Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described

Optimising froth stability of copper flotation tailings

Linking results from laboratory scale experiments to industrial flotation behaviour is challenging. Typically, such experiments involve batch tests in which the system does not operate at steady-state, making it difficult to infer the effects that operating conditions have on flotation performance. In order to overcome this limitation a 4-litre recirculating tank was previously developed at Imperial College London. This tank is capable of reaching, and operating at, steady-state by recycling overflowing concentrate back into the feed. As well as instruments to control operating conditions, it is fitted with a system of sensors that allow the surface of the froth to be dynamically monitored. From this information, it is possible to measure the air recovery a proxy for froth stability. Thus, this bench-scale tank can be used to understand the effect of differing operating conditions on flotation performance at steady state. However, so far, this cell has only been used to investigate idealised systems with only one or two species. Reprocessing of tailings dams is not only environmentally desirable but also increasingly economically feasible due to the declining head grades of primary deposits. There is also the added benefit of no further milling being required prior to flotation. However, the effects of fine and ultrafine particles on froth stability are not yet fully understood. In this work, the bench-scale continuous tank has been used for the first time to determine the flotation response of a complex feed, consisting of samples from a copper tailings dam, to changes in operating conditions. It was shown that the froth stability in the system is comparable to that of previous work and industrial tests, with a peak in air recovery being found at a superficial gas velocity of 1.13 cm/s. There is scope to optimise the froth stability of tailings flotation for enhanced metallurgical performance

Dynamic froth stability of copper flotation tailings

In this work, dynamic froth stability is used for the first time to investigate the flotation behaviour of copper tailings. Reprocessing of material from tailings dams is not only environmentally desirable, but also increasingly economically feasible as head grades can be high compared to new deposits. Flotation tailings, however, usually contain a large proportion of fine (10–50 m) and ultra fine (< ) material and the effect of these particle sizes on froth stability is not yet fully understood. For this study, samples were obtained from the overflow and underflow streams of the primary hydrocyclone at a concentrator that reprocesses copper flotation tailings. These samples were combined in different ratios to assess the dynamic froth stabilities at a wide range of particle size distributions and superficial gas velocities. The findings have shown that the effect of particle size on dynamic froth stability can be more complex than previously thought, with a local maximum in dynamic froth stability found at each air rate. Moreover, batch tests suggest that a local maximum in stability can be linked to improvements in flotation performance. Thus this work demonstrates that the dynamic froth stability can be used to find an optimum particle size distribution required to enhance flotation. This also has important implications for the reprocessing of copper tailings as it could inform the selection of the cut size for the hydrocyclones

Dynamic froth stability of copper flotation tailings

In this work, dynamic froth stability is used for the first time to investigate the flotation behaviour of copper tailings. Reprocessing of material from tailings dams is not only environmentally desirable, but also increasingly economically feasible as head grades can be high compared to new deposits. Flotation tailings, however, usually contain a large proportion of fine (10–50 μm) and ultra fine (<10μm) material and the effect of these particle sizes on froth stability is not yet fully understood. For this study, samples were obtained from the overflow and underflow streams of the primary hydrocyclone at a concentrator that reprocesses copper flotation tailings. These samples were combined in different ratios to assess the dynamic froth stabilities at a wide range of particle size distributions and superficial gas velocities. The findings have shown that the effect of particle size on dynamic froth stability can be more complex than previously thought, with a local maximum in dynamic froth stability found at each air rate. Moreover, batch tests suggest that a local maximum in stability can be linked to improvements in flotation performance. Thus this work demonstrates that the dynamic froth stability can be used to find an optimum particle size distribution required to enhance flotation. This also has important implications for the reprocessing of copper tailings as it could inform the selection of the cut size for the hydrocyclones

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

BACKGROUND: During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. METHODS: Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. RESULTS: The 73 COPD patients (88% male) had a mean (+/-SD) age 71(+/-8) years and FEV1 53(+/-16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(+/-1.3) and PEF fell by 7(+/-13) l/min. Mean daily step count fell from 4154(+/-2586) steps/day during a preceding baseline week to 3673(+/-2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). CONCLUSIONS: COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time

The link between particle size and froth stability - Implications for reprocessing of flotation tailings

Historic tailings dams can often be considered as valuable mineral reserves due to the declining head grades of primary deposits. The reprocessing of such material is of great interest to the minerals processing industry, not only from an economic point of view, but also from an environmental one. However, tailings material is generally comprised of fine particles, which poses a challenge for its reprocessing using froth flotation due to reduced recoveries of these particle sizes. In addition, there is some debate as to the effect that these fine particles have on the froth stability, which in turn is linked to mineral recovery. In this work, air recovery was used as a measure of froth stability to determine the flotation response of a copper tailings ore to changes in particle size distribution and superficial gas velocity. The system exhibited a maximum in air recovery, which correlates well with the local peak in dynamic froth stability presented in previous work. This maximum in froth stability is also shown to correspond to an improvement in flotation performance, thus highlighting the importance of considering the link between particle size, air rate and froth stability when determining the flotation strategy for tailings reprocessing. The results are discussed in terms of the implications for the reprocessing plant from where the ore samples were obtained and, more generally, for the efficient flotation reprocessing of tailings

Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study

OBJECTIVES: Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. METHODS: Fourteen individuals aged 40-60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. RESULTS: Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. CONCLUSIONS: Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. KEY POINTS: • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktrans demonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD

BACKGROUND: Prevalence and load of airway bacteria in stable and exacerbated chronic obstructive pulmonary disease (COPD) has been previously studied using microbiological culture. Molecular techniques, such as quantitative PCR (qPCR), may be more informative. METHODS: In this study, 373 sputum samples from 134 COPD outpatients were assessed for prevalence and load of typical airway bacteria (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis) by multiplex qPCR, with 176 samples analysed for atypical bacteria. Paired stable and exacerbation typical bacteria data were compared in 52 patients. We compared routine culture with qPCR in 177/373 samples. RESULTS: Typical bacteria were more prevalent in exacerbation than stable-state paired samples: 30/52 (57.7%) vs. 14/52 (26.9%); p=0.001. In patients who were bacteria-positive at both time points, mean (±1 SEM) load was significantly higher at exacerbation than stable state (108.5(±0.3) vs. 107.2(±0.5) cfu/ml), constituting a 20-fold increase (p=0.011). qPCR was more discriminatory at detecting typical bacteria than microbiological culture (prevalence 59.3% vs. 24.3%; p<0.001). At stable state, higher airway bacterial load correlated with more severe airflow limitation (FEV(1)%predicted) (r=-0.299; p=0.033) and higher inhaled corticosteroid dosage (r=0.382; p=0.008). Mean C-reactive protein was higher in bacterial-associated exacerbations (35.0 Vs 25.1 mg/L; p=0.032). CONCLUSIONS: Airway bacterial prevalence and load increase at COPD exacerbations and are an aetiological factor. qPCR is more discriminatory than culture, identifying higher airway bacterial prevalence. Exacerbations associated with bacterial detection showed a higher mean C-reactive protein level. In the stable state, airway bacterial load is related to more severe airflow limitation and higher inhaled corticosteroid dosage used