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Regional variability in therapeutic hypothermia eligibility criteria for neonatal hypoxic-ischemic encephalopathy
Early induced therapeutic hypothermia represents the cornerstone treatment in neonates with probable hypoxic-ischemic encephalopathy. The selection of patients for treatment usually involves meeting criteria indicating evidence of perinatal hypoxia-ischemia and the presence of moderate or severe encephalopathy. In this review, we highlight the variability that exists between some of the different regional and national eligibility guidelines. Determining the potential presence of perinatal hypoxia-ischemia may require either one, two or three signs amongst history of acute perinatal event, prolonged resuscitation at delivery, abnormal blood gases and low Apgar score, with a range of cutoff values. Clinical neurological exams often define the severity of encephalopathy differently, with varying number of domains required for determining eligibility and blurred interpretation of findings assigned to different severity grades in different systems. The role of early electrophysiological assessment is weighted differently. A clinical implication is that infants may receive different care depending on the location in which they are born. This could also impact epidemiological data, as inference of rates of moderate-severe encephalopathy based on therapeutic hypothermia rates are misleading and influenced by different eligibility methods used. We would advocate that a universally endorsed single severity staging of encephalopathy is vital for standardizing management and neonatal outcome.
Impact
Variability exists between regional and national therapeutic hypothermia eligibility guidelines for neonates with probable hypoxic-ischemic encephalopathy.
Differences are common in both criteria indicating perinatal hypoxia-ischemia and criteria defining moderate or severe encephalopathy. The role of early electrophysiological assessment is also weighted unequally.
This reflects in different individual care and impacts research data. A universally endorsed single severity staging of encephalopathy would be crucial for standardizing management.
Journal Article
Reactive application development
Mission-critical applications have to respond instantly to changes in load, recover gracefully from failure, and satisfy exacting requirements for performance, cost, and reliability. That's no small task! Reactive designs make it easier to meet these demands through modular, message-driven architecture, innovative tooling, and cloud-based infrastructure. Reactive Application Development teaches you how to build reliable enterprise applications using reactive design patterns. This hands-on guide begins by exposing you to the reactive mental model, along with a survey of core technologies like the Akka actors framework. Then, you'll build a proof-of-concept system in Scala, and learn to use patterns like CQRS and Event Sourcing. You'll master the principles of reactive design as you implement elasticity and resilience, integrate with traditional architectures, and learn powerful testing techniques.
Book
Pathways for balancing CO2 emissions and sinks
In December 2015 in Paris, leaders committed to achieve global, net decarbonization of human activities before 2100. This achievement would halt and even reverse anthropogenic climate change through the net removal of carbon from the atmosphere. However, the Paris documents contain few specific prescriptions for emissions mitigation, leaving various countries to pursue their own agendas. In this analysis, we project energy and land-use emissions mitigation pathways through 2100, subject to best-available parameterization of carbon-climate feedbacks and interdependencies. We find that, barring unforeseen and transformative technological advancement, anthropogenic emissions need to peak within the next 10 years, to maintain realistic pathways to meeting the COP21 emissions and warming targets. Fossil fuel consumption will probably need to be reduced below a quarter of primary energy supply by 2100 and the allowable consumption rate drops even further if negative emissions technologies remain technologically or economically unfeasible at the global scale.
COP21 led to a global commitment to decarbonization before 2100 to combat climate change, but leaves the timing and scale of mitigation efforts to individual countries. Here, the authors show that global carbon emissions need to peak within a decade to maintain realistic pathways for achieving the Paris Agreement.
Journal Article
The Metabolomic Profile of Umbilical Cord Blood in Neonatal Hypoxic Ischaemic Encephalopathy
Hypoxic ischaemic encephalopathy (HIE) in newborns can cause significant long-term neurological disability. The insult is a complex injury characterised by energy failure and disruption of cellular homeostasis, leading to mitochondrial damage. The importance of individual metabolic pathways, and their interaction in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defined population of full-term infants with HIE.
The injury severity was defined using both the modified Sarnat score and continuous multichannel electroencephalogram. Using these classification systems, our population was divided into those with confirmed HIE (n = 31), asphyxiated infants without encephalopathy (n = 40) and matched controls (n = 71). All had umbilical cord blood drawn and biobanked at -80 °C within 3 hours of delivery. A combined direct injection and LC-MS/MS assay (AbsolutIDQ p180 kit, Biocrates Life Sciences AG, Innsbruck, Austria) was used for the metabolomic analyses of the samples. Targeted metabolomic analysis showed a significant alteration between study groups in 29 metabolites from 3 distinct classes (Amino Acids, Acylcarnitines, and Glycerophospholipids). 9 of these metabolites were only significantly altered between neonates with Hypoxic ischaemic encephalopathy and matched controls, while 14 were significantly altered in both study groups. Multivariate Discriminant Analysis models developed showed clear multifactorial metabolite associations with both asphyxia and HIE. A logistic regression model using 5 metabolites clearly delineates severity of asphyxia and classifies HIE infants with AUC = 0.92. These data describe wide-spread disruption to not only energy pathways, but also nitrogen and lipid metabolism in both asphyxia and HIE.
This study shows that a multi-platform targeted approach to metabolomic analyses using accurately phenotyped and meticulously biobanked samples provides insight into the pathogenesis of perinatal asphyxia. It highlights the potential for metabolomic technology to develop a diagnostic test for HIE.
Journal Article
Localized Magnetopause Erosion at Geosynchronous Orbit by Reconnection
This study presents observations of magnetopause reconnection and erosion at geosynchronous
orbit, utilizing in situ satellite measurements and remote sensing ground‐based instruments. During the main
phase of a geomagnetic storm, Geostationary Operational Environmental Satellites (GOES) 15 was on the
dawnside of the dayside magnetopause (10.6 MLT) and observed significant magnetopause erosion, while
GOES 13, observing duskside (14.6 MLT), remained within the magnetosphere. Combined observations from
the THEMIS satellites and Super Dual Auroral Radar Network radars verified that magnetopause erosion was
primarily caused by reconnection. While various factors may contribute to asymmetric erosion, the observations suggest that the weak reconnection rate on the duskside can play a role in the formation of asymmetric magnetopause shape. This discrepancy in reconnection rate is associated with the presence of cold dense plasma on the duskside of the magnetosphere, which limits the reconnection rate by mass loading, resulting in more efficient magnetopause erosion on the dawnside.
Journal Article
Going Mobile to Address Emerging Climate Equity Needs in the Heterogeneous Urban Environment
The Brookhaven National Laboratory Center for Multiscale Applied Sensing (CMAS) aims to address environmental equity needs in the context of a changing climate. As a first step toward this goal, the center developed a one-of-a-kind observatory tailored to the study of highly heterogeneous urban environments. This article describes the features of the mobile observatory that enable its rapid deployment either on or off the power grid, as well as its instrument payload. Beyond its unique design, the observatory optimizes data collection within the obstacle-laden urban environment using a new smart sampling paradigm. This setup facilitated the collection of previously poorly documented environmental properties, including wind profiles throughout the atmospheric column. The mobile observatory captured unique observations during its first few intensive observation periods. Vertical air motion and infrared temperature measurements collected along the faces of the supertall One Vanderbilt skyscraper in Manhattan, NY, reveal how solar and anthropogenic heating affect wind flow and thus the venting of heat, pollution, and contaminants in urban street canyons. Also, air temperature measurements collected during travel along a 150-km transect between Upton and Manhattan, NY, offer a high-resolution view of the urban heat island and reveal that temperature disparities also exist within the city across different neighborhoods. Ultimately, the datasets collected by CMAS are poised to help guide equitable urban planning by highlighting existing disparities and characterizing the impact of urban features on the urban microclimate with the goal of improving human comfort.
Journal Article
Differences in standardized neonatal encephalopathy exam criteria may impact therapeutic hypothermia eligibility
BackgroundTherapeutic hypothermia (TH) is routinely provided to those with moderate or severe neonatal encephalopathy (NE). Subtle differences exist in the standardized exams used to define NE severity. We aimed to assess if an infant’s TH eligibility status differed if they were evaluated using either the NICHD/Neonatal Research Network’s (NICHD-NRN) or TOBY/British Association of Perinatal Medicine’s (TOBY-BAPM) neurological exam.MethodsEncephalopathic infants ≥36 weeks with evidence of perinatal asphyxia and complete documentation of the neurological exam <6 h of age were included. TH eligibility using the NICHD-NRN and TOBY-BAPM criteria was determined based upon the documented exams.ResultsNinety-one encephalopathic infants were included. Despite good agreement between the two exams (κ = 0.715, p < 0.001), TH eligibility differed between them (p < 0.001). A total of 47 infants were deemed eligible by at least one method—46 using NICHD-NRN and 35 using TOBY-BAPM. Of the 12 infants eligible per NICHD-NRN, but ineligible per TOBY-BAPM, two developed electrographic seizures and seven demonstrated hypoxic–ischemic cerebral injury.ConclusionsBoth the NICHD-NRN and TOBY-BAPM exams are evidence-based. Despite this, there is a significant difference in the number of infants eligible for TH depending on which exam is used. The NICHD-NRN exam identifies a greater proportion as eligible.ImpactThere are subtle differences in the NICHD-NRN and TOBY-BAPM’s encephalopathy exams used to determine eligibility for TH.This results in a significant difference in the proportion of infants determined to be eligible for TH depending on which encephalopathy exam is used.The NICHD-NRN encephalopathy exam identifies more infants as being eligible for TH than the TOBY-BAPM encephalopathy exam.This may result in different rates of cooling depending on which evidence-based neurological exam for evaluation of encephalopathy a center uses.
Journal Article
A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer
Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (
search.cancervariants.org
) for exploring the harmonized interpretations from these six knowledgebases.
This analysis presents a harmonized meta-knowledgebase to facilitate clinical interpretation of somatic genomic variants in cancer. This community-based project highlights the need for cooperative efforts to curate clinical interpretations of somatic variants for robust practice of precision oncology.
Journal Article
The impact of perinatal inflammation on the electroencephalogram in preterm infants: a systematic review
BackgroundTo summarise the association between perinatal inflammation (PI) exposure and electroencephalography (EEG) features in preterm infants.MethodsThis systematic review included clinical studies of preterm infants born <37 weeks of gestational age (GA), who had both a PI exposure and an EEG assessment performed during the neonatal period. Studies were identified from Medline and Embase databases on the 15th of September 2021. PI was defined by histological chorioamnionitis, clinical chorioamnionitis, or early-onset neonatal infection (EONI). The risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) appraisal tool. A narrative approach was used to synthesise results. This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement.ResultsTwo cross-sectional studies enrolling 130 preterm children born <32 weeks of GA assessed with one-channel amplitude-integrated EEG (aEEG) during the first four days of life were included. A PI exposure was described in 39 (30%) infants and was associated with a decrease in amplitude and a reduced incidence of sleep-wake cycling patterns.ConclusionThese results should be interpreted with caution because of the small number of included studies and their heterogeneity. Further clinical studies evaluating the association of PI with EEG findings are needed.ImpactA method to assess developmental trajectories following perinatal inflammation is required.Insufficient data exist to determine EEG features associated with perinatal inflammation.Further clinical studies evaluating this association are needed.
Journal Article