The DAFNEplus programme for sustained type 1 diabetes self management: Intervention development using the Behaviour Change Wheel

AIMS: Self-management programmes for type 1 diabetes, such as the UK's Dose Adjustment for Normal Eating (DAFNE), improve short-term clinical outcomes but difficulties maintaining behavioural changes attenuate long-term impact. This study used the Behaviour Change Wheel (BCW) framework to revise the DAFNE intervention to support sustained behaviour change. METHODS: A four-step method was based on the BCW intervention development approach: 1) Identifying self-management behaviours and barriers/enablers to maintaining them via stakeholder consultation and evidence synthesis, and mapping barriers/enablers to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. 2) Specifying behaviour change techniques (BCTs) in the existing DAFNE intervention using the Behaviour Change Techniques Taxonomy (BCTTv1). 3) Identifying additional BCTs to target the barriers/enablers using the BCW and BCTTv1. 4) Parallel stakeholder consultation to generate recommendations for intervention revision. Revised materials were co-designed by stakeholders (diabetologists, psychologists, specialist nurses and dietitians). RESULTS: Thirty-four barriers and five enablers to sustaining self-management post-DAFNE, were identified. The existing DAFNE intervention contained 24 BCTs, which partially addressed the enablers. Twenty-seven BCTs were added, including 'Habit formation', 'Credible source' and 'Conserving mental resources'. Fifteen stakeholder-agreed recommendations for content and delivery were incorporated into the final DAFNEplus intervention, comprising three co-designed components: (1) face-to-face group learning course, (2) individual structured follow-up sessions, (3) technological support, including blood glucose data management. CONCLUSIONS: This method provided a systematic approach to specifying and revising a behaviour change intervention incorporating stakeholder input. The revised DAFNEplus intervention aims to support the maintenance of behavioural changes by targeting barriers and enablers to sustaining self-management behaviours

The use and interpretation of anthropometric measures in cancer epidemiology: A perspective from the world cancer research fund international continuous update project

Anthropometric measures relating to body size, weight and composition are increasingly being associated with cancer risk and progression. Whilst practical in epidemiologic research, where population-level associations with disease are revealed, it is important to be aware that such measures are imperfect markers of the internal physiological processes that are the actual correlates of cancer development. Body mass index (BMI), the most commonly used marker for adiposity, may mask differences between lean and adipose tissue, or fat distribution, which varies across individuals, ethnicities, and stage in the lifespan. Other measures, such as weight gain in adulthood, waist circumference and waist-to-hip ratio, contribute information on adipose tissue distribution and insulin sensitivity. Single anthropometric measures do not capture maturational events, including the presence of critical windows of susceptibility (i.e., age of menarche and menopause), which presents a challenge in epidemiologic work. Integration of experimental research on underlying dynamic genetic, hormonal, and other non-nutritional mechanisms is necessary for a confident conclusion of the overall evidence in cancer development and progression. This article discusses the challenges confronted in evaluating and interpreting the current evidence linking anthropometric factors and cancer risk as a basis for issuing recommendations for cancer prevention

Assimilation of healthy and indulgent impressions from labelling influences fullness but not intake or sensory experience

Background: Recent evidence suggests that products believed to be healthy may be over-consumed relative to believed indulgent or highly caloric products. The extent to which these effects relate to expectations from labelling, oral experience or assimilation of expectations is unclear. Over two experiments, we tested the hypotheses that healthy and indulgent information could be assimilated by oral experience of beverages and influence sensory evaluation, expected satiety, satiation and subsequent appetite. Additionally, we explored how expectation-experience congruency influenced these factors. Results: Results supported some assimilation of healthiness and indulgent ratings—study 1 showed that indulgent ratings enhanced by the indulgent label persisted post-tasting, and this resulted in increased fullness ratings. In study 2, congruency of healthy labels and oral experience promoted enhanced healthiness ratings. These healthiness and indulgent beliefs did not influence sensory analysis or intake—these were dictated by the products themselves. Healthy labels, but not experience, were associated with decreased expected satiety. Conclusions: Overall labels generated expectations, and some assimilation where there were congruencies between expectation and experience, but oral experience tended to override initial expectations to determine ultimate sensory evaluations and intake. Familiarity with the sensory properties of the test beverages may have resulted in the use of prior knowledge, rather than the label information, to guide evaluations and behaviour

Direct Integration and Non-Perturbative Effects in Matrix Models

We show how direct integration can be used to solve the closed amplitudes of multi-cut matrix models with polynomial potentials. In the case of the cubic matrix model, we give explicit expressions for the ring of non-holomorphic modular objects that are needed to express all closed matrix model amplitudes. This allows us to integrate the holomorphic anomaly equation up to holomorphic modular terms that we fix by the gap condition up to genus four. There is an one-dimensional submanifold of the moduli space in which the spectral curve becomes the Seiberg--Witten curve and the ring reduces to the non-holomorphic modular ring of the group $\Gamma(2)$. On that submanifold, the gap conditions completely fix the holomorphic ambiguity and the model can be solved explicitly to very high genus. We use these results to make precision tests of the connection between the large order behavior of the 1/N expansion and non-perturbative effects due to instantons. Finally, we argue that a full understanding of the large genus asymptotics in the multi-cut case requires a new class of non-perturbative sectors in the matrix model.Comment: 51 pages, 8 figure

Correcting the Site Frequency Spectrum for Divergence-Based Ascertainment

Comparative genomics based on sequenced referenced genomes is essential to hypothesis generation and testing within population genetics. However, selection of candidate regions for further study on the basis of elevated or depressed divergence between species leads to a divergence-based ascertainment bias in the site frequency spectrum within selected candidate loci. Here, a method to correct this problem is developed that obtains maximum-likelihood estimates of the unascertained allele frequency distribution using numerical optimization. I show how divergence-based ascertainment may mimic the effects of natural selection and offer correction formulae for performing proper estimation into the strength of selection in candidate regions in a maximum-likelihood setting

Coordinated Regulation of Intestinal Functions in C. elegans by LIN-35/Rb and SLR-2

LIN-35 is the sole C. elegans representative of the pocket protein family, which includes the mammalian Retinoblastoma protein pRb and its paralogs p107 and p130. In addition to having a well-established and central role in cell cycle regulation, pocket proteins have been increasingly implicated in the control of critical and diverse developmental and cellular processes. To gain a greater understanding of the roles of pocket proteins during development, we have characterized a synthetic genetic interaction between lin-35 and slr-2, which we show encodes a C2H2-type Zn-finger protein. Whereas animals harboring single mutations in lin-35 or slr-2 are viable and fertile, lin-35; slr-2 double mutants arrest uniformly in early larval development without obvious morphological defects. Using a combination of approaches including transcriptome profiling, mosaic analysis, starvation assays, and expression analysis, we demonstrate that both LIN-35 and SLR-2 act in the intestine to regulate the expression of many genes required for normal nutrient utilization. These findings represent a novel role for pRb family members in the maintenance of organ function. Our studies also shed light on the mechanistic basis of genetic redundancy among transcriptional regulators and suggest that synthetic interactions may result from the synergistic misregulation of one or more common targets

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles

Finding Your Mate at a Cocktail Party: Frequency Separation Promotes Auditory Stream Segregation of Concurrent Voices in Multi-Species Frog Choruses

Vocal communication in crowded social environments is a difficult problem for both humans and nonhuman animals. Yet many important social behaviors require listeners to detect, recognize, and discriminate among signals in a complex acoustic milieu comprising the overlapping signals of multiple individuals, often of multiple species. Humans exploit a relatively small number of acoustic cues to segregate overlapping voices (as well as other mixtures of concurrent sounds, like polyphonic music). By comparison, we know little about how nonhuman animals are adapted to solve similar communication problems. One important cue enabling source segregation in human speech communication is that of frequency separation between concurrent voices: differences in frequency promote perceptual segregation of overlapping voices into separate “auditory streams” that can be followed through time. In this study, we show that frequency separation (ΔF) also enables frogs to segregate concurrent vocalizations, such as those routinely encountered in mixed-species breeding choruses. We presented female gray treefrogs (Hyla chrysoscelis) with a pulsed target signal (simulating an attractive conspecific call) in the presence of a continuous stream of distractor pulses (simulating an overlapping, unattractive heterospecific call). When the ΔF between target and distractor was small (e.g., ≤3 semitones), females exhibited low levels of responsiveness, indicating a failure to recognize the target as an attractive signal when the distractor had a similar frequency. Subjects became increasingly more responsive to the target, as indicated by shorter latencies for phonotaxis, as the ΔF between target and distractor increased (e.g., ΔF = 6–12 semitones). These results support the conclusion that gray treefrogs, like humans, can exploit frequency separation as a perceptual cue to segregate concurrent voices in noisy social environments. The ability of these frogs to segregate concurrent voices based on frequency separation may involve ancient hearing mechanisms for source segregation shared with humans and other vertebrates