Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies

RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster. Induction of GFPRNAi construct also alters the response of lifespan to nutrition, exacerbating the lifespan-shortening effects of food containing a high quantity of yeast. Our study indicates that activation of the RNAi machinery may have sequence-independent side-effects on lifespan, and that caution needs to be exercised when employing ubiquitous RNAi in Drosophila ageing studies. However, we also show that RNAi restricted to certain tissues may not be detrimental to lifespan

The Ras-Erk-ETS-signaling pathway is a drug target for longevity

Summary Identifying the molecular mechanisms that underlie aging and their pharmacological manipulation are key aims for improving lifelong human health. Here, we identify a critical role for Ras-Erk-ETS signaling in aging in Drosophila. We show that inhibition of Ras is sufficient for lifespan extension downstream of reduced insulin/IGF-1 (IIS) signaling. Moreover, direct reduction of Ras or Erk activity leads to increased lifespan. We identify the E-twenty six (ETS) transcriptional repressor, Anterior open (Aop), as central to lifespan extension caused by reduced IIS or Ras attenuation. Importantly, we demonstrate that adult-onset administration of the drug trametinib, a highly specific inhibitor of Ras-Erk-ETS signaling, can extend lifespan. This discovery of the Ras-Erk-ETS pathway as a pharmacological target for animal aging, together with the high degree of evolutionary conservation of the pathway, suggests that inhibition of Ras-Erk-ETS signaling may provide an effective target for anti-aging interventions in mammals. Video Abstrac

Interplay of dFOXO and Two ETS-Family Transcription Factors Determines Lifespan in Drosophila melanogaster

Forkhead box O (FoxO) transcription factors (TFs) are key drivers of complex transcriptional programmes that determine animal lifespan. FoxOs regulate a number of other TFs, but how these TFs in turn might mediate the anti-ageing programmes orchestrated by FoxOs in vivo is unclear. Here, we identify an E-twenty six (ETS)-family transcriptional repressor, Anterior open (Aop), as regulated by the single Drosophila melanogaster FoxO (dFOXO) in the adult gut. AOP, the functional orthologue of the human Etv6/Tel protein, binds numerous genomic sites also occupied by dFOXO and counteracts the activity of an ETS activator, Pointed (Pnt), to prevent the lifespan-shortening effects of co-activation of dFOXO and PNT. This detrimental synergistic effect of dFOXO and PNT appears to stem from a mis-regulation of lipid metabolism. At the same time, AOP activity in another fly organ, the fat body, has further beneficial roles, regulating genes in common with dfoxo, such as the secreted, non-sensory, odorant binding protein (Obp99b), and robustly extending lifespan. Our study reveals a complex interplay between evolutionarily conserved ETS factors and dFOXO, the functional significance of which may extend well beyond animal lifespan

Game of Stones:feasibility randomised controlled trial of how to engage men with obesity in text message and incentive interventions for weight loss

Objectives To examine the acceptability and feasibility of narrative text messages with or without financial incentives to support weight loss for men. Design Individually randomised three-arm feasibility trial with 12 months’ follow-up. Setting Two sites in Scotland with high levels of disadvantage according to Scottish Index for Multiple Deprivation (SIMD). Participants Men with obesity (n=105) recruited through community outreach and general practitioner registers. Interventions Participants randomised to: (A) narrative text messages plus financial incentive for 12 months (short message service (SMS)+I), (B) narrative text messages for 12 months (SMS only), or (C) waiting list control. Outcomes Acceptability and feasibility of recruitment, retention, intervention components and trial procedures assessed by analysing quantitative and qualitative data at 3, 6 and 12 months. Results 105 men were recruited, 60% from more disadvantaged areas (SIMD quintiles 1 or 2). Retention at 12 months was 74%. Fewer SMS+I participants (64%) completed 12-month assessments compared with SMS only (79%) and control (83%). Narrative texts were acceptable to many men, but some reported negative reactions. No evidence emerged that level of disadvantage was related to acceptability of narrative texts. Eleven SMS+I participants (31%) successfully met or partially met weight loss targets. The cost of the incentive per participant was £81.94 (95% CI £34.59 to £129.30). Incentives were acceptable, but improving health was reported as the key motivator for weight loss. All groups lost weight (SMS+I: −2.51 kg (SD=4.94); SMS only: −1.29 kg (SD=5.03); control: −0.86 kg (SD=5.64) at 12 months). Conclusions This three-arm weight management feasibility trial recruited and retained men from across the socioeconomic spectrum, with the majority from areas of disadvantage, was broadly acceptable to most participants and feasible to deliver

Text messaging and financial incentives to encourage weight loss in men with obesity: the Game of Stones feasibility RCT

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. 8, No. 11. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD

Designing financial incentives for health behaviour change: a mixed-methods case study of weight loss in men with obesity

Aim: Designing financial incentives for health behaviour change requires choices across several domains, including value (the size of the incentive), frequency of incentives, and direction (gain or loss). However, the rationale underlying complex incentive design is infrequently reported. Transparent reporting is important if we want to understand and improve the incentive development process. This paper describes a mixed methods approach for designing financial incentives for health behaviour change which involves stakeholders throughout the design process. Subject and methods: The mixed methods approach focuses on incentives for weight loss for men with obesity living in areas with high levels of disadvantage. The approach involves: (a) using an existing framework to identify all domains of a financial incentive scheme for which choices need to be made, deciding what criteria are relevant (such as effectiveness, acceptability and uptake) and making choices on each domain on the basis of the criteria; (b) conducting a survey of target population preferences to inform choices for domains and to design the incentive scheme; and (c) making final decisions at a stakeholder consensus workshop. Results: The approach was implemented and an incentive scheme for weight loss for men living with obesity was developed. Qualitative interview data from men receiving the incentives in a feasibility trial endorses our approach. Conclusion: This paper demonstrates that a mixed methods approach with stakeholder involvement can be used to design financial incentives for health behaviour change such as weight loss. Trial registration number: NCT03040518. Date: 2 February 2017

Recruiting men from across the socioeconomic spectrum via GP registers and community outreach to a weight management feasibility randomised controlled trial

Background Men, particularly those living in disadvantaged areas, are less likely to participate in weight management programmes than women despite similar levels of excess weight. Little is known about how best to recruit men to weight management interventions. This paper describes patient and public involvement in pre-trial decisions relevant to recruitment and aims to report on recruitment to the subsequent men-only weight management feasibility trial, including the: i) acceptability and feasibility of recruitment; and ii) baseline sample characteristics by recruitment strategy. Methods Men with BMI ≥30 kg/m2 and/or waist circumference ≥ 40 in. were recruited to the feasibility trial via two strategies; community outreach (venue information stands and word of mouth) and GP letters, targeting disadvantaged areas. Recruitment activities (e.g. letters sent, researcher venue hours) were recorded systematically, and baseline characteristics questionnaire data collated. Qualitative interviews (n = 50) were conducted three months post-recruitment. Analyses and reporting followed a complementary mixed methods approach. Results 105 men were recruited within four months (community n = 60, GP letter n = 45). Community outreach took 2.3 recruiter hours per participant and GP letters had an opt-in rate of 10.2% (n = 90/879). More men were interested than could be accommodated. Most participants (60%) lived in more disadvantaged areas. Compared to community outreach, men recruited via GP letters were older (mean = 57 vs 48 years); more likely to report an obesity-related co-morbidity (87% vs 44%); and less educated (no formal qualifications, 32% vs 10%, degree educated 11% vs 41%). Recruitment strategies were acceptable, a sensitive approach and trusting relationships with recruiters valued, and the ‘catchy’ study name drew attention. Conclusions Targeted community outreach and GP letters were acceptable strategies that successfully recruited participants to a men-only weight management feasibility trial. Both strategies engaged men from disadvantaged areas, a typically underserved population. Using two recruitment strategies produced samples with different health risk profiles, which could add value to research where either primary or secondary prevention is of interest. Further work is required to examine how these strategies could be implemented and sustained in practice

Acceptability of financial incentives for breastfeeding: thematic analysis of readers' comments to UK online news reports.

BACKGROUND: Whilst it is recommended that babies are breastfed exclusively for the first six months, many mothers do not maintain breastfeeding for this length of time. Previous research confirms that women and midwives value financial incentives for breastfeeding, but limited research has explored the wider acceptability of these interventions to the general public. This paper examines opinion towards financial incentives for breastfeeding using reader responses to UK on-line media coverage of a study undertaken in this area. METHODS: This study used netnography to undertake a thematic analysis of 3,373 reader comments posted in response to thirteen articles, published in November 2013, which reported findings from a feasibility study of financial incentives for breastfeeding. All articles were published on one of six UK news websites that achieved a monthly audience of at least five million viewers across laptop and desktop computers and mobile devices during April-May 2013. RESULTS: Nine analytical themes were identified, with a majority view that financial incentives for breastfeeding are unacceptable. These themes cover a range of opinions: from negligent parents unable to take responsibility for their own actions; through to psychologically vulnerable members of society who should be protected from coercion and manipulation; to capable and responsible women who can, and should be allowed to, make their own decisions. Many views focused on the immediate costs of the intervention, concluding that this was something that was currently unaffordable to fund (e.g. by the NHS). Others contrasted the value of the incentive against other 'costs' of breastfeeding. There was some consideration of the issue of cost-effectiveness and cost-saving, where the potential future benefit from initial investment was identified. Many commenters identified that financial incentives do not address the many structural and cultural barriers to breastfeeding. CONCLUSIONS: Overall, those commenting on the on-line UK news articles viewed financial incentives for breastfeeding as unacceptable and that alternative, structural, interventions were likely to be more effective. Further consideration of how best to conduct internet-based qualitative research to elicit opinion towards public health issues is required

Web mining for translators: automatic construction of comparable, genre-driven corpora

The aim of this paper is to evaluate the efficacy of the application WebBootCaT to create specialised corpora automatically, investigating the translation of articles of association from Italian into English. The first section reflects on the relevant literature and proposes the utility of corpora for translators. The second section discusses the methodology employed, and the third section analyses the results obtained and comments on how language professionals could possibly exploit the application to its full. The fourth section provides a few concrete usage examples of the thus built corpora, to then conclude that WebBootCaT is a genuinely powerful tool that could be implemented by professional translators in order to save time and improve their translations in the long term