193 research outputs found

    Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: A prospective observational study

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    BACKGROUND: Identifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients. METHODS: A single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1–2, days 3–4, and days 6–8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection. RESULTS: Twenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3–4 (p = 0.04) and days 6–8 (p = 0.002). The change in HLA-DR from days 1–2 to days 6–8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1–2 to days 3–4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection. CONCLUSIONS: Monocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1505-0) contains supplementary material, which is available to authorized users

    Deformed Base Antisymmetrized Molecular Dynamics and its Application to ^{20}Ne

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    A new theoretical framework named as deformed base antisymmetrized molecular dynamics that uses the localized triaxially deformed Gaussian as the single particle wave packet is presented. The model space enables us to describe sufficiently well the deformed mean-field structure as well as the cluster structure and their mixed structure within the same framework. The improvement over the original version of the antisymmetrized molecular dynamics which uses the spherical Gaussian is verified by the application to 20Ne^{20}{\rm Ne} nucleus. The almost pure α+16Og.s\alpha + ^{16}{\rm O_{g.s}} cluster structure of the KπK^\pi=00^- band, the distortion of the cluster structure in the KπK^\pi=01+0^+_1 band and the dominance of the deformed mean-field structure of the KπK^\pi=22^- band are confirmed and their observed properties are reproduced. Especially, the intra-band E2 transition probabilities in KπK^\pi=01+0^+_1 and 22^- bands are reproduced without any effective charge. Since it has been long known that the pure α+16Og.s.\alpha + ^{16}{\rm O}_{g.s.} cluster model underestimates the intra-band E2E2 transitions in the KπK^\pi=01+0^+_1 band by about 30%, we consider that this success is due to the sufficient description of the deformed mean-field structure in addition to the cluster structure by the present framework. From the successful description of 20Ne^{20}{\rm Ne}, we expect that the present framework presents us with a powerful approach for the study of the coexistence and interplay of the mean-field structure and the cluster structure

    T cells from patients with Candida sepsis display a suppressive immunophenotype

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    BACKGROUND: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections. METHODS: Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated. RESULTS: Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1). CONCLUSIONS: Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1182-z) contains supplementary material, which is available to authorized users

    Protocol for a prospective, observational cohort study of awareness in mechanically ventilated patients admitted from the emergency department: The ED-AWARENESS study

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    INTRODUCTION: Awareness with paralysis is a complication with potentially devastating psychological consequences for mechanically ventilated patients. While rigorous investigation into awareness has occurred for operating room patients, little attention has been paid outside of this domain. Mechanically ventilated patients in the emergency department (ED) have been historically managed in a way that predisposes them to awareness events: high incidence of neuromuscular blockade use, underdosing of analgesia and sedation, delayed administration of analgesia and sedation after intubation, and a lack of monitoring of sedation targets and depth. These practice patterns are discordant to recommendations for reducing the incidence of awareness, suggesting there is significant rationale to examine awareness in the ED population. METHODS AND ANALYSIS: This is a single centre, prospective cohort study examining the incidence of awareness in mechanically ventilated ED patients. A cohort of 383 mechanically ventilated ED patients will be included. The primary outcome is awareness with paralysis. Qualitative reports of all awareness events will be provided. Recognising the potential problem with conventional multivariable analysis arising from a small number of events (expected less than 10-phenomenon of separation), Firth penalised method, exact logistic regression model or penalised maximum likelihood estimation shrinkage (Ridge, LASSO) will be used to assess for predictors of awareness. ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data sharing with other investigators through academically established means

    Adverse events related to ultrasound-guided regional anesthesia performed by Emergency Physicians: Systematic review protocol

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    The use of ultrasound-guided regional anesthesia for pain management has become increasingly prevalent in Emergency Medicine, with studies noting excellent pain control while sparing opioid use. However, the use of ultrasound-guided regional anesthesia may be hampered by concern about risks for patient harm. This systematic review protocol describes our approach to evaluate the incidence of adverse events from the use of ultrasound-guided regional anesthesia by Emergency Physicians as described in the literature. This project will also seek to document the scope of ultrasound-guided regional anesthesia applications being performed in Emergency Medicine literature, and potentially serve as a framework for future systematic reviews evaluating adverse events in Emergency Medicine

    Latest results from NA60

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    The NA60 experiment has measured the production of muon pairs and of charged particles in In+In collisions at a beam energy of 158 AGeV. For invariant dimuon masses below the phi the space-time averaged rho spectral function was isolated by a novel procedure. It shows a strong broadening but essentially no shift in mass. The production of J/psi was measured as a function of the collision centrality. As in previous experiments studying Pb+Pb collisions an anomalous supression is observed, setting in at approximately 90 participant nucleons. Using the charged particles the reaction plane was reconstructed. The elliptic flow of charged particles increases with pt showing a saturation for pt > 2GeV/c. For the first time azimuthal distributions for J/psi are shown.Comment: 9 pages, 11 figures, talk given at the conference "Strangeness in Quark Matter 2006 (SQM2006)", March 2006, Los Angeles, USA, accepted for publication in Journal of Physics

    First results from the NA60 experiment at CERN

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    Since 1986, several heavy ion experiments have studied some signatures of the formation of the quark-gluon plasma and a few exciting results have been found. However, some important questions are still unanswered and require new measurements. The NA60 experiment, with a new detector concept that vastly improves dimuon detection in proton-nucleus and heavy-ion collisions, studies several of those open questions, including the production of open charm. This paper presents the experiment and some first results from data collected in 2002.Comment: Paper presented at the XXXVIII Rencontres de Moriond, QCD and High Energy Hadronic Interactions, Les Arcs, March 22-29, 2003. 4 pages, 6 figure

    First results from NA60 on low mass muon pair production in In-In collisions at 158 GeV/nucleon

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    The NA60 experiment at the CERN SPS studies dimuon production in proton-nucleus and nucleus-nucleus collisions. The combined information from a novel vertex telescope made of radiation-tolerant silicon pixel detectors and from the muon spectrometer previously used in NA50 allows for a precise measurement of the muon vertex and a much improved dimuon mass resolution. We report on first results from the data taken for Indium-Indium collisions at 158 AGeV/nucleon in 2003, concentrating on a subsample of about 370 000 muon pairs in the mass range <1.2<1.2 GeV/c2c^{2}. The light vector mesons ω\omega and ϕ\phi are completely resolved, with a mass resolution of about 23 MeV/c2c^{2} at the ϕ\phi. The transverse momentum spectra of the ϕ\phi are measured over the continuous range 0<pT<2.50<p_{\rm T}<2.5 GeV/c; the inverse slope parameter of the spectra is found to increase with centrality, with an average value of T=252±3T=252\pm3 MeV.Comment: 9 pages, 6 figures. Plenary talk, SQM2004 conference, Cape Town, South Africa 15-20 September, 2004. To be published in Journal of Physics G: Nuclear and Particle Physic

    Nuclear Alpha-Particle Condensates

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    The α\alpha-particle condensate in nuclei is a novel state described by a product state of α\alpha's, all with their c.o.m. in the lowest 0S orbit. We demonstrate that a typical α\alpha-particle condensate is the Hoyle state (Ex=7.65E_{x}=7.65 MeV, 02+0^+_2 state in 12^{12}C), which plays a crucial role for the synthesis of 12^{12}C in the universe. The influence of antisymmentrization in the Hoyle state on the bosonic character of the α\alpha particle is discussed in detail. It is shown to be weak. The bosonic aspects in the Hoyle state, therefore, are predominant. It is conjectured that α\alpha-particle condensate states also exist in heavier nαn\alpha nuclei, like 16^{16}O, 20^{20}Ne, etc. For instance the 06+0^+_6 state of 16^{16}O at Ex=15.1E_{x}=15.1 MeV is identified from a theoretical analysis as being a strong candidate of a 4α4\alpha condensate. The calculated small width (34 keV) of 06+0^+_6, consistent with data, lends credit to the existence of heavier Hoyle-analogue states. In non-self-conjugated nuclei such as 11^{11}B and 13^{13}C, we discuss candidates for the product states of clusters, composed of α\alpha's, triton's, and neutrons etc. The relationship of α\alpha-particle condensation in finite nuclei to quartetting in symmetric nuclear matter is investigated with the help of an in-medium modified four-nucleon equation. A nonlinear order parameter equation for quartet condensation is derived and solved for α\alpha particle condensation in infinite nuclear matter. The strong qualitative difference with the pairing case is pointed out.Comment: 71 pages, 41 figures, review article, to be published in "Cluster in Nuclei (Lecture Notes in Physics) - Vol.2 -", ed. by C. Beck, (Springer-Verlag, Berlin, 2011
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