Introduction Linear growth in early childhood is routinely measured in the UK, but it is unclear whether indicators of linear growth faltering can flag children with neurodevelopmental vulnerability, especially in ethnically diverse urban settings. We tested whether short stature (stunting) or being short for genetic potential identifies children at risk of failing routine developmental screening at age 2–2.5 years.Methods We conducted a cross-sectional analysis among 555 children aged 24–30 months (mean 26.0 months, SD 1.5) attending Healthy Child Programme reviews in East London. The sample was ethnically diverse, with substantial proportions of Bangladeshi, White and other minority ethnic groups. Developmental vulnerability was defined as scoring below the Ages and Stages Questionnaire, Third Edition (ASQ-3) cut-off in ≥1 domain. The exposures were stunting (height-for-age z score <−2 SD) and being short for genetic potential, defined as deviation from mid-parental height (DMPH) <−2 SD. Associations were examined using binomial multivariable logistic regression adjusted for age, sex, prematurity, maternal education, ethnicity and household benefits. A subset (n=94) completed the Griffiths III Mental Development Scales (GMDS-III) to validate ASQ-3 classification.Results Overall, 141/555 (25.4%) children screened positive for developmental vulnerability on the ASQ-3. Children with developmental vulnerability had significantly lower GMDS-III scaled scores across multiple domains supporting criterion validity. We did not find evidence of an association between stunting and developmental vulnerability (adjusted OR 1.35, 95% CI 0.47 to 3.49). In contrast, children who were short for genetic potential (DMPH <−2 SD) had higher odds of developmental vulnerability (adjusted OR 4.18, 95% CI 1.13 to 14.78).Conclusions In this urban UK cohort, deviation from genetic height potential, rather than stunting, identified children at increased risk of developmental vulnerability. Incorporating parental heights into routine growth surveillance could offer a simple trigger for earlier neurodevelopmental review.

In 2021 JET exploited its unique capabilities to operate with T and D-T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D-T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements-new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors-as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D-T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D-T plasmas to date and expanding our understanding of isotopes and D-T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D-T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D-T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D-T operations is presented in (King et al Nucl. Fusion submitted).

AIMS:The aim of this study was to examine the safety of e-cigarettes (EC) and nicotine patches (NRT) when used to help pregnant smokers quit. DESIGN:A recent trial of EC versus NRT reported safety outcomes in the randomized arms. We conducted a further analysis based on product use. SETTING:Twenty-three hospitals in England and a stop-smoking service in Scotland took part. PARTICIPANTS:The participants comprised 1140 pregnant smokers. INTERVENTIONS:We compared women using and not using EC and NRT regularly during pregnancy. MEASUREMENTS:Measurements included nicotine intake compared with baseline, birth weight, other pregnancy outcomes, adverse events, maternal respiratory symptoms and relapse in early abstainers. FINDINGS:Use of EC was more common than use of NRT (47.3% vs 21.6%, P < 0.001). Women who stopped smoking (abstainers) and used EC at the end-of-pregnancy (EOP) reduced their salivary cotinine by 45% [49.3 ng/ml, 95% confidence interval (CI) = -79.8 to -10]. Only one abstainer used NRT at EOP. In dual users, cotinine increased by 19% (24 ng/ml, 95% CI = 3.5-68). In women reporting a reduction of at least 50% in cigarette consumption, cotinine levels increased by 10% in those using nicotine products and by 9% in those who did not. Birth weights in dual users and exclusive smokers were the same (3.1 kg). Birth weight in abstainers using either nicotine product was higher than in smokers [3.3 kg, standard deviation (SD) = 0.7] versus 3.1 kg, SD = 0.6; difference = 0.15 kg, 95% CI = 0.05-0.25) and not different from abstainers not using nicotine products (3.1 kg, SD = 0.8). Abstainers and smokers using nicotine products had no worse pregnancy outcomes or more adverse events than abstainers and smokers not using them. EC users reported more improvements than non-users in cough [adjusted relative risk (aRR) = 0.59, 95% CI = 0.37-0.93] and phlegm (aRR = 0.53, 95% CI = 0.31-0.92), controlling for smoking status. EC or NRT use had no association with relapse. CONCLUSIONS:Regular use of e-cigarettes or nicotine patches by pregnant smokers does not appear to be associated with any adverse outcomes.

Bush et al. [1] question the conclusion from our study [2] that 'Regular use of e-cigarettes or nicotine patches by pregnant smokers does not appear to be associated with any adverse outcomes' because in animal studies, nicotine in pregnancy damaged offspring in ways our study may not have detected; other chemicals in e-cigarettes may be dangerous; and the conclusion may provide false reassurance and confuse the public. The effects of forced very high chronic dosing used in animal studies have unclear relevance for voluntary intermittent self-dosing in humans [3] and have indeed not been confirmed in studies of pregnant women using nicotine replacement therapy [4]. There is, however, clear evidence that other components of cigarette smoke such as carbon monoxide and lead are fetotoxic [5, 6]. There is, therefore, no doubt that removing smoke chemicals is beneficial for pregnancy, even if nicotine intake continues. Regarding other chemicals in e-cigarette aerosol, there is now a large body of evidence showing that they pose only a small fraction of the risks of smoking [7]. Regarding public misinformation and confusion, in sharp contrast to evidence, 57% of smokers in England believe that vaping is as harmful as or more harmful than smoking [8]. Bush et al. [1] support this opinion when they state that vaping in pregnancy may or may not be the lesser of evils. It is the gross misinformation about risks of vaping, rather than reassurances that vaping is much less dangerous than smoking, that threatens public health, because it puts smokers off using one of the best stop-smoking approaches we currently have. Both common sense and our results provide strong reassurances that for pregnant smokers who are unable to quit unaided, e-cigarettes are a valuable option. All authors have contributed to drafting the letter, reviewing and editing. No funding for this letter. None.

Abstract Background The Healthy Child Programme (HCP) in England, delivered by Health Visitors (HV) and Nursery Nurses (NN), aims to assess growth and development in pre-school age children. This qualitative analysis aimed to evaluate the perceptions and experiences of HCP providers and parents located in a London borough. Methods This qualitative analysis is part of a larger study piloting an automated growth screening algorithm in a London borough. We conducted three focus group discussions; two with parents of pre-school children participating in the pilot study, one in English (n = 6) and one in Sylheti (n = 5), and one with HVs and NNs (n = 11). Sampling was purposeful, and written informed consent was obtained. Groups were facilitated by the same bilingual researcher using semi-structured topic guides. Data were analysed using reflexive thematic analysis and assessed for intercoder reliability. Results Three broad themes were identified in the data: (1) lack of clarity around the role of the HV and NN; (2) a lack of resources; and (3) a desire for a preventative service. Underlying these themes was a sense of disempowerment shown by HVs/NNs and parents, as well as systemic issues in terms of the accessibility and practicality of the service. Nevertheless, parents and HVs/NNs all stressed the importance of the service in providing information, reassurance and advice. Conclusions Various challenges prevent the HCP from providing equitable and effective care to every child. However, the service was recognised as very valuable by users and providers despite systemic difficulties.

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

Asset-based approaches are becoming more common within public health interventions; however, due to variations in terminology, it can be difficult to identify asset-based approaches. The study aimed to develop and test a framework that could distinguish between asset-based and deficit-based community studies, whilst acknowledging there is a continuum of approaches. Literature about asset-based and deficit-based approaches were reviewed and a framework was developed based on the Theory of Change model. A scoring system was developed for each of the five elements in the framework based on this model. Measurement of community engagement was built in, and a way of capturing how much the study involved an asset approach. The framework was tested on 13 studies examining community-based interventions to investigate whether it could characterize asset-based versus deficit-based studies. The framework demonstrated how much the principles underpinning asset-based approaches were present and distinguished between studies where the approach was deficit-based to those that had some elements of an asset-based approach. This framework is useful for researchers and policymakers when determining how much of an intervention is asset-based and identifying which elements of asset-based approaches lead to an intervention working. Lay Summary Deficit-based approaches are a common approach to addressing public health issues within a community and involve identifying a health problem or need and finding a way to solve these. However, asset-based approaches, those that involve the community using its assets, or strengths, to enable community members to have more control over their health and wellbeing, are increasingly common. The terminology used to describe these methods varies greatly so it can be difficult to identify whether an approach is more deficit-based or asset-based. To address this a framework was developed to identify and score elements of asset-based studies. We did this by reviewing academic information describing asset-based approaches and built into this a scoring system. This framework was used to assess and measure the degree to which 13 community-based studies took an asset-based approach. The framework was able to identify studies which were more asset-based in their approach compared to those which were more deficit-focused, acknowledging that some studies may have elements of each approach. This framework will be useful for people working in health policy and research who want a resource to help identify asset-based approaches in practice and which aspects of the approach were important for its success in the community.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Background:Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives:To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design:A pragmatic multi-centre randomised controlled trial. Setting:Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. Participants:One thousand one hundred and forty pregnant daily smokers (12-24 weeks' gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Interventions:Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. Outcome measures:The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Results:Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (<2500 g) (9.6% vs. 14.8%, risk ratio = 0.65, 95% confidence interval 0.47 to 0.90; Bayes factor = 10.3). Limitations:Low rates of validation reduced the study power. A substantial proportion of participants did not use the support on offer sufficiently to test its benefits. Sample size may have been too small to detect differences in less frequent adverse effects. Conclusions:E-cigarettes were not significantly more effective than nicotine patches in the primary analysis, but when e-cigarettes use in the nicotine patches arm was accounted for, e-cigarettes were almost twice as effective as patches in all abstinence outcomes. In pregnant smokers seeking help, compared to nicotine patches, e-cigarettes are probably more effective, do not pose more risks to birth outcomes assessed in this study and may reduce the incidence of low birthweight. Future work:Routine monitoring of smoking cessation and birth outcomes in pregnant women using nicotine patches and e-cigarettes and further studies are needed to confirm these results. Trial registration:This trial is registered as ISRCTN62025374 and Eudract 2017-001237-65. Funding:This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 13. See the NIHR Journals Library website for further project information.

Nicotine replacement therapy, in the form of nicotine patches, is commonly offered to pregnant women who smoke to help them to stop smoking, but this approach has limited efficacy in this population. Electronic cigarettes (e-cigarettes) are also used by pregnant women who smoke but their safety and efficacy in pregnancy are unknown. Here, we report the results of a randomized controlled trial in 1,140 participants comparing refillable e-cigarettes with nicotine patches. Pregnant women who smoked were randomized to e-cigarettes ( n = 569) or nicotine patches ( n = 571). In the unadjusted analysis of the primary outcome, validated prolonged quit rates at the end of pregnancy in the two study arms were not significantly different (6.8% versus 4.4% in the e-cigarette and patch arms, respectively; relative risk (RR) = 1.55, 95%CI: 0.95–2.53, P = 0.08). However, some participants in the nicotine patch group also used e-cigarettes during the study. In a pre-specified sensitivity analysis excluding abstinent participants who used non-allocated products, e-cigarettes were more effective than patches (6.8% versus 3.6%; RR = 1.93, 95%CI: 1.14–3.26, P = 0.02). Safety outcomes included adverse events and maternal and birth outcomes. The safety profile was found to be similar for both study products, however, low birthweight (<2,500 g) was less frequent in the e-cigarette arm (14.8% versus 9.6%; RR = 0.65, 95%CI: 0.47–0.90, P = 0.01). Other adverse events and birth outcomes were similar in the two study arms. E-cigarettes might help women who are pregnant to stop smoking, and their safety for use in pregnancy is similar to that of nicotine patches. ISRCTN62025374.

Background Community pharmacies serve people with high levels of tobacco-related illness, but throughput in NHS Stop Smoking Services in pharmacies remains relatively low. We investigated the effectiveness of a complex intervention to increase service uptake and retention. Methods We randomised 60 pharmacies in England and Wales to the STOP intervention or usual practice in a pragmatic, parallel-group, controlled trial over 11 months. Smokers were blind to the allocation. The intervention was theory-based consultation skills training for pharmacy staff with environmental prompts (badges, calendars and behavioural cues). The primary outcome was the number of smokers attending an initial consultation and setting a quit date. Results The intervention made no significant difference in setting a quit date, retention or quit rate. A total of 631 adult smokers (service users) enrolled and set a quit date in intervention pharmacies compared to 641 in usual practice pharmacies, a rate ratio of 0.75 (95% CI 0.46 to 1.23) adjusted for site and number of prescriptions. A total of 432 (68%) service users were retained at 4 weeks in intervention and 500 (78%) in usual practice pharmacies (odds ratio 0.80, 0.41 to 1.55). A total of 265 (42%) service users quit smoking at 4 weeks in intervention and 276 (43%) in usual practice pharmacies (0.96, 0.65 to 1.43). The pharmacy staff were positive about the intervention with 90% (56/62) stating that it had improved their skills. Sixty-eight per cent would strongly recommend the training to others although there was no difference in self-efficacy for service delivery between arms. Seventy of 131 (53%) service users did not complete the 6-month follow-up assessment. However, 55/61 (90%) service users who completed follow-up were satisfied or very satisfied with the service. All usual practice arm service users ( n = 33) and all but one in the intervention arm ( n = 27) would recommend the service to smokers. Conclusions We found high levels of retention and acceptable quit rates in the NHS pharmacy stop smoking service. Despite pharmacy staff providing positive feedback on the STOP intervention, it made no difference to service throughput. Thus, other factors may currently limit service capacity to help smokers to quit. Trial registration ISRCTN, ISRCTN16351033 . Retrospectively registered.

Abstract Background In low- and middle-income countries, poverty and impaired growth prevent children from meeting their cognitive developmental potential. There are few studies investigating these relationships in high-income settings. Methods Participants were 12,536 children born between 2000 and 2002 in the UK and participating in the Millennium Cohort Study (MCS). Short stature was defined as having a height-for-age 2 or more standard deviations below the median (≤ − 2 SDS) at age 3 years. Standardized British Abilities Scales II (BAS II) language measures, used to assess language development at ages 3, 5, 7 and 11 years, were the main outcome assessed. Results Children with short stature at age 3 years (4.1%) had language development scores that were consistently lower from ages 3 to 11 years (− 0.26 standard deviations (SD) (95% CI − 0.37, − 0.15)). This effect was attenuated but remained significant after adjustment for covariates. Trajectory analysis produced four distinct patterns of language development scores (low-declining, low-improving, average and high). Multinomial logistic regression models showed that children with short stature had a higher risk of being in the low-declining group, relative to the average group (relative risk ratio (RRR) = 2.11 (95% CI 1.51, 2.95)). They were also less likely to be in the high-scoring group (RRR = 0.65 (0.52, 0.82)). Children with short stature at age 3 years who had ‘caught up’ by age 5 years (height-for-age ≥ 2 SDS) did not have significantly different scores from children with persistent short stature, but had a higher probability of being in the high-performing group than children without catch-up growth (RRR = 1.84 (1.11, 3.07)). Conclusions Short stature at age 3 years was associated with lower language development scores at ages 3 to 11 years in UK children. These associations remained significant after adjustment for socioeconomic, child and parental factors.

Background Stunting, defined as height-for-age under 2 standard deviations below the population median, is an important indicator of child health. Stunting has been extensively researched in low-and-middle income countries, but less is known about the extent and burden in high income settings. Objectives To map stunting prevalence in children aged 4–5 years in England between 2006 and 2019. Methods We used data from the National Child Measurement Programme (NCMP) for the school years 2006/07 to 2018/19. All children attending state-maintained primary schools in England are invited to participate in the NCMP, which has an average response rate of 93%. We used spatial analyses in SatScan to assess geographic clustering of stunting. A total of 7,062,071 children aged 4–5 years were analysed, and a subsample of 5,765,707 children with valid ethnicity and area-level deprivation data were included in adjusted analyses. Results The prevalence of stunting in England was 1.93% (95% confidence interval (95%CI) 1.92 to 1.94). Spatial analysis showed geographic heterogeneity in stunting, with high prevalence clusters more likely in the North and Midlands, leading to 4-fold variation between local authorities with highest and lowest stunting prevalence. Girls were more likely to be stunted than boys (2.09% (2.07 to 2.10) vs 1.77% (1.76 to 1.78), respectively). There was ethnic heterogeneity: stunting prevalence was lowest in Black children (0.64% (95%CI: 0.61 to 0.67)) and highest in Indian children (2.52% (2.45 to 2.60) and children in other ethnic categories (2.57% (2.51 to 2.64)). Stunting was linearly associated with IMD, with almost 2-fold higher prevalence in the most compared to least deprived decile (2.56% vs 1.38%; P<0.001). Stunting prevalence declined over time, from 2.03% (95%CI 2.01 to 2.05) in 2006–2010, to 1.82% (1.80 to 1.84) in 2016–2019. Stunting declined at all levels of area-deprivation, with faster declines in more deprived areas, but disparities by IMD quintile were persistent. Conclusions There is a clear social gradient and substantial regional variation in stunting across England. Many children in the most deprived areas of the country may be failing to reach their full growth potential.

Background Short stature, defined as height for age more than 2 standard deviations (SDs) below the population median, is an important indicator of child health. Short stature (often termed stunting) has been widely researched in low- and middle-income countries (LMICs), but less is known about the extent and burden in high-income settings. We aimed to map the prevalence of short stature in children aged 4-5 years in England between 2006 and 2019. Methods and findings We used data from the National Child Measurement Programme (NCMP) for the school years 2006-2007 to 2018-2019. All children attending state-maintained primary schools in England are invited to participate in the NCMP, and heights from a total of 7,062,071 children aged 4-5 years were analysed. We assessed short stature, defined as a height-for-age standard deviation score (SDS) below -2 using the United Kingdom WHO references, by sex, index of multiple deprivation (IMD), ethnicity, and region. Geographic clustering of short stature was analysed using spatial analysis in SaTScan. The prevalence of short stature in England was 1.93% (95% confidence interval (CI) 1.92-1.94). Ethnicity adjusted spatial analyses showed geographic heterogeneity of short stature, with high prevalence clusters more likely in the North and Midlands, leading to 4-fold variation between local authorities (LAs) with highest and lowest prevalence of short stature. Short stature was linearly associated with IMD, with almost 2-fold higher prevalence in the most compared with least deprived decile (2.56% (2.53-2.59) vs. 1.38% (1.35-1.41)). There was ethnic heterogeneity: Short stature prevalence was lowest in Black children (0.64% (0.61-0.67)) and highest in Indian children (2.52% (2.45-2.60)) and children in other ethnic categories (2.57% (2.51-2.64)). Girls were more likely to have short stature than boys (2.09% (2.07-2.10) vs. 1.77% (1.76-1.78), respectively). Short stature prevalence declined over time, from 2.03% (2.01-2.05) in 2006-2010 to 1.82% (1.80-1.84) in 2016-2019. Short stature declined at all levels of area deprivation, with faster declines in more deprived areas, but disparities by IMD quintile were persistent. This study was conducted cross-sectionally at an area level, and, therefore, we cannot make any inferences about the individual causes of short stature. Conclusions In this study, we observed a clear social gradient and striking regional variation in short stature across England, including a North-South divide. These findings provide impetus for further investigation into potential socioeconomic influences on height and the factors underlying regional variation.

Use of e-cigarettes (vaping) has potential to help pregnant women stop smoking. This study explored factors influencing adherence among participants in the vaping arm of the first trial of vaping for smoking cessation in pregnancy. We conducted semi-structured telephone interviews (n = 28) with women at three-months postpartum. Interviews were analysed using thematic analysis, informed by the Theoretical-Domains Framework, Necessity-Concerns Framework and Perceptions and Practicalities Approach. Interviewees generally reported high levels of vaping. We found that: (1) intervention adherence was driven by four necessity beliefs—stopping smoking for the baby, and vaping for harm reduction, smoking cessation or as a last resort; (2) necessity beliefs outweighed vaping concerns, such as dependence and safety; (3) adherence was linked to four practicalities themes, acting as barriers and facilitators to vaping—device and e-liquid perceptions, resources and support, whether vaping became habitual, and social and environmental factors; and (4) intentional non-adherence was rare; unintentional non-adherence was due to device failures, forgetting to vape, and personal circumstances and stress. Pregnant smokers provided with e-cigarettes, and with generally high levels of vaping, had positive beliefs about the necessity of vaping for smoking cessation which outweighed concerns about vaping. Non-adherence was mainly due to unintentional factors.

Web science researchers identify social structures that form as content is shared on social media. These structures channel the flow of content and the resulting experiences of ideas, feelings and actions. The human drive to seek shared experiences shapes structures that can tend toward homogeneity of interest, beliefs and even moment-by-moment experience. Improved modelling tools are needed to understand the ecosystems formed by these processes. We propose a generative model in which experiences build on each other; with past experiences filtering which content raises into awareness and how it is experienced. We then ask what simple social rules would cause individuals to flock together along the possible paths of experience supported by this model. We created a method for building Petri net models to explore these principles and to act as the foundation for future work. In the limit as the number of individuals is increased, the dynamics of this flocking behaviour becomes governed by differential equations; these form a solid foundation for the development of further theory. Software to recreate these results and to create and play with models is available.

To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F3 fish, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of slit3 mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased htr1aa mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.

AbstractIntroductionAssessing the fidelity of complex behavioural interventions and examining the contextual reasons why such interventions succeed, or fail are important activities but challenging and rarely reported. The Smoking Treatment Optimisation in Pharmacies (STOP) trial is a cluster randomised trial evaluating the effectiveness of a complex intervention to optimise the National Health Service (NHS) Stop Smoking Service delivered in community pharmacies. This complex intervention comprises a training package for pharmacy staff involving motivational interviewing and communication skills aimed at increasing smoking cessation knowledge and proactive client engagement. We report on a process evaluation which was planned alongside the trial to offer findings that will assist in the interpretation of the main trial results and help inform potential implementation in community pharmacy settings on a wider scale.Methods and analysisQuantitative data on recruitment and retention process of pharmacies, pharmacy staff and service users has been collected during the trial along with data on dose and fidelity of the intervention delivery from participating intervention arm pharmacies to identify potential implementation issues. Simulated client data on behaviour change skills and display of intervention materials from both control and intervention pharmacies is being assessed. These data will be combined with qualitative data; including adviser-smoker consultation recordings that provide a snapshot of behaviour skills delivery by stop smoking advisers and semi-structured interviews with pharmacy staff and services users from the intervention arm.DiscussionPublished protocols for process evaluations of complex health interventions are still rare despite increasing funding for this work to facilitate understanding of trial outcomes from an implementation perspective. This mixed methods protocol will contribute to the developing literature around the conduct of process evaluation and the value they add to health services research.Trial registration numberISRCTN16351033.Strengths and limitations of this studyA planned mixed methods process evaluation that draws together data from different sources to help explain the trial results and establish the feasibility of scaling this complex intervention up in community pharmacy settings.A strength is the use of a previously tested mystery shopping method to assess fidelity of skills performance at the pharmacy counterThe process evaluation relies on willing pharmacy staff and service users involved in the trial to collect some of the data, which may introduce bias.This paper also provides a detailed example of how to use the MRC framework for process evaluation of complex interventions to design an extensive process evaluation within trial settings.

Background: Smoking is one of the greatest threats to public health worldwide. We integrated phenome-wide association study (PheWAS) and Mendelian randomization (MR) approaches to explore causal effects of genetically predicted smoking intensity across the human disease spectrum. Methods: We conducted PheWAS case-control analyses in 152,483 ever smokers of White-British ancestry, aged 39-73 years. Disease diagnoses were based on hospital inpatient and mortality registrations. Smoking intensity was instrumented by four genetic variants, and disease risks estimated for one cigarette per day heavier intakes. Associations passing the FDR threshold (p<0.0025) were assessed for causality using several complementary MR approaches. Findings: Genetically instrumented smoking intensity was associated with 48 conditions, with MR supporting a possible causal effect for 28 distinct outcomes. Each cigarette smoked per day elevated the odds of respiratory diseases by 5% to 33% (nine distinct diseases, including pneumonia, emphysema, obstructive chronic bronchitis, pleurisy, pulmonary collapse, respiratory failure) and the odds of circulatory disease by 5% to 23% (seven diseases, including atherosclerosis, myocardial infarction, congestive heart failure, arterial embolisms). Further effects were seen for cancer within the respiratory system and other neoplasms, renal failure, septicaemia, and retinal disorders. No associations were observed in sensitivity analyses on 185,002 never smokers. Interpretation: These genetic data demonstrate the substantial adverse health impacts by smoking intensity and suggest notable increases in the risks of several diseases. Public health initiatives should highlight the damage caused by smoking intensity and the potential benefits of reducing or ideally quitting smoking. (C) 2020 The Authors. Published by Elsevier Ltd.