Online Cessation Support Networks (OCSNs) are associated with increased quit success rates, but few studies have examined their use over time. We identified usage patterns in New Zealand's largest OCSN over two years and explored implications for OCSN intervention design and evaluation.
We analysed metadata relating to 133,096 OCSN interactions during 2011 and 2012. Metrics covered aggregate network activity, user posting activity and longevity, and between-user commenting. Binary logistic regression models were estimated to investigate the feasibility of predicting low user engagement using early interaction data.
Repeating periodic peaks and troughs in aggregate activity related not only to seasonality (e.g., New Year), but also to day of the week. Out of 2,062 unique users, 69 Highly Engaged Users (180+ interactions each) contributed 69% of all OCSN interactions in 2012 compared to 1.3% contributed by 864 Minimally Engaged Users (< = 2 items each). The proportion of Highly Engaged Users increased with network growth between 2011 and 2012 (with marginal significance), but the proportion of Minimally Engaged Users did not decline substantively. First week interaction data enabled identification of Minimally Engaged Users with high specificity and sensitivity (AUROC = 0.94).
Results suggest future research should develop and test interventions that promote activity, and hence cessation support, amongst specific user groups or at key time points. For example, early usage information could help identify Minimally Engaged Users for tests of targeted messaging designed to improve their integration into, or re-engagement with, the OCSN. Furthermore, although we observed strong growth over time on varied metrics including posts and comments, this change did not coincide with large gains in first-time user persistence. Researchers assessing intervention effects should therefore examine multiple measures when evaluating changes in network dynamics over time.
We examined whether the supply routes via which New Zealand adolescents aged 14–15 years accessed tobacco had changed during a period of dynamic policy activity.
We analysed data from seven consecutive years (2006–2012) of the New Zealand Action on Smoking and Health (ASH) Year 10 survey, a nationwide cross-sectional annual survey.
All New Zealand schools teaching Year 10 students are invited to participate in the survey; school-level participation rates have ranged between 44% and 58% and more than 25 000 students have responded to the survey in each year. The results presented draw on the subsample who reported smoking when surveyed (N∼9200). The data were weighted by age, ethnicity and school socioeconomic status (SES) to remove effects of systematic over-response by New Zealand Europeans and under-response by those in lower SES groups from trend analyses.
Primary and secondary outcome measures
The survey measured adolescents’ main reported tobacco supply source.
Smoking prevalence declined significantly (8.1%) over the period examined (linear tend coefficient: −0.74; 95% CI −1.03 to −0.45, significant p<0.01). Friends showed a significant decline in relative importance as a supply source while caregivers and other sources showed a significant increase over the period examined.
The findings show that social supply, particularly via friends, caregivers and others, such as older siblings, is a key tobacco source for adolescents; commercial supply is much less important. The findings raise questions about the additional measures needed to reduce smoking among youth. Endgame policies that make tobacco more difficult to obtain and less appealing and convenient to gift merit further investigation.
Public Health; Preventive Medicine
Ocean acidification due to rising atmospheric CO2 is expected to affect the physiology of important calcifying marine organisms, but the nature and magnitude of change is yet to be established. In coccolithophores, different species and strains display varying calcification responses to ocean acidification, but the underlying biochemical properties remain unknown. We employed an approach combining tandem mass-spectrometry with isobaric tagging (iTRAQ) and multiple database searching to identify proteins that were differentially expressed in cells of the marine coccolithophore species Emiliania huxleyi (strain NZEH) between two CO2 conditions: 395 (∼current day) and ∼1340 p.p.m.v. CO2. Cells exposed to the higher CO2 condition contained more cellular particulate inorganic carbon (CaCO3) and particulate organic nitrogen and carbon than those maintained in present-day conditions. These results are linked with the observation that cells grew slower under elevated CO2, indicating cell cycle disruption. Under high CO2 conditions, coccospheres were larger and cells possessed bigger coccoliths that did not show any signs of malformation compared to those from cells grown under present-day CO2 levels. No differences in calcification rate, particulate organic carbon production or cellular organic carbon: nitrogen ratios were observed. Results were not related to nutrient limitation or acclimation status of cells. At least 46 homologous protein groups from a variety of functional processes were quantified in these experiments, of which four (histones H2A, H3, H4 and a chloroplastic 30S ribosomal protein S7) showed down-regulation in all replicates exposed to high CO2, perhaps reflecting the decrease in growth rate. We present evidence of cellular stress responses but proteins associated with many key metabolic processes remained unaltered. Our results therefore suggest that this E. huxleyi strain possesses some acclimation mechanisms to tolerate future CO2 scenarios, although the observed decline in growth rate may be an overriding factor affecting the success of this ecotype in future oceans.
High participation rates in sport and increasing recognition of how diet benefits athletic performance suggest sports settings may be ideal locations for promoting healthy eating. While research has demonstrated the effect of tobacco and alcohol sponsorship on consumption, particularly among youth, few studies have examined the extent or impact of food and beverage company sponsorship in sport. Studies using brand logos as a measure suggest unhealthy foods and beverages dominate sports sponsorship. However, as marketing goes beyond the use of brand livery, research examining how marketers support sponsorships that create brand associations encouraging consumer purchase is also required. This study aimed to identify the characteristics and extent of sponsorships and associated marketing by food and non-alcoholic beverage brands and companies through a case study of New Zealand sport.
We conducted a systematic review of 308 websites of national and regional New Zealand sporting organisations to identify food and beverage sponsors, which were then classified as healthy or unhealthy using nutrient criteria for energy, fat, sodium and fibre levels. We interviewed 18 key informants from national and regional sporting organisations about sponsorships.
Food and beverage sponsorship of sport is not extensive in New Zealand. However, both healthy and unhealthy brands and companies do sponsor sport. Relatively few support their sponsorships with additional marketing. Interviews revealed that although many sports organisations felt concerned about associating themselves with unhealthy foods or beverages, others considered sponsorship income more important.
While there is limited food and beverage sponsorship of New Zealand sport, unhealthy food and beverage brands and companies do sponsor sport. The few that use additional marketing activities create repeat exposure for their brands, many of which target children. The findings suggest policies that restrict sponsorship of sports by unhealthy food and beverage manufacturers may help limit children’s exposure to unhealthy food marketing within New Zealand sports settings. Given the global nature of the food industry, the findings of this New Zealand case study may be relevant elsewhere.
Sport; Sponsorship; Food; Beverage; Marketing
Severe asthma is associated with fixed airway obstruction attributable to inflammation, copious luminal mucus, and increased airway smooth muscle (ASM) mass. Paradoxically, studies demonstrated that the hypertrophic and hyperplastic ASM characteristic of severe asthma has reduced contractile capacity. We compared the G-protein–coupled receptor (GPCR)–induced Ca2+ mobilization and expression of GPCRs and signaling proteins related to procontractile signaling in ASM derived postmortem from subjects who died of nonrespiratory causes, with cells from subjects who died of asthma. Despite the increased or comparable expression of contraction-promoting GPCRs (bradykinin B2 or histamine H1 and protease-activated receptor 1, respectively) in asthmatic ASM cells relative to cells from healthy donors, asthmatic ASM cells exhibited reduced histamine-induced Ca2+ mobilization and comparable responses to bradykinin and thrombin, suggesting a postreceptor signaling defect. Accordingly, the expression of regulator of G-protein signaling–5 (RGS5), an inhibitor of ASM contraction, was increased in cultured, asthmatic ASM cells and in bronchial smooth muscle bundles of both human subjects with asthma and allergen-challenged mice, relative to those of healthy human subjects or naive mice. The overexpression of RGS5 impaired the release of Ca2+ to thrombin, histamine, and carbachol, and reduced the contraction of precision-cut lung slices to carbachol. These results suggest that increased RGS5 expression contributes to decreased myocyte shortening in severe and fatal asthma.
asthma; bronchial smooth muscle; signal transduction; G-protein–coupled receptors
The Framework Convention on Tobacco Control calls for the elimination of tobacco advertising, promotion and sponsorship. To test whether tobacco packaging functions as advertising by communicating attractive and distinctive brand attributes, we explored how young adult smokers and non-smokers interpreted familiar and unfamiliar tobacco brands.
We conducted an on-line survey of 1035 young adult smokers and non-smokers aged 18–30. Participants evaluated eight tobacco brands using ten attributes based on brand personality scales. We used factor analysis and ANOVA to examine patterns in brand-attribute associations.
Young adults distinguished between brands on the basis of their packaging alone, associated each brand with specific attributes, and were equally able to interpret familiar and unfamiliar brands. Contrary to our expectations, non-smokers made more favourable brand-attribute associations than smokers, but both groups described Basic, a near generic brand, as ‘plain’ or ‘budget’. There were no significant gender or ethnicity differences.
Tobacco packaging uses logos, colours and imagery to create desirable connotations that promote and reinforce smoking. By functioning in the same way as advertising, on-pack branding breaches Article 13 of the FCTC and refutes tobacco companies’ claims that pack livery serves only as an indentifying device that simplifies smokers’ decision-making. Given this evidence, signatories should see plain packaging policies as a priority consistent with their FCTC obligations to eliminate all tobacco advertising and promotion.
FCTC; Tobacco branding; Plain packaging; Health policy
There is increasing interest in ending the tobacco epidemic and in applying ‘endgame’ solutions to achieve that goal at national levels. We explored the understanding of, and reactions to, a tobacco-free vision and an endgame approach to tobacco control among New Zealand smokers and non-smokers.
We recruited participants in four focus groups held in June 2009: Māori (indigenous people) smokers (n=7); non-Māori smokers (n=6); Māori non-smokers (n=7); and non-Māori non-smokers (n=4). Participants were from the city of Whanganui, New Zealand. We introduced to them the vision of a tobacco-free New Zealand and the concept of a semi-autonomous agency (Tobacco-Free Commission [TFC]) that would control the tobacco market as part of an endgame approach.
There was mostly strong support for the tobacco-free New Zealand vision among all groups of participants. The reason most commonly given for supporting the vision was to protect children from tobacco. Most participants stated that they understood the TFC concept and reacted positively to it. Nevertheless, rather than focusing on organisational or structural arrangements, participants tended to focus on supporting the specific measures which a future TFC might facilitate such as plain packaging of tobacco products. Various concerns were also raised around the TFC, particularly around the feasibility of its establishment.
We were able to successfully communicate a complex and novel supply-side focused tobacco control policy intervention to smokers and non-smokers. The findings add to the evidence from national surveys that there is public support, including from smokers, for achieving a tobacco-free vision and using regulatory and policy measures to achieve it. Support for such measures may be enhanced if they are clearly communicated and explained with a rationale which stresses protecting children and future generations from tobacco smoking.
Large portions of higher eukaryotic proteomes are intrinsically disordered, and abundant evidence suggests that these unstructured regions of proteins are rich in regulatory interaction interfaces. A major class of disordered interaction interfaces are the compact and degenerate modules known as short linear motifs (SLiMs). As a result of the difficulties associated with the experimental identification and validation of SLiMs, our understanding of these modules is limited, advocating the use of computational methods to focus experimental discovery. This article evaluates the use of evolutionary conservation as a discriminatory technique for motif discovery. A statistical framework is introduced to assess the significance of relatively conserved residues, quantifying the likelihood a residue will have a particular level of conservation given the conservation of the surrounding residues. The framework is expanded to assess the significance of groupings of conserved residues, a metric that forms the basis of SLiMPrints (short linear motif fingerprints), a de novo motif discovery tool. SLiMPrints identifies relatively overconstrained proximal groupings of residues within intrinsically disordered regions, indicative of putatively functional motifs. Finally, the human proteome is analysed to create a set of highly conserved putative motif instances, including a novel site on translation initiation factor eIF2A that may regulate translation through binding of eIF4E.
Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.
High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharmacokinetic properties and showed no bioactivation liability in glutathione trapping studies. These highly potent, selective, and orally active EP3 antagonists are excellent tool compounds for investigating and validating potential therapeutic benefits from selectively inhibiting the EP3 receptor.
EP3 receptor; novel, potent, selective, and orally active antagonists; 3-oxazolidinedione-6-aryl-pyridinones
We aimed to describe use of a national quitline service and the variation in its use by smoker characteristics (particularly ethnicity and deprivation). The setting was New Zealand (NZ), which takes proactive measures to attract disadvantaged smokers to this service.
The NZ arm of the International Tobacco Control Policy Evaluation Survey (ITC Project) utilizes the New Zealand Health Survey (a national sample) from which we surveyed adult smokers in two waves (N = 1,376 and N = 923) 1 year apart.
Quitline use in the last 12 months rose from 8.1% (95% CI = 6.3%–9.8%) in Wave 1 to 11.2% (95% CI = 8.4%–14.0%) at Wave 2. Māori (the indigenous people of NZ) were significantly more likely to call the Quitline than were European/other smokers. Relatively higher call rates also occurred among those reporting higher deprivation, financial stress, a past mental health disorder, a past drug-related disorder, and higher psychological distress (Kessler 10-item index). Independent associations in the multivariate analyses of Quitline use were being Māori, reporting financial stress, and ever having been diagnosed with a mental health disorder.
This national Quitline service is successfully stimulating disproportionately more calls by Māori smokers and those with some measures of disadvantage. It may therefore be contributing to reducing health inequalities. It appears possible to target quitlines to reach those smokers in greatest need.
Tobacco control strategies have mainly targeted reducing demand. Supply-side focused measures, though less familiar, deserve consideration, particularly to achieve 'endgame' tobacco control aims (e.g. achieving close to zero smoking prevalence). We explored attitudes towards supply-side focused 'endgame' tobacco control approaches and how they can be best communicated with senior policymakers, journalists, and public health practitioners.
We identified five supply-side focused approaches which could potentially lead to the tobacco endgame: two structural models and three discrete actions. The structural models were: (i) a Nicotine Authority to coordinate tobacco control activities and regulate the nicotine/tobacco market for public health aims; and (ii) a Tobacco Supply Agency acting as a monopoly purchaser of tobacco products and controlling the tobacco supply for public health aims. The actions were: (a) allocating progressively reducing tobacco product import quotas (the 'sinking lid') until importation and commercial sale of tobacco products ceased; (b) making tobacco companies responsible for reducing smoking prevalence with stringent financial penalties if targets were missed; and (c) new laws to facilitate litigation against tobacco companies. These approaches were presented as means to achieve a tobacco free New Zealand by 2020 to 19 senior policymakers, journalists, and public health physicians in two focus groups and eight interviews, and their reactions sought.
The tobacco-free vision was widely supported. Participants engaged fully with the proposed tobacco control approaches, which were viewed as interesting or even intriguing. Most supported increasing the focus on supply-side measures. Views differed greatly about the desirability, feasibility and likely effectiveness of each approach. Participants identified a range of potential barriers to implementation and challenges to successfully advocating and communicating these approaches. The current framing of tobacco as a risky but legal commodity was noted as an important potential barrier to implementing endgame approaches.
Endgame tobacco control approaches were considered to be viable policy options. Further policy analysis, research and public discussion are needed to develop endgame approaches. A significant change in the public framing of tobacco may be a prerequisite for implementing endgame solutions.
Short, linear motifs (SLiMs) play a critical role in many biological processes. The SLiMSearch 2.0 (Short, Linear Motif Search) web server allows researchers to identify occurrences of a user-defined SLiM in a proteome, using conservation and protein disorder context statistics to rank occurrences. User-friendly output and visualizations of motif context allow the user to quickly gain insight into the validity of a putatively functional motif occurrence. For each motif occurrence, overlapping UniProt features and annotated SLiMs are displayed. Visualization also includes annotated multiple sequence alignments surrounding each occurrence, showing conservation and protein disorder statistics in addition to known and predicted SLiMs, protein domains and known post-translational modifications. In addition, enrichment of Gene Ontology terms and protein interaction partners are provided as indicators of possible motif function. All web server results are available for download. Users can search motifs against the human proteome or a subset thereof defined by Uniprot accession numbers or GO term. The SLiMSearch server is available at: http://bioware.ucd.ie/slimsearch2.html.
An innovative approach to learning public health by using feature-length commercial movies was piloted in the fourth year of a medical degree. We aimed to explore how students responded to this approach and the relative effectiveness of two promotional strategies. Firstly we placed DVDs of 15 movies (with public health-related content) in the medical school library. Then alternating groups of students (total n = 82 students) were exposed to either a brief promotional intervention or a more intensive intervention involving a class presentation. The response rates were 99% at baseline and 85% at follow-up.
The level and strength of support for using movies in public health training increased after exposure to the public health module with significantly more students "strongly agreeing". Student behaviour, in terms of movies viewed or accessed from the library, also suggested student interest. While there were no statistically significant differences in median viewing or library access rates between the two intervention groups, the distribution of viewing patterns was shifted favourably. Those exposed to the more intensive intervention (class presentation) were significantly more likely to have reported watching at least one movie (97% vs. 81%; p = 0.033) or to having accessed at least one movie from the library (100% vs. 70%, p = 0.0001).
This pilot study found that the students had very positive attitudes towards viewing public health-related commercial movies. Movie access rates from the library were also favourable.
Governments use law to constrain aspects of private activities for purposes of protecting health and social wellbeing. Policymakers have a range of perceptions and beliefs about what is public or private. An understanding of the possible drivers of policymaker decisions about where government can or should intervene for health is important, as one way to better guide appropriate policy formation. Our aim was to identify obstacles to, and opportunities for, government smokefree regulation of private and public spaces to protect children. In particular, to seek policymaker opinions on the regulation of smoking in homes, cars and public parks and playgrounds in a country with incomplete smokefree laws (New Zealand).
Case study, using structured interviews to ask policymakers (62 politicians and senior officials) about their opinions on new smokefree legislation for public and private places. Supplementary data was obtained from the Factiva media database, on the views of New Zealand local authority councillors about policies for smokefree outdoor public places.
Overall, interviewees thought that government regulation of smoking in private places was impractical and unwise. However, there were some differences on what was defined as 'private', particularly for cars. Even in public parks, smoking was seen by some as a 'personal' decision, and unlikely to be amenable to regulation. Most participants believed that educative, supportive and community-based measures were better and more practical means of reducing smoking in private places, compared to regulation.
The constrained view of the role of regulation of smoking in public and private domains may be in keeping with current political discourse in New Zealand and similar Anglo-American countries. Policy and advocacy options to promote additional smokefree measures include providing a better voice for childrens' views, increasing information to policymakers about the harms to children from secondhand smoke and the example of adult smoking, and changing the culture for smoking around children.
The aim of this study was to examine knowledge and attitudes to lower harm alternatives to cigarettes among New Zealand (NZ) smokers.
The NZ arm of the International Tobacco Control Policy Evaluation Survey (ITC Project) utilizes the NZ Health Survey (a national sample). From this sample, we surveyed adult smokers (N = 1,376).
Knowledge about smokeless tobacco was poor, with only 16% regarding such products as less harmful than ordinary cigarettes. Only 7% considered such products to be “a lot less” harmful. When participants were asked to assume that these products were much less harmful than cigarettes, 34% of smokers stated that they would be interested in trying smokeless tobacco products, with another 11% saying “maybe” or “don't know.” In the multivariate analysis, Māori smokers were significantly more interested in trying smokeless products than Europeans in all 3 models considered (e.g., Model 1: adjusted odds ratio [AOR] = 1.71, 95% CI = 1.23–2.37). There was also significantly increased interest for those concerned about the impact of smoking on health and quality of life in the future (AOR = 1.44, 95% CI = 1.17–1.78). But interest did not vary significantly by 2 measures of socioeconomic status and varied inconsistently by 2 measures of financial stress.
The finding that one third of smokers said that they would be interested in trying smokeless products suggests that these products could have a role as part of a tobacco epidemic endgame that phases out smoked tobacco. Differences in interest level by ethnic group may be relevant to stimulating further work in this area (e.g., among those health workers concerned for smokers with the highest need to quit).
Some countries have started to extend indoor smokefree laws to cover cars and various outdoor settings. However, policy-modifiable factors around smoker support for these new laws are not well described.
The New Zealand (NZ) arm of the International Tobacco Control Policy Evaluation Survey (ITC Project) derives its sample from the NZ Health Survey (a national sample). From this sample we surveyed adult smokers (n = 1376).
For the six settings considered, 59% of smokers supported at least three new completely smokefree areas. Only 2% favoured smoking being allowed in all the six new settings. Support among Maori, Pacific and Asian smokers relative to European smokers was elevated in multivariate analyses, but confidence intervals often included 1.0.
Also in the multivariate analyses, "strong support" by smokers for new smokefree area laws was associated with greater knowledge of the second-hand smoke (SHS) hazard, and with behaviours to reduce SHS exposure towards others. Strong support was also associated with reporting having smokefree cars (aOR = 1.68, 95% CI = 1.21 - 2.34); and support for tobacco control regulatory measures by government (aOR = 1.63, 95% CI = 1.32 - 2.01). There was also stronger support by smokers with a form of financial stress (not spending on household essentials).
Smokers from a range of population groups can show majority support for new outdoor and smokefree car laws. Some of these findings are consistent with the use of public health strategies to support new smokefree laws, such as enhancing public knowledge of the second-hand smoke hazard.
Short, linear motifs (SLiMs) play a critical role in many biological processes, particularly in protein–protein interactions. The Short, Linear Motif Finder (SLiMFinder) web server is a de novo motif discovery tool that identifies statistically over-represented motifs in a set of protein sequences, accounting for the evolutionary relationships between them. Motifs are returned with an intuitive P-value that greatly reduces the problem of false positives and is accessible to biologists of all disciplines. Input can be uploaded by the user or extracted directly from UniProt. Numerous masking options give the user great control over the contextual information to be included in the analyses. The SLiMFinder server combines these with user-friendly output and visualizations of motif context to allow the user to quickly gain insight into the validity of a putatively functional motif. These visualizations include alignments of motif occurrences, alignments of motifs and their homologues and a visual schematic of the top-ranked motifs. Returned motifs can also be compared with known SLiMs from the literature using CompariMotif. All results are available for download. The SLiMFinder server is available at: http://bioware.ucd.ie/slimfinder.html.
Cigarette smoking often starts in teenage years. It is not known whether teenagers are aware of the association of smoking with eye disease and blindness.
To explore the knowledge of the link between smoking, and eye diseases and blindness, and the likely impact of this knowledge among teenagers in UK.
A cross‐sectional survey, using a structured interview of teenagers attending four organised social events, was conducted. Awareness and fear of blindness, and of three smoking‐related diseases (lung cancer, heart disease and stroke) and a distractor condition (deafness) was investigated. The likelihood of smokers quitting on developing early signs of each condition was determined.
A 92% “opt in” response rate was achieved. Out of 260 teenagers (16–18 years), 15%, 27% and 81% believed that smoking caused stroke, heart disease and lung cancer, respectively. Only 5% believed smoking caused blindness. Subjects ranked their fear of each of the five conditions, scoring five for the most feared and one for the least feared. Subjects were significantly (p<0.01) more fearful (mean scores in brackets) of blindness (4.2) than of lung cancer (3.4), heart disease (2.3) and deafness (1.2). More teenagers (p<0.01) said they would stop smoking on developing early signs of blindness compared with early signs of lung or heart disease.
Awareness of the risk of blindness from smoking is low among teenagers, but fear of blindness may be more likely to motivate teenagers to stop smoking than fear of lung or heart disease. Teenagers should be made more aware of the ocular risks of cigarette smoking as a novel public health measure.
Large datasets of protein interactions provide a rich resource for the discovery of Short Linear Motifs (SLiMs) that recur in unrelated proteins. However, existing methods for estimating the probability of motif recurrence may be biased by the size and composition of the search dataset, such that p-value estimates from different datasets, or from motifs containing different numbers of non-wildcard positions, are not strictly comparable. Here, we develop more exact methods and explore the potential biases of computationally efficient approximations.
A widely used heuristic for the calculation of motif over-representation approximates motif probability by assuming that all proteins have the same length and composition. We introduce pv, which calculates the probability exactly. Secondly, the recently introduced SLiMFinder statistic Sig, accounts for multiple testing (across all possible motifs) in motif discovery. However, it approximates the probability of all other possible motifs, occurring with a score of p or less, as being equal to p. Here, we show that the exhaustive calculation of the probability of all possible motif occurrences that are as rare or rarer than the motif of interest, Sig', may be carried out efficiently by grouping motifs of a common probability (i.e. those which have permuted orders of the same residues). Sig'v, which corrects both approximations, is shown to be uniformly distributed in a random dataset when searching for non-ambiguous motifs, indicating that it is a robust significance measure.
A method is presented to compute exactly the true probability of a non-ambiguous short protein sequence motif, and the utility of an approximate approach for novel motif discovery across a large number of datasets is demonstrated.
To test the hypothesis that tobacco companies would not follow a regulation that required seven new graphic health warnings (GHWs) to be evenly distributed on cigarette packs and that they would distribute fewer packs featuring warnings regarded by smokers as being more disturbing.
Cross-sectional survey of purchased packs (n = 168) and street-collected discarded packs (convenience sample of New Zealand cities and towns, n = 1208 packs) with statistical analysis of seven types of new GHWs. A priori warning impact was judged using three criteria, which were tested against data from depth interviews with retailers.
The GHWs on the purchased packs and street-collected packs both showed a distribution pattern that was generally consistent with the hypothesis ie, there were disproportionately more packs featuring images judged as "least disturbing" and disproportionately fewer of those with warnings judged "more disturbing". The overall patterns were statistically significant, suggesting an unequal frequency of the different warnings for both purchased (p < 0.0001) and street-collected packs (p = 0.035). One of the least disturbing images (of a "corpse with toe-tag") dominated the distribution in both samples. Further analysis of the street-collected packs revealed that this image appeared disproportionately more frequently on manufactured cigarettes made by each of the three largest New Zealand tobacco companies. Although stock clustering could explain the purchase pack result, there were no obvious reasons why the same uneven warning distribution was also evident among the street-collected packs.
These results suggest that tobacco companies are not following the regulations, which requires even distribution of the seven different GHWs on cigarette packs; further monitoring is required to estimate the extent of this non-compliance. As an immediate measure, governments should strictly enforce all regulations applying to health warnings, particularly given that these are an effective tobacco control intervention that cost tax payers nothing.
Many smokers believe that "light" cigarettes are less harmful than regular cigarettes, which is at variance with the scientific evidence. The Framework Convention on Tobacco Control (FCTC) aims to address this problem in Article 11 which deals with misleading labelling of tobacco products. In this study we aimed to determine smokers' use and beliefs concerning "light" and "mild" cigarettes ("lights"), including in relation to ethnicity, deprivation and other socio-demographic characteristics.
The New Zealand (NZ) arm of the International Tobacco Control Policy Evaluation Survey (ITC Project) uses as its sampling frame the NZ Health Survey. This is a national sample with boosted sampling of Maori, Pacific peoples and Asians. From this sample we surveyed adult smokers (n = 1376) about use and beliefs relating to "light" cigarettes. We assessed the associations with smoking "lights" after adjusting for socio-demographic variables, and smoking-related behaviours and beliefs.
Many smokers of "lights" believed that smoking "lights" made it easier to quit smoking (25%), that "lights" are less harmful (42%), and that smokers of "lights" take in less tar (43%). Overall most "lights" smokers (60%) had at least one of these three beliefs, a proportion significantly higher than for smokers of "regular" cigarettes at 45% (adjusted odds ratio (aOR) = 1.96, 95% CI = 1.29 – 2.96). While "lights" smokers had significantly lower tobacco consumption and were more aware of smoking harms, they were no more likely to be intending to quit or have made a previous quit attempt.
By ethnicity, both Maori and Pacific people were less likely to smoke "lights" than Europeans (aOR = 0.53, 95% CI = 0.35 – 0.80 and aOR = 0.14, 95% CI = 0.05 – 0.40 respectively). In contrast there was no significant difference by level of deprivation. Roll-your-own (RYO) tobacco smokers were less likely to smoke "light" forms of RYO tobacco while both older and women smokers were more likely to smoke "lights".
Most "lights" smokers have one or more misperceptions about the product they use, and were no more likely to intend to quit or to have made a quit attempt. In response to such misperceptions, governments could act further to eliminate all misleading tobacco marketing. Ideally, they could not only adopt FCTC requirements, but go further by requiring plain packaging for all tobacco products.
Smokefree environments legislation is increasingly being implemented around the world. Evaluations largely find that the legislation is popular, compliance is high and report improved air quality and reduced exposure to secondhand smoke (SHS). The impact of the legislation on disadvantaged groups, including indigenous peoples has not been explored. We present findings from a multifaceted evaluation of the impact of the smokefree workplace provisions of the New Zealand Smokefree Environments Amendment Act on Māori people in New Zealand. Māori are the indigenous people of New Zealand. The Smokefree Environments Amendment Act extended existing smokefree legislation to almost all indoor workplaces in December 2004 (including restaurants and pubs/bars).
Review of existing data and commissioned studies to identify evidence for the evaluation of the new legislation: including attitudes and support for the legislation; stakeholders views about the Act and the implementation process; impact on SHS exposure in workplaces and other settings; and impact on smoking-related behaviours.
Support for the legislation was strong among Māori and reached 90% for smokefree restaurants and 84% for smokefree bars by 2006. Māori stakeholders interviewed were mostly supportive of the way the legislation had been introduced. Reported exposure to SHS in workplaces decreased similarly in Māori and non-Māori with 27% of employed adult Māori reporting SHS exposure indoors at work during the previous week in 2003 and 9% in 2006. Exposure to SHS in the home declined, and may have decreased more in Māori households containing one or more smokers. For example, the proportion of 14–15 year old Māori children reporting that smoking occurred in their home fell from 47% in 2001 to 37% in 2007. Similar reductions in socially-cued smoking occurred among Māori and non-Māori. Evidence for the effect on smoking prevalence was mixed. Māori responded to the new law with increased calls to the national Quitline service.
The New Zealand Smokefree Environments Amendment Act had a range of positive effects, including reducing SHS exposure among Māori communities. If the experience is replicated in other countries with indigenous populations, it suggests that comprehensive smokefree environments legislation will have beneficial effects on the health of indigenous groups and could contribute to reducing inequalities in health within societies.
Case-control studies and outbreak investigations are the major epidemiological tools for providing detailed information on enteric disease sources and risk factors, but these investigations can be constrained by cost and logistics.
We explored the advantages and disadvantages of comparing risk factors for enteric diseases using the case-case method. The main issues are illustrated with an analysis of routine notification data on enteric diseases for 2006 collected by New Zealand's national surveillance system.
Our analyses of aggregated New Zealand surveillance data found that the associations (crude odds ratios) for risk factors of enteric disease were fairly consistent with findings from local case-control studies and outbreak investigations, adding support for the use of the case-case analytical approach. Despite various inherent limitations, such an approach has the potential to contribute to the monitoring of risk factor trends for enteric diseases. Nevertheless, using the case-case method for analysis of routine surveillance data may need to be accompanied by: (i) reduction of potential selection and information biases by improving the quality of the surveillance data; and (ii) reduction of confounding by conducting more sophisticated analyses based on individual-level data.
Case-case analyses of enteric diseases using routine surveillance data might be a useful low-cost means to study trends in enteric disease sources and inform control measures. If used, it should probably supplement rather than replace outbreak investigations and case-control studies. Furthermore, it could be enhanced by utilising high quality individual-level data provided by nationally-representative sentinel sites for enteric disease surveillance.
Short linear motifs (SLiMs) in proteins are functional microdomains of fundamental importance in many biological systems. SLiMs typically consist of a 3 to 10 amino acid stretch of the primary protein sequence, of which as few as two sites may be important for activity, making identification of novel SLiMs extremely difficult. In particular, it can be very difficult to distinguish a randomly recurring “motif” from a truly over-represented one. Incorporating ambiguous amino acid positions and/or variable-length wildcard spacers between defined residues further complicates the matter.
In this paper we present two algorithms. SLiMBuild identifies convergently evolved, short motifs in a dataset of proteins. Motifs are built by combining dimers into longer patterns, retaining only those motifs occurring in a sufficient number of unrelated proteins. Motifs with fixed amino acid positions are identified and then combined to incorporate amino acid ambiguity and variable-length wildcard spacers. The algorithm is computationally efficient compared to alternatives, particularly when datasets include homologous proteins, and provides great flexibility in the nature of motifs returned. The SLiMChance algorithm estimates the probability of returned motifs arising by chance, correcting for the size and composition of the dataset, and assigns a significance value to each motif. These algorithms are implemented in a software package, SLiMFinder. SLiMFinder default settings identify known SLiMs with 100% specificity, and have a low false discovery rate on random test data.
The efficiency of SLiMBuild and low false discovery rate of SLiMChance make SLiMFinder highly suited to high throughput motif discovery and individual high quality analyses alike. Examples of such analyses on real biological data, and how SLiMFinder results can help direct future discoveries, are provided. SLiMFinder is freely available for download under a GNU license from http://bioinformatics.ucd.ie/shields/software/slimfinder/.