Assessment of Protein Binding Using Asymmetric-Flow Field-Flow Fractionation Combined with Multi-angle Light Scattering and Dynamic Light Scattering.

Asymmetric-flow field-flow fractionation (AF4) is a valuable tool to separate and assess different size populations in nanotherapeutics. When coupled with both static light scattering and dynamic light scattering, it can be used to qualitatively assess protein binding to nanoparticles by comparing the shape factors for both non-plasma-incubated samples and plasma-incubated samples. The shape factor is defined as the ratio of the derived root mean square radius (by static light scattering) to the measured hydrodynamic radius (by dynamic light scattering). The shape factor gives an idea of where the center of mass lies in a nanoparticle, and any shift in the shape factor to larger values is indicative of a mass addition to the periphery of the nanoparticle and suggests the presence of protein binding. This protocol will discuss how to set up an experiment to assess protein binding in nanoparticles using AF4, multi-angle light scattering (MALS), and dynamic light scattering (DLS).

Nanoparticle Size Distribution and Stability Assessment Using Asymmetric-Flow Field-Flow Fractionation.

Nanomaterials are inherently polydisperse. Traditional techniques, such as the widely used batch-mode dynamic light-scattering (DLS) analysis, are not ideal nor thoroughly descriptive enough to define the full complexity of these materials. Asymmetric-flow field-flow fractionation (AF4) with various in-line detectors, such as ultraviolet-visible (UV-vis), multi-angle light scattering (MALS), refractive index (RI), and DLS, is an alternative technique that can provide flow-mode analysis of not only size distribution but also shape, drug release/stability, and protein binding.

Emergency Department Pediatric Readiness and Disparities in Mortality Based on Race and Ethnicity.

Importance: Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. Objective: To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. Design, Setting, and Participants: This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. Exposure: Hospitalization for acute medical emergency or traumatic injury. Main Outcomes and Measures: The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. Results: The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. Conclusions and Relevance: In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

Point-of-Care Noninvasive Technology for Pediatric Dehydration Assessment.

OBJECTIVE: Dehydration is a commonly encountered problem worldwide. Current clinical assessment is limited by subjectivity and limited provider training with children. The objective of this study is to investigate a new noninvasive, point-of-care technology that measures capillary refill combined with patient factors to accurately diagnose dehydration. METHODS: This is a prospective observational study at a tertiary care children's hospital in Buenos Aires, Argentina. Patients were eligible if younger than 10 years who presented to the emergency department with vomiting and/or diarrhea whom the triage nurse deems to be potentially dehydrated. Patients had the digital capillary refill device done on presentation in addition to standard of care vital signs and weight. Patients had serial weights measured on hospital scales throughout their stay. The primary outcome was dehydration, which was calculated as a percent change in weight from admission to discharge. RESULTS: Seventy-six children were enrolled in the study with 56 included in the final analysis. A stepwise forward method selection chose malnutrition, temperature, and systolic blood pressure for the multivariable model. The area under the curve for the final model was fair (0.7431). To further look into the utility of such a device in the home setting where blood pressure is not available often, we reran the model without systolic blood pressure. The area under the curve for the final model was 0.7269. CONCLUSIONS: The digital capillary refill point-of-care device combined with readily available patient-specific factors may improve the ability to detect pediatric dehydration and facilitate earlier treatment or transfer to higher levels of care.

Assessment of intensive care unit-free and ventilator-free days as alternative outcomes in the pragmatic airway resuscitation trial.

OBJECTIVE: We sought to evaluate the utility and validity of ICU-free days and ventilator-free days as candidate outcomes for OHCA trials. METHODS: We conducted a secondary analysis of the Pragmatic Airway Resuscitation Trial. We determined ICU-free (days alive and out of ICU during the first 30 days) and ventilator-free days (days alive and without mechanical ventilation). We determined ICU-free and ventilator-free day distributions and correlations with Modified Rankin Scale (MRS). We tested associations with trial interventions (laryngeal tube (LT), endotracheal intubation (ETI)) using continuous (t-test), non-parametric (Wilcoxon Rank-Sum test - WRS), count (negative binomial - NB) and survival models (Cox proportional hazards (CPH) and competing risks regression (CRR)). We conducted bootstrapped simulations to estimate statistical power. MAIN RESULTS: ICU-free days was skewed; median 0 days (IQR 0, 0), survivors only 24 (18, 27). Ventilator-free days was skewed; median 0 (IQR 0, 0) days, survivors only 27 (IQR 23, 28). ICU-free and ventilator-free days correlated with MRS (Spearman's ρ = -0.95 and -0.97). LT was associated with higher ICU-free days using t-test (p = 0.001), WRS (p = 0.003), CPH (p = 0.02) and CRR (p = 0.04), but not NB (p = 0.13). LT was associated with higher ventilator-free days using t-test (p = 0.001), WRS (p = 0.001) and CRR (p = 0.03), but not NB (p = 0.13) or CPH (p = 0.13). Simulations suggested that t-test and WRS would have had the greatest power to detect the observed ICU- and ventilator-free days differences. CONCLUSION: ICU-free and ventilator-free days correlated with MRS and differentiated trial interventions. ICU-free and ventilator-free days may have utility in the design of OHCA trials.

Point-Of-Care Capillary Refill Technology Improves Accuracy of Peripheral Perfusion Assessment.

Background: Peripheral perfusion assessment is used routinely at the bedside by measuring the capillary refill time (CRT). Recent clinical trials have shown evidence to its ability to recognize conditions with decreased end organ perfusion as well as guiding therapeutic interventions in sepsis. However, the current standard of physician assessment at the bedside has shown large variability. New technology can improve the precision and repeatability of CRT affecting translation of previous high impact research. Methods: This was a prospective, observational study in the intensive care unit and emergency department at a quaternary care hospital using a non-invasive finger sensor for CRT. The device CRT was compared to the gold standard of trained research personnel assessment of CRT as well as to providers clinically caring for the patient. Results: Pearson correlations coefficients were performed across 89 pairs of measurements. The Pearson correlation for the device CRT compared to research personnel CRT was 0.693. The Pearson correlation for the provider CRT compared to research personnel CRT was 0.359. Conclusions: New point-of-care technology shows great promise in the ability to improve peripheral perfusion assessment performed at the bedside in the emergency department triage and during active resuscitation. This standardized approach allows for better translation of prior research that is limited by the subjectivity of manual visual assessment of CRT.

Rapid expansion of human impact on natural land in South America since 1985.

Across South America, the expansion of commodity land uses has underpinned substantial economic development at the expense of natural land cover and associated ecosystem services. Here, we show that such human impact on the continent's land surface, specifically land use conversion and natural land cover modification, expanded by 268 million hectares (Mha), or 60%, from 1985 to 2018. By 2018, 713 Mha, or 40%, of the South American landmass was impacted by human activity. Since 1985, the area of natural tree cover decreased by 16%, and pasture, cropland, and plantation land uses increased by 23, 160, and 288%, respectively. A substantial area of disturbed natural land cover, totaling 55 Mha, had no discernable land use, representing land that is degraded in terms of ecosystem function but not economically productive. These results illustrate the extent of ongoing human appropriation of natural ecosystems in South America, which intensifies threats to ecosystem-scale functions.

Cutting-Edge Technology for Rapid Bedside Assessment of Capillary Refill Time for Early Diagnosis and Resuscitation of Sepsis.

Sepsis currently affects over 30 million people globally with a mortality rate of ~30%. Prompt Emergency Department diagnosis and initiation of resuscitation improves outcomes; data has found an 8% increase in mortality for every hour delay in diagnosis. Once sepsis is recognized, the current Surviving Sepsis Guidelines for adult patients mandate the initiation of antibiotics within 3 h of emergency department triage as well as 30 milliliters per kilogram of intravenous fluids. While these are important parameters to follow, many emergency departments fail to meet these goals for a variety of reasons including turnaround on blood tests such as the serum lactate that may be delayed or require expensive laboratory equipment. However, patients routinely have vital signs assessed and measured in triage within 30 min of presentation. This creates a unique opportunity for implementation point for cutting-edge technology to significantly reduce the time to diagnosis of potentially septic patients allowing for earlier initiation of treatment. In addition to the practical and clinical difficulties with early diagnosis of sepsis, recent clinical trials have shown higher morbidity and mortality when septic patients are over-resuscitated. Technology allowing more real time monitoring of a patient's physiologic responses to resuscitation may allow for more individualized care in emergency department and critical care settings. One such measure at the bedside is capillary refill. This has shown favor in the ability to differentiate subsets of patients who may or may not need resuscitation and interpreting blood values more accurately (1, 2). This is a well-recognized measure of distal perfusion that has been correlated to sepsis outcomes. This physical exam finding is performed routinely, however, there is significant variability in the measurement based on who is performing it. Therefore, technology allowing rapid, objective, non-invasive measurement of capillary refill could improve sepsis recognition compared to algorithms that require lab tests included lactate or white blood count. This manuscript will discuss the broad application of capillary refill to resuscitation care and sepsis in particular for adult patients but much can be applied to pediatrics as well. The authors will then introduce a new technology that has been developed through a problem-based innovation approach to allow clinicians rapid assessment of end-organ perfusion at the bedside or emergency department triage and be incorporated into the electronic medical record. Future applications for identifying patient decompensation in the prehospital and home environment will also be discussed. This new technology has 3 significant advantages: [1] the use of reflected light technology for capillary refill assessment to provide deeper tissue penetration with less signal-to-noise ratio than transmitted infrared light, [2] the ability to significantly improve clinical outcomes without large changes to clinical workflow or provider practice, and [3] it can be used by individuals with minimal training and even in low resource settings to increase the utility of this technology. It should be noted that this perspective focuses on the utility of capillary refill for sepsis care, but it could be considered the next standard of care vital sign for assessment of end-organ perfusion. The ultimate goal for this sensor is to integrate it into existing monitors within the healthcare system.

Evaluation of Rural vs Urban Trauma Patients Served by 9-1-1 Emergency Medical Services.

Importance: Despite a large rural US population, there are potential differences between rural and urban regions in the processes and outcomes following trauma. Objectives: To describe and evaluate rural vs urban processes of care, injury severity, and mortality among injured patients served by 9-1-1 emergency medical services (EMS). Design, Setting, and Participants: This was a preplanned secondary analysis of a prospective cohort enrolled from January 1 through December 31, 2011, and followed up through hospitalization. The study included 44 EMS agencies transporting to 28 hospitals in 2 rural and 5 urban counties in Oregon and Washington. A population-based, consecutive sample of 67 047 injured children and adults served by EMS (1971 rural and 65 076 urban) was enrolled. Among the 53 487 patients transported by EMS, a stratified probability sample of 17 633 patients (1438 rural and 16 195 urban) was created to track hospital outcomes (78.9% with in-hospital follow-up). Data analysis was performed from June 12, 2015, to May 20, 2016. Exposures: Rural was defined at the county level by 60 minutes or more driving proximity to the nearest level I or II trauma center and/or rural designation in the Centers for Medicare & Medicaid Services ambulance fee schedule by zip code. Main Outcomes and Measures: Mortality (out-of-hospital and in-hospital), need for early critical resources, and transfer rates. Results: Of the 53 487 injured patients transported by EMS (17 633 patients in the probability sample), 27 535 were women (51.5%); mean (SD) age was 51.6 (26.1) years. Rural vs urban sensitivity of field triage for identifying patients requiring early critical resources was 65.2% vs 80.5%, and only 29.4% of rural patients needing critical resources were initially transported to major trauma centers vs 88.7% of urban patients. After accounting for transfers, 39.8% of rural patients requiring critical resources were cared for in major trauma centers vs 88.7% of urban patients. Overall mortality did not differ between rural and urban regions (1.44% vs 0.89%; P = .09); however, 89.6% of rural deaths occurred within 24 hours compared with 64% of urban deaths. Rural regions had higher transfer rates (3.2% vs 2.7%) and longer transfer distances (median, 97.4 km; interquartile range [IQR], 51.7-394.5 km; range, 47.8-398.6 km vs 22.5 km; IQR, 11.6-24.6 km; range, 3.5-97.4 km). Conclusions and Relevance: Most high-risk trauma patients injured in rural areas were cared for outside of major trauma centers and most rural trauma deaths occurred early, although overall mortality did not differ between regions. There are opportunities for improved timeliness and access to major trauma care among patients injured in rural regions.

Can carbon emissions from tropical deforestation drop by 50% in 5 years?

Halving carbon emissions from tropical deforestation by 2020 could help bring the international community closer to the agreed goal of <2 degree increase in global average temperature change and is consistent with a target set last year by the governments, corporations, indigenous peoples' organizations and non-governmental organizations that signed the New York Declaration on Forests (NYDF). We assemble and refine a robust dataset to establish a 2001-2013 benchmark for average annual carbon emissions from gross tropical deforestation at 2.270 Gt CO2 yr(-1). Brazil did not sign the NYDF, yet from 2001 to 2013, Brazil ranks first for both carbon emissions from gross tropical deforestation and reductions in those emissions - its share of the total declined from a peak of 69% in 2003 to a low of 20% in 2012. Indonesia, an NYDF signatory, is the second highest emitter, peaking in 2012 at 0.362 Gt CO2 yr(-1) before declining to 0.205 Gt CO2 yr(-1) in 2013. The other 14 NYDF tropical country signatories were responsible for a combined average of 0.317 Gt CO2 yr(-1) , while the other 86 tropical country non-signatories were responsible for a combined average of 0.688 Gt CO2 yr(-1). We outline two scenarios for achieving the 50% emission reduction target by 2020, both emphasizing the critical role of Brazil and the need to reverse the trends of increasing carbon emissions from gross tropical deforestation in many other tropical countries that, from 2001 to 2013, have largely offset Brazil's reductions. Achieving the target will therefore be challenging, even though it is in the self-interest of the international community. Conserving rather than cutting down tropical forests requires shifting economic development away from a dependence on natural resource depletion toward recognition of the dependence of human societies on the natural capital that tropical forests represent and the goods and services they provide.

Children's safety initiative: a national assessment of pediatric educational needs among emergency medical services providers.

OBJECTIVE: Emergency medical services (EMS) providers may have critical knowledge gaps in pediatric care due to lack of exposure and training. There is currently little evidence to guide educators to the knowledge gaps that most need to be addressed to improve patient safety. The objective of this study was to identify educational needs of EMS providers related to pediatric care in various domains in order to inform development of curricula. METHODS: The Children's Safety Initiative-EMS performed a three-phase Delphi survey on patient safety in pediatric emergencies among providers and content experts in pediatric emergency care, including physicians, nurses, and prehospital providers of all levels. Each round included questions related to educational needs of providers or the effect of training on patient safety events. We identified knowledge gaps in the following domains: case exposure, competency and knowledge, assessment and decision making, and critical thinking and proficiency. Individual knowledge gaps were ranked by portion of respondents who ranked them "highly likely" (Likert-type score 7-10 out of 10) to contribute to safety events. RESULTS: There were 737 respondents who were included in analysis of the first phase of the survey. Paramedics were 50.8% of respondents, EMT-basics/first responders were 22%, and physicians 11.4%. The top educational priorities identified in the final round of the survey include pediatric airway management, responder anxiety when working with children, and general pediatric skills among providers. The top three needs in decision-making include knowing when to alter plans mid-course, knowing when to perform an advanced airway, and assessing pain in children. The top 3 technical or procedural skills needs were pediatric advanced airway, neonatal resuscitation, and intravenous/intraosseous access. For neonates, specific educational needs identified included knowing appropriate vital signs and preventing hypothermia. CONCLUSIONS: This is the first large-scale Delphi survey related to pediatric prehospital education. Our results provide foundational information related to the educational needs of prehospital providers. Medical directors and educators can use the results to shape future curricular development.

The association between hospital type and mortality among critically ill children in US EDs.

STUDY AIM: Little is known about the setting of care for critically ill children and whether differences in outcomes are related to the presenting hospital type. This study describes the characteristics of hospitals to which critically ill children present and explores the associations between hospital factors and mortality. METHODS: This is a retrospective cohort study using data from the 2007 Healthcare Cost and Utilization Project National Emergency Department Sample, representative of all US ED visits. Subjects include children aged 0-18 with ICD9 codes for cardiac arrest, respiratory arrest and/or respiratory failure. Predictor variables include: age, sex, presence of chronic illness, self-pay, public insurance, trauma diagnosis, major trauma center, urban hospital, ED volume and teaching hospital. Multivariate logistic regression estimates predictors of mortality. Analyses integrate clusters, strata, and weights from the probability sample. RESULTS: There were an estimated 29 million pediatric ED visits in 2007 including 42,036 (0.1%) visits for cardiac or respiratory failure. Teaching hospitals (OR 0.57, 95% CI 0.50-0.66), trauma centers (OR 0.76, 95% CI 0.67-0.86), and urban hospitals (OR 0.78, 95% CI 0.63-0.97) were associated with lower mortality odds. Presence of a chronic illness (OR 14.5, 95% CI 10.5-20.1), diagnosis of an injury (OR 1.2, 95% CI 1.1-1.4) and self-pay status (OR 3.6, 95% CI 2.9-4.4) were associated with increased mortality odds. CONCLUSIONS: The majority of children with cardiac and respiratory arrest present to urban teaching hospitals and trauma centers. After accounting for important confounders, mortality is lower at teaching hospitals and/or major trauma centers.

Baseline map of carbon emissions from deforestation in tropical regions.

Policies to reduce emissions from deforestation would benefit from clearly derived, spatially explicit, statistically bounded estimates of carbon emissions. Existing efforts derive carbon impacts of land-use change using broad assumptions, unreliable data, or both. We improve on this approach using satellite observations of gross forest cover loss and a map of forest carbon stocks to estimate gross carbon emissions across tropical regions between 2000 and 2005 as 0.81 petagram of carbon per year, with a 90% prediction interval of 0.57 to 1.22 petagrams of carbon per year. This estimate is 25 to 50% of recently published estimates. By systematically matching areas of forest loss with their carbon stocks before clearing, these results serve as a more accurate benchmark for monitoring global progress on reducing emissions from deforestation.