2,275 research outputs found
Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide
INTRODUCTION: Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates TLR2 expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP). METHOD: Both in vitro and in vivo experiments were conducted. First, TLR2 expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). After a 24-hour period of cyclic stretch, the inflammatory response of the A549 cells to the synthetic BLP, Pam(3)CSK(4), was tested after 8 hours of exposure. In a second set of experiments, healthy anesthetized and paralyzed rabbits were submitted to 8-hour MV (tidal volume = 12 ml/kg, zero end-expiratory pressure; FIO(2 )= 50%; respiratory rate = 20/minute) before being sacrificed for TLR2 lung expression assessment. The lung inflammatory response to BLP was then tested in animals submitted to 24-hour MV before being sacrificed 8 hours after the tracheal instillation of Pam(3)CSK(4). RESULTS: Cyclic stretch of human pulmonary epithelial cell lines increased both TLR2 mRNA and protein expression. Cells submitted to cyclic stretch also increased IL-6 and IL-8 secretion in response to Pam(3)CSK(4), a classical TLR2 ligand. A mild-stretch MV protocol induced a 60-fold increase of TLR2 mRNA expression in lung tissue when compared with spontaneously breathing controls. Moreover, the combination of MV and airway exposure to Pam(3)CSK(4 )acted synergistically in causing lung inflammation and injury. CONCLUSIONS: Mild-stretch MV increases lung expression of TLR2 and sensitizes the lung to bacterial TLR2 ligands. This may account for the propensity of mechanically ventilated patients to develop acute lung injury in the context of airway bacterial colonization/infection
Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome
Mössbauer spectroscopy study of MgAl2O4-matrix nanocomposite powders containing carbon nanotubes and iron-based nanoparticles
Materials involved in the catalytic formation of carbon nanotubes are for the first time systematically studied by Mössbauer spectroscopy between 11 K and room temperature. Mg1âxFexAl2O4 (x=0.1, 0.2, 0.3, 0.4) solid solutions are transformed into carbon nanotubesâFe/Fe3CâMgAl2O4 composite powders by reduction in a H2âCH4 gas mixture. The oxides are defective spinels of general formulae (Mg1âx2+Fexâ3α2+Fe2α3+âĄÎ±Al23+)O42â. Ferromagnetic α-Fe, ferromagnetic Fe3C and a Îł-Fe form, the latter possibly corresponding to a Îł-FeâC alloy, are detected in the composite powders. An attempt is made to correlate these results with the microstructure of the powder. It seems that the nanoparticles, which catalyze the formation of the carbon nanotubes, are detected as Fe3C in the post-reaction Mössbauer spectroscopy analysis
An interferometric study of the Fomalhaut inner debris disk. I. Near-infrared detection of hot dust with VLTI/VINCI
The innermost parts of dusty debris disks around main sequence stars are
currently poorly known due to the high contrast and small angular separation
with their parent stars. Using near-infrared interferometry, we aim to detect
the signature of hot dust around the nearby A4 V star Fomalhaut, which has
already been suggested to harbor a warm dust population in addition to a cold
dust ring located at about 140 AU. Archival data obtained with the VINCI
instrument at the VLTI are used to study the fringe visibility of the Fomalhaut
system at projected baseline lengths ranging from 4 m to 140 m in the K band. A
significant visibility deficit is observed at short baselines with respect to
the expected visibility of the sole stellar photosphere. This is interpreted as
the signature of resolved circumstellar emission, producing a relative flux of
0.88% +/- 0.12% with respect to the stellar photosphere. While our
interferometric data cannot directly constrain the morphology of the excess
emission source, complementary data from the literature allow us to discard an
off-axis point-like object as the source of circumstellar emission. We argue
that the thermal emission from hot dusty grains located within 6 AU from
Fomalhaut is the most plausible explanation for the detected excess. Our study
also provides a revised limb-darkened diameter for Fomalhaut (2.223 +/- 0.022
mas), taking into account the effect of the resolved circumstellar emission.Comment: 13 pages, accepted for publication in Ap
Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report
<p>Abstract</p> <p>Background</p> <p>The usefulness of procalcitonin (PCT) measurement in critically ill medical patients with suspected nosocomial infection is unclear. The aim of the study was to assess PCT value for the early diagnosis of bacterial nosocomial infection in selected critically ill patients.</p> <p>Methods</p> <p>An observational cohort study in a 15-bed intensive care unit was performed. Seventy patients with either proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial infection were included. Procalcitonin measurements were obtained the day when the infection was suspected (D0) and at least one time within the 3 previous days (D-3 to D0). Patients with proven infection were compared to those without. The diagnostic value of PCT on D0 was determined through the construction of the corresponding receiver operating characteristic (ROC) curve. In addition, the predictive value of PCT variations preceding the clinical suspicion of infection was assessed.</p> <p>Results</p> <p>PCT on D0 was the best predictor of proven infection in this population of ICU patients with a clinical suspicion of infection (AUROCC = 0.80; 95% CI, 0.68â0.91). Thus, a cut-off value of 0.44 ng/mL provides sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin variation between D-1 and D0 was calculated in 45 patients and was also found to be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79â0.98) with a 100% positive predictive value if the +0.26 ng/mL threshold value was applied. Comparable results were obtained when PCT variation between D-2 and D0, or D-3 and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had a poor predictive value in our population.</p> <p>Conclusion</p> <p>PCT monitoring could be helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute values and variations should be considered and evaluated in further studies.</p
Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse.
The authors wish to thank the personnel of the IRCM animal facility team, the histology (RHEM) platform, the Affymetrix platform of Montpellier and Dr Caroline Mollevi from the Biostatistics platform at ICM for their help in this project. The constant support of ICM and SIRIC Montpellier-Cancer is gratefully acknowledged.International audiencePatient derived xenografts (PDXs) are increasingly appreciated models in cancer research, particularly for preclinical testing, as they reflect the patient's tumor biology more accurately than cancer cell lines. We have established a collection of 20 breast PDXs and characterized their biological and clinical features, as well as their genetic stability. While most PDXs originated from triple negative breast cancers (70%), our collection comprised five ER + cases (25%). Remarkably, the tumors that produced PDXs derived from a subset of aggressive breast cancers with a high proportion of grade 3 tumors and reduced recurrence-free survival. Consistent with this, we found significant differences between the transcriptomic signatures of tumors that produced a PDX (Take) and those that did not (No Take). The PDXs faithfully recapitulate the histological features of their primary tumors, and retain an excellent conservation of molecular classification assignment and Copy Number Change (CNC). Furthermore, the CNC profiles of different PDXs established from the same tumor overlap significantly. However, a small fraction of CNCs in the primary tumor that correspond to oligoclonal events were gradually lost during sequential passaging, suggesting that the PDXs' genetic structure eventually stabilizes around a dominant clone present in the tumor of origin. Finally, de novo occurring genetic events covering up to 9% of the genome were found in only a minority of the PDXs, showing that PDXs have limited genetic instability. These data show that breast cancer PDXs represent a subset of aggressive tumors prone to relapse, and that despite of an excellent conservation of original features, they remain genetically dynamic elements
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The catastrophic flash-flood event of 8â9 September 2002 in the Gard region, France: a first case study for the CĂ©vennesâVivarais Mediterranean Hydrometeorological Observatory
The CĂ©vennesâVivarais Mediterranean Hydrometeorological Observatory (OHM-CV) is a research initiative aimed at improving the understanding and modeling of the Mediterranean intense rain events that frequently result in devastating flash floods in southern France. A primary objective is to bring together the skills of meteorologists and hydrologists, modelers and instrumentalists, researchers and practitioners, to cope with these rather unpredictable events. In line with previously published flash-flood monographs, the present paper aims at documenting the 8â9 September 2002 catastrophic event, which resulted in 24 casualties and an economic damage evaluated at 1.2 billion euros (i.e., about 1 billion U.S. dollars) in the Gard region, France. A description of the synoptic meteorological situation is first given and shows that no particular precursor indicated the imminence of such an extreme event. Then, radar and rain gauge analyses are used to assess the magnitude of the rain event, which was particularly remarkable for its spatial extent with rain amounts greater than 200 mm in 24 h over 5500 km2. The maximum values of 600â700 mm observed locally are among the highest daily records in the region. The preliminary results of the postevent hydrological investigation show that the hydrologic response of the upstream watersheds of the Gard and Vidourle Rivers is consistent with the marked spaceâtime structure of the rain event. It is noteworthy that peak specific discharges were very high over most of the affected areas (5â10 m3 sâ1 kmâ2) and reached locally extraordinary values of more than 20 m3 sâ1 kmâ2. A preliminary analysis indicates contrasting hydrological behaviors that seem to be related to geomorphological factors, notably the influence of karst in part of the region. An overview of the ongoing meteorological and hydrological research projects devoted to this case study within the OHM-CV is finally presented
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Bourdieusian Reflections on Language: Unavoidable Conditions of the Real Speech Situation
The main purpose of this paper is to shed light on Pierre Bourdieuâs conception of language. Although he has dedicated a significant part of his work to the study of language and even though his analysis of language has been extensively discussed in the literature, almost no attention has been paid to the factthat Bourdieuâs account of language is based on a number of ontological presuppositions, that is, on a set of universal assumptions about the very nature of language. This article aims to fill this gap in the literature by offering a detailed overview of 10 key features which, from a Bourdieusian point of view, can be regarded as inherent in language. On the basis of this enquiry,the study seeks todemonstrate thatââcontraryto commonbeliefââthere is not only a Bourdieusian sociology of language but also a Bourdieusian philosophy of language, which provides a useful theoretical framework for examining the unavoidable conditions of the real speech situation. The paper draws to a close by reflecting on the flaws and limitations of Bourdieuâs approach to language
High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)
(abridged) A complete census of planetary systems around a volume-limited
sample of solar-type stars (FGK dwarfs) in the Solar neighborhood with uniform
sensitivity down to Earth-mass planets within their Habitable Zones out to
several AUs would be a major milestone in extrasolar planets astrophysics. This
fundamental goal can be achieved with a mission concept such as NEAT - the
Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne
extremely-high-precision astrometric measurements sufficient to detect
dynamical effects due to orbiting planets of mass even lower than Earth's
around the nearest stars. Such a survey mission would provide the actual
planetary masses and the full orbital geometry for all the components of the
detected planetary systems down to the Earth-mass limit. The NEAT performance
limits can be achieved by carrying out differential astrometry between the
targets and a set of suitable reference stars in the field. The NEAT instrument
design consists of an off-axis parabola single-mirror telescope, a detector
with a large field of view made of small movable CCDs located around a fixed
central CCD, and an interferometric calibration system originating from
metrology fibers located at the primary mirror. The proposed mission
architecture relies on the use of two satellites operating at L2 for 5 years,
flying in formation and offering a capability of more than 20,000
reconfigurations (alternative option uses deployable boom). The NEAT primary
science program will encompass an astrometric survey of our 200 closest F-, G-
and K-type stellar neighbors, with an average of 50 visits. The remaining time
might be allocated to improve the characterization of the architecture of
selected planetary systems around nearby targets of specific interest (low-mass
stars, young stars, etc.) discovered by Gaia, ground-based high-precision
radial-velocity surveys.Comment: Accepted for publication in Experimental Astronomy. The full member
list of the NEAT proposal and the news about the project are available at
http://neat.obs.ujf-grenoble.fr. The final publication is available at
http://www.springerlink.co
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