Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS).

INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.

A Wireless, Wearable Carotid Doppler Ultrasound Aids Diagnosis and Monitoring of Pericardial Tamponade: A Case Report.

Pericardial tamponade can often be diagnosed through clinical findings and echocardiography; however, the diagnosis can be aided by demonstrating the hemodynamic consequences of the effusion. We describe the use of a wearable carotid Doppler device to help diagnose and monitor pericardial tamponade. CASE SUMMARY: A 54-year-old man developed hypotension after an endobronchial biopsy for a lung mass. Echocardiography showed a pericardial effusion with sonographic evidence of tamponade. A wearable carotid Doppler device demonstrated low corrected carotid flow time (CFT) (a surrogate for stroke volume) with significant respiratory variation, supporting the diagnosis of tamponade. The patient underwent pericardiocentesis which revealed purulent pericardial fluid from a mediastinal abscess. After drainage there was increased CFT and reduced respiratory variability in Doppler, surrogates of improved stroke volume. CONCLUSION: A wearable carotid Doppler device is a noninvasive tool that can help determine the hemodynamic impact of a pericardial effusion, and potentially aid in the diagnosis of pericardial tamponade.

Systematic differences in visual working memory performance are not caused by differences in working memory storage.

People vary in their performance on visual working memory tasks, and these individual differences covary with a wide range of higher-level cognitive processes including fluid intelligence. Performance also varies across study displays, purportedly driven by both low- and higher-level processes. Understanding what causes these sources of systematic variability has been crucial for developing theories of working memory. However, here we find that all such variability in performance on a test of visual working memory can be accounted for by concurrent variability in visual iconic memory: A person with relatively high working memory capacity will have high iconic memory capacity, and a particularly easy working memory display will also be easy under iconic memory conditions. These results are supported by a nonparametric factor analysis and hierarchical Bayesian model comparison. In a second experiment the relationship between iconic and working memory holds even when they are measured with substantially different experimental paradigms, and a third experiment suggests that the relationship between tests of iconic and working memory is driven by mechanisms other than iconic or working memory storage, such as variation in perceptual or attentional processes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Organizing principles of astrocytic nanoarchitecture in the mouse cerebral cortex.

Astrocytes are increasingly understood to be important regulators of central nervous system (CNS) function in health and disease; yet, we have little quantitative understanding of their complex architecture. While broad categories of astrocytic structures are known, the discrete building blocks that compose them, along with their geometry and organizing principles, are poorly understood. Quantitative investigation of astrocytic complexity is impeded by the absence of high-resolution datasets and robust computational approaches to analyze these intricate cells. To address this, we produced four ultra-high-resolution datasets of mouse cerebral cortex using serial electron microscopy and developed astrocyte-tailored computer vision methods for accurate structural analysis. We unearthed specific anatomical building blocks, structural motifs, connectivity hubs, and hierarchical organizations of astrocytes. Furthermore, we found that astrocytes interact with discrete clusters of synapses and that astrocytic mitochondria are distributed to lie closer to larger clusters of synapses. Our findings provide a geometrically principled, quantitative understanding of astrocytic nanoarchitecture and point to an unexpected level of complexity in how astrocytes interact with CNS microanatomy.

Initial Diagnosis and Management of Acutely Elevated Intracranial Pressure.

Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult because of the variety of manifestations that it can cause disease states it is associated with. Several treatment guidelines exist for specific disease processes such as trauma or ischemic stroke, but their recommendations may not apply to other causes. In the acute setting, management decisions must often be made before the underlying cause is known. In this review, we present an organized, evidence-based approach to the recognition and management of patients with suspected or confirmed elevated ICP in the first minutes to hours of resuscitation. We explore the utility of invasive and noninvasive methods of diagnosis, including history, physical examination, imaging, and ICP monitors. We synthesize various guidelines and expert recommendations and identify core management principles including noninvasive maneuvers, neuroprotective intubation and ventilation strategies, and pharmacologic therapies such as ketamine, lidocaine, corticosteroids, and the hyperosmolar agents mannitol and hypertonic saline. Although an in-depth discussion of the definitive management of each etiology is beyond the scope of this review, our goal is to provide an empirical approach to these time-sensitive, critical presentations in their initial stages.

Indications, Clinical Impact, and Complications of Critical Care Transesophageal Echocardiography: A Scoping Review.

BACKGROUND: Critical care transesophageal echocardiography (ccTEE) is an increasingly popular tool used by intensivists to characterize and manage hemodynamics at the bedside. Its usage appears to be driven by expanded diagnostic scope as well as the limitations of transthoracic echocardiography (TTE) - lack of acoustic windows, patient positioning, and competing clinical interests (eg, the need to perform chest compressions). The objectives of this scoping review were to determine the indications, clinical impact, and complications of ccTEE. METHODS: MEDLINE, EMBASE, Cochrane, and six major conferences were searched without a time or language restriction on March 31st, 2021. Studies were included if they assessed TEE performed for adult critically ill patients by intensivists, emergency physicians, or anesthesiologists. Intraoperative or post-cardiac surgical TEE studies were excluded. Study demographics, indication for TEE, main results, and complications were extracted in duplicate. RESULTS: Of the 4403 abstracts screened, 289 studies underwent full-text review, with 108 studies (6739 patients) included. Most studies were retrospective (66%), performed in academic centers (84%), in the intensive care unit (73%), and were observational (55%). The most common indications for ccTEE were hemodynamic instability, trauma, cardiac arrest, respiratory failure, and procedural guidance. Across multiple indications, ccTEE was reported to change the diagnosis in 52% to 78% of patients and change management in 32% to79% patients. During cardiac arrest, ccTEE identified the cause of arrest in 25% to 35% of cases. Complications of ccTEE included two cases of significant gastrointestinal bleeding requiring intervention, but no other major complications (death or esophageal perforation) reported. CONCLUSIONS: The use of ccTEE has been described for the diagnosis and management of a broad range of clinical problems. Overall, ccTEE was commonly reported to offer additional diagnostic yield beyond TTE with a low observed complication rate. Additional high quality ccTEE studies will permit stronger conclusions and a more precise understanding of the trends observed in this scoping review.

Local motion pooling is continuous, global motion perception is discrete.

Perceiving the motion of an object is thought to involve two stages: Local motion energy is measured at each point in space, and these signals are then pooled across space to build coherent global motion. There are several theories of how local-to-global pooling occurs, but they all predict that global motion perception is a continuous process, such that increasing the strength of motion energy should gradually increase the precision of perceived motion directions. We test this prediction against the alternative that global motion perception is discrete: Motion is either perceived with high precision or fails to be perceived altogether. Data from human observers provides clear evidence that, whereas pooling local motion energy is continuous, the segmentation of local signals into coherent global motion patterns is a discrete process. This result adds motion perception to the growing list of processes that exhibit evidence of all-or-none visual awareness. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Characteristics and Outcomes for Low-Risk Hospital Admissions Admitted to the ICU: A Multisite Cohort Study.

IMPORTANCE: Prognostication following ICU admission can often be determined based on known risk factors, including demographics and illness severity; however, little is known about outcomes of patients deemed to be "low-risk" at the time of hospital admission who subsequently are admitted to the ICU. OBJECTIVES: The objectives of this study were to determine the characteristics, outcomes, and costs for patients requiring ICU admission despite having lower predicted mortality when they were admitted to the hospital. DESIGN SETTING AND PARTICIPANTS: In this historical cohort study, we used a prospectively maintained ICU registry that included all ICU admissions to The Ottawa Hospital for patients 18 years or older from January 2011 to December 2016. We classified patients as low-risk using the Hospital-patient 1-year Mortality Risk at admission score, a hospital admission score validated to predict 1-year mortality. MAIN OUTCOMES AND MEASURES: The primary outcome was inhospital mortality. Secondary outcomes included adverse events, resource utilization, and costs. RESULTS: Of the 17,173 total ICU patients, 3,445 (20.1%) were classified as low-risk at hospital admission. Low-risk patients were younger (48.7 vs 67.5 yr; p < 0.001) and had a lower Multiple Organ Dysfunction Score (2.37 vs 4.14; p < 0.001). Mortality for low-risk patients was significantly lower than for non-low-risk patients (4.1% vs 25.4%; p < 0.001). For low-risk patients, multivariable logistic regression showed mortality was independently associated with older age (odds ratio, 1.02 per 1 yr; 95% CI, 1.00-1.03 per 1 yr), Multiple Organ Dysfunction Score (odds ratio, 1.42 per 1 point; 95% CI, 1.31-1.54 per 1 point), fluid management adverse events (odds ratio, 2.84; 95% CI, 1.29-6.25), hospital-acquired infections (odds ratio, 1.60; 95% CI, 1.02-2.51), and mechanical ventilation (odds ratio, 1.98; 95% CI, 1.20-3.26). CONCLUSIONS AND RELEVANCE: Despite their robust premorbid status, low-risk patients admitted to the ICU had significant inhospital mortality. Fluid management adverse events, hospital-associated infections, multiple organ dysfunction, and mechanical ventilation are important prognostic factors for low-risk patients.

Content Analysis and Characterization of Medical Tweets During the Early Covid-19 Pandemic.

Objective The novel coronavirus disease 2019 (Covid-19) has infected millions worldwide and impacted the lives of many folds more. Many clinicians share new Covid-19-related resources, research, and ideas within the online Free Open Access to Medical Education (FOAM) community of practice. This study provides a detailed content and contributor analysis of Covid-19-related tweets among the FOAM community during the first months of the pandemic. Design, Setting, and Participants In this social media content analysis study, Twitter was searched from November 1, 2019, to March 21, 2020, for English tweets discussing Covid-19 in the FOAM community. Tweets were classified into one of 13 pre-specified content categories: original research, editorials, FOAM resource, public health, podcast or video, learned experience, refuting false information, policy discussion, emotional impact, blatantly false information, other Covid-19, and non-Covid-19. Further analysis of linked original research and FOAM resources was performed. One-thousand (1000) randomly selected contributor profiles and those deemed to have contributed false information were analyzed. Results The search yielded 8541 original tweets from 4104 contributors. The number of tweets in each content category were: 1557 other Covid-19 (18.2%), 1190 emotional impact (13.9%), 1122 FOAM resources (13.1%), 1111 policy discussion (13.0%), 928 advice (10.9%), 873 learned experience (10.2%), 424 non-Covid-19 (5.0%), 410 podcast or video (4.8%), 304 editorials (3.6%), 275 original research (3.2%), 245 public health (2.9%), 83 refuting false information (1.0%), and 19 blatantly false (0.2%). Conclusions Early in the Covid-19 pandemic, the FOAM community used Twitter to share Covid-19 learned experiences, online resources, crowd-sourced advice, and research and to discuss the emotional impact of Covid-19. Twitter also provided a forum for post-publication peer review of new research. Sharing blatantly false information within this community was infrequent. This study highlights several potential benefits from engaging with the FOAM community on Twitter.

Completeness of reporting for systematic reviews of point-of-care ultrasound: a meta-research study.

OBJECTIVES: Systematic reviews are often considered among the highest quality of evidence. Completely reported systematic reviews, however, are required so readers can assess for generalisability of the research to practice and risk of bias. The objective of this study was to assess the completeness of reporting for systematic reviews assessing the diagnostic accuracy of point-of-care ultrasound (POCUS) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Diagnostic Test Accuracy (PRISMA-DTA) checklist that was published in 2018. DESIGN AND SETTING: In this meta-research study, MEDLINE, EMBASE and Cochrane Library databases were searched, with no date restriction, on March 1st, 2020 for systematic reviews assessing the diagnostic accuracy of POCUS. Adherence to PRISMA-DTA for the main text and abstract was scored independently and in duplicate using a modified checklist. Prespecified subgroup analyses were performed. MAIN OUTCOME MEASURES: The primary outcome was the mean PRISMA-DTA checklist adherence for the full-text and abstract. RESULTS: A total of 71 studies published from 2008 to 2020 met the inclusion criteria. The overall adherence for the full-text was moderate: 19.8 out of 26.0 items (76%) and for the abstract was 7.0 out of 11.0 items (64%). Although many items in the PRISMA-DTA checklist were frequently reported, several were r infrequently reported (<33% of studies), including item 5 (protocol registration), item D2 (minimally acceptable test accuracy) and item 14 (variability in target condition, index test and reference standards). Subgroup analyses showed a higher PRISMA-DTA mean adherence (SD) for high impact journals (20.9 (2.52) vs 18.9 (1.95); p<0.001), studies including supplemental materials (20.6 (2.48) vs 18.9 (2.28); p=0.004), studies citing adherence to PRISMA reporting guidelines (20.4 (1.95) vs 19.0 (3.00); p=0.038) and studies published in journals endorsing PRISMA guidelines (20.2 (2.47) vs 18.6 (2.37); p=0.025). There was variable adherence based on journal of publication (p=0.006), but not for study population (adult vs paediatric vs mixed) (p=0.62), year of publication (p=0.94), body region (p=0.78) or country (p=0.40). There was no variability in abstract adherence based on whether the abstract was structured with subheadings or not (p=0.25). A Spearman's correlation found moderate correlation between higher word counts and abstractand full-text adherence (R=0.45, p<0.001 and R=0.38, p=0.001), respectively. CONCLUSIONS: Overall, the reporting of POCUS diagnostic accuracy systematic reviews and meta-analyses was moderate. We identified deficits in several key areas including the preregistration of systematic reviews in an online repository, handling of multiple definitions of target conditions, index tests and reference standards and specifying minimally acceptable test accuracy. Prospective registration of reviews and detailed reporting as per PRISMA-DTA during the research process could improve reporting completeness. At an editorial level, word count and supplemental material limitations may impede reporting completeness, whereas endorsement of reporting guidelines on journal websites could improve reporting.

Eriksen flanker delta plot shapes depend on the stimulus.

Several experimental paradigms are purported to measure response conflict, including the Stroop, Simon, and Eriksen flanker tasks. Although these tasks are often treated as being similar, delta plot analyses of response time distributions have revealed marked differences across them. Several theories have been proposed to explain these differences, however, assessing their veracity is difficult given the numerous differences across tasks. To explore what might cause delta plots to differ in a more controlled manner, here stimulus materials were manipulated across four Eriksen flanker tasks. The results reveal substantially different delta plot shapes for different stimuli: positive-going functions when color or motion served as the target and flankers, and delta plots with negative-going components when stimuli were arrows or orientated gratings. These results cast doubt on the proposal that negative-going delta plots occur only when spatial location serves as the interfering stimulus dimension. Moreover, because targets and flankers were always of the same stimulus type, the results also suggest that differences in materials across the relevant and irrelevant dimensions do not determine delta plot shapes. Instead, we propose that the delta plot shape is determined by several factors, including how early the interfering information is processed in the visual cortex.

Set size effects on working memory precision are not due to an averaging of slots.

Visual working memory is often characterized as a discrete system, where an item is either stored in memory or it is lost completely. As this theory predicts, increasing memory load primarily affects the probability that an item is in memory. However, the precision of items successfully stored in memory also decreases with memory load. The prominent explanation for this effect is the "slots-plus-averaging" model, which proposes that an item can be stored in replicate across multiple memory slots. Here, however, precision declined with set size even in iconic memory tasks that did not require working memory storage, ruling out such storage accounts. Moreover, whereas the slots-plus-averaging model predicts that precision effects should plateau at working memory capacity limits, precision continued to decline well beyond these limits in an iconic memory task, where the number of items available at test was far greater than working memory capacity. Precision also declined in tasks that did not require study items to be encoded simultaneously, ruling out perceptual limitations as the cause of set size effects on memory precision. Taken together, these results imply that set size effects on working memory precision do not stem from working memory storage processes, such as an averaging of slots, and are not due to perceptual limitations. This rejection of the prominent slots-plus-averaging model has implications for how contemporary models of discrete capacities theories can be improved, and how they might be rejected.

How well are Phase 2 cancer trial publications supported by preclinical efficacy evidence?

Major ethics policies require that human studies be preceded by animal experiments. We probed the extent to which trials testing efficacy of cancer drugs cited preclinical efficacy studies testing the same drug and disease indication. Using a sample of Phase 2 trial publications for novel cancer monotherapies approved by Food and Drug Administration 2005-2007, we conducted a systematic analysis of citations to preclinical efficacy evidence within trial publications. Citations were classified based on whether they "matched" the drug and indication of the trial. Our sample included 179 Phase 2 publications published 2004-2016. At least one preclinical study was cited for 113 of 179 publications (63%); 56 (31%) cited matching preclinical studies, and 74 (41%) did not cite either matching preclinical or matching clinical trial evidence. When excluding evidence that would likely not have been available to investigators before trial launch, 45 trials (25%) cited matching preclinical studies; 91 (51%) did not cite any matched preclinical or clinical, preceding evidence. No relationship between citation of matching and preceding preclinical evidence and trial outcomes was observed (28.4% of nonpositive trials vs. 26.9% of positive trials, p ~ 1). This suggests that many Phase 2 trial publications do not cite matching preclinical efficacy studies. Limited citation either suggests its absence or its exclusion from a publication. To ensure trials rest on a sound ethical basis and that publications support valid inference, journal editors and referees might encourage more complete descriptions of preclinical evidence or, where appropriate, active disclosure of its absence.

Swap errors in spatial working memory are guesses.

In typical visual working memory tasks, participants report the color of a previously studied item at some probed location. Alternatively, in some recent studies, a color is probed and participants must report the item's location. There is a surprising difference between these tasks: in location reports participants almost never guess randomly as they do when reporting color, but often incorrectly report the locations of non-probed items. This finding has been taken as evidence for feature binding errors in memory, and evidence against discrete capacity models, which predict that pure guessing should occur. We test an alternative possibility: that non-target responses are guesses, but intelligent ones. In particular, when asked to report the location of an item for which participants have no memory, they may guess near locations where they know something was presented. Here we present false-probe trials in which a color is probed that was not actually studied, and find that the responses, which are necessarily guesses, are nonetheless centered around studied locations. Moreover, we find that the confidence ratings for non-target responses are low, and similar to confidence for uniformly distributed guesses. In a second experiment, we find that manipulating the retention interval, which is known to affect guess rates, changes the rate of these low-confidence non-target responses. These results suggest that the tendency to report locations of non-probed items reflects a good guessing strategy; not something fundamental about how features and objects are represented in working memory.

Iconic Memories Die a Sudden Death.

Iconic memory is characterized by its large storage capacity and brief storage duration, whereas visual working memory is characterized by its small storage capacity. The limited information stored in working memory is often modeled as an all-or-none process in which studied information is either successfully stored or lost completely. This view raises a simple question: If almost all viewed information is stored in iconic memory, yet one second later most of it is completely absent from working memory, what happened to it? Here, I characterized how the precision and capacity of iconic memory changed over time and observed a clear dissociation: Iconic memory suffered from a complete loss of visual items, while the precision of items retained in memory was only marginally affected by the passage of time. These results provide new evidence for the discrete-capacity view of working memory and a new characterization of iconic memory decay.

Integrating Theoretical Models with Functional Neuroimaging.

The development of mathematical models to characterize perceptual and cognitive processes dates back almost to the inception of the field of psychology. Since the 1990s, human functional neuroimaging has provided for rapid empirical and theoretical advances across a variety of domains in cognitive neuroscience. In more recent work, formal modeling and neuroimaging approaches are being successfully combined, often producing models with a level of specificity and rigor that would not have been possible by studying behavior alone. In this review, we highlight examples of recent studies that utilize this combined approach to provide novel insights into the mechanisms underlying human cognition. The studies described here span domains of perception, attention, memory, categorization, and cognitive control, employing a variety of analytic and model-inspired approaches. Across these diverse studies, a common theme is that individually tailored, creative solutions are often needed to establish compelling links between multi-parameter models and complex sets of neural data. We conclude that future developments in model-based cognitive neuroscience will have great potential to advance our theoretical understanding and ability to model both low-level and high-level cognitive processes.

Accounting for stimulus-specific variation in precision reveals a discrete capacity limit in visual working memory.

If we view a visual scene that contains many objects, then momentarily close our eyes, some details persist while others seem to fade. Discrete models of visual working memory (VWM) assume that only a few items can be actively maintained in memory, beyond which pure guessing will emerge. Alternatively, continuous resource models assume that all items in a visual scene can be stored with some precision. Distinguishing between these competing models is challenging, however, as resource models that allow for stochastically variable precision (across items and trials) can produce error distributions that resemble random guessing behavior. Here, we evaluated the hypothesis that a major source of variability in VWM performance arises from systematic variation in precision across the stimuli themselves; such stimulus-specific variability can be incorporated into both discrete-capacity and variable-precision resource models. Participants viewed multiple oriented gratings, and then reported the orientation of a cued grating from memory. When modeling the overall distribution of VWM errors, we found that the variable-precision resource model outperformed the discrete model. However, VWM errors revealed a pronounced "oblique effect," with larger errors for oblique than cardinal orientations. After this source of variability was incorporated into both models, we found that the discrete model provided a better account of VWM errors. Our results demonstrate that variable precision across the stimulus space can lead to an unwarranted advantage for resource models that assume stochastically variable precision. When these deterministic sources are adequately modeled, human working memory performance reveals evidence of a discrete capacity limit. (PsycINFO Database Record

Radial bias is not necessary for orientation decoding.

Multivariate pattern analysis can be used to decode the orientation of a viewed grating from fMRI signals in early visual areas. Although some studies have reported identifying multiple sources of the orientation information that make decoding possible, a recent study argued that orientation decoding is only possible because of a single source: a coarse-scale retinotopically organized preference for radial orientations. Here we aim to resolve these discrepant findings. We show that there were subtle, but critical, experimental design choices that led to the erroneous conclusion that a radial bias is the only source of orientation information in fMRI signals. In particular, we show that the reliance on a fast temporal-encoding paradigm for spatial mapping can be problematic, as effects of space and time become conflated and lead to distorted estimates of a voxel's orientation or retinotopic preference. When we implement minor changes to the temporal paradigm or to the visual stimulus itself, by slowing the periodic rotation of the stimulus or by smoothing its contrast-energy profile, we find significant evidence of orientation information that does not originate from radial bias. In an additional block-paradigm experiment where space and time were not conflated, we apply a formal model comparison approach and find that many voxels exhibit more complex tuning properties than predicted by radial bias alone or in combination with other known coarse-scale biases. Our findings support the conclusion that radial bias is not necessary for orientation decoding. In addition, our study highlights potential limitations of using temporal phase-encoded fMRI designs for characterizing voxel tuning properties.

Sensory uncertainty decoded from visual cortex predicts behavior.

Bayesian theories of neural coding propose that sensory uncertainty is represented by a probability distribution encoded in neural population activity, but direct neural evidence supporting this hypothesis is currently lacking. Using fMRI in combination with a generative model-based analysis, we found that probability distributions reflecting sensory uncertainty could reliably be estimated from human visual cortex and, moreover, that observers appeared to use knowledge of this uncertainty in their perceptual decisions.