Anwendung von stetigen Runge-Kutta-Verfahren auf Probleme der optimalen Steuerung

In dieser Arbeit wird mit Hilfe stetiger Erweiterungen von Runge-Kutta-Verfahren eine stetige Diskretisierungsmethode für optimale Steuerungsprobleme vorgestellt. Stetige Diskretisierungsmethoden liefern dabei nicht nur eine Folge von Näherungen auf immer feiner werdenden Zeitgittern, sondern eine Folge von stetigen Näherungslösungen, welche die Optimallösung auf dem ganzen Zeitintervall bezüglich geeigneter Sobolev-Normen mit hoher Genauigkeit approximieren. Es wird in einer vollständigen mathematischen Konvergenzanalyse gezeigt, dass man unter einer Glattheitsvoraussetzung und der Koerzivitätsbedingung die gleiche Konvergenzordnung für die Diskretisierung des Steuerungsproblems erhält, wie das stetige Runge-Kutta-Verfahren in den Gitterpunkten und an allen Zwischenpunkten hat. Es wird ein indirektes Verfahren zur numerischen Lösung eines Problems der optimalen Steuerung vorgeschlagen, und gezeigt das die Verwendung des indirekten Verfahrens keine relevanten Nachteile, gegenüber einem direkten Verfahren, angewandt auf ein Steuerungsproblem, welches zuvor auf ein Zeitgitter diskretisiert wurde, mit sich bringt. An Modellbeispielen wird das Verfahren getestet und die Konvergenzordnung der Diskretisierung visualisiert. Als Grundlage dieser Arbeit dienten einige Arbeiten von A. Dontchev und W. W. Hager, in denen die diskrete Konvergenz von Runge-Kutta-basierten Diskretisierungen untersucht wurden. Die Diskretisierung mit stetigen Runge-Kutta-Verfahren hat den Vorteil, dass die diskretisierten Operatoren dieselben Bild- und Urbildräume haben wie der stetige Operator. Stetige Runge-Kutta-Verfahren sind bei der numerischen Lösung retardierter Differentialgleichungen verbreitet und dementsprechend gut untersucht. Eine ähnliche Diskretisierung von Steuerungsproblemen mit stetigen Runge-Kutta-Verfahren wurde bisher nur in einer Arbeit von Diele, Marangi und Ragni vorgeschlagen, wo man allerdings keine mathematisch begründete Fehlerabschätzung findet

Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network

INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care

A Minimal Hydrophobicity Is Needed To Employ Amphiphilic p(HPMA)-co-p(LMA) Random Copolymers in Membrane Research

Because a polymer environment might be milder than a detergent micelle, amphiphilic polymers have attracted attention as alternatives to detergents in membrane biochemistry. The polymer poly­[<i>N</i>-(2-hydroxypropyl)-methacrylamid] [p­(HPMA)] has recently been modified with hydrophobic lauryl methacrylate (LMA) moieties, resulting in the synthesis of amphiphilic p­(HPMA)-co-p­(LMA) polymers. p­(HPMA)-co-p­(LMA) polymers with a LMA content of 5 or 15% have unstable hydrophobic cores. This, on one hand, promotes interactions of the hydrophobic LMA moieties with membranes, resulting in membrane rupture, but at the same time prevents formation of a hydrophobic, membrane mimetic environment that is sufficiently stable for the incorporation of transmembrane proteins. On the other hand, the p­(HPMA)-co-p­(LMA) polymer with a LMA content of 25% forms a stable hydrophobic core structure, which prevents hydrophobic interactions with membrane lipids but allows stable incorporation of membrane proteins. On the basis of our data, it becomes obvious that amphiphilic polymers have to have threshold hydrophobicities should an application in membrane protein research be anticipated

Polymorphisms in FTO and MAF Genes and Birth Weight, BMI, Ponderal Index, Weight Gain in a Large Cohort of Infants with a Birth Weight below 1500 Grams.

<label>BACKGROUND</label>The FTO gene, located on chromosome 16q12.2, and the MAF gene, located on chromosome 16q22-23, were identified as genes harboring common variants with an impact on obesity predisposition. We studied the association of common variants with birth weight, gain of body weight, body mass index (BMI), Ponderal index and relevant neonatal outcomes in a large German cohort of infants with a birth weight below 1500 grams.<label>METHODS</label>The single nucleotide polymorphisms rs9939609 (FTO gene) and rs1424233 (MAF gene) were genotyped using allelic discrimination assays in a prospective multicenter cohort study conducted in 15 neonatal intensive care units in Germany from September 2003 until January 2008. DNA samples were extracted from buccal swabs according to standard protocols.<label>RESULTS</label>1946 infants were successfully genotyped at FTO and 2149 infants at MAF. Allele frequencies were not significantly different from other European cohorts. The polymorphisms were in Hardy-Weinberg equilibrium. The polymorphisms did not show associations with birth weight, BMI and Ponderal Index at discharge, and weight gain, neither testing for a dominant, additive nor for a recessive model.<label>DISCUSSION</label>Since an association of the polymorphisms with weight gain has been demonstrated in multiple populations, the lack of association in a population of preterm infants with regular tube feeding after birth and highly controlled feeding volumes provides evidence for the hypothesis that these polymorphisms affect food intake behavior and hunger rather than metabolism and energy consumption

Radioprotective effect of lidocaine on function and ultrastructure of salivary glands receiving fractionated radiation

Purpose: Radiation-induced xerostomia still represents a common side effect after radiotherapy for head-and-neck malignancies. The aim of the present study was to examine the radioprotective effect of lidocaine hydrochloride during fractionated radiation in an experimental animal model. Methods and Materials: To evaluate the influence of different radiation doses on salivary gland function and the radioprotective effect of lidocaine, rabbits were irradiated with 15, 25, 30, and 35 Gy (equivalent doses in 2-Gy fractions equivalent to 24, 40, 48, and 56 Gy, respectively). Lidocaine hydrochloride (10 and 12 mg/kg) was administered before every radiation fraction in the treatment groups. Salivary gland function was assessed by flow sialometry and sialoscintigraphy, and the morphologic changes were evaluated using transmission electron microscopy. Results: Functional impairment was first observed after 35 Gy and pretreatment with lidocaine improved radiation tolerance of both parotid and submandibular glands. The use of 12 mg/kg lidocaine was superior and displayed significant radioprotection with regard to flow sialometry and sialoscintigraphy. The ultrastructure was largely preserved after pretreatment with both lidocaine doses. Conclusions: Lidocaine represents an effective radioprotective agent and a promising approach for clinical application to avoid radiation-induced functional impairment of salivary glands. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.link_to_subscribed_fulltex

Mean outcome distribution according to genotype and phenotype.

*<p>Surgery for necrotizing enterocolitis.</p

Hypertrophy and hypotrophy and clinical data in German vlbw infant population.

<p>Hypertrophy and hypotrophy and clinical data in German vlbw infant population.</p

Outcome of patients in microclusters of blood-culture proven sepsis.

<p><b>Legend:</b> IVH intraventricular haemorrhage; Surgery for PDA Patent Ductus arteriosus, NEC necrotizing enterocolitis, FIP focal intestinal perforation, ROP retinopathy of prematurity (kryo- or laser therapy); BPD bronchopulmonary dysplasia; severe complication: IVH grade IV, posthaemorrhagic hydrocephalus with need for VP shunt, periventricular leukomalacia, surgery for NEC/FIP or ROP and BPD;</p><p>p-values were derived from chi-square test if not otherwise indicated (* Mann-Whitney-U test comparing linked cases vs. first patient in cluster.</p

Pathogenic spectrum of blood-culture proven sepsis episodes.

*<p>Estimate: estimated risk for specific pathogen/100 cases of blood-culture proven sepsis.</p

Clinical characteristics of the VLBW cohort stratified to occurrence of late-onset sepsis (LOS).

<p><b>Legend:</b> PPROM Preterm premature rupture of membranes, C/section Caesarean section, SGA small-for-gestational-age (<10th Voigt percentile).</p><p># p-values were derived from chi-square test if not otherwise indicated (* Mann-Whitney-U test).</p