Simulating Electromagnetic Cascades in Magnetospheres of Active Galactic Nuclei

Context: At the low accretion-rates typical for BL Lac-objects, magnetospheres of active galactic nuclei can develop vacuum gaps with strong electric fields accelerating charged seed particles parallel to the magnetic fields up to ultra-relativistic energies. The seed particles sustain electromagnetic cascades by inverse-Compton-scattering and subsequent pair-production in soft background-radiation-fields from the accretion-disk and/or photo-ionised clouds, along the direction of the primary particle beams. Method: The one-dimensional kinetic equation describing this linear inverse-Compton-Klein-Nishina-pair-cascade is inferred. We have developed a novel code, that can numerically solve this kinetic equation for an ample variety of input-parameters. By this, quasi-stationary particle- and photon-spectra are obtained. Application: We use the code to model the cascaded interaction of electrons, that have been accelerated in a vacuum gap in the magnetosphere of Mrk 501, with Lyman-alpha-photons. The resulting spectrum on top of a synchrotron-self-Compton-background can cause a narrow TeV-bump in the spectrum of Mrk 501.Comment: 6 pages, 3 figures, 1 table, Contribution to the 6th International Symposium on High-Energy Gamma-Ray Astronomy (Gamma2016), Heidelberg, Germany. To be published in the AIP Conference Proceeding

Design und Aufbau eines Szintillationsdetektors zur Identifizierung geladener Teilchen im Crystal-Barrel-Vorwärtsdetektor

Ein Ziel des Crystal-Barrel-Experimentes an ELSA ist es, die Struktur der Baryonen besser zu verstehen. Hierzu werden Baryonresonanzen über die Wechselwirkung von hochenergetischen Photonen mit Nukleonen angeregt und die Reaktionsprodukte in den verschiedenen Detektoren des Crystal-Barrel-Experimentes nachgewiesen. Durch den Aufbau als fixed target-Experiment ist dabei unter kleinen Polarwinkeln eine deutlich erhöhte Rate an Reaktionsprodukten zu verzeichnen. Für das Crystal-Barrel-Experiment wurde im Rahmen des transregionalen Sonderforschungsbereiches SFB/TR16 zwischen 2003 und 2006 ein Vorwärtskalorimeter aufgebaut, das den Polarwinkelbereich von 11,2° - 27,5° im Laborsystem abdeckt. Da für die Analyse der gewonnenen Messdaten eine sichere Identifizierung geladener Teilchen unabdingbar ist, wurde im Rahmen der vorliegenden Arbeit ein Subdetektor zur Identifikation geladener Teilchen entworfen, gebaut und in Betrieb genommen. Der aus 180 Plastikszintillatoren bestehende Detektor wird dabei über wellenlängenschiebende Fasern ausgelesen. Diese sind an thermoplastisch verformte, klare Kunststofffasern gekoppelt, die Detektion der Signale geschieht mittels Multianodenphotomultipliern. Der gesamte Subdetektor wurde als modulare, selbsttragende Struktur entwickelt. Durch einen zweilagigen, in φ versetzten Aufbau verdoppelt er die Winkelauflösung des Vorwärtsdetektors, sie beträgt damit für geladene Teilchen 6° in ? und φ. Die einzelnen Treffer können mit einer Zeitauflösung von σ=1,7 ns erkannt und anschließend Treffern im Kalorimeter des Vorwärtsdetektors zugeordnet werden. Weiterhin ermöglicht er mit seiner mittleren Detektionseffizienz von 94% und seiner nach 100 ns vorliegenden Trefferinformation stabile Zählrateninformationen und einen möglichen first Level Trigger auf geladene Teilchen im Vorwärtsdetektor. Der Detektor wird seit 2007 erfolgreich bei der Messung von Doppelpolarisationsobservablen eingesetzt.</p

Controllable Acoustic Mixing of Fluids in Microchannels for the Fabrication of Therapeutic Nanoparticles

Fifteen years ago, surface acoustic waves (SAW) were found to be able to drive fluids and numerous applications in microfluidics have been developed since. Here, we review the progress made and report on new approaches in setting-up microfluidic, continuous flow acoustic mixing. In a microchannel, chaotic advection is achieved by generation of a SAW driven fluid jet perpendicular to the mean flow direction. Using a high speed video camera and particle image velocimetry, we measure the flow velocities and show that mixing is achieved in a particularly controllable and fast way. The mixing quality is determined as a function of system parameters: SAW power, volume flux and fluid viscosity. Exploring the parameter space of mixing provides a practical guide for acoustic mixing in microchannels and allows for adopting conditions to different solvents, as e.g., required for the generation of nanoscale particles from alcoholic phases. We exemplarily demonstrate the potential of SAW based continuous flow mixing for the production of therapeutic nucleic acid nanoparticles assembled from polymer and lipid solutions

Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort

Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m$^{2}$ body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pH$_{min}$ 7.3 (7.18–7.31), HCO3−$_{min}$ 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Are people who participate in cultural activities more satisfied with life?

The influence of various aspects of life on wellbeing has been extensively researched. However, despite little empirical evidence, participation in leisure activities has been assumed to increase subjective wellbeing. Leisure is important because it is more under personal control than other sources of life satisfaction. This study asked whether people who participate in cultural leisure activities have higher life satisfaction than people who do not, if different types of leisure have the same influence on life satisfaction and if satisfaction is dependent on the frequency of participation or the number of activities undertaken. It used data from UKHLS Survey to establish associations between type, number and frequency of participation in leisure activities and life satisfaction. Results showed an independent and positive association of participation in sport, heritage and active-creative leisure activities and life satisfaction but not for participation in popular entertainment, theatre hobbies and museum/galleries. The association of reading hobbies and sedentary-creative activities and life satisfaction was negative. High life satisfaction was associated with engaging in a number of different activities rather than the frequency of participation in each of them. The results have implications for policy makers and leisure services providers, in particular those associated with heritage recreation. Subjective wellbeing measures, such as life satisfaction, and not economic measures alone should be considered in the evaluation of services. The promotion of leisure activities which are active and promote social interaction should be considered in programmes aimed at improving the quality of life

Outcomes of patients with acute respiratory failure on veno-venous extracorporeal membrane oxygenation requiring additional circulatory support by veno-venoarterial extracorporeal membrane oxygenation

ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28–57) years and SOFA score was 14 (12–17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12–123) at V-VA ECMO upgrade to 9 (3–37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6–22) days and ICU length of stay was 32 (16–46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score &gt; 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score &gt; 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome

Carboxyhemoglobin predicts oxygenator performance and imminent oxygenator change in extracorporeal membrane oxygenation

Background The continuous exposure of blood to a non-biological surface during extracorporeal membrane oxygenation (ECMO) may lead to progressive thrombus formation in the oxygenator, hemolysis and consequently impaired gas exchange. In most centers oxygenator performance is monitored only on a once daily basis. Carboxyhemoglobin (COHb) is generated upon red cell lysis and is routinely measured with any co-oximetry performed to surveille gas exchange and acid–base homeostasis every couple of hours. This retrospective cohort study aims to evaluate COHb in the arterial blood gas as a novel marker of oxygenator dysfunction and its predictive value for imminent oxygenator change. Results Out of the 484 screened patients on ECMO 89, cumulatively requiring 116 oxygenator changes within 1833 patient days, including 19,692 arterial COHb measurements were analyzed. Higher COHb levels were associated with lower post-oxygenator pO$_{2}$ (estimate for log(COHb): − 2.176 [95% CI − 2.927, − 1.427], p < 0.0001) and with a shorter time to oxygenator change (estimate for log(COHb): − 67.895 [95% CI − 74.209, − 61.542] hours, p < 0.0001). COHb was predictive of oxygenator change within 6 h (estimate for log(COHb): 5.027 [95% CI 1.670, 15.126], p = 0.004). Conclusion COHb correlates with oxygenator performance and can be predictive of imminent oxygenator change. Therefore, longitudinal measurements of COHb in clinical routine might be a cheap and more granular candidate for ECMO surveillance that should be further analyzed in a controlled prospective trial design