2(T) data. We demonstrate that this discrepancy can result from the presence of strong inhomogeneity or from two-band superconductivity in these systems. Both the approaches very well describe the H − T dependencies, but the present results as well as our previous studies give stronger arguments for the scenario based on the presence of nanoscopic inhomogeneity of the superconducting state. A comparative study of La-doped and Ce-doped Ca3Rh4Sn13 showed that in the disordered Ca3−xCexRh4Sn13 alloys the presence of spin-glass effects is the cause of the additional increase of T c in respect to the critical temperatures of disordered Ca3−xLaxRh4Sn13. We also revisited the nature of structural phase transition at T ∼ 130 170 K and documented that there might be another precursor transition at higher temperatures. Raman spectroscopy and thermodynamic properties suggest that this structural transition may be associated with a CDW-type instability.
Purpose
The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used ...pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing.
Methods
Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC.
In vitro
drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus.
Results
Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate
in vitro
release pattern.
Conclusions
Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.
The collapsin response mediator protein (CRMP) family proteins are intracellular mediators of neurotrophic factors regulating neurite structure/spine formation and are essential for dendrite ...patterning and directional axonal pathfinding during brain developmental processes. Among this family, CRMP5/DPYSL5 plays a significant role in neuronal migration, axonal guidance, dendrite outgrowth, and synapse formation by interacting with microtubules. Here, we report the identification of missense mutations in DPYSL5 in nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. A recurrent de novo p.Glu41Lys variant was found in eight unrelated patients, and a p.Gly47Arg variant was identified in one individual from the first family reported with Ritscher-Schinzel syndrome. Functional analyses of the two missense mutations revealed impaired dendritic outgrowth processes in young developing hippocampal primary neuronal cultures. We further demonstrated that these mutations, both located in the same loop on the surface of DPYSL5 monomers and oligomers, reduced the interaction of DPYSL5 with neuronal cytoskeleton-associated proteins MAP2 and βIII-tubulin. Our findings collectively indicate that the p.Glu41Lys and p.Gly47Arg variants impair DPYSL5 function on dendritic outgrowth regulation by preventing the formation of the ternary complex with MAP2 and βIII-tubulin, ultimately leading to abnormal brain development. This study adds DPYSL5 to the list of genes implicated in brain malformation and in neurodevelopmental disorders.
The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods ...for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10−12) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies <0.5%. The area under the receiver operating characteristic curve (AUC) for REVEL was 0.046–0.182 higher in an independent test set of 935 recent SwissVar disease variants and 123,935 putatively neutral exome sequencing variants and 0.027–0.143 higher in an independent test set of 1,953 pathogenic and 2,406 benign variants recently reported in ClinVar than the AUCs for other ensemble methods. We provide pre-computed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in scale.
Cerium (Ce) doped SnO2/g-C3N4 composites were synthesized by a facile hydrothermal method. The obtained Ce doped SnO2/g-C3N4 composites were characterized by X-ray diffraction (XRD), Fourier ...transform infrared spectroscopy (FTIR), UV–visible spectroscopy (UV–Vis), scanning electron microscope (SEM), energy dispersive spectra (EDS), elemental mapping and X-ray photoelectron spectroscopy (XPS). An electrode made of Ce doped SnO2/g-C3N4 exhibited a maximum specific capacitance of 274 F/g at 1 A/g current density. The supercapacitor device fabricated by using Ce-SnO2/g-C3N4//Activated Carbon as electrodes has showed an energy and power densities of 39.3 W h kg−1 and 7425 W kg−1. The asymmetric device gives the retention of 84.2% after completing 5000 cycles. When the same, Ce-SnO2/g-C3N4, composite is used as a photo-catalyst for reduction of methylene blue dye under visible light irradiation, exhibits a higher degradation efficiency of 98% which is higher efficiency compared to all other synthesized samples.
•The Ce-SnO2@g-C3N4 composites were synthesized using facile hydrothermal method.•An ASC device shows a maximum energy and power densities of 39.3 W h kg−1 and 7425 W kg−1.•The device reveals the cycling stability of 84.2% after 5000 charge-discharge cycles.•The Ce-SnO2@g-C3N4 composite reaches the high efficiency of (98%) using methylene blue dye.
Summary
Background
Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity ...correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials.
Objectives
To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers.
Methods
In this case–control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups.
Results
Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid‐derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016).
Conclusions
The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD.
What's already known about this topic?
Staphylococcus aureus frequently colonizes individuals with atopic dermatitis (AD), with increasing disease severity correlating with greater bacterial load of the organism.
Antimicrobial therapies are routinely used in AD for management and prevention of disease flares.
What does this study add?
Staphylococcus aureus isolates from children with AD differ in their antimicrobial resistance profiles from those in healthy, nonatopic nasally colonized children.
Fusidic acid resistance is significantly more prevalent in cases of AD, and arises through distinct genetic mechanisms when compared with healthy controls.
Carriage of plasmid‐derived genetic determinants associated with antiseptic resistance also clearly differentiated S. aureus from cases of AD and controls.
Linked Editorial: Leung. Br J Dermatol 2018; 179:807–808.
Plain language summary available online
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Soil-dwelling microbes are the principal inoculum for the root microbiota, but our understanding of microbe-microbe interactions in microbiota establishment remains fragmentary. We tested 39,204 ...binary interbacterial interactions for inhibitory activities in vitro, allowing us to identify taxonomic signatures in bacterial inhibition profiles. Using genetic and metabolomic approaches, we identified the antimicrobial 2,4-diacetylphloroglucinol (DAPG) and the iron chelator pyoverdine as exometabolites whose combined functions explain most of the inhibitory activity of the strongly antagonistic
R401. Microbiota reconstitution with a core of
root commensals in the presence of wild-type or mutant strains revealed a root niche-specific cofunction of these exometabolites as root competence determinants and drivers of predictable changes in the root-associated community. In natural environments, both the corresponding biosynthetic operons are enriched in roots, a pattern likely linked to their role as iron sinks, indicating that these cofunctioning exometabolites are adaptive traits contributing to pseudomonad pervasiveness throughout the root microbiota.
Moderate intraoperative hypothermia promotes myocardial injury, surgical site infections, and blood loss. Whether aggressive warming to a truly normothermic temperature near 37°C improves outcomes ...remains unknown. We aimed to test the hypothesis that aggressive intraoperative warming reduces major perioperative complications.
In this multicentre, parallel group, superiority trial, patients at 12 sites in China and at the Cleveland Clinic in the USA were randomly assigned (1:1) to receive either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35·5°C (routine thermal management group) during non-cardiac surgery. Randomisation was stratified by site, with computer-generated, randomly sized blocks. Eligible patients (aged ≥45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery expected to last 2–6 h with general anaesthesia, and were expected to have at least half of the anterior skin surface available for warming. Patients requiring dialysis and those with a body-mass index exceeding 30 kg/m2 were excluded. The primary outcome was a composite of myocardial injury (troponin elevation, apparently of ischaemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery, as assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03111875.
Between March 27, 2017, and March 16, 2021, 5056 participants were enrolled, of whom 5013 were included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients assigned to aggressive warming had a mean final intraoperative core temperature of 37·1°C (SD 0·3) whereas the routine thermal management group averaged 35·6°C (SD 0·3). At least one of the primary outcome components (myocardial injury after non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (9·9%) of 2497 patients in the aggressively warmed group and in 239 (9·6%) of 2490 patients in the routine thermal management group. The common effect relative risk of aggressive versus routine thermal management was an estimated 1·04 (95% CI 0·87–1·24, p=0·69). There were 39 adverse events in patients assigned to aggressive warming (17 of which were serious) and 54 in those assigned to routine thermal management (30 of which were serious). One serious adverse event, in an aggressively warmed patient, was deemed to be possibly related to thermal management.
The incidence of a 30-day composite of major cardiovascular outcomes did not differ significantly in patients randomised to 35·5°C and to 37°C. At least over a 1·5°C range from very mild hypothermia to full normothermia, there was no evidence that any substantive outcome varied. Keeping core temperature at least 35·5°C in surgical patients appears sufficient.
3M and the Health and Medical Research Fund, Food and Health Bureau, Hong Kong.
For the Chinese translation of the abstract see Supplementary Materials section.
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•Nano-additives influenced the oxidative thermokinetics of the fuel.•The CO emissions were reduced by using nano-additives.•E10 showed the lowest mean and maximum diameter of PM ...particles.
The main objective of the study was to improve the fuel properties, performance and reduce the level of hydrocarbon (HC) and carbon monoxide (CO) when running with water in diesel emulsion fuel (W/D) by adding various nano-additives. Aluminium Oxide (Al2O3), Copper(II) Oxide (CuO), Magnesium Oxide (MgO), Manganese(IV) Oxide (MnO) and Zinc Oxide (ZnO) nano-additives were selected for W/D with 10% water (E10). Each nano-additive was added to E10 at a dosage of 50 ppm and further denoted as nano-additive emulsion fuel: E10Al2O3, E10CuO, E10MgO, E10MnO and E10ZnO. The properties (density, viscosity, water droplet size, stability period and oxidative thermokinetics), performance (torque, brake power, brake specific fuel consumption (BSFC), and emission (nitrogen oxides (NOx), particulate matter (PM), carbon dioxide (CO2), CO and HC) of each test fuel were investigated. Overall, nano-additives tended to increase density, viscosity, water droplet size and oxidative thermokinetics but decrease the stability period. The nano-additives resulted in a marginal increase of performance with the E10Al2O3 yielding the highest reduction in BSFC. The nano-additives also lowered the brake specific CO (BSCO) emissions compared to Euro 2 standard diesel (D2) by up to 17% with E10ZnO. Nano-additives produced from different metals impact the fuel properties, performance and emissions differently. Al2O3 is nominated as the best nano-additive due to the smallest water droplet size, highest DTGmax and its consistency in increasing the torque and reducing the BSFC, brake specific NOx (BSNOx), BSCO compared to other nano-additives. That is to say, nano-additives coupled with a W/D has the potential to reduce BSFC and BSCO simultaneously.
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