Background: Candida auris is an emerging threat to hospitalized patients and invasive disease is associated with high mortality. This study describes clinical and microbiological characteristics of nine patients identified with C. auris at Ohio State Wexner Medical Center discovered through active surveillance or clinical investigation and uses whole genome sequencing (WGS) to compare isolates. Methods: In November 2022, an active C. auris surveillance program was implemented to screen patients admitted to high-risk units (intensive care units and progressive care units). Bilateral axilla and groin swabs were obtained upon unit admission and, if positive, were submitted for C. auris polymerase chain reaction (PCR) with culture and sensitivity testing. Patients with a positive screening or clinical isolate from November 2022 to November 2023 underwent chart review for clinical characteristics, microbiologic data, and index admission information. For each isolate, DNA was extracted and WGS was performed. Core single nucleotide polymorphism (SNP) variation identified from the sequence data was used to infer genetic relationships among the isolates. Results: Nine patients were identified between November 2022 and November 2023. The clinical and microbiologic characteristics are summarized in Table 1. All patients were hospitalized at various acute care facilities across the state at least once in the preceding 12 months. C. auris was determined to be present on admission for 6 patients. For 5 of these patients, it was their first interaction with our healthcare system. Three patients were not in contact isolation for >3 days before C. auris was identified. Unit wide point-prevalence screening was completed in these cases and no evidence of transmission was found. WGS showed eight of the nine isolates were related with 28 or less core SNP differences between isolates (Figure 1). One isolate (8) was genetically distinct with >45000 core SNP differences. Five isolates were highly related with a range of 4-15 SNP differences. No temporal or spatial overlap at our institution was identified among these five patients. Conclusions: The active surveillance program identified several patients colonized with C. auris in addition to those found through clinical testing. Multiple risk factors for C. auris were identified with high patient mortality (67%). Majority of the isolates were closely related without association with a known outbreak or epidemiologic link, suggesting a possible diffuse common reservoir. Next steps with surveillance in acute care and long-term care facilities will be critical for early detection to halt transmission of this organism.

Suicide is a leading cause of death in the United States, particularly among adolescents. In recent years, suicidal ideation, attempts, and fatalities have increased. Systems maps can effectively represent complex issues such as suicide, thus providing decision-support tools for policymakers to identify and evaluate interventions. While network science has served to examine systems maps in fields such as obesity, there is limited research at the intersection of suicidology and network science. In this paper, we apply network science to a large causal map of adverse childhood experiences (ACEs) and suicide to address this gap. The National Center for Injury Prevention and Control (NCIPC) within the Centers for Disease Control and Prevention recently created a causal map that encapsulates ACEs and adolescent suicide in 361 concept nodes and 946 directed relationships. In this study, we examine this map and three similar models through three related questions: (Q1) how do existing network-based models of suicide differ in terms of node- and network-level characteristics? (Q2) Using the NCIPC model as a unifying framework, how do current suicide intervention strategies align with prevailing theories of suicide? (Q3) How can the use of network science on the NCIPC model guide suicide interventions?

Oxygen isotopic compositions were determined for coexisting mixed-layer serpentine-chlorite (Sp-Ch) and illite-smectite (I-S) from 5 Tuscaloosa Formation sandstone cores sampled between 1937 and 5470 m burial depth. High gradient magnetic separation (HGMS) was used to concentrate Sp-Ch and I-S from the <0.5 μm fraction of each core sample into fractions with a range in the Sp-Ch: I-S ratio, and end-member δ18O compositions were determined by extrapolation. The Sp-Ch δ18O values range from + 10.4 to 13.7% and increase with burial between 3509 and 5470 m. The only exception is Sp-Ch from 1937 m, which has an anomalously high δ18O value of +12.6‰ The I-S δ18O values range from +16.1 to 17.3% and do not change significantly between 3509 and 5470 m burial depth.

Pore water δ18O compositions calculated from Sp-Ch and I-S values and measured borehole temperatures range from −2.6 to +10.3‰ The isotopically light values indicate that Sp-Ch formed at shallow burial depths in the presence of brackish to marine water and/or meteoric water. The depth-related increase in δ18O of Sp-Ch is attributed to oxygen exchange between mineral and pore water during diagenetic mineral reactions. Increasing δ18O values, in conjunction with XRD and SEM data, indicate that transformation of serpentine layers to chlorite layers and Ibb polytype layers to Iaa polytype layers occurred on a layer-by-layer basis when individual layers dissolved and recrystallized within the confines of coherent crystals. Possible explanations for the variation in I-S δ18O values include depth-related differences in pore water δ18O values present at the time of I-S crystallization, contamination by detrital 2M, mica and 1M polytype rotations that facilitated oxygen exchange.

Air displacement plethysmography (ADP) has been considered as the ‘standard’ method to determine body fat in children due to superior validity and reliability compared with bioelectrical impedance analysis (BIA). However, ADP and BIA are often used interchangeably despite few studies comparing measures of percentage body fat by ADP (%FMADP) with BIA (%FMBIA) in children with and without obesity. The objective of this study was to measure concurrent validity and reliability of %FMADP and %FMBIA in 6-to-12-year-old boys with and without obesity. Seventy-one boys (twenty-five with obesity) underwent body composition assessment. Ten boys participated in intra-day reliability analysis. %FMADP was estimated by Bodpod using sex- and age-specific equations of body density. %FMBIA was estimated by a multi-frequency, hand-to-foot device using child-specific equations based on impedance. Validity was assessed by t tests, correlation coefficients and limits of agreement (LoA); and reliability by technical error of measurement (TEM) and intraclass correlation coefficients (ICC). Compared with %FMADP, %FMBIA was significantly underestimated in the cohort (–3·4 ± 5·6 %; effect size = 0·42) and in both boys with obesity (–5·2 ± 5·5 %; ES = 0·90) and without obesity (–2·4 ± 5·5 %; ES = 0·52). A strong, significant positive correlation was found between %FMADP and %FMBIA (r = 0·80). Across the cohort, LoA were 22·3 %, and no proportional bias was detected. For reliability, TEM were 0·65 % and 0·55 %, and ICC were 0·93 and 0·95 for %FMBIA and %FMADP, respectively. Whilst both %FMADP and %FMBIA are highly reliable methods, considerable differences indicated that the devices cannot be used interchangeably in boys age 6-to-12 years.

Amiodarone may be considered for patients with junctional ectopic tachycardia refractory to treatment with sedation, analgesia, cooling, and electrolyte replacements. There are currently no published pediatric data regarding the hemodynamic effects of the newer amiodarone formulation, PM101, devoid of hypotensive agents used in the original amiodarone formulation. We performed a single-center, retrospective, descriptive study from January 2012 to December 2020 in a pediatric ICU. Thirty-three patients were included (22 male and 11 female) between the ages of 1.1 and 1,460 days who developed post-operative junctional ectopic tachycardia or other tachyarrhythmias requiring PM101. Data analysis was performed on hemodynamic parameters (mean arterial pressures and heart rate) and total PM101 (mg/kg) from hour 0 of amiodarone administration to hour 72. Adverse outcomes were defined as Vasoactive-Inotropic Score >20, patients requiring ECMO or CPR, or patient death. There was no statistically significant decrease in mean arterial pressures within the 6 hours of PM101 administration (p > 0.05), but there was a statistically significant therapeutic decrease in heart rate for resolution of tachyarrhythmia (p < 0.05). Patients received up to 25 mg/kg in an 8-hour time for rate control. Average rate control was achieved within 11.91 hours and average rhythm control within 62 hours. There were four adverse events around the time of PM101 administration, with three determined to not be associated with the medication. PM101 is safe and effective in the pediatric cardiac surgical population. Our study demonstrated that PM101 can be used in a more aggressive dosing regimen than previously reported in pediatric literature with the prior formulation.

OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

Enlist E3TM soybean cultivars permit over-the-top application of labeled glyphosate, glufosinate, and 2,4-D choline products. Increased Enlist E3TM trait adoption and use of 2,4-D choline postemergence across U.S. soybean production systems raise concerns regarding potential for 2,4-D off-target movement (OTM). A large-scale drift experiment was established near Sun Prairie, WI, and Arlington, WI, in 2019 and 2020, respectively. A 2,4-D-resistant soybean cultivar was planted in the center of the field (∼3 ha), while the surrounding area was planted with a 2,4-D-susceptible cultivar. An application of 785 ae ha−1 2,4-D choline plus 834 g ae ha−1 glyphosate was completed within the center block at R2 and V6 growth stages on August 1, 2019, and July 3, 2020, respectively. Filter papers were placed in-swath and outside of the treated area in one upwind transect and three downwind transects to estimate particle deposition. Low-volume air samplers ran for the 0.5-h to 48-h period following application to estimate 2,4-D air concentration. Injury to 2,4-D-susceptible soybean was assessed 21 d after treatment (0% to 100% injury). The 2,4-D deposition in-swath was 9,966 and 5,727 ng cm−2 in 2019 and 2020, respectively. Three-parameter log-logistic models estimated the distance to 90% reduction in 2,4-D deposition (D90) to be 0.63 m and 0.90 m in 2019 and 2020, respectively. In 2020, the 2,4-D air concentration detected was lower for the upwind (0.395 ng m−3) than the downwind direction (1.34 ng m−3), although both were lower than the amount detected in-swath (4.01 ng m−3). No soybean injury was observed in the downwind or upwind directions. Our results suggest that 2,4-D choline applications following label recommendations pose little risk to 2,4-D-susceptible soybean cultivars; however, further work is needed to understand 2,4-D choline OTM under different environmental conditions and the presence of other susceptible crops.

Despite prenatal diagnosis, prenatal intervention, and immediate postnatal intervention, patients with hypoplastic left heart syndrome and intact or highly restrictive atrial septum have the highest risk for mortality. Charts for all infants diagnosed with hypoplastic left heart syndrome from 2009 to 2017 were retrospectively reviewed and compared, including pulmonary vein Doppler patterns on fetal echocardiogram and evidence of pulmonary lymphangiectasia on fetal MRI. Of the 81 newborns with hypoplastic left heart syndrome, we defined two groups. Group 1 patients had an adequate atrial septal communication (n = 69), while Group 2 met criteria for intact/restrictive septum (n = 12). No patient in Group 1 had a type C pulmonary vein Doppler pattern, while no patient in Group 2 had a type A pulmonary vein Doppler pattern. The two patients with pulmonary lymphangiectasia had type C pulmonary vein Doppler pattern and an intact atrial septum and did not survive. Survival to discharge for Group 1 was 83% compared to 58% for Group 2 (p = 0.116). Survival to stage 2 palliation was 71% for Group 1 compared to 50% for Group 2 (p = 0.186). Only 4 of the initial 12 patients from Group 2 are alive, which is an overall survival of 33%. Our experience supports previous evidence that fetal echocardiography can identify those patients with the greatest likelihood for postnatal intervention as well as those at highest risk for mortality. Fetal MRI is a novel imaging modality that may help providers separate patients at highest risk for mortality, regardless of pulmonary vein Doppler pattern.

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6–23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (–1·93 (95 % CI –1·88, –1·97)) v. placebo (–1·88 (95 % CI –1·83, –1·92)), and the opposite occurred among initially anaemic children (final mean LAZ –1·90 (95 % CI –1·86, –1·94) in MNP v. –1·92 (95 % CI –1·88, –1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

White mold caused by the fungus, Sclerotinia sclerotiorum is a devastating disease of soybean (Glycine max) and other leguminous crops, including dry bean (Phaseolus vulgaris). Previous research has demonstrated that no-till planting soybean into rolled–crimped cereal rye residue can enhance weed management, improve soil health and reduce labor requirements in organic production. However, there are limited data on the effects of cereal rye residue on white mold suppression in no-till planted soybean and dry bean. Two field trials were conducted in 2016–2017 (Year 1) and repeated in 2017–2018 (Year 2) to evaluate the potential of cereal rye cover crop residue to suppress white mold in these crops. In each trial (soybean and dry bean), the experimental design was a randomized complete block with two treatments: (1) rolled–crimped cereal rye residue and (2) no cover crop control. Treatment effects on plant population, biomass and yield components varied between the main crops. Compared with the control treatment, cereal rye residue reduced the incidence of white mold in soybean in both years and in dry bean in Year 2. The reduction in white mold in cereal rye residue plots was due to a combination of (1) decreased sclerotial germination (no stipes formed) and (2) increased nonfunctional sclerotial germination defined here as sclerotia that germinated but produced stipes without the expanded cup where asci containing ascospores are formed. Weed density and biomass were lower in cereal rye residue plots in soybean and dry bean, except in Year 1 in soybean when weed biomass was low in both treatments. Our findings indicate that cereal rye residue could help organic and conventional farmers manage white mold in no-till planted soybean and dry bean. Germination of sclerotia resulting in nonfunctional apothecia could potentially exhaust soilborne inoculum in the upper soil profile and reduce infections in subsequent crops.

Tillage is a foundational management practice in many cropping systems. Although effective at reducing weed populations and preparing a crop seedbed, tillage and cultivation can also dramatically alter weed community composition. We examined the impact of soil tillage timing on weed community structure at four sites across the northeastern United States. Soil was tilled every 2 wk throughout the growing season (late April to late September 2013), and weed seedling density was quantified by species 6 wk after each tillage event. We used a randomized complete block design with four replicates for each tillage-timing treatment; a total of 196 plots were sampled. The timing of tillage was an important factor in shaping weed community composition and structure at all sites. We identified three main periods of tillage timing that resulted in similar communities. Across all sites, total weed density tended to be greatest and weed evenness tended to be lowest when soils were tilled early in the growing season. From the earliest to latest group of timings, total abundance decreased on average from 428±393 to 159±189 plants m−2, and evenness increased from 0.53±0.25 to 0.72±0.20. The effect of tillage timing on weed species richness varied by site. Our results show that tillage timing affects weed community structure, suggesting that farmers can manage weed communities and the potential for weed interference by adjusting the timing of their tillage and cropping practices.