Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenic E. coli adhesin.

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as human volunteers challenged with ETEC, diarrheal severity is significantly increased severity in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of human volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected human volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design. Author summary: Enterotoxigenic E. coli (ETEC), a leading cause of diarrhea disproportionately affecting young children in low-income regions, are a priority for vaccine development. Individuals possessing A blood-type are more susceptible to severe cholera-like disease. EtpA, a secreted, immunogenic, blood group A binding protein, is a current vaccine target antigen. Here, we determined the atomic structure of EtpA in complex with protective as well as non-protective monoclonal antibodies targeting two different domains of the protein, allowing us to pinpoint key regions involved in blood-group A antigen recognition and uncover the mechanism of antibody-based protection. In addition, we show through mass-spectrometry that EtpA is extensively and heterogeneously glycosylated at surface-exposed asparagine residues by a promiscuous and low-fidelity glycosyltransferase, EtpC, and that this unique form of bacterial glycosylation is critical for to development of protective immune responses. Lastly, polyclonal antibodies from vaccinated mice as well as monoclonal antibodies obtained from ETEC-infected human volunteers revealed that the highly antigenic surface of EtpA exhibits both protective and non-protective epitopes. These results greatly expand our understanding of ETEC pathogenesis, and the immune responses elicited by these common infections, providing valuable information to aid in the rational design and testing of subunit vaccines.

Label-free detection and profiling of individual solution-phase molecules.

Most chemistry and biology occurs in solution, in which conformational dynamics and complexation underlie behaviour and function. Single-molecule techniques1 are uniquely suited to resolving molecular diversity and new label-free approaches are reshaping the power of single-molecule measurements. A label-free single-molecule method2-16 capable of revealing details of molecular conformation in solution17,18 would allow a new microscopic perspective of unprecedented detail. Here we use the enhanced light-molecule interactions in high-finesse fibre-based Fabry-Pérot microcavities19-21 to detect individual biomolecules as small as 1.2 kDa, a ten-amino-acid peptide, with signal-to-noise ratios (SNRs) >100, even as the molecules are unlabelled and freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of subpopulations in mixed samples. Notably, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight and composition but different conformation can also be resolved. Detection is based on the creation of a new molecular velocity filter window and a dynamic thermal priming mechanism that make use of the interplay between optical and thermal dynamics22,23 and Pound-Drever-Hall (PDH) cavity locking24 to reveal molecular motion even while suppressing environmental noise. New in vitro ways of revealing molecular conformation, diversity and dynamics can find broad potential for applications in the life and chemical sciences.

Behind the Scenes: Facilitators and Barriers to Developing State Scarce Resource Allocation Plans for the COVID-19 Pandemic.

BACKGROUND: In response to COVID-19, many states revised, developed, or attempted to develop plans to allocate scarce critical care resources in the event that crisis standards of care were triggered. No prior analysis has assessed this plan development process, including whether plans were successfully adopted. RESEARCH QUESTION: How did states develop or revise scarce resource allocation plans during the COVID-19 pandemic, and what were the barriers and facilitators to their development and adoption at the state level? STUDY DESIGN AND METHODS: Plan authors and state leaders completed a semi-structured interview February to September 2022. Interview transcripts were qualitatively analyzed for themes related to plan development and adoption according to the principles of grounded theory. RESULTS: Thirty-six participants from 34 states completed an interview, from states distributed across all US regions. Among participants' states with plans that existed prior to 2020 (n = 24), 17 were revised and adopted in response to COVID-19. Six states wrote a plan de novo, with the remaining states failing to develop or adopt a plan. Thirteen states continued to revise their plans in response to disability or aging bias complaints or to respond to evolving needs. Many participants expressed that urgency in the early days of the pandemic prevented an ideal development process. Facilitators of successful plan development and adoption include: coordination or support from the state department of health and existing relationships with key community partners, including aging and disability rights groups and minoritized communities. Barriers include lack of perceived political interest in a plan and development during a public health emergency. INTERPRETATION: To avoid repeating mistakes from the early days of the COVID-19 response, states should develop or revise plans with community engagement and consider maintaining a standing committee with diverse membership and content expertise to periodically review plans and advise state officials on pandemic preparedness.

Factors that Impact Photochemical Cage Escape Yields.

The utilization of visible light to mediate chemical reactions in fluid solutions has applications that range from solar fuel production to medicine and organic synthesis. These reactions are typically initiated by electron transfer between a photoexcited dye molecule (a photosensitizer) and a redox-active quencher to yield radical pairs that are intimately associated within a solvent cage. Many of these radicals undergo rapid thermodynamically favored "geminate" recombination and do not diffuse out of the solvent cage that surrounds them. Those that do escape the cage are useful reagents that may undergo subsequent reactions important to the above-mentioned applications. The cage escape process and the factors that determine the yields remain poorly understood despite decades of research motivated by their practical and fundamental importance. Herein, state-of-the-art research on light-induced electron transfer and cage escape that has appeared since the seminal 1972 review by J. P. Lorand entitled "The Cage Effect" is reviewed. This review also provides some background for those new to the field and discusses the cage escape process of both homolytic bond photodissociation and bimolecular light induced electron transfer reactions. The review concludes with some key goals and directions for future research that promise to elevate this very vibrant field to even greater heights.

Between-task transfer of item-specific control is replicable and extends to novel conditions.

Learning-guided control refers to adjustments of cognitive control settings based on learned associations between predictive cues and the likelihood of conflict. In three preregistered experiments, we examined transfer of item-specific control settings beyond conditions under which they were learned. In Experiment 1, an item-specific proportion congruence (ISPC) manipulation was applied in a training phase in which target color in a Flanker task was biased (mostly congruent or mostly incongruent). In a subsequent transfer phase, participants performed a color-word Stroop task in which the same target colors were unbiased (50% congruent). The same design was implemented in Experiment 2, but training and transfer tasks were intermixed within blocks. Between-task transfer was evidenced in both experiments, suggesting learned control settings associated with the predictive cues were retrieved when encountering unbiased transfer items. In Experiment 3, we investigated a farther version of between-task transfer by using training (color-word Stroop) and transfer (picture-word Stroop) tasks that did not share the relevant (to-be-named) dimension or response sets. Despite the stronger, between-task boundary, we observed an ISPC effect for the transfer items, but it did not emerge until the second half of the experiment. The results provided converging evidence for the flexibility and automaticity of item-specific control. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Humans do not avoid reactively implementing cognitive control.

The ability to exert cognitive control allows us to achieve goals in the face of distraction and competing actions. However, control is costly-people generally aim to minimize its demands. Because control takes many forms, it is important to understand whether such costs apply universally. Specifically, reactive control, which is recruited in response to stimulus or contextual features, is theorized to be deployed automatically, and not depend on attentional resources. Here, we investigated whether people avoided implementing reactive control in three experiments. In all, participants performed a Stroop task in which certain items were mostly incongruent (MI), that is, associated with a high likelihood of conflict (triggering a focused control setting). Other items were mostly congruent, that is, associated with a low likelihood of conflict (triggering a relaxed control setting). Experiment 1 demonstrated that these control settings transfer to a subsequent unbiased transfer phase. In Experiments 2-3, we used a demand selection task to investigate whether people would avoid choice options that yielded items that were previously MI. In all, participants continued to retrieve focused control settings for previously MI items, but they did not avoid them in the demand selection task. Critically, we only found demand avoidance when there was an objective difference in demand between options. These findings are consistent with the idea that implementing reactive control does not register as costly. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emergency Department Sepsis Triage Scoring Tool Elements Associated With Hypotension Within 24 Hours in Children With Fever and Tachycardia.

OBJECTIVE: Pediatric sepsis screening is becoming the standard of care for children presenting to the emergency department (ED) and has been shown to improve recognition of severe sepsis, but it is unknown if these screening tools can predict progression of disease. The objective of this study was to determine if any elements of a sepsis triage trigger tool were predictive of progression to hypotensive shock in children presenting to the ED with fever and tachycardia. METHODS: This study is a retrospective case-control study of children ≤18 years presenting to an ED with fever and tachycardia, comparing those who went on to develop hypotensive shock in the subsequent 24 hours (case) to those who did not (control). Primary outcome was the proportion of encounters where the patient had specific abnormal vital signs or clinical signs as components of the sepsis triage score. The secondary outcomes were the proportion of encounters where the patient had a sepsis risk factor. RESULTS: During the study period, there were 94 patients who met case criteria and 186 controls selected. In the adjusted multivariable model, the 2 components of the sepsis triage score that were more common in case patients were the presence of severe cerebral palsy (adjusted odds ratio, 9.4 [3.7, 23.9]) and abnormal capillary refill at triage (adjusted odds ratio, 3.1 [1.4, 6.9]). CONCLUSIONS: Among children who present to a pediatric ED with fever and tachycardia, those with prolonged capillary refill at triage or severe cerebral palsy were more likely to progress to decompensated septic shock, despite routine ED care.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Trapdoor endarterectomy for coral reef plaque of the paravisceral aorta in the modern era.

Coral reef atherosclerosis of the paravisceral aorta is a rare disease whose description is confined to before contemporary vascular surgical techniques. This study aims to describe the characteristics and outcomes of patients with coral reef aorta treated with trapdoor endarterectomy at a single high-volume quaternary referral center since 2010. From 2010 to 2022, 14 patients with coral reef aorta were treated with trapdoor endarterectomy. The patient data were obtained via a retrospective medical record review. The patients were predominantly women (79%) with a median age of 65 years (interquartile range [IQR], 60-70 years). The patients universally had a tobacco smoking history and hypertension. More than 85% had previously diagnosed carotid stenosis. Two patients (14%) had undergone prior aortofemoral reconstruction, and one patient (7%) had undergone prior axillobifemoral bypass. The most common presenting symptoms were claudication (71%), chronic mesenteric ischemia (50%), and renovascular hypertension (43%). Of the 14 patients, 8 (57%) underwent isolated endarterectomy and 6 (43%) underwent concomitant aortobifemoral bypass. In addition, 13 patients (93%) required a supraceliac aortic clamp position with a median clamp time of 23 minutes (IQR, 20-30 minutes). The median estimated blood loss was 1650 mL (IQR, 1025-3000 mL). A cell saver was used in 13 procedures (93%), with a median transfusion of 563 mL (IQR, 231-900 mL). The median operative time was 341 minutes (IQR, 315-416 minutes). Eight patients (57%) experienced acute kidney injury in the postoperative period with a peak creatinine of 1.96 mg/dL (IQR, 1.50-2.84 mg/dL). The median length of stay was 11 days (IQR, 6-16 days), with an intensive care unit stay of 4 days (IQR, 2-7 days). One patient (7%) required reoperation in the immediate perioperative period for a retroperitoneal hematoma. The postoperative ankle brachial index increased from a median of 0.58 (right) and 0.57 (left) bilaterally in the preoperative period to 1.09 (right) and 1.10 (left) postoperatively. Eight patients (57%) had follow-up data available for >2 years postoperatively, with five patients (36%) having follow-up data available for >3 years. Two major adverse cardiac events were reported at the last follow-up. One patient reported mild recurrent symptoms of chronic mesenteric ischemia during 3 years of postoperatively, with no concurrent imaging findings or loss of patency found on computed tomography angiography. Symptomatic coral reef atherosclerosis of the paravisceral aorta is a complex disease rarely encountered even at high-volume referral centers. These patients can be expected to experience short-term postoperative morbidity and require intensive care. Despite these challenges, trapdoor endarterectomy is a safe and effective procedure for coral reef aorta, and most patients achieve dramatic symptomatic improvement with durable results.

Cold Agglutinin Disease and COVID-19: A Scoping Review of Treatments and Outcomes.

Background: Reports suggest that patients with both acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and cold agglutinin disease (CAD) may experience poorer survival when treated with rituximab. We conducted a scoping review to evaluate severe outcomes, including intensive care unit (ICU) admission and mortality, in coronavirus disease 2019 (COVID-19) patients with CAD on various treatments, including rituximab. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Four literature databases were searched on December 19, 2023, for studies reporting lab-confirmed SARS-CoV-2 and CAD, excluding rheumatological conditions. Results: Of the 741 screened articles, 19 were included. Studies, predominantly case reports (17/19) or case series (2/19), were mainly from the USA (8/19) and India (3/19), with others across Europe and Asia. Among 23 patients (61% female, median age 61 years), 21/23 had a new CAD diagnosis; only two had pre-existing CAD. Overall, 74% recovered, 21% died, and outcomes for one were unreported. Nine (39%) were ICU-admitted. Of rituximab-treated patients (n = 4), 25% were ICU-admitted, none died. Non-rituximab treatments (n = 19) saw 42% ICU admissions and 26% mortality. Conclusions: This review found no increased risk of severe outcomes in CAD and COVID-19 patients treated with rituximab.

Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity.

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms.

SOHO State-of-the-Art Updates and Next Questions: Treatment for Newly Diagnosed Peripheral T-Cell Lymphomas.

Although a rare subset of non-Hodgkin lymphomas, peripheral T-cell lymphomas (PTCL) account for a disproportionate proportion of patient mortality. Conventional therapies are derived from experience treating aggressive B-cell lymphomas and center around CHOP-based chemotherapy. However, due to the unique biology and diverse subtypes of PTCL, most patients fail to durably respond to this approach and 5-year survival is only 20% to 30%. There have been multiple attempts to improve outcomes for patients with PTCL. Among the more successful strategies are the use of consolidative autologous stem cell transplant, the augmentation of CHOP with etoposide (CHOEP), and the use of brentuximab vedotin in CD30-positive PTCL. Advances in the understanding of histology-specific biology has cultivated enthusiasm to evaluate hypomethylating agents, histone deacetylate inhibitors, and phosphoinositol-3-kinase inhibitors in the frontline setting. Improvements in monitoring disease response and prognostication including the use of cell-free DNA, mutational profiling, and interim PET/CT imaging are also on the horizon. For patients with acute T-cell leukemia/lymphoma, the use of mogamulizumab-based therapy in the frontline setting may lead to advances in care. The true impact of these new-era therapies will only be elucidated as clinical practices incorporate the rapidly changing evidence.

Sequence effects and speech processing: cognitive load for speaker-switching within and across accents.

Prior work in speech processing indicates that listening tasks with multiple speakers (as opposed to a single speaker) result in slower and less accurate processing. Notably, the trial-to-trial cognitive demands of switching between speakers or switching between accents have yet to be examined. We used pupillometry, a physiological index of cognitive load, to examine the demands of processing first (L1) and second (L2) language-accented speech when listening to sentences produced by the same speaker consecutively (no switch), a novel speaker of the same accent (within-accent switch), and a novel speaker with a different accent (across-accent switch). Inspired by research on sequential adjustments in cognitive control, we aimed to identify the cognitive demands of accommodating a novel speaker and accent by examining the trial-to-trial changes in pupil dilation during speech processing. Our results indicate that switching between speakers was more cognitively demanding than listening to the same speaker consecutively. Additionally, switching to a novel speaker with a different accent was more cognitively demanding than switching between speakers of the same accent. However, there was an asymmetry for across-accent switches, such that switching from an L1 to an L2 accent was more demanding than vice versa. Findings from the present study align with work examining multi-talker processing costs, and provide novel evidence that listeners dynamically adjust cognitive processing to accommodate speaker and accent variability. We discuss these novel findings in the context of an active control model and auditory streaming framework of speech processing.

Continental Scale Hydrostratigraphy: Basin-Scale Testing of Alternative Data-Driven Approaches.

Integrated hydrological modeling is an effective method for understanding interactions between parts of the hydrologic cycle, quantifying water resources, and furthering knowledge of hydrologic processes. However, these models are dependent on robust and accurate datasets that physically represent spatial characteristics as model inputs. This study evaluates multiple data-driven approaches for estimating hydraulic conductivity and subsurface properties at the continental-scale, constructed from existing subsurface dataset components. Each subsurface configuration represents upper (unconfined) hydrogeology, lower (confined) hydrogeology, and the presence of a vertical flow barrier. Configurations are tested in two large-scale U.S. watersheds using an integrated model. Model results are compared to observed streamflow and steady state water table depth (WTD). We provide model results for a range of configurations and show that both WTD and surface water partitioning are important indicators of performance. We also show that geology data source, total subsurface depth, anisotropy, and inclusion of a vertical flow barrier are the most important considerations for subsurface configurations. While a range of configurations proved viable, we provide a recommended Selected National Configuration 1 km resolution subsurface dataset for use in distributed large-and continental-scale hydrologic modeling.

Continental Scale Hydrostratigraphy: Comparing Geologically Informed Data Products to Analytical Solutions.

This study synthesizes two different methods for estimating hydraulic conductivity (K) at large scales. We derive analytical approaches that estimate K and apply them to the contiguous United States. We then compare these analytical approaches to three-dimensional, national gridded K data products and three transmissivity (T) data products developed from publicly available sources. We evaluate these data products using multiple approaches: comparing their statistics qualitatively and quantitatively and with hydrologic model simulations. Some of these datasets were used as inputs for an integrated hydrologic model of the Upper Colorado River Basin and the comparison of the results with observations was used to further evaluate the K data products. Simulated average daily streamflow was compared to daily flow data from 10 USGS stream gages in the domain, and annually averaged simulated groundwater depths are compared to observations from nearly 2000 monitoring wells. We find streamflow predictions from analytically informed simulations to be similar in relative bias and Spearman's rho to the geologically informed simulations. R-squared values for groundwater depth predictions are close between the best performing analytically and geologically informed simulations at 0.68 and 0.70 respectively, with RMSE values under 10 m. We also show that the analytical approach derived by this study produces estimates of K that are similar in spatial distribution, standard deviation, mean value, and modeling performance to geologically-informed estimates. The results of this work are used to inform a follow-on study that tests additional data-driven approaches in multiple basins within the contiguous United States.

CD62L expression marks a functionally distinct subset of memory B cells.

The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.

Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase.

There is growing appreciation for neuraminidase (NA) as an influenza vaccine target; however, its antigenicity remains poorly characterized. In this study, we isolated three broadly reactive N2 antibodies from the plasmablasts of a single vaccinee, including one that cross-reacts with NAs from seasonal H3N2 strains spanning five decades. Although these three antibodies have diverse germline usages, they recognize similar epitopes that are distant from the NA active site and instead involve the highly conserved underside of NA head domain. We also showed that all three antibodies confer prophylactic and therapeutic protection in vivo, due to both Fc effector functions and NA inhibition through steric hindrance. Additionally, the contribution of Fc effector functions to protection in vivo inversely correlates with viral growth inhibition activity in vitro. Overall, our findings advance the understanding of NA antibody response and provide important insights into the development of a broadly protective influenza vaccine.

Revealing object-based cognitive control in a moving object paradigm.

Object-based attention and flexible adjustments of cognitive control based on contextual cues signaling the likelihood of distraction are well documented. However, no prior research has conclusively demonstrated that people flexibly adjust cognitive control to minimize distraction based on learned associations between task-irrelevant objects and distraction likelihood (i.e., object-based cognitive control). To fill this gap, we developed a novel paradigm during which participants responded to flanker stimuli appearing in one of multiple locations on two simultaneously presented objects. One object predicted a low likelihood of encountering an incongruent flanker stimulus and the other a high likelihood. After each response, the objects rotated clockwise such that all locations on average were 50% congruent, thereby eliminating confounds between location and likelihood of incongruence. Object-based cognitive control was evidenced by reduced flanker compatibility effects in the high compared to low conflict object. Across four experiments, we demonstrated that object-based cognitive control was dependent on a strong manipulation of the likelihood of conflict between objects and movement of the objects between trials. The novel evidence for object-based cognitive control is important in showing that people exploit not only location as a cue to guide control, but additionally objects, mirroring evidence on object and location-based attention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).