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Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure–safety relationship is unknown.
Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines. Clinically significant hypotension was defined as hypotension with concomitant lactate >3 mg/dl. A prior population pharmacokinetic model was used to simulate milrinone exposures to evaluate exposure–safety relationships.
We included 399 children with a median (quarter 1, quarter 3) age of 1 year (0,5) who received 428 intravenous doses of milrinone (median infusion rate 0.31 mcg/kg/min [0.29,0.5]). Median maximum plasma milrinone concentration was 110.7 ng/ml (48.4,206.2). Median lowest systolic and diastolic blood pressures were 74 mmHg (60,85) and 35 mmHg (25,42), respectively. At least 1 episode of hypotension occurred in 178 (45%) subjects; clinically significant hypotension occurred in 10 (2%). The maximum simulated milrinone plasma concentrations were higher in subjects with clinically significant hypotension (251 ng/ml [129,329]) versus with hypotension alone (86 ng/ml [44, 173]) versus without hypotension (122 ng/ml [57, 208], p = 0.002); however, this relationship was not retained on multivariable analysis (odds ratio 1.01; 95% confidence interval 0.998, 1.01).
We successfully leveraged a population pharmacokinetic model and electronic health record data to evaluate the relationship between simulated plasma concentration of milrinone and systemic hypotension occurrence, respectively, supporting the broader applicability of our novel, efficient, and cost-effective study design for examining drug exposure–response and –safety relationships.
ABSTRACT IMPACT: Patients living in overcrowded zip codes were at increased risk of contracting severe COVID-19 after controlling for confounding disease and socioeconomic factors OBJECTIVES/GOALS: This study sought to examine whether residences in over-crowded zip codes with higher reported over-crowding represented an independent risk factor for severe COVID-19 infection, defined by presentation to an emergency department. METHODS/STUDY POPULATION: In this zip code tabulated area (ZCTA)-level analysis, we used NYC Department of Health disease surveillance data in March 2020 merged with data from the CDC and ACS to model suspected COVID-19 case rates by zip code over-crowdedness (households with greater than 1 occupant per room, in quartiles). We defined suspected COVID-19 cases as emergency department reported cases of pneumonia and influenza-like illness. Our final model employed a multivariate Poisson regression models with controls for known COVID-19 clinical (prevalence of obesity, coronary artery disease, and smoking) and related socioeconomic risk factors (percentage below federal poverty line, median income by zip-code, percentage White, and proportion of multigenerational households) after accounting for multicollinearity. RESULTS/ANTICIPATED RESULTS: Our analysis examined 39,923 suspected COVID-19 cases across 173 ZCTAs in NYC between March 1 and March 30 2020. We found that, after adjusted analysis, for every quartile increase in defined over-crowdedness, case rates increased by 32.8% (95% CI: 22.7%% to 34.0%, P < 0.001). DISCUSSION/SIGNIFICANCE OF FINDINGS: Over-crowdedness by zip code may be an independent risk factor for severe COVID-19. Social distancing measures such as school closures that increase house-bound populations may inadvertently worsen the risk of COVID-19 contraction in this setting.
Young patients suffering from rhythm disorders have a negative impact in their quality of life. In recent years, ablation has become the first-line therapy for supraventricular arrhythmias in children. In the light of the current expertise and advancement in the field, we decided to evaluate the quality of life in young patients with supraventricular arrhythmias before and after a percutaneous ablation procedure.
The prospective cohort consisted of patients <18 years with structurally normal hearts and non-pre-excited supraventricular arrhythmias, who had an ablation in our centre from 2013 to 2018. The cohort was evaluated with the PedsQL™ 4.0 Generic Core Scales self-questionnaire prior to and post-ablation.
The final cohort included 88 patients consisted of 52 males (59%), with a mean age at ablation of 12.5 ± 3.3 years. Forty-two patients (48%) had a retrograde-only accessory pathway mediating the tachycardia, 38 (43%) had atrio-ventricular nodal re-entrant tachycardia, 7 (8%) had ectopic atrial tachycardia, and 1 (1%) had atrial flutter. The main reason for an ablation was the patient’s choice in 53%. There were no severe complications. Comparison between the baseline and post-ablation assessments showed that patients reported significant improvement in the scores for physical health, emotional and social functioning, as well as in the total scores.
The present study demonstrates that the successful treatment of supraventricular arrhythmias by means of an ablation results in a significant improvement in the quality of self-reported life scores in young patients.
Plasmonic near-perfect absorbers, comprising metal films with a periodic array of subwavelength openings, were deposited on the surface of pyroelectric materials to create wavelength-selective far-infrared detectors. The detectors fabricated and investigated were based on one of two pyroelectric materials: (i) z-cut monocrystalline lithium tantalate (LiTaO3) wafers or, (ii) reactively sputtered aluminum nitride (AlN), with absorbers fabricated by contact photolithography. Spectrally selective absorption resonances were demonstrated by Fourier-transform spectroscopy. Spectrally-selective photoresponse was demonstrated with a tunable THz backward wave oscillator. Responsivity was estimated using a black body source to be ∼ 1 mV/W for AlN samples and ∼ 100 mV/W for LiTaO3 samples. Most similar work has focused on detectors for mid-wave and long-wave infrared spectral regions. Our focus on THz wavelengths beyond 20 μm is motivated by specific security and contraband sensing applications.
Lead carbonates were used as cosmetic and pigment since Antiquity. The pigment, known as lead white, was generally composed of cerussite and hydrocerussite. Unlike most ancient pigments, lead white was obtained by a synthetic route involving metallic lead, vinegar and organic matter. Fermentation of organic matter produces heat and CO2 emission, leading to the formation of carbonates. As lead white is formed by trapping CO2, radiocarbon (14C) dating can thus be considered. We have developed a protocol to prepare lead white. We selected modern pigments for the experiment implementation and ancient cosmetic and paintings for dating. After characterization of the samples by XRD, thermal decomposition of cerussite at various temperatures was explored in order to select the appropriate conditions for painting samples. CO2 extraction yield, SEM and XPS were used to characterize the process. Thermal decomposition at 400°C was successfully applied to mixtures of lead white with other paint components (oil as binder, calcite as filler/extender) and to historical samples. We obtained radiocarbon measurements in agreement with the expected dates, demonstrating that thermal decomposition at 400°C is efficient for a selective decomposition of lead white and that paintings can be directly 14C-dated by dating lead white pigment.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
We study the evolution of the decaying active region NOAA 12708, from the photosphere up to the corona using high resolution, multi-wavelength GREGOR observations taken on May 9, 2018. We utilize spectropolarimetric scans of the 10830 Å spectral range by the GREGOR Infrared Spectrograph (GRIS), spectral imaging time-series in the Na ID2 spectral line by the GREGOR Fabry-Pérot Interferometer (GFPI) and context imaging in the Ca IIH and blue continuum by the High-resolution Fast Imager (HiFI). Context imaging in the UV/EUV from the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO) complements our dataset. The region under study contains one pore with a light-bridge, a few micro-pores and extended clusters of magnetic bright points. We study the magnetic structure from the photosphere up to the upper chromosphere through the spectropolarimetric observations in He II and Si I and through the magnetograms provided by the Helioseismic and Magnetic Imager (HMI). The high-resolution photospheric images reveal the complex interaction between granular-scale convective motions and a range of scales of magnetic field concentrations in unprecedented detail. The pore itself shows a strong interaction with the convective motions, which eventually leads to its decay, while, under the influence of the photospheric flow field, micro-pores appear and disappear. Compressible waves are generated, which are guided towards the upper atmosphere along the magnetic field lines of the various magnetic structures within the field-of-view. Modelling of the He i absorption profiles reveals high velocity components, mostly associated with magnetic bright points at the periphery of the active region, many of which correspond to asymmetric Si I Stokes-V profiles revealing a coupling between upper photospheric and upper chromospheric dynamics. Time-series of Na ID2 spectral images reveal episodic high velocity components at the same locations. State-of-the-art multi-wavelength GREGOR observations allow us to track and understand the mechanisms at work during the decay phase of the active region.
The Sun is our dynamic host star due to its magnetic fields causing plentiful of activity in its atmosphere. From high energetic flares and coronal mass ejections (CMEs) to lower energetic phenomena such as jets and fibrils. Thus, it is of crucial importance to learn about formation and evolution of solar magnetic fields. These fields cover a wide range of spatial and temporal scales, starting on the larger end with active regions harbouring complex sunspots, via isolated pores, down to the smallest yet resolved elements – so-called magnetic bright points (MBPs). Here, we revisit the various manifestations of solar magnetic fields by the largest European solar telescope in operation, the 1.5-meter GREGOR telescope. We show images from the High-resolution Fast Imager (HiFI) and spectropolarimetric data from the GREGOR Infrared Spectrograph (GRIS). Besides, we outline resolved convective features inside the larger structures – so-called light-bridges occurring on large to mid-sized scales.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
Our current knowledge of star formation and accretion luminosity at high redshift (z > 3–4), as well as the possible connections between them, relies mostly on observations in the rest-frame ultraviolet, which are strongly affected by dust obscuration. Due to the lack of sensitivity of past and current infrared instrumentation, so far it has not been possible to get a glimpse into the early phases of the dust-obscured Universe. Among the next generation of infrared observatories, SPICA, observing in the 12–350 µm range, will be the only facility that can enable us to trace the evolution of the obscured star-formation rate and black-hole accretion rate densities over cosmic time, from the peak of their activity back to the reionisation epoch (i.e., 3 < z ≲ 6–7), where its predecessors had severe limitations. Here, we discuss the potential of photometric surveys performed with the SPICA mid-infrared instrument, enabled by the very low level of impact of dust obscuration in a band centred at 34 µm. These unique unbiased photometric surveys that SPICA will perform will fully characterise the evolution of AGNs and star-forming galaxies after reionisation.
The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood.
The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants.
We extracted information on sildenafil dosing and clinical characteristics from electronic health records of 348 neonatal ICUs from 1997 to 2013, and we predicted drug exposure using a population pharmacokinetic model.
We identified 232 infants receiving sildenafil at a median dose of 3.2 mg/kg/day (2.0, 6.0). The median steady-state area under the concentration–time curve over 24 hours (AUC24,SS) and maximum concentration of sildenafil (Cmax,SS,SIL) were 712 ng×hour/ml (401, 1561) and 129 ng/ml (69, 293), respectively. Systemic hypotension occurred in 9% of the cohort. In multivariable analysis, neither dosing nor exposure were associated with systemic hypotension: odds ratio=0.96 (95% confidence interval: 0.81, 1.14) for sildenafil dose; 0.87 (0.59, 1.28) for AUC24,SS; 1.19 (0.78, 1.82) for Cmax,SS,SIL.
We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil’s safety profile in infants is warranted.
The Atlantic–Mediterranean transition zone between the Alborán Sea and the Gulf of Cádiz constitutes the most prominent marine geographic barrier in European waters and includes known phylogeographic breaks such as the Strait of Gibraltar and the Almería-Oran Front. A genetic shift in this area has been previously documented for the European littoral shrimp Palaemon elegans. Here we carried out a phylogeographic analysis with the congeneric and sympatric species Palaemon serratus to test for similar intraspecific genetic differentiation and geographic structure. This littoral prawn is distributed in the Northeastern Atlantic Ocean, the Mediterranean Sea and the Black Sea. We compared DNA sequences from the mitochondrial genes Cox1 and to a lesser extent from 16S rRNA of several Atlantic and Mediterranean populations. Furthermore, sequences from the nuclear gene Enolase were included for corroborating differences between Mediterranean and Atlantic individuals. A pronounced genetic differentiation was detected between the Mediterranean and Atlantic populations, amounting to 10.14% in Cox1 and 2.0% in 16S, indicating the occurrence of two independent evolutionary lineages. Interestingly, specimens from the Atlantic Gulf of Cadiz cluster together with the Mediterranean individuals, indicating that a biogeographic barrier appears to be located west of the Strait of Gibraltar.
Chagas disease is one of the most important vector-borne zoonotic diseases in Latin America. Control strategies could be improved if transmissibility patterns of its aetiologic agent, Trypanosoma cruzi, were better understood. To understand transmissibility patterns of Chagas disease in Mexico, we inferred potential vectors and hosts of T. cruzi from geographic distributions of nine species of Triatominae and 396 wild mammal species, respectively. The most probable vectors and hosts of T. cruzi were represented in a Complex Inference Network, from which we formulated a predictive model and several associated hypotheses about the ecological epidemiology of Chagas disease. We compiled a list of confirmed mammal hosts to test our hypotheses. Our tests allowed us to predict the most important potential hosts of T. cruzi and to validate the model showing that the confirmed hosts were those predicted to be the most important hosts. We were also able to predict differences in the transmissibility of T. cruzi among triatomine species from spatial data. We hope our findings help drive efforts for future experimental studies.
The Carolina Sandhills is a physiographic region of the Atlantic Coastal Plain province in the southeastern United States. In Chesterfield County (South Carolina), the surficial sand of this region is the Pinehurst Formation, which is interpreted as eolian sand derived from the underlying Cretaceous Middendorf Formation. This sand has yielded three clusters of optically stimulated luminescence ages: (1) 75 to 37 thousand years ago (ka), coincident with growth of the Laurentide Ice Sheet; (2) 28 to 18 ka, coincident with the last glacial maximum (LGM); and (3) 12 to 6 ka, mostly coincident with the Younger Dryas through final collapse of the Laurentide Ice Sheet. Relict dune morphologies are consistent with winds from the west or northwest, coincident with modern and inferred LGM January wind directions. Sand sheets are more common than dunes because of effects of coarse grain size (mean range: 0.35-0.59 mm) and vegetation. The coarse grain size would have required LGM wind velocities of at least 4-6 m/sec, accounting for effects of colder air temperatures on eolian sand transport. The eolian interpretation of the Carolina Sandhills is consistent with other evidence for eolian activity in the southeastern United States during the last glaciation.
We present the observed “continuum” levels of polarization as a function of time for four well-observed Type II-Plateau supernovae (SNe II-P; Fig. 1), the class of SNe decisively determined to arise from red supergiant stars (Smartt 2009). All four objects show temporally increasing degrees of polarization through the end of the photospheric phase, with some exhibiting early-time polarization that challenge existing models (e.g., Dessart and Hillier 2011) to reproduce. A fundamental ejecta asymmetry is present in this photometrically diverse sample of type II SNe, and it probably takes different forms (e.g., 56Ni blobs/fingers, large scale deformation). We acknowledge support from NSF grants AST-1009571 and AST-1210311.
The objective of this work was to develop a field method for the determination of labile organic carbon in hyper-arid desert soils. Industry standard methods rely on expensive analytical equipment that are not possible to take into the field, while scientific challenges require fast turn-around of large numbers of samples in order to characterize the soils throughout this region. Here we present a method utilizing acid-hydrolysis extraction of the labile fraction of organic carbon followed by potassium permanganate oxidation, which provides a quick and inexpensive approach to investigate samples in the field. Strict reagent standardization and calibration steps within this method allowed the determination of very low levels of organic carbon in hyper-arid soils, in particular, with results similar to those determined by the alternative methods of Calcination and Pyrolysis–Gas Chromatography–Mass Spectrometry. Field testing of this protocol increased the understanding of the role of organic materials in hyper-arid environments and allowed real-time, strategic decision making for planning for more detailed laboratory-based analysis.
The 2011 investigations of the Caves Branch Archaeological Survey at the large and recently documented Maya site of Tipan Chen Uitz resulted in the discovery of the site's first monument with a glyphic inscription. Prior to this discovery, the site's glyphic corpus was limited to a small collection of texts rendered on fragmentary ceramics. In this paper, we describe these sherds as well as the monument (Monument 1), report on their archaeological contexts, provide an epigraphic analysis of the texts, and consider these written sources relative to our growing understanding of Tipan and its place in the ancient political landscape. The discovery of Monument 1 is important, for it stands to contribute to sociopolitical reconstructions in this part of the central Maya Lowlands and has significant implications for the possible presence of other, as yet undiscovered, Late Classic period (A.D. 550-830) monuments at Tipan.
Sand hills in the Savannah River valley in Jasper County (South Carolina, USA) are interpreted as the remnants of parabolic eolian dunes composed of sand derived from the Savannah River and stabilized by vegetation under prevailing climate conditions. Optically stimulated luminescence ages reveal that most of the dunes were active ca. 40 to 19 ka ago, coincident with the last glacial maximum (LGM) through early deglaciation. Modern surface winds are not sufficient for sustained eolian sand transport. When the dunes were active, winds blew at velocities of at least 4 m/s from west to east, and some vegetation was present. The ratio of annual precipitation to potential evapotranspiration (P:PE) was less than the modern ratio of 1.23 and may have been < 0.30, caused by stronger winds (which would have resulted in greater evaporation) and/or reduced precipitation. The Savannah River dunes are part of a larger assemblage of eolian dunes that were active in the eastern United States during and immediately after the LGM, suggesting that eolian sediment behavior in this region has been controlled by regional forcing mechanisms during the Quaternary.