371 research outputs found
Colistin dry powder inhalation with the Twincer (TM):An effective and more patient friendly alternative to nebulization
BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincerâą is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates
Twistor Strings with Flavour
We explore the tree-level description of a class of N=2 UV-finite SYM
theories with fundamental flavour within a topological B-model twistor string
framework. In particular, we identify the twistor dual of the Sp(N) gauge
theory with one antisymmetric and four fundamental hypermultiplets, as well as
that of the SU(N) theory with 2N hypermultiplets. This is achieved by suitably
orientifolding/orbifolding the original N=4 setup of Witten and adding a
certain number of new topological 'flavour'-branes at the orientifold/orbifold
fixed planes to provide the fundamental matter. We further comment on the
appearance of these objects in the B-model on CP(3|4). An interesting aspect of
our construction is that, unlike the IIB description of these theories in terms
of D3 and D7-branes, on the twistor side part of the global flavour symmetry is
realised geometrically. We provide evidence for this correspondence by
calculating and matching amplitudes on both sides.Comment: 38+12 pages; uses axodraw.sty. v2: References added, minor
clarification
Built-in and induced polarization across LaAlO/SrTiO heterojunctions
Ionic crystals terminated at oppositely charged polar surfaces are inherently
unstable and expected to undergo surface reconstructions to maintain
electrostatic stability. Essentially, an electric field that arises between
oppositely charged atomic planes gives rise to a built-in potential that
diverges with thickness. In ultra thin film form however the polar crystals are
expected to remain stable without necessitating surface reconstructions, yet
the built-in potential has eluded observation. Here we present evidence of a
built-in potential across polar \lao ~thin films grown on \sto ~substrates, a
system well known for the electron gas that forms at the interface. By
performing electron tunneling measurements between the electron gas and a
metallic gate on \lao ~we measure a built-in electric field across \lao ~of 93
meV/\AA. Additionally, capacitance measurements reveal the presence of an
induced dipole moment near the interface in \sto, illuminating a unique
property of \sto ~substrates. We forsee use of the ionic built-in potential as
an additional tuning parameter in both existing and novel device architectures,
especially as atomic control of oxide interfaces gains widespread momentum.Comment: 6 pages, 4 figures. Submitted to Nature physics on May 1st, 201
The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis
Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34Ă10<sup>â8</sup>, OR = 1.22, CI 95% = 1.14â1.30; rs2004640: P = 4.60Ă10<sup>â7</sup>, OR = 0.84, CI 95% = 0.78â0.90; rs10488631: P = 7.53Ă10<sup>â20</sup>, OR = 1.63, CI 95% = 1.47â1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04Ă10<sup>â22</sup>, OR = 1.75, CI 95% = 1.56â1.97) better explained the observed association (likelihood P-value = 1.48Ă10<sup>â4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific
Separating the wheat from the chaff: a prioritisation pipeline for the analysis of metabolomics datasets
Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful and widely applied method for the study of biological systems, biomarker discovery and pharmacological interventions. LC-MS measurements are, however, significantly complicated by several technical challenges, including: (1) ionisation suppression/enhancement, disturbing the correct quantification of analytes, and (2) the detection of large amounts of separate derivative ions, increasing the complexity of the spectra, but not their information content. Here we introduce an experimental and analytical strategy that leads to robust metabolome profiles in the face of these challenges. Our method is based on rigorous filtering of the measured signals based on a series of sample dilutions. Such data sets have the additional characteristic that they allow a more robust assessment of detection signal quality for each metabolite. Using our method, almost 80% of the recorded signals can be discarded as uninformative, while important information is retained. As a consequence, we obtain a broader understanding of the information content of our analyses and a better assessment of the metabolites detected in the analyzed data sets. We illustrate the applicability of this method using standard mixtures, as well as cell extracts from bacterial samples. It is evident that this method can be applied in many types of LC-MS analyses and more specifically in untargeted metabolomics
Networking Our Way to Better Ecosystem Service Provision.
The ecosystem services (EcoS) concept is being used increasingly to attach values to natural systems and the multiple benefits they provide to human societies. Ecosystem processes or functions only become EcoS if they are shown to have social and/or economic value. This should assure an explicit connection between the natural and social sciences, but EcoS approaches have been criticized for retaining little natural science. Preserving the natural, ecological science context within EcoS research is challenging because the multiple disciplines involved have very different traditions and vocabularies (common-language challenge) and span many organizational levels and temporal and spatial scales (scale challenge) that define the relevant interacting entities (interaction challenge). We propose a network-based approach to transcend these discipline challenges and place the natural science context at the heart of EcoS research.The QUINTESSENCE Consortium gratefully acknowledges the support of DĂ©partment SPE and MĂ©taprogramme ECOSERV of INRA, and the French ANR projects PEERLESS (ANR-12-AGRO-0006) and AgroBioSE (ANR-13-AGRO-0001).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.tree.2015.12.00
Mapping the Spatial Distribution of Charge Carriers in LaAlO3/SrTiO3 Heterostructures
At the interface between complex insulating oxides, novel phases with
interesting properties may occur, such as the metallic state reported in the
LaAlO3/SrTiO3 system. While this state has been predicted and reported to be
confined at the interface, some works indicate a much broader spatial
extension, thereby questioning its origin. Here we provide for the first time a
direct determination of the carrier density profile of this system through
resistance profile mappings collected in cross-section LaAlO3/SrTiO3 samples
with a conducting-tip atomic force microscope (CT-AFM). We find that, depending
upon specific growth protocols, the spatial extension of the high-mobility
electron gas can be varied from hundreds of microns into SrTiO3 to a few
nanometers next to the LaAlO3/SrTiO3 interface. Our results emphasize the
potential of CT-AFM as a novel tool to characterize complex oxide interfaces
and provide us with a definitive and conclusive way to reconcile the body of
experimental data in this system.Comment: This updated version contains new experimental dat
Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.
BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma
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