Electrogenic Biofilm Development Determines Charge Accumulation and Resistance to pH Perturbation

The electrogenic biofilm and the bio-electrode interface are the key biocatalytic components in bioelectrochemical systems (BES) and can have a large impact on cell performance. This study used four different anodic carbons to investigate electrogenic biofilm development to determine the influence of charge accumulation and biofilm growth on system performance and how biofilm structure may mitigate against pH perturbations. Power production was highest (1.40 W/m3) using carbon felt, but significant power was also produced when felt carbon was open-circuit acclimated in a control reactor (0.95 W/m3). The influence of carbon material on electrogenic biofilm development was determined by measuring the level of biofilm growth, using sequencing to identify the microbial populations and confocal microscopy to understand the spatial locations of key microbial groups. Geobacter spp. were found to be enriched in closed-circuit operation and these were in close association with the carbon anode, but these were not observed in the open-circuit controls. Electrochemical analysis also demonstrated that the highest mid-point anode potentials were close to values reported for cytochromes from Geobacter sulfurreductans. Biofilm development was greatest in felt anodes (closed-circuit acclimated 1209 ng/μL DNA), and this facilitated the highest pseudo-capacitive values due to the presence of redox-active species, and this was associated with higher levels of power production and also served to mitigate against the effects of low-pH operation. Supporting carbon anode structures are key to electrogenic biofilm development and associated system performance and are also capable of protecting electrochemically active bacteria from the effects of environmental perturbations

Simplified Reactor Design for Mixed Culture-Based Electrofermentation toward Butyric Acid Production

Mixed microbial culture (MMC) electrofermentation (EF) represents a promising tool to drive metabolic pathways toward the production of a specific compound. Here, the MMC-EF process has been exploited to obtain butyric acid in simplified membrane-less reactors operated by applying a difference of potential between two low-cost graphite electrodes. Ten values of voltage difference, from -0.60 V to -1.5 V, have been tested and compared with the experiment under open circuit potential (OCP). In all the tested conditions, an enhancement in the production rate of butyric acid (from a synthetic mixture of glucose, acetate, and ethanol) was observed, ranging from 1.3- to 2.7-fold relative to the OCP. Smaller enhancements in the production rate resulted in higher values of the calculated specific energy consumption. However, at all applied voltages, a low flow of current was detected in the one-chamber reactors, accounting for an average value of approximately -100 µA. These results hold a substantial potential with respect to the scalability of the electrofermentation technology, since they pinpoint the possibility to control MMC-based bioprocesses by simply inserting polarized electrodes into traditional fermenters

Intervention Synthesis: A Missing Link between a Systematic Review and Practical Treatment(s)

Paul Glasziou and colleagues discuss methods to guide selection of an intervention from individual trials within a systematic review. Please see later in the article for the Editors' Summary

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Pilot study evaluating a brief mindfulness intervention for those with chronic pain: study protocol for a randomized controlled trial.

BACKGROUND: The burden of chronic pain is a major challenge, impacting the quality of life of patients. Intensive programmes of mindfulness-based therapy can help patients to cope with chronic pain but can be time consuming and require a trained specialist to implement. The self-management model of care is now integral to the care of patients with chronic pain; home-based interventions can be very acceptable, making a compelling argument for investigating brief, self-management interventions. The aim of this study is two-fold: to assess the immediate effects of a brief self-help mindfulness intervention for coping with chronic pain and to assess the feasibility of conducting a definitive randomized controlled trial to determine the effectiveness of such an intervention. METHODS/DESIGN: A randomized controlled pilot study will be conducted to evaluate a brief mindfulness intervention for those with chronic pain. Ninety chronic pain patients who attend hospital outpatient clinics will be recruited and allocated randomly to either the control or treatment group on a 1:1 basis using the computer-generated list of random numbers. The treatment group receives mindfulness audios and the control group receives audios of readings from a non-fiction book, all of which are 15 minutes in length. Immediate effects of the intervention are assessed with brief psychological measures immediately before and after audio use. Mindfulness, mood, health-related quality of life, pain catastrophizing and experience of the intervention are assessed with standardized measures, brief ratings and brief telephone follow-ups, at baseline and after one week and one month. Feasibility is assessed by estimation of effect sizes for outcomes, patient adherence and experience, and appraisal of resource allocation in provision of the intervention. DISCUSSION: This trial will assess whether a brief mindfulness-based intervention is effective for immediately reducing perceived distress and pain with the side effect of increasing relaxation in chronic pain patients and will determine the feasibility of conducting a definitive randomized controlled trial. Patient recruitment began in January 2015 and is due to be completed in June 2016. TRIAL REGISTRATION: ISRCTN61538090 Registered 20 April 2015

Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom

Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. Methods: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. Results: 132 pts were included. Median age was 56 years (28–91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5–6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. Conclusion: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience

An intervention to support adherence to inhaled medication in adults with cystic fibrosis: the ACtiF research programme including RCT

Background People with cystic fibrosis frequently have low levels of adherence to inhaled medications. Objectives The objectives were to develop and evaluate an intervention for adults with cystic fibrosis to improve adherence to their inhaled medication. Design We used agile software methods to develop an online platform. We used mixed methods to develop a behaviour change intervention for delivery by an interventionist. These were integrated to become the CFHealthHub intervention. We undertook a feasibility study consisting of a pilot randomised controlled trial and process evaluation in two cystic fibrosis centres. We evaluated the intervention using an open-label, parallel-group randomised controlled trial with usual care as the control. Participants were randomised in a 1 : 1 ratio to intervention or usual care. Usual care consisted of clinic visits every 3 months. We undertook a process evaluation alongside the randomised controlled trial, including a fidelity study, a qualitative interview study and a mediation analysis. We undertook a health economic analysis using both a within-trial and model-based analysis. Setting The randomised controlled trial took place in 19 UK cystic fibrosis centres. Participants Participants were people aged ≥ 16 years with cystic fibrosis, on the cystic fibrosis registry, not post lung transplant or on the active transplant list, who were able to consent and not using dry-powder inhalers. Intervention People with cystic fibrosis used a nebuliser with electronic monitoring capabilities. This transferred data automatically to a digital platform. People with cystic fibrosis and clinicians could monitor adherence using these data, including through a mobile application (app). CFHealthHub displayed graphs of adherence data as well as educational and problem-solving information. A trained interventionist helped people with cystic fibrosis to address their adherence. Main outcome measures Randomised controlled trial – adjusted incidence rate ratio of pulmonary exacerbations meeting the modified Fuchs criteria over a 12-month follow-up period (primary outcome); change in percentage adherence; and per cent predicted forced expiratory volume in 1 second (key secondary outcomes). Process evaluation – percentage fidelity to intervention delivery, and participant and interventionist perceptions of the intervention. Economic modelling – incremental cost per quality-adjusted life-year gained. Results Randomised controlled trial – 608 participants were randomised to the intervention (n = 305) or usual care (n = 303). To our knowledge, this was the largest randomised controlled trial in cystic fibrosis undertaken in the UK. The adjusted rate of exacerbations per year (primary outcome) was 1.63 in the intervention and 1.77 in the usual-care arm (incidence rate ratio 0.96, 95% confidence interval 0.83 to 1.12; p = 0.638) after adjustment for covariates. The adjusted difference in mean weekly normative adherence was 9.5% (95% confidence interval 8.6% to 10.4%) across 1 year, favouring the intervention. Adjusted mean difference in forced expiratory volume in 1 second (per cent) predicted at 12 months was 1.4% (95% confidence interval –0.2% to 3.0%). No adverse events were related to the intervention. Process evaluation – fidelity of intervention delivery was high, the intervention was acceptable to people with cystic fibrosis, participants engaged with the intervention [287/305 (94%) attended the first intervention visit], expected mechanisms of action were identified and contextual factors varied between randomised controlled trial sites. Qualitative interviews with 22 people with cystic fibrosis and 26 interventionists identified that people with cystic fibrosis welcomed the objective adherence data as proof of actions to self and others, and valued the relationship that they built with the interventionists. Economic modelling – the within-trial analysis suggests that the intervention generated 0.01 additional quality-adjusted life-years at an additional cost of £865.91 per patient, leading to an incremental cost-effectiveness ratio of £71,136 per quality-adjusted life-year gained. This should be interpreted with caution owing to the short time horizon. The health economic model suggests that the intervention is expected to generate 0.17 additional quality-adjusted life-years and cost savings of £1790 over a lifetime (70-year) horizon; hence, the intervention is expected to dominate usual care. Assuming a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, the probability that the intervention generates more net benefit than usual care is 0.89. The model results are dependent on assumptions regarding the duration over which costs and effects of the intervention apply, the impact of the intervention on forced expiratory volume in 1 second (per cent) predicted and the relationship between increased adherence and drug-prescribing levels. Limitations Number of exacerbations is a sensitive and valid measure of clinical change used in many trials. However, data collection of this outcome in this context was challenging and could have been subject to bias. It was not possible to measure baseline adherence accurately. It was not possible to quantify the impact of the intervention on the number of packs of medicines prescribed. Conclusions We developed a feasible and acceptable intervention that was delivered to fidelity in the randomised controlled trial. We observed no statistically significant difference in the primary outcome of exacerbation rates over 12 months. We observed an increase in normative adherence levels in a disease where adherence levels are low. The magnitude of the increase in adherence may not have been large enough to affect exacerbations

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

The development and performance of anodic biofilms in microbial fuel cells

Microbial fuel cell (MFC) systems capable of both treating wastewaters and recovering energy have the potential for successful scale-up as a low carbon technology. These systems utilize microorganisms residing in biofilms as biocatalytic agents in the conversion of reduced substrates to electrical energy. As such, it is important to understand how MFC anodic biofilms develop over time and also how environmental parameters such as substrate type, temperature, carbon support material, anode architecture and optimized applied potentials also affect electrogenic performance. The type of substrate was found to have a large impact on the acclimation and performance of electrogenic biofilms. Acetate produced the highest power density of 7.2 W m•3 and butyrate the lowest at 0.29 W m•3, but it was also found that biofilm acclimation to these different trophic Conditions also determined the MFC response to different substrate types i.e. both acetate and butyrate substrates produced power densities of 1.07 and 1.0 W m•3 respectively in a sucrose enriched reactor. The use of MFCs for wastewater treatment in temperate regions requires the development of reactor systems that are robust to seasonal fluctuations and are energy efficient. As such, system performance was examined at three different operating temperatures (10°C, 20°C and 35°C). At each temperature a maximum steady-state voltage of 0.49 V ± 0.02V was achieved after an operational period of 47 weeks, with the time to reach steady-state voltage being dependent on acclimation temperature. The highest COD removal rates of 2.98g COD L-1d•1 were produced in the 35°C reactor but coulombic efficiencies (CE) were found to be significantly higher at pyschrophilic temperatures. Acclimation at different operating temperatures was found to a have a significant effect on the dynamic selection of psychrophilic, psychrotolerant and mesophilic anode respiring bacteria (ARB) and also influence the development of biofilm biomass, methanogenesis and electrogenic activity. Although start-up times were inversely influenced by temperature the amount of biomass accumulation increased with higher operational temperatures and this had a direct impact on biocatalytic performance. The three dimensional structure and porosity of different carbon anode materials affected anodic performance by determining the levels of surface area available for biofilm growth and the capacity for mass transfer to occur. Novel helical electrode configurations were used to look at the effect of altering turbulent flows to increase mass transfer rates and carbon surface areas available for electrogenic growth. The spiral with the highest amount of carbon veil and the smallest gap produced the highest power production of 11.63 Wm-3, Comparative studies of a logic controlled and un-controlled external load impedance showed that control affected the biocatalyst development and hence MFC performance. The controlled MFC better optimized the electrogenic anodic biofilm for power production, indicating that improved power and substrate conversion can be achieved by ensuring sustainable current demand, applied microbial selection pressures and near-optimal impedance for power transference.EThOS - Electronic Theses Online ServiceGBUnited Kingdo