Daily electronic monitoring of subjective and objective measures of illness activity in bipolar disorder using smartphones--the MONARCA II trial protocol: a randomized controlled single-blind parallel-group trial

BACKGROUND: Patients with bipolar disorder often show decreased adherence with mood stabilizers and frequently interventions on prodromal depressive and manic symptoms are delayed. Recently, the MONARCA I randomized controlled trial investigated the effect of electronic self-monitoring using smartphones on depressive and manic symptoms. The findings suggested that patients using the MONARCA system had more sustained depressive symptoms than patients using a smartphone for normal communicative purposes, but had fewer manic symptoms during the trial. It is likely that the ability of these self-monitored measures to detect prodromal symptoms of depression and mania may be insufficient compared to automatically generated objective data on measures of illness activity such as phone usage, social activity, physical activity, and mobility. The Monsenso system, for smartphones integrating subjective and objective measures of illness activity was developed and will be tested in the present trial. METHODS: The MONARCA II trial uses a randomized controlled single-blind parallel-group design. Patients with bipolar disorder according to ICD-10 who previously have been treated at the Copenhagen Clinic for Affective Disorder, Denmark are included and randomized to either daily use of the Monsenso system including an feedback loop between patients and clinicians (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for a 9-month trial period. The trial was started in September 2014 and recruitment is ongoing. The outcomes are: differences in depressive and manic symptoms; rate of depressive and manic episodes (primary); automatically generated objective data on measures of illness activity; number of days hospitalized; psychosocial functioning (secondary); perceived stress; quality of life; self-rated depressive symptoms; self-rated manic symptoms; recovery; empowerment and adherence to medication (tertiary) between the intervention group and the control group during the trial. Ethical permission has been obtained. Positive, neutral and negative findings will be published. DISCUSSION: If the system is effective in reducing depressive and/or manic symptoms (and other symptoms of bipolar disorder) and the rate of episodes, there will be basis for extending the use to the treatment of bipolar disorder in general and in larger scale. TRIAL REGISTRATION: ClinicalTrials.gov NCT02221336. Registered 26(th) of September 2014

A simple deterministic self-organized critical system

We introduce a new continuous cellular automaton that presents self-organized criticality. It is one-dimensional, totally deterministic, without any kind of embedded randomness, not even in the initial conditions. This system is in the same universality class as the Oslo rice pile system, boundary driven interface depinning and the train model for earthquakes. Although the system is chaotic, in the thermodynamic limit chaos occurs only in a microscopic level.Comment: System slightly modified. New results on Liapunov exponents. Submitted for publication (8 pages

Social Learning in Horses—Fact or Fiction?

Prima facie, the acquisition of novel behaviors in animals through observation of conspecifics seems straightforward. There are, however, various mechanisms through which the behavior of animals can be altered from observing others. These mechanisms range from simple hard-wired contagious processes to genuine learning by observation, which differ fundamentally in cognitive complexity. They range from social facilitation and local enhancement to true social learning. The different learning mechanisms are the subject of this review, largely because research on learning by observation can be confounded by difficulties in interpretation owing to the looming possibility of associative learning infecting experimental results. While it is often assumed that horses are capable of acquiring new behavior through intra-species observation, research on social learning in horses includes a variety of studies some of which may overestimate the possession of higher mental abilities. Assuming such abilities in their absence can have welfare implications, e.g., isolating stereotypical horses on the assumption that these behaviors can be learned though observation by neighboring horses. This review summarizes the definitions and criteria for the various types of social transmission and social learning and reviews the current documentation for each type in horses with the aim of clarifying whether horses possess the ability to learn through true social learning. As social ungulates, horses evolved in open landscapes, exposed to predators and grazing most of the day. Being in close proximity to conspecifics may theoretically offer an opportunity to learn socially, however anti-predator vigilance and locating forage may not require the neural complexity of social learning. Given the significant energetic expense of brain tissue, it is likely that social facilitation and local enhancement may have been sufficient in the adaptation of equids to their niche. As a consequence, social learning abilities may be maladaptive in horses. Collectively, the review proposes a novel differentiation between social transmission (social facilitation, local, and stimulus enhancement) and social learning (goal emulation, imitation). Horses are undoubtedly sensitive to intra-species transfer of information but this transfer does not appear to satisfy the criteria for social learning, and thus there is no solid evidence for true social learning in horses

Genetic and environmental determinants of O6-methylguanine DNA-methyltransferase (MGMT) gene methylation: a 10-year longitudinal study of Danish twins

Background: Epigenetic inactivation of O6-methylguanine DNA-methyltransferase (MGMT) is associated with increased sensitivity to alkylating chemotherapeutic agents in glioblastoma patients. The genetic background underlying MGMT gene methylation may explain individual differences in treatment response and provide a clue to a personalized treatment strategy. Making use of the longitudinal twin design, we aimed, for the first time, to estimate the genetic contributions to MGMT methylation in a Danish twin cohort. Methods: DNA-methylation from whole blood (18 monozygotic (MZ) and 25 dizygotic (DZ) twin pairs) repeated 10 years apart from the Longitudinal Study of Aging Danish Twins (LSADT) were used to search for genetic and environmental contributions to DNA-methylation at 170 CpG sites of across the MGMT gene. Both univariate and bivariate twin models were applied. The intraclass correlations, performed on cross-sectional data (246 MZ twin pairs) from an independent study population, the Middle-Aged Danish Twins (MADT), were used to assess the genetic influence at each CpG site of MGMT for replication. Results: Univariate twin model revealed twelve CpG sites showing significantly high heritability at intake (wave 1, h2 > 0.43), and seven CpG sites with significant heritability estimates at end of follow-up (wave 2, h2 > 0.5). There were six significant CpG sites, located at the gene body region, that overlapped among the two waves (h2 > 0.5), of which five remained significant in the bivariate twin model, which was applied to both waves. Within MZ pair correlation in these six CpGs from MADT demarks top level of genetic influence. There were 11 CpGs constantly have substantial common environmental component over the 10 years. Conclusions: We have identified 6 CpG sites linked to the MGMT gene with strong and persistent genetic control based on their DNA methylation levels. The genetic basis of MGMT gene methylation could help to explain individual differences in glioblastoma treatment response and most importantly, provide references for mapping the methylation Quantitative Trait Loci (meQTL) underlying the genetic regulation.Peer reviewe

Doubling the mobility of InAs/InGaAs selective area grown nanowires

Selective area growth (SAG) of nanowires and networks promise a route toward scalable electronics, photonics, and quantum devices based on III-V semiconductor materials. The potential of high-mobility SAG nanowires however is not yet fully realised, since interfacial roughness, misfit dislocations at the nanowire/substrate interface and nonuniform composition due to material intermixing all scatter electrons. Here, we explore SAG of highly lattice-mismatched InAs nanowires on insulating GaAs(001) substrates and address these key challenges. Atomically smooth nanowire/substrate interfaces are achieved with the use of atomic hydrogen (a-H) as an alternative to conventional thermal annealing for the native oxide removal. The problem of high lattice mismatch is addressed through an InxGa1-xAs buffer layer introduced between the InAs transport channel and the GaAs substrate. The Ga-In material intermixing observed in both the buffer layer and the channel is inhibited via careful tuning of the growth temperature. Performing scanning transmission electron microscopy and x-ray diffraction analysis along with low-temperature transport measurements we show that optimized In-rich buffer layers promote high-quality InAs transport channels with the field-effect electron mobility over 10 000 cm2 V-1 s-1. This is twice as high as for nonoptimized samples and among the highest reported for InAs selective area grown nanostructures.The project was supported by Microsoft Quantum, the European Research Council (ERC) under Grant No. 716655 (HEMs-DAM), and the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant No. 722176. The authors acknowledge Dr. Keita Ohtani for technical support and fruitful discussions. D.V.B. is grateful to Dr. Juan-Carlos Estrada Saldaña for careful reading of the manuscript. The authors thank Francesco Montalenti, Marco Albani and Leo Miglio for scientific discussions. ICN2 acknowledges funding from Generalitat de Catalunya 2017 SGR 327. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya. Part of the present work has been performed in the framework of Universitat Autònoma de Barcelona Materials Science Ph.D. program. The HAADF-STEM microscopy was conducted in the Laboratorio de Microscopias Avanzadas at Instituto de Nanociencia de Aragon-Universidad de Zaragoza. M.C.S. has received funding from the European Unionâs Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 754510 (PROBIST). The funding agency is Consejo Superior de Investigaciones Científicas (CSIC) and the project reference is “Research Platform on Quantum Technologies PTI-001”

Hard X-Ray emission from Sh 2-104: a NuSTAR search for Gamma-Ray counterparts

We present NuSTAR hard X-ray observations of Sh 2-104, a compact H ii region containing several young massive stellar clusters (YMSCs). We have detected distinct hard X-ray sources coincident with localized VERITAS TeV emission recently resolved from the giant gamma-ray complex MGRO J2019+37 in the Cygnus region. Fainter, diffuse X-rays coincident with the eastern YMSC in Sh2-104 likely result from the colliding winds of a component star. Just outside the radio shell of Sh 2-104 lies 3XMM J201744.7+365045 and a nearby nebula, NuSTAR J201744.3+364812, whose properties are most consistent with extragalactic objects. The combined XMM-Newton and NuSTAR spectrum of 3XMM J201744.7+365045 is well-fit to an absorbed power-law model with ${N}_{{\rm{H}}}=(3.1\pm 1.0)\times {10}^{22}$ cm−2 and a photon index ${\rm{\Gamma }}=2.1\pm 0.1$. Based on possible long-term flux variation and the lack of detected pulsations (≤43% modulation), this object is likely a background active galactic nucleus rather than a Galactic pulsar. The spectrum of the NuSTAR nebula shows evidence of an emission line at E = 5.6 keV, suggesting an optically obscured galaxy cluster at z = 0.19 ± 0.02 (d = 800 Mpc) and L X = 1.2 × 1044 erg s−1. Follow-up Chandra observations of Sh 2-104 will help identify the nature of the X-ray sources and their relation to MGRO J2019+37. We also show that the putative VERITAS excess south of Sh 2-104, is most likely associated with the newly discovered Fermi pulsar PSR J2017+3625 and not the H ii region

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure