In utero indomethacin alters O₂ [oxygen] delivery to the fetal ductus arteriosus : implications for persistent postnatal patency

Exposure of the fetus to indomethacin produces constriction of the fetal ductus arteriosus (DA) and hypoxia in the avascular muscle media of the vessel wall. Hypoxia induces cell death, which increases the incidence of patent DA in the newborn period. We used a fetal sheep model to determine the factors that were responsible for indomethacin-induced hypoxia at various degrees of DA constriction. Indomethacin produced DA constriction in all fetuses studied in vivo. Cell death in the DA wall was directly related to the degree of indomethacin-induced DA constriction and was present at both moderate (pressure gradient across DA \u3c16 \u3emmHg) and marked (≥16 mmHg) degrees of constriction. Indomethacin did not alter oxygen consumption in DA rings studied in vitro, indicating that oxygen demand in the constricting tissue is not significantly increased by indomethacin. Both moderate and marked degrees of DA constriction reduced vasa vasorum flow to the ductus (moderate = 69±25%; marked = 30±16% of pre-indomethacin exposure values) and increased the thickness of the ductus wall. In contrast, DA luminal blood flow was not affected by moderate degrees of constriction and was reduced only after marked constriction. Our findings suggest that changes in vasa vasorum blood flow and muscle media thickness are the primary contributors to hypoxia-induced cell death at moderate degrees of indomethacin-induced constriction. Diminished luminal blood flow only appears to contribute to the induction of cell death following the development of marked degrees of constriction. These findings help to explain why in utero exposure to indomethacin in late gestation fetuses, which depend on vasa vasorum to supply O2 to the DA muscle media, leads to hypoxia-induced remodeling and and increased incidence of postnatal patent DA. Note: Figures and Diagrams created with Cricket Graph for Macintosh may not open or be legible without the possession of that application

Investigation of Archiving Techniques for Evolutionary Multi-objective Optimizers

Abstract: The optimization of multi-objective problems from the Pareto dominance viewpoint can lead to huge sets of incomparable solutions. Many heuristic techniques proposed to these problems have to deal with approximation sets that can be limited or not. Usually, a new solution generated by a heuristic is compared with other archived non-dominated solutions generated previously. Many techniques deal with limited size archives, since comparisons within unlimited archives may require significant computational effort. To maintain limited archives, solutions need to be discarded. Several techniques were proposed to deal with the problem of deciding which solutions remain in the archive and which are discarded. Previous investigations showed that those techniques might not prevent deterioration of the archives. In this study, we propose to store discarded solutions in a secondary archive and, periodically, recycle them, bringing them back to the optimization process. Three recycling techniques were investigated for three known methods. The datasets for the experiments consisted of 91 instances of discrete and continuous problems with 2, 3 and 4 objectives. The results showed that the recycling method can benefit the tested optimizers on many problem classes

Coexistent Brugada Syndrome and Wolff-Parkinson-White Syndrome: What is the Optimal Management?

AbstractCoexistent Brugada syndrome and Wolff-Parkinson-White (WPW) syndrome is rare, and as such poses management challenges. The overlap of symptoms attributable to each condition, the timing of ventricular stimulation after accessory pathway ablation and the predictive value of programmed stimulation in Brugada syndrome are controversial. We describe a case of coexistent Brugada syndrome and WPW syndrome in a symptomatic young adult. We discuss our treatment approach and the existing literature along with the challenges in management of such cases

Inappropriate mode switching clarified by using a chest radiograph

AbstractAn 80-year-old woman with a history of paroxysmal atrial fibrillation and atrioventricular node disease status post-dual chamber pacemaker placement was noted to have abnormal pacing episodes during a percutaneous coronary intervention. Pacemaker interrogation revealed a high number of short duration mode switching episodes. Representative electrograms demonstrated high frequency nonphysiologic recordings predominantly in the atrial lead. Intrinsic pacemaker malfunction was excluded. A chest radiograph showed excess atrial and ventricular lead slack in the right ventricular inflow. It was suspected that lead–lead interaction resulted in artifacts and oversensing, causing frequent short episodes of inappropriate mode switching

O problema do caixeiro viajante com vários passageiros, cota de bônus opcional e tempo / The Traveling Salesman Problem with Multiple Passengers Optional Bonus Quota and Time

Este artigo apresenta o Problema do Caixeiro Viajante com Múltiplos Passageiros Bônus Optativos Quota e Tempo. O problema consiste em maximizar o lucro de um caixeiro viajante que realiza serviço de transporte de mercadorias, considerando a possibilidade de rateio das despesas da rota com eventuais passageiros embarcados em seu veículo. As mercadorias devem ser transportadas obrigatoriamente das suas origens até os seus destinos e devem contabilizar uma quota mínima definida a priori. Nesta variante, ao passar em uma cidade, o caixeiro decide se coleta ou não a mercadoria a ser transportada. A coleta da mercadoria requer tempo de carregamento e de descarregamento. É proposto um modelo de programação matemática que é resolvido por um solver. São propostas, também, três heurísticas, sendo duas desenvolvidas segundo as meta-heurísticas Colônia de Formigas e GRASP. Os resultados e análises de um experimento computacional são apresentados

Prize Collecting Traveling Salesman Problem with Ridesharing

The Prize Collecting Traveling Salesman Problem with Ridesharing is a model that joins elements from the Prize Collecting Traveling Salesman and the collaborative transport. The salesman is the driver of a capacitated vehicle and uses a ridesharing system to minimize travel costs. There are a penalty and a bonus associated with each vertex of a graph, G, that represents the problem. There is also a cost associated with each edge of G. The salesman must choose a subset of vertices to be visited so that the total bonus collection is at least a given a parameter. The length of the tour plus the sum of penalties of all vertices not visited is as small as possible. There is a set of persons demanding rides. The ride request consists of a pickup and a drop off location, a maximum travel duration, and the maximum amount the person agrees to pay. The driver shares the cost associated with each arc in the tour with the passengers in the vehicle. Constraints from ride requests, as well as the capacity of the car, must be satisfied. We present a mathematical formulation for the problem investigated in this study and solve it in an optimization tool. We also present three heuristics that hybridize exact and heuristic methods. These algorithms use a decomposition strategy that other enriched vehicle routing problems can utilize

Multi-Strategy <em>MAX-MIN</em> Ant System for Solving Quota Traveling Salesman Problem with Passengers, Incomplete Ride and Collection Time

This study proposes a novel adaptation of MAX-MIN Ant System algorithm for the Quota Traveling Salesman Problem with Passengers, Incomplete Ride, and Collection Time. There are different types of decisions to solve this problem: satisfaction of the minimum quota, acceptance of ride requests, and minimization of travel costs under the viewpoint of the salesman. The Algorithmic components proposed regards vehicle capacity, travel time, passenger limitations, and a penalty for delivering a passenger deliverance out of the required destination. The ant-based algorithm incorporates different sources of heuristic information for the ants and memory-based principles. Computational results are reported, showing the effectiveness of this ant-based algorithm