We present the report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010. The first part contains a review of the potential of hadronic decays of ...highly boosted particles as an aid for discovery at the LHC and a discussion of the status of tools developed to meet the challenge of reconstructing and isolating these topologies. In the second part, we present new results comparing the performance of jet grooming techniques and top tagging algorithms on a common set of benchmark channels. We also study the sensitivity of jet substructure observables to the uncertainties in Monte Carlo predictions.
The T2Candida magnetic resonance assay is a direct-from-blood pathogen detection assay that delivers a result within 3-5 h, targeting the most clinically relevant
species. Between February 2019 and ...March 2021, the study included consecutive patients aged >18 years admitted to an intensive care unit or surgical high-dependency unit due to gastrointestinal surgery or necrotizing pancreatitis and from whom diagnostic blood cultures were obtained. Blood samples were tested in parallel with T2Candida and 1,3-β-D-glucan. Of 134 evaluable patients, 13 (10%) were classified as having proven intraabdominal candidiasis (IAC) according to the EORTC/MSG criteria. Two of the thirteen patients (15%) had concurrent candidemia. The sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were 46%, 97%, 61%, and 94% for T2Candida and 85%, 83%, 36%, and 98% for 1,3-β-D-glucan. All positive T2Candida results were consistent with the culture results at the species level, except for one case of dual infection. The performance of T2Candida was comparable with that of 1,3-β-D-glucan for candidemic IAC but had a lower sensitivity for non-candidemic IAC (36% vs. 82%). In conclusion, T2Candida may be a valuable complement to 1,3-β-D-glucan in the clinical management of high-risk surgical patients because of its rapid results and ease of use.
The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, ...double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P = .02) and 3 (P = .04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P = .03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.
Objectives To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model. Methods Cefuroxime in concentrations ...simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose. Results The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001). Conclusions The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.
Thirteen patients (median age, 20 years) with life-threatening primary septic shock (10 meningococcal, 3 pneumococcal infections) were studied prospectively. All had a short history of sepsis (⩽ 24 ...h) and no severe underlying disease. Two (15%) died. The logarithm of the initial plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (ra), and plasminogen activator inhibitor (PAI)-1 correlated significantly with APACHE II scores (r2 = .67, .57, .68, .81, and .68, respectively). The plasma levels of endotoxin, TNF-α, IL-1β, and PAI-1 decreased toward normal levels within the first 24 h of treatment, but IL-6 and IL-1ra levels remained high until clinical recovery. On admission, the molar excess of IL-1ra to IL-1β was >2000-fold in 11 of the 13 patients. Acute plasmapheresis in 11 of the 13 patients significantly increased the plasma clearance of TNF-α (P = .02).
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation ...(SCT). The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition (HAI) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination, compared with the 53 who did not. In the subgroup of allogeneic SCT patients, HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group (P < .05). ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A (P < .05) and B (P < .01). At early vaccination, 4-12 months after stem cell transplantation, these responses were more pronounced. GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients, but only to a limited extent.
Treatments targeting complement receptors have been demonstrated to improve outcome in experimental sepsis. The regulation of the complement receptors in sepsis is not clear. Lipopolysaccharide (LPS) ...stimulation of granulocytes ex vivo has been shown to reduce C5a receptor (CD88) expression and to increase CD35 and CD11b/CD18 expressions in whole blood but not on isolated cells, indicating an indirect effect mediated via factors in the blood. With the aim to study whether these effects could be attributed to C5a, tumour necrosis factor (TNF)‐α and interleukin (IL)‐8, whole blood or isolated granulocytes and monocytes from healthy individuals were investigated. After incubation with C5a in a dose range of 1 × 10−9−1 × 10−7 mol/l, and TNF‐α and IL‐8 at doses of 1–100 ng/ml, the expressions of the complement receptors CD88, CD35, CD11b/CD18 were analysed by flow cytometry. Incubation with C5a reduced granulocyte CD88 expression by 44 ± 6.9% and 82 ± 4.2%, whereas monocyte CD88 expression decreased by 21 ± 4.0 and 30 ± 17% (whole blood and isolated cells). IL‐8 and TNF‐α incubation of granulocytes induced similar results. Granulocyte CD35 expression was significantly increased by 367, 175 and 336% by C5a, TNF‐α, IL‐8, respectively; CD11b expression was similarly increased. Consistent with findings in septic patients and after LPS incubation, it is concluded that all stimuli reduced granulocyte CD88 expression, whereas CD35 and CD11b were increased.
Animal experiments recently suggested that administration of anti‐C5a, anti‐C5a receptor or soluble complement receptor type‐1 may be of value in the treatment of septic shock. Because results ...regarding C5a receptor expression (C5a‐R, CD‐88) have been found to differ between septic animals and patients, the aim of this study was to investigate the neutrophil and monocyte receptor expression of CD‐88 and complement receptor‐1 (CR‐1, CD‐35) after stimulation with lipopolysaccharide (LPS) ex vivo.
Whole blood or isolated neutrophils and monocytes from healthy people were incubated with LPS in a dose range of 0.1–1000 ng/ml. The expressions of CD‐88 and CD‐35 were analysed by means of flow cytometry. For comparison, the expressions of complement receptor‐3 (CR‐3, CD‐11b/CD‐18), Fc‐γ receptor type‐I (CD‐64) and CEACAM‐8 (CD‐66b) were also investigated.
In whole blood, CD‐88 expression on neutrophils was reduced (P < 0.05). The expressions of CD‐35 and CD‐11b were increased both on neutrophils (P < 0.001; P < 0.05) and on monocytes (P < 0.001; P < 0.001). No effect was observed on isolated cells.
In agreement with the findings in septic patients, LPS reduced the neutrophil C5a‐R expression, whereas the expressions of CR‐1 and CR‐3 were increased. The effects of LPS were indirect and were mediated via factors in the blood. The clinical significance of this is not known, but may be associated with decreased chemotaxis.
Cerebrospinal fluid (CSF) concentration-time curves of rifampicin and fusidic acid were studied in a patient with post-operative meningitis caused by Staphylococcus epidermidis. The patient was ...treated with this combination of antimicrobial agents because of a severe hypersensitivity reaction to vancomycin. Peak CSF concentrations of rifampicin exceeded the MIC by > 60-fold, while those of fusidic acid just reached the MIC. CSF concentrations of fusidic acid were relatively stable within the range reported for patients with uninflamed meninges, but serum levels were surprisingly low. An increase in the metabolism of fusidic acid induced by rifampicin cannot be excluded.