A novel cognitive behaviour therapy for bipolar disorders (Think Effectively About Mood Swings or TEAMS): study protocol for a randomized controlled trial

BACKGROUND: Existing psychological therapies for bipolar disorders have been found to have mixed results, with a consensus that they provide a significant, but modest, effect on clinical outcomes. Typically, these approaches have focused on promoting strategies to prevent future relapse. An alternative treatment approach, termed ‘Think Effectively About Mood Swings’ (TEAMS) addresses current symptoms, including subclinical hypomania, depression and anxiety, and promotes long-term recovery. Following the publication of a theoretical model, a range of research studies testing the model and a case series have demonstrated positive results. The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial. METHODS/DESIGN: A target number of 84 patients with a diagnosis of bipolar I or II disorder, or bipolar disorder not-otherwise-specified are screened, allocated to a baseline assessment and randomized to either 16 sessions of TEAMS therapy plus treatment-as-usual (TAU) or TAU. Patients complete self-report inventories of depression, anxiety, recovery status and bipolar cognitions targeted by TEAMS. Assessments of diagnosis, bipolar symptoms, medication, access to services and quality of life are conducted by assessors blind to treatment condition at 3, 6, 12 and 18 months post-randomization. The main aim is to evaluate recruitment and retention of participants into both arms of the study, as well as adherence to therapy, to determine feasibility and acceptability. It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization. The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety, reduce bipolar cognitions, improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up. The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of TEAMS therapy that will be subject to qualitative analyses to inform future developments of the approach. DISCUSSION: The design will provide preliminary evidence of efficacy, feasibility, acceptability, uptake, attrition and barriers to treatment to design a definitive trial of this novel intervention compared to treatment as usual. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (ISRCTN83928726) on registered 25 July 2014

The Relationships Between Fluoride Intake Levels and Fluorosis of Late‐Erupting Permanent Teeth

Objectives To examine the relationships between fluoride intake levels and fluorosis of late‐erupting permanent teeth. Methods The current study used information collected from 437 children in the longitudinal Iowa Fluoride Study. Participants\u27 fluoride intake information was collected using questionnaires from birth to age 10 years. Estimated mean daily fluoride intake was categorized into low, moderate, and high intake tertiles for each age interval (2‐5, 5‐8, and 2‐8 years). Bivariate analyses were performed to study the relationships between self‐reported fluoride intake levels during three age intervals and dental fluorosis. Results For canines and second molars, the prevalence of mostly mild fluorosis was less than 10% in the lowest fluoride intake tertile and more than 25% in the highest intake tertile. For both first and second premolars, the prevalence in the low and high intake tertiles was approximately 10‐15% and 25‐40%, respectively. When estimated total daily fluoride intake was 0.04 mg/kg BW during ages 2‐8 years, the predicted probability of fluorosis was 16.0%, 20.5%, 21.8%, and 15.4% for canines, 1st and 2nd and premolars and 2nd molars, respectively. We found that an incremental increase in fluoride intake during the age 5‐ to 8‐year interval led to greater odds for development of mostly mild dental fluorosis in late‐erupting teeth compared to increases in fluoride intake during other age intervals. Conclusions Our results clearly show that dental fluorosis prevalence is closely related to fluoride intake levels and that teeth have greater susceptibility to fluoride intake during certain age intervals

An artificial therapist (manage your life online) to support the mental health of youth: Co-design and case series

Background: The prevalence of child and adolescent mental health issues is increasing faster than the number of services available, leading to a shortfall. Mental health chatbots are a highly scalable method to address this gap. Manage Your Life Online (MYLO) is an artificially intelligent chatbot that emulates the method of levels therapy. Method of levels is a therapy that uses curious questioning to support the sustained awareness and exploration of current problems. Objective: This study aimed to assess the feasibility and acceptability of a co-designed interface for MYLO in young people aged 16 to 24 years with mental health problems. Methods: An iterative co-design phase occurred over 4 months, in which feedback was elicited from a group of young people (n=7) with lived experiences of mental health issues. This resulted in the development of a progressive web application version of MYLO that could be used on mobile phones. We conducted a case series to assess the feasibility and acceptability of MYLO in 13 young people over 2 weeks. During this time, the participants tested MYLO and completed surveys including clinical outcomes and acceptability measures. We then conducted focus groups and interviews and used thematic analysis to obtain feedback on MYLO and identify recommendations for further improvements. Results: Most participants were positive about their experience of using MYLO and would recommend MYLO to others. The participants enjoyed the simplicity of the interface, found it easy to use, and rated it as acceptable using the System Usability Scale. Inspection of the use data found evidence that MYLO can learn and adapt its questioning in response to user input. We found a large effect size for the decrease in participants’ problem-related distress and a medium effect size for the increase in their self-reported tendency to resolve goal conflicts (the proposed mechanism of change) in the testing phase. Some patients also experienced a reliable change in their clinical outcome measures over the 2 weeks. Conclusions: We established the feasibility and acceptability of MYLO. The initial outcomes suggest that MYLO has the potential to support the mental health of young people and help them resolve their own problems. We aim to establish whether the use of MYLO leads to a meaningful reduction in participants’ symptoms of depression and anxiety and whether these are maintained over time by conducting a randomized controlled evaluation trial

Long-ranged attraction between charged polystyrene spheres at aqueous interfaces

We report an optical and atomic force microscopic study of interactions between charged polystyrene spheres at a water-air interface. Optical observations of bonded particle clusters and formation of circular chainlike structures at the interface demonstrate that the interaction potential is of dipole origin. Atomic force microscope phase images show patchy domains on the colloidal surface, indicating that the surface charge distribution is not uniform as is commonly believed. Such surface heterogeneity introduces inplane dipoles, leading to an attraction at short interparticle distances.Peer reviewedChemistr

Measured long-ranged attractive interaction between charged polystyrene latex spheres at a water-air interface

We report results of a systematic experimental study of interactions between charged polystyrene (PS) latex spheres at a water-air interface. Optical observations of stable bonded particle clusters and formation of circular chainlike structures at the interface demonstrate that the interaction potential is of dipole origin. Atomic force microscopy (AFM) is used to examine the distribution of charge groups on the colloidal surface. AFM phase images show patchy domains of size ~100 nm on the particle surface, indicating that the surface charge distribution of the PS spheres is not uniform, as is commonly believed. Such patchy charges can introduce fluctuating in-plane dipoles, leading to an attraction at short interparticle separations. A theoretical analysis is given to explain the mechanism for attractions between like-charged particles at the interface.Peer reviewedChemistr

Unsupervised system to classify SO2 pollutant concentrations in Salamanca, Mexico

Salamanca is cataloged as one of the most polluted cities in Mexico. In order to observe the behavior and clarify the influence of wind parameters on the Sulphur Dioxide (SO2) concentrations a Self-Organizing Maps (SOM) Neural Network have been implemented at three monitoring locations for the period from January 1 to December 31, 2006. The maximum and minimum daily values of SO2 concentrations measured during the year of 2006 were correlated with the wind parameters of the same period. The main advantages of the SOM Neural Network is that it allows to integrate data from different sensors and provide readily interpretation results. Especially, it is powerful mapping and classification tool, which others information in an easier way and facilitates the task of establishing an order of priority between the distinguished groups of concentrations depending on their need for further research or remediation actions in subsequent management steps. For each monitoring location, SOM classifications were evaluated with respect to pollution levels established by Health Authorities. The classification system can help to establish a better air quality monitoring methodology that is essential for assessing the effectiveness of imposed pollution controls, strategies, and facilitate the pollutants reduction

Barotropic Rossby waves radiating from tropical instability waves in the Pacific Ocean

Author Posting. © American Meteorological Society, 2011. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 41 (2011): 1160–1181, doi:10.1175/2011JPO4547.1.Tropical instability waves are triggered by instabilities of the equatorial current systems, and their sea level signal, with peak amplitude near 5°N, is one of the most prominent features of the dynamic topography of the tropics. Cross-spectral analysis of satellite altimetry observations shows that there is sea level variability in the Pacific Ocean as far north as Hawaii (i.e., 20°N) that is coherent with the sea level variability near 5°N associated with tropical instability waves. Within the uncertainty of the analysis, this off-equatorial variability obeys the dispersion relation for nondivergent, barotropic Rossby waves over a fairly broad range of periods (26–38 days) and zonal wavelengths (9°–23° of longitude) that are associated with tropical instability waves. The dispersion relation and observed wave properties further suggest that the waves are carrying energy away from the instabilities toward the North Pacific subtropical gyre, which, together with the observed coherence of the sea level signal of the barotropic waves with that of the tropical instability waves, suggests that the barotropic Rossby waves are being radiated from the tropical instability waves. The poleward transport of kinetic energy and westward momentum by these barotropic Rossby waves may influence the circulation in the subtropics.Funding for this research came from WHOI’s TropicalResearch Initiative, the Charles D. Hollister Fund for Assistant Scientist Support, the John E. and Anne W. Sawyer Endowed Fund in Special Support of Scientific Staff, and Grant OCE-0845150 from the National Science Foundation

Mechanisms of congenital heart disease caused by NAA15 haploinsufficiency

Rationale: NAA15 is a component of the N-terminal (Nt) acetyltransferase complex, NatA. The mechanism by which NAA15 haploinsufficiency causes congenital heart disease (CHD) remains unknown. To better understand molecular processes by which NAA15 haploinsufficiency perturbs cardiac development, we introduced NAA15 variants into human induced pluripotent stem cells (iPSCs) and assessed the consequences of these mutations on RNA and protein expression. Objective: We aim to understand the role of NAA15 haploinsufficiency in cardiac development by investigating proteomic effects on NatA complex activity, and identifying proteins dependent upon a full amount of NAA15. Methods and Results: We introduced heterozygous LoF, compound heterozygous and missense residues (R276W) in iPS cells using CRISPR/Cas9. Haploinsufficient NAA15 iPS cells differentiate into cardiomyocytes, unlike NAA15-null iPS cells, presumably due to altered composition of NatA. Mass spectrometry (MS) analyses reveal ~80% of identified iPS cell NatA targeted proteins displayed partial or complete Nt-acetylation. Between null and haploinsufficient NAA15 cells Nt-acetylation levels of 32 and 9 NatA-specific targeted proteins were reduced, respectively. Similar acetylation loss in few proteins occurred in NAA15 R276W iPSCs. In addition, steady-state protein levels of 562 proteins were altered in both null and haploinsufficient NAA15 cells; eighteen were ribosomal-associated proteins. At least four proteins were encoded by genes known to cause autosomal dominant CHD. Conclusions: These studies define a set of human proteins that requires a full NAA15 complement for normal synthesis and development. A 50% reduction in the amount of NAA15 alters levels of at least 562 proteins and Nt-acetylation of only 9 proteins. One or more modulated proteins are likely responsible for NAA15-haploinsufficiency mediated CHD. Additionally, genetically engineered iPS cells provide a platform for evaluating the consequences of amino acid sequence variants of unknown significance on NAA15 function