Plasma Disappearance Rate of Indocyanine Green for Determination of Liver Function in Three Different Models of Shock

The measurement of the liver function via the plasma disappearance rate of indocyanine green (PDRICG) is a sensitive bed-side tool in critical care. Yet, recent evidence has questioned the value of this method for hyperdynamic conditions. To evaluate this technique in different hemodynamic settings, we analyzed the PDRICG and corresponding pharmacokinetic models after endotoxemia or hemorrhagic shock in rats. Male anesthetized Sprague-Dawley rats underwent hemorrhage (mean arterial pressure 35 ± 5 mmHg, 90 min) and 2 h of reperfusion, or lipopolysaccharide (LPS) induced moderate or severe (1.0 vs. 10 mg/kg) endotoxemia for 6 h (each n = 6). Afterwards, PDRICG was measured, and pharmacokinetic models were analyzed using nonlinear mixed effects modeling (NONMEM®). Hemorrhagic shock resulted in a significant decrease of PDRICG, compared with sham controls, and a corresponding attenuation of the calculated ICG clearance in 1- and 2-compartment models, with the same log-likelihood. The induction of severe, but not moderate endotoxemia, led to a significant reduction of PDRICG. The calculated ICG blood clearance was reduced in 1-compartment models for both septic conditions. 2-compartment models performed with a significantly better log likelihood, and the calculated clearance of ICG did not correspond well with PDRICG in both LPS groups. 3-compartment models did not improve the log likelihood in any experiment. These results demonstrate that PDRICG correlates well with ICG clearance in 1- and 2-compartment models after hemorrhage. In endotoxemia, best described by a 2-compartment model, PDRICG may not truly reflect the ICG clearance

A Greedy Randomized Adaptive Search With Probabilistic Learning for solving the Uncapacitated Plant Cycle Location Problem

In this paper, we address the Uncapacitated Plant Cycle Location Problem. It is a location-routing problem aimed at determining a subset of locations to set up plants dedicated to serving customers. We propose a mathematical formulation to model the problem. The high computational burden required by the formulation when tackling large scenarios encourages us to develop a Greedy Randomized Adaptive Search Procedure with Probabilistic Learning Model. Its rationale is to divide the problem into two interconnected sub-problems. The computational results indicate the high performance of our proposal in terms of the quality of reported solutions and computational time. Specifically, we have overcome the best approach from the literature on a wide range of scenarios.</p

Automatización de los procesos de corrección y autoevaluación de prácticas en asignaturas con contenidos de programación mediante herramientas TIC

La programación informática se ha convertido en los últimos años en una herramienta transversal en múltiples áreas de conocimiento. A través de la programación el estu- diante crea programas que presentan un comportamiento deseado en un contexto práctico concreto. Sin embargo, el proceso de escritura de programación le demanda al estudiante habitualmente de conocimientos de múltiples áreas, dominio de lenguajes de programación, algoritmos de propósito específico y lógica formal, entre otros. Actualmente, la Universidad de La Laguna incluye la programación en múltiples titulaciones oficiales. En estas titulaciones el estudiante se enfrenta a la realización de múltiples prácticas de laboratorio donde tiene que demostrar sus conocimientos relativos a programación para la resolución de algún problema planteado por el profesorado dentro del contexto de la asignatura que imparte. El proceso de corrección de las prácticas involucra un análisis exhaustivo por parte del profesorado de las propuestas de programación realizadas por el alumnado. Esto habitualmente implica la corrección de un número elevado de propuestas durante las sesiones prácticas, lo cual da lugar a que el nivel de detalle en la evaluación sea inevitablemente inferior al deseado. Consecuentemente, se da lugar a que algunos alumnos presenten insatisfacción con las calificaciones ob- tenidas así como extenuación por parte del profesorado ante la carga de trabajo concentrada en las sesiones prácticas. En este trabajo se plantea el diseño, implementación y validación de una herra- mienta software que automatiza los procesos de corrección a la vez que facilita la autoevaluación por parte del alumnado durante el desarrollo de las prácticas.In recent years, computer programming has become a transversal tool in multiple areas of knowledge. The student creates programs that present a desired behavior in a given practical context through the programming. However, the writing process demands the student usually of knowledge about multiple areas, domaining program- ming languages, algorithms of specific purpose, and formal logic, among others. Nowadays, the Universidad de La Laguna includes computer programming in multiple official degrees. In these degrees the student faces the performance of multiple laboratory practices where he has to demonstrate his knowledge related to computer programming for solving a problem proposed by the teacher within the context of the subject he teaches. The process of correcting the practices involves a thorough analysis by the teachers of the programming proposals made by the students. This usually involves asses- sing a large number of proposals during the practice sessions, which results in the level of detail in the evaluation being inevitably lower than desired. Consequently, some students are dissatisfied with the grades obtained as well as exhaustion by the teachers in the face of the workload concentrated in the practical sessions. In this paper, the design, implementation, and validation of a software tool that automates the assessment processes while facilitating self-assessment by students during the development of practices is described

Repositorio interactivo para facilitar el aprendizaje de algoritmos heurísticos aplicados a problemas de optimización

La algoritmia es una de las ramas de aprendizaje principales en la formación de un Graduado en Ingeniería Informática, ya que permite abordar la resolución de un gran número de problemas de forma automatizada. Las (meta)heurísticas son técnicas aproximadas destinadas a resolver problemas de optimización mediante una demanda de recursos computacionales reducida. Esto hace que puedan resolver problemas de gran complejidad. En el presente trabajo se expone el repositorio creado con el fin de explicar el con- junto de algoritmos heurísticos de mayor utilización en la resolución de diferentes tipos de problemas, los cuales son impartidos frecuentemente en las asignaturas que componen el Grado de Ingeniería Informática. Con la idea de complementar la comprensión de los algoritmos, el repositorio incluye un conjunto de problemas de optimización altamente estudiados en la literatura, de tal forma que el alumno pueda comprender el comportamiento de los algoritmos disponibles sobre problemas de distintas características. Además de una explicación detallada de tanto los algoritmos heurísticos como de los problemas de optimización, se incluyen ejemplos interactivos de funcionamiento, sobre los cuales se puede realizar un análisis de resultados así como una compa- rativa entre los mismos. Con ello se pretende fomentar la interacción del alumno en el aprendizaje, mediante la ejecución paso a paso de los diferentes ejemplos de algoritmos a través de un software específico, consiguiendo que el alumno compren- da en profundidad los distintos algoritmos, sus características y sus posibles usos.Algorithmics is one of the main branches of learning in the studies of a Graduate on Computer Engineering, because it allows to address the resolution of a huge amount of problems on an automated way. (Meta)heuristics are approximate techniques aimed at solving optimization problems by means of a reduce number of compu- tational resources. This allows they can solve high complex optimization problems. The present work exposes the repository created with the goal to explain the set of heuristic algorithms with more use in the resolution of different types of pro- blems, and that are frequently taugh in the subjects that compose the Grade on Computer Engineering. With the idea of complement the understanding of the algorithms, the repository includes a set of optimization problems highly studied in the literature, in such a way that the student can learn the behaviour of the available algorithms in pro- blems with different characteristics. In addition to a detailed explanation of the heuristic algorithms as well the optimization problems, a set interactive examples of execution are included, on which an analysis of results can be carried out as well as a comparison between them. The idea is to encourage the interaction of the student in learning, through a step-by-step execution of different algorithm examples using a specific software, getting the student to un- derstand in depth the different algorithms, their characteristics and their possible uses

The European Eel NCCβ Gene Encodes a Thiazide-Resistant Na-Cl Cotransporter

The thiazide-sensitive Na-Cl cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes the primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCβ is present in the apical membrane of the rectum. Here we cloned and functionally characterized NCCβ from the European eel. The cRNA encodes a 1043-amino acid membrane protein that, when expressed in Xenopus oocytes, functions as an Na-Cl cotransporter with two major characteristics, making it different from other known NCCs. First, eel NCCβ is resistant to thiazides. Single-point mutagenesis supports that the absence of thiazide inhibition is, at least in part, due to the substitution of a conserved serine for a cysteine at position 379. Second, NCCβ is not activated by low-chloride hypotonic stress, although the unique Ste20-related proline alanine-rich kinase (SPAK) binding site in the amino-terminal domain is conserved. Thus, NCCβ exhibits significant functional differences from NCCs that could be helpful in defining several aspects of the structure-function relationship of this important cotransporter

Elevated levels of diesel range organic compounds in groundwater near Marcellus gas operations are derived from surface activities

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of American 112 (2015): 13184-13189, doi: 10.1073/pnas.1511474112 .Hundreds of organic chemicals are utilized during natural gas extraction via high volume hydraulic fracturing (HVHF). However, it is unclear if these chemicals, injected into deep shale horizons, reach shallow groundwater aquifers and impact local water quality, either from deep underground injection sites or from the surface or shallow subsurface. Here, we report detectable levels of organic compounds in shallow groundwater samples from private residential wells overlying the Marcellus Shale in northeastern Pennsylvania. Analyses of purgeable and extractable organic compounds from 64 groundwater samples revealed trace levels of volatile organic compounds, well below the Environmental Protection Agency’s maximum contaminant levels, and low levels of both gasoline range (GRO; 0-8 ppb) and diesel range organic compounds (DRO; 0-157 ppb). A compound-specific analysis revealed the presence of bis(2-ethylhexyl)phthalate, which is a disclosed HVHF additive, that was notably absent in a representative geogenic water sample and field blanks. Pairing these analyses with 1) inorganic chemical fingerprinting of deep saline groundwater, 2) characteristic noble gas isotopes, and 3) spatial relationships between active shale gas extraction wells and wells with disclosed environmental health and safety (EHS) violations, we differentiate between a chemical signature associated with naturally occurring saline groundwater and a one associated with alternative anthropogenic routes from the surface (e.g., accidental spills or leaks). The data support a transport mechanism of DRO to groundwater via accidental release of fracturing fluid chemicals derived from the surface rather than subsurface flow of these fluids from the underlying shale formation.The authors thank Duke University’s Pratt School of Engineering and the National Science Foundation’s CBET Grant Number 1336702 and NSF EAGER (EAR-1249255) for financial support.2016-04-1

Medical and cardio-vascular emergency department visits during the COVID-19 pandemic in 2020: is there a collateral damage? A retrospective routine data analysis

Background In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. Methods Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). Results A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was - 14% [CI (- 11)-(- 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [- 16%; CI (- 13)-(- 19)], less urgent [- 18%; CI (- 12)-(- 22)] and non-admitted cases [- 17%; CI (- 13)-(- 20)] in particular during the second wave. During the entire observation period admissions for chest pain [- 13%; CI (- 21)-2], myocardial infarction [- 2%; CI (- 9)-11] and heart failure [- 2%; CI (- 10)-6] were less affected and remained comparable to the previous year. Conclusions ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies. [GRAPHICS]

KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control

Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc-finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV-T and HERV-S) and ZNF genes, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in adult human peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1 regulated loci is necessary to prevent an interferon response, and KAP1-depletion leads to activation of some interferon-stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNF genes and an RNA-sensing response mediated through MAVS signaling. These data indicate that the KAP1-KZNF pathway contributes to genome stability and innate immune control in adult human cells

Broad-Spectrum Drugs Against Viral Agents

Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance

Medical and cardio-vascular emergency department visits during the COVID-19 pandemic in 2020: is there a collateral damage? A retrospective routine data analysis

Background In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. Methods Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). Results A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was − 14% [CI (− 11)–(− 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [− 16%; CI (− 13)–(− 19)], less urgent [− 18%; CI (− 12)–(− 22)] and non-admitted cases [− 17%; CI (− 13)–(− 20)] in particular during the second wave. During the entire observation period admissions for chest pain [− 13%; CI (− 21)–2], myocardial infarction [− 2%; CI (− 9)–11] and heart failure [− 2%; CI (− 10)–6] were less affected and remained comparable to the previous year. Conclusions ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies. Graphical abstractOpen Access funding enabled and organized by Projekt DEAL.Charité - Universitätsmedizin Berlin (3093