•Paradoxical hypertension occurs following repair of coarctation of the aorta in children•Elevated catecholamines activate the renin-angiotensin system•Labetalol prevented hypertension and activation ...of the renin-angiotensin system
Paradoxical hypertension after repair of coarctation of the aorta in children is associated with the release of catecholamines and activation of the renin-angiotensin system. The objective of the present study was to describe the effects of labetalol infusion on blood pressure, plasma catecholamine levels, and plasma renin activity in a series of children undergoing repair of coarctation of the aorta.
Prospective, observational cohort study.
Tertiary children's hospital with university affiliation.
The study was comprised of 15 consecutive children older than 1 year undergoing repair of coarctation of the aorta.
Intravenous infusion of labetalol, up to 20 µg/kg/min, was administered when patients became hypertensive after release of the aortic cross-clamp. Supplementation with nitroprusside was allowed as needed.
Blood pressure was maintained below baseline values throughout the labetalol infusion. Plasma norepinephrine increased from 160 ± 81 pg/mL (preoperative) to 657 ± 268 pg/mL (6 h after release of aortic cross-clamp). Plasma renin activity decreased from 16.6 ± 9.7 ng/kg/h (at cross-clamp release) to 2.2 ± 2.2 ng/kg/h (6 h after cross-clamp release). Nitroprusside was added for 12 patients, at a highest mean dose of 2.4 ± 2.5 μg/kg/min.
Labetalol inhibited activation of the renin-angiotensin system and helped control paradoxical hypertension after coarctation repair in children.
Calcium signaling plays a pivotal role in cardiomyocytes, coupling electrical excitation to mechanical contraction of the heart. Determining locations of active calcium release sites, and how their ...recruitment changes in response to stimuli and in disease states is therefore of central interest in cardiac physiology. Current algorithms for detecting release sites from live cell imaging data are however not easily validated against a known “ground truth,” which makes interpretation of the output of such algorithms, in particular the degree of confidence in site detection, a challenging task. Computational models are capable of integrating findings from multiple sources into a consistent, predictive framework. In cellular physiology, such models have the potential to reveal structure and function beyond the temporal and spatial resolution limitations of individual experimental measurements. Here, we create a spatially detailed computational model of calcium release in an eight sarcomere section of a ventricular cardiomyocyte, using electron tomography reconstruction of cardiac ultrastructure and confocal imaging of protein localization. This provides a high-resolution model of calcium diffusion from intracellular stores, which can be used as a platform to simulate confocal fluorescence imaging in the context of known ground truth structures from the higher resolution model. We use this capability to evaluate the performance of a recently proposed method for detecting the functional response of calcium release sites in live cells. Model permutations reveal how calcium release site density and mitochondria acting as diffusion barriers impact the detection performance of the algorithm. We demonstrate that site density has the greatest impact on detection precision and recall, in particular affecting the effective detectable depth of sites in confocal data. Our findings provide guidance on how such detection algorithms may best be applied to experimental data and give insights into limitations when using two-dimensional microscopy images to analyse three-dimensional cellular structures.
Cet article vise à clarifier le recours à une famille de métaphores qui entoure fréquemment le procès (ritualisation, théâtralisation, mise en scène, cérémonie de type religieux), et défend la thèse ...que la notion de ritualisation judiciaire exprime avant tout la louable intention d'accorder à la justice internationale pénale un temps et des occasions sans finalité préconçue, mais qui permettent la manifestation d'une diversité d'émotions. Il prend principalement appui sur la comparaison des Pensées et des Lettres provinciales de Pascal d'une part, sur les Remarques sur Le Rameau d'or de Frazer et les Leçons sur la croyance religieuse de Wittgenstein d'autre part. C'est en s'efforçant de rendre raison de notre tendance à inscrire le procès pénal dans différents contextes, qu'il pose la question du genre de connaissance qui nous conduit à former cette idée de ritualisation judiciaire.
This paper aims at clarifying our use of a metaphor family often surrounding the trial (ritualization, dramatization, performance, religious-type ceremony), and supports the idea that the notion of a judicial ritualization expresses the praiseworthy intention to allow time and occasions to the penal international justice - such occasions having no predetermined goal, however, though they make it possible for a variety of emotions to manifest themselves. This article is grounded on a comparison between Pascal's Pensées (Thoughts) and Lettres provinciales (Provincial letters) on the one hand, and Wittgenstein's Remarks on Frazer's Golden bough and his Lessons on religious belief on the other. In an effort to explain our tendency to put the trial in various contexts, it interrogates the kind of knowledge that leads us to form the very idea of a judicial ritualization.
Este artículo pretende arrojar luz sobre el uso de una familia de metáforas que rodean el juicio (ritualización, dramatización, realización, ceremonia cuasi-religiosa), y propone la idea de que la noción de una ritualización judicial expresa la encomiable intención de dar tiempo y oportunidad a la justicia penal internacional -pese a que dichas oportunidades no tengan objetivo cierto, aunque permitan la expresión de un abanico de emociones. El artículo se basa en una comparación entre las obras Pensamientos y Lettres provinciales (Cartas provinciales), de Blaise Pascal, por un lado, y Observaciones a La rama dorada de Frazer y Lecciones y conversaciones sobre estética, psicología y creencia religiosa, de Ludwig Wittgenstein, por el otro. En un intento de explicar nuestra tendencia a poner el juicio en diferentes contextos, se pregunta por el tipo de conocimiento que nos lleva a formarnos la idea misma de una ritualización judicial.
DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=3110770
We have synthesized and evaluated five series of polymeric gadolinium chelates which are of interest as potential MRI blood pool contrast agents. The polymers were designed so that important physical ...properties including molecular weight, relaxivity, metal content, viscosity, and chelate stability could be varied. We have shown that, by selecting polymers of the appropriate MW, extended blood pool retention can be achieved. In addition, relaxivity can be manipulated by changing the polymer rigidity, metal content affected by monomer selection, viscosity by polymer shape, and chelate stability by chelator selection.
Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune ...diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and infer B and T cell clonal relationships. However, currently available tools offer limited parallelization across samples, scalability or portability to high-performance computing infrastructures. To address this need, we developed nf-core/airrflow, an end-to-end bulk and single-cell AIRR-seq processing workflow which integrates the Immcantation Framework following BCR and TCR sequencing data analysis best practices. The Immcantation Framework is a comprehensive toolset, which allows the processing of bulk and single-cell AIRR-seq data from raw read processing to clonal inference. nf-core/airrflow is written in Nextflow and is part of the nf-core project, which collects community contributed and curated Nextflow workflows for a wide variety of analysis tasks. We assessed the performance of nf-core/airrflow on simulated sequencing data with sequencing errors and show example results with real datasets. To demonstrate the applicability of nf-core/airrflow to the high-throughput processing of large AIRR-seq datasets, we validated and extended previously reported findings of convergent antibody responses to SARS-CoV-2 by analyzing 97 COVID-19 infected individuals and 99 healthy controls, including a mixture of bulk and single-cell sequencing datasets. Using this dataset, we extended the convergence findings to 20 additional subjects, highlighting the applicability of nf-core/airrflow to validate findings in small in-house cohorts with reanalysis of large publicly available AIRR datasets.
Calcium (Ca2＋) plays a critical role in the excitation contraction coupling (ECC) process that mediates the contraction of cardiomyocytes during each heartbeat. While ryanodine receptors (RyRs) are ...the primary Ca2＋ channels responsible for generating the cell-wide Ca2＋ transients during ECC, Ca2＋ release, via inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are also reported in cardiomyocytes to elicit ECC-modulating effects. Recent studies suggest that the localization of IP3Rs at dyads grant their ability to modify the occurrence of Ca2＋ sparks (elementary Ca2＋ release events that constitute cell wide Ca2＋ releases associated with ECC) which may underlie their modulatory influence on ECC. Here, we aim to uncover the mechanism by which dyad-localized IP3Rs influence Ca2＋ spark dynamics. To this end, we developed a mathematical model of the dyad that incorporates the behaviour of IP3Rs, in addition to RyRs, to reveal the impact of their activity on local Ca2＋ handling and consequent Ca2＋ spark occurrence and its properties. Consistent with published experimental data, our model predicts that the propensity for Ca2＋ spark formation increases in the presence of IP3R activity. Our simulations support the hypothesis that IP3Rs elevate Ca2＋ in the dyad, sensitizing proximal RyRs towards activation and hence Ca2＋ spark formation. The stochasticity of IP3R gating is an important aspect of this mechanism. However, dyadic IP3R activity lowers the Ca2＋ available in the junctional sarcoplasmic reticulum (JSR) for release, thus resulting in Ca2＋ sparks with similar durations but lower amplitudes.
•IP3R activity in dyads increases propensity for RyR-mediated Ca2+ spark formation.•IP3R activity raises dyadic Ca2+ in the vicinity of RyRs, leading to their sensitization.•IP3R-influenced sparks have lower amplitudes but similar duration.
Natural gas (NG) has been treated as one of the main sources of energy for a wide range of residential and industrial applications for more than half a century. Liquefied Natural Gas (LNG) is the ...most economical way to transport NG, however, the liquefaction process can be very energy-intensive, thus offering an opportunity for increased efficiency for the technology utilized in this process. Currently, the liquefaction process consists of a series of cascading refrigeration cycles with various working fluids. This paper investigates the use of novel propane chilling technology as a portion of the liquefaction process. Based on multiple studies on performance benefits achieved with an ejector-expansion device, a novel cycle architecture employing a variable-geometry ejector combined with a pump to control the ejector motive nozzle inlet state is proposed for this application. The proposed architecture also presents a two-stage configuration to predict the performance benefit of the ejector for future application in the original three-stage evaporation process. The scaled-down test stand will be used as a proof of concept, while also aiming to validate performance benefits relative to conventional propane chilling processes. Cycle designs, thermodynamic modelling, and parametric studies are covered in this paper. Furthermore, limitations and future directions with the test setup are also discussed.
The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards ...(models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects.
OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level biophysical processes into organ-level processes. In the Heart Physiome project, for example, the large deformation mechanics of the myocardial wall need to be coupled to both ventricular flow and embedded coronary flow, and the reaction–diffusion equations that govern the propagation of electrical waves through myocardial tissue need to be coupled with equations that describe the ion channel currents that flow through the cardiac cell membranes.
In this paper we discuss the design principles and distributed memory architecture behind the OpenCMISS code. We also discuss the design of the interfaces that link the sets of physical equations across common boundaries (such as fluid-structure coupling), or between spatial fields over the same domain (such as coupled electromechanics), and the concepts behind CellML and FieldML that are embodied in the OpenCMISS data structures. We show how all of these provide a flexible infrastructure for combining models developed across the VPH/Physiome community.
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