Investigating electro- and sonoelectro-oxidation processes for sustainability on Earth and the exploration of space

In recent years, there has been an explosion in the adoption of electrochemical methods for tackling many of the environmental issues we face in modern society. This electrochemical approach encompasses a range of highly tuneable techniques which often remove the need for harmful chemicals and high temperatures. In this thesis, we will examine how electrochemistry can be utilised for the development of “green” processes based on electrooxidation. Demonstrating the versatility of these techniques the work herein covers a wide range of fields, the results from which can have consequences stretching from removal of pollutants from water to future space travel. Chapter 1 provides context to the research in chapters 3 to 5; namely in introducing the motivations and current state of research behind the development of anion exchange membrane electrolysers as a clean energy solution, the implementation of electrolysis systems in space missions, and the use of combined sono-electrochemical methods for water decontamination. In Chapter 2, the experimental techniques behind the research in this thesis is reported. Chapter 3 reports the development of a novel anion-exchange membrane electrolyser, and its use in the electrochemical degradation of the naturally occurring polymer, lignin. The performance of the membrane, a co-polymer of dehydrofluorinated poly(vinylidene fluoride-co-hexafluoropropylene) with (vinylbenzyl)trimethylammonium chloride and Nvinylimidazole, was benchmarked against a commercial equivalent yielding comparable results. In Chapter 4, we report an investigation into the efficiency of oxygen-evolving electrolysis at gravity levels between 0 and 1 g. The data collected from this experiment, carried out as part of the European Space Agency’s Fly Your Thesis programme, is the first study to examine the efficiency of this process at gravitational fields equal to that of the Moon and Mars. This process was tested not just at reduced gravity levels but also at those exceeding Earth’s gravity, finding that results collected in hypergravity can be extrapolated to predict the performance of the procedure in microgravity. In Chapter 5 we revisit the work introduced in Chapter 1 with an investigation in to the sonoelectrochemical degradation of the anti-inflammatory drug diclofenac. Coupling low-frequency sonication with electrolysis performed using a Pt/Ti anode, a degradation removal efficiency of 64% under optimal conditions was achieved. Comparison of this method with non-coupled electrolytic and sonolytic degradation indicated that at 80 kHz, there was a strong synergistic effect

The effects of ultrasound on the electro-oxidation of sulfate solutions at low pH

The electro‐oxidation of sulfate solutions is a well‐established route for the generation of powerful oxidants such as persulfate. Despite this, the effects of simultaneous ultrasound irradiation during this process has attracted little attention. Herein, we investigate the effects of a low‐intensity ultrasonic field on the generation of solution‐phase oxidants during the electro‐oxidation of sulfate solutions. Our results show that at high current densities and high sulfate concentrations, ultrasound has little effect on the Faradaic and absolute yields of solution‐phase oxidants. However, at lower current densities and sulfate concentrations, the amount of these oxidants in solution appears to decrease under ultrasonic irradiation. A mechanism explaining these results is proposed (and validated), whereby anodically‐generated sulfate and hydroxyl radicals are more effectively transported into bulk solution (where they are quenched) during sonication, whereas in the absence of an ultrasonic field these radicals combine with one another to form more persistent species (such as persulfate) that can be detected by iodometry

Decoupled electrochemical water splitting: from fundamentals to applications

Electrolytic water splitting to generate hydrogen and oxygen is one of the most promising ways in which to harness intermittent renewable power sources and store the energy these provide as a clean‐burning and sustainable fuel. In recent years, this has led to an explosion in reports on electrochemical water splitting, most of them focused on improving the efficiency of the electrochemical reactions themselves. However, efficient generation of hydrogen and oxygen is of little use if these products cannot be kept separate and the community is now coming to realize that there are considerable challenges associated with maintaining adequate separation between H2 and O2 during electrolysis driven by intermittent renewable sources. Decoupled electrolysis (whereby oxygen production occurs with reduction of a suitable mediator and hydrogen production is then paired with the reoxidation of this mediator) offers a solution to many of these challenges by allowing O2 and H2 to be produced at different times, at different rates, and even in completely different electrochemical cells. In this review, an overview of recent progress in the field of decoupled electrolysis for water splitting is given and the potential that this approach has for enabling a range of other sustainable chemical processes is explored

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe

A comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimens

Supported by the Global Alliance for TB Drug Development with support from the Bill & Melinda Gates Foundation, the Medical Research Council (MC_UU_12023/27), the European and Developing Countries Clinical Trials Partnership (grant IP.2007.32011.011), the US Agency for International Development, the UK Department for International Development, the Directorate General for International Cooperation of the Netherlands, Irish Aid, the Australia Department of Foreign Affairs and Trade and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636 and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin. Additional grants were from Chief Scientist Office, Scottish Government, British Society of Antimicrobial Chemotherapy.Background:  Tuberculosis kills more people than any other infectious disease, and new regimens are essential. The primary endpoint for confirmatory phase III trials for new regimens is a composite outcome that includes bacteriological treatment failure and relapse. Culture methodology is critical to the primary trial outcome. Patients in clinical trials can have positive cultures after treatment ends that may not necessarily indicate relapse, which was ascribed previously to laboratory cross-contamination or breakdown of old lesions. Löwenstein-Jensen (LJ) medium was the previous standard in clinical trials, but almost all current and future trials will use the Mycobacteria Growth Indicator Tube (MGIT) system due to its simplicity and consistency of use, which will affect phase III trial results. LJ was used for the definition of the primary endpoint in the REMoxTB trial, but every culture was also inoculated in parallel into the MGIT system. The data from this trial, therefore, provide a unique opportunity to investigate and compare the incidence of false ‘isolated positives’ in liquid and solid media and their potential impact on the primary efficacy results. Methods:  All post-treatment positive cultures were reviewed in the REMoxTB clinical trial. Logistic regression models were used to model the incidence of isolated positive cultures on MGIT and LJ. Results:  A total of 12,209 sputum samples were available from 1652 patients; cultures were more often positive on MGIT than LJ. In 1322 patients with a favourable trial outcome, 126 (9.5%) had cultures that were positive in MGIT compared to 34 (2.6%) patients with positive cultures on LJ. Among patients with a favourable outcome, the incidence of isolated positives on MGIT differed by study laboratory (p < 0.0001) with 21.9% of these coming from one laboratory investigating only 4.9% of patients. No other baseline factors predicted isolated positives on MGIT after adjusting for laboratory. There was evidence of clustering of isolated positive cultures in some patients even after adjusting for laboratory, p < 0.0001. The incidence of isolated positives on MGIT did not differ by treatment arm (p = 0.845, unadjusted). Compared to negative MGIT cultures, positive MGIT cultures were more likely to be associated with higher grade TB symptoms reported within 7 days either side of sputum collection in patients with an unfavourable primary outcome (p < 0.0001) but not in patients with a favourable outcome (p = 0.481). Conclusions:  Laboratory cross-contamination was a likely cause of isolated positive MGIT cultures which were clustered in some laboratories. Certain patients had repeated positive MGIT cultures that did not meet the definition of a relapse. This pattern was too common to be explained by cross-contamination only, suggesting that host factors were also responsible. We conclude that MGIT can replace LJ in phase III TB trials, but there are implications for the definition of the primary outcome and patient management in trials in such settings. Most importantly, the methodologies differ in the incidence of isolated positives and in their capacity for capturing non-tuberculosis mycobacteria. It emphasises the importance of effective medical monitoring after treatment ends and consideration of clinical signs and symptoms for determining treatment failure and relapse.Publisher PDFPeer reviewe

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

An Investigation of a (vinylbenzyl) trimethylammonium and N-vinylimidazole-substituted poly (vinylidene fluoride-co-hexafluoropropylene) copolymer as an anion-exchange membrane in a lignin-oxidising electrolyser

Electrolysis is seen as a promising route for the production of hydrogen from water, as part of a move to a wider “hydrogen economy”. The electro-oxidation of renewable feedstocks offers an alternative anode couple to the (high-overpotential) electrochemical oxygen evolution reaction for developing low-voltage electrolysers. Meanwhile, the exploration of new membrane materials is also important in order to try and reduce the capital costs of electrolysers. In this work, we synthesise and characterise a previously unreported anion-exchange membrane consisting of a fluorinated polymer backbone grafted with imidazole and trimethylammonium units as the ion-conducting moieties. We then investigate the use of this membrane in a lignin-oxidising electrolyser. The new membrane performs comparably to a commercially-available anion-exchange membrane (Fumapem) for this purpose over short timescales (delivering current densities of 4.4 mA cm−2 for lignin oxidation at a cell potential of 1.2 V at 70 °C during linear sweep voltammetry), but membrane durability was found to be a significant issue over extended testing durations. This work therefore suggests that membranes of the sort described herein might be usefully employed for lignin electrolysis applications if their robustness can be improved

Linking agri-environment scheme habitat area, predation and the abundance of chick invertebrate prey to the nesting success of a declining farmland bird

1. Across Europe, farmland bird populations have continued to decline since the 1970s owing to the intensification of farming practices. Studies of such declines have tended to focus specifically on either the impacts of habitats (nesting and foraging), nest predators or prey availability on bird demographics. The study presented here provides new insights into the relative effects of each of these factors on Yellowhammer nest survival. The Yellowhammer was selected for this study as it is a UK red-listed bird species whose population is in decline across much of Europe.2. We use a long-term dataset of 147 nests, monitored between 1995 and 2007, to provide an insight into how Yellowhammer nest survival is influenced by nesting habitat (nest concealment and nest height), foraging habitats (habitat coverage within 100 m of nests), the removal of nest predators (Magpie Pica pica abundance as an inverse measure of avian predator removal through gamekeeping) and food availability (measured with a D-vac invertebrate suction sampler). 3. Our results indicated that Yellowhammer hatching success was negatively related to the coverage of spring agri-environment scheme habitats, a group which represents invertebrate-rich agri-environment habitats, but hatching success increased with nest height. Fledging success was positively related to the coverage of the seed-rich habitat Wild Bird Seed mixture. The farm-level abundance of Yellowhammer chick-food invertebrates declined over the study period. 4. Synthesis and application. Our results highlight the importance of simultaneously considering multiple agents that shape avian breeding success, i.e. their ability to produce offspring, to inform conservation management. Our key finding for land managers relates to the positive relationship between the proportion seed rich foraging habitat within the Yellowhammer’s average foraging range and Yellowhammer fledging success, which shows that a habitat intended primarily to provide winter food resources is also important to breeding birds. Chick food abundance in this habitat was, however, similar to broadleaf and cereal crops. We recommend that this habitat should be provided near to potential Yellowhammer nesting sites and adjacent to invertebrate-rich agri-environment scheme habitats such as beetle banks and conservation headlands to further boost invertebrate resources for a declining farmland bird

Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership (Grant IP.2007.32011.011), US Agency for International Development, UK Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, National Institutes of Health, AIDS Clinical Trials Group. The study was also supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426). Bayer Healthcare for donated moxifloxacin and Sanofi donated rifampin.Background:  The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Methods:  Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Results:  Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24–41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318–535). Pre-treatment spot samples had a higher yield of positive Ziehl–Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan–Meier analyses in either EMS or spot samples. Conclusions:  Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.Publisher PDFPeer reviewe