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The interplay between SARS-CoV-2 and contemporaneous bacterial or fungal culture growth may have crucial implications for clinical outcomes of hospitalized patients. This study aimed to quantify the effect of microbiological culture positivity on mortality among hospitalized patients with SARS-CoV-2.
Methods:
In this retrospective cohort study, we included adult hospitalized patients from OPTUM COVID-19 specific data set, who tested positive for SARS-CoV-2 within 14 days of hospitalization between 01/20/2020 and 01/20/2022. We examined outcomes of individuals with organisms growing on cultures from the bloodstream infections (BSIs), urinary tract, and respiratory tract, and a composite of the three sites. We used propensity score matching on covariates included demographics, comorbidities, and hospitalization clinical parameters. In a sensitivity analysis, we included same covariates but excluded critical care variables such as length of stay, intensive care unit stays, mechanical ventilation, and extracorporeal membrane oxygenation.
Results:
The cohort included 104,560 SARS-CoV-2 positive adult hospitalized patients across the United States. The unadjusted mortality odds increased significantly with BSIs (98.7%) and with growth on respiratory cultures (RC) (176.6%), but not with growth on urinary cultures (UC). Adjusted analyses showed that BSIs and positive RC independently contribute to mortality, even after accounting for critical care variables.
Conclusions:
In SARS-CoV-2-positive hospitalized patients, positive bacterial and fungal microbiological cultures, especially BSIs and RC, are associated with an increased risk of mortality even after accounting for critical care variables associated with disease severity. These findings underscore the importance of stringent infection control and the effective management of secondary infections to improve patient outcomes.
Background: Indiscriminate urine culturing of patients with indwelling urinary catheters may lead to overdiagnosis of urinary tract infections, resulting in unnecessary antibiotic treatment and inaccurate reporting of catheter-associated urinary tract infections (CAUTIs) as a hospital quality metric. We evaluated the impact of a computerized diagnostic stewardship intervention to improve urine culture testing among patients with indwelling urinary catheters. Methods: We performed a single-center retrospective observational study at Rush University Medical Center from April 2018 – July 2023. In February 2021, we implemented a computerized clinical decision support tool to promote adherence to our internal urine culture guidelines for patients with indwelling urinary catheters. Providers were required to select one guideline criteria: 1) neutropenia, 2) kidney transplant, 3) recent urologic procedure, 4) urinary tract obstruction; or if none of the criteria were met, then an infectious diseases consultation was required for approval. We compared facility-wide CAUTI rate per 10,000 catheter days and standardized infection ratio (SIR) during baseline and intervention periods using ecologic models, controlling for time and for monthly Covid-19 hospitalizations. In the intervention period, we evaluated how providers responded to the intervention. Potential harm was defined as collection of a urine culture within 7 days of the intervention that resulted in a change in clinical management. Results: In unadjusted models, CAUTI rate decreased from 12.5 to 7.6 per 10,000 catheter days (p=0.04) and SIR decreased from 0.77 to 0.49 (p=0.09) during baseline vs intervention periods. In adjusted models, the CAUTI rate decreased from 6.9 to 5.5 per 10,000 catheter days (p=0.60) (Figure 1) and SIR decreased from 0.41 to 0.35 (p=0.65) during baseline vs intervention periods. Urine catheter standard utilization ratio (SUR) did not change (p=0.36). There were 598 patient encounters with ≥1 intervention. Selecting the first intervention for each encounter, 284 (47.5%) urine cultures met our guidelines for testing and 314 (52.5%) were averted (Figure 2). Of these, only 3 ( < 1 %) had a urine culture collected in the subsequent 7 days that resulted in change in clinical management. Conclusion: We observed a trend of decreased CAUTIs over time, but effect of our diagnostic stewardship intervention was difficult to assess due to healthcare disruption caused by Covid-19. Adverse outcomes were rare among patients who had a urine culture averted. A computerized clinical decision support tool may be safe and effective as part of a multimodal program to reduce unnecessary urine cultures in patients with indwelling urinary catheters.
This study identified 26 late invasive primary surgical site infection (IP-SSI) within 4–12 months of transplantation among 2073 SOT recipients at Duke University Hospital over the period 2015–2019. Thoracic organ transplants accounted for 25 late IP-SSI. Surveillance for late IP-SSI should be maintained for at least one year following transplant.
This contribution departs from an existing model, the Design Framework for Systems-of-Systems Resilience, to explore systems resilience issues across the health, environmental, and economic domains. The reported research activities include 1) a rapid review to collect a set of systems indicators and 2) a design workshop employing causal loop diagramming to map expected causal influences between indicators. Through this exercise, we examine key themes in this research domain and outline directions for further enquiry, while involving members of the design research community in an open dialogue.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Analyzing data from a national deidentified electronic health record-based data set using a matched case–control study design, we found that antibiotic use and severity of illness were independent risk factors for healthcare-associated candidemia in adult patients hospitalized with SARS-CoV-2 infection. Interleukin-6 inhibitor and corticosteroid use were not independent risk factors.
With the efflorescence of palaeoscientific approaches to the past, historians have been confronted with a wealth of new evidence on both human and natural phenomena, from human disease and migration to landscape change and climate. These new data require a rewriting of our narratives of the past, questioning what constitutes an authoritative historical source and who is entitled to recount history to contemporary societies. Humanities-based historical inquiry must embrace this new evidence, but to do so historians need to engage with it critically, just as they do with textual and material sources. This article highlights the most vital methodological issues, ranging from the spatiotemporal scales and heterogeneity of the new evidence to the new roles attributed to quantitative methods and the place of scientific data in narrative construction. It considers areas of study where the palaeosciences have “intruded” into fields and subjects previously reserved for historians, especially socioeconomic, climate, and environmental history. The authors argue that active engagement with new approaches is urgently needed if historians want to contribute to our evolving understanding of the challenges of the Anthropocene.
Hemodynamic collapse in multi-trauma patients with severe traumatic brain injury (TBI) poses both a diagnostic and therapeutic challenge for prehospital clinicians. Brain injury associated shock (BIAS), likely resulting from catecholamine storm, can cause both ventricular dysfunction and vasoplegia but may present clinically in a manner similar to hemorrhagic shock. Despite different treatment strategies, few studies exist describing this phenomenon in the early post-injury phase. This retrospective observational study aimed to describe the frequency of shock in isolated TBI in prehospital trauma patients and to compare their clinical characteristics to those patients with hemorrhagic shock and TBI without shock.
Methods:
All prehospital trauma patients intubated by prehospital medical teams from New South Wales Ambulance Aeromedical Operations (NSWA-AO) with an initial Glasgow Coma Scale (GCS) of 12 or less were investigated. Shock was defined as a pre-intubation systolic blood pressure under 90mmHg and the administration of blood products or vasopressors. Injuries were classified from in-hospital computed tomography (CT) reports. From this, three study groups were derived: BIAS, hemorrhagic shock, and isolated TBI without shock. Descriptive statistics were then produced for clinical and treatment variables.
Results:
Of 1,292 intubated patients, 423 had an initial GCS of 12 or less, 24 patients (5.7% of the original cohort) had shock with an isolated TBI, and 39 patients had hemorrhagic shock. The hemodynamic parameters were similar amongst these groups, including values of tachycardia, hypotension, and elevated shock index. Prehospital clinical interventions including blood transfusion and total fluids administered were also similar, suggesting they were indistinguishable to prehospital clinicians.
Conclusions:
Hemodynamic compromise in the setting of isolated severe TBI is a rare clinical entity. Current prehospital physiological data available to clinicians do not allow for easy delineation between these patients from those with hemorrhagic shock.
OBJECTIVES/GOALS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern due to its increasing prevalence and association with type 2 diabetes mellitus. Non-invasive magnetic resonance-based biomarkers can aid in the monitoring of disease progression and identification of patients at risk for chronic liver disease. METHODS/STUDY POPULATION: Over 600 subjects will be recruited from the San Antonio Mexican American Family Study and from a second study, which consists of (i) T2DM patients diagnosed with either MASLD or metabolic dysfunction-associated steatohepatitis (MASH) or (ii) metabolically healthy controls. Hydrogen-1 MRS and diffusion-weighted MRI (DW-MRI) will be used to measure liver fat fraction and liver stiffness biomarkers, respectively. Several potential biomarkers of liver stiffness will be evaluated in vivo using the intravoxel incoherent motion (IVIM) model for DW-MRI. To further improve the diagnostic accuracy of patients with liver fibrosis, we will integrate MRI/MRS data with relevant clinical indicators of hepatic metabolism. Results will be compared to biopsy samples to evaluate the model’s diagnostic accuracy. RESULTS/ANTICIPATED RESULTS: Based on preliminary data, we predict that IVIM will be able to accurately diagnose hepatic fibrosis in patients with MASLD, allowing it to be implemented in clinics with high-field MRI units easily. Previous studies have shown correlations between IVIM estimates and fibrosis stages, however, none included additional clinical indicators of liver disease in their models. We have already found significant differences in metabolic measurements such as fasting plasma glucose and HbA1c levels. Additionally, the use of machine learning in developing these models has shown improvements in the ability to extract features from the data. The aim is to achieve high accuracy and robustness in the staging of liver fibrosis. DISCUSSION/SIGNIFICANCE: Over 100 million people in the US are affected by MASLD. Without treatment, it progresses from hepatic steatosis to MASH, fibrosis (liver stiffening), and ultimately to hepatic cirrhosis and hepatocellular carcinoma (HCC). Continued research efforts and clinical implementation of MRI and MRS are vital in combating the growing burden of MASLD.
Solid particles trapped in an acoustic standing wave have been observed to undergo propulsion. This phenomenon has been attributed to the generation of a steady streaming flow, with a reversal in the propulsion direction at a distinct frequency. We explain the mechanism underlying this reversal by considering the canonical problem of a sphere executing oscillatory rotation in an unbounded fluid that undergoes rectilinear oscillation; these two oscillations occur at identical frequency but with an arbitrary phase difference. Two distinct bifurcations in the flow field occur: (1) a stagnation point first forms with increasing frequency, which (2) splits into a saddle node and a vortex centre. Reversal in the propulsion direction is driven by reversal in the flow far from the sphere, which coincides with the second bifurcation. This flow is identified with that of a Stokeslet whose strength is the net force exerted on the particle, which has implications for studying the flow field around particles of non-spherical geometries and for modelling suspensions of particles in acoustic fields.
Cooperative and caring behaviors are key drivers of human social progress, especially during catastrophes or pandemic events. While COVID-19 pandemics was arriving to Colombia in absence of any approved therapeutic strategy or vaccine, and based on evidence from other viral diseases, we anticipated to hypothesize the protective role of some nutritional supplements such as Vitamin D and C against SARS-CoV2. Therefore, for health workers, we proposed a voluntarily nutritional supplementation plan to fortify their immune system aiming to prevent or mitigate eventual COVID-19 infection and disease. Using the behavioral EAST framework, all our health workers (n = 1,063) were invited via email to participate voluntarily in a supplementation strategy for a period of 3 months. 77.4% accepted participation, and among them, we identified a group with optimal adherence to the proposed supplementation plan (20%) and a predominant group with no adherence at all (57.29%). Adherence seemed to be associated to a risk perception bias that was predominant in female workers and those workers performing in working areas with higher risk of infection. Of importance, adherence to the supplementation strategy was associated to a lower percentage of COVID-19 diagnostics (12%) as compared with that observed in non-adherence participants (19%). Moreover, the sustained adherence during the time of intervention seemed to promote adoption of this target behavior, as up to 35% of the adherent participants remained attached (on their own) to the supplementation habit, 3 months after the end of the intervention. All these data show the potential relevance of EAST frameworks as tools to trigger health care and altruistic behaviors to avoid the spread of pandemic diseases. In line with other authors, our observations suggest that nutritional vitamin D and C supplementation could mitigate the risk of COVID-19, highlighting the behavioral and biological relevance of this type of interventions during emerging or re-emerging infectious diseases.
This study investigates the impact of primary care utilisation of a symptom-based head and neck cancer risk calculator (Head and Neck Cancer Risk Calculator version 2) in the post-coronavirus disease 2019 period on the number of primary care referrals and cancer diagnoses.
Methods
The number of referrals from April 2019 to August 2019 and from April 2020 to July 2020 (pre-calculator) was compared with the number from the period January 2021 to August 2022 (post-calculator) using the chi-square test. The patients’ characteristics, referral urgency, triage outcome, Head and Neck Cancer Risk Calculator version 2 score and cancer diagnosis were recorded.
Results
In total, 1110 referrals from the pre-calculator period were compared with 1559 from the post-calculator period. Patient characteristics were comparable for both cohorts. More patients were referred on the cancer pathway in the post-calculator cohort (pre-calculator patients 51.1 per cent vs post-calculator 64.0 per cent). The cancer diagnosis rate increased from 2.7 per cent in the pre-calculator cohort to 3.3 per cent in the post-calculator cohort. A lower rate of cancer diagnosis in the non-cancer pathway occurred in the cohort managed using the Head and Neck Cancer Risk Calculator version 2 (10 per cent vs 23 per cent, p = 0.10).
Conclusion
Head and Neck Cancer Risk Calculator version 2 demonstrated high sensitivity in cancer diagnosis. Further studies are required to improve the predictive strength of the calculator.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Background: The FIRST Trial is a 5-year study funded by the Agency for Healthcare Research and Quality. Our investigation is situated within a more extensive study to restrict fluoroquinolone antibiotics by requiring providers to obtain authorization from an infectious disease physician before prescribing fluoroquinolones. Our research team is performing a systematic evaluation to identify organizational characteristics and influencers of the fluoroquinolone preprescription authorization implementation process to understand variables that may facilitate or hinder implementation success. Methods: To address this critical gap, we present a qualitative analysis from our ongoing, multisite research project aimed at systematically assessing the adoption of an antimicrobial stewardship intervention in the form of an EHR-integrated best-practice alert (BPA) at each site to identify work system factors that impact uptake and variability in the implementation of the BPA at each location. The evaluation provides a detailed explanation of activities through the implementation process (eg, before implementation, during implementation, and after implementation) to assess how an organization effectively negotiates the phases and transitions, ultimately influencing the impact of the intervention. We have used a contextual determinant framework (CFIR) that has enabled us to perform a systematic and comprehensive exploration and identification of potential explanatory themes or variables to shed light on the complex social phenomenon of implementation. Results: Participants who will be a part of our poster presentation will learn about implementing a BPA, the potential barriers to implementation, and strategies for overcoming these barriers. Stakeholders within our study include site coordinators, medical doctors, nurses, pharmacists, and clinical informaticists. Our analysis synthesizes their experiences implementing and sustaining this evidence-based antimicrobial stewardship intervention. It includes (1) a detailed description of the process of change, (2) work-system factors (eg, inner setting and outer setting) that they believe influenced the success of the intervention, (3) barriers and facilitators (eg, CFIR constructs) within the implementation process; and (4) description of how these could have influenced the outcomes of interest (eg, implementation and intervention effectiveness). Conclusions: Our research is expected to advance patient safety research and initiatives by providing a more robust approach to performing systematic intervention evaluations. By outlining stakeholders’ experiences within our study, implementation leaders within healthcare systems will utilize our findings to aid them in their design and implementation process when designing and implementing similar types of healthcare interventions.
Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.
Methods
Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.
Results
Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).
Conclusion
Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.
The oscillating relativistic electrons in the accelerating/focusing wakefields of plasma accelerators emit electromagnetic radiation known as betatron radiation (BR). The proton-driven plasma wakefield acceleration has been demonstrated in the Advanced Wakefield Experiment (AWAKE) at CERN; however, its accompanying radiation emission is less explored compared with those in the laser- and electron beam-driven plasma accelerators. In this paper, a detailed simulation study of BR in the AWAKE is presented. Considering the new set-up of the AWAKE Run 2 (2021–), the radiation emission from both the witness electron beam and the seeding electron beam is investigated using particle-in-cell simulations. The influence of radial size mismatch and misaligned off-axis injection on the witness beam dynamics, as well as the spectral features of the relevant BR are studied. These non-ideal electron injections are likely to occur in experiment. The proton self-modulation stage is also investigated with a close look at the seeding electron beam dynamics and its BR. As a footprint of the emitting particles, BR can provide valuable information about the beam dynamics. Some practical challenges to implement the betatron diagnostic in the AWAKE Run 2 experiment are also addressed.
Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.
Methods
Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.
Results
In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.
Conclusions
This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.
OBJECTIVES/GOALS: By establishing a youth-centric web-app as a central hub of information and inspiration in an attempt to engage a young demographic, this project aims to increase community awareness and reduce misconceptions surrounding clinical trials, in hopes of fairly representing marginalized communities among future clinical trial participants. METHODS/STUDY POPULATION: We designed a children’s web-app to host a collection of child-friendly educational materials (such as picture books, games, and age-appropriate articles about advances in clinical research) explaining clinical research and its process. An emphasis was put on ensuring the web-app and its contents were understandable and appealing to children. The effectiveness of this tool will be tested through a focus group study. Children ages 7-10 will be given a preliminary survey measuring their knowledge and opinions about clinical research, and then given time to explore the web-app. Afterwards, they will be given a secondary survey to gauge their acquired knowledge from the website and asked about their opinion on the design and usability of the web-app and its materials, as well as how likely they were to revisit the site. RESULTS/ANTICIPATED RESULTS: We anticipate a very positive response from the children regarding the design and usability of the web-app and its materials. By using an adolescent-focused design methodology at every step of the design process, we will ensure that all materials are attractive and engaging to our younger target audience. Exposing children to accessible information about clinical trials at a young age allows us to build their trust in the research process prior to the possible internalization and acceptance of cultural misconceptions. Over time, we hope to see a change in attitudes toward clinical research as well as increased participation, whether from under-represented groups or a younger demographic, and positively contribute to T3 and onwards in the translational continuum. DISCUSSION/SIGNIFICANCE: In a rapidly changing world, the best approach to making change is through targeting the younger demographic, the leaders of tomorrow. Our project will allow adolescents to foster a more well-rounded opinion of clinical research, increasing their participation and better paving a more positively received future for translational science as a whole.
This chapter examines the “nuts and bolts” of war, including the formidable problems of movement and supply, transportation and administration. Logistics represent a vital element of warfare, indispensable to the operations of armies ever since the emergence of organized warfare. Broadly defined, this concept involves moving, supplying, and maintaining military forces, as well as transportation of material, food and animals, communications, personnel replacement, quarters, depots, and rear administration. The Napoleonic Wars witnessed important developments in the logistics and one of its lasting effects was creation and successful dissemination of bureaucratic reforms that improved state’s ability to mobilize forces and extract resources
What inductive biases must be incorporated into multi-agent artificial intelligence models to get them to capture high-fidelity imitation? We think very little is needed. In the right environments, both instrumental- and ritual-stance imitation can emerge from generic learning mechanisms operating on non-deliberative decision architectures. In this view, imitation emerges from trial-and-error learning and does not require explicit deliberation.