Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome.

The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, WDR5, RbBp5, Ash2L, and DPY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex.

User-generated content and influencer marketing involving e-cigarettes on social media: a scoping review and content analysis of YouTube and Instagram.

BACKGROUND: Evidence suggests that experimentation with e-cigarettes among young people is increasing. Social media is widely used by young people with user-generated content and influencer marketing particularly influential in promoting products. This paper documents a snapshot of online user-generated content and influencer marketing related to e-cigarettes on YouTube and Instagram. METHODS: Scoping review of relevant e-cigarette-related content on two social media platforms popular with youths, YouTube and Instagram, between June and August 2021. Content analysis was undertaken to examine text, audio, and video content, recording age restrictions, health warnings, page characteristics, and post characteristics. Narrative post content was coded using a coding frame that was developed inductively in response to emergent categories. RESULTS: Vaping was portrayed positively on social media; of the posts analysed, 86.5% (n = 90 of 104) of Instagram posts and 66.0% (n = 64 of 97) of YouTube videos. Warnings about age restrictions and health (e.g., nicotine addiction/toxicity) did not feature in the majority of posts; 43.3% (n = 42) of YouTube videos (n = 42) contained an age warning compared to 20.2% of Instagram posts (n = 21). While 25.8% (n = 25) of YouTube videos and 21.2% of Instagram (n = 22) posts contained a health warning. CONCLUSION: Of concern is the fact that the vast majority of YouTube and Instagram content about e-cigarettes promoted their use, and typically the content does not contain age and/or health warnings. These findings may highlight a priority for governmental policy to restrict the ability of marketers to reach youths with social media content promoting e-cigarettes.

Expert views on high fat, salt and sugar food marketing policies to tackle obesity and improve dietary behaviours in the UK: a qualitative study.

BACKGROUND: There has been a lack of progress in reducing obesity in the United Kingdom (UK) despite Government strategies released over the last 30 years. These strategies, including the most recent publication from July 2020, have focused on childhood obesity and high fat, sugar and/or salt (HFSS) marketing restrictions, particularly broadcast advertising. In this study, we aimed to examine a range of expert views on the potential impact and the relative importance of such policies. METHODS: Semi-structured interviews were conducted with 42 experts in policy (n = 19), industry (n = 10), and advocacy (n = 13) with an interest in obesity. The UK Government's 2020 obesity strategy was used as a prompt to guide discussion on policy options. Qualitative thematic analysis was employed to answer the three research questions and themes were inductively coded within each research question. Data were also cross compared using matrix coding and a form of framework analysis to examine the views expressed by the different types of stakeholders. RESULTS: Reactions to the July 2020 proposal were mixed among policy and advocacy stakeholders, while commercial stakeholders expressed disappointment. A main theme emerging in all groups was frustration with the policy process and wishing to see more clarity regarding restrictions and their implementation. There was an overall lack of trust that the government would carry out their proposed plan and agreement that a more comprehensive, multi-sector approach aimed at the underlying drivers of obesity would be most effective, with some stakeholders indicating that some of the proposed policies could make a difference if implemented robustly. On the theme of promoting healthier options, some stakeholders suggested lowering the prices of 'healthy' products and making them more accessible to combat regressivity. There was a potentially surprising level of agreement between policy/advocacy stakeholders and commercial stakeholders, although commercial stakeholders were more likely to advocate for collaboration between government and industry as well as voluntary industry measures. CONCLUSION: While HFSS marketing restrictions have a role to play and send a strong signal - provided they are implemented comprehensively - investment in these policies needs to be part of wider efforts to tackle the underlying drivers of obesity.

Implementation of the polluter pay's principle in tobacco control in the UK: a stakeholder analysis.

BACKGROUND: The polluter's pay principle (PPP) aims to internalise external costs and assign liability to the polluter for the harmful cost of their products to society. Tobacco companies continue to manufacture and sell harmful cigarettes, earning billions in profits each year from these products. Meanwhile, governments and their people are left to 'clean up' and deal with the detrimental health consequences. This paper explores with expert stakeholders how the PPP could be implemented within the context of tobacco control in the United Kingdom (UK). METHODS: Twenty-four semi-structured interviews and two follow-up discussion groups were conducted with UK and international experts on tobacco control, public health, economics, or law from the academic, public, private and third sector. Participants considered the facilitators and barriers to implementing the PPP to tobacco control in the UK. Thematic analysis was employed, aided by NVivo 12, and data were compared to examine the views expressed by the different types of experts. RESULTS: Stakeholders favoured the implementation of the PPP in the context of tobacco control and indicated that it could be acceptable and feasible to implement and that it would likely have support from policymakers and the public alike. Stakeholders unanimously agreed that any legislation and administration should be free from tobacco industry influence; however, differences arose concerning who should oversee the implementation. CONCLUSION: The PPP from environmental law was predominantly seen as an approach that could be usefully applied to the tobacco industry. However, there is no one size fits all template, therefore its implementation would need to be adapted to fit the UK context.

Contextual influences on the role of evidence in e-cigarette recommendations: a multi-method analysis of international and national jurisdictions.

Background: E-cigarette policy has varied across jurisdictions, contrasting with the previous coordinated approach of international tobacco control communities. Aims and objectives: A multi-method case study approach was used to understand the role of evidence and external and internal contextual factors in the development of public health recommendations across four purposively selected jurisdictions (WHO, UK, Australia and USA). Methods: Informed by Dobrow et al.'s (2004) conceptual framework for context-based evidencebased decision-making, four data sources were drawn upon: 1) 15 public health bodies' e-cigarette recommendation documents, 2) seven development documents produced by the public health bodies, 3) sources of evidence cited in the public health bodies' recommendation documents and 4) 15 qualitative interviews with experts. Thematic analysis and citation analysis were conducted to aid triangulation of evidence. Findings: We found a complex interplay between internal and external factors which influence the role and use of evidence in the development of e-cigarette recommendations. For example, recommendation documents' remit (internal factor) was influenced by various external factors such as epidemiology and policy history, with decisions made over time having reshaped the external context. Considering the findings with respect to evidence utilisation, we propose a modified version of Dobrow et al.'s (2004) framework, highlighting the important interplay between internal and external contextual factors. Discussion and conclusion: This research suggest internal and external contextual factors mutually interact and influence how evidence is incorporated into recommendations. This dynamic interplay of contextual factors may help explain the why different policy approaches are pursued concerning public health topics, particularly e-cigarettes.

Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1.

Poly-ADP-ribosyltransferases play a critical role in DNA repair and cell death, and poly(ADP-ribosyl) polymerase 1 (PARP1) is a particularly important therapeutic target for the treatment of breast cancer because of its synthetic lethal relationship with breast cancer susceptibility proteins 1 and 2. Numerous PARP1 inhibitors have been developed, and their efficacy in cancer treatment is attributed to both the inhibition of enzymatic activity and their ability to trap PARP1 on to the damaged DNA, which is cytotoxic. Of the clinical PARP inhibitors, talazoparib is the most effective at trapping PARP1 on damaged DNA. Biochemically, talazoparib is also suspected to be a potent inhibitor of PARP5a/b (tankyrase1/2 [TNKS1/2]), which is an important regulator of Wnt/ß-catenin pathway. Here we show using competition experiments in cell lysate that, at a clinically relevant concentration, talazoparib can potentially bind and engage TNKS1. Using surface plasmon resonance, we measured the dissociation constants of talazoparib, olaparib, niraparib, and veliparib for their interaction with PARP1 and TNKS1. The results show that talazoparib has strong affinity for PARP1 as well as uniquely strong affinity for TNKS1. Finally, we used crystallography and hydrogen deuterium exchange mass spectroscopy to dissect the molecular mechanism of differential selectivity of these PARP1 inhibitors. From these data, we conclude that subtle differences between the ligand-binding sites of PARP1 and TNKS1, differences in the electrostatic nature of the ligands, protein dynamics, and ligand conformational energetics contribute to the different pharmacology of these PARP1 inhibitors. These results will help in the design of drugs to treat Wnt/ß-catenin pathway-related cancers, such as colorectal cancers.

Characterization of organophosphate pesticides in urine and home environment dust in an agricultural community.

CONTEXT: Organophosphorus insecticides (OPs) have been used to control agricultural pests found in Washington state. Farmworkers (FW) have higher exposure to OP pesticides than non-farmworkers (NFW), and FW children may in turn have higher exposure than NFW children. OBJECTIVE: To examine the association between the concentration in house dust of five OPs used commonly in pome fruit orchards and the concentration in urine of dialkylphosphate metabolites (DAP), in a cohort of Hispanic FW and NFW and their children. METHODS: Parents and children participated in three data collection periods over the course of one year. Urine samples were evaluated for the DAPs characteristic of OP exposure, and dust from homes and vehicles was evaluated for intact OP residues. RESULTS: Geometric mean (GM) concentrations of OPs in house and vehicle dust were higher in FW households than NFW households in all agricultural seasons. GM concentration of urinary DAPs was higher for children in FW households than NFW households. DISCUSSION: Regression analysis found a positive association between OP residues in house dust and the children's urinary DAPs. CONCLUSIONS: To our knowledge, this study is the first to report an association between pesticides in house dust and their biological metabolites in urine.

Caregivers' Advice and Children's Bystander Behaviors During Bullying Incidents.

Many bullying prevention programs take a bystander approach, which encourages children to intervene when they are bystanders to bullying incidents. Little is known about how caregivers' advice to children might promote or undermine the positive bystander behaviors targeted by these programs. Accordingly, the aim of the current study was to investigate relations between caregivers' advice and children's bystander behavior during bullying situations. Participants were 106 racially/ethnically diverse 4th- and 5th-grade students (M age = 10.5 years, SD = .71 years), their classmates, and their caregivers. During classroom visits, peers reported on children's bystander behaviors. During home visits, caregivers and children completed a coded interaction task in which caregivers advised children about how to respond to bullying situations at school. Results suggested that (a) bystander intervention was positively predicted by caregivers' advice to help/comfort the victim, (b) bystander passivity was positively predicted by caregivers' advice to not intervene and negatively predicted by caregivers' advice to help/comfort the victim, and (c) bystander reinforcement/assistance of the bully was positively predicted by caregivers' advice not to intervene and not to tell adults. Results support a link between caregivers' advice at home and children's corresponding behavior when they are bystanders to bullying situations at school. These results emphasize the importance of collaboration between families and schools to reduce school bullying. Implications and directions for future research are discussed.

Symptom-Guided Emergency Department Discharge Instructions for Children With Concussion.

OBJECTIVES: The objective was to evaluate the use and utility of a novel set of emergency department discharge instructions (DIs) for concussion based on a child's ongoing symptoms: symptom-guided DIs (symptom DIs). Differences in clinical outcomes were also assessed. METHODS: A convenience sample of 114 children aged 7 to 17 years presenting to an urban pediatric emergency department with a complaint of concussion was assembled. Children were randomized to standard DIs or symptom DIs. Children completed a graded symptom checklist (GSC) and completed daily the GSC for 1 week. Telephone follow-up was performed at 7 days after enrollment using a standardized survey. RESULTS: Fifty-eight children received the symptom DIs, and 56 received the standard DIs. Rates of use were similar with reported rates of 92% for symptom DIs and 84% for standard DIs. Caregivers with symptom DIs reported that the DIs were more helpful in determining when their child could return to school and physical activity (P < 0.05) than caregivers with standard DIs. Children continued to have postconcussive symptoms days and weeks after their injury with 44% of children with symptom DIs and 51% of children with standard DIs reporting symptoms on the GSC at 1 week. CONCLUSIONS: Both study groups reported frequent use of the DIs. Caregivers with symptom DIs found them particularly helpful in determining when their child could return to school and physical activity. Larger-scale investigations are needed to further develop instructions that are easy to use and that may decrease the postconcussive period.

Urinary microRNAs as potential biomarkers of pesticide exposure.

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response.

Seasonal variation in cortisol biomarkers in Hispanic mothers living in an agricultural region.

CONTEXT: Characterization of stress exposure requires understanding seasonal variability in stress biomarkers. OBJECTIVE: To compare acute and chronic stress biomarkers between two seasons in a cohort of rural, Hispanic mothers. METHODS: Stress questionnaires and cortisol measurements (hair, blood and saliva) were collected in the summer and fall. RESULTS: Cortisol biomarkers were significantly different and stress questionnaires were significantly correlated between seasons. DISCUSSION: The variability in cortisol and relative stability of questionnaires between seasons may indicate that cortisol responds to subtle stressors not addressed in questionnaires. CONCLUSIONS: There are significant differences in stress biomarkers in our cohort between seasons.

A first look at women's perspectives on noninvasive prenatal testing to detect sex chromosome aneuploidies and microdeletion syndromes.

OBJECTIVE: The aim of this study is to explore women's opinions about the use of noninvasive prenatal testing (NIPT) to assess the risk of sex chromosome aneuploidies and microdeletion syndromes. METHODS: Focus groups were conducted with women who were currently pregnant or had recently delivered. Qualitative analysis using interpretive description was used to generate study findings. RESULTS: Thirty-one women (mean age 32.4 years) participated in the focus groups. Participants were unfamiliar with sex chromosome aneuploidies but expressed support for the use of NIPT to detect these conditions. Participants were uncertain about the utility and actionability of receiving information about microdeletion syndromes with variable or unknown phenotypic expression. Participants voiced their desire to be informed of all conditions assessed by NIPT prior to testing. They considered clinicians to be the key provider of such information, although stated that patients have a responsibility to be knowledgeable prior to testing in order to support informed decision making. CONCLUSIONS: The use of NIPT to identify sex chromosome aneuploidies and microdeletion syndromes will introduce new challenges for clinicians to ensure pregnant women have the information and resources to make informed choices about NIPT when used for these conditions.

Beta-cell-tropin is associated with short-term stimulation of food intake in chicks.

Beta-cell-tropin, a peptide derived from adrenocorticotropic hormone, is an insulin secretagogue. When centrally injected, it increases food intake in rats, but its appetite-associated effects have not been reported in any other species. Thus, the present study was designed to evaluate the effects of central beta-cell-tropin on appetite-associated parameters in an alternative vertebrate model, the chick. Central injection of 2 or 4 nmol beta-cell-tropin increased food intake for 60 min. Whole hypothalamus was collected at 60 min post-injection, and real-time PCR performed to measure mRNA abundance of agouti-related peptide, corticotropin releasing factor, galanin, melanin concentrating hormone, neuropeptide Y, orexin, prohormone convertase 2, pro-opiomelanocortin, peroxisome proliferator-activated receptor γ, urotensin 2, and visfatin, not one of which were affected by beta-cell-tropin treatment. Results demonstrate that beta-cell-tropin is associated with short-term stimulation of food intake.

A Hazard-Based Framework for Identifying Safer Alternatives to Classes of Chemicals: A Case Study on Phthalates in Consumer Products.

BACKGROUND: Humans are exposed to hazardous chemicals found in consumer products. In 2019, the Pollution Prevention for Healthy People and Puget Sound Act was passed in Washington State. This law is meant to reduce hazardous chemicals in consumer products and protect human health and the environment. The law directs the Washington State Department of Ecology to assess chemicals and chemical classes found in products, determine whether there are safer alternatives, and make regulatory determinations. OBJECTIVES: To implement the law, the Department of Ecology developed a hazard-based framework for identifying safer alternatives to classes of chemicals. METHODS: We developed a hazard-based framework, termed the "Criteria for Safer," to set a transparent bar for determining whether new chemical alternatives are safer than existing classes of chemicals. Our "Criteria for Safer" is a framework that builds on existing hazard assessment methodologies and published approaches for assessing chemicals and chemical classes. DISCUSSION: We describe implementation of our criteria using a case study on the phthalates chemical class in two categories of consumer products: vinyl flooring and fragrances used in personal care and beauty products. Additional context and considerations that guided our decision-making process are also discussed, as well as benefits and limitations of our approach. This paper gives insight into our development and implementation of a hazard-based framework to address classes of chemicals in consumer products and will aid others working to build and employ similar approaches. https://doi.org/10.1289/EHP13549.

Use of latent profile analysis to assess the validity of a peer-rejected group of children.

The goal of this article was to validate the existence and qualities of a peer-rejected group of children using latent profile analysis (LPA). Two separate racially/ethnically diverse samples (Study 1: N = 2,052 second graders; Study 2: N = 594 fourth and fifth graders) completed peer nominations of liking and disliking, from which we calculated Social Preference and Social Impact scores. These scores served as indicators in the LPAs to form LPA groups. In addition, we collected self-, teacher-, and peer-report report data on aggression, depressive symptoms, peer victimization, and social competence. In each sample, an LPA group emerged in which most children were classified as rejected using the Coie, Dodge, and Coppotelli ( 1982 ; CDC) approach (Study 1: 95%; Study 2: 86%). However, in both samples, only a minority of children classified as rejected using the CDC approach fell into this LPA group (Study 1: 46%; Study 2: 36%). The LPA group that mirrored the CDC rejected group received more maladjusted scores than all other LPA groups on aggression, depressive symptoms, peer victimization, and social competence. Furthermore, when compared to children classified as rejected using only the CDC approach, children classified as rejected under both the LPA and CDC approaches were more maladjusted in terms of all sociometric and socioemotional variables. LPA analyses across two developmental levels validated the existence of an empirically derived group of children who overlapped closely with the CDC rejected group. However, this group was considerably smaller and more maladjusted than the CDC rejected group.

Youth's exposure to and engagement with e-cigarette marketing on social media: a UK focus group study.

OBJECTIVE: Electronic-cigarettes (e-cigarette) are promoted creatively through social media and considering the potential influence of social media marketing on young people, we explored young people's exposure to and engagement with social media marketing of e-cigarettes. DESIGN: Semistructured discussion groups. SUBJECTS: Twenty focus groups with 82 young people aged 11-16 living in the Central belt of Scotland. METHODS: Youths were asked about smoking and vaping behaviours, social media use, vaping advertisement exposure and were shown illustrative examples of social media content (eg, images and videos) about different messages, presentations and contextual features. Transcripts were imported into NVivo V.12, coded thematically and analysed. RESULTS: Youths highlighted a variety of tactics e-cigarette companies use, including influencer or celebrity endorsement, attractive youth flavours, bright colours and emotional appeal to advertise and promote their products directly to young people. Social media influencers who advertise e-cigarettes were described as portraying e-cigarettes as 'cool' and 'fashionable' to entice viewers to try the products. Youths considered that there is a need for more restrictions on social media content to protect youths while also still allowing smokers to purchase them as a cessation device. CONCLUSIONS: Our study highlights that the e-cigarette industry is using previously employed tactics similar to the tobacco industry to advertise and promote its products on social media. These findings suggest the growing need for governments to work together to develop and implement policies to restrict the advertising and marketing of e-cigarettes on social media.

Youth's engagement and perceptions of disposable e-cigarettes: a UK focus group study.

OBJECTIVES: Evidence suggests that use of flavoured disposable electronic cigarettes (e-cigarettes) is increasing. Considering the growing popularity and rapid evolution of e-cigarettes, we explored youth's perceptions and engagement with disposable e-cigarettes. DESIGN: Twenty focus groups were conducted between March and May 2022, with 82 youths aged 11-16 living in the Central belt of Scotland. METHODS: Youths were asked about smoking and vaping behaviours and disposable e-cigarettes and were shown vaping-related images and videos from social media which were used to stimulate discussion about different messages, presentations and contextual features. Transcripts were imported into NVivo V.12, coded thematically, and analysed. RESULTS: Youths described disposable e-cigarettes as 'cool', 'fashionable' and enticing and viewed as a modern lifestyle 'accessory'. Tank models were perceived as being used by older adults. Youths stated that disposable e-cigarettes were designed in a way to target youths and the brightly coloured devices and range of flavourings encouraged youths to want to try the products, particularly sweet flavourings. Participants perceived e-cigarettes to be less harmful compared with combustible cigarettes but noted the uncertainty of ingredients in disposable e-cigarettes. CONCLUSIONS: Youths distinguish between e-cigarettes with varying characteristics and social perceptions of users. These findings provide evidence that disposable e-cigarettes are attractive to youths. Future research is needed to understand the factors that contribute to youth perceptions of disposable e-cigarettes. Policymakers should work together to design and implement policies and strategies to prevent youth uptake of vaping.

Alteration of oral microbiome composition in children living with pesticide-exposed farm workers.

Our prior work shows that azinphos-methyl pesticide exposure is associated with altered oral microbiomes in exposed farmworkers. Here we extend this analysis to show the same association pattern is also evident in their children. Oral buccal swab samples were analyzed at two time points, the apple thinning season in spring-summer 2005 for 78 children and 101 adults and the non-spray season in winter 2006 for 62 children and 82 adults. The pesticide exposure for the children were defined by the farmworker occupation of the cohabitating household adult and the blood azinphos-methyl detection of the cohabitating adult. Oral buccal swab 16S rRNA sequencing determined taxonomic microbiota proportional composition from concurrent samples from both adults and children. Analysis of the identified bacteria showed significant proportional changes for 12 of 23 common oral microbiome genera in association with azinphos-methyl detection and farmworker occupation. The most common significantly altered genera had reductions in the abundance of Streptococcus, suggesting an anti-microbial effect of the pesticide. Principal component analysis of the microbiome identified two primary clusters, with association of principal component 1 to azinphos-methyl blood detection and farmworker occupational status of the household. The children's buccal microbiota composition clustered with their household adult in ∼95% of the households. Household adult farmworker occupation and household pesticide exposure is associated with significant alterations in their children's oral microbiome composition. This suggests that parental occupational exposure and pesticide take-home exposure pathways elicit alteration of their children's microbiomes.

Experts' views on how to design a tobacco control fund in the UK.

OBJECTIVE: To explore expert views on the potential value, and approaches to establishing and administering a tobacco control fund in the UK. DESIGN: Semistructured interviews and follow-up discussion groups. SUBJECTS: Twenty-four UK and international experts on tobacco control regulation, public health, economics or law from the academic, public, private and third sector. METHODS: Participants considered the relative merit of (1) general excise tax on retail tobacco sales; (2) ring-fenced hypothecation of excise taxes on retail tobacco sales; and (3) a direct levy on tobacco manufacturers. Preliminary synthesis of interview findings was deliberated on in two follow-up discussion groups to identify key considerations for policy design. RESULT: Most experts agreed that a ring-fenced tobacco control fund would be a valuable method of raising predictable and reliable funds from tobacco producers either using either companies' sales volume or market share as a way to establish the proportion they should pay. Experts predominantly recommended that a fund in the UK should be administered by a government body with devolved nation input and with an independent advisory group. They typically indicated that funding should be allocated yearly with a distribution at local, regional and national levels to support smoking prevention and cessation rather than treatment activities with priority given to measures that tackle smoking-related inequalities. CONCLUSION: There was overwhelming agreement by experts on the need to establish a tobacco control fund to help meet the proposed government tobacco-free targets to reduce adult smoking prevalence to 5% by 2030 (England) and 2034 (Scotland).