Smartphone application for preventing depression: Study protocol for a workplace randomised controlled trial

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Depression is the leading cause of life years lost due to disability. Appropriate prevention has the potential to reduce the incidence of new cases of depression, however, traditional prevention approaches face significant scalability issues. Prevention programmes delivered by via smartphone applications provide a potential solution. The workplace is an ideal setting to roll out this form of intervention, particularly among industries that are unlikely to access traditional health initiatives and whose workplace characteristics create accessibility and portability issues. The study aims to evaluate the effectiveness of a smartphone application designed to prevent depression and improve well-being. The effectiveness of the app as a universal, selective and indicated prevention tool will also be evaluated. Methods and analysis A multicentre randomised controlled trial, to determine the effectiveness of the intervention compared with an active mood monitoring control in reducing depressive symptoms (primary outcome) and the prevalence of depression at 3 months, with secondary outcomes assessing well-being and work performance. Employees from a range of industries will be invited to participate. Participants with likely current depression at baseline will be excluded. Following baseline assessment, participants, blinded to their allocation, will be randomised to receive one of two versions of the application: headgear (a 30-day mental health intervention) or a control application (mood monitoring for 30 days). Both versions of the app contain a risk calculator to provide a measure of future risk. Analyses will be conducted within an intention-To-Treat framework using mixed modelling, with additional analyses conducted to compare the moderating effect of baseline risk level and depression symptom severity on the intervention's effectiveness. Ethics and dissemination The current trial has received ethics approval from the University of New South Wales Human Research Ethics Committee (HC17021). Study results will be disseminated through peer-reviewed journals and conferences. Trial registration number ACTRN12617000548336; Results

The early-type dwarf galaxy population of the Centaurus cluster

We present a photometric study of the early-type dwarf galaxy population of the Centaurus cluster, aiming at investigating the galaxy luminosity function (LF) and galaxy scaling relations down to the regime of galaxies with M_V~-10 mag. On deep VLT/FORS1 V- and I-band images of the central part of the cluster, we identify cluster dwarf-galaxy candidates using both morphological and surface brightness selection criteria. Photometric and structural parameters of the candidates are derived from analysis of their surface brightness profiles. Fundamental scaling relations, such as the colour-magnitude and the magnitude-surface brightness relation, are used to distinguish the cluster from the background. We find a flat LF with a slope of \alpha = -1.14 \pm 0.12 for M_V>-14 mag, when fitting a power law to the completeness-corrected galaxy number counts. When plotting the central surface brightness of a Sersic model vs. the galaxy magnitude, we find a continuous relation for magnitudes -20<M_V<-10 mag, with only the brightest core galaxies deviating from this relation, in agreement with previous studies of other clusters. In a size-luminosity diagram of early-type galaxies from a range of environments, we observe that R_eff slowly decreases with decreasing luminosity for -21<M_V<-13 mag and decreases more rapidly at fainter magnitudes. This trend continues to the ultra-faint Local Group dwarf galaxies (M_V~-4 mag). The continuous central surface brightness vs. absolute magnitude relation and the smooth relation in the size-luminosity diagram over a wide range of magnitudes are consistent with the interpretation of dwarf galaxies and more massive elliptical galaxies being one family of objects with gradually changing structural properties. The most massive core galaxies and the rare cE galaxies are the only exceptions.Comment: 14 pages, 10 figures, 4 tables, accepted for publication in A&

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

A statistical downscaling framework for environmental mapping

In recent years, knowledge extraction from data has become increasingly popular, with many numerical forecasting models, mainly falling into two major categories—chemical transport models (CTMs) and conventional statistical methods. However, due to data and model variability, data-driven knowledge extraction from high-dimensional, multifaceted data in such applications require generalisations of global to regional or local conditions. Typically, generalisation is achieved via mapping global conditions to local ecosystems and human habitats which amounts to tracking and monitoring environmental dynamics in various geographical areas and their regional and global implications on human livelihood. Statistical downscaling techniques have been widely used to extract high-resolution information from regional-scale variables produced by CTMs in climate model. Conventional applications of these methods are predominantly dimensional reduction in nature, designed to reduce spatial dimension of gridded model outputs without loss of essential spatial information. Their downside is twofold—complete dependence on unlabelled design matrix and reliance on underlying distributional assumptions. We propose a novel statistical downscaling framework for dealing with data and model variability. Its power derives from training and testing multiple models on multiple samples, narrowing down global environmental phenomena to regional discordance through dimensional reduction and visualisation. Hourly ground-level ozone observations were obtained from various environmental stations maintained by the US Environmental Protection Agency, covering the summer period (June–August 2005). Regional patterns of ozone are related to local observations via repeated runs and performance assessment of multiple versions of empirical orthogonal functions or principal components and principal fitted components via an algorithm with fully adaptable parameters. We demonstrate how the algorithm can be extended to weather-dependent and other applications with inherent data randomness and model variability via its built-in interdisciplinary computational power that connects data sources with end-users

D-brane potentials in the warped resolved conifold and natural inflation

In this paper we obtain a model of Natural Inflation from string theory with a Planckian decay constant. We investigate D-brane dynamics in the background of the warped resolved conifold (WRC) throat approximation of Type IIB string compactifications on Calabi-Yau manifolds. When we glue the throat to a compact bulk Calabi-Yau, we generate a D-brane potential which is a solution to the Laplace equation on the resolved conifold. We can exactly solve this equation, including dependence on the angular coordinates. The solutions are valid down to the tip of the resolved conifold, which is not the case for the more commonly used deformed conifold. This allows us to exploit the effect of the warping, which is strongest at the tip. We inflate near the tip using an angular coordinate of a D5-brane in the WRC which has a discrete shift symmetry, and feels a cosine potential, giving us a model of Natural Inflation, from which it is possible to get a Planckian decay constant whilst maintaining control over the backreaction. This is because the decay constant for a wrapped brane contains powers of the warp factor, and so can be made large, while the wrapping parameter can be kept small enough so that backreaction is under control.Comment: 41 pages, 3 appendices, 1 figure, PDFLaTex; various clarifications added along with a new appendix on b-axions and wrapped D5 branes;version matches the one published in JHE

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

Large Scale Structure of the Universe

Galaxies are not uniformly distributed in space. On large scales the Universe displays coherent structure, with galaxies residing in groups and clusters on scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space, known as voids, contain very few galaxies and span the volume in between these structures. This observed large scale structure depends both on cosmological parameters and on the formation and evolution of galaxies. Using the two-point correlation function, one can trace the dependence of large scale structure on galaxy properties such as luminosity, color, stellar mass, and track its evolution with redshift. Comparison of the observed galaxy clustering signatures with dark matter simulations allows one to model and understand the clustering of galaxies and their formation and evolution within their parent dark matter halos. Clustering measurements can determine the parent dark matter halo mass of a given galaxy population, connect observed galaxy populations at different epochs, and constrain cosmological parameters and galaxy evolution models. This chapter describes the methods used to measure the two-point correlation function in both redshift and real space, presents the current results of how the clustering amplitude depends on various galaxy properties, and discusses quantitative measurements of the structures of voids and filaments. The interpretation of these results with current theoretical models is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets, Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume editor W. C. Keel, v2 includes additional references, updated to match published versio

Intraoperative blood pressure changes as a risk factor for anastomotic leakage in colorectal surgery

Anastomotic leakage is a serious complication after colorectal surgery. Pre- and intraoperative factors may contribute to failure of colorectal anastomosis. In this study we have tried to determine risk factors for anastomotic leakage, with special emphasis on intraoperative blood pressure changes. During a 24-month period, patients receiving a colorectal anastomosis were prospectively evaluated. For each patient preoperative characteristics, intraoperative adverse events and surgical outcome data were collected. Blood pressure changes were calculated as a relative decrease (> 25% and > 40%) from preoperative baseline values. During the study period, 285 patients underwent colorectal surgery with an anastomosis. Fifteen patients developed an anastomotic leakage (5.3%). All patients who developed a leakage had a left-sided procedure (P 40% decrease in diastolic blood pressure (P = 0.049)] were identified as univariate risk factors for anastomotic leakage. The development of an anastomotic leakage after colorectal surgery is related to surgical, patient and anaesthetic risk factors. A high preoperative diastolic blood pressure and profound intraoperative hypotension combined with complex surgery, marked by a blood loss of a parts per thousand yen250 mL and the occurrence of intraoperative adverse events, is associated with an increased risk of developing anastomotic leakag