A supplementary home dose of oral ondansetron given in anticipation of recurrent emesis in paediatric acute gastroenteritis

Ondansetron is a useful adjunct for the treatment of acute gastroenteritis in the paediatric ED. The use of ondansetron is associated with many benefits including decreased emesis, decreased need for intravenous fluids, decreased rate of admission, decreased length of stay, decreased revisit rates and increased cost savings (15-18). There may be value in giving patients a second as-needed home dose of ondansetron as part of ED discharge planning, with the appropriate patient education, in anticipation of recurrent emesis. This practice may further reduce ED revisit rates and also prevent morbidity and hospitalization associated with severe dehydration for patients who do eventually return to the ED, especially those in rural communities where timely treatment and access to an ED is difficult. The decision to dispense ondansetron should be made clinically by the ED physician for patients who have failed ORT whose symptoms are predominantly emesis as opposed to diarrhea, and when the discharging physician is reasonably certain of a diagnosis of acute gastroenteritis and not something more sinister. There is currently no consensus on the role of ED-provided ondansetron for out-of-hospital use for paediatric patients with acute gastroenteritis. Future studies are needed to determine the potential impact on morbidity and the health care economy. ©2014 Pulsus Group Inc. All rights reserved

Statistical periodicity in driven quantum systems: General formalism and application to noisy Floquet topological chains

Much recent experimental effort has focused on the realization of exotic quantum states and dynamics predicted to occur in periodically driven systems. But how robust are the sought-after features, such as Floquet topological surface states, against unavoidable imperfections in the periodic driving? In this work, we address this question in a broader context and study the dynamics of quantum systems subject to noise with periodically recurring statistics. We show that the stroboscopic time evolution of such systems is described by a noise-averaged Floquet superoperator. The eigenvectors and -values of this superoperator generalize the familiar concepts of Floquet states and quasienergies and allow us to describe decoherence due to noise efficiently. Applying the general formalism to the example of a noisy Floquet topological chain, we re-derive and corroborate our recent findings on the noise-induced decay of topologically protected end states. These results follow directly from an expansion of the end state in eigenvectors of the Floquet superoperator.Comment: 13 pages, 5 figures. This is the final, published versio

Gender-Specific Protection from Microvessel Rarefaction in Female Hypertensive Rats

Epidemiologic studies reveal that women have a significantly lower age-adjusted morbidity and mortality from cardiovascular disease than men, suggesting that gender is a cardiovascular disease risk factor. The mechanism of the “gender protection” is unknown. In this study, we investigated the microvascular remodeling in reduced renal mass plus a high salt (4.0% NaCl) diet model of hypertension (RRM + HS). We hypothesized that women would be protected from the increase in blood pressure and from the microvascular rarefaction associated with RRM + HS hypertension. Studies were designed to determine whether female rats were less susceptible to changes in microvessel density during RRM + HS. Microvessel density was measured in male and female low salt (0.4% LS) sham-operated controls (Sham + LS) and after 3 days or 4 weeks of RRM + HS hypertension. The microcirculation of hind limb (medial and lateral gastrocnemius, plantaris, soleus) muscles was visualized using rhodamine-labeled Griffonia simplicifolia I lectin. Tissue sections were examined by videomicroscopy and microvessel density was determined by quantitative stereology. As shown previously, mean arterial pressure increased to 160 ± 8 mm Hg and microvessel density decreased (\u3e30% decrease in all beds) in male RRM + HS. In contrast, mean arterial pressure of female RRM + HS rats was modestly increased from 101 ± 2 to 118 ± 4 mm Hg. Despite previous results showing a reduction in microvessel density of both normotensive and hypertensive male rats on a high salt diet, microvessel density of female RRM + HS rats was not reduced at either time. These results suggest that gender protection in the RRM rat extends beyond an attenuation of the increase in pressure to an immunity from microvascular rarefaction

Azithromycin use in paediatrics: A practical overview

Azithromycin is an antibiotic that is commonly prescribed for upper and lower respiratory tract infections in children. While it has proven benefits, some concerns regarding azithromycin use have arisen in recent years. This practice point considers azithromycin therapy for acute respiratory infections in otherwise healthy children. Pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects are considered, along with recommendations for use and contraindications. Azithromycin should be avoided in patients with a significant risk of bacteremia. It is associated with pneumococcal resistance and, with stated exceptions, is generally not recommended for the treatment of acute pharyngitis, acute otitis media or pneumococcal community-acquired pneumonia in the paediatric population. © Canadian Paediatric Society 2013

Allele Frequency Matching Between SNPs Reveals an Excess of Linkage Disequilibrium in Genic Regions of the Human Genome

Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage disequilibrium (LD), between single nucleotide polymorphisms (SNPs) across the human genome. LD describes the nonrandom association between SNP pairs and can be used as a metric when designing maximally informative panels of SNPs for association studies in human populations. Using data from the 1.58 million SNPs genotyped by Perlegen, we explored the allele frequency dependence of the LD statistic r (2) both empirically and theoretically. We show that average r (2) values between SNPs unmatched for allele frequency are always limited to much less than 1 (theoretical [Image: see text] approximately 0.46 to 0.57 for this dataset). Frequency matching of SNP pairs provides a more sensitive measure for assessing the average decay of LD and generates average r (2) values across nearly the entire informative range (from 0 to 0.89 through 0.95). Additionally, we analyzed the extent of perfect LD (r (2) = 1.0) using frequency-matched SNPs and found significant differences in the extent of LD in genic regions versus intergenic regions. The SNP pairs exhibiting perfect LD showed a significant bias for derived, nonancestral alleles, providing evidence for positive natural selection in the human genome

Hybrid HVDC circuit breaker with self-powered gate drives

The ever increasing electric power demand and the advent of renewable energy sources have revived the interest in high-voltage direct current (HVDC) multi-terminal networks. However, the absence of a suitable circuit breaker or fault tolerant VSC station topologies with the required characteristics (such as operating speed) have, until recently, been an obstacle in the development of large scale multi-terminal networks for HVDC. This paper presents a hybrid HVDC circuit breaker concept which is capable of meeting the requirements of HVDC networks. Simulation results are presented which are validated by experimental results taken from a 2.5kV, 700A rated laboratory prototype

Impact of Extreme Weather on North American Transmission System Outages

The impact of weather on the power grid has been a focus of multiple studies, and its importance has grown with the number and magnitude of extreme weather events. This paper uses transmission outage and inventory data collected in Transmission Availability Data System (TADS) to identify and analyze weather related transmission events and quantify their impact on the North American Bulk Electric System. The impact of a transmission event is measured by several factors: the number of outages, affected miles and MVA, event duration, and number of groups of simultaneous outages (known as generations of outages). We analyze the largest events from 2015 to 2019, and use an event propagation metric to estimate the probability of small, medium, and large events, and track how these probabilities change from year-to-year

Novel CYP2C9 Promoter Variants and Assessment of Their Impact on Gene Expression □ S

ABSTRACT There are a considerable number of reports identifying and characterizing genetic variants within the CYP2C9 coding region. Much less is known about polymorphic promoter sequences that also might contribute to interindividual differences in CYP2C9 expression. To address this problem, approximately 10,000 base pairs of CYP2C9 upstream information were resequenced using 24 DNA samples from the Coriell Polymorphism Discovery Resource. Thirty-one single-nucleotide polymorphisms (SNPs) were identified; nine SNPs were novel, whereas 22 were reported previously. Using both sequencing and multiplex single-base extension, individual SNP frequencies were determined in 193 DNA samples obtained from unrelated, selfreported Hispanic Americans of Mexican descent, and they were compared with similar data obtained from a non-Latino white cohort. Significant interethnic differences were observed in several SNP frequencies, some of which seemed unique to the Hispanic population. Analysis using PHASE 2.1 inferred nine common (Ͼ1%) variant haplotypes, two of which included the g.3608CϾT (R144C) CYP2C9*2 and two the g.42614AϾC (I359L) CYP2C9*3 SNPs. Haplotype variants were introduced into a CYP2C9/luciferase reporter plasmid using site-directed mutagenesis, and the impact of the variants on promoter activity assessed by transient expression in HepG2 cells. Both constitutive and pregnane X receptor-mediated inducible activities were measured. Haplotypes 1B, 3A, and 3B each exhibited a 65% decrease in constitutive promoter activity relative to the reference haplotype. Haplotypes 1D and 3B exhibited a 50% decrease and a 40% increase in induced promoter activity, respectively. These data suggest that genetic variation within CYP2C9 regulatory sequences is likely to contribute to differences in CYP2C9 phenotype both within and among different populations

Inhibitors of Foot and Mouth Disease Virus Targeting a Novel Pocket of the RNA-Dependent RNA Polymerase

Foot-and-Mouth Disease Virus (FMDV) is a picornavirus that infects cloven-hoofed animals and leads to severe losses in livestock production. In the case of an FMD outbreak, emergency vaccination requires at least 7 days to trigger an effective immune response. There are currently no approved inhibitors for the treatment or prevention of FMDV infections.Using a luciferase-based assay we screened a library of compounds and identified seven novel inhibitors of 3Dpol, the RNA-dependent RNA polymerase of FMDV. The compounds inhibited specifically 3Dpol (IC(50)s from 2-17 µM) and not other viral or bacterial polymerases. Enzyme kinetic studies on the inhibition mechanism by compounds 5D9 and 7F8 showed that they are non-competitive inhibitors with respect to NTP and nucleic acid substrates. Molecular modeling and docking studies into the 3Dpol structure revealed an inhibitor binding pocket proximal to, but distinct from the 3Dpol catalytic site. Residues surrounding this pocket are conserved among all 60 FMDV subtypes. Site directed mutagenesis of two residues located at either side of the pocket caused distinct resistance to the compounds, demonstrating that they indeed bind at this site. Several compounds inhibited viral replication with 5D9 suppressing virus production in FMDV-infected cells with EC(50) = 12 µM and EC(90) = 20 µM).We identified several non-competitive inhibitors of FMDV 3Dpol that target a novel binding pocket, which can be used for future structure-based drug design studies. Such studies can lead to the discovery of even more potent antivirals that could provide alternative or supplementary options to contain future outbreaks of FMD