FUT2 Variants Confer Susceptibility to Familial Otitis Media

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10−5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants—namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗—reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait

Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we built and validated supervised neuroanatomical machine learning models for individual-level inferences, using a case–control design and the largest known neuroimaging database on youth anxiety disorders: the ENIGMA-Anxiety Consortium (N = 3,343; age = 10–25 years; global sites = 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (panic disorder), but also transdiagnostically for all anxiety disorders when patients were subgrouped according to their sex, medication status and symptom severity (area under the receiver operating characteristic curve, 0.59–0.63). Classifications were driven by neuroanatomical features (cortical thickness, cortical surface area and subcortical volumes) in fronto-striato-limbic and temporoparietal regions. This benchmark study within a large, heterogeneous and multisite sample of youth with anxiety disorders reveals that only modest classification performances can be realistically achieved with machine learning using neuroanatomical data.NWORubicon 019.201SG.022Advanced Behavioural Research MethodsHealth and Well-bein

Analysis of health behaviour change interventions for preventing dental caries delivered in primary schools

To improve oral health in children, the key behaviours (tooth brushing and sugar control) responsible for development of dental caries need to be better understood, as well as how to promote these behaviours effectively so they become habitual; and, the specific, optimal techniques to use in interventions. The aim of this paper is to describe and analyse the behaviour change techniques that have been used in primary school-based interventions to prevent dental caries (utilizing a Cochrane systematic review that we have undertaken) and to identify opportunities for improving future interventions by incorporating a comprehensive range of behaviour change techniques. Papers of five interventions were reviewed and data were independently extracted. Results indicate that behaviour change techniques were limited to information-behaviour links, information on consequences, instruction and demonstration of behaviours. None of the interventions were based on behaviour change theory. We conclude that behaviour change techniques used in school interventions to reduce dental caries were limited and focused around providing information about how behaviour impacts on health and the consequences of not developing the correct health behaviours as well as providing oral hygiene instruction. Establishing which techniques are effective is difficult due to poor reporting of interventions in studies. Future design of oral health promotion interventions using behaviour change theory for development and evaluation (and reporting results in academic journals) could strengthen the potential for efficacy and provide a framework to use a much wider range of behaviour change techniques. Future studies should include development and publication of intervention manuals which is becoming standard practice in other health promoting programmes

An intervention programme to establish regular toothbrushing: understanding parent’s beliefs and motivating children.

Temporal changes in occupancy of the Georges Bank (NE USA) fish and invertebrate community were examined and interpreted in the context of systems ecological theory of extinction debt (EDT). EDT posits that in a closed system with a mix of competitor and colonizer species and experiencing habitat fragmentation and loss, the competitor species will show a gradual decline in fitness (occupancy) eventually leading to their extinction (extirpation) over multiple generations. A corollary of this is a colonizer credit, where colonizer species occupancy may increase with fragmentation because the disturbance gives that life history a transient relative competitive advantage. We found that competitor species occupancy decreased in time concomitant with an increase in occupancy of colonizer species and this may be related to habitat fragmentation or loss owing to industrialized bottom trawl fishing. Mean species richness increased over time which suggests less specialization (decreased dominance) of the assemblage that may result from habitat homogenization. These analyses also showed that when abundance of species was decreased by fishing but eventually returned to previous levels, on average it had a lower occupancy than earlier in the series which could increase their vulnerability to depletion by fishing. Changing occupancy and diversity patterns of the community over time is consistent with EDT which can be exacerbated by direct impacts of fishery removals as well as climate change impacts on the fish community assemblage

An intervention programme to establish regular toothbrushing : understanding parents' beliefs and motivating children

Aims/Objectives: To determine the benefit of twice daily toothbrushing on newly erupted first permanent molars. To investigate, through the Health Belief Model, how parents' beliefs influence the likelihood of their children brushing twice a day. To identify aspects of a toothbrushing intervention programme that can be used in general dental practice. Design: Randomised controlled trial. Setting: Schools in deprived communities in Scotland. Participants: 461, 5-year-old children. Interventions/methods: Supervised toothbrushing on schooldays with a 1,000ppm chalk-based fluoride toothpaste for two years. A school and home-based incentive scheme including toothbrushing charts, 6-monthly dental examinations and parental questionnaires. Main outcome measures: Caries increment and twice daily toothbrushing. Results: In the control group, children who brushed once a day or less had 64% more caries than those who brushed at least twice a day (P=0.001). In the intervention group this difference in caries was reduced to 16% (P>0.05). The most significant parental belief explaining variation in twice-daily brushing was whether parents feel strongly that there is time to check their child's toothbrushing (P=0.0001). The odds of these parents reporting that their child brushes twice daily are nearly three times greater. 95% of parents felt that toothbrushing charts would be a good way for dentists in practice to encourage children to brush regularly. Conclusions: The benefit of twice daily toothbrushing on caries development in newly erupted first permanent molar teeth is around 50% compared to brushing once a day or less. Parents' beliefs do influence the likelihood of their children brushing twice a day. Key parts of the intervention programme can be used when children attend general dental practice and would be welcomed by parents