Functional landscape of SARS-CoV-2 cellular restriction.

A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.

AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5.

The mitochondrial intermembrane space protein AIFM1 has been reported to mediate the import of MIA40/CHCHD4, which forms the import receptor in the mitochondrial disulfide relay. Here, we demonstrate that AIFM1 and MIA40/CHCHD4 cooperate beyond this MIA40/CHCHD4 import. We show that AIFM1 and MIA40/CHCHD4 form a stable long-lived complex in vitro, in different cell lines, and in tissues. In HEK293 cells lacking AIFM1, levels of MIA40 are unchanged, but the protein is present in the monomeric form. Monomeric MIA40 neither efficiently interacts with nor mediates the import of specific substrates. The import defect is especially severe for NDUFS5, a subunit of complex I of the respiratory chain. As a consequence, NDUFS5 accumulates in the cytosol and undergoes rapid proteasomal degradation. Lack of mitochondrial NDUFS5 in turn results in stalling of complex I assembly. Collectively, we demonstrate that AIFM1 serves two overlapping functions: importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay that ensures efficient interaction of MIA40/CHCHD4 with specific substrates.

Why do US source plasma donors stop donating?

BACKGROUND: In the United States, source plasma (SP) donors can donate up to 104 times per year. Considering the global need for SP and plasma-derived medicinal products, it is critical to maintain the health of frequent donors. This study explores SP donors' self-reported reasons for a lapse in donating. STUDY DESIGN AND METHODS: There were 5608 SP donors from 14 SP centers who enrolled in a longitudinal cohort study to assess self-reported functional health and well-being. Donors were assigned to one of four groups, according to the frequency of SP donation in the 12 months before enrollment. One thousand four hundred forty-eight SP donors who lapsed in donating during 6 months or greater during the study follow-up were asked to complete a survey. RESULTS: There were 545 lapsed SP donors who returned surveys (37.6%); 63% were female. Most responses given for stopping SP donation were categorized as convenience reasons (69.1%). Self-reported health concerns, including being deferred multiple times, which were categorized as possibly related or unable to determine a relationship to plasmapheresis, represented 45.5% of the responses. DISCUSSION: Primary reasons US SP donors report for a lapse in donation were categorized as convenience (e.g., schedule conflicts/lack of time). Donor responses categorized as health concerns which have a possible or uncertain relationship to plasmapheresis were less frequent but present in all frequency groups. This study adds to the body of evidence that SP donors cease donating for a variety of self-reported reasons with the majority not directly related to a perceived negative impact on their health.

Effects of donation frequency on U.S. source plasma donor health.

BACKGROUND: Plasma-derived medicinal products (PDMPs) are essential, life-saving medicines manufactured from plasma donated by healthy human volunteers. PDMPs are used to treat a range of rare, serious, and chronic conditions, often genetic in origin. Approximately 70% of the Source Plasma (SP) used for PDMP manufacturing comes from United States (US). The hypothesis of the study is that US donation frequency does not impair donor self-reported functional health and well-being. STUDY DESIGN AND METHODS: A total of 5608 SP donors from 14 US SP centers were enrolled in a cross-sectional study to assess self-reported health related quality of life (HRQoL) and well-being. By sex, donors were assigned to one of four groups, according to their frequency of SP donation in the 12 months before enrollment. The SF-36v2® Health Survey (SF-36v2) and a survey assessing the frequency of various health conditions that may be associated with impaired immune function over different time periods were used. RESULTS: There were no statistically significant differences in SF-36v2 scores between any of the donor frequency groups, compared with new donors after controlling for potential confounding and accounting for multiple comparisons among males and females. Cough, cold, occasional fatigue, and sore throat were the most reported health conditions or symptoms, but there was no clear difference among sex or frequency groups. DISCUSSION: The self-reported data in this study support the hypothesis that compensated donations at US FDA permitted frequencies and volumes are consistent with maintaining donor health. Compared with the general population, SP donors have comparable or better health than the general population.

Revisiting the self-generation effect in proofreading.

The self-generation effect refers to the finding that people's memory for information tends to be better when they generate it themselves. Counterintuitively, when proofreading, this effect may make it more difficult to detect mistakes in one's own writing than in others' writing. We investigated the self-generation effect and sources of individual differences in proofreading performance in two eye-tracking experiments. Experiment 1 failed to reveal a self-generation effect. Experiment 2 used a studying manipulation to induce overfamiliarity for self-generated text, revealing a weak but non-significant self-generation effect. Overall, word errors (i.e., wrong words) were detected less often than non-word errors (i.e., misspellings), and function word errors were detected less often than content word errors. Fluid intelligence predicted proofreading performance, whereas reading comprehension, working memory capacity, processing speed, and indicators of miserly cognitive processing did not. Students who made more text fixations and spent more time proofreading detected more errors.

Identifying over-the-counter information to prioritize for the purpose of reducing adverse drug reactions in older adults: A national survey of pharmacists.

BACKGROUND: Over-the-counter (OTC) medication use is associated with risks of adverse drug reactions (ADRs), particularly among older adults. The Drug Facts Label (DFL) is supposed to provide consumers with information that would avoid ADRs, yet research suggests that consumers frequently fail to interact with this critical information. We postulate that emphasizing critical information by placing it on the front of the package may increase its usage. Before doing so, the most critical information from the DFL needs to be identified. OBJECTIVES: This study aimed to determine which information from the DFL is most critical in reducing ADRs at the time of purchase or use by older adults. METHODS: A national survey of practicing pharmacists knowledgeable about OTC medication use by older adults asked participants to rank order the importance of the DFL sections to reduce ADRs in older adults. Open-ended questions focused on identifying ways of improving OTC medication labeling. Quantitative rankings were used to calculate the content validity ratio and analyzed using Wilcoxon signed rank tests. Qualitative results were categorized into themes. RESULTS: A total of 318 responses (12% response rate) were analyzed. There was high consensus that uses and purpose, active ingredient, warnings, and directions for use were the most important sections of the DFL. Within the warning section, 2 specific warnings, "Do not use" and "Ask a doctor or pharmacist," were deemed most important. Similarly, qualitative themes focused on seeking health care provider assistance or were specific to age-related precautions. CONCLUSIONS: Prioritizing warnings that highlight the importance of possible drug-drug and drug-disease precautions and the need to seek medical advice before taking OTC medications were deemed most critical. Moving this type of information to the front of the package may help reduce ADRs among older adults.

Plasmavigilance-Adverse events among US Source plasma donors.

BACKGROUND: Source plasma (SP) is the primary starting material for 87% of plasma-derived medicinal products globally. Plasmavigilance is a program designed to collect, analyze, and monitor donor adverse events (AEs) across the SP collection industry. Donor retention depends on donors having a safe and satisfactory experience. This study analyzes AE rates and SP donor characteristics that may be predictors of an AE. STUDY DESIGN AND METHODS: Donation data for 1.1 million donors making 12,183,182 SP donations over a 4-month period were analyzed. This represented approximately 72% of the donations collected by the U.S. plasma industry. The Standard for Recording Donor Adverse Events was used for AE definitions and classifications. RESULTS: The overall AE rate was 15.85/104 donations. The two AEs with the highest rates were Hypotensive and Phlebotomy events (8.32 and 5.91/104 donations, respectively). Females had higher overall AE rates than males (25.76 vs. 9.85/104 donations), and first-time donors had higher overall AE rates than repeat donors (136.66 vs. 12.37/104 donations). Weight, body mass index, age, and pre-donation estimated blood volume also were predictors of AE. DISCUSSION: SP donors have low AE rates with 90% being events classified as Hypotensive or Phlebotomy. Special attention and mitigation strategies should be directed to donors who are young, lightweight (between 100 and 124 pounds), female, or first-time donors to further reduce the incidence of AE, continue to ensure the donor has a safe experience, and facilitate donor retention.

Aldehyde and Volatile Organic Compound Yields in Commercial Cigarette Mainstream Smoke Are Mutually Related and Depend on the Sugar and Humectant Content in Tobacco.

INTRODUCTION: The World Health Organization (WHO) Framework Convention on Tobacco control recognizes the need for tobacco product regulation. In line with that, the WHO Study Group on Tobacco Product Regulation (TobReg) proposed to regulate nine toxicants in mainstream cigarette smoke, including aldehydes, volatile organic compounds (VOCs), and carbon monoxide (CO). We analyzed their relations in 50 commercially available cigarette brands, using two different smoking regimes, and their dependence on sugar and humectant concentrations in tobacco filler. METHODS: We measured sugar and humectant in tobacco filler and aldehydes, VOCs, and tar, nicotine, and CO (TNCO) in mainstream smoke. The general statistics, correlations between emission yields, and correlations between contents and emissions yields were determined for these data. RESULTS: For aldehydes, several significant correlations were found with precursor ingredients in unburnt tobacco when smoked with the Intense regime, most prominently for formaldehyde with sucrose, glucose, total sugars, and glycerol. For VOCs, 2,5-dimethylfuran significantly correlates with several sugars under both International Standards Organization (ISO) and Intense smoking conditions. A correlation network visualization shows connectivity between a sugar cluster, an ISO cluster, and an Intense cluster, with Intense formaldehyde as a central highest connected hub. CONCLUSIONS: Our multivariate analysis showed several strong connections between the compounds determined. The toxicants proposed by WHO, in particular, formaldehyde, can be used to monitor yields of other toxicants under Intense conditions. Emissions of formaldehyde, acetaldehyde, acrolein, and 2,5-dimethylfuran may decrease when sugar and humectants contents are lowered in tobacco filler. IMPLICATIONS: Our findings suggest that the aldehydes and VOCs proposed by TobReg are a representative selection for smoke component market monitoring purposes. In particular, formaldehyde yields may be useful to monitor emissions of other toxicants under Intense conditions. Since the most and strongest correlations were observed with the Intense regime, policymakers are advised to prescribe this regime for regulatory purposes. Policymakers should also consider sugars and humectants contents as targets for future tobacco product regulations, with the additional advantage that consumer acceptance of cigarette smoke is proportional to their concentrations in the tobacco blend.

Value-based attention capture: Differential effects of loss and gain contingencies.

There is evidence that attention can be captured by a feature that is associated with reward. However, it is unclear how associating a feature with loss impacts attentional capture. Some have found evidence for attentional capture by loss-associated stimuli, suggesting that attention is biased toward stimuli predictive of consequence, regardless of the valence of that consequence. However, in those studies, efficient attention to the loss-associated stimulus reduced the magnitude of the loss during training, so attention to the loss-associated stimulus was rewarded in relative terms. In Experiment 1 we associated a color with loss, gain, or no consequence during training and then investigated whether attention is captured by each color. Importantly, our training did not reward, even in a relative sense, attention to the loss-associated color. Although we found robust attentional capture by gain-associated colors, we found no evidence for capture by loss-associated colors. A second experiment showed that the observed effects cannot be explained by selection history and, hence, are specific to value learning. These results suggest that the learning mechanisms of value-based attentional capture are driven by reward, but not by loss or the predictability of consequences in general.

Individual differences point to two separate processes involved in the resolution of binocular rivalry.

Although binocular rivalry is different from other perceptually bistable phenomena in requiring interocular conflict, it also shares numerous features with those phenomena. This raises the question of whether, and to what extent, the neural bases of binocular rivalry and other bistable phenomena overlap. Here we examine this question using an individual-differences approach. In a first experiment, observers reported perception during four binocular rivalry tasks that differed in the features and retinal locations of the stimuli used. Perceptual dominance durations were highly correlated when compared between stimuli that differed in location only. Correlations were substantially weaker, however, when comparing stimuli comprised of different features. Thus, individual differences in binocular-rivalry perception partly reflect a feature-specific factor that is not shared among all variants of binocular rivalry. Our second experiment again included several binocular rivalry variants, but also a different form of bistability: moving plaid rivalry. Correlations in dominance durations between binocular rivalry variants that differed in feature content were again modest. Moreover, and surprisingly, correlations between binocular rivalry and moving plaid rivalry were of similar magnitude. This indicates a second, more general, factor underlying individual differences in binocular rivalry perception: one that is shared across binocular rivalry and moving plaid rivalry. We propose that the first, feature-specific factor corresponds to feature-tuned mechanisms involved in the treatment of interocular conflict, whereas the second, general factor corresponds to mechanisms involved in representing surfaces. These latter mechanisms would operate at a binocular level and be central to both binocular rivalry and other forms of bistability.

Revisiting individual differences in the time course of binocular rivalry.

Simultaneously showing an observer two incompatible displays, one to each eye, causes binocular rivalry, during which the observer regularly switches between perceiving one eye's display and perceiving the other. Observers differ in the rate of this perceptual cycle, and these individual differences have been reported to correlate with differences in the perceptual switch rate for other bistable perception phenomena. Identifying which psychological or neural factors explain this variability can help clarify the mechanisms underlying binocular rivalry and of bistable perception generally. Motivated by the prominent theory that perceptual switches during binocular rivalry are brought about by neural adaptation, we investigated whether perceptual switch rates are correlated with the strength of neural adaptation, indexed by visual aftereffects. We found no compelling evidence for such correlations. Moreover, we did not corroborate previous findings that switch rates are correlated between binocular rivalry and other forms of bistable perception. This latter nonreplication prompted us to perform a meta-analysis of existing research into correlations among forms of bistable perception, which revealed that evidence for such correlations is much weaker than is generally believed. By showing no common factor linking individual differences in binocular rivalry and in our other paradigms, these results fit well with other work that has shown such common factors to be rare among visual phenomena generally.

Screening for depression in cancer patients receiving radiotherapy: Feasibility and identification of effective tools in the NRG Oncology RTOG 0841 trial.

BACKGROUND: Brief tools are needed to screen oncology outpatients for depressive symptoms. METHODS: Patients starting radiotherapy for the first diagnosis of any tumor completed distress screening tools, including the 9-item Patient Health Questionnaire (PHQ-9), the 2-item Patient Health Questionnaire (PHQ-2), the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT), and the Hopkins Symptom Checklist (HSCL) (25-item version). Patients exceeding validated cutoff scores and a systematic sample of patients whose screening was negative completed the Structured Clinical Interview for DSM-IV (SCID) mood disorder modules via telephone. RESULTS: Four hundred sixty-three patients from 35 community-based radiation oncology sites and 2 academic radiation oncology sites were recruited. Sixty-six percent of the 455 eligible patients (n = 299) were women, and the eligible patients had breast (45%), gastrointestinal (11%), lung (10%), gynecologic (6%), or other cancers (27%). Seventy-five (16.5%) exceeded screening cutoffs for depressive symptoms. Forty-two of these patients completed the SCID. Another 37 patients whose screening was negative completed the SCID. Among the 79 patients completing the SCID, 8 (10.1%) met the criteria for major depression, 2 (2.5%) met the criteria for dysthymia, and 6 (7.6%) met the criteria for an adjustment disorder. The PHQ-2 demonstrated good psychometric properties for screening for mood disorders with a cutoff score of ≥3 (receiver operating characteristic area under the curve [AUC], 0.83) and was comparable to the PHQ-9 ( > 9; AUC = 0.85). The NCCN-DT did not detect depression (AUC = 0.59). CONCLUSIONS: The PHQ-2 demonstrated good psychometric properties for screening for mood disorders, which were equivalent to the PHQ-9 and superior to the NCCN-DT. These findings support using the PHQ-2 to identify patients in need of further assessment for depression, which has a low prevalence but is a clinically significant comorbidity. These findings could inform the implementation of distress screening accreditation standards. Cancer 2017;123:485-493. © 2016 American Cancer Society.

Working Memory Capacity Predicts Selection and Identification Errors in Visual Search.

As public safety relies on the ability of professionals, such as radiologists and baggage screeners, to detect rare targets, it could be useful to identify predictors of visual search performance. Schwark, Sandry, and Dolgov found that working memory capacity (WMC) predicts hit rate and reaction time in low prevalence searches. This link was attributed to higher WMC individuals exhibiting a higher quitting threshold and increasing the probability of finding the target before terminating search in low prevalence search. These conclusions were limited based on the methods; without eye tracking, the researchers could not differentiate between an increase in accuracy due to fewer identification errors (failing to identify a fixated target), selection errors (failing to fixate a target), or a combination of both. Here, we measure WMC and correlate it with reaction time and accuracy in a visual search task. We replicate the finding that WMC predicts reaction time and hit rate. However, our analysis shows that it does so through both a reduction in selection and identification errors. The correlation between WMC and selection errors is attributable to increased quitting thresholds in those with high WMC. The correlation between WMC and identification errors is less clear, though potentially attributable to increased item inspection times in those with higher WMC. In addition, unlike Schwark and coworkers, we find that these WMC effects are fairly consistent across prevalence rates rather than being specific to low-prevalence searches.

Front of Pack Labels Enhance Attention to Nutrition Information in Novel & Commercial Brands.

OBJECTIVES: 1) To assess whether Front-of-Pack (FOP) nutrition labels garner attention more readily than more complete, mandated nutrition information (the Nutrition Facts Panel (NFP), required in the US), and 2) To determine whether label design characteristics, specifically, color coding and/or coding with facial icons, increase attention to the FOP label. METHODS: In two experiments, we tracked the allocation of attention while participants (n=125) viewed novel and commercial packages with varied FOP designs using a change detection methodology. RESULTS: We found empirical evidence that FOP labels are attended more often, and earlier, than the currently mandated NFP, and that this benefit is due both to its placement on the front of the package and to the design characteristics of the FOP. Specifically, the use of color in FOPs increased attention to the label, but there was no evidence that coding information via facial icons impacted attention. CONCLUSIONS: Our work supports a growing body of evidence supporting the use of FOP labels to attract attention to nutritional information. Findings may be relevant to inform policy decisions on labeling standards.

Isolating the impact of a visual search template's color and form information on search guidance and verification times.

Visual search can be guided by biasing one's attention towards features associated with a target. Prior work has shown that high-fidelity, picture-based cues are more beneficial to search than text-based cues. However, typically picture cues provide both detailed form information and color information that is absent from text-based cues. Given that visual resolution deteriorates with eccentricity, it is not clear that high-fidelity form information would benefit guidance to peripheral objects - much of the picture benefit could be due to color information alone. To address this, we conducted a search task with eye-tracking that had four types of cues that comprised a 2 (text/pictorial cue) × 2 (no color/color) design. We hypothesized that color information would be important for efficient search guidance while high-fidelity form information would be important for efficient verification times. In Experiment 1 cues were a colored picture of the target, a gray-scaled picture of the target, a text-based cue that included color (e.g., "blue shoe"), or a text-based cue without color (e.g., "shoe"). Experiment 2 was a replication of Experiment 1, except that the color word in the text-based cue was presented in the precise color that was the dominant color in the target. Our results show that high-fidelity form information is important for efficient verifications times (with color playing less of a role) and color is important for efficient guidance, but form information also benefits guidance. These results suggest that different features of the cue independently contribute to different aspects of the search process.

Serial consolidation of orientation information into visual short-term memory.

Previous research suggests that there is a limit to the rate at which items can be consolidated in visual short-term memory (VSTM). This limit could be due to either a serial or a limited-capacity parallel process. Historically, it has proven difficult to distinguish between these two types of processes. In the present experiment, we took a novel approach that allowed us to do so. Participants viewed two oriented gratings either sequentially or simultaneously and reported one of the gratings' orientation via method of adjustment. Performance was worse for the simultaneous than for the sequential condition. We fit the data with a mixture model that assumes performance is limited by a noisy memory representation plus random guessing. Critically, the serial and limited-capacity parallel processes made distinct predictions regarding the model's guessing and memory-precision parameters. We found strong support for a serial process, which implies that one can consolidate only a single orientation into VSTM at a time.

Live imaging of the airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread.

SARS-CoV-2 initiates infection in the conducting airways, which rely on mucocilliary clearance (MCC) to minimize pathogen penetration. However, it is unclear how MCC impacts SARS-CoV-2 spread after infection is established. To understand viral spread at this site, we performed live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 9 days. Fluorescent markers for cilia and mucus allowed longitudinal monitoring of MCC, ciliary motion, and infection. The number of infected cells peaked at 4 days post-infection in characteristic foci that followed mucus movement. Inhibition of MCC using physical and genetic perturbations limited foci. Later in infection, MCC was diminished despite relatively subtle ciliary function defects. Resumption of MCC and infection spread after mucus removal suggests that mucus secretion mediates this effect. We show that MCC facilitates SARS-CoV-2 spread early in infection while later decreases in MCC inhibit spread, suggesting a complex interplay between SARS-CoV-2 and MCC.

A novel strategy to optimize critical information on over the counter labels for older adults.

Background and Aims: Labels designed to communicate critical information are paramount for the safe and effective use of over-the-counter medications; in recognition of this, the content and formatting of over the counter (OTC) labels sold in interstate commerce has been regulated for decades. Yet, available studies suggest that consumers frequently rely on limited information during decision making, failing to access the information required in the Drug Facts Label. This is particularly important for older consumers, who are at greater risk for adverse reactions to medicines. In two experiments we objectively evaluate how novel label designs that employ highlighting and a warning label placed on the package's front impact older consumers' attention to, and use of, critical information. Methods: In Experiment 1, 68 OTC patients (65+) engaged with a computer-based task answering yes/no scenario-based questions about a drug's appropriateness. In Experiment 2, 63 OTC patients (65+) conducted a forced-choice task where one of two drugs presented on a computer screen was appropriate for a provided scenario while the other was not. Both tasks required participants to access and use critical label information (i.e., warnings or active ingredients) to respond correctly. Dependent variables analyzed were the proportion of correct responses and time to correct response. Results: Highlighting or placing critical information on the front of the package significantly improved response accuracy and time to correct response in Experiment 1 as compared to responses utilizing the standard label. For Experiment 2, participants were faster and more accurate when critical information was highlighted. Conclusions: Results provide direct measures of the efficacy of novel labeling strategies. This information is relevant for regulations which dictate label design in ways that enhance ease and safety of use of medications for older adults.

Vibrio cholerae Alkalizes Its Environment via Citrate Metabolism to Inhibit Enteric Growth In Vitro.

Vibrio cholerae is a Gram-negative pathogen, living in constant competition with other bacteria in marine environments and during human infection. One competitive advantage of V. cholerae is the ability to metabolize diverse carbon sources, such as chitin and citrate. We observed that when some V. cholerae strains were grown on a medium with citrate, the medium's chemical composition turned into a hostile alkaline environment for Gram-negative bacteria, such as Escherichia coli and Shigella flexneri. We found that although the ability to exclude competing bacteria was not contingent on exogenous citrate, V. cholerae C6706 citrate metabolism mutants ΔoadA-1, ΔcitE, and ΔcitF were not able to inhibit S. flexneri or E. coli growth. Lastly, we demonstrated that while the V. cholerae C6706-mediated increased medium pH was necessary for the enteric exclusion phenotype, secondary metabolites, such as bicarbonate (protonated to carbonate in the raised pH) from the metabolism of citrate, enhanced the ability to inhibit the growth of E. coli. These data provide a novel example of how V. cholerae outcompetes other Gram-negative bacteria. IMPORTANCE Vibrio cholerae must compete with other bacteria in order to cause disease. Here, we show that V. cholerae creates an alkaline environment, which is able to inhibit the growth of other enteric bacteria. We demonstrate that V. cholerae environmental alkalization is linked to the capacity of the bacteria to metabolize citrate. This behavior could potentially contribute to V. cholerae's ability to colonize the human intestine.

Quitting thresholds in visual search are impacted by target present detection times but not their variability.

Models of visual search posit that target absent responses occur when the quitting threshold for the trial is reached before a target is detected, and that feedback about missed targets allows the quitting threshold to be adaptively set to the difficulty of the search task. While these models may effectively capture processes in lab-based tasks, in real-world searches feedback is often impossible to provide. Instead, observers have little information about their errors, and may only be aware of when they successfully detect the target. We posit that in the absence of feedback the time required to find a target might influence quitting thresholds. In three experiments, we investigate how manipulating the mean time and the standard deviation of time to detect a target influence quitting thresholds in target absent trials. To vary target detection times while holding the search stimuli constant, we used an eye-movement contingent change to surreptitiously introduce a target near fixation at a particular time. Results show that decreasing the mean time to find a target also decreases the number of items inspected and reaction time in target absent trials, the hallmark of a shift in the quitting threshold. By contrast, varying the standard deviation around a fixed mean had no impact on target absent search times. These findings suggest that people are sensitive to the typical time required to find a target in a given task and use that information to flexibly adjust target absent quitting thresholds, but people are not sensitive to the variability.