Effect of hemofiltration on hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis

OBJECTIVE: To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. DESIGN: Prospective observation study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 16 patients with severe sepsis. INTERVENTIONS: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2 l/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0 = 676.9 +/- 99.7 ng/ml vs t12 = 467.8 +/- 71, p < 0.01; C5adesArg: 26.6 +/- 4.7 ng/ml vs 17.6 +/- 6.2, p < 0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669 +/- 85 dyne.s/cm5 vs SVR at t12: 864 +/- 75, p < 0.01; MAP at t0: 69.9 +/- 3.5 mmHg vs MAP at t12: 82.2 +/- 3.7, p < 0.01). CONCLUSIONS: HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.     

Auff?llige Unterschiede in der genetischen Variabilit?t freilebender Gro?s?uger und ihre m?glichen Ursachen

Zusammenfassung Im Gegensatz zu Evertebraten und Kleinsäugern steht die Erforschung der genetischen Variabilität freilebender Großsäuger erst in den Anfängen. Bisherige Ergebnisse zeigen zum Teil gravierende interspezifische Unterschiede im Ausmaß genetischer Variation in Protein-und Enzymsystemen. Die vorliegende Arbeit gibt einen Überblick über bei großen Wildtierarten ermittelte Polymorphie- und Heterozygotieraten. Weiters wird die Vergleichbarkeit populationsgenetischer Daten erörtert und mögliche Ursachen für ausreichend gesicherte Unterschiede diskutiert. Das weitgehende Fehlen von genetischen Polymorphismen bei einigen Arten kann als Folge von Gründereffekten, Inzucht und genetischer Zufallsdrift im Zusammenhang mit ihrer Verbreitungsgeschichte interpretiert werden. Es muß jedoch angenommen werden, daß Unterschieden in der genetischen Variabilität von Eiweißsystemen auch eine adaptive Bedeutung im Zuge verschiedener ökologischer Anpassungsstrategien zukommt.

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Obvious genetic variability in large mammals living in the wild and the possible causes thereof

Summary The study of large mammals living in the wild, unlike that of invertebrates and small mammals, is only in its infancy. Results so far show some large interspecific differences in the extent of genetic variation in protein and enzyme systems. This report provides a survey of the polymorph and heterozygote types identified in large game animals. The comparability of data on population genetics is also discussed, as are possible causes of established significant differences. The absence to a great extent of genetic polymorphisms in some species can be interpreted as the result of ancestor species effects, inbreeding and random genetic drift in conjunction with their historical spread. It must, however, be assumed that differences in the genetic variability of protein systems have an adaptive significance in the course of various ecilogical adaptation strategies.

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Différences frappantes dans la variabilité génétique de grands mammifères sauvages et causes possibles

Résumé Contrairement à celle des invertébrés et petits mammifères, la recherche de la variabilité des grands mammifères sauvages n'en est qu'à ses débuts. A ce jour, les résultats montrent parfois des différences interspécifiques majeures au niveau de la variation génétique des systèmes protéiniques et enzymatiques. La présente contribution donne un aperçu des taux de polymorphisme et d'hétérozygotie constatés chez les grands mammifères sauvages. En outre, on discute de la possibilité de comparer des données de la génétique des populations et des causes possibles en vue d'établir des différences satisfaisantes. La diminution générale du polymorphisme génétique chez certaines espèces peut être interprétée comme résultant du principe des fondateurs, de la consanguinité ou de la dérive génétique aléatoire en relation avec l'historique de leur dispersion. On doit cependant accepter que la différenciation de la variabilité génétique des systèmes protéiniques n'est pas indépendante d'une portée adaptative dans la perspective de différentes stratégies écologiques adaptatives.

     

Heuristics for the multi-period orienteering problem with multiple time windows

We present the multi-period orienteering problem with multiple time windows (MuPOPTW), a new routing problem combining objective and constraints of the orienteering problem (OP) and team orienteering problem (TOP), constraints from standard vehicle routing problems, and original constraints from a real-world application. The problem itself comes from a real industrial case. Specific route duration constraints result in a route feasibility subproblem. We propose an exact algorithm for this subproblem, and we embed it in a variable neighborhood search method to solve the whole routing problem. We then provide experimental results for this method. We compare them to a commercial solver. We also adapt our method to standard benchmark OP and TOP instances, and provide comparative tables with state-of-the-art algorithms.     

Variable neighborhood search for the dial-a-ride problem

In dial-a-ride problems passengers have to be transported between pre-specified pickup and delivery locations under user inconvenience considerations. The problem variant considered in this paper aims at minimizing total routing costs while respecting maximum route duration limits, time windows, and maximum user ride time limits. We propose a competitive variable neighborhood search-based heuristic, using three classes of neighborhoods. The first neighborhood class uses simple swap operations tailored to the dial-a-ride problem; the second neighborhood class is based on the ejection chain idea; and the third neighborhood class exploits the existence of arcs where the vehicle load is zero, giving rise to natural sequences of requests. We report new best results for 16 out of 20 benchmark instances.     

Metaheuristics for the dynamic stochastic dial-a-ride problem with expected return transports

The problem of transporting patients or elderly people has been widely studied in literature and is usually modeled as a dial-a-ride problem (DARP). In this paper we analyze the corresponding problem arising in the daily operation of the Austrian Red Cross. This nongovernmental organization is the largest organization performing patient transportation in Austria. The aim is to design vehicle routes to serve partially dynamic transportation requests using a fixed vehicle fleet. Each request requires transportation from a patient's home location to a hospital (outbound request) or back home from the hospital (inbound request). Some of these requests are known in advance. Some requests are dynamic in the sense that they appear during the day without any prior information. Finally, some inbound requests are stochastic. More precisely, with a certain probability each outbound request causes a corresponding inbound request on the same day. Some stochastic information about these return transports is available from historical data. The purpose of this study is to investigate, whether using this information in designing the routes has a significant positive effect on the solution quality. The problem is modeled as a dynamic stochastic dial-a-ride problem with expected return transports. We propose four different modifications of metaheuristic solution approaches for this problem. In detail, we test dynamic versions of variable neighborhood search (VNS) and stochastic VNS (S-VNS) as well as modified versions of the multiple plan approach (MPA) and the multiple scenario approach (MSA). Tests are performed using 12 sets of test instances based on a real road network. Various demand scenarios are generated based on the available real data. Results show that using the stochastic information on return transports leads to average improvements of around 15%. Moreover, improvements of up to 41% can be achieved for some test instances.     

Ant colony optimization for the two-dimensional loading vehicle routing problem

In this paper a combination of the two most important problems in distribution logistics is considered, known as the two-dimensional loading vehicle routing problem. This problem combines the loading of the freight into the vehicles, and the successive routing of the vehicles along the road network, with the aim of satisfying the demands of the customers.     

Application of transcranial Doppler sonography to evaluate cerebral hemodynamics in carotid artery disease. Comparative analysis of different hemodynamic variables

BACKGROUND AND PURPOSE: Transcranial Doppler sonography in combination with manipulation of cerebral resistance vessels is widely used to screen patients with suspected intracranial hemodynamic disturbances. Maximal flow velocity (Vmax), mean flow velocity (Vmean), cerebral pulsatility index (CPi), and cerebral resistance index (CRi) have all been used to describe cerebral hemodynamics. The present study examined CO2 reactivity of the above hemodynamic variables with respect to its variability between different age groups and its capability to discriminate between normal and abnormal findings. METHODS: Absolute and relative CO2 reactivity of Vmax, Vmean, CRi, and CPi were determined in both hemispheres in 30 young and 37 elderly control subjects and in 245 consecutive patients with strictly unilateral symptomatic (n = 101) or asymptomatic (n = 144) carotid artery disease (> 80% stenosis or occlusion). RESULTS: Hemispheric reactivities of Vmean, CRi, and CPi were significantly age dependent. Hemispheric Vmax reactivity and interhemispheric differences of individual reactivities (except absolute CPi reactivity) did not vary with age and could therefore be used to define normal values. Patient classification according to these values revealed different frequencies of subjects with pathological findings (3% for hemispheric Vmax reactivity, 5% to 7% for interhemispheric differences of Vmax or Vmean reactivity, 39% and 45% for interhemispheric differences of relative CRi and CPi reactivity, respectively). CONCLUSIONS: Hemispheric reactivities are less suitable to evaluate cerebral hemodynamics than interhemispheric differences, since most of the latter do not vary with age. However, interhemispheric differences vary with respect to their discriminatory power. Power is low for interhemispheric differences of Vmax and Vmean reactivity, since the corresponding frequencies of abnormal findings do not differ from the 5% frequency expected in the reference population (reference range defined as mean +/- 2 SD). With respect to the discriminatory power, interhemispheric differences of relative CRi and CPi reactivity may be superior to other parameters.     

Asymmetrical interaction of GroEL and GroES in the ATPase cycle of assisted protein folding

The chaperonins GroEL and GroES of Escherichia coli facilitate protein folding in an adenosine triphosphate (ATP)-dependent reaction cycle. The kinetic parameters for the formation and dissociation of GroEL-GroES complexes were analyzed by surface plasmon resonance. Association of GroES and subsequent ATP hydrolysis in the interacting GroEL toroid resulted in the formation of a stable GroEL:ADP:GroES complex. The complex dissociated as a result of ATP hydrolysis in the opposite GroEL toroid, without formation of a symmetrical GroEL:(GroES)2 intermediate. Dissociation was accelerated by the addition of unfolded polypeptide. Thus, the functional chaperonin unit is an asymmetrical GroEL:GroES complex, and substrate protein plays an active role in modulating the chaperonin reaction cycle.     

Ermittlung der Aktivität des Kohlenstoffs im System Eisen–Chrom–Kohlenstoff mittels des Diffusionsverfahrens

Beschreibung des Diffusionsverfahrens als Möglichkeit zur Ermittlung von Aktivitätskoeffizienten und seiner besonderen Vorteile. Herstellung von Diffusionspaaren aus Eisen-Chrom-Kohlenstoff-Legierungen und weitgehend entkohltem Reineisen. Aufnahme von Konzentrations-Weg-Kurven und Ermittlung des Wirkungsparameters. Beeinflussung des Diffusionskoeffizienten von Kohlenstoff in Eisen durch Chrom.     

High-speed path-length scanning with a multiple-pass cavity delay line

Techniques for high-speed delay scanning are important for low-coherence interferometry, optical coherence tomography, pump probe measurements, and other applications. We demonstrate a novel scanning delay line using a multiple-pass cavity. Differential delays are accumulated with each pass so that millimeter delays can be generated with tens of micrometer mirror displacements. With special design criteria, misalignment sensitivity can be dramatically reduced. The system is demonstrated to scan 6 m/s at 2-kHz repetition rates. Real-time optical coherence tomography imaging with 500 pixel images at four frames/s is performed. Using a Cr:forsterite laser source, we obtained axial image resolutions of 6 microm with 92-dB sensitivity.