Evaluation of artificial neural network algorithms for predicting the effect of the urine flow rate on the power performance of microbial fuel cells.

Microbial fuel cell (MFC) power performance strongly depends on the biofilm growth, which in turn is affected by the feed flow rate. In this work, an artificial neural network (ANN) approach has been used to simulate the effect of the flow rate on the power output by ceramic MFCs fed with neat human urine. To this aim, three different second-order algorithms were used to train our network and then compared in terms of prediction accuracy and convergence time: Quasi-Newton, Levenberg-Marquardt, and Conjugate Gradient. The results showed that the three training algorithms were able to accurately simulate power production. Amongst all of them, the Levenberg-Marquardt was the one that presented the highest accuracy (R = 95%) and the fastest convergence (7.8 s). These results show that ANNs are useful and reliable tools for predicting energy harvesting from ceramic-MFCs under changeable flow rate conditions, which will facilitate the practical deployment of this technology.

Response of ceramic microbial fuel cells to direct anodic airflow and novel hydrogel cathodes.

The presence of air in the anode chamber of microbial fuel cells (MFCs) might be unavoidable in some applications. This study purposely exposed the anodic biofilm to air for sustained cycles using ceramic cylindrical MFCs. A method for improving oxygen uptake at the cathode by utilising hydrogel was also trialled. MFCs only dropped by 2 mV in response to the influx of air. At higher air-flow rates (up to 1.1 L/h) after 43-45 h, power did eventually decrease because chemical oxygen demand (COD) was being consumed (up to 96% reduction), but recovered immediately with fresh feedstock, highlighting no permanent damage to the biofilm. Two months after the application of hydrogel to the cathode chamber, MFC power increased 182%, due to better contact between cathode and ceramic surface. The results suggest a novel way of improving MFC performance using hydrogels, and demonstrates the robustness of the electro-active biofilm both during and following exposure to air.

Modelling the energy harvesting from ceramic-based microbial fuel cells by using a fuzzy logic approach.

Microbial fuel cells (MFCs) is a promising technology that is able to simultaneously produce bioenergy and treat wastewater. Their potential large-scale application is still limited by the need of optimising their power density. The aim of this study is to simulate the absolute power output by ceramic-based MFCs fed with human urine by using a fuzzy inference system in order to maximise the energy harvesting. For this purpose, membrane thickness, anode area and external resistance, were varied by running a 27-parameter combination in triplicate with a total number of 81 assays performed. Performance indices such as R2 and variance account for (VAF) were employed in order to compare the accuracy of the fuzzy inference system designed with that obtained by using nonlinear multivariable regression. R2 and VAF were calculated as 94.85% and 94.41% for the fuzzy inference system and 79.72% and 65.19% for the nonlinear multivariable regression model, respectively. As a result, these indices revealed that the prediction of the absolute power output by ceramic-based MFCs of the fuzzy-based systems is more reliable than the nonlinear multivariable regression approach. The analysis of the response surface obtained by the fuzzy inference system determines that the maximum absolute power output by the air-breathing set-up studied is 450  µ W when the anode area ranged from 160 to 200 cm2, the external loading is approximately 900 Ω and a membrane thickness of 1.6 mm, taking into account that the results also confirm that the latter parameter does not show a significant effect on the power output in the range of values studied.

The exclusion problem in seasonally forced epidemiological systems.

The pathogen exclusion problem is the problem of finding control measures that will exclude a pathogen from an ecological system or, if the system is already disease-free, maintain it in that state. To solve this problem we work within a holistic control theory framework which is consistent with conventional theory for simple systems (where there is no external forcing and constant controls) and seamlessly generalises to complex systems that are subject to multiple component seasonal forcing and targeted variable controls. We develop, customise and integrate a range of numerical and algebraic procedures that provide a coherent methodology powerful enough to solve the exclusion problem in the general case. An important aspect of our solution procedure is its two-stage structure which reveals the epidemiological consequences of the controls used for exclusion. This information augments technical and economic considerations in the design of an acceptable exclusion strategy. Our methodology is used in two examples to show how time-varying controls can exploit the interference and reinforcement created by the external and internal lag structure and encourage the system to 'take over' some of the exclusion effort. On-off control switching, resonant amplification, optimality and controllability are important issues that emerge in the discussion.

Imaging COX-2 expression in cancer using PET/SPECT radioligands: current status and future directions.

The role of cyclooxygenase (COX)-2 as a driving force in early tumourigenesis and the current interest in the combination of COX-2 inhibitors with standard therapy in clinical trials creates an urgent need to establish clinically relevant diagnostic tests for COX-2 expression. Molecular imaging using small-molecule probes radiolabelled for both positron emission tomography (PET) and single photon emission computed tomography (SPECT) offers the potential to meet this need, providing a minimally invasive readout for the whole disease burden. This review summarises current approaches to the radiolabelling of small-molecule COX-2 inhibitors and their analogues for PET and SPECT imaging, and gives an overview of their biological evaluation and likely success of clinical application.

Use of an in vitro flat-bed biofilm model to measure biologically active anti-odour compounds.

The objective of this study was to demonstrate the utility of a modified flat-bed perfusion biofilm matrix system for testing toothpaste formulations directly, without dilution, as a layer in direct contact with the biofilm matrix surface. Final biofilm yields and volatile sulphur compounds (VSC) biogenesis were measured to show the relative efficacy of toothpaste formulations. Diffusion characteristics of the flat-bed system to exposure with Meridol® tooth and tongue gel (TTG; 1,400 ppm F(-) from amine fluoride/stannous fluoride, 0.5 % zinc lactate, oral malodour counteractives) was assessed using a bioluminescent target species Escherichia coli Nissle 1917/pGLITE coupled with a low-light photon camera to visualise the kill kinetics. Tongue-flora derived, mixed culture biofilms (n = 4) received 5, 15 and 30 min treatment with TTG, respectively, to determine the optimum time of exposure. VSC biogenesis was measured from headspace samples by gas chromatography prior to and following treatment of two daily applications for 4 days of treatment (TTG), positive control (CHX gel) and negative controls (placebo and sham treatment). Viable counts were performed at the end of experiments by destructive sampling of the biofilms and plating onto selective and non-selective agar. Following a single treatment with TTG, the E. coli biofilm with lux target gave >50 % reduction of luminescence within 2 to 3 h before recovering to a steady state over 10 h, suggesting biofilm cidal activity rather biostasis. For mixed culture biofilms, 15- and 30-min treatment exposure with TTG gave almost identical reductions in final biofilm yields. For comparing efficacy of treatments, biofilms treated with TTG gave greatest reductions in both pre-post levels of H2S (P < 0.01) and CH3SH (P < 0.05) and population yields at the end of the experiments (P < 0.001) compared to placebo and positive control. The in vitro flat-bed perfusion model may be used to replicate many of the activities and reactions believed to be occurring by the tongue biofilm microflora within a real mouth, including VSC biogenesis and its inhibition by exposure to active agents as components of toothpastes and gels applied in direct contact with the biofilm.

Markers of cell division cycle in glioblastoma: significance in prediction of treatment response and patient prognosis.

OBJECTIVE: To investigate whether expression of regulatory components of the cell division cycle can be used independently to predict survival and response to adjuvant therapy in glioblastomas. METHOD: A tissue micro-array, constructed using glioblastomas (n = 66), was stained using antibodies against minichromosome maintenance protein-2 (Mcm-2), expressed throughout the cell-division cycle; geminin, a protein that prevents re-initiation of DNA replication; and cyclin A, an S-phase cyclin. A semi-quantitative labelling index (LI) was calculated using an average of 18 high-power fields (hpf) in three replicate cores. The patients were divided into two groups: Group 1 (n = 50) underwent surgery and radiotherapy with 24 patients receiving temozolomide, and Group 2 (n = 16) received surgical treatment only. RESULTS: The LIs (median +/- IQR) for Group 1 were as follows: Mcm-2, 36.7% (22.9%-51.8%); geminin, 7.8% (5.8%-10.5%); and cyclin A, 4.2% (2.4%-6.9%). Elevated LIs, higher than the median, for geminin and cyclin A correlated with prolonged survival when the tumours received adjuvant therapy (Kaplan-Meier curves, p = 0.0046 and p = 0.0063 for geminin and cyclin A, respectively). Linear regression analysis revealed positive correlations with survival for Mcm-2 (p = 0.0376), geminin (p = 0.0006) and cyclin A (p = 0.004). In Group 2, there was no relationship between the patient survival and the LI for any marker. CONCLUSIONS: Geminin and cyclin A, each show potential as independent prognostic markers in glioblastomas receiving adjuvant therapy. This may reflect the fact that both geminin and cyclin A estimate proliferating tumour cell subpopulations sensitive to radio/chemotherapy. These markers could provide valuable prognostic information, even in small biopsies, especially if combined with O(6)MGMT expression and 1p;19q deletion status.

Threshold dynamics for periodically forced ecological systems: the control of population invasion and exclusion.

Ecosystems are under increasing threat as a result of anthropogenic activity, through pollution, unregulated harvesting, habitat destruction and the inadvertent spread of pathogens and vertebrate and non-vertebrate species through global transportation links. Many of the necessary interventions to restore or restructure natural ecosystems require the exclusion of a population from the ecosystem or the inclusion of a population if robust biodiversity is the objective. The problem of how best to bring this about is not easy to solve in highly nonlinear systems, especially if the system is exposed to significant time varying external forces. We wish here to build on the understanding gained from previous work by developing an algebraic methodology that yields explicit formulae to analyse the effect of moderate multi-component forcing on the invasion/exclusion process. This can be of assistance to management in designing suitable intervention strategies if one or more of the forcing components is under management control. We apply this methodology to look at three important issues, involving the relationships between resonance and control, between vaccination policy and the stage structure of a disease and between apparent competition and coexistence.

Electrochemically activated solutions: evidence for antimicrobial efficacy and applications in healthcare environments.

Due to the limitations associated with the use of existing biocidal agents, there is a need to explore new methods of disinfection to help maintain effective bioburden control, especially within the healthcare environment. The transformation of low mineral salt solutions into an activated metastable state, by electrochemical unipolar action, produces a solution containing a variety of oxidants, including hypochlorous acid, free chlorine and free radicals, known to possess antimicrobial properties. Electrochemically activated solutions (ECAS) have been shown to have broad-spectrum antimicrobial activity, and have the potential to be widely adopted within the healthcare environment due to low-cost raw material requirements and ease of production (either remotely or in situ). Numerous studies have found ECAS to be highly efficacious, as both a novel environmental decontaminant and a topical treatment agent (with low accompanying toxicity), but they are still not in widespread use, particularly within the healthcare environment. This review provides an overview of the scientific evidence for the mode of action, antimicrobial spectrum and potential healthcare-related applications of ECAS, providing an insight into these novel yet seldom utilised biocides.

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

BACKGROUND: The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. METHODS: Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. RESULTS: There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. CONCLUSION: In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Halitology (breath odour: aetiopathogenesis and management).

This article reviews the aetiopathogenesis of halitosis (oral malodour) and management. Halitosis is any disagreeable breath odour. In most patients, the odour originates from the oral cavity. In some patients, it has an extra-oral aetiology and, in a few, metabolic anomalies are responsible. In other patients complaining of malodour, this is imagined rather than real. Volatile sulphur compounds (VSCs) and other elements appear largely responsible for the malodour. Predisposing factors include poor oral hygiene, hyposalivation, dental appliances, gingival and periodontal disease and mucosal disease. The first step in assessment is objective measurement to determine whether malodour is present. If present, the oral or extra-oral origin should be determined, because the latter requires medical investigation and support in therapy, as is also the case where the malodour is imagined rather than real. Oral malodour is managed largely by oral health improvement, plus use of one or more of the wide range of antimalodour therapies, and sometimes also with use of a malodour counteractive. Emergent treatments include probiotics and vaccines targeted against causal micro-organisms or their products.

Phase control of resonant systems: interference, chaos and high periodicity.

Much progress has been made in understanding the effect of periodic forcing on epidemiological and ecological systems when that forcing acts on just one part of the system. Much less is known about situations in which several parts of the system are affected. In this case the interaction between the impacts of the different forcing components can lead to reinforcement of system responses or to their interference. This interference phenomenon is significant if some forcing components are anthropogenic for then management might be able to exercise sufficient control to bring about suppression of undesirable aspects of the forcing, for example resonant amplification and the problems this can cause. We set out the algebraic theory when forcing is weak and illustrate by example what can happen when forcing is strong enough to create subharmonics and chaotic states. Phase is the key control variable that can bring about interference, advantageously shift nonlinear response curves and create periodic states out of chaos. The phenomenon in which high period fluctuations appear to be generated by low period forcing is examined and different mechanisms compared in a two-strain epidemiological model. The effect of noise as a source of high period fluctuations is also considered.

Comparative effects of various commercially available mouthrinse formulations on oral malodor.

OBJECTIVES: The primary aim of this study was to compare a new mouthwash (SB12®) containing 0.025% chlorhexidine and 0.3% zinc for oral malodor reduction against four commercially available mouthwashes and negative control. A secondary aim was to compare the two methods for measuring volatile sulphur compounds (VSC) by halimetry and OralChroma. METHODS: Organoleptic scale, halimeter and the OralChroma were used to assess oral malodour and VSC. The effects of five test formulations and water (negative control) were assessed after 30, 60, 90 and 180 min, with 1 week between the treatments to avoid any cross-over effect. RESULTS: Reduction in H(2) S by halimetry and malodour levels by organoleptic assessment ranged from, slight (LacerFresh®) (P > 0.05), moderate (BreathRx®, SmartMouth® (P < 0.01) to marked effects (SB12®, Listerine®) (P < 0.001) at all time points compared with water. The largest differences were observed at 30 min and decreased with time. SB12® showed separation from Listerine® at 180 min, using ANOVA plus Bonferroni's Multiple Comparison post-test (P < 0.05). Relationships between organoleptic, halimeter and OralChroma were between R² = 0.795 and 0.926. CONCLUSION: SB12 shows a consistent and reproducible inhibitory effect on oral malodor parameters, which in turn correlate well with each other.

Effect of microbial fuel cell operation time on the disinfection efficacy of electrochemically synthesised catholyte from urine.

Microbial fuel cells (MFCs) offer an excellent solution to tackle some of the major challenges currently faced by humankind: sustainable energy sources, waste management and water stress. Besides treating wastewater and producing useful electricity from urine, ceramic MFCs can also generate biocidal catholyte in-situ. It has been proved that the electricity generation from the MFCs has a high impact in the catholyte composition. Therefore, the catholyte composition constantly changes while electricity is generated. However, these changes in catholyte composition with time has not yet been studied and that could highly contribute to the disinfection efficacy. In this work, the evolution of the catholyte generation and composition with the MFC operation time has been chemically and microbiologically evaluated, during 42 days. The results show an increase in pH and conductivity with the operation time, reaching pH 11.5. Flow cytometry and luminometer analyses of bioluminescent pathogenic E. coli exposed to the synthesised catholyte revealed killing properties against bacterial cells. A bio-electrochemical system, capable of electricity generation and simultaneous production of bactericidal catholyte from human urine is presented. The possibility to electrochemically generate in-situ a bacterial killing agent from urine, offers a great opportunity for water reuse and resource recovery for practical implementations.

Pathogen exclusion from eco-epidemiological systems.

Increasing concerns about the changing environment and the emergence of pathogens that cross species boundaries have added to the urgency of understanding the dynamics of complex ecological systems infected by pathogens. Of particular interest is the often counterintuitive way in which infection and predation interact and the consequent difficulties in designing control strategies to manage the system. To understand the mechanisms involved, we focus on the pathogen exclusion problem, using control maps (on which the network of exclusion thresholds are plotted) in order to readily identify which exclusion strategies will work and why others will not. We apply this approach to the analysis of parasite exclusion in two game bird ecologies. For higher dimensions, we propose a computational scheme that will generate the optimal exclusion strategy, taking into account all operational constraints on the pathogen invasion matrix, populations, and controls. The situation is further complicated when external forcing distorts pathogen thresholds. This distortion is highly sensitive to the lags between forcing components, a sensitivity that can be exploited by management using correctly lagged cyclically varying controls to reduce the effort involved in pathogen exclusion.

Differences in cytokine levels due to gender in colorectal cancer patients.

INTRODUCTION: Female gender is associated with longer survival after treatment for colorectal cancer (CRC). Reasons behind this phenomenon are not entirely clear. In addition, higher interleukin-6 (IL-6) and interleukin-1 (IL-1) levels have been found to be associated with poorer prognosis in CRC patients. The aim of this study was to investigate if cytokine levels were different in male and female CRC patients. METHODS: Pre- and post-operative levels of IL-1, interleukin-1 receptor antagonist (IL-1ra), IL-6 and tumour necrosis factor-alpha (TNF-alpha) were measured using standard solid phase sandwich ELISA in 104 consecutive eligible patients undergoing elective resection for CRC. RESULTS: Seventy (67.3%) participants were male and the mean age of the group was 67.6years (standard deviation 10.4years, range 39-86years). Pre-operative IL-1beta and post-operative IL-6 levels were significantly higher in males compared with females (U=486.5, p=0.03, U=424, p=0.04), values approaching statistical significance were obtained for pre-operative IL-6 (U=508.5, p=0.06) and post-operative IL-1beta (U=448, p=0.07). Differences in the levels of TNF-alpha and IL-1ra were not statistically significant. Multiple regression analysis using TNM stage as a covariate, showed that gender was an independent predictor of post-operative IL-6 levels (p=0.04). CONCLUSION: IL-1beta and IL-6 levels were significantly higher in men than in women. This provides evidence of a possible link between gender and cytokine levels in patients with colorectal cancer.

Evaluation of the efficacy of electrochemically activated solutions against nosocomial pathogens and bacterial endospores.

AIMS: Electrochemically activated solutions (ECAS) are generated from halide salt solutions via specially designed electrolytic cells. The active solutions are known to possess high biocidal activity against a wide range of target microbial species, however, literature revealing the kill-kinetics of these solutions is limited. The aim of the study was to identify the kill-rate and extent of population kill for a range of target species (including endospores) using ECAS generated at the anode (anolyte). METHODS AND RESULTS: Standard suspensions of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus atrophaeus spores and Clostridium difficile spores were treated with anolyte in a quantitative suspension assay. For vegetative cells, all concentrations of anolyte tested reduced the viable population to below the detection limit within 10 s. At a concentration of 99%, anolyte produced a log(10) reduction factor of greater than five in viable B. atrophaeus endospores within 90 s and reduced numbers of C. difficile endospores to below the experimental detection limit within 20 s at concentrations of 5% or greater. CONCLUSIONS: Anolyte was highly effective in killing test-bacteria and spores. The bactericidal efficacy was retained against vegetative cells at dilutions as low as 1% and against C. difficile spores as low as 5%. SIGNIFICANCE AND IMPACT OF STUDY: The results of this study demonstrate that ECAS are effective at lower concentrations and act more rapidly than previously reported. Potent bactericidal and sporicidal activity coupled with point-of-use generation, low production-costs and environmental compatibility suggest that acidic ECAS has the potential to be a useful addition to the current armoury of disinfectants.

A novel in vitro flat-bed perfusion biofilm model for determining the potential antimicrobial efficacy of topical wound treatments.

AIMS: To develop an in vitro flat-bed perfusion biofilm model that could be used to determine the antimicrobial efficacy of topically applied treatments. METHODS AND RESULTS: Pseudomonas aeruginosa and Staphylococcus aureus biofilms were grown within continuously perfused cellulose matrices. Enumeration of the biofilm density and eluate was performed at various sampling times, enabling determination of the biofilm growth rate. Two antimicrobial wound dressings were applied to the surface of mature biofilms and periodically sampled. To enable real-time imaging of biofilm growth and potential antimicrobial kinetics, a bioluminescent Ps. aeruginosa biofilm was monitored using low-light photometry. Target species produced reproducible steady-state biofilms at a density of c. 10(7) per biofilm support matrix, after 24-h perfusion. Test dressings elicited significant antimicrobial effects, producing differing kill kinetic profiles. There was a good correlation between photon and viable count data. CONCLUSIONS: The model enables determination of the antimicrobial profile of topically applied treatments against target species biofilms, accurately differentiating bactericidal from bacteriostatic effects. Moreover, these effects could be monitored in real time using bioluminescence. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first in vitro biofilm model which can assess the antimicrobial potential of topical therapies in a dynamic growth environment.

In vitro comparison of antimicrobial activity of iodine and silver dressings against biofilms.

OBJECTIVE: To compare the antimicrobial effectiveness of silver- and iodine-containing wound dressings against preformed mature biofilms of pathogenic wound bacteria grown in vitro. METHOD: Biofilms of Pseudomonas aeruginosa and Staphylococcus aureus were grown within an in vitro flat bed perfusion biofilm model. Mature biofilms were removed and exposed to wound dressings containing either silver or iodine (Aquacel Ag and Iodozyme) within a static diffusion method, for up to 24 hours. This method was designed to reflect certain key features that determine antimicrobial activity within the wound. The numbers of viable bacteria surviving in the biofilms were determined at set time intervals over the test period. RESULTS: Both test dressings exerted an antimicrobial effect against the target species biofilms, although the iodine dressing was more efficacious under the experimental conditions employed. CONCLUSION: There are large and potentially significant differences (as measured in vitro) in the effectiveness of wound dressings containing broad-spectrum antimicrobial agents such as silver and iodine against specific types of bacterial biofilms.

A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens.

Development of personalised cancer models to predict response to radiation would benefit patient care; particularly in malignancies where treatment resistance is prevalent. Herein, a robust, easy to use, tumour-on-a-chip platform which maintains precision cut head and neck cancer for the purpose of ex vivo irradiation is described. The device utilises sintered discs to separate the biopsy and medium, mimicking in vivo microvascular flow and diffusion, maintaining tissue viability for 68 h. Integrity of tissues is demonstrated by the low levels of lactate dehydrogenase release and retained histology, accompanied by assessment of cell viability by trypan blue exclusion and flow cytometry; fluid dynamic modelling validates culture conditions. An irradiation jig is described for reproducible delivery of clinically-relevant doses (5 × 2 Gy) to newly-presenting primary tumours (n = 12); the addition of concurrent cisplatin is also investigated (n = 8) with response analysed by immunohistochemistry. Fractionated irradiation reduced proliferation (BrdU, p = 0.0064), increased DNA damage (Æ´H2AX, p = 0.0043) and caspase-dependent apoptosis (caspase-cleaved cytokeratin-18) compared to control; caspase-dependent apoptosis was further increased by concurrent cisplatin compared to control (p = 0.0063). This is a proof of principle study showing the response of cancer tissue to irradiation ex vivo in a bespoke system. The novel platform described has the potential to personalise treatment for patients in a cost-effective manner with applicability to any solid tumour.