Interconnected or disconnected? Promotion of mental health and prevention of mental disorder in the digital age

To date there have been few peer-reviewed studies on the feasibility, acceptability and effectiveness of digital technologies for mental health promotion and disorder prevention. Any evaluation of these evolving technologies is complicated by a lack of understanding about the specific risks and possible benefits of the many forms of internet use on mental health. To adequately meet the mental health needs of today's society, psychiatry must engage in rigorous assessment of the impact of digital technologies

R/BHC: fast Bayesian hierarchical clustering for microarray data

BACKGROUND: Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data analysis, little attention has been paid to uncertainty in the results obtained. RESULTS: We present an R/Bioconductor port of a fast novel algorithm for Bayesian agglomerative hierarchical clustering and demonstrate its use in clustering gene expression microarray data. The method performs bottom-up hierarchical clustering, using a Dirichlet Process (infinite mixture) to model uncertainty in the data and Bayesian model selection to decide at each step which clusters to merge. CONCLUSION: Biologically plausible results are presented from a well studied data set: expression profiles of A. thaliana subjected to a variety of biotic and abiotic stresses. Our method avoids several limitations of traditional methods, for example how many clusters there should be and how to choose a principled distance metric

Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

Novel O-palmitolylated beta-E1 subunit of pyruvate dehydrogenase is phosphorylated during ischemia/reperfusion injury

<p>Abstract</p> <p>Background</p> <p>During and following myocardial ischemia, glucose oxidation rates are low and fatty acids dominate as a source of oxidative metabolism. This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized.</p> <p>Results</p> <p>2-D gel electrophoresis of mitochondria from working rat hearts subjected to 25 minutes of global no flow ischemia followed by 40 minutes of aerobic reperfusion identified 32 changes in protein abundance compared to aerobic controls. Of the five proteins with the greatest change in abundance, two were increased (long chain acyl-coenzyme A dehydrogenase (48 ± 1 versus 39 ± 3 arbitrary units, n = 3, P < 0.05) and α subunit of ATP synthase (189 ± 15 versus 113 ± 23 arbitrary units, n = 3, P < 0.05)), while two were decreased (24 kDa subunit of NADH-ubiquinone oxidoreductase (94 ± 7 versus 127 ± 9 arbitrary units, n = 3, P < 0.05) and D subunit of ATP synthase (230 ± 11 versus 368 ± 47 arbitrary units, n = 3, P < 05)). Two forms of pyruvate dehydrogenase βE1 subunit, the rate-limiting enzyme for glucose oxidation, were also identified. The protein level of the more acidic form of pyruvate dehydrogenase was reduced during reperfusion (37 ± 4 versus 56 ± 7 arbitrary units, n = 3, P < 05), while the more basic form remained unchanged. The more acidic isoform was found to be O-palmitoylated, while both isoforms exhibited ischemia/reperfusion-induced phosphorylation. <it>In silico </it>analysis identified the putative kinases as the insulin receptor kinase for the more basic form and protein kinase Cζ or protein kinase A for the more acidic form. These modifications of pyruvate dehydrogenase are associated with a 35% decrease in glucose oxidation during reperfusion.</p> <p>Conclusions</p> <p>Cardiac ischemia/reperfusion induces significant changes to a number of metabolic proteins of the mitochondrial proteome. In particular, ischemia/reperfusion induced the post-translational modification of pyruvate dehydrogenase, the rate-limiting step of glucose oxidation, which is associated with a 35% decrease in glucose oxidation during reperfusion. Therefore these post-translational modifications may have important implications in the regulation of myocardial energy metabolism.</p

Reach-scale bankfull channel types can exist independently of catchment hydrology

© 2020 John Wiley &amp; Sons, Ltd. Reach-scale morphological channel classifications are underpinned by the theory that each channel type is related to an assemblage of reach- and catchment-scale hydrologic, topographic, and sediment supply drivers. However, the relative importance of each driver on reach morphology is unclear, as is the possibility that different driver assemblages yield the same reach morphology. Reach-scale classifications have never needed to be predicated on hydrology, yet hydrology controls discharge and thus sediment transport capacity. The scientific question is: do two or more regions with quantifiable differences in hydrologic setting end up with different reach-scale channel types, or do channel types transcend hydrologic setting because hydrologic setting is not a dominant control at the reach scale? This study answered this question by isolating hydrologic metrics as potential dominant controls of channel type. Three steps were applied in a large test basin with diverse hydrologic settings (Sacramento River, California) to: (1) create a reach-scale channel classification based on local site surveys, (2) categorize sites by flood magnitude, dimensionless flood magnitude, and annual hydrologic regime type, and (3) statistically analyze two hydrogeomorphic linkages. Statistical tests assessed the spatial distribution of channel types and the dependence of channel type morphological attributes by hydrologic setting. Results yielded 10 channel types. Nearly all types existed across all hydrologic settings, which is perhaps a surprising development for hydrogeomorphology. Downstream hydraulic geometry relationships were statistically significant. In addition, cobble-dominated uniform streams showed a consistent inverse relationship between slope and dimensionless flood magnitude, an indication of dynamic equilibrium between transport capacity and sediment supply. However, most morphological attributes showed no sorting by hydrologic setting. This study suggests that median hydraulic geometry relations persist across basins and within channel types, but hydrologic influence on geomorphic variability is likely due to local influences rather than catchment-scale drivers. © 2020 John Wiley &amp; Sons, Ltd

Observation of interstellar lithium in the low-metallicity Small Magellanic Cloud

The primordial abundances of light elements produced in the standard theory of Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to photons, a quantity inferred from observations of the microwave background. The predicted primordial 7Li abundance is four times that measured in the atmospheres of Galactic halo stars. This discrepancy could be caused by modification of surface lithium abundances during the stars' lifetimes or by physics beyond the Standard Model that affects early nucleosynthesis. The lithium abundance of low-metallicity gas provides an alternative constraint on the primordial abundance and cosmic evolution of lithium that is not susceptible to the in situ modifications that may affect stellar atmospheres. Here we report observations of interstellar 7Li in the low-metallicity gas of the Small Magellanic Cloud, a nearby galaxy with a quarter the Sun's metallicity. The present-day 7Li abundance of the Small Magellanic Cloud is nearly equal to the BBN predictions, severely constraining the amount of possible subsequent enrichment of the gas by stellar and cosmic-ray nucleosynthesis. Our measurements can be reconciled with standard BBN with an extremely fine-tuned depletion of stellar Li with metallicity. They are also consistent with non-standard BBN.Comment: Published in Nature. Includes main text and Supplementary Information. Replaced with final title and abstrac

Genome-wide association studies and genetic architecture of common human diseases

Genome-wide association scans provide the first successful method to identify genetic variation contributing to risk for common complex disease. Progress in identifying genes associated with melanoma show complex relationships between genes for pigmentation and the development of melanoma. Novel risk loci account for only a small fraction of the genetic variation contributing to this and many other diseases. Large meta-analyses find additional variants, but there is current debate about the contribution of common polymorphisms, rare polymorphisms or mutations to disease risk

Protecting Clinical Trial Participants and Protecting Data Integrity: Are We Meeting the Challenges?

Susan Ellenberg discusses alternative approaches towards evaluating data as it accumulates in clinical trials, and to protecting the integrity and preventing undue risks to participants, as the trial continues

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions