The relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder: A systematic review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis explored the relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder (OCD). METHODS: We searched Pubmed, Scopus, Cochrane Library and PsychINFO databases until February 2023 for studies comparing patients with OCD and healthy controls on cognitive tests of compulsivity and impulsivity. The study followed PRISMA guidelines and was pre-registered on PROSPERO (CRD42021299017). RESULTS: Meta-analyses of 112 studies involving 8313 participants (4289 patients with OCD and 4024 healthy controls) identified significant impairments in compulsivity (g = -0.58, [95%CI -0.68, -0.47]; k = 76) and impulsivity (g = -0.48, [95%CI -0.57, -0.38]; k = 63); no significant difference between impairments. Medication use and comorbid psychiatric disorders were not significantly related to impairments. No associations were revealed with OCD severity, depression/anxiety, or illness duration. CONCLUSION: Cognitive phenotypes of compulsivity and impulsivity in patients with OCD appear to be orthogonal to clinical variables, including severity of OCD symptomatology. Their clinical impact is poorly understood and may require different clinical assessment tools and interventions.

New Genera and Species of Caulobacter and Brevundimonas Bacteriophages Provide Insights into Phage Genome Evolution.

Previous studies have identified diverse bacteriophages that infect Caulobacter vibrioides strain CB15 ranging from small RNA phages to four genera of jumbo phages. In this study, we focus on 20 bacteriophages whose genomes range from 40 to 60 kb in length. Genome comparisons indicated that these diverse phages represent six Caulobacter phage genera and one additional genus that includes both Caulobacter and Brevundimonas phages. Within species, comparisons revealed that both single base changes and inserted or deleted genetic material cause the genomes of closely related phages to diverge. Among genera, the basic gene order and the orientation of key genes were retained with most of the observed variation occurring at ends of the genomes. We hypothesize that the nucleotide sequences of the ends of these phage genomes are less important than the need to maintain the size of the genome and the stability of the corresponding mRNAs.

Meta-analysis of cognitive behaviour therapy and selective serotonin reuptake inhibitors for the treatment of hypochondriasis: Implications for trial design.

BACKGROUND: Classification of hypochondriasis as an obsessive-compulsive and related disorder in the International Classification of Diseases 11th Revision (ICD-11) has generated new heuristics for treatment of this common, chronic and disabling disorder. Standard treatment involves cognitive behaviour therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs), but no meta-analysis has so far considered hypochondriasis as a structured diagnosis or assessed the role of medication. A clearer understanding of the relative effectiveness of these interventions and identification of clinically relevant factors moderating the treatment response is needed for clinical guideline development. METHODS: The current systematic review and meta-analysis of interventions for hypochondriasis was preregistered on PROSPERO (CRD42020185768) and follows PRISMA guidelines. We searched MEDLINE, PsycINFO, and Cochrane Library databases until July 2021 for randomized controlled trials (RCTs) of interventions for patients diagnosed with hypochondriasis (or historical diagnostic equivalents). We assessed aspects of study quality using: the CONSORT Checklist for evaluation of RCTs, the Cochrane Risk of Bias 2 tool, researcher allegiance and treatment fidelity. The primary outcome was improvement in hypochondriasis symptoms, comparing intervention and control groups at trial endpoint. Moderator variables were assessed using subgroup and meta-regression analyses. RESULTS: Searches identified 13 randomised controlled trials (RCTs) (N = 1405); 12 included CBT (N = 1212) and three included SSRI (N = 193) arms as the experimental intervention. Random effects meta-analysis yielded a moderate-to-large effect size for CBT versus all controls (g = -0.70 [95% CI -0.99 to -0.41], k = 18, I2 = 81.1%). Funnel plot asymmetry indicated possible publication bias and two potentially missing trials, reducing the effect size (g = -0.60 [95% CI -0.88 to -0.32]). Subgroup analysis showed that choice of control significantly moderated effect size, with those in CBT vs. wait-list (g = -1.32 [95% CI -1.75 to -0.90], k = 7, I2 = 0%) being double those of CBT vs. psychological or pharmacological placebo controls (g = -0.58 [95% CI -0.95 to -0.22], k = 7, I2 = 82%). Analysis of studies directly comparing CBT and SSRIs found a numerical, but not statistical advantage for SSRIs (g = 0.21 [95% CI -0.46 to 0.87], k = 2, I2 = 58.34%) and a modest effect size emerged for SSRIs vs. pill placebo (g = -0.29 [95% CI -0.57 to -0.01], k = 3, I2 = 0%). Most studies (11/13) were rated as high on potential researcher allegiance bias in favour of CBT. Meta-regressions revealed that effect sizes were larger in younger participants, and smaller in better quality and more recent RCTs and those with greater CBT fidelity. CONCLUSION: CBT and SSRIs are effective in the acute treatment of hypochondriasis, with some indication that intervention at a younger age produces better outcomes for CBT. In the case of CBT, effect sizes appear to have been significantly inflated by the use of wait list controls, and researcher allegiance bias. We recommend that a definitive, adequately controlled trial, designed with respect to the methodological issues raised in this meta-analysis, is needed to determine the magnitude effects for CBT and SSRIs with confidence and the long-term effect of treatments, to inform mental health service provision for this overlooked patient group.

Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE).

BACKGROUND: Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer. OBJECTIVE: To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase. RESULTS: This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis. DISCUSSION: The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant's progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.

Individual obsessive-compulsive traits are associated with poorer adjustment to the easing of COVID-19 restrictions.

BACKGROUND: As COVID-19 restrictions ease, the public are expected to relinquish previously enforced safety behaviors and resume a more normal lifestyle. Despite these aims, our recent survey of 438 adults from the general population, during a temporary release of lockdown in the United Kingdom (July-November 2020), showed that 25% of the public find re-adjustment problematic. This was especially the case in those with a history of mental disorder and obsessive-compulsive (OC) traits and symptoms, including rigidity as measured by a neurocognitive test of attentional flexibility. To aid in identifying those most at risk, we performed a secondary analysis on the data to determine which specific OC traits were related to specific aspects of behavioral adjustment. METHODS: Correlational and multiple regression analyses were performed to determine associations between the eight individual personality traits constituting DSM-5 Obsessive-Compulsive Personality Disorder (OCPD), as measured by the self-rated Compulsive Personality Assessment Scale (CPAS) and a range of self-rated Post-Pandemic Adjustment Questionnaire items. RESULTS: Three items on the Post-Pandemic Adjustment Questionnaire correlated with individual CPAS items: 'General difficulties adjusting' correlated with perfectionism, preoccupation with details, over-conscientiousness and need for control; 'social avoidance' correlated with perfectionism and preoccupation with details; and 'disinfecting behaviors' correlated with preoccupation with details and miserliness (Pearson's r - all p < .001). Intriguingly, none of the adjustment items correlated significantly with self-rated rigidity. CONCLUSIONS: Several OCPD traits predict post-pandemic adjustment difficulties, but perfectionism and preoccupation-with-details showed the most robust correlations. These traits constitute a platform for the development of new screening and interventional strategies aimed at restoring public mental health and wellbeing. Cognitive rigidity may be more reliably evaluated using an objective form of assessment.

Helicobacter pylori Biofilm Confers Antibiotic Tolerance in Part via A Protein-Dependent Mechanism.

Helicobacter pylori, a WHO class I carcinogen, is one of the most successful human pathogens colonizing the stomach of over 4.4 billion of the world's population. Antibiotic therapy represents the best solution but poor response rates have hampered the elimination of H. pylori. A growing body of evidence suggests that H. pylori forms biofilms, but the role of this growth mode in infection remains elusive. Here, we demonstrate that H. pylori cells within a biofilm are tolerant to multiple antibiotics in a manner that depends partially on extracellular proteins. Biofilm-forming cells were tolerant to multiple antibiotics that target distinct pathways, including amoxicillin, clarithromycin, and tetracycline. Furthermore, this tolerance was significantly dampened following proteinase K treatment. These data suggest that H. pylori adapts its phenotype during biofilm growth resulting in decreased antibiotic susceptibility but this tolerance can be partially ameliorated by extracellular protease treatment.

No evidence for a common factor underlying visual abilities in healthy older people.

The world's population is aging at an increasing rate. Even in the absence of neurodegenerative disorders, healthy aging affects perception and cognition. In the context of cognition, common factors are well established. Much less is known about common factors for vision. Here, we tested 92 healthy older and 104 healthy younger participants in 19 visual tests (including visual search and contrast sensitivity) and three cognitive tests (including verbal fluency and digit span). Unsurprisingly, younger participants performed better than older participants in almost all tests. Surprisingly, however, the performance of older participants was mostly uncorrelated between visual tests, and we found no evidence for a common factor. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Beyond Bouma's window: How to explain global aspects of crowding?

In crowding, perception of an object deteriorates in the presence of nearby elements. Although crowding is a ubiquitous phenomenon, since elements are rarely seen in isolation, to date there exists no consensus on how to model it. Previous experiments showed that the global configuration of the entire stimulus must be taken into account. These findings rule out simple pooling or substitution models and favor models sensitive to global spatial aspects. In order to investigate how to incorporate global aspects into models, we tested a large number of models with a database of forty stimuli tailored for the global aspects of crowding. Our results show that incorporating grouping like components strongly improves model performance.

What to Choose Next? A Paradigm for Testing Human Sequential Decision Making.

Many of the decisions we make in our everyday lives are sequential and entail sparse rewards. While sequential decision-making has been extensively investigated in theory (e.g., by reinforcement learning models) there is no systematic experimental paradigm to test it. Here, we developed such a paradigm and investigated key components of reinforcement learning models: the eligibility trace (i.e., the memory trace of previous decision steps), the external reward, and the ability to exploit the statistics of the environment's structure (model-free vs. model-based mechanisms). We show that the eligibility trace decays not with sheer time, but rather with the number of discrete decision steps made by the participants. We further show that, unexpectedly, neither monetary rewards nor the environment's spatial regularity significantly modulate behavioral performance. Finally, we found that model-free learning algorithms describe human performance better than model-based algorithms.

About individual differences in vision.

In cognition, audition, and somatosensation, performance strongly correlates between different paradigms, which suggests the existence of common factors. In contrast, visual performance in seemingly very similar tasks, such as visual and bisection acuity, are hardly related, i.e., pairwise correlations between performance levels are low even though test-retest reliability is high. Here we show similar results for visual illusions. Consistent with previous findings, we found significant correlations between the illusion magnitude of the Ebbinghaus and Ponzo illusions, but this relationship was the only significant correlation out of 15 further comparisons. Similarly, we found a significant link for the Ponzo illusion with both mental imagery and cognitive disorganization. However, most other correlations between illusions and personality were not significant. The findings suggest that vision is highly specific, i.e., there is no common factor. While this proposal does not exclude strong and stable associations between certain illusions and between certain illusions and personality traits, these associations seem to be the exception rather than the rule.

Motion-based nearest vector metric for reference frame selection in the perception of motion.

We investigated how the visual system selects a reference frame for the perception of motion. Two concentric arcs underwent circular motion around the center of the display, where observers fixated. The outer (target) arc's angular velocity profile was modulated by a sine wave midflight whereas the inner (reference) arc moved at a constant angular speed. The task was to report whether the target reversed its direction of motion at any point during its motion. We investigated the effects of spatial and figural factors by systematically varying the radial and angular distances between the arcs, and their relative sizes. We found that the effectiveness of the reference frame decreases with increasing radial- and angular-distance measures. Drastic changes in the relative sizes of the arcs did not influence motion reversal thresholds, suggesting no influence of stimulus form on perceived motion. We also investigated the effect of common velocity by introducing velocity fluctuations to the reference arc as well. We found no effect of whether or not a reference frame has a constant motion. We examined several form- and motion-based metrics, which could potentially unify our findings. We found that a motion-based nearest vector metric can fully account for all the data reported here. These findings suggest that the selection of reference frames for motion processing does not result from a winner-take-all process, but instead, can be explained by a field whose strength decreases with the distance between the nearest motion vectors regardless of the form of the moving objects.

What crowding can tell us about object representations.

In crowding, perception of a target usually deteriorates when flanking elements are presented next to the target. Surprisingly, adding further flankers can lead to a release from crowding. In previous work we showed that, for example, vernier offset discrimination at 9° of eccentricity deteriorated when a vernier was embedded in a square. Adding further squares improved performance. The more squares presented, the better the performance, extending across 20° of the visual field. Here, we show that very similar results hold true for shapes other than squares, including unfamiliar, irregular shapes. Hence, uncrowding is not restricted to simple and familiar shapes. Our results provoke the question of whether any type of shape is represented at any location in the visual field. Moreover, small changes in the orientation of the flanking shapes led to strong increases in crowding strength. Hence, highly specific shape-specific interactions across large parts of the visual field determine vernier acuity.

Beyond the Ribosome: Extra-translational Functions of tRNA Fragments.

High-throughput sequencing studies of small RNAs reveal a complex milieu of noncoding RNAs in biological samples. Early data analysis was often limited to microRNAs due to their regulatory nature and potential as biomarkers; however, many more classes of noncoding RNAs are now being recognized. A class of fragments initially excluded from analysis were those derived from transfer RNAs (tRNAs) because they were thought to be degradation products. More recently, critical cellular function has been attributed to tRNA fragments (tRFs), and their conservation across all domains of life has propelled them into an emerging area of scientific study. The biogenesis of tRFs is currently being elucidated, and initial studies show that a diverse array of tRFs are generated from all parts of a tRNA molecule. The goal of this review was to present what is currently known about tRFs and their potential as biomarkers for the earlier detection of disease.

A computational model for reference-frame synthesis with applications to motion perception.

As discovered by the Gestaltists, in particular by Duncker, we often perceive motion to be within a non-retinotopic reference frame. For example, the motion of a reflector on a bicycle appears to be circular, whereas, it traces out a cycloidal path with respect to external world coordinates. The reflector motion appears to be circular because the human brain subtracts the horizontal motion of the bicycle from the reflector motion. The bicycle serves as a reference frame for the reflector motion. Here, we present a general mathematical framework, based on vector fields, to explain non-retinotopic motion processing. Using four types of non-retinotopic motion paradigms, we show how the theory works in detail. For example, we show how non-retinotopic motion in the Ternus-Pikler display can be computed.

Human and machine learning in non-Markovian decision making.

Humans can learn under a wide variety of feedback conditions. Reinforcement learning (RL), where a series of rewarded decisions must be made, is a particularly important type of learning. Computational and behavioral studies of RL have focused mainly on Markovian decision processes, where the next state depends on only the current state and action. Little is known about non-Markovian decision making, where the next state depends on more than the current state and action. Learning is non-Markovian, for example, when there is no unique mapping between actions and feedback. We have produced a model based on spiking neurons that can handle these non-Markovian conditions by performing policy gradient descent [1]. Here, we examine the model's performance and compare it with human learning and a Bayes optimal reference, which provides an upper-bound on performance. We find that in all cases, our population of spiking neurons model well-describes human performance.

Why vision is not both hierarchical and feedforward.

In classical models of object recognition, first, basic features (e.g., edges and lines) are analyzed by independent filters that mimic the receptive field profiles of V1 neurons. In a feedforward fashion, the outputs of these filters are fed to filters at the next processing stage, pooling information across several filters from the previous level, and so forth at subsequent processing stages. Low-level processing determines high-level processing. Information lost on lower stages is irretrievably lost. Models of this type have proven to be very successful in many fields of vision, but have failed to explain object recognition in general. Here, we present experiments that, first, show that, similar to demonstrations from the Gestaltists, figural aspects determine low-level processing (as much as the other way around). Second, performance on a single element depends on all the other elements in the visual scene. Small changes in the overall configuration can lead to large changes in performance. Third, grouping of elements is key. Only if we know how elements group across the entire visual field, can we determine performance on individual elements, i.e., challenging the classical stereotypical filtering approach, which is at the very heart of most vision models.

Visual crowding illustrates the inadequacy of local vs. global and feedforward vs. feedback distinctions in modeling visual perception.

Experimentalists tend to classify models of visual perception as being either local or global, and involving either feedforward or feedback processing. We argue that these distinctions are not as helpful as they might appear, and we illustrate these issues by analyzing models of visual crowding as an example. Recent studies have argued that crowding cannot be explained by purely local processing, but that instead, global factors such as perceptual grouping are crucial. Theories of perceptual grouping, in turn, often invoke feedback connections as a way to account for their global properties. We examined three types of crowding models that are representative of global processing models, and two of which employ feedback processing: a model based on Fourier filtering, a feedback neural network, and a specific feedback neural architecture that explicitly models perceptual grouping. Simulations demonstrate that crucial empirical findings are not accounted for by any of the models. We conclude that empirical investigations that reject a local or feedforward architecture offer almost no constraints for model construction, as there are an uncountable number of global and feedback systems. We propose that the identification of a system as being local or global and feedforward or feedback is less important than the identification of a system's computational details. Only the latter information can provide constraints on model development and promote quantitative explanations of complex phenomena.

Is there a common factor for vision?

In cognition, common factors play a crucial role. For example, different types of intelligence are highly correlated, pointing to a common factor, which is often called g. One might expect that a similar common factor would also exist for vision. Surprisingly, no one in the field has addressed this issue. Here, we provide the first evidence that there is no common factor for vision. We tested 40 healthy students' performance in six basic visual paradigms: visual acuity, vernier discrimination,two visual backward masking paradigms, Gabor detection, and bisection discrimination. One might expect that performance levels on these tasks would be highly correlated because some individuals generally have better vision than others due to superior optics,better retinal or cortical processing, or enriched visual experience. However, only four out of 15 correlations were significant, two of which were nontrivial. These results cannot be explained by high intraobserver variability or ceiling effects because test­retest reliability was high and the variance in our student population is commensurate with that from other studies with well sighted populations. Using a variety of tests (e.g., principal components analysis, Bayes theorem, test­retest reliability), we show the robustness of our null results. We suggest that neuroplasticity operates during everyday experience to generate marked individual differences. Our results apply only to the normally sighted population (i.e., restricted range sampling). For the entire population, including those with degenerate vision, we expect different results.

Deleterious effects of roving on learned tasks.

In typical perceptual learning experiments, one stimulus type (e.g., a bisection stimulus offset either to the left or right) is presented per trial. In roving, two different stimulus types (e.g., a 30' and a 20' wide bisection stimulus) are randomly interleaved from trial to trial. Roving can impair both perceptual learning and task sensitivity. Here, we investigate the relationship between the two. Using a bisection task, we found no effect of roving before training. We next trained subjects and they improved. A roving condition applied after training impaired sensitivity.