Exact approximation of Rao-Blackwellised particle filters

Particle methods are a category of Monte Carlo algorithms that have become popular for performing inference in non-linear non-Gaussian state-space models. The class of 'Rao-Blackwellised' particle filters exploits the analytic marginalisation that is possible for some state- space models to reduce the variance of the Monte Carlo estimates. Despite being applicable to only a restricted class of state-space models, such as conditionally linear Gaussian models, these algorithms have found numerous applications. In scenarios where no such analytical integration is possible, it has recently been proposed in Chen et al. [2011] to use 'local' particle filters to carry out this integration numerically. We propose here an alternative approach also relying on \local" particle filters which is more broadly applicable and has attractive theoretical properties. Proof-of-concept simulation results are presented

Assessing the performance of protective winter covers for outdoor marble statuary: pilot investigation

Outdoor statuary in gardens and parks in temperate climates has a tradition of being covered during the winter, to protect against external conditions. There has been little scientific study of the environmental protection that different types of covers provide. This paper examines environmental conditions provided by a range of covers used to protect marble statuary at three sites in the UK. The protection required depends upon the condition of the marble. Although statues closely wrapped and with a layer of insulation provide good protection, this needs to be considered against the potential physical damage of close wrapping a fragile deteriorated surface

In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

Background: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS. Aim: To investigate the effects of salbutamol on neutrophil function. Methods: The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days’ treatment with placebo or salbutamol (ALI/ARDS group). Alveolar–capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured. Results: In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar– capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils. Conclusion: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways

Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury

Background: Reduced bioactive vascular endothelial growth factor (VEGF) has been demonstrated in several inflammatory lung conditions including the acute respiratory distress syndrome (ARDS). sVEGFR-1, a soluble form of VEGF-1 receptor, is a potent natural inhibitor of VEGF. We hypothesised that sVEGFR-1 plays an important role in the regulation of the bioactivity of VEGF within the lung in patients with ARDS. Methods: Forty one patients with ARDS, 12 at risk of developing ARDS, and 16 normal controls were studied. Bioactive VEGF, total VEGF, and sVEGFR-1 were measured by ELISA in plasma and bronchoalveolar lavage (BAL) fluid. Reverse transcriptase polymerase chain reaction for sVEGFR-1 was performed on BAL cells. Results: sVEGFR-1 was detectable in the BAL fluid of 48% (20/41) of patients with early ARDS (1.4– 54.8 ng/ml epithelial lining fluid (ELF)) compared with 8% (1/12) at risk patients (p = 0.017) and none of the normal controls (p = 0.002). By day 4 sVEGFR-1 was detectable in only 2/18 ARDS patients (p = 0.008). Patients with detectable sVEGFR-1 had lower ELF median (IQR) levels of bioactive VEGF than those without detectable sVEGFR-1 (1415.2 (474.9–3192) pg/ml v 4761 (1349–7596.6) pg/ml, median difference 3346 pg/ml (95% CI 305.1 to 14711.9), p = 0.016), but there was no difference in total VEGF levels. BAL cells expressed mRNA for sVEGFR-1 and produced sVEGFR-1 protein which increased following incubation with tumour necrosis factor a. Conclusion: This study shows for the first time the presence of sVEGFR-1 in the BAL fluid of patients with ARDS. This may explain the presence of reduced bioactive VEGF in patients early in the course of ARDS

The effect of particulate matter on paper degradation

Background: In this work we explore the chemical effects of particulate matter on paper. We exposed paper made of pure cellulose to the environment in different locations in central London, outdoors (in sheltered conditions) and indoors, for a period of up to 6 months. We monitored particulate matter (PM) deposition by counting the particles deposited every month with a scanning electron microscope. We analysed elemental composition of the deposited particles using inductively coupled plasma mass spectrometry. After accelerated degradation of the exposed samples, we determined the degree of polymerisation using viscometry. Results: We observed higher deposition rates and higher metal concentration outdoors than indoors. Elemental analysis of the deposited particles revealed the presence of some transition metals (Fe, Cu, Cr) that can contribute to the degradation of cellulose fibres through the Fenton reaction. By comparing the degree of polymerisation of pro‑ tected, unprotected and unexposed samples we could determine the relative contribution of PM deposition on the increase of the degradation rate. We found that the surface concentration of iron correlates with the reduction in the degree of polymerisation of the exposed paper. Conclusions: The results suggest that the presence of Fenton metals in PM has a significant effect on the accelera‑ tion of the degradation of cellulose. However, we estimate that this will unlikely occur at the levels of area coverage by PM that are typically avoided in indoor heritage through preventive maintenance and cleaning

Bench-to-bedside review: β(2)-Agonists and the acute respiratory distress syndrome

The acute respiratory distress syndrome (ARDS) is a devastating constellation of clinical, radiological and pathological signs characterized by failure of gas exchange and refractory hypoxia. Despite nearly 30 years of research, no specific pharmacological therapy has yet proven to be efficacious in manipulating the pathophysiological processes that underlie this condition. Several in vitro and in vivo animal or human studies suggest a potential role for β(2)-agonists in the treatment of ARDS. These agents have been shown to reduce pulmonary neutrophil sequestration and activation, accelerate alveolar fluid clearance, enhance surfactant secretion, and modulate the inflammatory and coagulation cascades. They are also used widely in clinical practice and are well tolerated in critically ill patients. The present review examines the evidence supporting a role for β(2)-agonists as a specific pharmacological intervention in patients with ARDS

Evidence for chemokine synergy during neutrophil migration in ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. OBJECTIVES: The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. METHODS: CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. RESULTS: CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. CONCLUSION: This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Introduction: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods: A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results: 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions: Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration: International Standard Randomized Control Trial Registry ISRCTN64637517