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Der Titel lässt eine Behandlung von Streitschriften und anderen Zeugnissen aus der Zeit des großen abendländischen Schismas erwarten, mit denen sich Vertreter der zwei bzw. drei Obödienzen positionierten und einander bekämpften. Doch vor die Quellen hat die Verfasserin die Theorie gesetzt: Ohne Habermas, Bourdieu und Foucault kein Jean Gerson, Simon de Cramaud oder Nicolas Eymerich. Man wähnt sich anfangs weniger in der Welt der Pariser Universität und der avignonesischen Kurie um 1400 als im soziologischen und literaturtheoretischen Oberseminar (die klassische Ideengeschichte wird kurzerhand als "très périmée" beiseite geschoben [S. 13]) und fürchtet, zumindest als nicht eben theorieversessener Historiker, schon den anstehenden Marsch durch entsprechende Textwüsten, zumal die Autorin expressis verbis einen anderen Ansatz als Hélène Millet vertritt, die sich mit ihren – am Dictum Lucien Febvres "Et l’homme dans tout cela?" orientierten – biografischen und prosopografischen Arbeiten um die Erforschung des Schismas bekanntlich sehr verdient gemacht hat: "Hélène Millet aime cerner les hommes du temps, quand j’aime scruter les textes" (S. 16). ...
Selten dürfte es einem Gelehrten vergönnt sein, die Summe seiner über 50 Jahre währenden Tätigkeit in zwei Alterswerken ziehen zu können, wie es bei Philippe Contamine der Fall ist mit dem wesentlich von ihm gestalteten "Dictionnaire de Jeanne d’Arc" und der nunmehr vorliegenden Biografie Karls VII. Diese beiden Persönlichkeiten markieren Schwerpunkte in einem staunenswerte Kontinuität, Intensität und Konsequenz zeigenden Œuvre, in dem nicht nur, so doch immer wieder die Geschichte Frankreichs im 14. und vor allem 15.Jahrhundert im Zentrum steht. Der Verfasser pflegt eine politisch akzentuierte Geschichtsschreibung, die sich abseits aller Moden und Theoriedebatten grundsätzlich der Quellenerschließung und -interpretation verpflichtet weiß. Geschrieben wurde auch der hier anzuzeigende Band stets entlang den oft in Auszügen zitierten und im Fall von Traktaten eines Alain Chartier oder Jean Juvénal des Ursins gar eigene Unterkapitel ausfüllenden Quellen, darin einmal mehr eingeschlossen handschriftliches Material. Unspektakulär geht der Autor diesen seinen Weg; dabei erfolgt auch, bis auf eine kurze lobende Erwähnung der monumentalen Monografie von Du Fresne de Beaucourt (1881/1891, vgl. S. 16), keine Auseinandersetzung mit früheren Biografien Karls VII., selbst nicht mit der – trotz fragwürdiger Grundthese lohnenswerten – von M.G. A. Vale oder der jüngsten, übrigens ebenfalls bei Perrin erschienenen – und m. E. weniger lohnenden – von Georges Minois; von dem noch 2001 wieder aufgelegten und recht eigenwilligen, da Karls VII. Schwiegermutter Yolande von Aragón als dessen mystère in den Mittelpunkt stellenden Buch eines Philippe Erlanger ganz zu schweigen. ...
Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria.
Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria.
Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate.
Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.
Cytokine regulation of high-output nitric oxide (NO) derived from inducible NO synthase (iNOS) is critically involved in inflammation biology and host defense. Herein, we set out to characterize the role of type I interferon (IFN) as potential regulator of hepatic iNOS in vitro and in vivo. In this regard, we identified in murine Hepa1-6 hepatoma cells a potent synergism between pro-inflammatory interleukin-β/tumor necrosis factor-α and immunoregulatory IFNβ as detected by analysis of iNOS expression and nitrite release. Upregulation of iNOS by IFNβ coincided with enhanced binding of signal transducer and activator of transcription-1 to a regulatory region at the murine iNOS promoter known to support target gene expression in response to this signaling pathway. Synergistic iNOS induction under the influence of IFNβ was confirmed in alternate murine Hepa56.1D hepatoma cells and primary hepatocytes. To assess iNOS regulation by type I IFN in vivo, murine acetaminophen (APAP)-induced sterile liver inflammation was investigated. In this model of acute liver injury, excessive necroinflammation drives iNOS expression in diverse liver cell types, among others hepatocytes. Herein, we demonstrate impaired iNOS expression in type I IFN receptor-deficient mice which associated with diminished APAP-induced liver damage. Data presented indicate a vital role of type I IFN within the inflamed liver for fine-tuning pathological processes such as overt iNOS expression.
Background: Caloric restriction is associated with broad therapeutic potential in various diseases and an increase in health and life span. In this study, we assessed the impact of caloric restriction on acute and inflammatory nociception in mice, which were either fed ad libitum or subjected to caloric restriction with 80% of the daily average for two weeks.
Results: The behavioral tests revealed that inflammatory nociception in the formalin test and in zymosan-induced mechanical hypersensitivity were significantly decreased when mice underwent caloric restriction. As potential mediators of the diet-induced antinociception, we assessed genes typically induced by inflammatory stimuli, AMP-activated kinase, and the endocannabinoid system which have all already been associated with nociceptive responses. Zymosan-induced inflammatory markers such as COX-2, TNFα, IL-1β, and c-fos in the spinal cord were not altered by caloric restriction. In contrast, AMPKα2 knock-out mice showed significant differences in comparison to C57BL/6 mice and their respective wild type littermates by missing the antinociceptive effects after caloric restriction. Endocannabinoid levels of anandamide and 2-arachidonyl glyceroldetermined in serum by LC-MS/MS were not affected by either caloric restriction alone or in combination with zymosan treatment. However, cannabinoid receptor type 1 expression in the spinal cord, which was not altered by caloric restriction in control mice, was significantly increased after caloric restriction in zymosan-induced paw inflammation. Since increased cannabinoid receptor type 1 signaling might influence AMP-activated kinase activity, we analyzed effects of anandamide on AMP-activated kinase in cell culture and observed a significant activation of AMP-activated kinase. Thus, endocannabionoid-induced AMP-activated kinase activation might be involved in antinociceptive effects after caloric restriction.
Conclusion: Our data suggest that caloric restriction has an impact on inflammatory nociception which might involve AMP-activated kinase activation and an increased activity of the endogenous endocannabinoid system by caloric restriction-induced cannabinoid receptor type 1 upregulation.
"Ihr sollt euch nicht zu den Götzen wenden, und gegossene Götter sollt ihr euch nicht machen [...](Lev 19,4) [...] sollen wir nicht meinen, daß das Göttliche dem Gold und Silber oder Stein, einem Gebilde der Kunst und der Erfindung des Menschen gleich sei. (Acta 17,29) Pfui über euch und über das, was ihr an Gottes Statt verehrt! [...] (Q 21,67)"
Diese drei Sätze stammen nacheinander aus der hebräischen Bibel, dem Neuen Testament und dem Koran. Man kann sie beinahe wie einen Text lesen, an dem sich die These des Ägyptologen Jan Assmann belegen ließe, dass mit der Herausbildung monotheistischer Religionen wie Judentum, Christentum und Islam im Allgemeinen und dem Bilderverbot im Besonderen die Unterscheidung zwischen wahr und falsch in die Götterwelt gekommen sei (Assmann 1998, S. 17). ...
Tortonian teleost otoliths from northern Italy: taxonomic synthesis and stratigraphic significance
(2017)
The Tortonian fish otoliths of northern Italy have been studied for more than a century and represent one of the best known otolith-based teleost faunas in the Miocene of the Mediterranean Basin. Yet with the growing knowledge on Recent otoliths, an updated taxonomic overview of this fauna is needed. Moreover, new material from hemipelagic Tortonian marls sampled at nine localities is described herein, revealing 109 taxa of which 88 are recognised at species level. Four of these are new: Coryphaenoides biobtusus sp. nov., “Merluccius” rattazzii sp. nov., Neobythites auriculatus sp. nov. and Lesueurigobius stironensis sp. nov. The compilation of previously studied and newly acquired material revealed a total of 118 nominal Tortonian species. At generic level, the fauna is characterised by many modern forms; more than 90% can be assigned to present day genera. At species level, however, more than half of the represented taxa are extinct. Based on the fossil otolith record, the Tortonian fauna of the Mediterranean is most similar to that of the Langhian (Badenian) of the Central Paratethys by sharing many extinct Miocene species, but it is also very close to that of the Pliocene Mediterranean, by sharing many modern Atlantic-Mediterranean forms. The Tortonian fauna is further characterised by many species that are apparently confined to the upper Miocene, resulting in a unique combination of its taxonomic composition.
Recently, Aumüller and Dietzfelbinger proposed a version of a dual-pivot Quicksort, called "Count", which is optimal among dual-pivot versions with respect to the average number of key comparisons required. In this master's thesis we provide further probabilistic analysis of "Count". We derive an exact formula for the average number of swaps needed by "Count" as well as an asymptotic formula for the variance of the number of swaps and a limit law. Also for the number of key comparisons the asymptotic variance and a limit law are identified. We also consider both complexity measures jointly and find their asymptotic correlation.
Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.
By analyzing the large-angle Bhabha scattering events e+e− → (γ)e+e− and diphoton events e+e− → (γ)γγ for the data sets collected at center-of-mass (c.m.) energies between 2.2324 and 4.5900 GeV (131 energy points in total) with the upgraded Beijing Spectrometer (BESIII) at the Beijing Electron-Positron Collider (BEPCII), the integrated luminosities have been measured at the different c.m. energies, individually. The results are important inputs for the R value and J/ψ resonance parameter measurements.
In this study, we construct a new monthly zonal mean carbon dioxide (CO2) distribution from the upper troposphere to the stratosphere over the 2000–2010 time period. This reconstructed CO2 product is based on a Lagrangian backward trajectory model driven by ERA-Interim reanalysis meteorology and tropospheric CO2 measurements. Comparisons of our CO2 product to extratropical in situ measurements from aircraft transects and balloon profiles show remarkably good agreement. The main features of the CO2 distribution include (1) relatively large mixing ratios in the tropical stratosphere; (2) seasonal variability in the extratropics, with relatively high mixing ratios in the summer and autumn hemisphere in the 15–20 km altitude layer; and (3) decreasing mixing ratios with increasing altitude from the upper troposphere to the middle stratosphere ( ∼ 35 km). These features are consistent with expected variability due to the transport of long-lived trace gases by the stratospheric Brewer–Dobson circulation. The method used here to construct this CO2 product is unique from other modelling efforts and should be useful for model and satellite validation in the upper troposphere and stratosphere as a prior for inversion modelling and to analyse features of stratosphere–troposphere exchange as well as the stratospheric circulation and its variability.
AirCore-HR : a high-resolution column sampling to enhance the
vertical description of CH₄ and CO₂
(2017)
An original and innovative sampling system called AirCore was presented by NOAA in 2010 (Karion et al., 2010). It consists of a long ( > 100 m) and narrow (< 1 cm) stainless steel tube that can retain a profile of atmospheric air. The captured air sample has then to be analyzed with a gas analyzer for trace mole fraction. In this study, we introduce a new AirCore aiming to improve resolution along the vertical with the objectives to (i) better capture the vertical distribution of CO2 and CH4, (ii) provide a tool to compare AirCores and validate the estimated vertical resolution achieved by AirCores. This (high-resolution) AirCore-HR consists of a 300 m tube, combining 200 m of 0.125 in. (3.175 mm) tube and a 100 m of 0.25 in. (6.35 mm) tube. This new configuration allows us to achieve a vertical resolution of 300 m up to 15 km and better than 500 m up to 22 km (if analysis of the retained sample is performed within 3 h). The AirCore-HR was flown for the first time during the annual StratoScience campaign from CNES in August 2014 from Timmins (Ontario, Canada). High-resolution vertical profiles of CO2 and CH4 up to 25 km were successfully retrieved. These profiles revealed well-defined transport structures in the troposphere (also seen in CAMS-ECMWF high-resolution forecasts of CO2 and CH4 profiles) and captured the decrease of CO2 and CH4 in the stratosphere. The multi-instrument gondola also carried two other low-resolution AirCore-GUF that allowed us to perform direct comparisons and study the underlying processing method used to convert the sample of air to greenhouse gases vertical profiles. In particular, degrading the AirCore-HR derived profiles to the low resolution of AirCore-GUF yields an excellent match between both sets of CH4 profiles and shows a good consistency in terms of vertical structures. This fully validates the theoretical vertical resolution achievable by AirCores. Concerning CO2 although a good agreement is found in terms of vertical structure, the comparison between the various AirCores yields a large and variable bias (up to almost 3 ppm in some parts of the pro- files). The reasons of this bias, possibly related to the drying agent used to dry the air, are still being investigated. Finally, the uncertainties associated with the measurements are assessed, yielding an average uncertainty below 3 ppb for CH4 and 0.25 ppm for CO2 with the major source of uncertainty coming from the potential loss of air sample on the ground and the choice of the starting and ending point of the collected air sample inside the tube. In an ideal case where the sample would be fully retained, it would be possible to know precisely the pressure at which air was sampled last and thus to improve the overall uncertainty to about 0.1 ppm for CO2 and 2 ppb for CH4
Background: High reproducibility and low intra- and interobserver variability are important strengths of cardiac magnetic resonance (CMR). In clinical practice a significant learning curve may however be observed. Basic CMR courses offer an average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV) function analysis. The purpose of this study was to evaluate the effect of initial teaching on complete and intermediate beginners’ quantitative measurements of LV volumes and function by CMR.
Methods: Standard clinical cine CMR sequences were acquired in 15 patients. Five observers (two complete beginners, one intermediate, two experienced) measured LV volumes. Before initial evaluation beginners read the SCMR guidelines on CMR analysis. After initial evaluation, beginners participated in a two-hour teaching session including cases and hands-on training, representative for most basic CMR courses, after which it is uncertain to what extent different centres provide continued teaching and feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations. Agreement, accuracy, precision, repeatability and reliability were assessed by Bland-Altman, coefficient of variation, and intraclass correlation coefficient methods.
Results: Endocardial DSC improved after teaching (+0.14 ± 0.17;p < 0.001) for complete beginners. Low intraobserver variability was found before and after teaching, however with wide limits of agreement. Beginners underestimated volumes by up to 44 ml (EDV), 27 ml (ESV) and overestimated LVM by up to 53 g before teaching, improving to an underestimation of up to 9 ml (EDV), 7 ml (ESV) and an overestimation of up to 30 g (LVM) after teaching. For the intermediate beginner, however, accuracy was quite high already before teaching.
Conclusions: Initial teaching to complete beginners increases accuracy for assessment of LV volumes, however with high bias and low precision even after standardised teaching as offered in most basic CMR courses. Even though the intermediate beginner showed quite high accuracy already before teaching, precision did generally not improve after standardised teaching. To maintain CMR as a technique known for high accuracy and reproducibility and low intra- and inter-observer variability for quantitative measurements, internationally standardised training should be encouraged including high-quality feedback mechanisms. Objective measurements of training methods, training duration and, above all, quality of assessments are required.
Kurt Oppert hat, vor allem gestützt auf Rilkes "Neue Gedichte", die Verbreitung der Bezeichnung 'Dinggedicht' initiiert. Obwohl die Forschung längst die Inadäquatheit der meisten Charakteristika, die Oppert unter anderem aus Rilkes Dinggedichten zu destillieren versuchte, herausgearbeitet hat, ist die Bezeichnung noch immer weit verbreitet. Aus guten Gründen, wie die folgende Analyse von "Die Flamingos" vor dem Hintergrund von Rilkes nuancierten kunsttheoretischen Reflexionen des Dingbegriffs zeigen wird.
Allerdings haften der vielfach rejustierten Typusbezeichnung 'Dinggedicht' noch immer hartnäckig und nicht immer offensichtlich Reste einer intuitiven Konstellation von 'Ding' und lyrischem Sprechen an, die einst das Zentrum von Opperts Überlegungen gebildet hatte. Es ist daher das Projekt dieses Beitrags, Rilkes Arbeit an einem neuen, andersartigen Verhältnis von 'Gedicht' und 'Ding' freizulegen. Oppert versteht das 'Dinggedicht' als einen "Gegentypus" zu Goethes "werdende[m] Gedicht mit seiner subjektiven, echt lyrischen Stimmungshandlung ", "der auf unpersönliche, episch-objektive Beschreibung eines Seienden angelegt ist".
Judith Kaspers und Cornelia Wilds kommentierte Anthologie Rom Rückwärts ist der konstatierten "Allgegenwart der Tropen" von Rom gewidmet, die 35 sehr unterschiedliche Beiträge vor Augen stellen. Dabei gilt das Interesse dem genauen Funktionieren dieser Referenz, die offenbar weite Teile des europäischen kulturellen Selbstverständnisses auf vielfältige Art und Weise stabilisiert hat und noch immer stabilisiert. Es handelt sich dabei keineswegs um einen weiteren Sammelband, der sich damit begnügte, lediglich Rahmen und Anlass zur Publikation der enthaltenen Beiträge zu bieten. Rom Rückwärts ist vielmehr ein gewitztes und ambitioniertes Buch, das sich an eine komplizierte Intervention wagt: "die versteckten Vielfältigkeiten in der Referenz Rom" herauszuarbeiten und ihre "nicht institutionalisierten Dimensionen" zu entziffern.
Background Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.
Methods We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.
Results When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.
Conclusions Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
Der Begriff 'apokryph' taucht bei Johann Georg Hamann (1730-1788), dem 'Magus in Norden', seltener auf als man es vielleicht erwarten würde, jedenfalls so man Hamann noch immer nach dem gängigen Klischee für 'dunkel', einen 'Mystiker' oder einen 'Obskurantisten' oder gar für den Ursprung des modernen und spezifisch deutschen Irrationalismus und extremsten Feind der Aufklärung hält, gegenüber dessen "gewollter und künstlicher Dunkelheit", die er wie eine "Nebelwand um sich zog", sogar Hegels Phänomenologie des Geistes "eine wahre Ferienlektüre" sei. Ein schöpferischer Kopf also, "der manche tiefsinnigen Einfälle hatte, aber in welch geheimnisvolle Gewänder pflegte er sie zu verkleiden!" Entsprechend ist Hamanns Ruf: "Dunkelheit ist das traditionelle Prädicat, das jedem deutschen Primaner über ihn geläufig ist." Mit seiner Dunkelheit, so die unausgesprochene Annahme, möchte Hamann willentlich und wissentlich etwas verbergen, vielleicht nicht nur bei sich, sondern letztlich sogar das Licht der Aufklärung überhaupt; ein Umstand, der auf das Schönste zum griechischen apokryptein: 'verbergen, verdunkeln' (so die Übersetzung in Josef Nadlers Schlüssel zu Hamanns Werken) zu passen scheint. Entsprechend ist es, um eine weitere Bedeutung des Begriffes "apokryph" als des 'Gegen-Kanonischen' heranzuziehen, kaum verwunderlich, dass Texte Hamanns es nicht in den akademisch etablierten Kanon philosophischer Werke geschafft haben, ja sogar gegen entsprechende kanonische Texte (etwa die Metakritik über den Purismum der Vernunft gegen die Kritik der reinen Vernunft oder Golgatha und Scheblimini gegen Mendelssohns Jerusalem) gerichtet zu sein scheinen.
Inhibition of the IκB kinase complex (IKK) has been implicated in the therapy of several chronic inflammatory diseases including inflammatory bowel diseases. In this study, using mice with an inactivatable IKKα kinase (IkkαAA/AA), we show that loss of IKKα function markedly impairs epithelial regeneration in a model of acute colitis. Mechanistically, this is caused by compromised secretion of cytoprotective IL-18 from IKKα-mutant intestinal epithelial cells because of elevated caspase 12 activation during an enhanced unfolded protein response (UPR). Induction of the UPR is linked to decreased ATG16L1 stabilization in IkkαAA/AA mice. We demonstrate that both TNF-R and nucleotide-binding oligomerization domain stimulation promote ATG16L1 stabilization via IKKα-dependent phosphorylation of ATG16L1 at Ser278. Thus, we propose IKKα as a central mediator sensing both cytokine and microbial stimulation to suppress endoplasmic reticulum stress, thereby assuring antiinflammatory function during acute intestinal inflammation.
Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis
(2017)
Background: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.
Aim: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.
Methods: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.
Results: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.
Conclusions: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions.