638 research outputs found

    Modelling and controlling traffic behaviour with continuous Petri nets

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    Traffic systems are discrete systems that can be heavily populated. One way of overcoming the state explosion problem inherent to heavily populated discrete systems is to relax the discrete model. Continuous Petri nets (PN) represent a relaxation of the original discrete Petri nets that leads to a compositional formalism to model traffic behaviour. This paper introduces some new features of continuous Petri nets that are useful to obtain realistic but compact models for traffic systems. Combining these continuous PN models with discrete PN models of traffic lights leads to a hybrid Petri net model that is appropriate for predicting traffic behaviour, and for designing trac light controllers that minimize the total delay of the vehicles in the system

    Evidence-Based Elements of Child Welfare In-Home Services

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    In this article we discuss evidence-based elements of effective in-home child welfare services as a foundation for advancing the evidence base for family-centered child welfare practice. In 2009 the U.S. Children’s Bureau established the National Resource Center for In-Home Services to build the capacity of state and tribal child welfare agencies to ensure the safety and well-being of children and youth in their homes, prevent their initial placement or re-entry into out-of-home care, and to support families in their role as primary caregivers. Through a nationwide assessment of in-home services conducted over four years of research and technical assistance, we developed a set of core elements for in-home services. These core elements are supported by empirical research and are congruent with evidence-based practices and programs. We review each of the elements with its underlying research base. We also discuss five evidence-supported in-home services interventions that share many of the elements. We conclude with a discussion of how evidence-based elements can be implemented to strengthen family centered child welfare practice

    CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis

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    Retinoblastoma is a pediatric eye tumor in which bi-allelic inactivation of the Retinoblastoma 1 (RB1) gene is the initiating genetic lesion. Although recently curative rates of retinoblastoma have increased, there are at this time no molecular targeted therapies available. This is, in part, due to the lack of highly penetrant and rapid retinoblastoma animal models that facilitate rapid identification of targets that allow therapeutic intervention. Different mouse models are available, all based on genetic deactivation of both Rb1 and Retinoblastoma-like 1 (Rbl1), and each showing different kinetics of retinoblastoma development. Here, we show by CRISPR/Cas9 techniques that similar to the mouse, neither rb1 nor rbl1 single mosaic mutant Xenopus tropicalis develop tumors, whereas rb1/rbl1 double mosaic mutant tadpoles rapidly develop retinoblastoma. Moreover, occasionally presence of pinealoblastoma (trilateral retinoblastoma) was detected. We thus present the first CRISPR/Cas9 mediated cancer model in Xenopus tropicalis and the first genuine genetic non-mammalian retinoblastoma model. The rapid kinetics of our model paves the way for use as a pre-clinical model. Additionally, this retinoblastoma model provides unique possibilities for fast elucidation of novel drug targets by triple multiplex CRISPR/Cas9 gRNA injections (rb1 + rbl1 + modifier gene) in order to address the clinically unmet need of targeted retinoblastoma therapy

    Optimal pressure for mimicking clinical breath holding inspiratory CT in the deceased for VPMCT

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    Introduction Ventilated PMCT (VPMCT) has been reported to provide better quality of pulmonary structures in PMCT in adults and children. However, there are no consensus regarding optimal inflation pressure, and the practical use of VPMCT is still limited by cost of ventilation equipment. Here, we describe a simple and cost-efficient inflation-device for VPMCT and investigate optimal inflation pressure. Aim To elucidate the effect of different ventilation pressures on total lung volume and the volume of ground glass opacities (GGO), air-filled tissue, consolidations, and bronchi in VPMCT. Materials and method A precise inflation device was assembled using standard components: a back-pressure regulator, a water manometer and silicone tubing. Each case had PMCT performed at 0, 10, 20, 30 and 40 cmH2O pressure. Volumes were measured using stereology. Results 14 cases were enrolled in the study. The total lung volume increased significantly by 3612 mL (median) from 0 to 30 cmH2O (p = 0.001). The volume of consolidations was significantly reduced by 455.86 mL (median) between 0 and 30 cmH2O (p = 0.001). A significant reduction of GGO-volume of 133 mL (median) was observed at the pressure interval 30–40 cmH2O (p = 0.031), but not at lower pressures. Conclusion The constructed inflation device allowed precise and reproducible inflation of the lungs in deceased humans. We found a maximum effect of inflation at 30 cmH2O. At further inflation pressure, only the volume of GGOs decreased , but the effect was minor. For mimicking an in vivo breath-hold scan in PMCT we recommend inflation pressure of 30 cmH2O. + Graphical abstrac

    The filtering equations revisited

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    The problem of nonlinear filtering has engendered a surprising number of mathematical techniques for its treatment. A notable example is the change-of--probability-measure method originally introduced by Kallianpur and Striebel to derive the filtering equations and the Bayes-like formula that bears their names. More recent work, however, has generally preferred other methods. In this paper, we reconsider the change-of-measure approach to the derivation of the filtering equations and show that many of the technical conditions present in previous work can be relaxed. The filtering equations are established for general Markov signal processes that can be described by a martingale-problem formulation. Two specific applications are treated

    Voorstel bouwstenen nieuwe weidevogelpakketten agrarisch natuurbeheer in een notendop : wat regelen we in Nederland, wat in Brussel?

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    In opdracht van directie Kennis van het ministerie van LNV is een voorstel ontwikkeld voor bouwstenen voor nieuwe pakketten weidevogelbeheer. De doelstellingen worden per gebiedsplan vastgesteld. De verantwoordelijkheid hiervoor ligt bij provincies en Rijk, die daarvoor desgewenst een gebiedscommissie in het leven kunnen roepen. Het minimum dat altijd (in alle gebiedsplannen) geldt is: 35 bp /100 ha, bestaande uit Ă©Ă©n of meer van de volgende soorten: Grutto, Tureluur, Watersnip, Kemphaan, Slobeend, Zomertaling, Veldleeuwerik, Wulp, Kluut, Krakeend, Kuifeend, Wintertaling, Graspieper, Gele kwikstaart, Kievit, Scholekster. Per gebied kan deze doelstelling nader worden gefocust op Ă©Ă©n of meerdere van bovengenoemde soorten en/of naar boven worden bijgestel

    Target-Controlled Infusion of Cefepime in Critically Ill Patients:single center experience

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    Attainment of appropriate pharmacokinetic-pharmacodynamic (PK-PD) targets for antimicrobial treatment is challenging in critically ill patients, particularly for cefepime, which exhibits a relative narrow therapeutic-toxic window compared to other beta-lactam antibiotics. Target-controlled infusion (TCI) systems, which deliver drugs to achieve specific target drug concentrations, have successfully been implemented for improved dosing of sedatives and analgesics in anesthesia. We conducted a clinical trial in an intensive care unit (ICU) to investigate the performance of TCI for adequate target attainment of cefepime. Twenty-one patients treated with cefepime according to the standard of care were included. Cefepime was administered through continuous infusion using TCI for a median duration of 4.5 days. TCI was based on a previously developed population PK model incorporating the estimated creatinine clearance based on the Cockcroft-Gault formula as the input variable to calculate cefepime clearance. A cefepime blood concentration of 16 mg/liter was targeted. To evaluate the measured versus predicted plasma concentrations, blood samples were taken (median of 10 samples per patient), and total cefepime concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. The performance of the TCI system was evaluated using Varvel criteria. Half (50.3%) of the measured cefepime concentrations were within +/- 30% around the target value of 16 mg liter(-1). The wobble was 11.4%, the median performance error (MdPE) was 21.1%, the median absolute performance error (MdAPE) was 32.0%, and the divergence was -3.72% h(-1). Based on these results, we conclude that TCI is useful for dose optimization of cefepime in ICU patients

    The First Plasmodium vivax Relapses of Life Are Usually Genetically Homologous

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    In a prospective infant cohort, 21 infants developed Plasmodium vivax malaria during their first year. Twelve of their mothers also had vivax malaria in the corresponding pregnancies or postpartum period. The genotypes of the maternal and infant infections were all different. Eight of the 12 mothers and 9 of the 21 infants had recurrent infections. Relapse parasite genotypes were different to the initial infection in 13 of 20 (65%) mothers compared with 5 of 24 (21%) infants (P = .02). The first P. vivax relapses of life are usually genetically homologous, whereas relapse in adults may result from activation of heterologous latent hypnozoites acquired from previous inoculations
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