Development of an integrated cognitive behavioral therapy for anxiety and opioid use disorder: Study protocol and methods

Opioid use disorder is a highly disabling psychiatric disorder, and is associated with both significant functional disruption and risk for negative health outcomes such as infectious disease and fatal overdose. Even among those who receive evidence-based pharmacotherapy for opioid use disorder, many drop out of treatment or relapse, highlighting the importance of novel treatment strategies for this population. Over 60% of those with opioid use disorder also meet diagnostic criteria for an anxiety disorder; however, efficacious treatments for this common co-occurrence have not be established. This manuscript describes the rationale and methods for a behavioral treatment development study designed to develop and test an integrated cognitive-behavioral therapy for those with co-occurring opioid use disorder and anxiety disorders. The aims of the study are (1) to develop and pilot test a new manualized cognitive behavioral therapy for co-occurring opioid use disorder and anxiety disorders, (2) to test the efficacy of this treatment relative to an active comparison treatment that targets opioid use disorder alone, and (3) to investigate the role of stress reactivity in both prognosis and recovery from opioid use disorder and anxiety disorders. Our overarching aim is to investigate whether this new treatment improves both anxiety and opioid use disorder outcomes relative to standard treatment. Identifying optimal treatment strategies for this population are needed to improve outcomes among those with this highly disabling and life-threatening disorder.This study was funded by NIDA grant DA035297. The funding source had no involvement in the study design, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. (DA035297 - NIDA)Accepted manuscrip

IOME, A Toolkit for Distributed and Collaborative Computational Science and Engineering

The internet provides a media rich communications platform enabling communities to share content. Alongside the increased activity in collaborative work, recent developments on workflow tools are now enabling researchers from different disciplines to collaborate by feeding data and results between large multi-disciplinary, optimization problems. Researchers developing computational models require development kits and tools enabling them to provide simulations with a range of methods that facilitate collaboration. This paper presents a unique, multi-purpose tool-kit, enabling researchers to easily develop simulations which may be run as web services and accessed interactively. The development kit is based on a protocol that uses an XML markup called IOME ML, "the Interactive Object Management Environment Markup Language". The paper describes the IOME ML and it's development kit. We illustrate the capabilities of IOME with two case studies. Firstly, a medical image processing application which is wrapped as a web service and accessed through a web browser offering medical professionals image analysis tools. Secondly, a method of collaborative visualisation and computational steering of a tsunami simulation based on a shallow water wave model. The paper concludes with a review of further developments including refinements to the mark up language and the development of a service factory enabling dynamic invocation of published simulations as IOME web service applications

Body representation difficulties in children and adolescents with autism may be due to delayed development of visuo-tactile temporal binding

Recent research suggests visuo-tactile binding is temporally extended in autism spectrum disorders (ASD), although it is not clear whether this specifically underlies altered body representation in this population. In the current study children and adolescents with ASD, and typically developing controls, placed their hand into mediated reality system (MIRAGE) and saw two identical live video images of their own right hand. One image was in the proprioceptively correct location (veridical hand) and the other was displaced to either side. While visuotactile feedback was applied via brushstroke to the participant’s (unseen) right finger, they viewed one hand image receiving synchronous brushstrokes and the other receiving brushstrokes with a temporal delay (60, 180 and 300ms). After brushing, both images disappeared from view and participants pointed to a target, with direction of movement indicating which hand was embodied. ASD participants, like younger mental aged-matched controls, showed reduced embodiment of the spatially incongruent, but temporally incongruent, hand compared to chronologically age-matched controls at shorter temporal delays. This suggests development of visuo-tactile integration may be delayed in ASD. Findings are discussed in relation to atypical body representation in ASD and how this may contribute to social and sensory difficulties within this population

What’s Worth Talking About? Information Theory Reveals How Children Balance Informativeness and Ease of Production

Of all the things we could say, what determines what is worth saying? Greenfield’s principle of informativeness states that, right from the onset of language, humans selectively comment on whatever they find unexpected. We quantify this tendency using information theoretic measures, and test the counterintuitive prediction that children will produce words that are low frequency given the context because these will be most informative. Using corpora of child directed speech, we identified adjectives that varied in how informative (i.e., unexpected) they were given the noun they modified. Three-year-olds (N=31, replication N=13) heard an experimenter use these adjectives to describe pictures. The children’s task was then to describe the pictures to another person. As the information content of the experimenter’s adjective increased, so did children’s tendency to comment on the feature that adjective had encoded. Furthermore, our analyses suggest that children balance this informativeness with a competing drive to ease production

Intrathecal B-cell activation in LGI1 antibody encephalitis.

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies

Sexually dimorphic expression of secreted frizzled-related (SFRP) genes in the developing mouse Mullerian duct

In developing male embryos, the female reproductive tract primordia (Müllerian ducts) regress due to the production of testicular anti-Müllerian hormone (AMH). Because of the association between secreted frizzled-related proteins (SFRPs) and apoptosis, their reported developmental expression patterns and the role of WNT signaling in female reproductive tract development, we examined expression of Sfrp2 and Sfrp5 during development of the Müllerian duct in male (XY) and female (XX) mouse embryos. We show that expression of both Sfrp2 and Sfrp5 is dynamic and sexually dimorphic. In addition, the male-specific expression observed for both genes prior to the onset of regression is absent in mutant male embryos that fail to undergo Müllerian duct regression. We identified ENU-induced point mutations in Sfrp5 and Sfrp2 that are predicted to severely disrupt the function of these genes. Male embryos and adults homozygous for these mutations, both individually and in combination, are viable and apparently fertile with no overt abnormalities of reproductive tract development

Linearization of Cohomology-free Vector Fields

We study the cohomological equation for a smooth vector field on a compact manifold. We show that if the vector field is cohomology free, then it can be embedded continuously in a linear flow on an Abelian group

Carbohydrate restriction for glycemic control in Type 2 diabetes : a systematic review and meta-analysis

Aim To conduct a systematic review and meta‐analysis to evaluate the effect of carbohydrate restriction on glycaemic control in Type 2 diabetes. Methods We searched Medline, EMBASE and CINAHL for the period between 1976 and April 2018. We included randomized controlled trials comparing carbohydrate restriction with a control diet which aimed to maintain or increase carbohydrate intake, and that reported HbA1c as an outcome and reported the amount of carbohydrate consumed during or at the end of the study, with outcomes reported at ≥3 months. Results We identified 1402 randomized controlled trials, 25 of which met the inclusion criteria, incorporating 2132 participants for the main outcome. Definitions of low carbohydrate varied among the studies. The pooled effect estimate from meta‐analysis was a weighted mean difference of –0.09% [95% CI –0.27, 0.08 (P = 0.30); I2 72% (P <0.001)], suggesting no effect on HbA1c of restricting the quantity of carbohydrate. A subgroup analysis of diets containing 50–130 g carbohydrate resulted in a pooled effect estimate of –0.49% [95% CI –0.75, –0.23 (P <0.001); I2 0% (P = 0.56)], suggesting a clinically and statistically significant effect on HbA1c in favour of low‐carbohydrate diets in studies of ≤6 months’ duration. Conclusions There was no overall pooled effect on HbA1c in favour of restricting carbohydrate; however, restriction of carbohydrate to 50–130 g per day had beneficial effects on HbA1c in trials up to 6 months. Future randomized controlled trials should be of >12 months’ duration, assess pre‐study carbohydrate intake, use recognized definitions of low‐carbohydrate diets and examine reasons for non‐concordance in greater detail

Splitting of the Dipole and Spin-Dipole Resonances

Cross sections for the 90,92,94Zr(p,n) reactions were measured at energies of 79.2 and 119.4 MeV. A phenomenological model was developed to describe the variation with bombarding energy of the position of the L=1 peak observed in these and other (p,n) reactions. The model yields the splitting between the giant dipole and giant spin dipole resonances. Values of these splittings are obtained for isotopes of Zr and Sn and for 208Pb.Comment: 14 pages, 4 figure