Complete heart block is a significant predictor of mortality in immune checkpoint inhibitor myocarditis.

BACKGROUND: Immune checkpoint inhibitor (ICI) myocarditis is associated with significant mortality risk. Electrocardiogram (ECG) changes in ICI myocarditis have strong prognostic value. However the impact of complete heart block (CHB) is not well defined. This study sought to evaluate the impact of CHB on mortality in ICI myocarditis, and to identify clinical predictors of mortality and CHB incidence. METHODS: We conducted a retrospective cohort study of patients with ICI myocarditis at three Mayo Clinic sites from 1st January 2010 to 31st September 2022 to evaluate mortality rates at 180 days. Clinical, laboratory, ECG, echocardiographic, and cardiac magnetic resonance imaging (CMR) characteristics were assessed. Cox and logistic regression were performed for associations with mortality and CHB respectively. RESULTS: Of 34 identified cases of ICI myocarditis, 7 (20.6%) had CHB. CHB was associated with higher mortality (HR 7.41, p = 0.03, attributable fraction 86.5%). Among those with CHB, troponin T (TnT) < 1000 ng/dL, low white blood cell count and high ventricular rate at admission were protective. There was trend towards increased survival among patients who underwent permanent pacemaker insertion (p = 0.051), although most experienced device lead complications. Factors associated with development of CHB included prolonged PR and QRS intervals and low Sokolow Lyon Index. Where these were normal and TnT was < 1000 ng/dL, no deaths occurred. Impaired myocardial longitudinal strain was sensitive for ICI myocarditis but was not prognostically significant. CONCLUSION: There is a strong temporal association between CHB and early mortality in people with ICI myocarditis. Focusing on arrhythmogenic complications can be helpful in predicting outcomes for this group of critically ill individuals.

Acoustic Cry Characteristics in Preterm Infants and Developmental and Behavioral Outcomes at 2 Years of Age.

Importance: Acoustic cry characteristics have been associated with severe medical problems in newborns. However, little is known about the utility of neonatal acoustic cry characteristics in the prediction of long-term outcomes of very preterm infants. Objectives: To evaluate whether acoustic characteristics of infant cry at neonatal intensive care unit (NICU) discharge are associated with behavioral and developmental outcomes at age 2 years in infants born very preterm. Design, Setting, and Participants: Infants born less than 30 weeks postmenstrual age (PMA) were enrolled from April 2014 through June 2016 as part of a multicenter (9 US university affiliated NICUs) cohort study and followed to adjusted age 2 years. Reported analyses began on September 2021. Data were analyzed from September 2021 to September 2022. Exposures: The primary exposure was premature birth (<30 weeks PMA). Main Outcomes and Measures: Cries were recorded during a neurobehavioral examination administered during the week of NICU discharge. Cry episodes were analyzed using a previously published computerized system to characterize cry acoustics. Year-2 outcomes included the Bayley-III Composite scores, Child Behavior Checklist (CBCL) and the Modified Checklist for Autism in Toddlers (M-CHAT R/F), dichotomized using clinically significant cutoffs (<85 on Bayley Language, Cognitive and/or Motor Composite scores, T-score >63 on the CBCL Internalizing, Externalizing and/or Total Problem Scales and total M-CHAT R/F score >2). Results: Analyzed infants (363 participants) were primarily male (202 participants [55.65%]) and had a mean [SD] gestational age of 27.08 [1.95] weeks). Cross-validated random forest models revealed that cry acoustics were associated with 2-year outcomes. Tests of diagnostic odds ratios (DOR) revealed that infants who exhibited total problem behavior CBCL scores greater than 63 at age 2 years were 3.3 times more likely (95% CI, 1.44-7.49) to be identified as so by random forest model estimates relative to other infants (scores ≤63); this association was robust to adjustment for family-wise type-I error rates and covariate measures. Similar associations were observed for internalizing (DOR, 2.39; 95% CI, 1.04-5.47) and externalizing (DOR, 2.25; 95% CI, 1.12-4.54) scores on the CBCL, clinically significant language (DOR, 1.71; 95% CI, 1.10-2.67) and cognitive (DOR, 1.70; 95% CI, 1.00-2.88) scores on the Bayley-III, and a positive autism screen on the M-CHAT (DOR, 1.91; 95% CI, 1.05-3.44). Conclusions and Relevance: In this cohort study of preterm infants, findings pointed to the potential use of acoustic cry characteristics in the early identification of risk for long-term developmental and behavioral deficits.

Developing an Echocardiography-Based, Automatic Deep Learning Framework for the Differentiation of Increased Left Ventricular Wall Thickness Etiologies.

AIMS: Increased left ventricular (LV) wall thickness is frequently encountered in transthoracic echocardiography (TTE). While accurate and early diagnosis is clinically important, given the differences in available therapeutic options and prognosis, an extensive workup is often required to establish the diagnosis. We propose the first echo-based, automated deep learning model with a fusion architecture to facilitate the evaluation and diagnosis of increased left ventricular (LV) wall thickness. METHODS AND RESULTS: Patients with an established diagnosis of increased LV wall thickness (hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA), and hypertensive heart disease (HTN)/others) between 1/2015 and 11/2019 at Mayo Clinic Arizona were identified. The cohort was divided into 80%/10%/10% for training, validation, and testing sets, respectively. Six baseline TTE views were used to optimize a pre-trained InceptionResnetV2 model. Each model output was used to train a meta-learner under a fusion architecture. Model performance was assessed by multiclass area under the receiver operating characteristic curve (AUROC). A total of 586 patients were used for the final analysis (194 HCM, 201 CA, and 191 HTN/others). The mean age was 55.0 years, and 57.8% were male. Among the individual view-dependent models, the apical 4-chamber model had the best performance (AUROC: HCM: 0.94, CA: 0.73, and HTN/other: 0.87). The final fusion model outperformed all the view-dependent models (AUROC: HCM: 0.93, CA: 0.90, and HTN/other: 0.92). CONCLUSION: The echo-based InceptionResnetV2 fusion model can accurately classify the main etiologies of increased LV wall thickness and can facilitate the process of diagnosis and workup.

Triggering palliative care referrals through the identification of poor prognosis in older patients presented to emergency departments in rural Australia.

Background: Without objective screening for risk of death, the palliative care needs of older patients near the end of life may be unrecognised and unmet. Aim: This study aimed to estimate the usefulness of the Criteria for Screening and Triaging to Appropriate aLternative care (CriSTAL) tool in determining older patients' risk of death within 3-months after initial hospital admission. Methods: A prospective cohort study of 235 patients aged 70+ years, who presented to two rural emergency departments in two adjacent Australian states, was utilised. The 'risk of death' of each patient was screened with the CriSTAL prognostic tool. Their 3-month follow-up outcomes were assessed through telephone interviews and a clinical record review. Findings: A CriSTAL cut-off score of more than 7 yielded a sensitivity of 80.7% and specificity of 70.81% for a 3-month risk of death. Palliative care services were only used by 31% of the deceased in their last trimester of life. Conclusion: Prognostic tools provide a viable means of identifying individuals with a poor prognosis. Identification can trigger an earlier referral to palliative care, which will benefit the patient's wellbeing and quality of life.

Communicating COVID-19: Analyzing Higher Education Institutional Responses in Canada, China, and the USA.

The study aims to examine how higher education institutions (HEIs) in three countries responded to the challenges of COVID-19 over a six-month period at the outbreak of the global pandemic. Employing document analysis, we examined 732 publicly available communications from 27 HEIs in Canada, China, and the USA. Through theoretical frameworks of crisis management and Situational Crisis Communication Theory (SCCT), we explore how HEIs respond to the pandemic and protect campus stakeholders. The study revealed common patterns in communication strategies during different stages of the pandemic that include accepting responsibility, emotional reassurance, and compensating victims. It also revealed key differences across social contexts and environments and distinct leadership styles. Findings offer insight into how HEIs communicated at the outset of the COVID-19 pandemic and inform the application of SCCT and crisis management theory to institutional behavior in the context of prolonged and intersecting disasters.

Road sediment, an underutilized material in environmental science research: A review of perspectives on United States studies with international context.

Road sediment is a pervasive environmental medium that acts as both source and sink for a variety of natural and anthropogenic particles and often is enriched in heavy metals. Road sediment is generally understudied in the United States (U.S.) relative to other environmental media and compared to countries such as China and the United Kingdom (U.K.). However, the U.S. is an ideal target for these studies due to the diverse climates and wealth of geochemical, socioeconomic, demographic, and health data. This review outlines the existing U.S. road sediment literature while also providing key international perspectives and context. Furthermore, the most comprehensive table of U.S. road sediment studies to date is presented, which includes elemental concentrations, sample size, size fraction, collection and analytical methods, as well as digestion procedure. Overall, there were observed differences in studies by sampling time period for elemental concentrations, but not necessarily by climate in the U.S. Other key concepts addressed in this road sediment review include the processes controlling its distribution, the variety of nomenclature used, anthropogenic enrichment of heavy metals, electron microscopy, health risk assessments, remediation, and future directions of road sediment investigations. Going forward, it is recommended that studies with a higher geographic diversity are performed that consider smaller cities and rural areas. Furthermore, environmental justice must be a focus as community science studies of road sediment can elucidate pollution issues impacting areas of high need. Finally, this review calls for consistency in sampling, data reporting, and nomenclature to effectively expand work on understudied elements, particles, and background sediments.

NEOage clocks - epigenetic clocks to estimate post-menstrual and postnatal age in preterm infants.

Epigenetic clocks based on DNA methylation (DNAm) can accurately predict chronological age and are thought to capture biological aging. A variety of epigenetic clocks have been developed for different tissue types and age ranges, but none have focused on postnatal age prediction for preterm infants. Epigenetic estimators of biological age might be especially informative in epidemiologic studies of neonates since DNAm is highly dynamic during the neonatal period and this is a key developmental window. Additionally, markers of biological aging could be particularly important for those born preterm since they are at heightened risk of developmental impairments. We aimed to fill this gap by developing epigenetic clocks for neonatal aging in preterm infants. As part of the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, buccal cells were collected at NICU discharge to profile DNAm levels in 542 very preterm infants. We applied elastic net regression to identify four epigenetic clocks (NEOage Clocks) predictive of post-menstrual and postnatal age, compatible with the Illumina EPIC and 450K arrays. We observed high correlations between predicted and reported ages (0.93 - 0.94) with root mean squared errors (1.28 - 1.63 weeks). Epigenetic estimators of neonatal aging in preterm infants can be useful tools to evaluate biological maturity and associations with neonatal and long-term morbidities.

Lead Pollution, Demographics, and Environmental Health Risks: The Case of Philadelphia, USA.

Lead (Pb) soil contamination in urban environments represents a considerable health risk for exposed populations, which often include environmental justice communities. In Philadelphia, Pennsylvania (PA), Pb pollution is a major concern primarily due to extensive historical Pb-smelting/processing activity and legacy use of Pb-based paints and leaded gasoline. The U.S. Environmental Protection Agency (USEPA) organized and/or compiled community-driven soil sampling campaigns to investigate Pb content in surface soils across Philadelphia. Using these data (n = 1277), combined with our own dataset (n = 1388), we explored the spatial distribution of Pb content in soils across the city using ArcGIS. While assessing Zone Improvement Plan (ZIP)-code level data, we found strong correlations between factors, such as the percentage of children with elevated blood lead levels (% EBLL) and % minority population as well as between % EBLL and % children in poverty. We developed a "Lead Index" that took demographics, median measured Pb-in-soil content, and % EBLLs into account to identify ZIP codes in need of further assessment. Our results will be used to help lower the Pb-exposure risk for vulnerable children living in disproportionately burdened communities.

Predicting performance in 4 x 200-m freestyle swimming relay events.

AIM: The aim was to predict and understand variations in swimmer performance between individual and relay events, and develop a predictive model for the 4x200-m swimming freestyle relay event to help inform team selection and strategy. DATA AND METHODS: Race data for 716 relay finals (4 x 200-m freestyle) from 14 international competitions between 2010-2018 were analysed. Individual 200-m freestyle season best time for the same year was located for each swimmer. Linear regression and machine learning was applied to 4 x 200-m swimming freestyle relay events. RESULTS: Compared to the individual event, the lowest ranked swimmer in the team (-0.62 s, CI = [-0.94, -0.30]) and American swimmers (-0.48 s [-0.89, -0.08]) typically swam faster 200-m times in relay events. Random forest models predicted gold, silver, bronze and non-medal with 100%, up to 41%, up to 63%, and 93% sensitivity, respectively. DISCUSSION: Team finishing position was strongly associated with the differential time to the fastest team (mean decrease in Gini (MDG) when this variable was omitted = 31.3), world rankings of team members (average ranking MDG of 18.9), and the order of swimmers (MDG = 6.9). Differential times are based on the sum of individual swimmer's season's best times, and along with world rankings, reflect team strength. In contrast, the order of swimmers reflects strategy. This type of analysis could assist coaches and support staff in selecting swimmers and team orders for relay events to enhance the likelihood of success.

Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital.

BACKGROUND: Prescribing error represent a significant source of preventable harm to patients. Prescribing errors at discharge, including omission of pre-admission medications (PAM), are particularly harmful as they frequently propagate following discharge. This study assesses the impact of an educational intervention and introduction of an electronic patient record (EPR) in the same centre on omission of PAM at discharge using a pragmatic design. A survey of newly qualified doctors is used to contextualise findings. METHODS: Discharge prescriptions and discharge summaries were reviewed at discharge, and compared to admission medicine lists, using a paper-based chart system. Discrepancies were noted, using Health Information and Quality Authority guidelines for discharge prescribing. An educational intervention was conducted. Further review of discharge prescriptions and discharge summaries took place. Following introduction of an EPR, review of discharge summaries and discharge prescriptions was repeated. A survey was administered to recently qualified doctors (interns), and analysed using descriptive statistics and thematic analysis. RESULTS: Omission of PAM as prescribed or discontinued items at discharge occurs frequently. An educational intervention did not significantly change prescribing error rates (U = 1255.5, p = 0.206). EPR introduction did significantly reduce omission of PAM on discharge prescribing (U = 694, p < 0.001), however there was also a reduction in the rate of deliberate discontinuation of PAM at discharge (U = 1237.5, p = 0.007). Survey results demonstrated that multiple sources are required to develop a discharge prescription. Time pressure, access to documentation and lack of admission medicine reconciliation are frequently cited causes of discharge prescribing error. CONCLUSION: This study verified passive educational interventions alone do not improve discharge prescribing. Introduction of EPR improved discharge prescribing, but negatively impacted deliberate discontinuation of PAM at discharge. This is attributable to reduced access to key sources of information used in formulating discharge prescriptions, and separation of the discontinuation function from the prescribing function on the EPR discharge application.

Investigation of Pb-contaminated soil and road dust in a polluted area of Philadelphia.

A multi-analytical geochemical investigation of Pb-contaminated collocated road dust and soils, at two size fractions, was performed in Fishtown, Philadelphia, PA, USA. The combinations of methods employed in this case study were chosen to better characterize the contamination, enhance identification of pollution sources, improve understanding of the impact of former Pb smelters, and to study the relationships between two media and between two size fractions. High concentrations of Cu and Sn were observed in both bulk and finer road dust, whereas large concentrations of Zn and Pb were found in both bulk and finer soil samples, implying pollution. There were no obvious associations between Pb soil concentrations and former smelter locations. Therefore, the primary source of the high mean Pb content in bulk (595 ppm) and fine soils (687 ppm) was likely legacy lead paint and/or leaded-gasoline products. Using electron microscopy, we found that Pb particles were mainly 0.1-10 µm in diameter and were ubiquitous in both soil and dust samples. Two-way analysis of variance tests revealed that, for most chemical elements explored here, there were statistically significant differences in concentrations based on media and size fractions, with finer sizes being more polluted than the bulk. The mineralogical composition and the sources of several pollutant elements (Cr, Cu, Zn, Pb), however, were similar for both soil and dust, pointing to material exchange between the two media. We suggest that future investigations of collocated road dust and soils in urban environments use the methodologies applied in this study to obtain detailed insights into sources of roadside pollution and the relationships between neighboring media.

Multi-scale characterization of glaucophane from Chiavolino (Biella, Italy): implications for international regulations on elongate mineral particles.

In this paper, we present the results of a multi-analytical characterization of a glaucophane sample collected in the Piedmont region of northwestern Italy. Investigation methods included optical microscopy, powder X-ray diffraction, Fourier-transform infrared spectroscopy, µ-Raman spectroscopy, Mössbauer spectroscopy, electron probe microanalysis, environmental scanning electron microscopy and energy-dispersive X-ray spectroscopy, and scanning/transmission electron microscopy combined with energy-dispersive X-ray spectroscopy and electron energy-loss spectroscopy. In addition to the crystal-chemical characterization of the sample from the mesoscale to the near-atomic scale, we have also conducted an extended study on the morphology and dimensions of the mineral particles. The main finding is that studying the same particle population at different magnifications yields different results for mineral habit, dimensions, and dimensional distributions. As glaucophane may occur as an elongate mineral particle (e.g., asbestiform glaucophane occurrences in California and Nevada), the observed discrepancies therefore need to be considered when assessing potential breathability of such particles, with implications for future regulations on elongate mineral particles. While the sample preparation and particle counting methods are not directly investigated in this work, our findings suggest that different magnifications should be used when characterizing an elongate mineral particle population, irrespective of whether or not it contains asbestiform material. These results further reveal the need for developing improved regulation for elongate mineral particles. We thus propose a simple methodology to merge the datasets collected at different magnifications to provide a more complete description and a better risk evaluation of the studied particle population.

Baseline thrombocytopenia in acute coronary syndrome: The lower, the worse.

BACKGROUND: Patients with baseline thrombocytopenia can have increased mortality and morbidity, but are typically excluded from randomized clinical trials studying acute coronary syndromes (ACS). We sought to better define the effect thrombocytopenia on clinical outcomes in ACS patients. METHODS: Patients identified from the NCDR Chest Pain registry at Mayo Clinic Arizona from Oct 2015 to Sep 2018 were retrospectively classified into two groups: TP (platelet <150 × 103 µL) and control (platelet ≥150 × 103 µL). The groups were analyzed for the clinical outcome (all-cause mortality, major adverse cardiac events (MACE), and bleeding events). The TP group was divided into moderate-severe thrombocytopenia (TPmod; platelet 50-100 × 103 µL) and mild thrombocytopenia (TPmild; platelet 100-150 × 103 µL) for further analysis. P-value <0.05 is considered significant. RESULTS: Five hundred and thirty-six patients were identified, and 72 patients (13%) had thrombocytopenia. The median follow-up time was 1.1 years. The TP group was older (TP vs. control: mean age 73 ± 13 years vs. 70 ± 13 years; P = 0.026). In patients discharged on dual-antiplatelet therapy, the TP group had higher all-cause mortality (23% vs. 7.3%; P = 0.007) but not major bleeding events (11% vs. 5.0%; P = 0.123). Only all-cause mortality increased with the severity of thrombocytopenia (TPmod vs. TPmild vs. control: 33% vs. 24% vs. 7.3%; P = 0.007). CONCLUSIONS: In patients with ACS, baseline thrombocytopenia is associated with increased all-cause mortality and all bleeding events without net MACE benefit. Further study is needed to identify the optimal antiplatelet strategy in this higher risk population.

Interneuronal mechanisms for learning-induced switch in a sensory response that anticipates changes in behavioral outcomes.

Sensory cues in the natural environment predict reward or punishment, important for survival. For example, the ability to detect attractive tastes indicating palatable food is essential for foraging while the recognition of inedible substrates prevents harm. While some of these sensory responses are innate, they can undergo fundamental changes due to prior experience associated with the stimulus. However, the mechanisms underlying such behavioral switching of an innate sensory response at the neuron and network levels require further investigation. We used the model learning system of Lymnaea stagnalis1-3 to address the question of how an anticipated aversive outcome reverses the behavioral response to a previously effective feeding stimulus, sucrose. Key to the switching mechanism is an extrinsic inhibitory interneuron of the feeding network, PlB (pleural buccal4,5), which is inhibited by sucrose to allow a feeding response. After multi-trial aversive associative conditioning, pairing sucrose with strong tactile stimuli to the head, PlB's firing rate increases in response to sucrose application to the lips and the feeding response is suppressed; this learned response is reversed by the photoinactivation of a single PlB. A learning-induced persistent change in the cellular properties of PlB that results in an increase rather than a decrease in its firing rate in response to sucrose provides a neurophysiological mechanism for this behavioral switch. A key interneuron, PeD12 (Pedal-Dorsal 12), of the defensive withdrawal network5,6 does not mediate the conditioned suppression of feeding, but its facilitated output contributes to the sensitization of the withdrawal response.

Alteration of yellow traffic paint in simulated environmental and biological fluids.

Pollution from heavy metals in urban environments is a topic of growing concern because many metals, including Pb and Cr, are a human health hazard. Exposure to Pb and Cr has been linked to the inhibition of neurological development as well as toxic effects on many organs. Yellow traffic paint (YTP) is a mixture that contains organic polymers, binders, and pigments, which in some cases consist of crocoite (PbCrO4) that may be coated by silica. The primary aim of this study was to investigate the behavior of the crocoite pigment grains within YTP and their silica coatings in simulated environmental and human body conditions. To do this, both YTP and asphalt were collected in Philadelphia, PA, USA. These samples as well as a standard PbCrO4 were investigated with powder X-ray diffraction, X-ray fluorescence, environmental scanning electron microscopy (ESEM), transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Using this multi-analytical approach, mineral phases were determined in the YTP, their shape, dimensional distributions, crystallinity, and chemical composition, as well as elemental distributions before and after experimental interactions. Three batch dissolution experiments with YTP, asphalt, and standard PbCrO4 were performed to simulate ingestion, inhalation, and environmental interaction with rainwater. Elemental releases were determined with inductively coupled plasma-optical emission spectrometry, and results indicated that little (ingestion) to no (environmental and inhalation) Pb and Cr were leached from the YTP during the three experimental procedures. This is likely due to the silica coating that encapsulates the crocoite particles, which persisted during all interactions. The ESEM results for YTP showed dimensional reductions after interactions with all three fluids. The silica coating must be further explored to determine how it breaks down in real environmental conditions.

Effect of High-Dose Erythropoietin on Blood Transfusions in Extremely Low Gestational Age Neonates: Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure. Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions. Design, Setting, and Participants: The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019. Interventions: In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks. Main Outcomes and Measures: Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein. Results: A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P < .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P < .001). Conclusions and Relevance: These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

A mineralogical and chemical investigation of road dust in Philadelphia, PA, USA.

Road dust was investigated within Philadelphia, a major United States city with a long history of industrial activities, in order to determine pollution levels. Almost all of the investigated minor elements were enriched relative to the continental crust. Furthermore, mean concentrations of Cr, Co, Cu, and Pb were high compared with those reported in cities in other countries. Lead pollution should be investigated further in Philadelphia, where 8 of the 30 sample sites, including those heavily trafficked by civilians, were at or above the EPA's child safety threshold for Pb in bare soil. High Spearman correlations between Zn and Cu, Zn and Cr, Cu and Cr, and Sn and V, as well as factor analysis of minor elements suggests that the primary sources of these elements were anthropogenic. Potential sources included the breakdown of alloys, non-exhaust traffic emissions, paint, smelting, and industry. We found that higher organic content in road dust may be related to higher traffic densities, which could be due to tire-wear particles. Additionally, higher mean concentrations of Fe, Cr, Cu, and Zn were found at sites with elevated traffic densities. Land use impacted some of the elements not influenced by traffic density, including Co, Sn, and Pb. Bulk mineral content was similar across different land uses and traffic densities and, thus, did not appear to be influenced by these factors. Our research emphasized the complexity of road dust and utilized a more comprehensive approach than many previous studies. This study established fundamental groundwork for future risk assessment in Philadelphia, as it identified several key pollutants in the city. Overall, this assessment serves as an informative reference point for other formerly heavily industrialized cities in the USA and abroad.

Proactive and retroactive interference with associative memory consolidation in the snail Lymnaea is time and circuit dependent.

Interference-based forgetting occurs when new information acquired either before or after a learning event attenuates memory expression (proactive and retroactive interference, respectively). Multiple learning events often occur in rapid succession, leading to competition between consolidating memories. However, it is unknown what factors determine which memory is remembered or forgotten. Here, we challenge the snail, Lymnaea, to acquire two consecutive similar or different memories and identify learning-induced changes in neurons of its well-characterized motor circuits. We show that when new learning takes place during a stable period of the original memory, proactive interference only occurs if the two consolidating memories engage the same circuit mechanisms. If different circuits are used, both memories survive. However, any new learning during a labile period of consolidation promotes retroactive interference and the acquisition of the new memory. Therefore, the effect of interference depends both on the timing of new learning and the underlying neuronal mechanisms.

Oxcarbazepine Therapy for Complete Central Diabetes Insipidus.

Oxcarbazepine and carbamazepine cause hyponatremia by unknown mechanisms. We describe a patient with complete central diabetes insipidus and seizures who developed worsening hyponatremia when her dose of oxcarbazepine was increased. The patient maintained a normal serum sodium level and has had appropriately concentrated urine for 5 years on just oxcarbazepine, despite undetectable antidiuretic hormone (ADH) levels. This suggests that oxcarbazepine (or one of its metabolites) may stimulate collecting tubule V2 receptor-G protein complex independent of ADH, resulting in increased renal tubular water reabsorption. Oxcarbazepine may be useful as an alternative therapy for patients with central diabetes insipidus.