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Electrical impedance segmentography offers a new radiation-free possibility of continuous bedside ventilation monitoring. The aim of this study was to evaluate the efficacy and reproducibility of this bedside tool by comparing synchronized intermittent mandatory ventilation (SIMV) with neurally adjusted ventilatory assist (NAVA) in critically-ill children. In this prospective randomized case–control crossover trial in a pediatric intensive care unit of a tertiary center, including eight mechanically-ventilated children, four sequences of two different ventilation modes were consecutively applied. All children were randomized into two groups; starting on NAVA or SIMV. During ventilation, electric impedance segmentography measurements were recorded. The relative difference of vertical impedance between both ventilatory modes was measured (median 0.52, IQR 0–0.87). These differences in left apical lung segments were present during the first (median 0.58, IQR 0–0.89, p = 0.04) and second crossover (median 0.50, IQR 0–0.88, p = 0.05) as well as across total impedance (0.52 IQR 0–0.87; p = 0.002). During NAVA children showed a shift of impedance towards caudal lung segments, compared to SIMV. Electrical impedance segmentography enables dynamic monitoring of transthoracic impedance. The immediate benefit of personalized ventilatory strategies can be seen when using this simple-to-apply bedside tool for measuring lung impedance.

Summary Background Despite current progress in research of congenital diaphragmatic hernia, its management remains challenging, requiring an interdisciplinary team for optimal treatment. Objective Aim of the present study was to evaluate potential risk factors for mortality of infants with congenital diaphragmatic hernia. Methods A single-center chart review of all patients treated with congenital diaphragmatic hernia over a period of 16 years, at the Medical University of Vienna, was performed. A comparison of medical parameters between survivors and non-survivors, as well as to published literature was conducted. Results During the observational period 66 patients were diagnosed with congenital diaphragmatic hernia. Overall survival was 84.6%. Left-sided hernia occurred in 51 patients (78.5%) with a mortality of 7.8%. In comparison, right-sided hernia occurred less frequently (n = 12) but showed a higher mortality (33.3%, p = 0.000). Critically instable patients were provided with venoarterial extracorporeal membrane oxygenation (ECMO, 32.3%, n = 21). Survival rate among these patients was 66.7%. Right-sided hernia, treatment with inhaled nitric oxide (iNO) over 15 days and the use of ECMO over 10 days were significant risk factors for mortality. Conclusion The survival rate in this cohort is comparable to the current literature. Parameters such as the side of the diaphragmatic defect, duration of ECMO and inhaled nitric oxide were assessed as mortality risk factors. This analysis of patients with congenital diaphragmatic hernia enhances understanding of risk factors for mortality, helping to improve management and enabling further evaluation in prospective clinical trials.

Sepsis is, worldwide, one of the leading causes of death among infants and children. Over the past two decades, mortality rates have declined due to advanced treatment options; however, the incidence of sepsis and septic shock is still on the rise in many hospital settings. The objective of this study was to evaluate the course of this disease in pediatric intensive care patients.An evaluation of pediatric patients in the intensive care unit diagnosed with infections or sepsis between 2005 and 2015 was performed via a retrospective exploratory data analysis.During the observational period, 201 patients were diagnosed with infection or sepsis. The study population was divided into five age subgroups. The majority of patients were newborns, infants, and toddlers. Forty percent had sepsis; 6% had septic shock. Viral infection was the most prevalent (59%). The overall survival rate was 83%; newborns and adolescents had the lowest survival rates.With this registry, children divided into five age subgroups with infection or sepsis were evaluated and treatment strategies were examined. We have shown that our findings on children treated in our pediatric intensive care unit conform with current literature about pediatric sepsis. In addition to maintaining strict hygiene standards, optimal aspects of sepsis care should be stringently observed, such as the quick administration of empirical broad-spectrum antibiotics, initial adequate fluid resuscitation, and a reliable and frequent routine of source control.HINTERGRUND: Sepsis ist weltweit eine der häufigsten Todesursachen bei Säuglingen und Kindern. In den letzten 2 Jahrzehnten sank die Sterblichkeitsrate durch verbesserte Behandlungsoptionen, die Inzidenz der Sepsis und des septischen Schocks nimmt jedoch weiterhin zu. Ziel dieser Studie war es, den Krankheitsverlauf bei pädiatrischen IntensivpatientInnen mit Sepsis oder Infektion zu beurteilen.Es erfolgte eine retrospektive explorative Datenanalyse von pädiatrischen PatientInnen, die zwischen 2005 und 2015 aufgrund einer Infektion oder Sepsis auf der Intensivstation stationär aufgenommen worden waren.Während des Beobachtungszeitraums wurde bei 201 Patienten eine Infektion oder Sepsis diagnostiziert. Die Studienpopulation wurde in 5 Altersuntergruppen eingeteilt, die Mehrheit davon waren Neugeborene, Säuglinge und Kleinkinder. Eine Sepsis wurde bei 40 % und ein septischer Schock bei 6 % der PatientInnen diagnostiziert. Am häufigsten waren Virusinfektionen (59 %). Die Gesamtüberlebensrate betrug 83 %, dabei wiesen Neugeborene und Jugendliche die niedrigste Überlebensrate auf.Mit dieser Registeranalyse wurden die Daten von Kindern mit Infektion oder Sepsis evaluiert und Behandlungsstrategien untersucht. Es wurde dabei gezeigt, dass die vorliegenden Ergebnisse mit der aktuellen Literatur vergleichbar sind. Strenge Hygienestandards und optimale Sepsisversorgung sollten korrekt durchgeführt werden, wie z. B. rasche Verabreichung empirischer Breitbandantibiotika, entsprechendes Flüssigkeitsmanagement sowie zuverlässige und regelmäßige Laborkontrollen hinsichtlich der Infektionsquelle.

Aim Since therapeutic hypothermia (TH) is known for its inhibitory effects on leucocyte migration and cytokine synthesis, our aim was to underline the necessity of early monitoring for potential immunomodulatory risks. Methods Using a 13‐year retrospective case‐control study at the paediatric intensive care unit (PICU) of the Medical University in Vienna, all newborn infants and children receiving TH were screened and compared with a diagnosis‐matched control group undergoing conventional normothermic treatment (NT). TH was accomplished by using a non‐invasive cooling device. Target temperature was 32‐34°C. Children with evident infections, a medical history of an immunodeficiency or undergoing immunosuppressive therapy, were excluded. Results During the observational period, 108 patients were screened, 27 of which underwent TH. Culture‐proven infections occurred in 22% of the TH group compared with 4% of the normothermic controls (P = .1). From the second day following PICU admission, median C‐reactive protein (CRP) values were higher in the TH group (day two P = .002, day three P = .0002, day six P = .008). Conclusion Children undergoing TH showed earlier and higher increases in CRP levels when compared to normothermic controls. These data underline the necessity of early and continuous monitoring for possible infectious complications.

Objectives:In critical care it is crucial to appropriately assess the risk of mortality for each patient. This is especially relevant in pediatrics, with its need for accurate and repeatable scoring. Aim of this study was to evaluate an age-adapted version of the expanded Simplified Acute Physiology Score II; (p-SAPS II), a repeatable, newly-designed scoring system compared to established scores (Pediatric Sequential Organ Failure Assessment Score/pSOFA, Pediatric Logistic Organ Dysfunction Score-2/PELOD-2 and Pediatric Index of Mortality 3/PIM3).Design:This retrospective cohort pilot study included data collected from patients admitted to the Pediatric Intensive Care Unit (PICU) at the Medical University of Vienna between July 2017 through December 2018.Patients:231 admissions were included, comprising neonates (gestational age of ≥ 37 weeks) and patients up to 18 years of age with a PICU stay longer than 48 h.Main Outcomes:Mortality risk prediction and discrimination between survivors and non-survivors were the main outcomes of this study. The primary statistical methods for evaluating the performance of each score were the area under the receiver operating characteristic curve (AUROC) and goodness-of-fit test.Results:Highest AUROC curve was calculated for p-SAPS II (AUC = 0.86; 95% CI: 0.77–0.96;p< 0.001). This was significantly higher than the AUROCs of PELOD-2/pSOFA but not of PIM3. However, in a logistic regression model including p-SAPS II and PIM3 as covariates, p-SAPS II had a significant effect on the accuracy of prediction (p= 0.003). Nevertheless, according to the goodness-of-fit test for p-SAPS II and PIM3, p-SAPS II overestimated the number of deaths, whereas PIM3 showed acceptable estimations. Repeatability testing showed increasing AUROC values for p-SAPS II throughout the clinical stay (0.96 at day 28) but still no significant difference to PIM 3. The prediction accuracy, although improved over the days and even exceeded PIM 3.Conclusions:The newly-created p-SAPS II performed better than the established PIM3 in terms of discriminating between survivors and non-survivors. Furthermore, p-SAPS II can be assessed repeatably throughout a patient's PICU stay what improves mortality prediction. However, there is still a need to optimize calibration of the score to accurately predict mortality sooner throughout the clinical stay.

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/)., The transcriptional programs of nuclei in the muscle syncytium were assumed to be homogenous except at the neuromuscular and myotendinous junctions. Here, using single-nucleus transcriptomics, the authors reveal a previously unrecognized diversity and dynamics of myonuclear transcriptional programs.

Zusammenfassung Hintergrund Hausarzte zahlen zu den Facharztgruppen mit den haufigsten Medikamenten-verordnungen. Die Vertiefung pharmakologischer Kenntnisse ist deshalb ein wichtiger Bestandteil der hausarztlichen Fort- und Weiterbildung. Das hausarztliche Selbstverstandnis, als erster Ansprechpartner bei allen Gesundheitsproblemen zu helfen, macht es zu einer Herausforderung, Weiterbildungsinhalte zu definieren und zu erwerben. Wahrend das von der Deutschen Gesellschaft fur Allgemeinmedizin entwickelte „Kompetenzbasierte Curriculum Allgemeinmedizin" essentielle Diagnosen, Beratungsanlasse und Kompetenzen fur die hausarztliche Tatigkeit definiert, fehlt eine solche Orientierung fur den pharmakologischen Bereich. Ziel dieser Arbeit ist, Wirkstoffe zu identifizieren und zu charakterisieren, die jeder Hausarzt so gut beherrschen sollte, dass er dazu beraten und Monitoringmasnahmen einleiten und durchfuhren kann. Methodik Es wurden die Verordnungen von Privat- und Kassenrezepten aller am CONTENT-Projekt teilnehmenden Praxen des Zeitraums 2009 bis 2014 analysiert. Die Analyse wurde auf oral applizierbare Wirkstoffe beschrankt, die von mindestens 25% (n=11) der Hausarztpraxen mindestens einmal verordnet wurden. Wahrend die hundert am haufigsten verordneten Wirkstoffe, die bereits uber 80% der Gesamtverordnungen ausmachten, aufgrund ihrer Verordnungshaufigkeit eingeschlossen wurden, wurden die weniger haufig verordneten Wirkstoffe in einem Rating-Verfahren zusatzlich nach ihrem Risikopotential und der hausarztlichen Relevanz beurteilt. Die auf dieser Basis eingeschlossenen Wirkstoffe wurden nach Beratungsanlassen/Diagnosen klassifiziert dargestellt. Ergebnisse Es wurden 1.912.896 Einzelverordnungen auf Basis der anatomisch-therapeutisch-chemischen Klassifikation (ATC) aus 44 Hausarztpraxen von 112.535 Patienten analysiert. Nach Anwendung der Einschlusskriterien verblieben 453 Wirkstoffe, von denen 302 Wirkstoffe als hausarztlich-relevant eingeschatzt wurden. Diese konnten 45 Beratungsanlassen/Diagnosen zugeordnet werden. Schlussfolgerung Das Ergebnis dieser Arbeit kann als Entwicklungsversion eines hausarztlich-pharmakologischen Curriculums gesehen werden und perspektivisch das kompetenzbasierte Curriculum Allgemeinmedizin sinnvoll erganzen.

General practitioners (GPs) are among the specialists who prescribe the highest number of medication. Therefore the improvement of pharmacological competencies is an important part of the GP specialist training. The self-concept of general practice stating that GPs are the first contact persons for all health problems makes it challenging to define and acquire competencies for specialist training. While the "Competence-based Curriculum" developed by the German College of General Practitioners and Family Physicians defines diagnoses, reasons for counselling and competencies which are essential for general practice, a similar orientation guide is lacking for the pharmacological field. The aim of this study is to define and characterize pharmacological substances which every GP should know so well that he or she is able to conduct counselling and monitoring.We analysed private and public health insurance prescriptions of all general practices participating in the CONTENT project in the period from 2009 to 2014. The analysis was limited to substances with oral application which were prescribed at least once by at least 25 % (n = 11) of the practices. While the 100 most frequent prescriptions were included due to their frequency, less frequently prescribed substances were assessed concerning their relevance for general practice in a rating procedure. The substances included were classified by diagnoses and reasons for counselling.We analysed 1,912,896 prescriptions from 44 practices and 112,535 patients on the basis of the Anatomical Therapeutic Chemical (ATC) classification system. After applying the inclusion criteria, 453 substances were left, 302 of which were considered relevant for general practice and could be assigned to 45 diagnoses / reasons for counselling.The result of this study could be considered a working draft for a pharmacological curriculum for general practice, which may complement the "Competence-based Curriculum" in the medium term.

Peter Burger reflects on the reception of his Theory of the Avant-Garde and crafts a spirited response to his critics, while expanding on and refining his original claims. For Burger, what continues to distinguish the avant-garde are two interrelated principles: the attack on the institution of art and the revolutionary transformation of everyday life. Underscoring the explicitly theoretical, rather than merely historical, thrust of this definition, he defends this generalizing strategy as a necessary means of achieving clarity about the changing role of art in society. He reiterates his argument about the failure of the historical avant-garde (to overcome the distinction of art and life), while placing a new emphasis on its equal measure of success (in transforming the internal logic of the art institution). The avant-garde’s appropriation of outdated and popular materials, for example, played a key role in challenging the norms of the art world, helping to bring about the leveling of distinctions often associated with postmodernism. On the one hand, the avant-garde failed in its attempt to revolutionize social reality; on the other hand, its impact on the norms and values of the art institution was significant and far-reaching. Contemporary or neo-avant-gardes remain caught on the horns of this contradiction, insofar as their aesthetic experiments—whatever the explicit intentions of the artist—only shore up the walls of the institution rather than breaking them down.

The following conversation centers on a rare book: Ein Gedicht fur ein Buch or A Poem for a Book (1996), a collaboration between Yoko Tawada (I960-), author, Stephan Kohler (1959-), photographer and papermaker, and Cle mens-Tobias Lange (I960-), book artist and designer.1 Robert Rainwater, former curator of the New York Public Library's Spencer collection which houses one of the 45 editions, described^ Poemfor a Book as "a perfect mar riage between the Japanese handmade book and the more recent European tradition of livres d'artistes," and lauded it as "a paean to the act of reading and to the art of the book."2 Recently, the book was prominently displayed at the New York Public Library as part of the exhibit Ehon: The Artist and the Book in Japan. Yoko Tawada, who writes in Japanese and in German, was born as #ftffl*T(fcfrfc 0 or Tawada Yoko in Tokyo, Japan, in 1960. She established residency in Germany twenty-two years later and has been living there ever since. Tawada has published collections of poems, short stories, radio plays, texts for the theater, novels, literary essays, and experimental performance pieces.3 In the following dialogue?a revised version of a podium discussion that took place in conjunction with the exhibit?Yoko Tawada and Bettina Brandt discuss the relationship between artist books and migration.

Yoko Tawada, who writes and publishes both in German and in Japanese, is one of the most important "foreign" authors writing in Germany today. Tawada discusses in her poems, plays, stories, essays, and novels not only questions of national and cultural identity but also questions of gender. The following interview focuses on the use of different languages in Tawada's writing and their relationship to such topics as metaphor, creativity, childhood, collecting, art, metamorphosis, and the material world.

In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response.

Author(s): Brandt, Bettina; Tawada, Yoko | Abstract: The texts published here were originally presented together at the "Imaginary Cities" conference at Penn State University on April 13, 2007. They are being published here for the first time.

Galectin-1 (gal-1), an endogenous β-galactoside-binding protein, triggers T-cell death through several mechanisms including the death receptor and the mitochondrial apoptotic pathway. In this study we first show that gal-1 initiates the activation of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 4 (MKK4), and MKK7 as upstream JNK activators in Jurkat T cells. Inhibition of JNK activation with sphingomyelinase inhibitors (20 μM desipramine, 20 μM imipramine), with the protein kinase C-δ (PKCδ) inhibitor rottlerin (10 μM), and with the specific PKCθ pseudosubstrate inhibitor (30 μM) indicates that ceramide and phosphorylation by PKCδ and PKCθ mediate gal-1-induced JNK activation. Downstream of JNK, we observed increased phosphorylation of c-Jun, enhanced activating protein-1 (AP-1) luciferase reporter, and AP-1/DNA-binding in response to gal-1. The pivotal role of the JNK/c-Jun/AP-1 pathway for gal-1-induced apoptosis was documented by reduction of DNA fragmentation after inhibition JNK by SP600125 (20 μM) or inhibition of AP-1 activation by curcumin (2 μM). Gal-1 failed to induce AP-1 activation and DNA fragmentation in CD3-deficient Jurkat 31-13 cells. In Jurkat E6.1 cells gal-1 induced a proapoptotic signal pattern as indicated by decreased antiapoptotic Bcl-2 expression, induction of proapoptotic Bad, and increased Bcl-2 phosphorylation. The results provide evidence that the JNK/c-Jun/AP-1 pathway plays a key role for T-cell death regulation in response to gal-1 stimulation.Cell Death and Disease (2010) 1, e23; doi:10.1038/cddis.2010.1; published online 4 February 2010.