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Background There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (infection with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] or vaccination against coronavirus disease 2019 [COVID-19]). From a multi-site cohort of frontline workers, we examined the heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. Methods Exposures included event count and event order, categorized into 7 permutations. Outcome was level of serum antibodies against receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding immunoglobulin). Means were examined up to 365 days after each of the first to seventh events. Results Analysis included 5793 participants measured from 7 August 2020 to 15 April 2023. Hybrid immunity from infection before 1 or 2 vaccine doses elicited modestly superior antibody responses after the second and third events (compared with infections or vaccine doses alone). This superiority was not repeated after additional events. Among adults infected before vaccination, adjusted geometric mean ratios (95% confidence interval [CI]) of anti-RBD early response (versus vaccinated only) were 1.23 (1.14–1.33), 1.09 (1.03–1.14), 0.87 (.81–.94), and 0.99 (.85–1.15) after the second to fifth events, respectively. Post-vaccination infections elicited superior responses; adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated only) were 0.93 (.75–1.17), 1.11 (1.06–1.16), 1.17 (1.11–1.24), and 1.20 (1.07–1.34) after the second to fifth events, respectively. Conclusions Evidence of heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy. [ABSTRACT FROM AUTHOR]

On-farm losses of peanuts (Arachis hypogaea L. Fabales: Fabaceae) pose a persistent threat to the sustainable production and value of peanuts in the United States. This study presents empirical data on the spatial distribution of subterranean insect pests and various quality aspects of peanuts. Surveys were conducted in 20 randomly selected peanut fields in 10 counties in Northeast, Southeast, and Southwest Georgia. The primary insect pests found in Georgia's peanut production counties were Pangaeus bilineatus (Say), Elasmopalpus lignosellus (Zeller), and Diabrotica undecimpunctata Howardi. In the northeast counties, a high prevalence of P. bilineatus led to a significant increase in insect-damaged pods (%IDP), insect-damaged kernels (%IDK), discolored kernels (%DK), pod weight loss (%PWL), and kernel weight loss (%KWL). Similarly, southeast counties had a high %DK, cracked pods (%CP), and E. lignosellus infestation. In southwest counties, predominantly high D. undecimpunctata infestations resulted in the highest %IDP. Moisture content (%MC) was excessively high in all the counties (22.19%–23.17%). Preharvest aflatoxin contamination in peanuts was prevalent across all studied locations, particularly in counties with a high incidence of P. bilineatus and may cause increased risk in aflatoxin levels along the supply chain. Nevertheless, the diverse regional abundance of insect pests and the widespread presence of aflatoxins in Georgia's peanut fields offer valuable insights for developing integrated pest management strategies targeting subterranean insect pests. This is especially crucial in addressing the impact of P. bilineatus , E. lignosellus , and D. undecimpunctata on aflatoxins content of peanuts and determining the pathway for mitigation of aflatoxin contaminations in peanuts at harvest. [ABSTRACT FROM AUTHOR]

Aims The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. Methods and results In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. Conclusion The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy. [ABSTRACT FROM AUTHOR]

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation. [ABSTRACT FROM AUTHOR]

Aims Coronary computed tomography angiography (CTA) imaging is used to diagnose patients with suspected coronary artery disease (CAD). A novel artificial intelligence-guided quantitative computed tomography ischaemia algorithm (AI-QCTischaemia) aims to identify myocardial ischaemia directly from CTA images and may be helpful to improve risk stratification. The aims were to investigate (i) the prognostic value of AI-QCTischaemia amongst symptomatic patients with suspected CAD entering diagnostic imaging with coronary CTA and (ii) the prognostic value of AI-QCTischaemia separately amongst patients with no/non-obstructive CAD (≤50% visual diameter stenosis) and obstructive CAD (>50% visual diameter stenosis). Methods and results For this cohort study, AI-QCTischaemia was calculated by blinded analysts amongst patients with suspected CAD undergoing coronary CTA. The primary endpoint was the composite of death, myocardial infarction (MI), or unstable angina pectoris (uAP) (median follow-up 6.9 years). A total of 1880/2271 (83%) patients had conclusive AI-QCTischaemia result. Patients with an abnormal AI-QCTischaemia result (n = 509/1880) vs. patients with a normal AI-QCTischaemia result (n = 1371/1880) had significantly higher crude and adjusted rates of the primary endpoint [adjusted hazard ratio (HRadj) 1.96, 95% confidence interval (CI) 1.46–2.63, P < 0.001; covariates: age/sex/hypertension/diabetes/smoking/typical angina]. An abnormal AI-QCTischaemia result was associated with significantly higher crude and adjusted rates of the primary endpoint amongst patients with no/non-obstructive CAD (n = 1373/1847) (HRadj 1.81, 95% CI 1.09–3.00, P = 0.022), but not amongst those with obstructive CAD (n = 474/1847) (HRadj 1.26, 95% CI 0.75–2.12, P = 0.386) (P -interaction = 0.032). Conclusion Amongst patients with suspected CAD, an abnormal AI-QCTischaemia result was associated with a two-fold increased adjusted rate of long-term death, MI, or uAP. AI-QCTischaemia may be useful to improve risk stratification, especially amongst patients with no/non-obstructive CAD on coronary CTA. [ABSTRACT FROM AUTHOR]

Environmental inequalities are often large and consequential, exacerbating vertical inequalities of income and class and horizontal inequalities along lines of race and ethnicity. Climate policies can widen these inequalities as well as mitigate them, depending on their design. Decarbonization of the US electricity sector illustrates these possibilities. A strategy narrowly focused on carbon reduction alone is likely in some regions to increase disparities in exposure to localized co-pollutants emitted by fossil fuel combustion and, in some cases, to increase exposure in absolute terms. Strategies that in addition explicitly mandate improvements in air quality, both overall and specifically for frontline communities, can couple decarbonization with remediation of environmental inequalities and broad-based gains in public health. [ABSTRACT FROM AUTHOR]

Large widefield surveys make possible the serendipitous discovery of rare subclasses of pulsars. One such class are 'spider'-type pulsar binaries, comprised of a pulsar in a compact orbit with a low-mass (sub)stellar companion. In a search for circularly polarized radio sources in Australian Square Kilometre Array Pathfinder (ASKAP) Pilot Survey observations, we discovered highly variable and circularly polarized emission from a radio source within the error region of the γ-ray source 4FGL J1646.5−4406. The variability is consistent with the eclipse of a compact, steep-spectrum source behind ablated material from a companion in an ∼5.3 h binary orbit. Based on the eclipse properties and spatial coincidence with 4FGL J1646.5−4406, we argue that the source is likely a recycled pulsar in a 'redback' binary system. Using properties of the eclipses from ASKAP and Murchison Widefield Array observations, we provide broad constraints on the properties of the eclipse medium. We identified a potential optical/infrared counterpart in archival data consistent with a variable low-mass star. Using the Parkes radio telescope 'Murriyang' and the Meer Karoo Array Telescope (MeerKAT) , we searched extensively for radio pulsations but yielded no viable detections of pulsed emission. We suggest that the non-detection of pulses is due to scattering in the intra-binary material, but scattering from the interstellar medium can also plausibly explain the pulse non-detections if the interstellar dispersion measure exceeds ∼600 pc cm−3. Orbital constraints derived from optical observations of the counterpart would be highly valuable for future γ-ray pulsation searches, which may confirm the source nature as a pulsar. [ABSTRACT FROM AUTHOR]

The Tidal Disruption Event (TDE) AT 2018hyz exhibited a delayed radio flare almost three years after the stellar disruption. Here, we report new radio observations of the TDE AT 2018hyz with the AMI-LA and ATCA spanning from a month to more than four years after the optical discovery and 200 d since the last reported radio observation. We detected no radio emission from 30–220 d after the optical discovery in our observations at 15.5 GHz down to a 3σ level of <0.14 mJy. The fast-rising, delayed radio flare is observed in our radio data set and continues to rise almost ∼1580 d after the optical discovery. We find that the delayed radio emission, first detected 972 d after optical discovery, evolves as t 4.2 ± 0.9, at 15.5 GHz. Here, we present an off-axis jet model that can explain the full set of radio observations. In the context of this model, we require a powerful narrow jet with an isotropic equivalent kinetic energy E k, iso ∼ 1055 erg, an opening angle of ∼7°, and a relatively large viewing angle of ∼42°, launched at the time of the stellar disruption. Within our framework, we find that the minimal collimated energy possible for an off-axis jet from AT 2018hyz is Ek ≥ 3 × 1052 erg. Finally, we provide predictions based on our model for the light curve turnover time, and for the proper motion of the radio emitting source. [ABSTRACT FROM AUTHOR]

The mosquito family Culicidae is divided into 2 subfamilies named the Culicinae and Anophelinae. Nix , the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Aedes albopictus , 2 important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from 3 highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133 to 165 million years ago (MYA). Heterologous expression of 1 of 3 divergent Nix open reading frames (ORFs) in Ae. aegypti resulted in partial masculinization of genetic females as evidenced by morphology and doublesex splicing. Phylogenetic analysis suggests Nix is related to femaleless (fle), a recently described intermediate sex-determining factor found exclusively in anopheline mosquitoes. Nix from all species has a conserved structure, including 3 RNA-recognition motifs (RRMs), as does fle. However, Nix has evolved at a much faster rate than fle. The RRM3 of both Nix and fle are distantly related to the single RRM of a widely distributed and conserved splicing factor transformer-2 (tra2). The RRM3-based phylogenetic analysis suggests this domain in Nix and fle may have evolved from tra2 or a tra2 -related gene in a common ancestor of mosquitoes. Our results provide insights into the evolution of sex determination in mosquitoes and will inform broad applications of mosquito-control strategies based on manipulating sex ratios toward nonbiting males. [ABSTRACT FROM AUTHOR]

Tumour heterogeneity is increasingly recognized as a major obstacle to therapeutic success across neuro-oncology. Gliomas are characterized by distinct combinations of genetic and epigenetic alterations, resulting in complex interactions across multiple molecular pathways. Predicting disease evolution and prescribing individually optimal treatment requires statistical models complex enough to capture the intricate (epi)genetic structure underpinning oncogenesis. Here, we formalize this task as the inference of distinct patterns of connectivity within hierarchical latent representations of genetic networks. Evaluating multi-institutional clinical, genetic and outcome data from 4023 glioma patients over 14 years, across 12 countries, we employ Bayesian generative stochastic block modelling to reveal a hierarchical network structure of tumour genetics spanning molecularly confirmed glioblastoma, IDH-wildtype; oligodendroglioma, IDH-mutant and 1p/19q codeleted; and astrocytoma, IDH-mutant. Our findings illuminate the complex dependence between features across the genetic landscape of brain tumours and show that generative network models reveal distinct signatures of survival with better prognostic fidelity than current gold standard diagnostic categories. [ABSTRACT FROM AUTHOR]

Background Fever and leukocytosis are 2 parameters commonly cited in clinical practice as indications to perform an infectious workup in patients receiving extracorporeal membrane oxygenation (ECMO), but their utility is unknown. Methods All patients who received ECMO between December 2014 and December 2020 with influenza or COVID-19 were included in this retrospective cohort study. Cultures were included if they were drawn from patients without signs of decompensation. Maximum temperature and white blood cell count were recorded on the day of culture collection. Workups with infections were compared with those that were negative. Results Of the 137 infectious workups in this 45-patient cohort, 86 (63%) were performed in patients with no signs of decompensation, totaling 165 cultures. These workups yielded 10 (12%) true infections. There were no differences in median (IQR) temperature (100.4 °F [100.2–100.8] vs 100.4 °F [99.3–100.9], P =.90) or white blood cell count (18.6 cells/mL [16.8–20.1] vs 16.7 cells/mL [12.8–22.3], P =.90) between those with and without infections. Conclusions In patients with influenza or COVID-19 who require ECMO, fever and leukocytosis were common indications for infectious workups, yet results were frequently negative. Despite their use in clinical practice, fever and leukocytosis are not reliable indicators of infection in patients who are hemodynamically stable and receiving ECMO. [ABSTRACT FROM AUTHOR]

Clinically significant tricuspid regurgitation (TR) has historically been managed with either medical therapy or surgical interventions. More recently, percutaneous trans-catheter tricuspid valve (TV) replacement and tricuspid trans-catheter edge-to-edge repair have emerged as alternative treatment modalities. Patients with cardiac implantable electronic devices (CIEDs) have an increased incidence of TR. Severe TR in this population can occur for multiple reasons but most often results from the interactions between the CIED lead and the TV apparatus. Management decisions in patients with CIED leads and clinically significant TR, who are undergoing evaluation for a percutaneous TV intervention, need careful consideration as a trans-venous lead extraction (TLE) may both worsen and improve TR severity. Furthermore, given the potential risks of 'jailing' a CIED lead at the time of a percutaneous TV intervention (lead fracture and risk of subsequent infections), consideration should be given to performing a TLE prior to a percutaneous TV intervention. The purpose of this 'state-of-the-art' review is to provide an overview of the causes of TR in patients with CIEDs, discuss the available therapeutic options for patients with TR and CIED leads, and advocate for including a lead management specialist as a member of the 'heart team' when making treatment decisions in patients TR and CIED leads. [ABSTRACT FROM AUTHOR]

Introduction Following graduate medical education duty hour reform, many programs have migrated to a night float model to achieve duty hour compliance. This has led to increased focus on optimizing nighttime education. A 2018 internal program evaluation of the newborn night rotation revealed that most pediatric residents received no feedback and perceived little didactic education during their four-week, night float rotation. One hundred percent of resident respondents were interested in increased feedback, didactics, and procedural opportunities. Our objective was to develop a newborn night curriculum to ensure timely formative feedback, enhance trainee didactic experience, and guide formal education. Materials and Methods A multimodal curriculum was designed to include senior resident-led, case-based scenarios, a pre- and post-test, a pre- and post-confidence assessment, a focused procedure "passport," weekly feedback sessions, and simulation cases. The San Antonio Uniformed Services Health Education Consortium implemented the curriculum starting from July 2019. Results Thirty-one trainees completed the curriculum in over 15 months. There was a 100% pre- and post-test completion rate. Test scores rose from an average of 69% to 94% (25% increase, P  < .0001) for interns and an average of 84% to 97% (13% increase, P  < .0001) for third-year residents (PGY-3s). When averaged across domains assessed, intern confidence rose by 1.2 points and PGY-3 confidence rose by 0.7 points on a 5-point Likert scale. One hundred percent of trainees utilized the on-the-spot feedback form to initiate at least one in-person feedback session. Conclusions As resident schedules evolve, there is an increased need for focused didactics during the night shift. The results and feedback from this resident-led and multimodal curriculum suggest that it is a valuable tool to improve knowledge and confidence for future pediatricians. [ABSTRACT FROM AUTHOR]

Initial fluid infusion rates for resuscitation of burn injuries typically use formulas based on patient weight and total body surface area (TBSA) burned. However, the impact of this rate on overall resuscitation volumes and outcomes have not been extensively studied. The purpose of this study was to determine the impact of initial fluid rates on 24-hour volumes and outcomes using the Burn Navigator (BN). The BN database is composed of 300 patients with ≥20% TBSA, >40 kg that were resuscitated utilizing the BN. Four study arms were analyzed based on the initial formula—2 ml/kg/TBSA, 3 ml/kg/TBSA, 4 ml/kg/TBSA or the Rule of Ten. Total fluids infused at 24 hours after admission were compared as well as resuscitation-related outcomes. A total of 296 patients were eligible for analysis. Higher starting rates (4 ml/kg/TBSA) resulted in significantly higher volumes at 24 hours (5.2 ± 2.2 ml/kg/TBSA) than lower rates (2 ml/kg/TBSA resulted in 3.9 ± 1.4 ml/kg/TBSA). No shock was observed in the high resuscitation cohort, whereas the lowest starting rate exhibited a 12% incidence, lower than both the Rule of Ten and 3 ml/kg/TBSA arms. There was no difference in 7-day mortality across groups. Higher initial fluid rates resulted in higher 24-hour fluid volumes. The choice of 2ml/kg/TBSA as initial rate did not result in increased mortality or more complications. An initial rate of 2ml/kg/TBSA is a safe strategy. [ABSTRACT FROM AUTHOR]

Radio transient searches using traditional variability metrics struggle to recover sources whose evolution time-scale is significantly longer than the survey cadence. Motivated by the recent observations of slowly evolving radio afterglows at gigahertz frequency, we present the results of a search for radio variables and transients using an alternative matched-filter approach. We designed our matched-filter to recover sources with radio light curves that have a high-significance fit to power-law and smoothly broken power-law functions; light curves following these functions are characteristic of synchrotron transients, including 'orphan' gamma-ray burst afterglows, which were the primary targets of our search. Applying this matched-filter approach to data from Variables and Slow Transients Pilot Survey conducted using the Australian SKA Pathfinder, we produced five candidates in our search. Subsequent Australia Telescope Compact Array observations and analysis revealed that: one is likely a synchrotron transient; one is likely a flaring active galactic nucleus, exhibiting a flat-to-steep spectral transition over 4 months; one is associated with a starburst galaxy, with the radio emission originating from either star formation or an underlying slowly evolving transient; and the remaining two are likely extrinsic variables caused by interstellar scintillation. The synchrotron transient, VAST J175036.1–181454, has a multifrequency light curve, peak spectral luminosity, and volumetric rate that is consistent with both an off-axis afterglow and an off-axis tidal disruption event; interpreted as an off-axis afterglow would imply an average inverse beaming factor |$\langle f^{-1}_{\text{b}} \rangle = 860^{+1980}_{-710}$|⁠ , or equivalently, an average jet opening angle of |$\langle \theta _{\textrm {j}} \rangle = 3^{+4}_{-1}\,$| deg. [ABSTRACT FROM AUTHOR]

Glioblastoma stem cells (GSCs) have unique properties of self-renewal and tumor initiation that make them potential therapeutic targets. Development of effective therapeutic strategies against GSCs requires both specificity of targeting and intracranial penetration through the blood-brain barrier. We have previously demonstrated the use of in vitro and in vivo phage display biopanning strategies to isolate glioblastoma targeting peptides. Here we selected a 7-amino acid peptide, AWEFYFP, which was independently isolated in both the in vitro and in vivo screens and demonstrated that it was able to target GSCs over differentiated glioma cells and non-neoplastic brain cells. When conjugated to Cyanine 5.5 and intravenously injected into mice with intracranially xenografted glioblastoma, the peptide localized to the site of the tumor, demonstrating intracranial tumor targeting specificity. Immunoprecipitation of the peptide with GSC proteins revealed Cadherin 2 as the glioblastoma cell surface receptor targeted by the peptides. Peptide targeting of Cadherin 2 on GSCs was confirmed through ELISA and in vitro binding analysis. Interrogation of glioblastoma databases demonstrated that Cadherin 2 expression correlated with tumor grade and survival. These results confirm that phage display can be used to isolate unique tumor-targeting peptides specific for glioblastoma. Furthermore, analysis of these cell specific peptides can lead to the discovery of cell specific receptor targets that may serve as the focus of future theragnostic tumor-homing modalities for the development of precision strategies for the treatment and diagnosis of glioblastomas. [ABSTRACT FROM AUTHOR]

Predatory mites display diverse ecological mechanisms to suppress pest population density below certain thresholds known to cause economic loss. The current study explored the numerical responses of the predatory mites, Cheyletus eruditus (Schrank) (Trombidiformes: Cheyletidae) and Cheyletus malaccensis Oudemans, to Liposcelis decolor (Pearman) (Psocodea: Liposcelididae). The numerical responses of these 2 cheyletid mites to nymphs, adult males, and adult females of L. decolor were determined under laboratory conditions at 24 ± 1 °C, 85 ± 5 RH, and 0:24 (L:D) photoperiod. Oviposition rate, oviposition efficiency, and efficiency of conversion of ingested (ECI) food resources were the key numerical response parameters assessed. The present study revealed a general trend of a strong negative and positive correlation between oviposition rates and increase in prey densities (number of prey per 16.98 cm2) for C. eruditus and C. malaccensis, respectively. The oviposition efficiency was mostly similar for both predatory mites and was inversely related to prey density. Generally, ECI (%) decreased considerably with increasing prey density across different prey types for both predators, however, C. malaccensis was more efficient than C. eruditus in utilizing prey biomass. Given the relatively weak numerical responses, we recommended further assessment of these predatory mites before recommending their use for managing stored-product insect pests in the United States. [ABSTRACT FROM AUTHOR]

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements. [ABSTRACT FROM AUTHOR]

Accurately determining the black hole mass (M BH) in active galactic nuclei (AGNs) is crucial to constraining their properties and to studying their evolution. While direct methods yield reliable measurements of M BH in unobscured type 1 AGNs, where the dynamics of stellar or gas components can be directly observed, only indirect methods can be applied to the vast majority of heavily absorbed type 2 AGNs, which represent most of the AGN population. Since it is difficult to evaluate the accuracy and precision of these indirect methods, we utilize the nearby X-ray bright Seyfert galaxy NGC 4151, whose M BH has been tightly constrained with several independent direct methods, as a laboratory to assess the reliability of three indirect methods that have been applied to obscured AGNs. All three, the X-ray scaling method, the Fundamental Plane of BH activity, and the M –σ correlation, yield M BH values consistent with those inferred from direct methods and can therefore be considered accurate. However, only the X-ray scaling method and the M –σ correlation are precise because the substantial scatter in the Fundamental Plane of BH activity allows only for crude estimates. Of the four M –σ correlations we used, only the one from Kormendy and Ho yields a value consistent with the dynamical estimates. This study suggests that the best approach to estimating the BH mass in systems where direct dynamical methods cannot be applied is to utilize a combination of indirect methods, taking into account their different ranges of applicability. [ABSTRACT FROM AUTHOR]

Background Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. Methods Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. Results Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2–3.0) in group 2 and 2.9-fold (95% CI = 2.6–3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213–246] after dose 2) did not increase significantly after dose 3. Conclusions A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster. [ABSTRACT FROM AUTHOR]

Introduction U.S. military pilots are required to meet certain medical standards in order to maintain an active flying status. Military pilots face potential temporary or permanent loss of flying privileges in the setting of a new condition or symptom that does not meet required standards, which could result in negative social and occupational repercussions for the pilot. For this reason, it has been proposed that U.S. military pilots participate in health care avoidance behavior, but little evidence exists to characterize such a trend in this population. Materials and Methods We conducted a non-probabilistic Internet survey of the general population of U.S. pilots from November 1, 2019 through August 1, 2021. The current study is a sub-analysis of military pilots. Results A total of 4,320 pilots answered the informed consent question, and 264 selected one military pilot type and were included in this sub-analysis. There were 72% of military pilots who reported a history of health care avoidance behavior (n  = 190), and no statistical difference was found between age groups, gender, and military pilot types. There were 55.5% of pilots who reported a history of seeking informal medical care (n  = 147), 33.7% of pilots who have flown despite a new symptom they felt required medical evaluation, 42.5% of pilots who reported withholding information on aeromedical screening (n  = 111), and 11.4% of pilots who reported a history of undisclosed prescription medication use (n  = 30). Conclusions U.S. military pilots may participate in health care avoidance behavior because of fear for loss of flying status. [ABSTRACT FROM AUTHOR]

The goal of burn resuscitation is to provide the optimal amount of fluid necessary to maintain end-organ perfusion and prevent burn shock. The objective of this analysis was to examine how the Burn Navigator (BN), a clinical decision support tool in burn resuscitation, was utilized across five major burn centers in the United States, using an observational trial of 300 adult patients. Subject demographics, burn characteristics, fluid volumes, urine output, and resuscitation-related complications were examined. Two hundred eighty-five patients were eligible for analysis. There was no difference among the centers on mean age (45.5 ± 16.8 years), body mass index (29.2 ± 6.9), median injury severity score (18 [interquartile range: 9–25]), or total body surface area (TBSA) (34 [25.8–47]). Primary crystalloid infusion volumes at 24 h differed significantly in ml/kg/TBSA (range: 3.1 ± 1.2 to 4.5 ± 1.7). Total fluids, including colloid, drip medications, and enteral fluids, differed among centers in both ml/kg (range: 132.5 ± 61.4 to 201.9 ± 109.9) and ml/kg/TBSA (3.5 ± 1.0 to 5.3 ± 2.0) at 24 h. Post-hoc adjustment using pairwise comparisons resulted in a loss of significance between most of the sites. There was a total of 156 resuscitation-related complications in 92 patients. Experienced burn centers using the BN successfully titrated resuscitation to adhere to 24 h goals. With fluid volumes near the Parkland formula prediction and a low prevalence of complications, the device can be utilized effectively in experienced centers. Further study should examine device utility in other facilities and on the battlefield. [ABSTRACT FROM AUTHOR]

Background Chemoprevention plays an important role in malaria control strategy. Perennial malaria chemoprevention (PMC) using sulfadoxine/pyrimethamine (SP) is a WHO-approved strategy to combat malaria in young children and may lead to drug pressure. Introducing SP-PMC may therefore be compromised due to the emergence of Plasmodium falciparum resistant to SP, particularly mutation at K540E of the dihydropteroate synthase (dhps) gene. Molecular surveillance of resistance markers can support assessment of antimalarial efficacy and effectiveness. High prevalence of 540E is associated with reduced effectiveness of SP, and areas with more than 50% prevalence are considered unsuitable for intermittent preventative treatment in pregnancy (IPTp) implementation. Assessing 540E prevalence is an important undertaking before implementation of SP-PMC. Methods We conducted a rapid surveillance of dhps- 540E to assess the suitability of SP as PMC in field studies from Ebonyi and Osun states in Nigeria. We used an in-house developed amplicon deep-sequencing method targeting part of the dhps gene. Results Our data reveal that 18.56% of individuals evaluated carried the 540E mutation mixed with the WT K540. Mutant variant 540E alone was not found, and 80% of isolates harboured only WT (K540). Clonal analysis of the sequencing data shows a very low proportion of 540E circulating in both states. Conclusions Our data show that both states are suitable for SP-PMC implementation and, based on this finding, SP-PMC was implemented in Osun in 2022. Continuous monitoring of 540E will be required to ensure the chemoprevention effectiveness of SP in Nigeria. [ABSTRACT FROM AUTHOR]

Fluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated 'multiple demand' frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it. We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven's Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects. Impaired performance was confined to patients with frontal lesions [ F (2,387) = 18.491; P < 0.001; frontal worse than non-frontal and healthy participants P < 0.01, P <0.001], more marked on the right than left [ F (4,385) = 12.237; P < 0.001; right worse than left and healthy participants P < 0.01, P < 0.001]. Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localization was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses. Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven's Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Extracorporeal membrane oxygenation (ECMO) support prior to ventricular assist device (VAD) therapy is frequently used for stabilizing INTERMACS 1 and 2 paediatric patients. Data regarding outcomes with this strategy is limited. METHODS Patient characteristics and outcomes post-VAD therapy with and without preop ECMO support were compared. Survival and risk factor analysis was performed for all patients and INTERMACS profile 1 subgroup. RESULTS Of 541 INTERMACS 1 and 2 patients enrolled in Paediatric Interagency Registry for Mechanical Circulatory Support registry, 391 received primary VAD implantation and ECMO prior to VAD therapy was utilized in 150 patients. Younger age (P  < 0.0001) and shock (P  < 0.0001) were more common in group 2, with lower survival at 1, 6 and 12 months compared to group 1 (P  < 0.0001). Freedom from infection (P  = 0.03) was higher in group 1. Freedom from stroke (P  = 0.7) was similar. Paracorporeal continuous flow devices led to poor survival in both groups 1 and 2 (P  = 0.4). Implantable continuous flow (P  < 0.0001) and paracorporeal pulsatile devices (P  = 0.007) had better survival in primary VAD group. INTERMACS profile 1, lower weight, hepatic dysfunction, renal failure, paracorporeal continuous and percutaneous devices were associated with higher mortality. Preop ECMO therapy was not associated with higher mortality (P  = 0.12). Survival of INTERMACS profile 1 patient was similar at 1, 6 and 12 months in both groups (P  = 0.1). CONCLUSIONS INTERMACS profile 1, lower weight, hepatic dysfunction, renal failure and use of paracorporeal continuous flow or percutaneous assist devices are associated with a higher postoperative mortality. Preop ECMO therapy however is not independently associated with higher postop mortality. [ABSTRACT FROM AUTHOR]

Pain management is a challenge when treating patients with burn injuries. Understanding the behavioral and interpersonal aspects of the experience of burn pain may aid in its management. Attachment style-which influences how an individual relates to other people-is one aspect that may affect the experience of burn pain. Past research has shown a relationship between an individual's attachment style and certain types of pain and disorders. The study builds upon that past work to investigate specifically how attachment style affects the experience of acute burn pain. Participants were at least 18 years old and admitted to an American Burn Association verified burn center with burns encompassing 30% or less TBSA. Participants completed demographic questionnaires and a standardized measure of adult attachment style. Data regarding use of analgesics, daily pain scores, and burn-related information were collected through medical chart review. Participants who reported a secure attachment style required less pain medication and reported less pain compared with participants who reported an insecure attachment style. There was no difference in burn-related variables between participants with secure and insecure attachment styles, suggesting that these differences were not due to burn-related factors. Attachment, therefore, may play a role in an individual's perception of acute burn pain, which impacts analgesic requirements needed to manage the pain. These results have potential implications for the use of psychosocial interventions to reduce the experience of pain and the amount of pain medication needed to manage acute burn pain. [ABSTRACT FROM AUTHOR]

Throughout human history, Indigenous and local communities have stewarded nature. In the present article, we revisit the ancestral principle of reciprocity between people and nature and consider it as a conceptual intervention to the current notion of ecosystem services commonly used to inform sustainability transformation. We propose the concept of reciprocal contributions to encompass actions, interactions, and experiences between people and other components of nature that result in positive contributions and feedback loops that accrue to both, directly or indirectly, across different dimensions and levels. We identify reciprocal contributions and showcase examples that denote the importance of reciprocity for our ecological legacy and its relevance for biocultural continuity. We suggest that the concept of reciprocal contribution can support transformation pathways by resituating people as active components of nature and restructuring institutions so that ethical principles and practices from Indigenous and local communities can redirect policy approaches and interventions worldwide. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the effects of diet energy density on ranking for dry matter intake (DMI), residual feed intake (RFI), and greenhouse gas emissions. Forty-two mature, gestating Angus cows (600 ± 69 kg body weight [ BW ]; body condition score [ BCS ] 5.3 ± 1.1) with a wide range in DMI expected progeny difference (−1.38 to 2.91) were randomly assigned to two diet sequences; forage then concentrate (FC) or concentrate then forage (CF). The forage diet consisted of long-stem native grass hay plus protein supplement (HAY; 1.96 Mcal ME/kg DM). The concentrate diet consisted of 35% chopped grass hay and 65% concentrate feeds on a dry matter basis (MIX; 2.5 Mcal ME/kg DM). The GreenFeed Emission Monitoring system was used to determine carbon dioxide (CO 2 ), oxygen (O 2 ), and methane (CH 4 ) flux. Cow performance traits, ultrasound back fat and rump fat, feed DMI, and gas flux data were analyzed in a crossover design using a mixed model including diet, period, and sequence as fixed effects and pen and cow within sequence as random effects. For all measured traits excluding DMI, there was a diet × sequence interaction (P < 0.05). The correlation between MIX and HAY DMI was 0.41 (P = 0.067) and 0.47 (P = 0.03) for FC and CF sequences, respectively. There was no relationship (P > 0.66) between HAY and MIX average daily gain (ADG), regardless of sequence. Fifty-seven percent of the variation in DMI was explained by metabolic BW, ADG, and BCS for both diets during the first period. During the second period, the same three explanatory variables accounted for 38% and 37% of the variation in DMI for MIX and HAY diets, respectively. The negative relationship between BCS and DMI was more pronounced when cows consumed the MIX diet. There was no relationship between MIX and HAY RFI, regardless of sequence (P > 0.18). During the first period, correlations for CO2, CH4, and O2 with MIX DMI were 0.69, 0.81, and 0.56 (P ≤ 0.015), respectively, and 0.76, 0.74, and 0.64 (P < 0.01) with HAY DMI. During the second period, correlations for CO2, CH4, and O2 with MIX DMI were 0.62, 0.47, and 0.56 (P ≤ 0.11), respectively. However, HAY DMI during the second period was not related to gas flux (P > 0.47). Results from this experiment indicate that feed intake of two energy-diverse diets is moderately correlated while ADG while consuming the two diets is not related. Further experimentation is necessary to determine if gas flux data can be used to predict feed intake in beef cows. [ABSTRACT FROM AUTHOR]

Background Most hospitals use traditional infection prevention (IP) methods for outbreak detection. We developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning (ML) of the electronic health record (EHR) to identify undetected outbreaks and the responsible transmission routes, respectively. Methods We performed WGS surveillance of healthcare-associated bacterial pathogens from November 2016 to November 2018. EHR ML was used to identify the transmission routes for WGS-detected outbreaks, which were investigated by an IP expert. Potential infections prevented were estimated and compared with traditional IP practice during the same period. Results Of 3165 isolates, there were 2752 unique patient isolates in 99 clusters involving 297 (10.8%) patient isolates identified by WGS; clusters ranged from 2–14 patients. At least 1 transmission route was detected for 65.7% of clusters. During the same time, traditional IP investigation prompted WGS for 15 suspected outbreaks involving 133 patients, for which transmission events were identified for 5 (3.8%). If EDS-HAT had been running in real time, 25–63 transmissions could have been prevented. EDS-HAT was found to be cost-saving and more effective than traditional IP practice, with overall savings of $192 408–$692 532. Conclusions EDS-HAT detected multiple outbreaks not identified using traditional IP methods, correctly identified the transmission routes for most outbreaks, and would save the hospital substantial costs. Traditional IP practice misidentified outbreaks for which transmission did not occur. WGS surveillance combined with EHR ML has the potential to save costs and enhance patient safety. [ABSTRACT FROM AUTHOR]

Progesterone receptor membrane component (PGRMC) proteins play important roles in tumor growth, progression, and chemoresistance, of which PGRMC1 is the best characterized. The ancestral member predates the evolution of metazoans, so it is perhaps not surprising that many of the purported actions of PGRMC proteins are rooted in fundamental metabolic processes such as proliferation, apoptosis, and DNA damage responses. Despite mediating some of the actions of progesterone (P4) and being fundamentally required for female fertility, PGRMC1 and PGRMC2 are broadly expressed in most tissues. As such, these proteins likely have both progesterone-dependent and progesterone-independent functions. It has been proposed that PGRMC1 acquired the ability to mediate P4 actions over evolutionary time through acquisition of its cytochrome b5-like heme/sterol-binding domain. Diverse reproductive and nonreproductive diseases associate with altered PGRMC1 expression, epigenetic regulation, or gene silencing mechanisms, some of which include polycystic ovarian disease, premature ovarian insufficiency, endometriosis, Alzheimer disease, and cancer. Although many studies have been completed using transformed cell lines in culture or in xenograft tumor approaches, recently developed transgenic model organisms are offering new insights in the physiological actions of PGRMC proteins, as well as pathophysiological and oncogenic consequences when PGRMC expression is altered. The purpose of this mini-review is to provide an overview of PGRMC proteins in cancer and to offer discussion of where this field must go to solidify PGRMC proteins as central contributors to the oncogenic process. [ABSTRACT FROM AUTHOR]

In the Lac de Gras (LDG) kimberlite field, Northwest Territories, Canada, coherent kimberlites (CKs) occur as tabular dykes, pipe-shaped diatremes, and irregular bodies without well-defined geometries. Combining the morphology of CK bodies with the occurrence of fragmented olivine microcrysts allows distinction of four CK types at LDG: (1) dykes with no broken olivine; (2) CK without well-defined but probable sheet geometry and no broken olivine; (3) pipe-filling CK (pfCK) with abundant broken olivine and (4) pfCK with no broken olivine. These features suggest an intrusive origin for type 1 and, probably, type 2 CK; a high-energy extrusive emplacement for CK type 3 and a low-energy intrusive or extrusive emplacement for the CK type 4. Here, we compare petrographic and whole-rock, olivine and spinel compositional data for high-energy extrusive pfCK, low-energy pfCK and intrusive CK units to understand the factors controlling their variable emplacement styles. Extrusive CK contain more abundant groundmass phlogopite and monticellite, lower carbonate/silicate mineral abundance ratios and significantly lower dolomite and pleonaste-spinel abundances compared to intrusive CK. This indicates greater CO2 loss and higher H2O/CO2 in the melt phase for the extrusive CK during emplacement. Lower incompatible element concentrations in the extrusive CKs and different chromite Ti# and olivine rim Mg# indicate derivation from distinct primitive melt compositions. The extrusive CK feature higher ɛNdi and marginally higher ɛHfi compositions than the intrusive CK, pointing to derivation from distinct sources. These findings strongly imply that distinct primary melt compositions were largely responsible for the differences in emplacement styles of CK at LDG. Low-energy pfCKs have similar olivine rim Mg#, chromite Ti# and, hence, primitive melt compositions to the high-energy extrusive CK samples. Their marginally different emplacement styles may depend on local factors, such as changing stress regimes, or slightly different volatile concentrations. Both types of pfCK might reflect the waning stages of volcanic sequences resulting from the eruption of a segregated magma column that started with pipe excavation and the explosive emplacement of gas-rich magma (volcaniclastic kimberlite), followed by the less energetic emplacement of melt-rich magma (pfCK). This hypothesis underscores different primary melt compositions for dyke vs pipe-forming (and filling) kimberlites and hence a fundamental primary melt control on the explosivity of kimberlites. [ABSTRACT FROM AUTHOR]

Motivation CRAM has established itself as a high compression alternative to the BAM file format for DNA sequencing data. We describe updates to further improve this on modern sequencing instruments. Results With Illumina data CRAM 3.1 is 7–15% smaller than the equivalent CRAM 3.0 file, and 50–70% smaller than the corresponding BAM file. Long-read technology shows more modest compression due to the presence of high-entropy signals. Availability and implementation The CRAM 3.0 specification is freely available from https://samtools.github.io/hts-specs/CRAMv3.pdf. The CRAM 3.1 improvements are available in a separate OpenSource HTScodecs library from https://github.com/samtools/htscodecs , and have been incorporated into HTSlib. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

We present Champagne, a whole-genome method for generating character matrices for phylogenomic analysis using large genomic indel events. By rigorously picking orthologous genes and locating large insertion and deletion events, Champagne delivers a character matrix that considerably reduces homoplasy compared with morphological and nucleotide-based matrices, on both established phylogenies and difficult-to-resolve nodes in the mammalian tree. Champagne provides ample evidence in the form of genomic structural variation to support incomplete lineage sorting and possible introgression in Paenungulata and human–chimp–gorilla which were previously inferred primarily through matrices composed of aligned single-nucleotide characters. Champagne also offers further evidence for Myomorpha as sister to Sciuridae and Hystricomorpha in the rodent tree. Champagne harbors distinct theoretical advantages as an automated method that produces nearly homoplasy-free character matrices on the whole-genome scale. [ABSTRACT FROM AUTHOR]

Phylogenetic diversity analyses were used to interpret the timing and assembly of vegetation communities in temperate New Zealand. A data set comprising 1638 permanent vegetation plots provided plant-distributional data, and a plastid rbcL phylogenetic tree provided phylogenetic metrics. Mean crown age, standardized effect size of mean pairwise distance and standardized effect size of mean nearest taxon distance were analysed in relation to taxonomic groups (angiosperms, gymnosperms and pteridophytes), life form (woody angiosperms, non-woody angiosperms) and temperature and precipitation using generalized additive models. Angiosperms in South Island have a younger crown age than those in most North Island sites, and phylogenetic clustering is prevalent throughout. Angiosperms and pteridophytes from drier and cooler open-habitat communities in central and eastern South Island have younger crown ages and phylogenetic clustering compared to wetter and warmer closed-habitat communities of western South Island and North Island, with older crown ages and phylogenetic over-dispersion. Phylogenetic clustering is consistent with species-rich radiations that have diversified into newly available niches during the late Miocene to Plio-Pleistocene. Pteridophytes displayed less phylogenetic relatedness than angiosperms, reflecting their older crown ages. These findings are consistent with a view that northern New Zealand retained older lineages of subtropical origin during glaciations, whereas novel habitats in cool, dry climates in southern New Zealand facilitated more recent radiations. These results emphasize the strong legacy of history in the modern-day composition of plant communities. [ABSTRACT FROM AUTHOR]

Over the past four decades, no class of drugs has had more impact on cardiovascular health than the 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins. Developed as potent lipid-lowering agents, statins were later shown to reduce morbidity and mortality of patients who are at risk for cardiovascular disease. However, retrospective analyses of some of these clinical trials have uncovered some aspects of their clinical benefits that may be additional to their lipid-lowering effects. Such 'pleiotropic' effects of statins garnered intense interest and debate over its contribution to cardiovascular risk reduction. This review will provide a brief background of statin pleiotropy, assess the available clinical evidence for and against their non-lipid-lowering benefits, and propose future research directions in this field. [ABSTRACT FROM AUTHOR]

The article presents case study of 49-year-old male with a remote history of alcohol use disorder presented with a 5-day history of subjective fever, nausea, vomiting, watery diarrhea, and right upper quadrant abdominal pain. It mentions diagnosis of Amoebic liver abscess and associated amoebic colitis.

Background Traditional methods of outbreak investigations utilize reactive whole genome sequencing (WGS) to confirm or refute the outbreak. We have implemented WGS surveillance and a machine learning (ML) algorithm for the electronic health record (EHR) to retrospectively detect previously unidentified outbreaks and to determine the responsible transmission routes. Methods We performed WGS surveillance to identify and characterize clusters of genetically-related Pseudomonas aerugin osa infections during a 24-month period. ML of the EHR was used to identify potential transmission routes. A manual review of the EHR was performed by an infection preventionist to determine the most likely route and results were compared to the ML algorithm. Results We identified a cluster of 6 genetically related P. aeruginosa cases that occurred during a 7-month period. The ML algorithm identified gastroscopy as a potential transmission route for 4 of the 6 patients. Manual EHR review confirmed gastroscopy as the most likely route for 5 patients. This transmission route was confirmed by identification of a genetically-related P. aeruginosa incidentally cultured from a gastroscope used on 4of the 5 patients. Three infections, 2 of which were blood stream infections, could have been prevented if the ML algorithm had been running in real-time. Conclusions WGS surveillance combined with a ML algorithm of the EHR identified a previously undetected outbreak of gastroscope-associated P. aeruginosa infections. These results underscore the value of WGS surveillance and ML of the EHR for enhancing outbreak detection in hospitals and preventing serious infections. [ABSTRACT FROM AUTHOR]