Detection of suspicious interactions of spiking covariates in methylation data

BACKGROUND: In methylation analyses like epigenome-wide association studies, a high amount of biomarkers is tested for an association between the measured continuous outcome and different covariates. In the case of a continuous covariate like smoking pack years (SPY), a measure of lifetime exposure to tobacco toxins, a spike at zero can occur. Hence, all non-smokers are generating a peak at zero, while the smoking patients are distributed over the other SPY values. Additionally, the spike might also occur on the right side of the covariate distribution, if a category "heavy smoker" is designed. Here, we will focus on methylation data with a spike at the left or the right of the distribution of a continuous covariate. After the methylation data is generated, analysis is usually performed by preprocessing, quality control, and determination of differentially methylated sites, often performed in pipeline fashion. Hence, the data is processed in a string of methods, which are available in one software package. The pipelines can distinguish between categorical covariates, i.e. for group comparisons or continuous covariates, i.e. for linear regression. The differential methylation analysis is often done internally by a linear regression without checking its inherent assumptions. A spike in the continuous covariate is ignored and can cause biased results. RESULTS: We have reanalysed five data sets, four freely available from ArrayExpress, including methylation data and smoking habits reported by smoking pack years. Therefore, we generated an algorithm to check for the occurrences of suspicious interactions between the values associated with the spike position and the non-spike positions of the covariate. Our algorithm helps to decide if a suspicious interaction can be found and further investigations should be carried out. This is mostly important, because the information on the differentially methylated sites will be used for post-hoc analyses like pathway analyses. CONCLUSIONS: We help to check for the validation of the linear regression assumptions in a methylation analysis pipeline. These assumptions should also be considered for machine learning approaches. In addition, we are able to detect outliers in the continuous covariate. Therefore, more statistical robust results should be produced in methylation analysis using our algorithm as a preprocessing step

Towards the development of music as an intervention for Insomnia treatment: A research synthesis

Though research has been conducted with regards to music and sleep over the last two decades, there is still a significant uncertainty to its effectiveness due to the lack of scientific validation through objective testing and data analysis (Jespersen et al 2015). It has been proven that music can help in the management of physical pain and psychological conditions such as depression and anxiety, hence, music is already being implemented in medical treatments in the form of music therapy (Jespersen et al 2015). The literature review commences with a brief consideration of conventional treatment methods including pharmaceutical and talking therapy-based methods. It then investigates various research trials using music as the main intervention and contributes to the field by introducing and exploring certain sleep-music products which are available on the open market. The thesis aims to compare research regarding the psychology of music and sleep, sleep sciences, music as an intervention for insomnia, music-assisted relaxation (PMR) for Insomnia, Cognitive Behavioural Therapy for Insomnia (CBTi), and Sleep Medication. From these two main areas of interest comparisons and contrasts can be drawn up which highlight specific areas which may need more attention. From the research certain gaps can be acknowledged and suggestions can be made for the continuation of sleep-music research including the need for familiarity and preference in surroundings and music choice, but also highlights the confusion on the open market with regard to binaural beats technology for example. It is suggested in this thesis that more time is required for the evidence in support of sleep-music to build, but also that care must be given as certain online sleep-music products may restrict or obscure genuine research-driven outputs

Estimands in epigenome-wide association studies

Background: In DNA methylation analyses like epigenome-wide association studies, effects in differentially methylated CpG sites are assessed. Two kinds of outcomes can be used for statistical analysis: Beta-values and M-values. M-values follow a normal distribution and help to detect differentially methylated CpG sites. As biological effect measures, differences of M-values are more or less meaningless. Beta-values are of more interest since they can be interpreted directly as differences in percentage of DNA methylation at a given CpG site, but they have poor statistical properties. Different frameworks are proposed for reporting estimands in DNA methylation analysis, relying on Beta-values, M-values, or both. Results: We present and discuss four possible approaches of achieving estimands in DNA methylation analysis. In addition, we present the usage of M-values or Beta-values in the context of bioinformatical pipelines, which often demand a predefined outcome. We show the dependencies between the differences in M-values to differences in Beta-values in two data simulations: a analysis with and without confounder effect. Without present confounder effects, M-values can be used for the statistical analysis and Beta-values statistics for the reporting. If confounder effects exist, we demonstrate the deviations and correct the effects by the intercept method. Finally, we demonstrate the theoretical problem on two large human genome-wide DNA methylation datasets to verify the results. Conclusions: The usage of M-values in the analysis of DNA methylation data will produce effect estimates, which cannot be biologically interpreted. The parallel usage of Beta-value statistics ignores possible confounder effects and can therefore not be recommended. Hence, if the differences in Beta-values are the focus of the study, the intercept method is recommendable. Hyper- or hypomethylated CpG sites must then be carefully evaluated. If an exploratory analysis of possible CpG sites is the aim of the study, M-values can be used for inference

Soluble versions of outer membrane cytochromes function as exporters for heterologously produced cargo proteins

This study reveals that it is possible to secrete truncated versions of outer membrane cytochromes into the culture supernatant and that these proteins can provide a basis for the export of heterologously produced proteins. Different soluble and truncated versions of the outer membrane cytochrome MtrF were analyzed for their suitability to be secreted. A protein version with a very short truncation of the N-terminus to remove the recognition sequence for the addition of a lipid anchor is secreted efficiently to the culture supernatant, and moreover this protein could be further truncated by a deletion of 160 amino acid and still is detectable in the supernatant. By coupling a cellulase to this soluble outer membrane cytochrome, the export efficiency was measured by means of relative cellulase activity. We conclude that outer membrane cytochromes of S. oneidensis can be applied as transporters for the export of target proteins into the medium using the type II secretion pathway

Extracellular riboflavin induces anaerobic biofilm formation in Shewanella oneidensis

Background Some microorganisms can respire with extracellular electron acceptors using an extended electron transport chain to the cell surface. This process can be applied in bioelectrochemical systems in which the organisms produce an electrical current by respiring with an anode as electron acceptor. These organisms apply flavin molecules as cofactors to facilitate one-electron transfer catalyzed by the terminal reductases and in some cases as endogenous electron shuttles. Results In the model organism Shewanella oneidensis, riboflavin production and excretion trigger a specific biofilm formation response that is initiated at a specific threshold concentration, similar to canonical quorum-sensing molecules. Riboflavin-mediated messaging is based on the overexpression of the gene encoding the putrescine decarboxylase speC which leads to posttranscriptional overproduction of proteins involved in biofilm formation. Using a model of growth-dependent riboflavin production under batch and biofilm growth conditions, the number of cells necessary to produce the threshold concentration per time was deduced. Furthermore, our results indicate that specific retention of riboflavin in the biofilm matrix leads to localized concentrations, which by far exceed the necessary threshold value. Conclusion This study describes a new quorum-sensing mechanism in S. oneidensis. Biofilm formation of S. oneidensis is induced by low concentrations of riboflavin resulting in an upregulation of the ornithine-decarboxylase speC. The results can be applied for the development of strains catalyzing increased current densities in bioelectrochemical systems

The strength of frustration and quantum fluctuations in LiVCuO4

For the 1D-frustrated ferromagnetic J_1-J_2 model with interchain coupling added, we analyze the dynamical and static structure factor S(k,omega), the pitch angle phi of the magnetic structure, the magnetization curve of edge-shared chain cuprates, and focus on LiCuVO4 for which neither a perturbed spinon nor a spin wave approach can be applied. phi is found to be most sensitive to the interplay of frustration and quantum fluctuations. For LiVCuO4 the obtained exchange parameters J are in accord with the results for a realistic 5-band extended Hubbard model and LSDA + U predictions yielding alpha=J_2/|J_1| about 0.75 in contrast to 5.5 > alpha > 1.42 suggested in the literature. The alpha-regime of the empirical phi-values in NaCu2O2 and linarite are considered, too.Comment: 7 pages, 7 figures, (1 figure added), improved text including also the abstract (the present second version has been submitted to EPL 26.10.2011, so far with one missing first referee report

Regulatory and coding sequences of TRNP1 co-evolve with brain size and cortical folding in mammals

Brain size and cortical folding have increased and decreased recurrently during mammalian evolution. Identifying genetic elements whose sequence or functional properties co-evolve with these traits can provide unique information on evolutionary and developmental mechanisms. A good candidate for such a comparative approach is TRNP1, as it controls proliferation of neural progenitors in mice and ferrets. Here, we investigate the contribution of both regulatory and coding sequences of TRNP1 to brain size and cortical folding in over 30 mammals. We find that the rate of TRNP1 protein evolution (omega) significantly correlates with brain size, slightly less with cortical folding and much less with body size. This brain correlation is stronger than for >95% of random control proteins. This co-evolution is likely affecting TRNP1 activity, as we find that TRNP1 from species with larger brains and more cortical folding induce higher proliferation rates in neural stem cells. Furthermore, we compare the activity of putative cis-regulatory elements (CREs) of TRNP1 in a massively parallel reporter assay and identify one CRE that likely co-evolves with cortical folding in Old World monkeys and apes. Our analyses indicate that coding and regulatory changes that increased TRNP1 activity were positively selected either as a cause or a consequence of increases in brain size and cortical folding. They also provide an example how phylogenetic approaches can inform biological mechanisms, especially when combined with molecular phenotypes across several species

Health Inequalities in Children and Adolescents: A Scoping Review of the Mediating and Moderating Effects of Family Characteristics

This scoping review systematically mapped evidence of the mediating and moderating effects of family characteristics on health inequalities in school-aged children and adolescents (6–18 years) in countries with developed economies in Europe and North America. We conducted a systematic scoping review following the PRISMA extension for Scoping Reviews recommendations. We searched the PubMed, PsycINFO and Scopus databases. Two reviewers independently screened titles, abstracts and full texts. Evidence was synthesized narratively. Of the 12,403 records initially identified, 50 articles were included in the synthesis. The included studies were conducted in the United States (n = 27), Europe (n = 18), Canada (n = 3), or in multiple countries combined (n = 2). We found that mental health was the most frequently assessed health outcome. The included studies reported that different family characteristics mediated or moderated health inequalities. Parental mental health, parenting practices, and parent-child-relationships were most frequently examined, and were found to be important mediating or moderating factors. In addition, family conflict and distress were relevant family characteristics. Future research should integrate additional health outcomes besides mental health, and attempt to integrate the complexity of families. The family characteristics identified in this review represent potential starting points for reducing health inequalities in childhood and adolescence.Peer Reviewe

Empatía, cognición social y calidad de vida subjetiva en esquizofrenia

Fundamento. Las personas con diagnóstico de esquizofrenia presentan déficits en empatía que se han relacionado con su pobre funcionamiento psicosocial. Los objetivos fueron: 1) analizar la relación entre empatía, cognición social, y calidad de vida en sujetos con diagnóstico de esquizofrenia y otros trastornos psicóticos 2) evaluar estas variables según la gravedad del cuadro clínico Material y métodos. Participaron 41 pacientes divididos en dos grupos según el nivel de gravedad del cuadro clínico. Se aplicó una batería de pruebas: el Índice de Reactividad Interpersonal (IRI), escala GEOPTE de Cognición Social para la psicosis, Instrumento de Evaluación de la Calidad de Vida de la Organización Mundial de la Salud – Versión breve (WHOQOL-BREF), Escala de Impresión Clínica Global (CGI), Escala para la evaluación de Síntomas Positivos (SAPS) y Síntomas Negativos (SANS). Resultados. Las subescalas angustia personal y fantasía del IRI presentaron una relación directa con la escala GEOPTE, e inversa con varias dimensiones de calidad de vida del WHOQOL-BREF. La escala GEOPTE, tuvo una relación inversa con todas las dimensiones de la calidad de vida evaluadas. El grupo levemente enfermo obtuvo puntuaciones significativamente menores en fantasía (15,44 vs. 20,12; p=,001) y significativamente más elevadas en salud psicológica (58,63 vs. 45,40; p=0,017) y ambiente (67,00 vs. 53,68; p=0,006). Conclusiones. Se halla relación entre empatía, cognición social y calidad de vida subjetiva en personas con diagnóstico de esquizofrenia en programas de rehabilitación psicosocial, Asimismo, destaca la existencia de diferencias relevantes en estas variables según el nivel de gravedad del cuadro clínicoBackground. People diagnosed with schizophrenia present empathy deficits that have been related to their poor psychosocial functioning. The objectives were: 1) analyse the relation between empathy, social cognition and quality of life in subjects diagnosed with schizophrenia and other psychotic disorders; 2) evaluate these variables according to the severity of the features. Methods. Forty-one patients, divided into two groups according to the level of severity, were included. A battery of tests was applied: Interpersonal Reactivity Index (IRI), GEOPTE scale of social cognition for psychosis, World Health Organization Quality of Life Assessment: Brief Version (WHOQOL-BREF), Clinical Global Impression scale (CGI), Scale for the Assessment of Positive Symptoms (SAPS) and Negative Symptoms (SANS). Results. There was a direct relationship between personal anxiety and fantasy sub-scales of the IRI and the GEOPTE scale, and an inverse relationship with several dimensions of quality of life of the WHOQOL-BREF. The GEOPTE scale had an inverse relation with all the dimensions of quality of life evaluated. The mildly sick group obtained scores that were significantly lower in fantasy (15.44 vs. 20.12; p=0.001) and significantly higher in psychological health (58.63 vs. 45.40; p=0.017) and environment (67.00 vs. 53.68; p=0.006). Conclusions. A relationship is found between empathy, social condition and perceived quality of life in people diagnosed with schizophrenia on programs of psycho-social rehabilitation. Similarly, the existence of relevant differences in these variables according to the level of severity of the clinical features is underscore

ProMeQuaLab - Projeto de Melhoria da Qualidade Laboratorial para Países de Língua Portuguesa: trabalhos realizados e em curso 2017

Apresentação sobre os trabalhos realizados e em curso no âmbito do projeto de Melhoria da Qualidade Laboratorial para Países de Língua Portuguesa (ProMeQuaLab).N/