Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD.

OBJECTIVE: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). METHOD: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. RESULTS: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (α > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. CONCLUSION: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment

Developing Digital Tools for Remote Clinical Research:How to Evaluate the Validity and Practicality of Active Assessments in Field Settings

The ability of remote research tools to collect granular, high-frequency data on symptoms and digital biomarkers is an important strength because it circumvents many limitations of traditional clinical trials and improves the ability to capture clinically relevant data. This approach allows researchers to capture more robust baselines and derive novel phenotypes for improved precision in diagnosis and accuracy in outcomes. The process for developing these tools however is complex because data need to be collected at a frequency that is meaningful but not burdensome for the participant or patient. Furthermore, traditional techniques, which rely on fixed conditions to validate assessments, may be inappropriate for validating tools that are designed to capture data under flexible conditions. This paper discusses the process for determining whether a digital assessment is suitable for remote research and offers suggestions on how to validate these novel tools

A comparison of machine learning methods for classification using simulation with multiple real data examples from mental health studies

Background: Recent literature on the comparison of machine learning methods has raised questions about the neutrality, unbiasedness and utility of many comparative studies. Reporting of results on favourable datasets and sampling error in the estimated performance measures based on single samples are thought to be the major sources of bias in such comparisons. Better performance in one or a few instances does not necessarily imply so on an average or on a population level and simulation studies may be a better alternative for objectively comparing the performances of machine learning algorithms. Methods: We compare the classification performance of a number of important and widely used machine learning algorithms, namely the Random Forests (RF), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA) and k-Nearest Neighbour (kNN). Using massively parallel processing on high-performance supercomputers, we compare the generalisation errors at various combinations of levels of several factors: number of features, training sample size, biological variation, experimental variation, effect size, replication and correlation between features. Results: For smaller number of correlated features, number of features not exceeding approximately half the sample size, LDA was found to be the method of choice in terms of average generalisation errors as well as stability (precision) of error estimates. SVM (with RBF kernel) outperforms LDA as well as RF and kNN by a clear margin as the feature set gets larger provided the sample size is not too small (at least 20). The performance of kNN also improves as the number of features grows and outplays that of LDA and RF unless the data variability is too high and/or effect sizes are too small. RF was found to outperform only kNN in some instances where the data are more variable and have smaller effect sizes, in which cases it also provide more stable error estimates than kNN and LDA. Applications to a number of real datasets supported the findings from the simulation study

A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease

Peer reviewedPublisher PD

Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

<p>Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.</p> <p>Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.</p> <p>Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS</p&gt

Testing the association between tobacco and cannabis use and cognitive functioning: findings from an observational and Mendelian randomization study

Background Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures assessed on five occasions from age 13–18 in a large UK population cohort (Avon Longitudinal Study of Parents and Children). Cognitive functioning measures comprised of working memory, response inhibition, and emotion recognition assessed at 24 years of age. Mendelian randomization was used to examine the possible causal relationship between smoking initiation, lifetime cannabis use and cognitive functioning. Results We found evidence of a relationship between tobacco and cannabis use and diminished cognitive functioning for each of the outcomes in the observational analyses. There was evidence to suggest that late-onset regular tobacco smokers (b=-0.29, 95 %CI=-0.45 to -0.13), early-onset regular tobacco smokers (b=-0.45, 95 %CI=-0.84 to -0.05), and early-onset regular cannabis users (b=-0.62, 95 %CI=-0.93 to -0.31) showed poorer working memory. Early-onset regular tobacco smokers (b = 0.18, 95 %CI = 0.07 to 0.28), and early-onset regular cannabis users (b = 0.30, 95 %CI = 0.08 to 0.52) displayed poorer ability to inhibit responses. Late-onset regular (b=-0.02, 95 %CI=-0.03 to - 0.00), and early-onset regular tobacco smokers (b=-0.04, 95 %CI=-0.08 to -0.01) showed poorer ability to recognise emotions. Mendelian randomization analyses were imprecise and did not provide additional support for the observational results. Conclusion There was some evidence to suggest that adolescent tobacco and cannabis use were associated with deficits in working memory, response inhibition and emotion recognition. Better powered genetic studies are required to determine whether these associations are causal

Alcohol use and cognitive functioning in young adults : improving causal inference

Background and Aims: There have been few longitudinal studies of association between alcohol use and cognitive functioning in young people. We aimed to examine whether alcohol use is a causal risk factor for deficient cognitive functioning in young adults. Design: Linear regression was used to examine the relationship between longitudinal latent class patterns of binge drinking and subsequent cognitive functioning. Two-sample Mendelian randomisation (MR) tested evidence for the causal relationship between alcohol use and cognitive functioning. Setting: South West England. Participants: The observational study included 3,155 adolescents and their parents (fully adjusted models) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Genetic instruments for alcohol use were based on almost 1,000,000 individuals from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Genome-wide association studies for cognitive outcomes were based on 2,500 individuals from ALSPAC. Measurements: Binge drinking was assessed at approximately 16, 17, 18, 21, and 23 years. Cognitive functioning comprised working memory, response inhibition, and emotion recognition assessed at 24 years of age. Ninety-nine independent genome-wide significant SNPs associated with ‘number of drinks per week’ were used as the genetic instrument for alcohol consumption. Potential confounders were included in the observational analyses. Findings: Four binge drinking classes were identified: ‘low-risk’ (41%), ‘early-onset monthly’ (19%), ‘adult frequent’ (23%), and ‘early-onset frequent’ (17%). The association between early-onset frequent binge drinking and cognitive functioning: working memory (b=0.09, 95%CI=-0.10 to 0.28), response inhibition (b=0.70, 95%CI=-10.55 to 11.95), and emotion recognition (b=0.01, 95%CI=-0.01 to 0.02) in comparison to low-risk drinkers were inconclusive as to whether a difference was present. Two-sample MR analyses similarly provided little evidence that alcohol use is associated with deficits in working memory using the inverse variance weight (b=0.29, 95%CI=-0.42 to 0.99), response inhibition (b=-0.32, 95%CI=-1.04 to 0.39), and emotion recognition (b=0.03, 95%CI=-0.55 to 0.61). Conclusions: Binge drinking in adolescence and early adulthood may not be causally related to deficiencies in working memory, response inhibition, or emotion recognition in youths

Temporal lobe surgery in childhood and neuroanatomical predictors of longterm declarative memory outcome

The temporal lobes play a prominent role in declarative memory function, including episodic memory (memory for events) and semantic memory (memory for facts and concepts). Surgical resection for medication-resistant and well-localized temporal lobe epilepsy has good prognosis for seizure freedom, but is linked to memory difficulties in adults, especially when the removal is on the left side. Children may benefit most from surgery, since brain plasticity may facilitate post-surgical reorganization, and seizure cessation may promote cognitive development. However, the long-term impact of this intervention in children is not known. We examined memory function in 53 children (25 boys, 28 girls) who were evaluated for epilepsy surgery: 42 underwent unilateral temporal lobe resections (25 left, 17 right, mean age at surgery 13.8 years), 11 were treated only pharmacologically. Average follow-up was 9 years (range 5-15). Postsurgical change in visual and verbal episodic memory, and semantic memory at follow-up were examined. Pre- and post-surgical T1-weighted MRI brain scans were analysed to extract hippocampal and resection volumes, and evaluate post-surgical temporal lobe integrity. Language lateralization indices were derived from functional magnetic resonance imaging. There were no significant pre-to post-operative decrements in memory associated with surgery. In contrast, gains in verbal episodic memory were seen after right temporal lobe surgery, and visual episodic memory improved after left temporal lobe surgery, indicating a functional release in the unoperated temporal lobe after seizure reduction or cessation. Pre-to post-surgical change in memory function was not associated with any indices of brain structure derived from MRI. However, better verbal memory at follow-up was linked to greater post-surgical residual hippocampal volumes, most robustly in left surgical participants. Better semantic memory at follow-up was associated with smaller resection volumes and greater temporal pole integrity after left temporal surgery. Results were independent of post-surgical intellectual function and language lateralization. Our findings indicate post-surgical, hemisphere-dependent materialspecific improvement in memory functions in the intact temporal lobe. However, outcome was linked to the anatomical integrity of the temporal lobe memory system, indicating that compensatory mechanisms are constrained by the amount of tissue which remains in the operated temporal lobe. Careful tailoring of resections for children undergoing epilepsy surgery may enhance long-term memory outcome