A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

Application of the rainbow trout derived intestinal cell line (RTgutGC) for ecotoxicological studies: molecular and cellular responses following exposure to copper.

There is an acknowledged need for in vitro fish intestinal model to help understand dietary exposure to chemicals in the aquatic environment. The presence and use of such models is however largely restrictive due to technical difficulties in the culturing of enterocytes in general and the availability of appropriate established cell lines in particular. In this study, the rainbow trout (Oncorhynchus mykiss) intestinal derived cell line (RTgutGC) was used as a surrogate for the "gut sac" method. To facilitate comparison, RTgutGC cells were grown as monolayers (double-seeded) on permeable Transwell supports leading to a two-compartment intestinal model consisting of polarised epithelium. This two-compartment model divides the system into an upper apical (lumen) and a lower basolateral (portal blood) compartment. In our studies, these cells stained weakly for mucosubstances, expressed the tight junction protein ZO-1 in addition to E-cadherin and revealed the presence of polarised epithelium in addition to microvilli protrusions. The cells also revealed a comparable transepithelial electrical resistance (TEER) to the in vivo situation. Importantly, the cell line tolerated apical saline (1:1 ratio) thus mimicking the intact organ to allow assessment of uptake of compounds across the intestine. Following an exposure over 72 h, our study demonstrated that the RTgutGC cell line under sub-lethal concentrations of copper sulphate (Cu) and modified saline solutions demonstrated uptake of the metal with saturation levels comparable to short term ex situ gut sac preparations. Gene expression analysis revealed no significant influence of pH or time on mRNA expression levels of key stress related genes (i.e. CYP3A, GST, mtA, Pgp and SOD) in the Transwell model. However, significant positive correlations were found between all genes investigated suggesting a co-operative relationship amongst the genes studied. When the outlined characteristics of the cell line are combined with the division of compartments, the RTgutGC double seeded model represents a potential animal replacement model for ecotoxicological studies. Overall, this model could be used to study the effects and predict aquatic gastrointestinal permeability of metals and other environmentally relevant contaminants in a cost effective and high throughput manner

Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature

Measurement of the W+W−γW^{+}W^{-} \gamma Cross-section and First direct Limits on Anomalous Electroweak Quartic Gauge Couplings

A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W+W- events accompanied by hard photon radiation produced in e+e- collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183pb^-1 of data recorded at root{s}=189GeV. From these data, 17 W+W-gamma candidates are selected with photon energy greater than 10GeV, consistent with the Standard Model expectation. These events are used to measure the e+e- to W+W-gamma cross-section within a set of geometric and kinematic cuts; sigma{W+W-gamma} = 136+-37+-8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the {W+ W- gamma gamma} and {W+ W- gamma Z0} vertices: -0.070GeV^{-2} < a_0/Lambda^2 < 0.070GeV^{-2}, -0.13GeV^{-2} < a_c/Lambda^2 < 0.19GeV^{-2}, -0.61GeV^{-2} < a_n/Lambda^2 < 0.57GeV^{-2}, where Lambda represents the energy scale for new physics.A study of W + W − events accompanied by hard photon radiation produced in e + e − collisions at LEP is presented. Events consistent with two on-shell W-bosons and an isolated photon are selected from 183 pb −1 of data recorded at s =189 GeV. From these data, 17 W + W − γ candidates are selected with photon energy greater than 10 GeV, consistent with the Standard Model expectation. These events are used to measure the e + e − →W + W − γ cross-section within a set of geometric and kinematic cuts, σ ̂ WW γ =136±37±8 fb, where the first error is statistical and the second systematic. The photon energy spectrum is used to set the first direct, albeit weak, limits on possible anomalous contributions to the W + W − γγ and W + W − γ Z 0 vertices: −0.070 GeV −

τ\tau decays with neutral kaons

The branching ratio of the tau lepton to a neutral K meson is measured from a sample of approximately 200,000 tau decays recorded by the OPAL detector at centre-of-mass energies near the Z0 resonance. The measurement is based on two samples which identify one-prong tau decays with KL and KS mesons. The combined branching ratios are measured to be B(tau- -->pi- K0bar nutau) = (9.33+-0.68+-0.49)x10^-3 B(tau- -->pi- K0bar [>=1pi0] nutau) = (3.24+-0.74+-0.66)x10^-3 B(tau- -->K- K0bar [>=0pi0] nutau) = (3.30+-0.55+-0.39)x10^-3 where the first error is statistical and the second systematic.The branching ratio of the tau lepton to a neutral K meson is measured from a sample of approximately 200,000 tau decays recorded by the OPAL detector at centre-of-mass energies near the Z0 resonance. The measurement is based on two samples which identify one-prong tau decays with KL and KS mesons. The combined branching ratios are measured to be B(tau- -->pi- K0bar nutau) = (9.33+-0.68+-0.49)x10^-3 B(tau- -->pi- K0bar [>=1pi0] nutau) = (3.24+-0.74+-0.66)x10^-3 B(tau- -->K- K0bar [>=0pi0] nutau) = (3.30+-0.55+-0.39)x10^-3 where the first error is statistical and the second systematic

Transverse and Longitudinal Bose Einstein Correlations in hadronic Z0Z^0 Decays

Bose-Einstein correlations in pairs of identical charged pions produced in asample of 4.3 million Z0 hadronic decays are studied as a function of the threecomponents of the momentum difference, transverse ("out" and "side") andlongitudinal with respect to the thrust direction of the event. A significantdifference between the transverse, r_t_side, and longitudinal, r_l, dimensionsis observed, indicating that the emitting source of identical pions, asobserved in the Longitudinally CoMoving System, has an elongated shape. This isobserved with a variety of selection techniques. Specifically, the values ofthe parameters obtained by fitting the extended Goldhaber parametrisation tothe correlation function C'= C^{DATA}}/C^{MC} for two-jet events, selected withthe Durham algorithm and resolution parameter ycut=0.04, arer_t_out=(0.647+-0.011(stat})+0.022-0.124(syst)) fm,r_t_side=(0.809+-0.009(stat)+0.019-0.032}(syst)) fm, r_l=(0.989+-0.011(stat)+0.030-0.015(syst})) fm andr_l/r_t_side=1.222+- 0.027(stat})+0.075-0.012(syst). The results are discussedin the context of a recent model of Bose-Einstein correlations based on stringfragmentation.Bose-Einstein correlations in pairs of identical charged pions produced in a sample of 4.3 million Z0 hadronic decays are studied as a function of the three components of the momentum difference, transverse ("out" and "side") and longitudinal with respect to the thrust direction of the event. A significant difference between the transverse, r_t_side, and longitudinal, r_l, dimensions is observed, indicating that the emitting source of identical pions, as observed in the Longitudinally CoMoving System, has an elongated shape. This is observed with a variety of selection techniques. Specifically, the values of the parameters obtained by fitting the extended Goldhaber parametrisation to the correlation function C'= C^{DATA}}/C^{MC} for two-jet events, selected with the Durham algorithm and resolution parameter ycut=0.04, are r_t_out=(0.647+-0.011(stat})+0.022-0.124(syst)) fm, r_t_side=(0.809+-0.009(stat)+0.019-0.032}(syst)) fm, r_l=(0.989+-0.011(stat)+0.030-0.015(syst})) fm and r_l/r_t_side=1.222+-0.027(stat})+0.075-0.012(syst). The results are discussed in the context of a recent model of Bose-Einstein correlations based on string fragmentation

Experimental properties of gluon and quark jets from a point source

Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013