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Context: Malaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy. Methods: The drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å. [ABSTRACT FROM AUTHOR]

Key Points: Question: What are the best-performing organ dysfunction–based criteria to implement the definition of sepsis and septic shock in children with suspected infection? Findings: In this international, multicenter, retrospective cohort study including more than 3.6 million pediatric encounters, a novel score, the Phoenix Sepsis Score, was derived and validated to predict mortality in children with suspected or confirmed infection. The new criteria for pediatric sepsis and septic shock based on the score performed better than existing organ dysfunction scores and the International Pediatric Sepsis Consensus Conference criteria. Meaning: The new data-driven criteria for pediatric sepsis and septic shock based on measures of organ dysfunction had improved performance compared with prior pediatric sepsis criteria. Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria. This cohort study derives and validates novel criteria for diagnosis of pediatric sepsis and septic shock across high-resource and low-resource international settings. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The goal of this study was to determine the incidence, prognostic performance, and generalizability of the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) organ dysfunction criteria using electronic health record (EHR) data. Additionally, we sought to compare the performance of the PODIUM criteria with the organ dysfunction criteria proposed by the 2005 International Pediatric Sepsis Consensus Conference (IPSCC). METHODS: Retrospective observational cohort study of critically ill children at 2 medical centers in the United States between 2010 and 2018. We assessed prevalence of organ dysfunction based on the PODIUM and IPSCC criteria for each 24-hour period from admission to 28 days. We studied the prognostic performance of the criteria to discriminate in-hospital mortality. RESULTS: Overall, 22 427 PICU admissions met inclusion criteria, and in-hospital mortality was 2.3%. The cumulative incidence of each PODIUM organ dysfunction ranged from 15% to 30%, with an in-hospital mortality of 6% to 10% for most organ systems. The number of concurrent PODIUM organ dysfunctions demonstrated good-to-excellent discrimination for inhospital mortality (area under the curve 0.87-0.93 for day 1 through 28) and compared favorably to the IPSCC criteria (area under the curve 0.84-0.92, P < .001 to P = .06). CONCLUSIONS: We present the first evaluation of the PODIUM organ dysfunction criteria in 2 EHR databases. The use of the PODIUM organ dysfunction criteria appears promising for epidemiologic and clinical research studies using EHR data. More studies are needed to evaluate the PODIUM criteria that are not routinely collected in structured format in EHR databases. [ABSTRACT FROM AUTHOR]

Along the western slope of the Central Andes in the southernmost part of the Pampean flat-slab subduction zone segment (∼33°S), crustal Quaternary west-vergent reverse faults are found, but little is known about them. To better understand and characterize these faults, grouped as the Cariño Botado thrust fault system (CBF), we undertook a multidisciplinary study focused on remote sensing and field geomorphic and geologic mapping, sedimentary relationships, and fault characterization. Optically Stimulated Luminescence (OSL) and U Pb dating samples were obtained from faulted deposits to constrain the timing of fault motion. We combined the mapping, fault relationship descriptions, and age control to understand this system better and quantify tectonic rates here for the first time. The main CBF is best expressed with Late-Cenozoic hanging wall fault rocks over thrusting Quaternary coarse-grained alluvial fan deposits, and the fault zone is found over a large area and with an altered fault zone (∼0.5–2 km wide). The principal reverse fault segment of the CBF is well exposed in creeks, with an average dip of 40°E and an associated vertical throw (up to the east) of the hanging wall from ∼3.2 m up to ∼30 m. Five OSL samples, taken from tilted and untilted alluvial fan deposits adjacent to the CBF's main fault, yielded ages between 2.5 ± 0.2 ka and 9.0 ± 0.7 ka, supporting Holocene activity and ∼4.9 m of fault slip in the last ∼8.7 ka. Ninety-nine detrital zircons from fluvial terrace deposits in the study area were dated using U Pb ICPMS, giving mainly Oligo-Miocene ages. The youngest ages of detrital zircons are Quaternary (n = 3; ∼0.9–4.4 Ma), which indicates that CBF activity could have started as early as ∼0.9 Ma producing an accumulated hanging wall uplift of ∼130 m. The alignment of the fault profiles, creek and river knickpoints, and alluvial and fluvial deposits allows the most recent activity of the main CBF to be traced between 5 km and up to 15 km along the fault trace. Based on fault length, slip characteristics, and earthquake scaling relationships, earthquakes up to Mw 7.5 could be associated with the fault. Because of the clear relationship between the river incision, distribution of fluvial terraces, variation in sinuosity and stream power, and the location of the faults, we suggest that the tectonic uplift controls the hanging wall fluvial incision from ∼0.9 Ma to the present. The Quaternary (at least 0.9 Ma to present) active CBF shares geometric, structural, and rupture timing similarities with the nearby better-characterized San Ramón Fault system. The latter is located ∼50 km to the south along the eastern border of Santiago, the capital city of Chile. Both fault systems share a comparable morpho-structural setting with a consistent average N-S trend. Significant seismic hazard is associated with both the CBF and the San Ramon System, which may be linked structurally and temporally regarding previous surface ruptures and major earthquakes, and therefore remain important research targets. • Tectonic geomorphology of a west-vergent thrust at a flat-slab of the Andes • Studies fault exposures, uplifted terraces, and tilted alluvial fan deposits • Fault activity dated by OSL and U Pb applied to geomorphic markers • Space-time similarities between the San Ramón and Cariño Botado faults • Cariño Botado faults suggests a possible seismic hazard of up to Mw 7.5. [ABSTRACT FROM AUTHOR]

The release of nanomaterials into the environment is the cause of an emerging concern. Titanium dioxide nanoparticles (nano-TiO 2) among the most produced nanomaterials, has been documented in marine coastal areas posing a threat on marine biota. Sea urchin embryos are recognized as suitable bioindicators in ecological risk assessment and recently for nanomaterials. This study investigated the impact of nano-TiO 2 on fertilization, embryonic and larval development of the tropical sea urchin Lytechinus variegatus in a range of concentrations (0.005–5 μg/mL) which includes environmentally relevant ones. The behavior of nano-TiO 2 in tropical natural seawater was determined by dynamic light scattering (DLS) and toxicity was evaluated through fertilization and embryotoxicity tests, and morphological/morphometric analyses of sea urchin's larvae. Limited toxicity was recorded for nano-TiO 2 in tropical sea urchin embryos and larvae, except for effects at the gastrula stage at 0.005 μg/mL. Large agglomerates of nano-TiO 2 (5 μg/mL) were observed adhering onto sea urchin larvae thus probably preventing nanoparticles uptake at the highest concentrations (>0.005 μg/mL). Environmental levels of nano-TiO 2 are able to cause toxicity on tropical sea urchin L. variegatus embryos with potential consequences on populations and their ecological role in tropical coastal areas. • Nano-TiO 2 showed agglomeration at the microscale in natural seawater • Nano-TiO 2 significantly reduced sea urchin fertilization rate at 0.5 and 5 μg/mL • Nano-TiO 2 induced higher toxicity in gastrulae at environmentally relevant concentration (0.005 μg/mL) • Nano-TiO 2 decreased the length of post-oral arms of larvae at all concentrations • Nano-TiO 2 was toxic to larval development at the highest concentration tested (5 μg/mL). [ABSTRACT FROM AUTHOR]

Chalcopyrite ores are processed mostly by pyrometallurgical techniques due to the refractory nature of the mineral to the current hydrometallurgical techniques. In order to overcome such refractoriness, pretreatment steps such as sulfurization may be applied to produce different copper phases and therefore improve the metal dissolution in the leaching step. The current study investigated the reaction products of the reaction between chalcopyrite and elemental sulfur at different chalcopyrite/sulfur ratios (1/1 and 1/2), reaction time (60 min and 90 min), and temperature (350ºC, 400°C and 450ºC). The sulfurization experiments revealed that covellite, nukundamite, bornite, and pyrite-like compounds were produced according to the experimental conditions applied. Then, the sulfurization products were submitted to chemical leaching tests at temperatures ranging from 32ºC to 70ºC, whereas bioleaching tests were also carried out with Acidithiobacillus ferrooxidans, at 32ºC. In the chemical leaching experiments at 70ºC, only 14% copper was recovered from the original chalcopyrite sample while the maximum copper extraction was 78% from bornite produced at 450ºC (90 min and mass ratio of chalcopyrite/sulfur of 1/2). On the other hand, copper extraction achieved 96% from the same sulfurization product containing synthetic bornite within 20 days of bioleaching. Bioleaching of the original chalcopyrite sample implied in a copper recovery of only 25% in the same period. Summarizing, the current work showed that chalcopyrite sulfurization at 450ºC was able to transform chalcopyrite into a bornite-like phase, which was chemically leached and bioleached by At. ferrooxidans. [ABSTRACT FROM AUTHOR]

• Study of a system of quasilinear PDEs that can be used to model drug release from a polymeric structure enhanced by light. • A numerical scheme to compute the numerical solution of the IBVP based on the system of PDEs is proposed. • The theoretical support (stability and convergence) under weaker assumptions than those usually used is developed. • Numerical results illustrating the theoretical results established are provided. • A comparation between experimental data and simulation results is also presented. In this paper, we analyze a numerical scheme for a nonlinear coupled system of partial differential equations. Our study is motivated by the mathematical modeling of light-triggered drug delivery, a technique that can have a significant impact on cancer treatment. The numerical scheme combines a finite difference method (FDM) in space with an implicit-explicit (IMEX) method in time. For the main variable of interest - free drug concentration - we prove that the scheme is second-order supraconvergent in space in a discrete H 1 -norm and first-order convergent in time in a discrete L 2 -norm. We give numerical results illustrating the theoretical findings and computational simulations based on a laboratory experiment concerned with light-triggered drug delivery. [ABSTRACT FROM AUTHOR]

Chloride load's association with VFD, hospital LOS, in-hospital mortality, and change in serum chloride from baseline was not significant after adjusting for confounders. B Introduction: b Hyperchloremia is associated with increased morbidity and mortality in critically ill children, but it is unknown if the intravenous (IV) chloride amount administered (chloride load) is associated with hyperchloremia or poor outcomes. B Conclusions: b IV chloride load is independently associated with decreased odds of day 2 and 3 severe AKI, increased odds of hyperchloremia, and higher day 2 serum chloride in critically ill children. [Extracted from the article]

Convection enhanced drug delivery (CED) is a technique used to make therapeutic agents reach, through a catheter, sites of difficult access. The name of this technique comes from the convective flow originated by a pressure gradient induced at the tip of the catheter. This flow enhances passive diffusion and allows a more efficient spread of the agents by the target site. CED is particularly useful in the treatment of diseases that affect the central nervous system, where the blood–brain barrier prevents the diffusion of most therapeutic agents from the cerebral blood vessels to the brain interstitial space. In this work we deal with the numerical analysis of a coupled system of partial differential equations that can be used to simulate CED in an elastic medium like brain tissue. The model variables are the fluid velocity, the pressure, the tissue deformation, and the agents concentration. We prove the stability of the coupled problem and from the numerical point of view we propose a fully discrete piecewise linear finite element method (FEM). The convergence analysis shows that the method has second order convergence for the pressure, displacement, and concentration. Numerical experiments illustrating the theoretical convergence rates and the behavior of the system are also given. [ABSTRACT FROM AUTHOR]

• A mathematical methodology to find the optimal NIR light protocol in transdermal drug delivery; • Strategy based on an optimization problem minimizing the difference between target and simulated drug absorption profile; • The optimization problem relies on a 2D mathematical model for NIR light controlled transdermal drug delivery; • Validation of the transdermal model against laboratory data; • Convergence and stability analysis of a finite difference spatial scheme for a generalization of the transdermal model. Near-infrared light-controlled transdermal drug delivery (NIRTDD) has several advantages over traditional delivery methods, and it is now undergoing extensive research. One prominent aspect of NIRTDD is the possibility of keeping the drug concentration in its optimal therapeutic window using a suitable near-infrared light protocol. The problem is that this ideal protocol is usually unknown. In this paper, we propose a computational tool that aims at solving this issue. The computational tool relies on an optimization problem involving the numerical simulation of a two-dimensional mathematical model for NIRTDD. We also analyze the convergence and stability of a finite difference spatial scheme for a generalized version of this mathematical model. [ABSTRACT FROM AUTHOR]

This paper aims at inspiring a change in the traditional approach of sales and operations planning (S&OP) of integrated steel industries that have reached a maturity planning level allowing the use of sophisticated technologies. Therefore, we propose a two-stage stochastic programming model suitable for reproducing the rolling horizon framework of tactical planning. Simulations of one year of operations in an integrated steel industry showed a potential improvement of about 15% on overall supply chain profit in comparison with a plan produced traditionally. Besides, we evaluated two scenarios to analyze the effects of a flexible plan when facing a tax raise and a capacity reduction. As a practical implication, the model provides a consensus view of the S&OP stages at once, supporting top managers to make better decisions. The two-stage modeling approach also reinforces the need for interaction of the sales team with procurement, production, and distribution teams. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine whether use of a language other than English (LOE) would be associated with medical complexity, and whether medical complexity and LOE together would be associated with worse clinical outcomes. METHODS: The primary outcome of this single-site retrospective cohort study of PICU encounters from September 1, 2017, through August 31, 2022 was an association between LOE and medical complexity. Univariable and multivariable analyses were performed between demographic factors and medical complexity, both for unique patients and for all encounters. We investigated outcomes of initial illness severity (using Pediatric Logistic Organ Dysfunction-2), length of stay (LOS), days without mechanical ventilation or organ dysfunction using a mixed effects regression model, controlling for age, sex, race and ethnicity, and insurance status. RESULTS: There were 6802 patients and 10 011 encounters. In multivariable analysis for all encounters, Spanish use (adjusted odds ratio [aOR], 1.29; 95% confidence interval [CI], 1.11-1.49) and language other than English or Spanish (LOES) (aOR, 1.36; 95% CI, 1.02-1.80) were associated with medical complexity. Among unique patients, there remained an association between use of Spanish and medical complexity in multivariable analysis (aOR, 1.26; 95% CI, 1.05-1.52) but not between LOES and medical complexity (aOR, 1.30; 95% CI, 0.92-1.83). Children with medical complexity (CMC) who used an LOES had fewer organ dysfunction-free days (P = .003), PICU LOS was 1.53 times longer (P = .01), and hospital LOS was 1.45 times longer (P = .01) compared with CMC who used English. CONCLUSIONS: Use of an LOE was independently associated with medical complexity. CMC who used an LOES had a longer LOS. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) that improves in the pediatric intensive care unit (PICU) is associated with better outcomes compared to AKI that persists, but no study has investigated whether this also occurs in children undergoing cardiopulmonary bypass (CPB). Methods: A retrospective study of children ≤18 years who underwent CPB in three children's hospitals was conducted. Patients were classified into groups by kidney recovery after AKI according to Acute Disease Quality Initiative (ADQI) guidelines. Adjusted regression models evaluated associations between kidney recovery group and hospital outcomes. Results: Among 3620 children, AKI developed in 701 (19.4%): 610 transient AKI, 47 persistent AKI, and 44 acute kidney disease (AKD). Mortality increased with severity of kidney recovery group: 4.5% in the never developed AKI group, 8.9% in the transient AKI group, 25.5% in the persistent AKI group, and 31.8% in the AKD group (p <0.0001). In adjusted analysis, transient AKI (HR 1.4, CI 1.02, 2), persistent AKI (HR 22.4, CI 10.2, 49.2), and AKD (HR 3.7, CI 1.7, 7.9) had a greater hazard of mortality when compared to the never developed AKI group. Patients with transient AKI had a longer length of PICU stay than those with never developed AKI (HR 5.1, CI 2.9, 7.3). Conclusions: Patterns of kidney recovery after AKI were associated with worse PICU outcomes in children after CPB compared to those who did not develop AKI, even after rapid AKI recovery. Identification of factors that increase risk for these AKI patterns is necessary for prevention of AKI during CPB in children. [ABSTRACT FROM AUTHOR]

Ultrasound enhanced drug transport is a multiphysics problem involving acoustic waves propagation, bioheat transfer, and drug transport. In this paper, we study a model for this problem that consists of a wave-type equation for acoustic pressure, a diffusion-reaction equation for bioheat transfer, and a convection-diffusion-reaction equation for drug transport. We focus in particular on the numerical analysis of such a system. We propose and derive convergence estimates for a piecewise linear finite element method (FEM) with quadrature. We prove that the FEM is second order convergent for concentration in a discrete L 2 -norm. Since concentration depends on the gradient of acoustic pressure, this result shows that the FEM is superconvergent. Note that one expects the FEM to be convergent of order one in the L 2 -norm because the optimal convergence rate for the acoustic pressure is two in the H 1 -norm. We include numerical results backing the theoretical findings and an application of the model to a laboratory experiment of ultrasound enhanced transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Dupilumab, blocking IL‐4 and IL‐13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab‐treated patients with moderate‐to‐ severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate‐to‐severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty‐nine patients with moderate‐to‐severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL‐33 tear fluid levels and a significantly lower tear break‐up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management. [ABSTRACT FROM AUTHOR]

This article reports on two cases of successful treatment with tralokinumab in patients with atopic dermatitis (AD) and dupilumab-induced psoriasis. The first case involves a 75-year-old woman who experienced psoriatic lesions after receiving dupilumab treatment. Methotrexate was added to manage the psoriatic eruption, but it was discontinued due to side effects. Tralokinumab was then started, resulting in the resolution of both AD and psoriatic lesions. The second case involves an 18-year-old woman who also developed psoriasis while on dupilumab. Tralokinumab was started after topical steroids showed minimal improvement, leading to remission of the psoriatic lesions and maintenance of AD remission. The article suggests that tralokinumab may be a valid option for treating AD in patients with dupilumab-induced psoriasis. [Extracted from the article]

Background: Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients. Methods: We performed a retrospective cohort study of first‐time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10–20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator‐free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)‐III score. Results: We included 129 patients with median PRISM‐III score of 9 (interquartile range, IQR 7–15) and calculated Pediatric End‐stage Liver Disease score of 15 (IQR 2–23). A total of 37 patients (28.7%) had 10–20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18–2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10–1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74–0.97). There were no differences between groups in the likelihood of postoperative complications. Conclusions: In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes. [ABSTRACT FROM AUTHOR]

B Methods: b We performed a retrospective observational study of PICU admissions > 72 hours from July 2012-June 2021 at a single tertiary care children's hospital to determine associations with our primary outcome of bedside family presence percentage in the first 72 hours of admission. We completed descriptive bivariate analyses of the predictor variables and family presence percentage (Spearman Rho for continuous variables and Kruskal Wallis for categorical variables). [Extracted from the article]

B Conclusions: b Biomarker-based pediatric ARDS sub-phenotypes can be identified using routinely available EHR data in an acute timeframe, improving the ability to leverage sub-phenotypes for trial enrichment. Machine learning algorithms can predict ARDS sub-phenotypes in adults using exclusively clinical data. B Introduction: b In an effort to mitigate heterogeneity in Acute Respiratory Distress Syndrome (ARDS), biomarker-based sub-phenotyping has been used. [Extracted from the article]

B Introduction: b Genetic etiologies of pediatric disease represent an increasing proportion of pediatric intensive care unit (PICU) admissions due to more accessible diagnostic and therapeutic techniques. The central hypothesis is that if a PICU patient has ever had WES performed, then they will carry a higher disease burden on admission than other PICU patients. Comparing all admissions for each patient, those with WES performed demonstrated a higher median PRISM III score of 7 (IQR 3, 12) relative to the general PICU population median of 3 (IQR 0, 8) (p < 0.001). [Extracted from the article]

CONTEXT: Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE: To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES: PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION: Included studies evaluated critically ill childrenwith renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studieswith adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in Englishwith inability to determine eligibility criteriawere excluded. DATA EXTRACTION: Data were extracted from included studies into a standard data extraction form by task force members. RESULTS: The systematic reviewsupported the following criteria for renal dysfunction: (1) urine output < 0.5mL/kg per hour for ≥ 6 hours and serumcreatinine increase of 1.5 to 1.9 times baseline or ≥0.3mg/dL, or (2) urine output < 0.5mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73m², or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS: All included studies were observational and many were retrospective. CONCLUSIONS: We present consensus criteria for renal dysfunction in critically ill children. [ABSTRACT FROM AUTHOR]

Summary: Identifying genes or genomic regions influencing carcass‐quality traits such as fatness (FTN) is essential to optimize the genetic selection processes in beef cattle. The aim of this study was to identify genomic regions associated with FTN in Nellore cattle as well as to elucidate the metabolic pathways related to the phenotypic expression. Ultrasound‐based measurements of FTN were collected in 11 750 animals, with 39 903 animals in the pedigree file. Additionally, 1440 animals were genotyped using the GGP‐indicus 35K SNP panel, which contained 33 623 SNPs after quality control. Twenty genes related to FTN were found on 11 chromosomes, explaining 12.96% of the total additive genetic variance. Gene ontology revealed seven genes: NR1L2, PKD2, GSK3β, EXT1, RAD51B, SORCS1 and DPH6, associated with important processes related to FTN. In addition, novel candidate genes (MAATS1, LYPD1, CDK5RAP2, RAD51B, c13H2Oorf96 and TRAPPC11) were detected and could provide further knowledge to uncover genetic regions associated to carcass fatness in beef cattle. [ABSTRACT FROM AUTHOR]

Andean fold-and-thrust belts (FTBs) in the western border of South America show important along-strike variations in their structural style (thin- or thick-skinned) and shortening magnitudes, among others. These variations can arise from multiple factors, such as depth-to-detachment, geometry, and thickness of underlying basins, structural highs, the competence of the units involved in deformation, pre-orogenic structure of the basement, the rheological state of the upper crust or latitudinal gradients in shortening, among others. We carry out a set of new analogue models to understand how two of these factors affect the development and the geometry of the thrust systems within the Andean Principal Cordillera and adjacent fold-and-thrust belts at 32°-34°S (La Ramada and Aconcagua FTBs). In this contribution, we present the results of analogue modeling of doubly-vergent thrust systems with a built-in heterogeneity that allow us to evaluate the influence of differential shortening and presence of competent blocks (of relatively higher cohesion) in the generation, evolution, and structural setting of Andean FTBs. We highlight that despite the similar pattern of differential shortening in the models, the presence of the competent block has a significant influence on the structural configuration and leads to greater topographic uplift. Differential shortening plays a role in accommodating deformation, but when a competent block is present, the faults bounding the block control the deformation, producing a notable curvature of the FTBs. Summarizing, the presence of a competent block significantly influences the structural configuration within a doubly-vergent thrust system, emphasizing the role of inherited architecture in the orogenic growth of the Southern Central Andes. • Analogue models were carried out to assess the impact of differential shortening and competent blocks on FTB formation. • We ran a series of models to establish comparisons with the Principal Cordillera and neighboring FTBs in the Central Andes. • We recognize that pre-orogenic architecture controls the structural development of the Southern Central Andes. • We recognize that competent blocks within a doubly-vergent wedge induces the generation of curved thrust systems. • We propose that differential shortening and competent blocks exert critical control on obliquity andmcurvatures of structures. [ABSTRACT FROM AUTHOR]

At least 2hrs were required between boluses and every bolus had at least 30sec of adequate pre-bolus arterial waveform data. We hypothesized that as dp/dtmax has previously been associated with SV response, dp/dtmax would also be associated with mean arterial pressure (MAP) response to bolus. Future studies of dp/dtmax in particular - and fluid responsiveness in general - may want to consider the effects of SVR in addition to SV when assessing clinical response to IV fluid bolus. [Extracted from the article]

These events also pose increased mortality risk throughout an ICU stay and thus could offer a valuable target outcome for risk prediction models within the ICU B Introduction: b Critical deterioration in hospitalized children has been defined in the literature as ward to intensive care unit (ICU) transfer followed by events such as mechanical ventilation (MV) or vasopressor administration within 12 hours. Children who experience MV or vasopressor events within 12 hours of ICU transfer are at the highest risk for mortality and constitute a target cohort for risk prediction models in pre-ICU settings. [Extracted from the article]

To honor Lauren and her many contributions to our academic community, her family and we have established the endowed Lauren Marsillio-Craney Annual Lectureship in Pediatric Critical Care Science or Autonomic Medicine. Upon graduation, Lauren worked for the Health and Human Services (HHS) in the office of the Assistant Surgeon General. To honor Lauren and her many contributions to our academic community, her family and we have established the endowed Lauren Marsillio-Craney Annual Lectureship in Pediatric Critical Care Science or Autonomic Medicine Intrinsic to Lauren were her prodigious talent, her innovative predictive analytics in the critical care unit setting, and her great passion for highly applied big data research to help children survive critical illness and injury. [Extracted from the article]

B Introduction: b Fluid boluses are commonly administered to children with hypotension, but response is variable. At least 2hrs were required between boluses and every bolus had at least 30sec of adequate pre-bolus arterial waveform data. Fluid responsiveness (FR) was defined as increase by >= 10% in MAP from pre-bolus to average 20 min post-bolus. [Extracted from the article]

Our aim was to determine whether heart rate variability, which is a measure of autonomic nervous system function, is associated with pro-inflammatory biomarker levels in critically ill children. B Results: b Sixty-two patients met inclusion criteria in the prospective cohort and 599 patients in the retrospective cohort. Heart rate variability (HRV) was measured using the age-adjusted integer HRV (HRVi), which is the standard deviation of the heart rate sampled every 1 second over 5 consecutive minutes and age-normalized. [Extracted from the article]

Future studies are needed to determine whether HRV monitoring may play a role in predicting which patients are more likely to need liver transplantation to survive and which patients may recover with their native liver. B Introduction/Hypothesis: b Hepatic encephalopathy (HE) is a known determinant of outcomes in pediatric acute liver failure (PALF), but early and accurate recognition of neurologic dysfunction is difficult in children. PALF was defined using standard criteria and patients were stratified into patients with favorable and unfavorable outcomes (died or were listed for transplant). [Extracted from the article]

B Results: b Our population consisted of 141 patients, 71 (50.4%) with biliary atresia, median PELD/MELD score of 15 (2-24), and 47 (33.3%) patients were admitted to the hospital prior to LT. Bivariate and multivariate regression analyses were done to assess the relationship between FO (cumulative fluid balance (CFB) through POD 3 divided by pre-LT weight) and intensive care unit (ICU) and hospital length of stay (LOS), ventilator-free days in 28 (VFD), in-hospital mortality, and severe AKI (stage 2 or 3). Post-LT, there was a median PRISMIII score of 9 (7-14), 10 (7.1%) had hepatic artery and/or portal vein thrombosis, and 31 (22.0%) received >=40 mL/kg of blood product by POD 3. 70 (49.6%) patients had < 10% CFB, 41 (29.1%) patients had 10-20% CFB, and 30 (21.3%) patients had > 20% CFB. [Extracted from the article]

Our goal was to determine whether low heart rate variability (HRV), a measure of autonomic nervous system dysfunction, is associated with re-hospitalization in pediatric septic shock survivors. B Introduction: b Re-hospitalization after septic shock can lead to impaired quality of life. B Conclusions: b Lower discharge HRV and a smaller improvement in HRV during admission are significantly associated with re-hospitalization in survivors of pediatric septic shock. [Extracted from the article]