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.

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.

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.

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.

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.

Erratum: "A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow" [Biomicrofluidics 10, 064101 (2016)].

[This corrects the article DOI: 10.1063/1.4964813.].

Implications of selective predation on the macroevolution of eukaryotes: evidence from Arctic Canada.

Existing paleontological data indicate marked eukaryote diversification in the Neoproterozoic, ca. 800 Ma, driven by predation pressure and various other biotic and abiotic factors. Although the eukaryotic record remains less diverse before that time, molecular clock estimates and earliest crown-group affiliated microfossils suggest that the diversification may have originated during the Mesoproterozoic. Within new assemblages of organic-walled microfossils from the ca. 1150 to 900 Ma lower Shaler Supergroup of Arctic Canada, numerous specimens from various taxa display circular and ovoid perforations on their walls, interpreted as probable traces of selective protist predation, 150-400 million years before their first reported incidence in the Neoproterozoic. Selective predation is a more complex behavior than phagotrophy, because it requires sensing and selection of prey followed by controlled lysis of the prey wall. The ca. 800 Ma eukaryotic diversification may have been more gradual than previously thought, beginning in the late Mesoproterozoic, as indicated by recently described microfossil assemblages, in parallel with the evolution of selective eukaryovory and the spreading of eukaryotic photosynthesis in marine environments.

A New Method for Modulation, Control and Power Boosting in Microbial Fuel Cells.

Microbial fuel cells (MFCs) are energy transducers, which through the metabolic reactions of facultative anaerobic microorganisms, transform the energy in organic matter directly into electricity. Extrinsic parameters such as hydraulic retention time, fuel quality (type and concentration) and physicochemical environment of electrodes and biofilms (e.g., temperature, pH, salinity, and redox), can all influence system efficiency. This work proposes that MFCs can be "fine-tuned" by adjustment of any of the physicochemical conditions including redox potential; in this context, an entirely novel method was investigated as a practical means of tuning, modulating and monitoring the redox potential within the electrode chambers. The method uses additional electrodes - known as 3rd and 4th-pins for anode and cathode chambers, respectively - which can be used in individual units, modules, cascades or stacks, for optimising the production of a large variety of chemicals, as well as biomass, water and power. The results have shown that the power output modulation resulted in an up to 79% and 33% increase, when connected via 3rd and 4th pins, respectively. Apart from power improvement, this study also demonstrated a method of open circuit potential (OCP) sensing, by using the same additional electrodes to both monitor and control the MFC signal in real time.

A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow.

The study of inflammatory bowel disease, including Ulcerative Colitis and Crohn's Disease, has relied largely upon the use of animal or cell culture models; neither of which can represent all aspects of the human pathophysiology. Presented herein is a dual flow microfluidic device which holds full thickness human intestinal tissue in a known orientation. The luminal and serosal sides are independently perfused ex vivo with nutrients with simultaneous waste removal for up to 72 h. The microfluidic device maintains the viability and integrity of the tissue as demonstrated through Haematoxylin & Eosin staining, immunohistochemistry and release of lactate dehydrogenase. In addition, the inflammatory state remains in the tissue after perfusion on the device as determined by measuring calprotectin levels. It is anticipated that this human model will be extremely useful for studying the biology and testing novel interventions in diseased tissue.

PO-48 - Assessment of the procoagulant potential state of tumour-MP in cancer patients.

INTRODUCTION: The venous thromboembolism is considered one of the highest risk factor in cancer patients for instance ovarian and pancreas. This hypercoagulability state is believed to be caused by tumour cells that can produce a variety of procaogulant factors including tissue factor (TF) bearing microparticles (MP). Chemotherapy is an independent risk factor for venous thromboembolism (VTE) in patients and it can leads to coagulation activation and may increase microparticles that can increase risk of thrombosis. AIM: Therefore, our current hypothesis is that this increased risk of VTE is due to release of tumour MP into the blood. To further investigate this mechanism an ex-vivo microfluidic model system was developed wherein tumour spheroids were grown and transferred onto a microfluidic chip and assessed, under flow conditions, for procoagulant activity (PCA). MATERIALS AND METHODS: Tumour spheroids from pancreatic cancer cell line AsPC1 and human glioblastoma cell line U87 were generated using the liquid overlay method in a 96-well plate, then transferred to a microfluidic chip, designed with a trap within the device to immobilise the spheroid. The procoagulant potential of cell-free supernatant was measured using a prothrombin time clotting assay. Procoagulant activity was assessed under flow rate of 3.0 µL min-1 for 6 hours. RESULTS: Several tumour cell lines (A2780, SKOV3, MIA Paca2, AsPC1 and U87) were assessed for PCA of media (MP associated) and then subsequently assessed for spheroid formation. Prothrombin time of cell-free media was A2780: 794s, SKOV3: 203.4s, MIA Paca2: 412s, AsPC1: 69s and U87: 50.3s. The pancreatic cell line AsPC-1 and glioblastoma cell line U87 were selected for further study on the basis of relatively high PCA and ability to form stable spheroids. When transferred to a microfluidic chip, AsPC1 tumour spheroids showed a slowing of PCA of media over a 6-hour period from 36.6 to 309s. U87 tumour spheroids showed a reduction in PCA of media over a 6-hour period from 51.3 to 108.9s. CONCLUSIONS: This is the first report of tumour spheroids maintained in a microfluidic device and then subsequently assessed for PCA. Tumour spheroids of AsPC1 were shown to produce continuous procaogulant activity and this is presumably due to tumour microparticle release. This new model system offers a way to assess tumour associated PCA under flow conditions.

Microalgae as substrate in low cost terracotta-based microbial fuel cells: Novel application of the catholyte produced.

In this work, the by-product generated during the operation of cylindrical MFCs, made out of terracotta material, is investigated as a feasible means of degrading live microalgae for the first time. In addition to the low cost materials of this design, the reuse of the solution produced in the cathode renders the technology truly green and capable of generating bioenergy. In this study, the effect of a light/dark cycle or dark conditions only on the digestion of live microalgae with the catholyte is investigated. The results show that a combination of light/dark improves degradation and allows algae to be used as substrate in the anode. The addition of 12.5mL of a 1:1 mix of catholyte and microalgae (pre-digested over 5days under light/dark) to the anode, increases the power generation from 7µW to 44µW once all the organic matter in the anode had been depleted.

Daily reduction of oral malodor with the use of a sonic tongue brush combined with an antibacterial tongue spray in a randomized cross-over clinical investigation.

The objective of this clinical investigation was to test the effectiveness on breath odor of a newly designed sonic tongue brush (TongueCare+, TC). It consists of a soft silicone brush optimally designed based on the tongue's anatomy to remove bacterial biofilm from the tongue's complex surface, and it is coupled with a sonic power toothbrush handle. TC was used in combination with an antibacterial tongue spray (BreathRx, BRx) containing 0.09% cetylpyridinium chloride and 0.7% zinc gluconate. A total of 21 participants with oral malodor exceeding the threshold for recognition took part in this cross-over clinical investigation, which consisted of a single use of four treatment arms with one week washout period in between. The treatments consisted of: (1) TC + BRx, (2) TC + water, (3) BRx and (4) water. Malodor levels and bacterial density were monitored up to 6 h by organoleptic scoring and selective plating, respectively. The organoleptic score and bacterial density were significantly lower after using TC + BRx compared to all alternative treatments at all time points. A significant decrease in both parameters was detected after a single use of TC + BRx, from levels characteristic of high oral malodor, to barely noticeable levels after treatment and this was maintained up to 6 h. Moreover, we identified a significant positive correlation between bacterial density and organoleptic score, confirming that bacterial tongue biofilm is the root cause of oral malodor in these subjects. The results of this clinical investigation demonstrated that the combined treatment of a sonic tongue brush with the antibacterial tongue spray is able to deliver more than 6 h of fresh breath following a single use. The clinical investigation was registered at the ISRCTN registry under study identification number ISRCTN38199132.

Self sufficient wireless transmitter powered by foot-pumped urine operating wearable MFC.

The first self-sufficient system, powered by a wearable energy generator based on microbial fuel cell (MFC) technology is introduced. MFCs made from compliant material were developed in the frame of a pair of socks, which was fed by urine via a manual gaiting pump. The simple and single loop cardiovascular fish circulatory system was used as the inspiration for the design of the manual pump. A wireless programmable communication module, engineered to operate within the range of the generated electricity, was employed, which opens a new avenue for research in the utilisation of waste products for powering portable as well as wearable electronics.

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.

Intermittent load implementation in microbial fuel cells improves power performance.

This study reports on the response of small-scale MFCs to intermittent loading, in terms of power output over time. The aim was to understand the evolution with time of power output under different duty cycles, in conditions close to practical implementation. Inexpensive ceramic membranes were compared to cation exchange membranes, under continuous flow and with a pre-digester connected. Results show that at the minute-scale, all the duty cycles investigated, produced 78% higher power bursts from the MFCs (500µW) than when under continuous loading (280µW). These results were recorded from MFCs employing ceramic membranes, whereas the difference in performance for MFCs employing commercially available cation-exchange-membranes was insignificant. When normalising to daily energy production, only specific duty cycles produced more power than continuous loading. Furthermore, the introduction of a pre-digester increased the MFC power outputs 10-fold, thus confirming that separating fermentation from electro-active respiration, significantly enhances the system performance.

Effect of resection of localized pancreaticobiliary adenocarcinoma on angiogenic markers and tissue factor related pro-thrombotic and pro-angiogenic activity.

In this study, 52 patients were studied to elucidate the relative impact of resection of localized pancreaticobiliary adenocarcinoma (PBC) on circulating factors of tumour-associated angiogenesis e.g. tissue factor bearing microparticles (TFMP) and vascular endothelial growth factor (VEGF) and their clinicopathological significance to angiogenesis markers in cancer tissue from PBC patients. Angiogenesis array analysis on serum samples revealed that surgical resection of tumour lesion in PBC patients affects the levels of a panel of angiogenesis-related molecules, including VEGF that was verified by ELISA to significantly reduce (median & IQR: 1003(369-2000) vs. 457(159-834) pg/ml; p<0.05). Correspondingly, a significant decrease in the angiogenic activity (decreased capillary tube formation; p<0.05) of serum samples after the surgery was also found. Despite a decrease in number of circulating TFMP after surgery, this did not reach statistical significance; there was a significant reduction in pro-coagulant activity (prolonged prothrombin time, p<0.001) post-operatively. In addition, the activity of total microparticles (MP activity assay, p<0.05) was decreased significantly. Immunohistochemical staining of tumour tissue revealed a strong correlation between the microvessel density (MVD) and VEGF expression. Also, higher levels of circulating TFMP or TF related activity (prothrombin time) correlated significantly with TF expression and MVD on tumour tissues from PBC patients. These findings suggest that in pancreaticobiliary adenocarcinoma TF related angiogenesis drivers are equally significant to VEGF ones, raising the clinical question of whether the effectiveness of angiogenesis targeting studies could be improved through the 'dual' targeting of these pathways in PBC.

Halitosis management by the general dental practitioner--results of an international consensus workshop.

Clinical investigations on patients suffering from halitosis clearly reveal that in the vast majority of cases the source for an offensive breath odor can be found within the oral cavity (90%). Based on these studies, the main sources for intra-oral halitosis where tongue coating, gingivitis/periodontitis or a combination of the two. Thus, it is perfectly logical that general dental practitioners (GDPs) should be able to manage intra-oral halitosis under the conditions found in a normal dental practice. However, GDPs who are interested in diagnosing and treating halitosis are challenged to incorporate scientifically based strategies for use in their clinics. Therefore, the present paper summarizes the results of a consensus workshop of international authorities held with the aim to reach a consensus on general guidelines on how to assess and diagnose patients' breath odor concerns and general guidelines on regimens for the treatment of halitosis.

Organoleptic assessment of halitosis for dental professionals--general recommendations.

An organoleptic assessment of an odor is defined as a method that can measure the strength of target odors and expresses the value in terms of a point or number with reference to a pre-defined organoleptic scale. Organoleptic assessments are performed using different scales and are used widely in industry (e.g. for measuring the effectiveness of anti-odor agents), in research (to discover relationships between bad breath and microbiology of the tongue, or the generation of particular volatile compounds), but it is also a prerequisite for the diagnosis of halitosis in individual patients required before directing appropriate treatment. An organoleptic assessment of halitosis patients may be carried out in specialized institutions but--based on the fact that in most cases the odor originates from oral structures--also by dental professionals including general dental practitioners (GDPs). Thus, this paper describes the scientific background for recommendations on how a GDP or dental hygienist or general practitioner with cases of bad breath should use organoleptic methods as a valid approach to assess malodor in patients, with a view to diagnosis and treatment, and subsequent treatment monitoring.

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.