Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department.

BACKGROUND: Asthma is a chronic respiratory condition characterised by airways inflammation, constriction of airway smooth muscle and structural alteration of the airways that is at least partially reversible. Exacerbations of asthma can be life threatening and place a significant burden on healthcare services. Various guidelines have been published to inform management personnel in the acute setting; several include the use of a single bolus of intravenous magnesium sulfate (IV MgSO4) in cases that do not respond to first-line treatment. However, the effectiveness of this approach remains unclear, particularly in less severe cases. OBJECTIVES: To assess the safety and efficacy of IV MgSO4 in adults treated for acute asthma in the emergency department. SEARCH METHODS: We identified trials from the Cochrane Airways Review Group Specialised Register (CAGR) up to 2 May 2014. We also searched www.ClinicalTrials.gov and reference lists of other reviews, and we contacted trial authors to ask for additional information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults treated in the emergency department (ED) for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo. DATA COLLECTION AND ANALYSIS: All review authors screened titles and abstracts for inclusion, and at least two review authors independently extracted study characteristics, risk of bias and numerical data. Disagreements were resolved by consensus, and we contacted trial investigators to obtain missing information.We analysed dichotomous data as odds ratios using study participants as the unit of analysis, and we analysed continuous data as mean differences or standardised mean differences using fixed-effect models. We rated all outcomes using GRADE and presented results in Summary of findings table 1.We carried out subgroup analyses on the primary outcome for baseline severity of exacerbations and whether or not ipratropium bromide was given as a co-medication. Unpublished data and studies at high risk of bias for blinding were removed from the main analysis in sensitivity analyses. MAIN RESULTS: Fourteen studies met the inclusion criteria, randomly assigning 2313 people with acute asthma to the comparisons of interest in this review.Most studies were double-blinded trials comparing a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes versus a matching placebo. Eleven were conducted at a single centre, and three were multi-centre trials. Participants in almost all of the studies had already been given at least oxygen, nebulised short-acting beta2-agonists and IV corticosteroids in the ED; in some studies, investigators also administered ipratropium bromide. Ten studies included only adults, and four included both adults and children; these were included because the mean age of participants was over 18 years.Intravenous MgSO4 reduced hospital admissions compared with placebo (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60 to 0.92; I(2) = 28%, P value 0.18; n = 972; high-quality evidence). In absolute terms, this odds ratio translates into a reduction of seven hospital admissions for every 100 adults treated with IV MgSO4 (95% CI two to 13 fewer). The test for subgroup differences revealed no statistical heterogeneity between the three severity subgroups (I(2) = 0%, P value 0.73) or between the four studies that administered nebulised ipratropium bromide as a co-medication and those that did not (I(2) = 0%, P value 0.82). Sensitivity analyses in which unpublished data and studies at high risk for blinding were removed from the primary analysis did not change conclusions.Within the secondary outcomes, high- and moderate-quality evidence across three spirometric indices suggests some improvement in lung function with IV MgSO4. No difference was found between IV MgSO4and placebo for most of the non-spirometric secondary outcomes, all of which were rated as low or moderate quality (intensive care admissions, ED treatment duration, length of hospital stay, readmission, respiration rate, systolic blood pressure).Adverse events were inconsistently reported and were not meta-analysed. The most commonly cited adverse events in the IV MgSO4 groups were flushing, fatigue, nausea and headache and hypotension (low blood pressure). AUTHORS' CONCLUSIONS: This review provides evidence that a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes reduces hospital admissions and improves lung function in adults with acute asthma who have not responded sufficiently to oxygen, nebulised short-acting beta2-agonists and IV corticosteroids. Differences in the ways the trials were conducted made it difficult for the review authors to assess whether severity of the exacerbation or additional co-medications altered the treatment effect of IV MgSO4. Limited evidence was found for other measures of benefit and safety.Studies conducted in these populations should clearly define baseline severity parameters and systematically record adverse events. Studies recruiting participants with exacerbations of varying severity should consider subgrouping results on the basis of accepted severity classifications

Speed without fear: composable self-timed GaAs circuits

technical reportWe have designed a set of self-timed gallium arsenide building blocks that are suitable for composing into larger systems. Systems designed using these modules can be easier to design and modify than their globally clocked counterparts, while maintaining high performance. The modules are suitable for use in a translation systems that automatically translates an OCCAM program into a circuit netlist

A comparison of self-timed design using FPGA, CMOS, and GaAs technologies

Journal ArticleAsynchronous or self-timed systems that do not rely on U global clock to keep system components synchronized can offer significant advantages over traditional clocked circuits in a variety of applications. One advantage is that because of the separation of timing, from, functionality in these systems, the same circuit may he implemented in U variety of technologies without modification to the circuit. In this paper we explore one approach to self-timed design and describe implementations of an example circuit in three different technologies. The simple routing chip used us the example has been described by writing U program in OCCAM, translated into U circuit consisting of a small set of basic modules, and implemented using Actel FPGA, CMOS, and GuAs technologies

Visualising disease progression on multiple variables with vector plots and path plots.

BACKGROUND: It is often desirable to observe how a disease progresses over time in individual patients, rather than graphing group averages; and since multiple outcomes are typically recorded on each patient, it would be advantageous to visualise disease progression on multiple variables simultaneously. METHODS: A variety of vector plots and a path plot have been developed for this purpose, and data from a longitudinal Huntington's disease study are used to illustrate the utility of these graphical methods for exploratory data analysis. RESULTS: Initial and final values for three outcome variables can be easily visualised per patient, along with the change in these variables over time. In addition to the disease trajectory, the path individual patients take from initial to final observation can be traced. Categorical variables can be coded with different types of vectors or paths (e.g. different colours, line types, line thickness) and separate panels can be used to include further categorical or continuous variables, allowing clear visualisation of further information for each individual. In addition, summary statistics such as mean vectors, bivariate interquartile ranges and convex polygons can be included to assist in interpreting trajectories, comparing groups, and detecting multivariate outliers. CONCLUSION: Vector and path plots are useful graphical methods for exploratory data analysis when individual-level information on multiple variables over time is desired, and they have several advantages over plotting each variable separately.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Mountain-and brown hare genetic polymorphisms to survey local adaptations and conservation status of the heath hare (Lepus timidus sylvaticus, Nilsson 1831)

We provide the first whole genome sequences from three specimens of the mountain hare subspecies the heath hare (Lepus timidus sylvaticus), along with samples from two mountain hares (Lepus timidus timidus) and two brown hares (Lepus europaeus) from Sweden. The heath hare has a unique grey winter pelage as compared to other mountain hares (white) and brown hares (mostly brown), and face regional extinction, likely due to competitive exclusion from the non-native brown hare. Whole genome resequencing from the seven hare specimens were mapped to the Lepus timidus pseudoreference genome and used for detection of 11,363,883 polymorphic nucleotide positions. The data presented here could be useful for addressing local adaptations and conservation status of mountain hares and brown hares in Sweden, including unique subspecies

Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis

addresses: Biosciences, College of Life and Environmental Sciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, Devon, EX4 4QD, UK.notes: PMCID: PMC3025829types: Journal Article; Research Support, Non-U.S. Gov't© 2011 Wand et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, B. thailandensis and B. oklahomensis, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (Galleria mellonella) infection models

The relationship of calcium to receptor-controlled stimulation of phosphatidylinositol turnover. Effects of acetylcholine, adrenaline, calcium ions, cinchocaine and a bivalent cation ionophore on rat parotid-gland fragments

The possibility that Ca2+ ions are involved in the control of the increased phosphatidylinositol turnover which is provoked by alpha-adrenergic or muscarinic cholinergic stimulation of rat parotid-gland fragments has been investigated. Both types of stimulation provoked phosphatidylinositol breakdown, which was detected either chemically or radiochemically, and provoked a compensatory synthesis of the lipid, detected as an increased rate of incorporation of 32Pi into phosphatidylinositol. Acetylcholine had little effect on the incorporation of labelled glycerol, whereas adrenaline stimulated it significantly, but to a much lower extent than 32P incorporation: this suggests that the response to acetylcholine was entirely accounted for by renewal of the phosphorylinositol head-group of the lipid, but that some synthesis de novo was involved in the response to adrenaline. The responses to both types of stimulation, whether measured as phosphatidylinositol breakdown or as phosphatidylinositol labelling, occurred equally well in incubation media containing 2.5 mm-Ca2+ or 0.2 mm-EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid]. Incubation with a bivalent cation ionophore (A23187) led to a small and more variable increase in phosphatidylinositol labelling with 32Pi, which occurred whether or not Ca2+ was available in the extracellular medium: this was not accompanied by significant phosphatidylinositol breakdown. Cinchocaine, a local anaesthetic, produced parallel increases in the incorporation of Pi and glycerol into phosphatidylinositol. This is compatible with its known ability to inhibit phosphatidate phosphohydrolase (EC 3.1.3.4) and increase phosphatidylinositol synthesis de novo in other cells. These results indicate that the phosphatidylinositol turnover evoked by alpha-adrenergic or muscarinic cholinergic stimuli in rat parotid gland probably does not depend on an influx of Ca2+ into the cells in response to stimulation. This is in marked contrast with the K+ efflux from this tissue, which is controlled by the same receptors, but is strictly dependent on the presence of extracellular Ca2+. The Ca2+-independence of stimulated phosphatidylinositol metabolism may mean that it is controlled through a mode of receptor function different from that which controls other cell responses. Alternatively, it can be interpreted as indicating that stimulated phosphatidylinositol breakdown is intimately involved in the mechanisms of action of alpha-adrenergic and muscarinic cholinergic receptor systems

Differentially Private Exponential Random Graphs

We propose methods to release and analyze synthetic graphs in order to protect privacy of individual relationships captured by the social network. Proposed techniques aim at fitting and estimating a wide class of exponential random graph models (ERGMs) in a differentially private manner, and thus offer rigorous privacy guarantees. More specifically, we use the randomized response mechanism to release networks under $\epsilon$-edge differential privacy. To maintain utility for statistical inference, treating the original graph as missing, we propose a way to use likelihood based inference and Markov chain Monte Carlo (MCMC) techniques to fit ERGMs to the produced synthetic networks. We demonstrate the usefulness of the proposed techniques on a real data example.Comment: minor edit

Tick Haller\u27s Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects

Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller\u27s organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller\u27s organ), we characterized 1st leg specific and putative Haller\u27s organ specific transcripts from adult American dog ticks, Dermacentor variabilis. The analysis suggested that the Haller\u27s organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller\u27s organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, Gαo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller\u27s organ specific, were examined in unfed and blood-fed adult female and male D. variabilis. Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller\u27s organ in N,N-diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller\u27s organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction