Effects of Thermo-mechanical Loading From In-situ Studies of EB-PVD Thermal Barrier Coatings

The thermo-mechanical effects on the strain evolution within an EB-PVD thermal barrier coating (TBC) is presented in this work using in-situ characterization. Synchrotron X-ray diffraction at sector 1-ID at the Argonne National Laboratory provided both qualitative and quantitative in-situ data on the strain evolution under a thermal cycle with mechanical loading. The results show that at a critical combination of temperature and load, the stress in the thermally grown oxide (TGO) layer in the TBC reaches a tensile region. These significant findings enhance existing literature showing purely compressive strains within the TGO where mechanical loads have been neglected. The results have important implications on the effects on the overall life of the coating. Depth resolved quantitative strain is presented as contour plots over a thermal cycle highlighting the complementary strains in the adjacent layers including the bond coat and the TBC with time and temperature. Systematic identification of the appropriate peaks within the multi-layer TBC system provides guidelines for future strain studies using high energy X-rays. Piezospectroscopic studies with applied mechanical loading are further presented as verification of the room temperature XRD data for future development of the method as an operational technique to be used outside the laboratory environment

Transcriptional profiling of the epigenetic regulator Smchd1

Available online 31 December 2015Smchd1 is an epigenetic repressor with important functions in healthy cellular processes and disease. To elucidate its role in transcriptional regulation, we performed two independent genome-wide RNA-sequencing studies comparing wild-type and Smchd1 null samples in neural stem cells and lymphoma cell lines. Using an R-based analysis pipeline that accommodates observational and sample-specific weights in the linear modeling, we identify key genes dysregulated by Smchd1 deletion such as clustered protocadherins in the neural stem cells and imprinted genes in both experiments. Here we provide a detailed description of this analysis, from quality control to read mapping and differential expression analysis. These data sets are publicly available from the Gene Expression Omnibus database (accession numbers GSE64099 and GSE65747).Ruijie Liu, Kelan Chen, Natasha Jansz, Marnie E. Blewitt, Matthew E. Ritchi

Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing

Background: The presence of histone 3 lysine 9 (H3K9) methylation on the mouse inactive X chromosome has been controversial over the last 15 years, and the functional role of H3K9 methylation in X chromosome inactivation in any species has remained largely unexplored. Results: Here we report the first genomic analysis of H3K9 di- and tri-methylation on the inactive X: we find they are enriched at the intergenic, gene poor regions of the inactive X, interspersed between H3K27 tri-methylation domains found in the gene dense regions. Although H3K9 methylation is predominantly non-genic, we find that depletion of H3K9 methylation via depletion of H3K9 methyltransferase Set domain bifurcated 1 (Setdb1) during the establishment of X inactivation, results in failure of silencing for around 150 genes on the inactive X. By contrast, we find a very minor role for Setdb1-mediated H3K9 methylation once X inactivation is fully established. In addition to failed gene silencing, we observed a specific failure to silence X-linked long-terminal repeat class repetitive elements. Conclusions: Here we have shown that H3K9 methylation clearly marks the murine inactive X chromosome. The role of this mark is most apparent during the establishment phase of gene silencing, with a more muted effect on maintenance of the silent state. Based on our data, we hypothesise that Setdb1-mediated H3K9 methylation plays a role in epigenetic silencing of the inactive X via silencing of the repeats, which itself facilitates gene silencing through alterations to the conformation of the whole inactive X chromosome.Andrew Keniry, Linden J. Gearing, Natasha Jansz, Joy Liu, Aliaksei Z. Holik, Peter F. Hickey, Sarah A. Kinkel, Darcy L. Moore, Kelsey Breslin, Kelan Chen, Ruijie Liu, Catherine Phillips, Miha Pakusch, Christine Biben, Julie M. Sheridan, Benjamin T. Kile, Catherine Carmichael, Matthew E. Ritchie, Douglas J. Hilton and Marnie E. Blewit

Interlaboratory comparison of sample preparation methods, database expansions, and cutoff values for identification of yeasts by matrix-assisted laser desorption ionization-time of flight mass spectrometry using a yeast test panel

An interlaboratory study using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) to determine the identification of clinically important yeasts (n35) was performed at 11 clinical centers, one company, and one reference center using the Bruker Daltonics MALDI Biotyper system. The optimal cutoff for the MALDI-TOF MS score was investigated using receiver operating characteristic (ROC) curve analyses. The percentages of correct identifications were compared for different sample preparation methods and different databases. Logistic regression analysis was performed to analyze the association between the number of spectra in the database and the percentage of strains that were correctly identified. A total of 5,460 MALDI-TOF MS results were obtained. Using all results, the area under the ROC curve was 0.95 (95% confidence interval [CI], 0.94 to 0.96). With a sensitivity of 0.84 and a specificity of 0.97, a cutoff value of 1.7 was considered optimal. The overall percentage of correct identifications (formic acid-ethanol extraction method, score>1.7) was 61.5% when the commercial Bruker Daltonics database (BDAL) was used, and it increased to 86.8% by using an extended BDAL supplemented with a Centraalbureau voor Schimmelcultures (CBS)-KNAW Fungal Biodiversity Centre in-house database (BDALCBS in-house). A greater number of main spectra (MSP) in the database was associated with a higher percentage of correct identifications (odds ratio [OR], 1.10; 95% CI, 1.05 to 1.15; P<0.01). The results from the direct transfer method ranged from 0% to 82.9% correct identifications, with the results of the top four centers ranging from 71.4% to 82.9% correct identifications. This study supports the use of a cutoff value of 1.7 for the identification of yeasts using MALDI-TOF MS. The inclusion of enough isolates of the same species in the database can enhance the proportion of correctly identified strains. Further optimization of the preparation methods, especially of the direct transfer method, may contribute to improved diagnosis of yeast-related infections

Scholars’ open debate paper on the World Health Organization ICD-11 gaming disorder proposal

Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world

The pre-history of health psychology in the UK: From natural science and psychoanalysis to social science, social cognition and beyond

Health psychology formally came of age in the United Kingdom in the 1980s, but it was prefigured by much discussion about challenges to the dominance of biomedicine in healthcare and debates. This articles focuses on what could be termed the pre-history of health psychology in the UK. This was the period in the earlier 20th century when psychological approaches were dominated by psychoanalysis which was followed by behaviourism and then cognitivism. Review of this pre-history provides the backdrop for the rise of health psychology in the UK and also reveals the tensions between the different theoretical perspectives

A weak scientific basis for gaming disorder: let us err on the side of caution

We greatly appreciate the care and thought that is evident in the 10 commentaries that discuss our debate paper, the majority of which argued in favor of a formalized ICD-11 gaming disorder. We agree that there are some people whose play of video games is related to life problems. We believe that understanding this population and the nature and severity of the problems they experience should be a focus area for future research. However, moving from research construct to formal disorder requires a much stronger evidence base than we currently have. The burden of evidence and the clinical utility should be extremely high, because there is a genuine risk of abuse of diagnoses. We provide suggestions about the level of evidence that might be required: transparent and preregistered studies, a better demarcation of the subject area that includes a rationale for focusing on gaming particularly versus a more general behavioral addictions concept, the exploration of non-addiction approaches, and the unbiased exploration of clinical approaches that treat potentially underlying issues, such as depressive mood or social anxiety first. We acknowledge there could be benefits to formalizing gaming disorder, many of which were highlighted by colleagues in their commentaries, but we think they do not yet outweigh the wider societal and public health risks involved. Given the gravity of diagnostic classification and its wider societal impact, we urge our colleagues at the WHO to err on the side of caution for now and postpone the formalization