Confidence in visual detection, familiarity and recollection judgments is preserved in schizophrenia spectrum disorder.

An effective way to quantify metacognitive performance is to ask participants to estimate their confidence in the accuracy of their response during a cognitive task. A recent meta-analysis1 raised the issue that most assessments of metacognitive performance in schizophrenia spectrum disorders may be confounded with cognitive deficits, which are known to be present in this population. Therefore, it remains unclear whether the reported metacognitive deficits are metacognitive in nature or rather inherited from cognitive deficits. Arbitrating between these two possibilities requires equating task performance between experimental groups. Here, we aimed to characterize metacognitive performance among individuals with schizophrenia across three tasks (visual detection, familiarity, recollection) using a within-subject design while controlling experimentally for intra-individual task performance and statistically for between-subject task performance. In line with our hypotheses, we found no metacognitive deficit for visual detection and familiarity judgments. While we expected metacognition for recollection to be specifically impaired among individuals with schizophrenia, we found evidence in favor of an absence of a deficit in that domain also. We found no specific metacognitive deficit in schizophrenia spectrum disorder in the visual or memory domain. The clinical relevance of our findings is discussed in light of a hierarchical framework of metacognition.

Prior information differentially affects discrimination decisions and subjective confidence reports.

According to Bayesian models, both decisions and confidence are based on the same precision-weighted integration of prior expectations ("priors") and incoming information ("likelihoods"). This assumes that priors are integrated optimally and equally in decisions and confidence, which has not been tested. In three experiments, we quantify how priors inform decisions and confidence. With a dual-decision task we create pairs of conditions that are matched in posterior information, but differ on whether the prior or likelihood is more informative. We find that priors are underweighted in discrimination decisions, but are less underweighted in confidence about those decisions, and this is not due to differences in processing time. The same patterns remain with exogenous probabilistic cues as priors. With a Bayesian model we quantify the weighting parameters for the prior at both levels, and find converging evidence that priors are more optimally used in explicit confidence, even when underused in decisions.

Preserved Metacognition for Undetected Visuomotor Deviations.

Humans can successfully correct deviations of movements without conscious detection of such deviations, suggesting limited awareness of movement details. We ask whether such limited awareness impairs confidence (metacognition). We recorded functional magnetic resonance imaging data while 31 human female and male participants detected cursor deviations during a visuomotor reaching task and rated their confidence retrospectively. We show that participants monitor a summary statistic of the unfolding visual feedback (the peak cursor error) to detect visuomotor deviations and adjust their confidence ratings, even when they report being unaware of a deviation. Crucially, confidence ratings were as metacognitively efficient for aware and unaware deviations. At the neural level, activity in the ventral striatum tracks high confidence, whereas a broad network encodes cursor error but not confidence. These findings challenge the notion of limited conscious action monitoring and uncover how humans monitor their movements as they unfold, even when unaware of ongoing deviations.SIGNIFICANCE STATEMENT We are unaware of the small corrections we apply to our movements as long as our goals are achieved. Here, although we replicate the finding that participants deny perceiving small deviations they correct, we show that their confidence reliably reflects the presence or absence of a deviation. This observation shows they can metacognitively monitor the presence of a deviation, even when they deny perceiving it. We also describe the hemodynamic correlates of confidence ratings. Our study questions the extent to which humans are unaware of the details of their movements; describes a plausible mechanism for metacognition in a visuomotor task, along with its neural correlates; and has important implications for the construction of the sense of self.

Preserved electrophysiological markers of confidence in schizophrenia spectrum disorder.

A large number of behavioral studies suggest that confidence judgments are impaired in schizophrenia, motivating the search for neural correlates of an underlying metacognitive impairment. Electrophysiological studies suggest that a specific evoked response potential reflecting performance monitoring, namely the error-related negativity (ERN), is blunted in schizophrenia compared to healthy controls. However, attention has recently been drawn to a potential confound in the study of metacognition, namely that lower task-performance in schizophrenia compared to healthy controls involves a decreased index of metacognitive performance (where metacognitive performance is construed as the ability to calibrate one's confidence relative to response correctness), independently of metacognitive abilities among patients. Here, we assessed how this confound might also apply to ERN-blunting in schizophrenia. We used an adaptive staircase procedure to titrate task-performance on a motion discrimination task in which participants (N = 14 patients and 19 controls) had to report their confidence after each trial while we recorded high density EEG. Interestingly, not only metaperceptual abilities were preserved among patients at the behavioral level, but contrary to our hypothesis, we also found no electrophysiological evidence for altered EEG markers of performance monitoring. These results bring additional evidence suggesting an unaltered ability to monitor perceptual performance on a trial by trial basis in schizophrenia.

Polyimide aerogels for ballistic impact protection.

The ballistic performance of edge-clamped monolithic polyimide aerogel blocks (12 mm thickness) has been studied through a series of impact tests using a helium-filled gas gun connected to a vacuum chamber and a spherical steel projectile (approximately 3 mm diameter) with an impact velocity range of 150-1300 m s-1. The aerogels had an average bulk density of 0.17 g cm-3 with high porosity of approximately 88%. The ballistic limit velocity of the aerogels was estimated to be in the range of 175-179 m s-1. Moreover, the aerogels showed a robust ballistic energy absorption performance (e.g., at the impact velocity of 1283 m s-1 at least 18% of the impact energy was absorbed). At low impact velocities, the aerogels failed by ductile hole enlargement followed by a tensile failure. By contrast, at high impact velocities, the aerogels failed through an adiabatic shearing process. Given the substantially robust ballistic performance, the polyimide aerogels have a potential to combat multiple constraints such as cost, weight, and volume restrictions in aeronautical and aerospace applications with high blast resistance and ballistic performance requirements such as in stuffed Whipple shields for orbital debris containment application.

Diagnostic performance of patient self-collected oral swab (tongue and cheek) in comparison with healthcare worker-collected nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 detection.

The present study was conducted to compare the performance of patient self-collected oral swab (OS) with healthcare worker (HCW)-collected nasopharyngeal swab (NPS) for SARS-CoV-2 detection by reverse transcription polymerase chain reaction (RT-PCR) in real-world setting. Paired OS and NPS were collected from 485 consecutive individuals presenting with symptoms of coronavirus disease-19 (COVID-19) or asymptomatic contacts of COVID-19 cases. Both specimens were processed for RT-PCR and cycle threshold (Ct) value for each test was obtained. Positive percent agreement (PPA), negative percent agreement (NPA), overall percent agreement (OPA) and kappa were calculated for OS RT-PCR compared with NPS RT-PCR as reference. A total of 116/485 (23.9%) participants were positive by NPS RT-PCR. OS had PPA of 71.6%, NPA of 98.8%, OPA of 92.4% and kappa of 0.771. Almost all participants (483/485, 99.6%) reported OS as a convenient and comfortable sample for SARS-CoV-2 testing over NPS. All participants with Ct values <25 and majority (90.8%) with Ct values <30 were detected by OS. To conclude, OS self-sampling was preferred in comparison with NPS due the ease and comfort during collection. The performance of OS RT-PCR for SARS-CoV-2 detection, however, was sub-optimal in comparison with NPS RT-PCR.

Migration of Calypso beacon transponders for hepatic stereotactic body radiotherapy: a report of two cases.

Background: The Calypso 4-dimensional Localization System allows the delivery of high-dose of radiation to a target guided by the implanted transponders. Calypso beacons are used for prostate and liver tumors treated with stereotactic body radiation therapy (SBRT). Several risks associated with this procedure have been previously observed. Here, we report on two cases where Calypso soft tissue transponders migrated to the lung shortly after implantation in liver. Case Description: Two male patients with hepatocellular carcinoma (HCC) underwent insertion of Calypso beacons in liver under image-guidance in preparation for SBRT. Post-procedure images confirmed the presence of the transponders within the liver. However, few days after implant, further imaging revealed a missing marker, in each patient, that had migrated to the right lung. Patients were asymptomatic and SBRT was delivered uneventfully. Conclusions: This is the first report of migration of Calypso beacons from liver to lung. In order to reduce the risk of migration, a Doppler ultrasound (US) prior to insertion could be performed to ensure that the transponders are at a safe distance from blood vessels. Anchored Calypso beacons, currently approved for insertion in the lung, could be tested as a suitable alternative to soft tissue beacons with a lower risk of migration.

VlsE, the nexus for antigenic variation of the Lyme disease spirochete, also mediates early bacterial attachment to the host microvasculature under shear force.

Hematogenous dissemination is a critical step in the evolution of local infection to systemic disease. The Lyme disease (LD) spirochete, which efficiently disseminates to multiple tissues, has provided a model for this process, in particular for the key early event of pathogen adhesion to the host vasculature. This occurs under shear force mediated by interactions between bacterial adhesins and mammalian cell-surface proteins or extracellular matrix (ECM). Using real-time intravital imaging of the Lyme spirochete in living mice, we previously identified BBK32 as the first LD spirochetal adhesin demonstrated to mediate early vascular adhesion in a living mouse; however, deletion of bbk32 resulted in loss of only about half of the early interactions, suggesting the existence of at least one other adhesin (adhesin-X) that promotes early vascular interactions. VlsE, a surface lipoprotein, was identified long ago by its capacity to undergo rapid antigenic variation, is upregulated in the mammalian host and required for persistent infection in immunocompetent mice. In immunodeficient mice, VlsE shares functional overlap with OspC, a multi-functional protein that displays dermatan sulfate-binding activity and is required for joint invasion and colonization. In this research, using biochemical and genetic approaches as well as intravital imaging, we have identified VlsE as adhesin-X; it is a dermatan sulfate (DS) adhesin that efficiently promotes transient adhesion to the microvasculature under shear force via its DS binding pocket. Intravenous inoculation of mice with a low-passage infectious B. burgdorferi strain lacking both bbk32 and vlsE almost completely eliminated transient microvascular interactions. Comparative analysis of binding parameters of VlsE, BBK32 and OspC provides a possible explanation why these three DS adhesins display different functionality in terms of their ability to promote early microvascular interactions.

Diagnostic performance of oral swab specimen for SARS-CoV-2 detection with rapid point-of-care lateral flow antigen test.

We evaluated the performance of oral swab specimen both health-care worker (HCW) collected and self-collected for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection with rapid antigen test (RAT) as compared to reverse transcriptase polymerase chain reaction (RT-PCR). Of the 529 participants enrolled, 121 (22.8%) were RT-PCR positive. Among the RT-PCR positives, 62 (51.2%) were RAT positive using oral swab. When compared with RT-PCR, RAT with oral swab had sensitivity and specificity of 63.3 and 96.8% respectively among symptomatic individuals. No statistically significant difference was observed in RAT positivity with HCW collection and self-collection, p = 0.606. Ct values were significantly lower in RT-PCR and RAT positive samples (ORF gene: 18.85 ± 4.36; E gene: 18.72 ± 4.84) as compared to RT-PCR positive and RAT negative samples (ORF gene: 26.98 ± 7.09; E gene: 26.97 ± 7.07), p < 0.0001. Our study demonstrated moderate sensitivity of RAT with oral swab in symptomatic individuals. Oral swab was the preferred sampling by almost all participants in terms of convenience and comfort as compared to nasopharyngeal swab. Oral swabs have utility for SARS-CoV-2 antigen detection among symptomatic individuals residing in remote rural areas and can serve as an initial screening tool during COVID-19 spikes when cases rise exponentially and laboratory capacities for RT-PCR testing become overwhelmed.

A leaky evidence accumulation process for perceptual experience.

The neural correlates supporting our perceptual experience of the world remain largely unknown. Recent studies have shown how stimulus detection and related confidence involve evidence accumulation (EA) processes similar to those involved in perceptual decision-making. Here, we propose that independently from any tasks, percepts are not static but fade in and out of consciousness according to the dynamics of a leaky evidence accumulation process (LEAP), and that confidence corresponds to the maximal evidence accumulated by this process. We discuss the implications and limitations of our proposal, assess how it may qualify as a neural correlate of consciousness, and illustrate how it brings us closer to a mechanistic understanding of phenomenal aspects of perceptual experience like intensity and duration, beyond mere detection.

Lipoproteome screening of the Lyme disease agent identifies inhibitors of antibody-mediated complement killing.

Spirochetal pathogens, such as the causative agent of Lyme disease, Borrelia burgdorferi sensu lato, encode an abundance of lipoproteins; however, due in part to their evolutionary distance from more well-studied bacteria, such as Proteobacteria and Firmicutes, few spirochetal lipoproteins have assigned functions. Indeed, B. burgdorferi devotes almost 8% of its genome to lipoprotein genes and interacts with its environment primarily through the production of at least 80 surface-exposed lipoproteins throughout its tick vector­vertebrate host lifecycle. Several B. burgdorferi lipoproteins have been shown to serve roles in cellular adherence or immune evasion, but the functions for most B. burgdorferi surface lipoproteins remain unknown. In this study, we developed a B. burgdorferi lipoproteome screening platform utilizing intact spirochetes that enables the identification of previously unrecognized host interactions. As spirochetal survival in the bloodstream is essential for dissemination, we targeted our screen to C1, the first component of the classical (antibody-initiated) complement pathway. We identified two high-affinity C1 interactions by the paralogous lipoproteins, ElpB and ElpQ (also termed ErpB and ErpQ, respectively). Using biochemical, microbiological, and biophysical approaches, we demonstrate that ElpB and ElpQ bind the activated forms of the C1 proteases, C1r and C1s, and represent a distinct mechanistic class of C1 inhibitors that protect the spirochete from antibody-mediated complement killing. In addition to identifying a mode of complement inhibition, our study establishes a lipoproteome screening methodology as a discovery platform for identifying direct host­pathogen interactions that are central to the pathogenesis of spirochetes, such as the Lyme disease agent.

Increased Functional Connectivity of the Intraparietal Sulcus Underlies the Attenuation of Numerosity Estimations for Self-Generated Words.

Previous studies have shown that self-generated stimuli in auditory, visual, and somatosensory domains are attenuated, producing decreased behavioral and neural responses compared with the same stimuli that are externally generated. Yet, whether such attenuation also occurs for higher-level cognitive functions beyond sensorimotor processing remains unknown. In this study, we assessed whether cognitive functions such as numerosity estimations are subject to attenuation in 56 healthy participants (32 women). We designed a task allowing the controlled comparison of numerosity estimations for self-generated (active condition) and externally generated (passive condition) words. Our behavioral results showed a larger underestimation of self-generated compared with externally generated words, suggesting that numerosity estimations for self-generated words are attenuated. Moreover, the linear relationship between the reported and actual number of words was stronger for self-generated words, although the ability to track errors about numerosity estimations was similar across conditions. Neuroimaging results revealed that numerosity underestimation involved increased functional connectivity between the right intraparietal sulcus and an extended network (bilateral supplementary motor area, left inferior parietal lobule, and left superior temporal gyrus) when estimating the number of self-generated versus externally generated words. We interpret our results in light of two models of attenuation and discuss their perceptual versus cognitive origins.SIGNIFICANCE STATEMENT We perceive sensory events as less intense when they are self-generated compared with when they are externally generated. This phenomenon, called attenuation, enables us to distinguish sensory events from self and external origins. Here, we designed a novel fMRI paradigm to assess whether cognitive processes such as numerosity estimations are also subject to attenuation. When asking participants to estimate the number of words they had generated or passively heard, we found bigger underestimation in the former case, providing behavioral evidence of attenuation. Attenuation was associated with increased functional connectivity of the intraparietal sulcus, a region involved in numerosity processing. Together, our results indicate that the attenuation of self-generated stimuli is not limited to sensory consequences but is also impact cognitive processes such as numerosity estimations.

Improved Aerodynamics of a Hollow-Blade Axial Flow Fan by Controlling the Leakage Flow Rate by Air Injection at the Rotating Shroud.

Axial flow fans are used in many fields in order to ensure the mass and heat transfer from air, chiefly in the heating, ventilation and air conditioning industry (HVAC). A more proper understanding of the airflow behavior through the systems is necessary to manage and optimize the fan operation. Computational fluid dynamics (CFD) represents a real tool providing the ability to access flow structures in areas that measuring equipment cannot reach. Reducing the leakage flow rate, inherent in operation, by synthetic-jet techniques improves performance. This paper presents the CFD results performed on a hollow blade fan developed by our team. The leakage flow is controlled by blowing air from 16 designated circular holes and arranged on the fan shroud. We discuss the results for two rotational speeds (1000 and 2000 rpm) and two injection rates (400 and 800 L/min). The numerical results consistent with the experimental show, for the low rotation speed and high injection ratio, significant gains in power (53%), torque (80%) and leakage flow rate (80%).

Evidence accumulation relates to perceptual consciousness and monitoring.

A fundamental scientific question concerns the neural basis of perceptual consciousness and perceptual monitoring resulting from the processing of sensory events. Although recent studies identified neurons reflecting stimulus visibility, their functional role remains unknown. Here, we show that perceptual consciousness and monitoring involve evidence accumulation. We recorded single-neuron activity in a participant with a microelectrode in the posterior parietal cortex, while they detected vibrotactile stimuli around detection threshold and provided confidence estimates. We find that detected stimuli elicited neuronal responses resembling evidence accumulation during decision-making, irrespective of motor confounds or task demands. We generalize these findings in healthy volunteers using electroencephalography. Behavioral and neural responses are reproduced with a computational model considering a stimulus as detected if accumulated evidence reaches a bound, and confidence as the distance between maximal evidence and that bound. We conclude that gradual changes in neuronal dynamics during evidence accumulation relates to perceptual consciousness and perceptual monitoring in humans.

Systematic review and meta-analysis of metacognitive abilities in individuals with schizophrenia spectrum disorders.

Metacognitive deficits are well documented in schizophrenia spectrum disorders as a decreased capacity to adjust confidence to performance in a cognitive task. Because metacognitive ability directly depends on task performance, metacognitive deficits might be driven by lower task performance among patients. To test this hypothesis, we conducted a Bayesian meta-analysis of 42 studies comparing metacognitive abilities in 1425 individuals with schizophrenia compared to 1256 matched controls. We found a global metacognitive deficit in schizophrenia (g = -0.57, 95 % CrI [-0.72, -0.43]), which was driven by studies which did not control task performance (g = -0.63, 95 % CrI [-0.78, -0.49]), and inconclusive among controlled-studies (g = -0.23, 95 % CrI [-0.60, 0.16], BF01 = 2.2). No correlation was found between metacognitive deficit and clinical features. We provide evidence that the metacognitive deficit in schizophrenia is inflated due to non-equated task performance. Thus, efforts should be made to develop experimental protocols accounting for lower task performance in schizophrenia.

Immunoadsorption for the Treatment of Acquired Hemophilia: New Observational Data, Systematic Review, and Meta-Analysis.

The treatment of patients with acquired hemophilia is challenging due to life-threatening hemorrhages, delayed response, and adverse effects to immunosuppressive agents. Even though immunoadsorption (IA) rapidly removes autoantibodies against factor VIII, this intervention's effectiveness is still a matter of debate. We aimed to study important outcomes of IA as adjunctive treatment in patients with acquired hemophilia. We performed comprehensive literature searches in MEDLINE and EMBASE databases. Clinical and laboratory data of all patients treated in our institution were additionally included. Literature searching yielded 498 records, of which 10 studies describing 106 patients were finally included. The number of patients varied from 1 to 65, and patients' ages ranged between 14 and 89. Treatment criteria in most patients were (1) failed response to immunosuppressive treatment alone, and/or (2) uncontrollable bleeding episodes, and/or (3) high inhibitor titer. Methodological quality was moderate. The number of IA sessions varied from 1 to 24. Within our institution, 12 patients have been treated since 2002; median age was 76 years (range 34-86); median titer of factor VIII inhibitor was 20 Bethesda units (range 3-214). Pooled estimates, modeling a random-effect binominal distribution incorporating the Freeman-Tukey double arcsine transformation, were 86% in case of factor VIII recovery (95% confidence interval 76%-94%), 95% for reduction of factor VIII inhibitor (83%, 100%), and 7% in case of death (0%, 18%). Our data suggest that IA might be a beneficial adjunctive treatment in patients with high-risk acquired hemophilia, but future studies shall confirm this observation.

The Anterior Cingulate Cortex Predicts Future States to Mediate Model-Based Action Selection.

Behavioral control is not unitary. It comprises parallel systems, model based and model free, that respectively generate flexible and habitual behaviors. Model-based decisions use predictions of the specific consequences of actions, but how these are implemented in the brain is poorly understood. We used calcium imaging and optogenetics in a sequential decision task for mice to show that the anterior cingulate cortex (ACC) predicts the state that actions will lead to, not simply whether they are good or bad, and monitors whether outcomes match these predictions. ACC represents the complete state space of the task, with reward signals that depend strongly on the state where reward is obtained but minimally on the preceding choice. Accordingly, ACC is necessary only for updating model-based strategies, not for basic reward-driven action reinforcement. These results reveal that ACC is a critical node in model-based control, with a specific role in predicting future states given chosen actions.

Confidence in visual motion discrimination is preserved in individuals with schizophrenia.

BACKGROUND: Metacognition is the set of reflexive processes that allows humans to evaluate the accuracy of their mental operations. Metacognitive deficits have been described in people with schizophrenia using mostly narrative assessment, and they have been linked to several key symptoms. METHODS: We assessed metacognitive performance objectively by asking people with schizophrenia or schizoaffective disorder (n = 20) and matched healthy participants (n = 21) to perform a visual discrimination task and report their confidence in their performance. Metacognitive performance was defined as the adequacy between visual discrimination performance and confidence. RESULTS: Bayesian analyses revealed equivalent metacognitive performance in the 2 groups, despite a weaker association between confidence and trajectory tracking during task execution among people with schizophrenia. We reproduced these results using an evidence accumulation model, which showed similar decisional processes in the 2 groups. LIMITATIONS: These results from a relatively small study sample cannot be generalized to other perceptual and nonperceptual tasks. To meet this purpose, ecological tasks are needed. As well, the role of antipsychotic medication and design deserves greater attention in the future. CONCLUSION: We found similar decisional and metacognitive capabilities between people with schizophrenia and healthy controls in a visual discrimination task.