Views of young people in rural Australia on SPARX, a fantasy world developed for New Zealand youth with depression.

Background: A randomized control trial demonstrated that a computerized cognitive behavioral therapy (cCBT) program (Smart, Positive, Active, Realistic, X-factor thoughts [SPARX]) was an appealing and efficacious treatment for depression for adolescents in New Zealand. Little is known about the acceptability of computerized therapy programs for rural Australians and the suitability of computerized programs developed in one cultural context when used in another country. Issues such as accents and local differences in health care access might mean adjustments to programs are required. Objective: This study sought to explore the acceptability of SPARX by youth in rural Australia and to explore whether and how young people would wish to access such a program. Methods: Focus groups and semistructured interviews were conducted with 16 young people attending two youth-focused community services in a small, rural Tasmanian town. An inductive data-driven approach was used to identify themes using the interview transcripts as the primary data source. Interpretation was supported by demographic data, observer notes, and content analysis. Results: Participants reported that young people want help for mental health issues but they have an even stronger need for controlling how they access services. In particular, they considered protecting their privacy in their small community to be paramount. Participants thought computerized therapy was a promising way to increase access to treatment for youth in rural and remote areas if offered with or without therapist support and via settings other than school. The design features of SPARX that were perceived to be useful, included the narrative structure of the program, the use of different characters, the personalization of an avatar, “socialization” with the Guide character, optional journaling, and the use of encouraging feedback. Participants did not consider (New Zealand) accents off-putting. Young people believed the SPARX program would appeal to those who play computer games generally, but may be less appealing for those who do not. Conclusions: The findings suggest that computerized therapy offered in ways that support privacy and choice can improve access to treatment for rural youth. Foreign accents and style may not be off-putting to teenage users when the program uses a playful fantasy genre, as it is consistent with their expectation of fantasy worlds, and it is in a medium with which they already have a level of competence. Rather, issues of engaging design and confidential access appeared to be more important. These findings suggest a proven tool once formally assessed at a local level can be adopted cross-nationally

Statistical Inference of Selection and Divergence from a Time-Dependent Poisson Random Field Model

We apply a recently developed time-dependent Poisson random field model to aligned DNA sequences from two related biological species to estimate selection coefficients and divergence time. We use Markov chain Monte Carlo methods to estimate species divergence time and selection coefficients for each locus. The model assumes that the selective effects of non-synonymous mutations are normally distributed across genetic loci but constant within loci, and synonymous mutations are selectively neutral. In contrast with previous models, we do not assume that the individual species are at population equilibrium after divergence. Using a data set of 91 genes in two Drosophila species, D. melanogaster and D. simulans, we estimate the species divergence time (or 1.68 million years, assuming the haploid effective population size years) and a mean selection coefficient per generation . Although the average selection coefficient is positive, the magnitude of the selection is quite small. Results from numerical simulations are also presented as an accuracy check for the time-dependent model

Mechanical compression attenuates normal human bronchial epithelial wound healing

Background: Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods: Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1) unperturbed control cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH(2)O), and 4) 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results: We found that mechanical compression and scrape injury increase TGF-beta 2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE(2) media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE(2), but not EGF. Conclusion: Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE(2) and a compromised cytoskeleton

Bayesian modeling of recombination events in bacterial populations

Background: We consider the discovery of recombinant segments jointly with their origins within multilocus DNA sequences from bacteria representing heterogeneous populations of fairly closely related species. The currently available methods for recombination detection capable of probabilistic characterization of uncertainty have a limited applicability in practice as the number of strains in a data set increases. Results: We introduce a Bayesian spatial structural model representing the continuum of origins over sites within the observed sequences, including a probabilistic characterization of uncertainty related to the origin of any particular site. To enable a statistically accurate and practically feasible approach to the analysis of large-scale data sets representing a single genus, we have developed a novel software tool (BRAT, Bayesian Recombination Tracker) implementing the model and the corresponding learning algorithm, which is capable of identifying the posterior optimal structure and to estimate the marginal posterior probabilities of putative origins over the sites. Conclusion: A multitude of challenging simulation scenarios and an analysis of real data from seven housekeeping genes of 120 strains of genus Burkholderia are used to illustrate the possibilities offered by our approach. The software is freely available for download at URL http://web.abo.fi/fak/ mnf//mate/jc/software/brat.html

Quantifying Adaptive Evolution in the Drosophila Immune System

It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, and as organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a likely cause. To quantify the effect, and to identify which genes and pathways are most likely to be involved in the host–parasite arms race, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of the McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. We find the rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host–parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution in both species, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. In summary, our data provide quantitative estimates of the elevated rate of adaptive evolution in immune system genes relative to the rest of the genome, and they suggest that adaptation to parasites is an important force driving molecular evolution

Utilization of health services in relation to mental health problems in adolescents: A population based survey

BACKGROUND: Only a minority of adolescents reporting symptoms above case-levels on screenings for mental health seeks and receives help from specialist health services. The objective of this study was to a) examine help-seeking for symptoms of anxiety and depression in relation to symptom load dimensionally, b) identify the level of specialization in mental health among service-providers, and c) identify associations between mental health problems and contact with different types of health services. METHODS: This cross-sectional school-based study (response-rate 88%, n = 11154) is based on Norwegian health surveys among 15 and 16 year olds. RESULTS: We found a dose-response association between symptom-load and help seeking. Only 34% of individuals with mental symptom-load above 99(th )percentile reported help-seeking in the last 12 months. Forty percent of help seekers were in contact with specialists (psychiatrists or psychologists), the remaining were mainly in contact with GPs. Mental health problems increased help seeking to all twelve service providers examined. CONCLUSION: It might not be reasonable to argue that all adolescents with case-level mental health problems are in need of treatment. However, concerning the 99(th )percentile, claiming treatment need is less controversial. Even in the Norwegian context where mental health services are relatively available and free of charge, help-seeking in individuals with the highest symptom-loads is still low. Most help seekers achieved contact with health care providers, half of them at a non specialized level. Our results suggest that adolescents' recognition of mental health problems or intention to seek help for these are the major "filters" restricting treatment

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript