Antimicrobial activity of fosfomycin and tobramycin in combination against cystic fibrosis pathogens under aerobic and anaerobic conditions

There is a need for new antibiotics or combination of antibiotics that possess activity against increasingly resistant cystic fibrosis (CF) respiratory pathogens such as Pseudomonas aeruginosa and MRSA.

Alternative method for producing organic fertiliser from anaerobic digestion liquor and limestone powder:High Shear wet granulation

Generally, the solid and liquid fractions (digestate) from Anaerobic Digestion (AD) energy production are considered as waste. This has a negative impact on the sustainability of AD processes because of the financial outlay required to treat digestate before being discharged into municipal water treatment plants or natural water bodies. The main aim of this research was to investigate feasibility of producing an organic fertiliser using anaerobic digestate and limestone powders as the raw materials employing a high shear granulation process. Two-level factorial experimental design was used to determine the influence of granulation process variables on, the strength, resistance to attrition and yield of the granules. It was concluded from the study that it is technically feasible to produce organic fertiliser granules of acceptable strength and product yield. Increasing the liquid-to-solid ratio during granulation leads to increased granule strength and better product yield. Although the strength of the granules produced was lower than typical strength of commercial synthetic fertiliser granules (about 5 to 7. MPa), this could be improved by mixing the digestate with a polymeric binder or coating the particles post granulation. © 2012 Elsevier B.V.

Delamination threshold load for dynamic impact on plates

A criterion is derived for delamination onset in transversely isotropic laminated plates under small mass, high velocity impact. The resulting delamination threshold load is about 21% higher than the corresponding quasi-static threshold load. A closed form approximation for the peak impact load is then used to predict the delamination threshold velocity. The theory is validated for a range of test cases by comparison with 3D finite element simulation using LS-DYNA and a newly developed interface element to model delamination onset and growth. The predicted delamination threshold loads and velocities are in very good agreement with the finite element simulations. Good agreement is also shown in a comparison with published experimental results. In contrast to quasi-static impacts, delamination growth occurs under a rapidly decreasing load. Inclusion of finite thickness effects and a proper description of the contact stiffness are found to be vital for accurate prediction of the delamination threshold velocity

The variability in nutrient composition of Anaerobic Digestate granules produced from high shear granulation

This study investigates the production of organic fertilizer using Anaerobic Digestate (as a nutrient source) and limestone powder as the raw materials. A two-level factorial experimental design was used to determine the influence of process variables on the nutrient homogeneity within the granules. Increasing the liquid-to-solid ratio during granulation resulted in increased granule nutrient homogeneity. Increasing the processing time and the impeller speed were also found to increase the nutrient homogeneity. In terms of nutrients release into deionized water, the granules effectively released both potassium and phosphate into solution. © 2012 Elsevier Ltd.

Detection of visual-field deterioration by Glaucoma Progression Analysis and Threshold Noiseless Trend programs

BACKGROUND: To compare the ability of Glaucoma Progression Analysis (GPA) and Threshold Noiseless Trend (TNT) programs to detect visual-field deterioration.

METHODS: Patients with open-angle glaucoma followed for a minimum of 2 years and a minimum of seven reliable visual fields were included. Progression was assessed subjectively by four masked glaucoma experts, and compared with GPA and TNT results. Each case was judged to be stable, deteriorated or suspicious of deterioration

RESULTS: A total of 56 eyes of 42 patients were followed with a mean of 7.8 (SD 1.0) tests over an average of 5.5 (1.04) years. Interobserver agreement to detect progression was good (mean kappa = 0.57). Progression was detected in 10-19 eyes by the experts, in six by GPA and in 24 by TNT. Using the consensus expert opinion as the gold standard (four clinicians detected progression), the GPA sensitivity and specificity were 75% and 83%, respectively, while the TNT sensitivity and specificity was 100% and 77%, respectively.

CONCLUSION: TNT showed greater concordance with the experts than GPA in the detection of visual-field deterioration. GPA showed a high specificity but lower sensitivity, mainly detecting cases of high focality and pronounced mean defect slopes.

Quantification of interpoint topographic correlations of threshold values in glaucomatous visual fields

Purpose: The authors sought to quantify neighboring and distant interpoint correlations of threshold values within the visual field in patients with glaucoma. Methods: Visual fields of patients with confirmed or suspected glaucoma were analyzed (n = 255). One eye per patient was included. Patients were examined using the 32 program of the Octopus 1-2-3. Linear regression analysis among each of the locations and the rest of the points of the visual field was performed, and the correlation coefficient was calculated. The degree of correlation was categorized as high (r > 0.66), moderate (0.66 = r > 0.33), or low (r = 0.33). The standard error of threshold estimation was calculated. Results: Most locations of the visual field had high and moderate correlations with neighboring points and with distant locations corresponding to the same nerve fiber bundle. Locations of the visual field had low correlations with those of the opposite hemifield, with the exception of locations temporal to the blind spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB with an r reduction of 0.1. Conclusion: Locations of the visual field have highest interpoint correlation with neighboring points and with distant points in areas corresponding to the distribution of the retinal nerve fiber layer. The quantification of interpoint correlations may be useful in the design and interpretation of visual field tests in patients with glaucoma.

Sensitivity and specificity of frequency-doubling technology, tendency-oriented perimetry, and Humphrey Swedish interactive threshold algorithm-fast perimetry in a glaucoma practice

PURPOSE: To evaluate the sensitivity and specificity of the screening mode of the Humphrey-Welch Allyn frequency-doubling technology (FDT), Octopus tendency-oriented perimetry (TOP), and the Humphrey Swedish Interactive Threshold Algorithm (SITA)-fast (HSF) in patients with glaucoma. DESIGN: A comparative consecutive case series. METHODS: This was a prospective study which took place in the glaucoma unit of an academic department of ophthalmology. One eye of 70 consecutive glaucoma patients and 28 age-matched normal subjects was studied. Eyes were examined with the program C-20 of FDT, G1-TOP, and 24-2 HSF in one visit and in random order. The gold standard for glaucoma was presence of a typical glaucomatous optic disk appearance on stereoscopic examination, which was judged by a glaucoma expert. The sensitivity and specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curves of two algorithms for the FDT screening test, two algorithms for TOP, and three algorithms for HSF, as defined before the start of this study, were evaluated. The time required for each test was also analyzed. RESULTS: Values for area under the ROC curve ranged from 82.5%-93.9%. The largest area (93.9%) under the ROC curve was obtained with the FDT criteria, defining abnormality as presence of at least one abnormal location. Mean test time was 1.08 ± 0.28 minutes, 2.31 ± 0.28 minutes, and 4.14 ± 0.57 minutes for the FDT, TOP, and HSF, respectively. The difference in testing time was statistically significant (P <.0001). CONCLUSIONS: The C-20 FDT, G1-TOP, and 24-2 HSF appear to be useful tools to diagnose glaucoma. The test C-20 FDT and G1-TOP take approximately 1/4 and 1/2 of the time taken by 24 to 2 HSF. © 2002 by Elsevier Science Inc. All rights reserved.

State Estimation for Anaerobic Digesters using the ADM1

The optimization of full-scale biogas plant operation is of great importance to make biomass a competitive source of renewable energy. The implementation of innovative control and optimization algorithms, such as Nonlinear Model Predictive Control, requires an online estimation of operating states of biogas plants. This state estimation allows for optimal control and operating decisions according to the actual state of a plant. In this paper such a state estimator is developed using a calibrated simulation model of a full-scale biogas plant, which is based on the Anaerobic Digestion Model No.1. The use of advanced pattern recognition methods shows that model states can be predicted from basic online measurements such as biogas production, CH4 and CO2 content in the biogas, pH value and substrate feed volume of known substrates. The machine learning methods used are trained and evaluated using synthetic data created with the biogas plant model simulating over a wide range of possible plant operating regions. Results show that the operating state vector of the modelled anaerobic digestion process can be predicted with an overall accuracy of about 90%. This facilitates the application of state-based optimization and control algorithms on full-scale biogas plants and therefore fosters the production of eco-friendly energy from biomass.

Resistance Development of Cystic Fibrosis Respiratory Pathogens When Exposed to Fosfomycin and Tobramycin Alone and in Combination under Aerobic and Anaerobic Conditions

Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4:1 (w/w) combination of fosfomycin and tobramycin (F:T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F:T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F:T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F:T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F:T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F:T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F:T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F:T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F:T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa.

Fosfomycin and tobramycin in combination downregulate nitrate reductase genes narG and narH, resulting in increased activity against Pseudomonas aeruginosa under anaerobic conditions

The activity of aminoglycosides, used to treat Pseudomonas aeruginosa respiratory infection in cystic fibrosis (CF) patients, is reduced under the anaerobic conditions that reflect the CF lung in vivo. In contrast, a 4:1 (w/w) combination of fosfomycin and tobramycin (F:T), under investigation for use in the treatment of CF lung infection, has increased activity against P. aeruginosa under anaerobic conditions. The aim of this study was to elucidate the mechanisms underlying the increased activity of F:T under anaerobic conditions. Microarray analysis was used to identify the transcriptional basis of increased F:T activity under anaerobic conditions, and key findings were confirmed by microbiological tests including nitrate utilization assays, growth curves and susceptibility testing. Notably, growth in sub-inhibitory concentrations of F:T, but not tobramycin or fosfomycin alone, significantly downregulated (p <0.05) nitrate reductase genes narG and narH, essential for normal anaerobic growth of P. aeruginosa. Under anaerobic conditions, F:T significantly decreased (p