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Supplementary Data. Supplementary data containing supporting figure legends and mat and meth.

Supplementary Figures, Table, and Materials and Methods. Supplementary Figures S1-4. S1: Skin sections of control and 4OHT treated mice. S2: Immunohistochemical analysis of murine back skin sections from vehicle- (Ctrl) and 4OHT-treated mice with antibodies against P-Cofilin, and IgG control. S3: Quantitative RT-PCR of YAP/TAZ signaling markers. S4: CD98hc-deficient keratinocytes (GFP positive) reconstituted with different chimeras were seeded on 50kPa stiffness collagen-coated hydrogels for 48 hours. Supplemental Table 1. Set of qRT-PCR specific primers Sup Materials and Methods

Efficient methodologies to fully extract and analyse large datasets remain the Achilles heels of 3D tissue imaging. Here we present PACESS, a pipeline for large-scale data extraction and spatial statistical analysis from 3D biological images. First, using 3D object detection neural networks trained on annotated 2D data, we identify and classify the location of hundreds of thousands of cells contained in large biological images. Then, we introduce a series of statistical techniques tailored to work with spatial data, resulting in a 3D statistical map of the tissue from which multi-cellular interactions can be clearly understood. As illustration of the power of this new approach, we apply this analysis pipeline to an organ known to have a complex and still poorly understood cellular structure: the bone marrow. The analysis reveals coherent, useful biological information on multiple cell population interactions. This novel and powerful spatial analysis pipeline can be broadly used to unravel complex multi-cellular interaction towards unlocking tissue complexity.

Acute myeloid leukemia (AML) is a blood cancer of the myeloid lineage. Its prognosis remains poor, highlighting the need for new therapeutic and precision medicine approaches. AML symptoms often include cytopenias linked to loss of healthy hematopoietic stem and progenitor cells (HSPCs). The mechanisms behind HSPC decline are complex and still poorly understood. Here, intravital microscopy (IVM) of a well-established experimental model of AML allows direct observation of the interactions between healthy and malignant cells in the bone marrow (BM), suggesting that physical dislodgment of healthy cells by AML through damaged vasculature may play an important role. Multiple matrix metalloproteinases (MMPs), known to remodel extracellular matrix, are expressed by AML cells and the BM microenvironment. We reason MMPs could be involved in cell displacement and vascular leakiness; therefore, we evaluate the therapeutic potential of MMP pharmacological inhibition using the broad-spectrum inhibitor prinomastat. IVM analyses of prinomastat-treated mice reveal reduced vascular permeability and healthy cell clusters in circulation and lower AML infiltration, proliferation, and cell migration. Furthermore, treated mice have increased retention of healthy HSPCs in the BM and increased survival following chemotherapy. Analysis of a human AML transcriptomic database reveals widespread MMP deregulation, and human AML cells show susceptibility to MMP inhibition. Overall, our results suggest that MMP inhibition could be a promising complementary therapy to reduce AML growth and limit HSPC loss and BM vascular damage caused by MLL-AF9 and possibly other AML subtypes.

Adult stem cell fate is tightly balanced by the local microenvironment called niche and sustain tissue regeneration1–4. How niche signals are integrated and regulate regeneration remains largely unexplored. The extracellular matrix and integrin ligand fibronectin is a crucial and well-characterized wound healing actor that has never been involved in skin regeneration. Here, we show that fibronectin displays a highly specific enrichment in hair follicle stem cells (HFSC) at the onset of regeneration. Conditional deletion of fibronectin in HFSC compartment (Lrig1, K19) leads to hair regeneration blockade, impaired stem cell location and fate. Dermal injection of exogenous fibronectin rescues these phenotypes. To elucidate molecular mechanism underlying fibronectin function, we used conditional deletion models of SLC3A2, the main integrin coreceptor. We show that, via its role in integrin-dependent assembly of fibronectin matrix, SLC3A2 acts as molecular relay of niche signals. Thus, fibronectin-integrin-SLC3A2 cascade finely tunes HFSC fate and tissue regenerative power.

Skin homeostasis relies on fine-tuning of epidermis-dermis interactions and is affected by aging. While extracellular matrix (ECM) proteins, such as integrins, are involved in aging, the molecular basis of the skin changes needs to be investigated further. Here, we showed that integrin co-receptor, SLC3A2, required for cell proliferation, is expressed at the surface of resting dermal fibroblasts in young patients and is reduced drastically with aging. In vivo SLC3A2 dermal fibroblast deletion induced major skin phenotypes resembling premature aging. Knockout mice (3 months old) presented strong defects in skin elasticity due to altered ECM assembly, which impairs epidermal homeostasis. SLC3A2 dermal fibroblast loss led to an age-associated secretome profile, with 77% of identified proteins belonging to ECM and ECM-associated proteins. ECM not only contributes to skin mechanical properties, but it is also a reservoir of growth factors and bioactive molecules. We demonstrate that dermal fibroblast SLC3A2 is required for ECM to fully exert its structural and reservoir role allowing proper and efficient TGF-beta localization and activation. We identified SLC3A2 as a protective controller of dermal ECM stiffness and quality required to maintain the epidermis to dermis interface as functional and dynamic.

Mechanical cues are essential for the regulation of cell and tissue physiology. Hence, it has become an utmost necessity for cell biologists to account for those mechanical parameters when investigating biological processes and they need devices to manipulate cells accordingly. Here, we report a simple mechanical cell-stretching system that can generate uniaxial cyclic mechanical stretch on cells in tissue culture. This system is based upon a low-cost battery-powered uniaxial cyclic mechanical stretcher exclusively built out of LEGO

CD98hc functions as an amino acid (AA) transporter (together with another subunit) and integrin signaling enhancer. It is overexpressed in highly proliferative cells in both physiological and pathological conditions. CD98hc deletion induces strong impairment of cell proliferation in vivo and in vitro Here, we investigate CD98hc-associated AA transport in cell survival and proliferation. By using chimeric versions of CD98hc, the two functions of the protein can be uncoupled. Although recovering the CD98hc AA transport capacity restores the in vivo and in vitro proliferation of CD98hc-null cells, reconstitution of the integrin signaling function of CD98hc is unable to restore in vitro proliferation of those cells. CD98hc-associated transporters (i.e. xCT, LAT1, and y(+)LAT2 in wild-type cells) are crucial to control reactive oxygen species and intracellular AA levels, thus sustaining cell survival and proliferation. Moreover, in CD98hc-null cells the deficiency of CD98hc/xCT cannot be compensated, leading to cell death by ferroptosis. Supplementation of culture media with β-mercaptoethanol rescues CD98hc-deficient cell survival. Under such conditions null cells show oxidative stress and intracellular AA imbalance and, consequently, limited proliferation. CD98hc-null cells also present reduced intracellular levels of branched-chain and aromatic amino acids (BCAAs and ARO AAs, respectively) and induced expression of peptide transporter 1 (PEPT1). Interestingly, external supply of dipeptides containing BCAAs and ARO AAs rescues cell proliferation and compensates for impaired uptake of CD98hc/LAT1 and CD98hc/y(+)LAT2. Our data establish CD98hc as a master protective gene at the cross-road of redox control and AA availability, making it a relevant therapeutic target in cancer.

PURPOSE: F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, (18)F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and (18)F-FDOPA PET imaging results in PPGL. METHODS: From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by (18)F-FDOPA PET/CT for initial diagnosis/staging and follow-up. (18)F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. RESULTS: The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the (18)F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 (18)F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, (18)F-FDOPA uptake was positive and attributed to LAT4 expression. CONCLUSIONS: We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce (18)F-FDOPA uptake.

Skin, by nature, is very similar to the Rouquayrol-Denayrouze suit mentioned by Jules Verne in Twenty Thousand Leagues Under the Sea: it allows "to risk (…) new physiological conditions without suffering any organic disorder". Mechanical cues, to the same extent as other environmental parameters, are such "new physiological conditions". Indeed, skin's primary function is to form a protective barrier to shield inner tissues from the external environment. This requires unique mechanical properties as well as the ability to sense mechanical cues from the environment in order to prevent or repair mechanical damages as well as to function as the primary mechanosensory interface of the whole body.

Intubating patients with facial burn is difficult to most anesthesiologists. Awake flexible fiberoptic intubation is the gold standard for management of anticipated difficult tracheal intubation. However, serious facial burn and dysmorphic syndrome can make fiberoptic intubation more difficult or impossible. We report the use of awake oral intubation using the Pentax-Airway Scope (AWS) in two major burn patients with facial injury, in whom awake fiberoptic intubation was impossible. As shown in morbidly obese patient and in patients with unstable necks, AWS could be useful to facilitate tracheal intubation in awake, facial burn patients presenting with a potentially difficult airway. Awake AWS intubation seems as a potential alternative to awake fiberoptic intubation.

This paper presents a complete description of Virgo, the French-Italian gravitational wave detector. The detector, built at Cascina, near Pisa (Italy), is a very large Michelson interferometer, with 3 km-long arms. In this paper, following a presentation of the physics requirements, leading to the specifications for the construction of the detector, a detailed description of all its different elements is given. These include civil engineering infrastructures, a huge ultra-high vacuum (UHV) chamber (about 6000 cubic metres), all of the optical components, including high quality mirrors and their seismic isolating suspensions, all of the electronics required to control the interferometer and for signal detection. The expected performances of these different elements are given, leading to an overall sensitivity curve as a function of the incoming gravitational wave frequency. This description represents the detector as built and used in the first data-taking runs. Improvements in different parts have been and continue to be performed, leading to better sensitivities. These will be detailed in a forthcoming paper. © 2012 IOP Publishing Ltd and Sissa Medialab srl.

The uniformity of fertiliser spreading mainly depends on the evenness of the transversal distribution. During the last few years, more than 300 fertiliser spreaders have been tested on farms. The results have shown big differences between machines (coefficient of variation, CV, between 5 and more than 50%). The spreading homogeneity is linked to spreader features, fertiliser characteristics and user skills. The contamination of ground water by nitrogen depends on the locally applied quantity of fertiliser. Using farm spreading patterns, a simulation of the risk of contamination has been established, based on the increase of typical spreading errors. The risk of ground water contamination is assessed by using curves of residual nitrogen observed under field conditions in Belgium. It is thus possible to determine an acceptable level of fertiliser spreading heterogeneity. Copyright © 2002 John Wiley & Sons, Ltd.

CD98hc (SLC3A2) is the heavy chain component of the dimeric transmembrane glycoprotein CD98, which comprises the large neutral amino acid transporter LAT1 (SLC7A5) in cells. Overexpression of CD98hc occurs widely in cancer cells and is associated with poor prognosis clinically, but its exact contributions to tumorigenesis are uncertain. In this study, we showed that genetic deficiency of CD98hc protects against Ras-driven skin carcinogenesis. Deleting CD98hc after tumor induction was also sufficient to cause regression of existing tumors. Investigations into the basis for these effects defined two new functions of CD98hc that contribute to epithelial cancer beyond an intrinsic effect of CD98hc on tumor cell proliferation. First, CD98hc increased the stiffness of the tumor microenvironment. Second, CD98hc amplified the capacity of cells to respond to matrix rigidity, an essential factor in tumor development. Mechanistically, CD98hc mediated this stiffness sensing by increasing Rho kinase (ROCK) activity, resulting in increased transcription mediated by YAP/TAZ, a nuclear relay for mechanical signals. Our results suggest that CD98hc contributes to carcinogenesis by amplifying a positive feedback loop, which increases both extracellular matrix stiffness and resulting cellular responses. This work supports a rationale to explore the use of CD98hc inhibitors as cancer therapeutics. Cancer Res; 74(23); 6878–89. ©2014 AACR.

The homogeneous application of fertilizers depends on the physical properties of the particles, such as particle size distribution, bulk density, particle shape and breaking strength. Often with blended fertilizers, each component has its own physical characteristics. Experiments were carried out to determine the transversal distribution patterns of the components of two blended fertilizers after spreading. It was found that components were segregated according to the projection distance and that this resulted in an uneven chemical application over the field. Several tests show that the application rate of some components can vary by more than 40%. The granulometry of the particles explains only partly the behaviour of the blend, others factors linked to the motion of the particles on the disc must be taken into account.

In order to check the system aspects of the forward-backward MSGC tracker designed for the future CMS experiment at LHC: 38 trapezoidal MSGC counters assembled in six multi-substrates detector modules were built and exposed to a muon beam at the CERN SPS. Results on the gain uniformity along the wedge-shaped strip pattern and across the detector modules are shown together with measurements of the detection efficiency and the spatial resolution. (C) 1999 Elsevier Science B.V. All rights reserved.

Loss of CD98hc expression in young adult skin induces changes similar to those associated with aging, including improper skin homeostasis and epidermal wound healing., Skin aging is linked to reduced epidermal proliferation and general extracellular matrix atrophy. This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro. We unravel CD98hc functions in vivo in skin. We report that CD98hc invalidation has no appreciable effect on cell adhesion, clearly showing that CD98hc disruption phenocopies neither CD98hc knockdown in cultured keratinocytes nor epidermal β1 integrin loss in vivo. Instead, we show that CD98hc deletion in murine epidermis results in improper skin homeostasis and epidermal wound healing. These defects resemble aged skin alterations and correlate with reduction of CD98hc expression observed in elderly mice. We also demonstrate that CD98hc absence in vivo induces defects as early as integrin-dependent Src activation. We decipher the molecular mechanisms involved in vivo by revealing a crucial role of the CD98hc/integrins/Rho guanine nucleotide exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis. Finally, we demonstrate that the deregulation of RhoA activation in the absence of CD98hc is also a result of impaired CD98hc-dependent amino acid transports.

To evaluate a monitor of pulmonary gas exchange (Deltatrac, Datex) in a clinical setting.After in vitro evaluation, comparison over 2 min between VO2 and VCO2 values measured by the Deltatrac and the Douglas bag technique. Comparisons were also achieved over 8 h periods between the Deltatrac and a system using a mass-spectrometer.Polyvalent intensive care unit (ICU 15 beds) in a 1200 bed general hospital.Comparison with the Douglas bag technique in 10 patients undergoing controlled ventilation. Comparison with the mass-spectrometer system in 25 other patients undergoing controlled or pressure support ventilation.Compared to the results obtained by the Douglas bag technique, the bias (+/- 2 SD) for VO2 and VCO2 was -3.5 +/- 26.6 and 6.1 +/- 12.7 ml.min-1, respectively. By comparison with the mass-spectrometer system, the bias for VO2 and RQ was -5.8 +/- 16.0 ml.min-1 and 0.018 +/- 0.048, respectively. No drift between the two systems was observed over time.The Deltatrac appears suitable for VO2 and VCO2 measurements in ventilated patients and equivalent to a mass-spectrometer system for long term measurements.

Intubating patients with facial burn is difficult to most anesthesiologists. Awake flexible fiberoptic intubation is the gold standard for management of anticipated difficult tracheal intubation. However, serious facial burn and dysmorphic syndrome can make fiberoptic intubation more difficult or impossible. We report the use of awake oral intubation using the Pentax-Airway Scope (AWS) in two major burn patients with facial injury, in whom awake fiberoptic intubation was impossible. As shown in morbidly obese patient and in patients with unstable necks, AWS could be useful to facilitate tracheal intubation in awake, facial burn patients presenting with a potentially difficult airway. Awake AWS intubation seems as a potential alternative to awake fiberoptic intubation.

The component test as well as the setting up of the of the large interferometer of the Virgo project requires accurate monitoring of the laser beam position and shape. Such a monitoring should work in real time and should be well integrated to the interferometer control system. In this paper we present a beam imaging system based on a CCD camera interfaced to VME and graphic analysis tools specially developed for this application.

Gas chromatography/isotope ratio mass spectrometry (GC/IRMS) allows the detection of low 13C enrichment. However, this method needs to set up new metabolite derivatives suitable for GC/IRMS. In this work we describe a new derivative for plasma lactate analysis. After plasma extraction, diazomethane is used to methylate the lactate carboxyl group. The lactate methylester reacts with acetic anhydride in pyridine to give an acetylated methyl ester of lactate. The isotopic 13C enrichment of this compound is determined by GC/IRMS. A correction method for the effects of the added derivative carbon atoms on measurements of the derivatized compounds is also described. This method appears reproducible and allows the detection of 13C enrichment as low as 0.01 mol.%. A practical application for the measurement of 13C plasma lactate enrichment after ingestion of an oral glucose load (0.5 g kg−1) enriched with 0.1% D-(U-13C)glucose is shown.

Measurement of the nutrient oxidation rate with 13C as a tracer requires knowledge of the value of its coefficient of fractional recovery in the expired gas (FR). We measured FR in nine intensive care patients who were mechanically ventilated and received total parenteral nutrition. NaH13CO3 was administered at a priming dose (3.75 mumol.kg-1.min-1) followed by a continuous infusion (0.05 mumol.kg-1.min-1). Metabolic rate and pulmonary carbon dioxide elimination (VCO2) were measured by using a mass-spectrometer system. The 13C-12C ratio was measured in the expired gas with an isotopic-ratio mass spectrometer and FR was calculated by using standard equations. The average value of FR was 0.899 +/- 0.026 (means +/- SE) and remained stable for each patient on 2 consecutive days. Between patients, the coefficient of variation of FR was 8.6%. Metabolic rate was the only physiological factor found to affect the FR value.

The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4±0.7 mg·kg−1· min−1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1±1.1 mg· kg−1· min−1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g· kg·−1), 1 g· kg ·−1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97±0.04 g· kg·−1 and 1.2±0.04 g· kg·−1, exogenous glucose appearance was 0.51±0.02 g· kg·−1 and 0.84±0.04 g· kg·−1, endogenous glucose production was 0.44±0.04 g· kg·−1 and 0.35±0.06 g·kg·−1 after the 0.5 and 1 g·kg·−1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes. These results show that reliable kinetic parameters of glucose metabolism can be determined, without health hazard, in humans, at low cost, using 13C labelled glucose analysed with a new gas chromatograph-isotope ratio mass spectrometer.

If the intimacy of the private conversation between the doctor and his patient cannot be penetrated by any external observer, it remains that historical, social, and cultural factors around this meeting can be examined and contextualized. With this perspective, this publication presents a reflection on the context of the therapeutic relationship in the second part of the 18th century. This study is based on about 1,300 consultations written to Dr. Tissot, famous Swiss physician who practised between 1750 and 1797. Most of these accounts, coming from patients or their lay mediators, show how the authors perceived the figure of the doctor, and their relation to money, time, and space. All of these elements are considered to determine the nature of this relationship.

Introduction La liberation systemique de mediateurs de l’inflammation apres une brulure grave contribue a une dysfonction cardiovasculaire de type choc distributif. En complement du remplissage vasculaire et afin de maintenir un debit cardiaque suffisant, l’ajout precoce d’un vasopresseur est recommande. Toutefois, l’utilisation inappropriee des vasopresseurs pourrait initialement aggraver les lesions et secondairement retarder la cicatrisation. L’utilisation d’hemisuccinate d’hydrocortisone (HSHC) reduit la duree du choc mais les mecanismes impliques sont mal connus [1] . Nous avons etudie la modulation du transcriptome induite par l’HSHC dans les suites d’une brulure grave. Materiel et methodes Trente patients brules grave (> 30 % de la surface totale) presentant un etat de choc refractaire (> 0,5 μg/kg/min de noradrenaline) ont ete inclus dans un essai prospectif, randomise, evaluant l’administration d’HSHC contre placebo. Nous avons analyse la modulation du transcriptome de cette cohorte de patients a partir de prelevements realises a l’inclusion avant l’administration d’HSHC (J0), a J1, J5 et J7. Des prelevements realises chez 13 volontaires sains ont egalement ete inclus dans cette analyse. L’analyse du transcriptome a ete realisee sur puces pan-genomiques Affymetrix (HG-U133 plus 2). Resultats En comparaison aux volontaires sains, la brulure grave induit la modulation d’un tres grand nombre de genes (n > 2200 a J0), avec un effet d’amplification au cours du temps. Parmi les patients brules, le traitement par HSHC modifie l’expression de 339 genes a J1 et 627 a J5, avec seulement 24 genes modules a J7. Les genes modules a J1 sont impliques dans une inhibition des fonctions de croissance, developpement et production des leucocytes. Aucune fonction specifique n’a ete retrouvee enrichie a J5 ce qui suggere que l’effet de l’HSHC sur la modulation du transcriptome sanguin est de courte duree. ( Tableau 1 ). Nombre de genes modules entre les patients brules et les volontaires sains, ainsi qu’entre les patients traites par HSHC ou placebo, au cours du temps. Discussion Cette etude apporte des informations interessantes concernant la modulation de la reponse de l’hote par l’adjonction d’un traitement par HSHC dans les suites d’une brulure grave, notamment sur un eventuel mecanisme d’action de l’HSHC dans la reduction de la duree du choc apres brulure grave.

Introduction L’ecologie bacterienne dans un service de reanimation a un impact majeur en termes de morbi-mortalite, a fortiori dans un centre de traitement des brules ou la duree de sejour des patients est augmentee par rapport a une reanimation polyvalente. Materiel et methodes Une etude retrospective a ete realisee dans le service de reanimation du centre de traitement des brules pendant 4 ans, entre 2008 et 2011. Les germes, les infections et la susceptibilite aux antibiotiques ont ete colliges. Une infection a un meme germe a 15 jours d’intervalle etait consideree comme une nouvelle infection. Les resultats sont exprimes en mediane [1er quartile ; 3e quartile]. Resultats Deux mille cent soixante-quinze prelevements chez 227 patients ont ete realises de 2008 a 2011, dont 751 prelevements positifs. Le sex-ratio (homme/femme) etait de 2,2. L’âge des patients etait de 44 [27 ; 61] ans. La surface corporelle brulee (SB) etait de 26 [17 ; 40] %. La duree mediane de sejour etait de 41 [26 ; 43] jours. Le detail des prelevements et leur positivite sont resumes dans le Tableau 1 . Ces 751 prelevements positifs ont permis de diagnostiques 558 infections. Il y avait une majorite d’infections pulmonaires (n = 296, 53 %). Les autres infections comprenaient : 28 % (n = 157) d’infections urinaires et 19 % (n = 105) de septicemies. Le ratio d’infection par patient preleve etait de 2,46. Le delai moyen de survenue de la premiere infection au cours de l’hospitalisation etait de 16 ± 10 jours. Les principaux germes identifies etaient : Escherichia coli (n = 71, 13 %), Candida spp. (n = 62, 11 %), Staphyloccocus aureus (n = 42, 8 %), Pseudomonas aeruginosa (n = 30, 5 %), Haemophilus influenzae (n = 30, 5 %). Seuls 2 prelevements ont ete positifs a Acinetobacter baumani. Klebsiella pneumoniae n’a ete identifie que pour 16 (3 %) des prelevements. Concernant les Staphylococcus aureus nous n’avons identifie qu’un seul cas de resistance a la Meticilline dans un LBA, et aucune resistance a la vancomycine, teicoplanine et linezolide. Seuls 6 (0,2 %) Pseudomonas aeruginosa resistants a l’imipenem ont ete isoles. Discussion Les 2 Acinetobacter baumani identifies dans cette etude sont des cas importes, presents des l’admission chez des patients qui avaient recu prealablement une antibiotherapie probabiliste a large spectre. L’ecologie de notre service differe de l’a priori negatif repandu au sujet des brules, ainsi que de l’ecologie rencontree dans d’autres centres de traitement des brules [1] , [2] . La singularite de notre ecologie est probablement liee en partie a notre gestion des antibiotiques (pas d’antibioprophylaxie, pas de traitement antibiotique des portages cutanes). Une gestion raisonnee et ciblee de l’antibiotherapie peut permettre de diminuer le nombre de germes resistants et ce de facon stable dans le temps.

The effects of lipid administration on carbohydrate oxidation rate remain controversial, particularly in critically ill patients. The aim of this study was to determine the effects of these patients of a continuous lipid infusion on glucose metabolism using indirect calorimetry and stable isotopes. We studied seven patients, mechanically ventilated, during two consecutive 24-h periods. Throughout the first period they received a continuous infusion of glucose (2 mg.kg-1.min-1) and amino acids. During the second period, in addition to the glucose, they received a continuous infusion of 1 mg.kg-1.min-1 of long-chain triglycerides emulsion. Substrate oxidation rates were calculated from pulmonary gas exchange and nitrogen excretion measurements. Glucose kinetic parameters were measured using primed constant infusions of [6,6-2H2]glucose and [1-13C]glucose. The lipid infusion did not modify the glucose metabolism parameters; 45% of the lipid supply was stored.

The construction of two broad bandwidth gravitational antennae (Virgo and Ligo) is now started. Such interferometric detectors will do a constant survey of the sky. It results in a huge amount of continuously recorded data, inconsistent with the need for a flexible and tunable off-line signal search. This requires on line triggers, selecting “gravitational wave signal candidates”. Such triggers do not perform on-line analysis but only a preselection of candidates which should then go trough a fully detailed off-line analysis. This work is a first attempt to study some simple on-line trigger algorithms for the future interferometric Virgo detector, looking for signals induced by binary coalescences. Firstly, we point out the conditions that on-line triggers must obey. Then, we show that, used as an on-line trigger, the standard method of matched-filtering has some problems to fulfil these conditions. In a third step, we propose and study possible trigger algorithms, focusing our attention on their efficiency, their ability to reduce the amount of data, their robustness in front of the first post-Newtonian term and, of course, their processing speed.

Pulmonary gas exchange measurements can be performed in ICU with commercially available devices. During open-circuit anaesthesia, measurement of VO2 and VCO2 requires the acquisition of fractional concentration of inspired and expired nitrogen, the appropriate calibration of sensors according to the use of anaesthetic gases and to take into account the unsteady state of nitrogen body stores after a change in FiN2. This technique can be readily used to measure energetic expenditure or to specific applications as oxygen cost of breathing, respiratory effects of parenteral nutrition or the metabolic effects of various anaesthetic procedures in man.

A 65-year-old man developed postsurgical septic shock, unresponsive to plasma volume expansion and administration of dopamine and dobutamine. A continuous norepinephrine infusion was then started and the dose increased to 0.62 micrograms.kg-1.min-1 until the mean arterial pressure was 70 mmHg. Prior to and during the norepinephrine infusion, oxygen consumption was continuously measured with a mass spectrometer system. There was a parallel increase in mean arterial pressure and oxygen consumption (+ 35%). There was also an increase in cardiac index and oxygen delivery. Systemic vascular resistance was only transiently increased. In this case with septic shock, norepinephrine infusion improved hemodynamic variables with an associated increase in oxygen consumption.