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Abstract Background Numerous tissue-derived factors have been postulated to be involved in tissue migration of circulating monocytes. The aim of this study was to evaluate whether a defined hypoxic gradient can induce directed migration of naïve human monocytes and to identify responsible autocrine/paracrine factors. Methods Monocytes were isolated from peripheral blood mononuclear cells, transferred into chemotaxis chambers and subjected to a defined oxygen gradient with or without the addition of CCL26. Cell migration was recorded and secretome analyses were performed. Results Cell migration recordings revealed directed migration of monocytes towards the source of hypoxia. Analysis of the monocyte secretome demonstrated a reduced secretion of 70% (19/27) of the analyzed cytokines under hypoxic conditions. The most down-regulated factors were CCL26 (− 99%), CCL1 (− 95%), CX3CL1 (− 95%), CCL17 (− 85%) and XCL1 (− 83%). Administration of recombinant CCL26 abolished the hypoxia-induced directed migration of human monocytes, while the addition of CCL26 under normoxic conditions resulted in a repulsion of monocytes from the source of CCL26. Conclusions Hypoxia induces directed migration of human monocytes in-vitro. Autocrine/paracrine released CCL26 is involved in the hypoxia-mediated monocyte migration and may represent a target molecule for the modulation of monocyte migration in-vivo.

Abstract Background Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. Methods This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. Results Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. Conclusions Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Abstract Background This study aimed to evaluate the accuracy of procalcitonin (PCT) serum concentrations to diagnose Gram-negative bacteremia and the association of PCT serum concentrations with more specific pathogens and the focus of infection. Methods Secondary analysis of the prospectively collected patient-level dataset from a cluster randomized quality improvement trial was performed. The trial included sepsis patients with organ dysfunction treated in the participating intensive care units from 2011 to 2015. Test performance for the prediction of Gram-negative bacteremia was assessed by receiver operating curve analysis. Independent effects of specific pathogen groups and foci of infection on PCT concentrations were assessed by linear logistic regression models. Results Blood cultures (BC) and PCT concentrations had been taken in 4858 of 6561 documented patients. PCT was significantly higher in Gram-negative bacteremia compared to Gram-positive bacteremia or candidemia (p

Introduction Observational studies have demonstrated an association between vitamin D deficiency and increased risk of morbidity and mortality in critically ill patients. Cohort studies and pilot trials have suggested promising beneficial effects of vitamin D replacement in the critical ill, at least in patients with severe vitamin D deficiency. As vitamin D is a simple, low-cost and safe intervention, it has potential to improve survival in critically ill patients.Methods and analysis In this randomised, placebo-controlled, double-blind, multicentre, international trial, 2400 adult patients with severe vitamin D deficiency (25-hydroxyvitamin D≤12 ng/mL) will be randomised in a 1:1 ratio by www.randomizer.at to receive a loading dose of 540 000 IU cholecalciferol within 72 hours after intensive care unit (ICU) admission, followed by 4000 IU daily for 90 days or placebo. Hypercalcaemia may occur as a side effect, but is monitored by regular checks of the calcium level. The primary outcome is all-cause mortality at 28 days after randomisation. Secondary outcomes are: ICU, hospital, 90-day and 1-year mortality; hospital and ICU length of stay, change in organ dysfunction on day 5 as measured by Sequential Organ Function Assessment (SOFA) score, number of organ failures; hospital and ICU readmission until day 90; discharge destination, self-reported infections requiring antibiotics until day 90 and health-related quality of life. Recruitment status is ongoing.Ethics and dissemination National ethical approval was obtained by the Ethics Committee of the University of Graz for Austria, Erasme University Brussels (Belgium) and University Hospital Frankfurt (Germany), and will further be gained according to individual national processes. On completion, results will be published in a peer-reviewed scientific journal. The study findings will be presented at national and international meetings with abstracts online.Trial registration NCT03188796, EudraCT-No: 2016-002460-13.

INTRODUCTION:Patients with acute respiratory distress syndrome (ARDS) typically show a high degree of ventilation inhomogeneity, which is associated with morbidity and unfavorable outcomes. Electrical impedance tomography (EIT) is able to detect ventilation inhomogeneity, but it is unclear which method for defining the region of interest (ROI) should be used for this purpose. The aim of our study was to compare the functional region of interest (fROI) method to both the lung area estimation method (LAEM) and no ROI when analysing global parameters of ventilation inhomogeneity. We assumed that a good method for ROI determination would lead to a high discriminatory power for ventilation inhomogeneity, as defined by the area under the receiver operating characteristics curve (AUC), comparing patients suffering from ARDS and control patients without pulmonary pathologies. METHODS:We retrospectively analysed EIT data from 24 ARDS patients and 12 control patients without pulmonary pathology. In all patients, a standardized low-flow-pressure volume maneuver had been performed and was used for EIT image generation. We compared the AUC for global inhomogeneity (GI) index and coefficient of variation (CV) between ARDS and control patients using all EIT image pixels, the fROI method and the LAEM for ROI determination. RESULTS:When analysing all EIT image pixels, we found an acceptable AUC both for the GI index (AUC = 0.76; 95% confidence interval (CI) 0.58-0.94) and the CV (AUC = 0.74; 95% CI 0.55-0.92). With the fROI method, we found a deteriorating AUC with increasing threshold criteria. With the LAEM, we found the best AUC both for the GI index (AUC = 0.89; 95% CI 0.78-1.0) and the CV (AUC = 0.89; 95% CI 0.78-1.0) using a threshold criterion of 50% of the maximum tidal impedance change. CONCLUSION:In the assessment of ventilation inhomogeneity with EIT, functional regions of interest obscure the difference between patients with ARDS and control patients without pulmonary pathologies. The LAEM is preferable to the fROI method when assessing ventilation inhomogeneity.

Acid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation.40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome plus a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (PCT before), during (PCT peak) and after (PCT low) onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed.ASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and PCT before was not different, but further increased at PCT peak in non-survivors and was significantly higher at PCT low compared to survivors. Survivors exhibited decreased ASM at PCT peak and PCT low. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at PCT low.In summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation.

Abstract Background In mesocosms, the fate and effects of chemicals can be investigated under more realistic conditions than in laboratory-scale experiments and most mesocosm studies for higher-tier risk assessment are conducted in lentic test systems. However, particularly for the assessment of EPT taxa (Ephemeroptera, Plecoptera, Trichoptera) and gammarids (Amphipoda), which are considered to be ecologically vulnerable macroinvertebrates, lotic systems seem to be more appropriate. Within this pilot study, eight newly constructed stream mesocosms were tested for their suitability in the effect assessment of plant protection products (PPP). By using the insecticide carbaryl as an example test item, five concentrations without replicates were tested under a worst case exposure scenario and three stream mesocosms served as controls. Results 15 out of the 51 invertebrate taxa found during the study belonged to EPT taxa, while the common lotic amphipod Gammarus sp. (G. pulex and G. roesili) was the most dominant taxa. Estimation of minimum detectable differences based on mean abundances and variance of taxa in the eight mesocosms before application indicate that for five arthropoda taxa and two non-arthropoda taxa, an analysis of effects would have probably would have been possible in a typical test design for a higher-tier study with more test units. Five of these taxa were typical stream taxa, i.e. mayflies, caddisflies and gammarids. With respect to the effects of carbaryl, multivariate analysis (principal response curve) indicates long-term effects on the macroinvertebrates community over several weeks for the highest carbaryl concentration (120 µg a.i./L). Potential effects were observed for the amphipod Gammarus sp., the mayfly Ephemera danica and the caddisfly family Limnephilidae. Conclusions Through this study it was shown that the stream mesocosms provided suitable habitats for potential sensitive and vulnerable taxa, including those typical for lotic systems. To enable a reliable statistical analysis of the effects within the higher-tier ecological risk assessment, the number of stream mesocosms needs to be enhanced. In addition, colonisation and sampling should be improved to increase the number of taxa with sufficiently high abundances for evaluation.

Abstract Background Surfactants are widely used across the globe both in industrial and consumer products. The n-octanol/water partition ratio or coefficient (log K ow) and n-octanol/water distribution coefficient (log D) are key parameters in environmental risk assessment of chemicals as they are often used to estimate the environmental fate and bioavailability and thus exposure and toxicity of a compound. Determining log K ow data for surfactants is a technical challenge due to their amphiphilic properties. Currently several existing experimental OECD methods (e.g. slow-stirring, HPLC, solubility ratio) and QSPR models are available for log K ow/D measurement or prediction. However, there are concerns that these methods have not been fully validated for surfactants and may not be applicable due to the specific phase behaviour of surfactants. Results The current methods were evaluated for the four surfactant classes (non-ionic, anionic, cationic and amphoteric). The solubility ratio approach, based on comparative n-octanol and water solubility measurements, did not generate robust or accurate data. The HPLC method generates consistently higher log K ow values than the slow-stirring method for non-ionics, but this positive bias could be removed using reference surfactants with log K ow values determined using the slow-stirring method. The slow-stirring method is the most widely applicable experimental method for generating log K ow/D data for all the surface-active test compounds. Generally, QSPR-predicted log K ow/D values do not correlate well with experimental values, apart for the group of non-ionic surfactants. Relatively, large differences in predicted log K ow/D values were observed when comparing various QSPR models, which were most noticeable for the ionised surfactants. Conclusions The slow-stirring method is the most widely applicable experimental method for generating log K ow/D data for all the four surfactant classes. A weight of evidence approach is considered appropriate for non-ionic surfactants using experimental and model predications. However, it is more difficult to apply this approach to ionisable surfactants. Recommendations are made for the preferred existing QSPR predictive methods for determination of log K ow/D values for the surfactant classes. Investigation of newer alternative experimental log K ow methods as well as more biologically relevant and methodologically defensible alternative methods for describing partitioning of surfactants are recommended.

Per- and polyfluoroalkyl substances (PFAS) represent a versatile group of ubiquitously occurring chemicals of increasing regulatory concern. The past years lead to an ever expanding portfolio of detected anthropogenic PFAS in numerous products encountered in daily life. Yet no clear picture of the full range of individual substance that comprise PFAS is available and this challenges analytical and engineering sciences. Authorities struggle to cope with uncertainties in managing risk of harm posed by PFAS. This is a result of an incomplete understanding of the range of compounds that they comprise in differing products. There are analytical uncertainties identifying PFAS and estimating the concentrations of the total PFAS load individual molecules remain unknown. There are four major trends from the chemical perspective that will shape PFAS research for the next decade. Mobility: A wide and dynamic distribution of short chain PFAS due to their high polarity, persistency and volatility.Substitution of regulated substances: The ban or restrictions of individual molecules will lead to a replacement with substitutes of similar concern.Increase in structural diversity of existing PFAS molecules: Introduction of e.g., hydrogens and chlorine atoms instead of fluorine, as well as branching and cross-linking lead to a high versatility of unknown target molecules.Unknown “Dark Matter”: The amount, identity, formation pathways, and transformation dynamics of polymers and PFAS precursors are largely unknown.These directions require optimized analytical setups, especially multi-methods, and semi-specific tools to determine PFAS-sum parameters in any relevant matrix.

"Interpretative Sozialforschung. Eine Einführung" ["Interpretative social research: An Introduction"] by Gabriele ROSENTHAL introduces the methods of and background to interpretative social research. The author describes the roots of interpretative social research, including the work of the Chicago School, of the early "Verstehende Soziologie" in Germany and Austria, and of grounded theory methodology. ROSENTHAL presents participant observation and narrative interviews as the main methods of interpretative social research. Although she also talks about case reconstruction, qualitative content analysis, and other relevant forms of analysis, the book's focus on biographical research—the author's area of interest—means the overall picture appears incomplete . URN: urn:nbn:de:0114-fqs0802216

Der sogenannte Kampf gegen den Terrorismus wird vorwiegend mit Informationen geführt. Mächtig ist, wer sie besitzt und über ihre Verwendung bestimmt. Die Europäische Union hat sich in diesem Kampf mit der Rolle des Erfüllungsgehilfen begnügt. Sie hat Sanktionen gegen einen Mann erlassen, auf Grundlage zweifelhafter amerikanischer Geheimdienstinformationen, in die sie selbst keinen Einblick hatte. Mit dem Kadi II-Urteil verwirft nun der EuGH diese Rollenverteilung endgültig als Verstoß gegen europäische Grundrechte. Die Entscheidung, der zwölf Jahre rechtlicher Auseinandersetzung in unterschiedlichen Foren vorausgingen, zeichnet ein grelles Bild der von vernetzten Exekutiven dominierten „Neuen Weltordnung“. Sie zeigt indes auch einen Gerichtshof, der – vor der öffentlichen Aufmerksamkeit versteckt im Märchenland Luxemburg und nach Meinung mancher angeblich ohne die Legitimität und den Willen zu einer ernsthaften Grundrechtsrechtsprechung – zum bedeutenden Akteur in der Auseinandersetzung zwischen Freiheit und Sicherheit gereift ist.

Wenig lässt sich so verlässlich vorhersagen wie der Verlauf des politischen Diskurses. Es war daher nur eine Frage der Zeit, bis die Toten von Paris (erneut) instrumentalisiert würden. Die Rede sei hier nicht von abendländischen Demonstranten in Dresden und anderswo, auch nicht von manch einem Sicherheitspolitiker, der seit Jahren bei jeder Gelegenheit dieselben Behauptungen wiederholt. Angesprochen seien stattdessen einige Zeitgenossen, die offenbar durch die weltweite Solidarisierung das (Vor-)Urteil „Lügenpresse“ revidiert und sich wieder im Aufwind sehen. Sie bedienen sich einer altbewährten Textgattung: der Kolumne. Diese erlaubt es ihnen, in mehr oder weniger gehobener Form dasselbe zu tun wie ihre tumben Kritiker auf Dresdner Straßen: eine von Fakten weitgehend unbeeinflusste Meinung in die Welt zu setzen.

Welch gravierendes Versäumnis ist dem EuGH im PSPP-Fall unterlaufen, dass sein Urteil der Senatsmehrheit im BVerfG als „schlechterdings nicht mehr nachvollziehbar“ , „methodisch nicht mehr vertretbar“ und „objektiv willkürlich“ gilt? Im Kern lautet der Vorwurf, der EuGH habe den Verhältnismäßigkeitsgrundsatz verkannt. Indes ergeben sich bei näherem Hinsehen erhebliche Zweifel am so drastisch formulierten Befund.

Der Tagespresse lässt sich entnehmen, dass ein „Bündnis Bürgerwille“ vor dem Bundesverfassungsgericht gegen „die Finanzierung der EU-Corona-Hilfen“ vorgehe. Hierzu sei eine Verfassungsbeschwerde nebst Antrag auf einstweilige Anordnung angekündigt. Damit verbunden sei eine Bitte an das Gericht, den Bundespräsidenten darum zu ersuchen, „der ständigen Staatspraxis entsprechend“, das betreffende Gesetz vorläufig nicht auszufertigen. Was steckt dahinter?