Exploring the uptake and use of electronic cigarettes provided to smokers accessing homeless centres: a four-centre cluster feasibility trial

Background: Smoking prevalence is extremely high in adults experiencing homelessness, and there is little evidence regarding which cessation interventions work best. This study explored the feasibility of providing free electronic cigarette starter kits to smokers accessing homeless centres in the UK. / Objectives: Seven key objectives were examined to inform a future trial: (1) assess willingness of smokers to participate in the study to estimate recruitment rates; (2) assess participant retention in the intervention and control arms; (3) examine the perceived value of the intervention, facilitators of and barriers to engagement, and influence of local context; (4) assess service providers’ capacity to support the study and the type of information and training required; (5) assess the potential efficacy of supplying free electronic cigarette starter kits; (6) explore the feasibility of collecting data on contacts with health-care services as an input to a main economic evaluation; and (7) estimate the cost of providing the intervention and usual care. / Design: A prospective cohort four-centre pragmatic cluster feasibility study with embedded qualitative process evaluation. / Setting: Four homeless centres. Two residential units in London, England. One day centre in Northampton, England. One day centre in Edinburgh, Scotland. / Intervention: In the intervention arm, a single refillable electronic cigarette was provided together with e-liquid, which was provided once per week for 4 weeks (choice of three flavours: fruit, menthol or tobacco; two nicotine strengths: 12 or 18 mg/ml). There was written information on electronic cigarette use and support. In the usual-care arm, written information on quitting smoking (adapted from NHS Choices) and signposting to the local stop smoking service were provided. / Results: Fifty-two per cent of eligible participants invited to take part in the study were successfully recruited (56% in the electronic cigarette arm; 50.5% in the usual-care arm; total n = 80). Retention rates were 75%, 63% and 59% at 4, 12 and 24 weeks, respectively. The qualitative component found that perceived value of the intervention was high. Barriers were participants’ personal difficulties and cannabis use. Facilitators were participants’ desire to change, free electronic cigarettes and social dynamics. Staff capacity to support the study was generally good. Carbon monoxide-validated sustained abstinence rates at 24 weeks were 6.25% (3/48) in the electronic cigarette arm compared with 0% (0/32) in the usual-care arm (intention to treat). Almost all participants present at follow-up visits completed measures needed for input into an economic evaluation, although information about staff time to support usual care could not be gathered. The cost of providing the electronic cigarette intervention was estimated at £114.42 per person. An estimated cost could not be calculated for usual care. / Limitations: Clusters could not be fully randomised because of a lack of centre readiness. The originally specified recruitment target was not achieved and recruitment was particularly difficult in residential centres. Blinding was not possible for the measurement of outcomes. Staff time supporting usual care could not be collected. / Conclusions: The study was associated with reasonable recruitment and retention rates and promising acceptability in the electronic cigarette arm. Data required for full cost-effectiveness evaluation in the electronic cigarette arm could be collected, but some data were not available in the usual-care arm. / Future work: Future research should focus on several key issues to help design optimal studies and interventions with this population, including which types of centres the intervention works best in, how best to retain participants in the study, how to help staff to deliver the intervention, and how best to record staff treatment time given the demands on their time. / Trial registration: Current Controlled Trials ISRCTN14140672; the protocol was registered as researchregistry4346. / Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 9, No. 7. See the NIHR Journals Library website for further project information

Women and Illegal Activities: Gender Differences and Women's Willingness to Comply Over Time

In recent years the topics of illegal activities such as corruption or tax evasion have attracted a great deal of attention. However, there is still a lack of substantial empirical evidence about the determinants of compliance. The aim of this paper is to investigate empirically whether women are more willing to be compliant than men and whether we observe (among women and in general) differences in attitudes among similar age groups in different time periods (cohort effect) or changing attitudes of the same cohorts over time (age effect) using data from eight Western European countries from the World Values Survey and the European Values Survey that span the period from 1981 to 1999. The results reveal higher willingness to comply among women and an age rather than a cohort effect. Working Paper 06-5

Exploring the uptake and use of electronic cigarettes provided to smokers accessing homeless centres: a four-centre cluster feasibility trial

Background Smoking prevalence is extremely high in adults experiencing homelessness and there is little evidence regarding which cessation interventions work best. This study explored the feasibility of providing free e-cigarette (EC) starter kits to smokers accessing homeless centres in the UK Objectives Seven key objectives were examined to inform a future trial. 1: Assess willingness of smokers to participate in the study to estimate recruitment rates. 2: Assess participant retention in the intervention and control groups. 3: Examine the perceived value of the intervention, facilitators and barriers to engagement and influence of local context. 4: Assess service providers’ capacity to support the study and the type of information and training required. 5: Assess the potential efficacy of supplying free EC starter kits. 6: Explore the feasibility of collecting data on contact with health care services as an input to a main economic evaluation. 7: Estimate the cost of providing the intervention and usual care. Design A prospective cohort four-centre pragmatic cluster feasibility study with embedded qualitative process evaluation. Setting Four homeless centres. Two residential units in London, England. One day centre in Northampton, England. One day centre in Edinburgh, Scotland. Intervention Intervention arm: A single refillable EC was provided with e-liquid provided once a week for four weeks (choice of three flavours: fruit, menthol, tobacco and two nicotine strengths: 12mg/mL or 18mg/mL). Written information for EC use and support. Usual care arm: Written information on quitting smoking (adapted from NHS Choices) and signposting to the local stop smoking service (SSS). Results Fifty-two percent of eligible participants invited to take part in the study were successfully recruited (56% in the EC arm; 50.5% in the UC arm; total N=80). Retention rates were 75%, 63% and 59% respectively at 4, 12 and 24 weeks. The qualitative component found perceived value of the intervention was high. Barriers were participant’s personal difficulties and cannabis use. Facilitators were participants’ desire to change, free EC and social dynamics. Staff capacity to support the study was generally good. Carbon Monoxide (CO) validated sustained abstinence rates at 24 weeks were 6.25% (3/48) in the EC arm vs. 0/32 (0%) in the UC arm (intention to treat). Almost all participants present at follow-up visits completed measures needed for input into an economic evaluation although information about staff time to support UC could not be gathered. The cost of providing the EC intervention was estimated to be £114.42 per person. Estimated cost could not be completed for UC. Limitations Clusters could not be fully randomised due to lack of centre readiness. The originally specified recruitment target was not achieved and recruitment was particularly difficult in residential centres. Blinding was not possible for the measurement of outcomes. Staff time supporting UC could not be collected. Conclusions The study was associated with reasonable recruitment and retention rates and promising acceptability in the EC arm. Data required for full cost-effectiveness evaluation in the EC arm could be collected but some data was not available in the UC arm. Future work: Future research should focus on several key issues to help design optimal studies and interventions with this population, including: which types of centres the intervention works best in; how best to retain participants in the study; how to help staff to deliver the intervention and how best to record staff treatment time given the demands on their time

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Clinical effectiveness of the psychological therapy Mental Health Intervention for Children with Epilepsy in addition to usual care compared with assessment-enhanced usual care alone: a multicentre, randomised controlled clinical trial in the UK

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant

Probing human sperm metabolism using 13C-magnetic resonance spectroscopy

STUDY QUESTION: Can 13C-Magnetic Resonance Spectroscopy (MRS) of selected metabolites provide useful information about human sperm metabolism and how glycolysis or oxidative phosphorylation are used by different sperm populations? SUMMARY ANSWER: Sperm populations, prepared by density gradient centrifugation (DGC) and incubated with either 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate, showed consistent evidence of metabolism generating principally lactate and more intermittently bicarbonate, and significantly more lactate was produced from 13Cu-glucose by vital or motile sperm recovered from the 40/80% interface compared to those from the pellet, which could not be accounted for by differences in the non-sperm cells present. WHAT IS KNOWN ALREADY: Previous studies have focused on CO2 or other specific metabolite production by human sperm and there remains considerable debate about whether glycolysis and/or oxidative phosphorylation is the more important pathway for ATP production in sperm. STUDY DESIGN SIZE, DURATION: Sperm populations were prepared by DGC and subjected to 13C-MRS to answer the following questions. (i) Is it possible to detect human sperm metabolism of 13C substrates implicated in energy generation? (ii) What are the kinetics of such reactions? (iii) Do different sperm populations (e.g. '80%' pellet sperm and '40%' interface sperm) utilise substrates in the same way? Semen samples from 97 men were used in these experiments; 52 were used in parallel for aims (i) and (ii) and 45 were used for aim (iii). PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm populations were prepared from ejaculates of healthy men using a Percoll/Phosphate Buffered Saline (PBS) DGC and then incubated with a range of 13C-labelled substrates (13Cu-glucose, 13Cu-fructose, 13C1-pyruvate, 13C1-butyrate, 13C3-lactate, 13C2,4-D-3-hydroxybutyrate, 13C5-L-glutamate, 13C1,2-glycine or 13Cu-galactose) along with penicillin/streptomycin antibiotic at 37°C for 4 hours, 24 hours or over 48 hours for an estimated rate constant. Sperm concentration, vitality and motility were measured and, for a subset of experiments, non-sperm cell concentration was determined. A 9.4T magnetic resonance spectrometer was used to acquire 1D 13C, inverse gated 1H decoupled, MRS spectra. Spectrum processing was carried out using spectrometer software and Matlab scripts to determine peak integrals for each spectrum. MAIN RESULTS AND THE ROLE OF CHANCE: 13Cu-glucose, 13Cu-fructose and 13C1-pyruvate were consistently converted into lactate and, to a lesser extent, bicarbonate. There was a significant correlation between sperm concentration and lactate peak size for 13Cu-glucose and 13Cu-fructose, which was not observed for 13C1-pyruvate. The lactate peak did not correlate with the non-sperm cell concentration up to 6.9 × 106/ml. The concentration of 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate (1.8, 3.6, 7.2 or 14.4 mM) had no influence on the size of the observed lactate peak over a 4 hour incubation. The rate of conversion of 13C1-pyruvate to lactate was approximately three times faster than for 13Cu-glucose or 13Cu-fructose which were not significantly different from each other. After incubating for 4 hours, the utilisation of 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate by sperm from the '40%' interface of the DGC was no different from those from the pellet when normalised to total sperm concentration. However, after normalising by either the vital or motile sperm concentration, there was a significant increase in conversion of 13Cu-glucose to lactate by '40%' interface sperm compared to pellet sperm (Vital = 3.3 ± 0.30 × 106 vs 2.0 ± 0.21 × 106; p = 0.0049; Motile = 7.0 ± 0.75 × 106 vs 4.8 ± 0.13 × 106; p = 0.0032. Mann-Whitney test p < 0.0055 taken as statistically significant). No significant differences were observed for 13Cu-fructose or 13C1-pyruvate. LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: Only 13C labelled metabolites that accumulate to a sufficiently high concentration can be observed by 13C MRS. For this reason, intermediary molecules in the metabolic chain are difficult to observe without trapping the molecule at a particular step using inhibitors. Non-sperm cell concentration was typical of the general population and no link was found between these cells and the magnitude of the 13C-lactate peak. However, it is possible that higher concentrations than the maximum observed (6.9 × 106/ml) may contribute to exogenous substrate metabolism in other experiments. WIDER IMPLICATIONS OF THE FINDINGS: 13C-MRS can provide information on the underlying metabolism of multiple pathways in live sperm. Dysfunction in sperm metabolism, as a result of either impaired enzymes of lack of metabolisable substrate, could be detected in sperm by a non-destructive assay, potentially offering new treatment options to improve overall sperm quality and outcomes for reproduction. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest

Satisfaction with Creativity: A Study of Organizational Characteristics and Individual Motivation

In answering the question of what influences satisfaction with creativity in the workplace, this work takes into account the extent to which the organization supports human aspiration to act creatively. The work throughout reflects a pragmatist approach to creativity and fulfillment, bridging it with needs theory in psychology. The empirical model uses survey data encompassing over 4,000 workers in Italian social enterprises. Results show that satisfaction with creativity is supported, at organizational level, by teamwork, autonomy, domain-relevant competences, as well as by inclusive, fair processes and relationships. At the individual level, satisfaction with creativity is enhanced by the strength of intrinsic initial motivations. The analysis of interaction terms shows that teamwork and workers' initial motivations are complementary in enhancing satisfaction with creativity, while a high degree of domain-relevant competences appears to substitute advice and supervision by superiors in accomplishing the desired level of creative action