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Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study
(2020)
Objectives: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium.
Design: Prospective observational study.
Setting: Single-centre at a European academic hospital.
Primary: and secondary outcome measures In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD.
Results: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD.
Conclusions: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD.
Measurement of inclusive J/ψ polarization in p + p collisions at √s=200 GeV by the STAR experiment
(2020)
We report on new measurements of inclusive 𝐽/𝜓 polarization at midrapidity in 𝑝+𝑝 collisions at √𝑠=200 GeV by the STAR experiment at the Relativistic Heavy Ion Collider. The polarization parameters, 𝜆𝜃, 𝜆𝜙, and 𝜆𝜃𝜙, are measured as a function of transverse momentum (𝑝T) in both the helicity and Collins-Soper (CS) reference frames within 𝑝T<10 GeV/𝑐. Except for 𝜆𝜃 in the CS frame at the highest measured 𝑝T, all three polarization parameters are consistent with 0 in both reference frames without any strong 𝑝T dependence. Several model calculations are compared with data, and the one using the Color Glass Condensate effective field theory coupled with nonrelativistic QCD gives the best overall description of the experimental results, even though other models cannot be ruled out due to experimental uncertainties.
Measurement of inclusive charged-particle jet production in Au + Au collisions at √sNN=200 GeV
(2020)
The STAR Collaboration at the Relativistic Heavy Ion Collider reports the first measurement of inclusive jet production in peripheral and central Au+Au collisions at √𝑠𝑁𝑁=200 GeV. Jets are reconstructed with the anti-𝑘𝑇 algorithm using charged tracks with pseudorapidity |𝜂|<1.0 and transverse momentum 0.2<𝑝ch
𝑇,jet<30 GeV/𝑐, with jet resolution parameter 𝑅=0.2, 0.3, and 0.4. The large background yield uncorrelated with the jet signal is observed to be dominated by statistical phase space, consistent with a previous coincidence measurement. This background is suppressed by requiring a high-transverse-momentum (high-𝑝𝑇) leading hadron in accepted jet candidates. The bias imposed by this requirement is assessed, and the 𝑝𝑇 region in which the bias is small is identified. Inclusive charged-particle jet distributions are reported in peripheral and central Au+Au collisions for 5<𝑝ch
𝑇,jet<25 GeV/𝑐 and 5<𝑝ch
𝑇,jet<30 GeV/𝑐, respectively. The charged-particle jet inclusive yield is suppressed for central Au+Au collisions, compared to both the peripheral Au+Au yield from this measurement and to the 𝑝𝑝 yield calculated using the PYTHIA event generator. The magnitude of the suppression is consistent with that of inclusive hadron production at high 𝑝𝑇 and that of semi-inclusive recoil jet yield when expressed in terms of energy loss due to medium-induced energy transport. Comparison of inclusive charged-particle jet yields for different values of 𝑅 exhibits no significant evidence for medium-induced broadening of the transverse jet profile for 𝑅 <0.4 in central Au+Au collisions. The measured distributions are consistent with theoretical model calculations that incorporate jet quenching.
We report on the measurement of the Central Exclusive Production of charged particle pairs h+h− (h = π, K, p) with the STAR detector at RHIC in proton-proton collisions at √s = 200 GeV. The charged particle pairs produced in the reaction pp → p′ + h+h− + p′ are reconstructed from the tracks in the central detector and identified using the specific energy loss and the time of flight method, while the forward-scattered protons are measured in the Roman Pot system. Exclusivity of the event is guaranteed by requiring the transverse momentum balance of all four final-state particles. Differential cross sections are measured as functions of observables related to the central hadronic final state and to the forward-scattered protons. They are measured in a fiducial region corresponding to the acceptance of the STAR detector and determined by the central particles’ transverse momenta and pseudorapidities as well as by the forward-scattered protons’ momenta. This fiducial region roughly corresponds to the square of the four-momentum transfers at the proton vertices in the range 0.04 GeV2 < −t1, −t2 < 0.2 GeV2, invariant masses of the charged particle pairs up to a few GeV and pseudorapidities of the centrally-produced hadrons in the range |η| < 0.7. The measured cross sections are compared to phenomenological predictions based on the Double Pomeron Exchange (DPE) model. Structures observed in the mass spectra of π+π− and K+K− pairs are consistent with the DPE model, while angular distributions of pions suggest a dominant spin-0 contribution to π+π− production. For π+π− production, the fiducial cross section is extrapolated to the Lorentz-invariant region, which allows decomposition of the invariant mass spectrum into continuum and resonant contributions. The extrapolated cross section is well described by the continuum production and at least three resonances, the f0(980), f2(1270) and f0(1500), with a possible small contribution from the f0(1370). Fits to the extrapolated differential cross section as a function of t1 and t2 enable extraction of the exponential slope parameters in several bins of the invariant mass of π+π− pairs. These parameters are sensitive to the size of the interaction region.
We report results on the total and elastic cross sections in proton-proton collisions at √s = 200 GeV obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section was measured in the squared four-momentum transfer range 0.045 ≤ −t ≤ 0.135 GeV2. The value of the exponential slope parameter B of the elastic differential cross section dσ/dt ∼ e−Bt in the measured −t range was found to be B = 14.32 ± 0.09(stat.)+0.13 −0.28(syst.) GeV−2. The total cross section σtot, obtained from extrapolation of the dσ/dt to the optical point at −t = 0, is σtot = 54.67 ± 0.21(stat.)+1.28 −1.38(syst.) mb. We also present the values of the elastic cross section σel = 10.85 ± 0.03(stat.)+0..49 −0.41(syst.) mb, the elastic cross section integrated within the STAR t-range σ det el = 4.05 ± 0.01(stat.)+0.18−0.17(syst.) mb, and the inelastic cross section σinel = 43.82 ± 0.21(stat.)+1.37−1.44(syst.) mb. The results are compared with the world data
Investigation of the linear and mode-coupled flow harmonics in Au+Au collisions at √sNN = 200 GeV
(2020)
Flow harmonics (vn) of the Fourier expansion for the azimuthal distributions of hadrons are commonly employed to quantify the azimuthal anisotropy of particle production relative to the collision symmetry planes. While lower order Fourier coefficients (v2 and v3) are more directly related to the corresponding eccentricities of the initial state, the higher-order flow harmonics (vn>3) can be induced by a modecoupled response to the lower-order anisotropies, in addition to a linear response to the same-order anisotropies. These higher-order flow harmonics and their linear and mode-coupled contributions can be used to more precisely constrain the initial conditions and the transport properties of the medium in theoretical models. The multiparticle azimuthal cumulant method is used to measure the linear and mode-coupled contributions in the higher-order anisotropic flow, the mode-coupled response coefficients, and the correlations of the event plane angles for charged particles as functions of centrality and transverse momentum in Au+Au collisions at nucleon-nucleon center-of-mass energy √sN N= 200 GeV. The results are compared to similar LHC measurements as well as to several viscous hydrodynamic calculations with varying initial conditions.
Measurement of groomed jet substructure observables in p+p collisions at √s = 200 GeV with STAR
(2020)
In this letter, measurements of the shared momentum fraction (zg) and the groomed jet radius (Rg), as defined in the SoftDrop algorithm, are reported in p+p collisions at √s = 200 GeV collected by the STAR experiment. These substructure observables are differentially measured for jets of varying resolution parameters from R = 0.2 − 0.6 in the transverse momentum range 15 < pT,jet < 60 GeV/c. These studies show that, in the pT,jet range accessible at √s = 200 GeV and with increasing jet resolution parameter and jet transverse momentum, the zg distribution asymptotically converges to the DGLAP splitting kernel for a quark radiating a gluon. The groomed jet radius measurements reflect a momentum-dependent narrowing of the jet structure for jets of a given resolution parameter, i.e., the larger the pT,jet, the narrower the first splitting. For the first time, these fully corrected measurements are compared to Monte Carlo generators with leading order QCD matrix elements and leading log in the parton shower, and to state-of-the-art theoretical calculations at next-to-leading-log accuracy. We observe that PYTHIA 6 with parameters tuned to reproduce RHIC measurements is able to quantitatively describe data, whereas PYTHIA 8 and HERWIG 7, tuned to reproduce LHC data, are unable to provide a simultaneous description of both zg and Rg, resulting in opportunities for fine parameter tuning of these models for p+p collisions at RHIC energies. We also find that the theoretical calculations without non-perturbative corrections are able to qualitatively describe the trend in data for jets of large resolution parameters at high pT,jet, but fail at small jet resolution parameters and low jet transverse momenta.
Two-particle angular correlations were measured in pp collisions at s√=7 TeV for pions, kaons, protons, and lambdas, for all particle/anti-particle combinations in the pair. Data for mesons exhibit an expected peak dominated by effects associated with mini-jets and are well reproduced by general purpose Monte Carlo generators. However, for baryon-baryon and anti-baryon--anti-baryon pairs, where both particles have the same baryon number, a near-side anti-correlation structure is observed instead of a peak. This effect is interpreted in the context of baryon production mechanisms in the fragmentation process. It currently presents a challenge to Monte Carlo models and its origin remains an open question.
Zur Reform der Einlagensicherung: Elemente einer anreizkompatiblen Europäischen Rückversicherung
(2020)
Bankeinlagen bis 100.000 Euro sind de jure überall im Euroraum gleichermaßen vor Verlusten geschützt. De facto hängt der Wert dieser gesetzlichen Haftungszusage unter anderem von der Ausstattung des nationalen Sicherungsfonds und der relativen Größe des Bankensektors in einer Volkswirtschaft ab. Um die Homogenität des Einlagenschutzes zu gewährleisten und die Bankenunion zu vollenden, bedarf es einer einheitlichen europäischen Einlagensicherung. Die bestehende implizite Risikoteilung im Euroraum ist ordnungspolitisch nicht wünschenswert. Ferner kann eine explizite und glaubwürdige Zweitsicherung Fehlanreize zur Übernahme exzessiver Risiken verhindern, bevor es zum Schadensfall kommt. Daher plädiert dieser Beitrag für ein zweistufiges, streng subsidiär organisiertes Rückversicherungsmodell: Nationale Erstversicherungen würden einen festgeschriebenen Teil, die europäische Rückversicherung nachrangig den Rest der Deckungssumme besichern. Die Rückversicherung gewährt diese Liquiditätshilfen in Form von Kassenkrediten. Weil die Haftung auf nationaler Ebene verbleibt, werden Risiken geteilt aber nicht vergemeinschaftet. Marktgerechte Prämien müssen nicht nur das individuelle Risikogewicht einer Bank sondern auch länderspezifische Risikofaktoren berücksichtigen. Zuletzt braucht der Rückversicherer umfangreiche Aufsichtsrechte, um die Zahlungsfähigkeit der Erstversicherer mit Hinblick auf die nationalen Haftungspflichten jederzeit sicherzustellen.
Der Inhalt dieser Arbeit ist die Entwicklung und Evaluation einer mobilen Webanwendung für die Annotation von Texten. Dem Benutzer ist es durch diese Webanwendung, im folgenden auch MobileAnnotator genannt, möglich Wörter und Textausschnitte zu kategorisieren oder auch mit Wissensquellen, zum Beispiel Wikipedia, zu verknüpfen. Der MobileAnnotator ist dabei für mobile Endgeräte ausgelegt und insbesondere für Smartphones optimiert worden.
Für die Funktionalität verwendet der MobileAnnotator die Architektur des bereits existierenden und etablierten TextAnnotators. Dieser stellt bereits eine Vielzahl von Annotations Werkzeugen bereit, von denen zwei auf den MobileAnnotator übertragen wurden. Da der TextAnnotator vollständig für einen Desktopbetrieb ausgelegt wurde, ist es jedoch nicht möglich diese Werkzeuge ohne Anpassungen für ein mobiles Gerät umzubauen. Der MobileAnnotator beschränkt sich somit auf ein Mindestmaß an Funktionen dieser Werkzeuge um sie dem Benutzer in geeigneter Art und Weise verfügbar zu machen.
Für die Evaluation der Benutzerfreundlichkeit des MobileAnnotator und dessen Werkzeuge wurde anschließend eine Studie durchgeführt. Den Probanten war es innerhalb der Studie möglich Aussagen über die Bedienbarkeit des MobileAnnotators zu treffen und einen Vergleich zwischen dem Mobile- und TextAnnotator zu ziehen.
Enthält 2 Teile:
Oliva Menozzi: Introduction S. 1-10
Gloria Adinolfi, Silvano Agostini, Valentina Belfiore, Rodolfo Carmagnola, Maria Violeta Carniel, Vincenzo d’Ercole, Rocco D’Errico, Maria Giorgia Di Antonio, Eugenio Di Valerio, Maria Emilia Masci, Maria CristinaMancini, Oliva Menozzi, Donato Palumbo, Ilaria Zelante: Le metodologie, il team risultati preliminari del digital imaging. S. 11-52
Monitoring is an indispensable tool for the operation of any large installation of grid or cluster computing, be it high energy physics or elsewhere. Usually, monitoring is configured to collect a small amount of data, just enough to enable detection of abnormal conditions. Once detected, the abnormal condition is handled by gathering all information from the affected components. This data is processed by querying it in a manner similar to a database.
This contribution shows how the metaphor of a debugger (for software applications) can be transferred to a compute cluster. The concepts of variables, assertions and breakpoints that are used in debugging can be applied to monitoring by defining variables as the quantities recorded by monitoring and breakpoints as invariants formulated via these variables. It is found that embedding fragments of a data extracting and reporting tool such as the UNIX tool awk facilitates concise notations for commonly used variables since tools like awk are designed to process large event streams (in textual representations) with bounded memory. A functional notation similar to both the pipe notation used in the UNIX shell and the point-free style used in functional programming simplify the combination of variables that commonly occur when formulating breakpoints.
The production of Ξ(1321)− and Ξ¯¯¯¯(1321)+ hyperons in inelastic p+p interactions is studied in a fixed target experiment at a beam momentum of 158 GeV/c. Double differential distributions in rapidity y and transverse momentum pT are obtained from a sample of 33M inelastic events. They allow to extrapolate the spectra to full phase space and to determine the mean multiplicity of both Ξ− and Ξ¯¯¯¯+. The rapidity and transverse momentum spectra are compared to transport model predictions. The Ξ− mean multiplicity in inelastic p+p interactions at 158 GeV/c is used to quantify the strangeness enhancement in A+A collisions at the same centre-of-mass energy per nucleon pair.
A measurement of charged hadron pair correlations in two-dimensional ηφ space is presented. The analysis is based on total 30 million central Be + Be collisions observed in the NA61/SHINE detector at the CERN SPS for incident beam momenta of 19A, 30A, 40A, 75A, and 150A GeV/c. Measurements were carried out for unlike-sign and like-sign charge hadron pairs independently. The C(η, φ) correlation functions were compared with results from a similar analysis on p + p interactions at similar beam momenta per nucleon. General trends of the backto-back correlations are similar in central Be + Be collisions and p + p interactions, but are suppressed in magnitude due to the increased combinatorial background. Predictions from the Epos and UrQMD models are compared to the measurements. Evolution of an enhancement around (η, φ) = (0, 0) with incident energy is observed in central Be + Be collisions. It is not predicted by both models and almost non-existing in proton–proton collisions at the same momentum per nucleon.
In der vorliegenden Studie wurden Patienten mit struktureller Epilepsie bedingt durch eine fokale kortikale Dysplasie (FCD) mittels moderner Magnetresonanztomographie (MRT)-Verfahren untersucht.
Bei FCDs handelt es sich um Fehlbildungen der Großhirnrinde, die mit einer hohen epileptogenen Aktivität vergesellschaftet sind. Einige dieser Patienten unterziehen sich einer epilepsiechirurgischen Resektion, sind jedoch hiernach hinsichtlich ihrer Anfallsfrequenz dennoch nicht ausreichend kontrollierbar, weshalb Grund zur Annahme besteht, dass es neben der fokalen kortikalen Dysplasie andere Faktoren geben könnte, die epileptische Anfälle verursachen.
Basierend auf dieser Überlegung wurde mittels T2-Relaxometrie untersucht, ob bei Patienten mit FCDs mikrostrukturelle Veränderungen in Teilen des Kortex vorhanden sind, die mittels konventioneller MRT-Verfahren normal bzw. gesund erscheinen. Es wird angenommen, dass bei diesen Patienten auch außerhalb der FCD mikrostrukturelle Veränderungen, beispielsweise bedingt durch Schädigung im Rahmen von Anfällen oder durch Therapieeffekte, vorzufinden sind.
Für die Studie wurden 16 Patienten mit einer neuroradiologisch gesicherten FCD und 16 hinsichtlich des Alters und des Geschlechts gematchte gesunde Probanden rekrutiert.
Die Daten wurden an einem 3 Tesla (T) MRT-Scanner erhoben. Um die T2-Relaxationszeit zu messen, wurden Spin-Echo Datensätze mit verschiedenen Echozeiten (TE) aufgezeichnet. Zur Erfassung der Ausdehnung der FCD wurden konventionelle fluid-attenuated inversion recovery (FLAIR)-Datensätze akquiriert. Zur Segmentierung des Gewebes wurden synthetische T1-gewichtete magnetization-prepared rapid acquisition of gradient echos (MP-RAGE)-Datensätze aus quantitativen T1-Karten berechnet. Der Kortex und dessen Grenzflächen wurden mittels FreeSurfer anhand der MP-RAGE-Datensätze identifiziert und die kortikale Dicke wurde gemessen. Die FCD-Areale wurden in den FLAIR-Datensätzen manuell markiert und aus den T2-Karten exkludiert, um die FCD-assoziierten Veränderungen nicht in die Analyse einzubeziehen.
Anschließend wurden kortikale T2-Werte ausgelesen und in Oberflächendatensätzen gespeichert, um dann durchschnittliche kortikale T2-Werte für jeden Probanden zu ermitteln und mittels ungepaartem t-Test zwischen den Gruppen zu vergleichen. Zudem wurde der Pearson-Korrelationskoeffizient zwischen den kortikalen T2 Werten und klinischen Parametern berechnet. Außerdem wurde eine oberflächenbasierte Gruppenanalyse kortikaler T2-Werte und der kortikalen Dicke durchgeführt. Hierbei wurden Permutationssimulationen durchgeführt, um kortikale Cluster zu erkennen, die fokale Gruppenunterschiede anzeigen, und um für Mehrfachvergleiche zu korrigieren.
Die Analyse ergab, dass die durchschnittlichen kortikalen T2-Werte außerhalb der FCD in der Patientenkohorte im Vergleich zu den gesunden Probanden signifikant erhöht waren. Diese T2-Veränderungen zeigten weder eine signifikante Korrelation mit der Anzahl der Anfälle der letzten drei Monate, noch mit der Anzahl der jemals eingenommenen antiepileptischen Medikamente. Insbesondere wurden T2-Erhöhungen in den frontalen, parietalen und manchen temporalen Regionen festgestellt. Die oberflächenbasierte Analyse der Kortexdicke zeigte keine signifikanten Gruppenunterschiede.
Mittels T2-Relaxometrie und oberflächenbasierten Analyse-Techniken wurden demnach T2-Veränderungen des mittels konventioneller MRT-Bildgebung unauffällig erscheinenden zerebralen Kortex bei Patienten mit FCD und Epilepsie festgestellt.
Die Ergebnisse deuten auf das Vorhandensein von mikrostrukturellen Veränderungen hin, die sich mit konventionellen MRT-Verfahren nicht erfassen lassen. Potentielle Ursachen dieser Veränderungen sind neben Effekten der antikonvulsiven Medikation möglicherweise auch gliotischer Gewebeumbau bedingt durch stattgehabte epileptische Anfälle. Die Studie legt nahe, dass strukturelle Epilepsien mehr als ein Symptom bedingt durch eine fokale Läsion sind und stattdessen das Gehirn als Ganzes betreffen.
Cortical changes in epilepsy patients with focal cortical dysplasia: new insights with T2 mapping
(2020)
Background: In epilepsy patients with focal cortical dysplasia (FCD) as the epileptogenic focus, global cortical signal changes are generally not visible on conventional MRI. However, epileptic seizures or antiepileptic medication might affect normal-appearing cerebral cortex and lead to subtle damage. Purpose: To investigate cortical properties outside FCD regions with T2-relaxometry. Study Type: Prospective study. Subjects: Sixteen patients with epilepsy and FCD and 16 age-/sex-matched healthy controls. Field Strength/Sequence: 3T, fast spin-echo T2-mapping, fluid-attenuated inversion recovery (FLAIR), and synthetic T1-weighted magnetization-prepared rapid acquisition of gradient-echoes (MP-RAGE) datasets derived from T1-maps. Assessment: Reconstruction of the white matter and cortical surfaces based on MP-RAGE structural images was performed to extract cortical T2 values, excluding lesion areas. Three independent raters confirmed that morphological cortical/juxtacortical changes in the conventional FLAIR datasets outside the FCD areas were definitely absent for all patients. Averaged global cortical T2 values were compared between groups. Furthermore, group comparisons of regional cortical T2 values were performed using a surface-based approach. Tests for correlations with clinical parameters were carried out. Statistical Tests: General linear model analysis, permutation simulations, paired and unpaired t-tests, and Pearson correlations. Results: Cortical T2 values were increased outside FCD regions in patients (83.4 ± 2.1 msec, control group 81.4 ± 2.1 msec, P = 0.01). T2 increases were widespread, affecting mainly frontal, but also parietal and temporal regions of both hemispheres. Significant correlations were not observed (P ≥ 0.55) between cortical T2 values in the patient group and the number of seizures in the last 3 months or the number of anticonvulsive drugs in the medical history. Data Conclusion: Widespread increases in cortical T2 in FCD-associated epilepsy patients were found, suggesting that structural epilepsy in patients with FCD is not only a symptom of a focal cerebral lesion, but also leads to global cortical damage not visible on conventional MRI. Evidence Level: 21. Technical efficacy Stage: 3 J. MAGN. RESON. IMAGING 2020;52:1783–1789.
Fallzahlaufkommen und Qualitätsindikatoren bei der Versorgung des abdominellen Bauchaortenaneurysmas
(2020)
Hintergrund: Der MTL30 (Mortalität, Transfer, Liegezeit) wurde als Surrogatparameter zur Evaluation der Qualität potenziell komplikationsträchtiger viszeralchirurgischer Eingriffe vorgeschlagen.
Zielsetzung: Es wurde überprüft, inwieweit sich der MTL30 zu den Ergebnissen des Bauchaortenaneurysma(AAA)-Registers des Deutschen Instituts für Gefäßmedizinische Gesundheitsforschung (DIGG) der Deutschen Gesellschaft für Gefäßchirurgie und Gefäßmedizin (DGG) und zum Fallaufkommen der Kliniken korrelieren lässt.
Material und Methoden: Insgesamt 14.282 Patienten wurden endovaskulär (EVAR) und 3923 Patienten offen (OAR) elektiv wegen eines AAA versorgt. Bestimmt wurden Fallaufkommen der behandelnden Kliniken, Klinikletalität, Liegezeit und Verlegung in ein anderes Akutkrankenhaus 30 Tage nach dem Indexeingriff.
Ergebnisse: Die Klinikletalität machte bei EVAR 1,3 %, bei OAR 4,9 % aus (p = 0,000), der MTL30 5,0 % vs. 14,4 % (p = 0,000). Für EVAR ließ sich keine Beziehung zwischen Fallaufkommen und Klinikletalität (Quintile 1: 1,0 %; Quintile 5: 1,3 %) sowie Fallaufkommen und MTL30 (Quintile 1: 5,3 %; Quintile 5: 5,3 %) nachweisen. Auch bei OAR bestand keine signifikante Beziehung zwischen Fallaufkommen und Klinikletalität (Quintile 1: 5,8 %, Quintile 5: 3,5 %; p = 0,505) und Fallaufkommen und MTL30 (Quintile 1: 16,4 %, Quintile 5: 12,2 %, p = 0,110). Bei einer Klinikletalität von 7,2 (5–10) % betrug der MTL30 bei OAR 17,6 %. Sowohl bei EVAR als auch bei OAR korrelierte die stationäre Aufenthaltsdauer signifikant mit Klinikletalität und MTL30.
Diskussion: Eine eindeutige Beziehung zwischen Krankenhausfallaufkommen und Klinikletalität ließ sich im AAA-Register des DIGG nicht aufzeigen. Das gleiche galt für den MTL30. Ob demnach der MTL30 gegenüber der Erfassung von Klinikletalität und stationärer Liegezeit als Qualitätsparameter einen Zusatznutzen bietet, muss offenbleiben.
Über problematische Straßennamen und Denkmäler wird politisch debattiert. Wie der öffentliche Raum aussieht, wird gemeinhin nicht als juristische Frage behandelt. Trotzdem taucht die Frage, was die Gesellschaft im öffentlichen Raum sehen will, auch als rechtliches Argument auf. Wann erkennt der Diskurs solche Fragen politischer Ästhetik als juristisches Argument an? Und welche Bedingungen entscheiden darüber?
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
Aim: The aim of this study is to utilize the niche measurement guidelines outlined by Jordans et al. in order to establish normal values and accurate description of caesarean section scars in a normal population. After defining the normal distribution, abnormal pregestational scar characteristics will be identified for predicting adverse pregnancy outcomes. Methods: This is a prospective observational multicenter clinical study where women with a history of only one caesarean section and yet open family planning are enrolled. The uterine length, cervical length, niche length, niche depth, niche width, residual myometrial thickness, endometrial thickness, scar to internal os distance, anterior myometrial thickness superior and inferior to the scar and the posterior myometrial thickness opposite the scar, superior and inferior to it are measured in a pregestational uterus. The lower uterine segment is measured over a length of 3 cm during subsequent pregnancy and followed up until delivery. Results: Data from 500 patients will yield normal distribution curves for all predefined measurements. Establishing a correlation between deviations from the normal measures and adverse events would be instrumental for counseling women regarding subsequent pregnancy and mode of delivery.
Conclusion: This study will demonstrate the changes of the post-caesarean scar from a non-pregnant uterus until delivery and can confirm the importance of the scar characteristics in predicting pregnancy outcome.
Accurate neutron capture cross section data for minor actinides (MAs) are required to estimate the production and transmutation rates of MAs in light water reactors with a high burnup, critical fast reactors like Gen-IV systems and other innovative reactor systems such as accelerator driven systems (ADS). Capture reactions of 244Cm open the path for the formation of heavier Cm isotopes and of heavier elements such as Bk and Cf. In addition, 244Cm shares nearly 50% of the total actinide decay heat in irradiated reactor fuels with a high burnup, even after three years of cooling.
Experimental data for this isotope are very scarce due to the difficulties of providing isotopically enriched samples and because the high intrinsic activity of the samples requires the use of neutron facilities with high instantaneous flux. The only two previous experimental data sets for this neutron capture cross section have been obtained in 1969 using a nuclear explosion and, more recently, at J-PARC in 2010. The neutron capture cross sections have been measured at n_TOF with the same samples that the previous experiments in J-PARC. The samples were measured at n_TOF Experimental Area 2 (EAR-2) with three C6D6 detectors and also in Experimental Area 1 (EAR-1) with the Total Absorption Calorimeter (TAC). Preliminary results assessing the quality and limitations of these new experimental datasets are presented for the experiments in both areas. Preliminary yields of both measurements will be compared with evaluated libraries for the first time.
We develop a novel empirical approach to identify the effectiveness of policies against a pandemic. The essence of our approach is the insight that epidemic dynamics are best tracked over stages, rather than over time. We use a normalization procedure that makes the pre-policy paths of the epidemic identical across regions. The procedure uncovers regional variation in the stage of the epidemic at the time of policy implementation. This variation delivers clean identification of the policy effect based on the epidemic path of a leading region that serves as a counterfactual for other regions. We apply our method to evaluate the effectiveness of the nationwide stay-home policy enacted in Spain against the Covid-19 pandemic. We find that the policy saved 15.9% of lives relative to the number of deaths that would have occurred had it not been for the policy intervention. Its effectiveness evolves with the epidemic and is larger when implemented at earlier stages.
In this paper, we discuss the damping of density oscillations in dense nuclear matter in the temperature range relevant to neutron star mergers. This damping is due to bulk viscosity arising from the weak interaction “Urca” processes of neutron decay and electron capture. The nuclear matter is modelled in the relativistic density functional approach. The bulk viscosity reaches a resonant maximum close to the neutrino trapping temperature, then drops rapidly as temperature rises into the range where neutrinos are trapped in neutron stars. We investigate the bulk viscous dissipation timescales in a post-merger object and identify regimes where these timescales are as short as the characteristic timescale ∼10 ms, and, therefore, might affect the evolution of the post-merger object. Our analysis indicates that bulk viscous damping would be important at not too high temperatures of the order of a few MeV and densities up to a few times saturation density.
Inklusion ist (k)eine Frage der Persönlichkeit - Inklusive Kompetenzen institutionell verankern!
(2020)
Orientiert am Themenschwerpunkt der „theoretischen und empirischen Klärung des Verständnisses pädagogischer Fachlichkeit“ beschäftigt sich unser Beitrag mit den Barrieren und Chancen, die sich in der Hochschulstruktur und –kultur und der universitären Lehre darstellen, wobei wir uns exemplarisch der Ausbildung inklusionsbezogener pädagogischer Fachlichkeit bei angehenden Lehrkräften zuwenden. Mit Bezug zu aktuellen Entwicklungen der bildungspolitischen Landschaft in Deutschland wird zunächst die Notwendigkeit eines Umdenkens in der Lehramtsausbildung, wie auch in der gesamten Hochschullandschaft, dargelegt und diskutiert. Dabei wird das dem Beitrag zugrunde liegende Verständnis von Inklusion verdeutlicht. Die sich daraus ergebenden Anforderungen an Hochschulen, besonders in Bezug auf ihr Selbstverständnis, das Verständnis von Wissenschaftlichkeit und die gelebte Hochschulkultur, werden daraufhin formuliert. Daran schließen Überlegungen zur Umsetzung inklusionsorientierter Praxen in der Lehrer*innenbildung an. Ein besonderer Fokus liegt dabei auf der partizipativen Lehre als möglichem Werkzeug für eine inklusionssensible Hochschulentwicklung. Am Beispiel partizipativer Lehre gemeinsam mit Menschen mit Lernschwierigkeiten1 werden Möglichkeiten aufgezeigt, wie Menschen, die bisher keinen Zugang zur akademischen Wissensvermittlung hatten, als Lehrende tätig sein und so sowohl von Biografien unter der Erfahrung von Diskriminierung berichten, als auch diese Erfahrungen in die Produktion von Wissen einfließen lassen können. In der Diskussion um partizipative Lehre werden verschiedene Widersprüche und Diskurse deutlich, die geeignet sind, um über Hochschulkulturen und -praxen neu nachzudenken.
We examined the feedback between the major protein degradation pathway, the ubiquitin-proteasome system (UPS), and protein synthesis in rat and mouse neurons. When protein degradation was inhibited, we observed a coordinate dramatic reduction in nascent protein synthesis in neuronal cell bodies and dendrites. The mechanism for translation inhibition involved the phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated kinase inhibitor (HRI). Under basal conditions, neuronal expression of HRI is barely detectable. Following proteasome inhibition, HRI protein levels increase owing to stabilization of HRI and enhanced translation, likely via the increased availability of tRNAs for its rare codons. Once expressed, HRI is constitutively active in neurons because endogenous heme levels are so low; HRI activity results in eIF2α phosphorylation and the resulting inhibition of translation. These data demonstrate a novel role for neuronal HRI that senses and responds to compromised function of the proteasome to restore proteostasis.
CD8+ T cells are key players in immunity against intracellular infections and tumors. The main cytokine associated with these protective responses is interferon-γ (IFN-γ), whose production is known to be regulated at the transcriptional level during CD8+ T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-γ expression by CD8+ T cells, since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-γ by both thymic and peripheral CD8+ T cells. Using a gene reporter mouse for IFN-γ locus activity, we compared the microRNA repertoires associated with the presence or absence of IFN-γ expression. This allowed us to identify a set of candidates, including miR-181a and miR-451, which were functionally tested in overexpression experiments using synthetic mimics in peripheral CD8+ T cell cultures. We found that miR-181a limits IFN-γ production by suppressing the expression of the transcription factor Id2, which in turn promotes the Ifng expression program. Importantly, upon MuHV-4 challenge, miR-181a-deficient mice showed a more vigorous IFN-γ+ CD8+ T cell response and were able to control viral infection significantly more efficiently than control mice. These data collectively establish a novel role for miR-181a in regulating IFN-γ–mediated effector CD8+ T cell responses in vitro and in vivo.
Accurate measurement of the standard 235U(n,f) cross section from thermal to 170 keV neutron energy
(2020)
An accurate measurement of the 235U(n,f) cross section from thermal to 170 keV of neutron energy has recently been performed at n_TOF facility at CERN using 6Li(n,t)4He and 10B(n,α)7Li as references. This measurement has been carried out in order to investigate a possible overestimation of the 235U fission cross section evaluation provided by most recent libraries between 10 and 30 keV. A custom experimental apparatus based on in-beam silicon detectors has been used, and a Monte Carlo simulation in GEANT4 has been employed to characterize the setup and calculate detectors efficiency. The results evidenced the presence of an overestimation in the interval between 9 and 18 keV and the new data may be used to decrease the uncertainty of 235U(n,f) cross section in the keV region.
Jens Amendt hat die internationale Konferenz der Forensischen Entomologie von seinem Rechner aus in Frankfurt geleitet. Sein Resümee: Die virtuelle Veranstaltung mit 260 Teilnehmenden hat insgesamt sehr gut geklappt, aber Mikrofon und Kamera sollte man gerade als Organisator immer gut im Auge behalten.
Introduction: Reliable and cost-effective diagnostics for hepatitis E virus (HEV) infection are necessary. The aim of our study was to investigate which diagnostic test is most accurate to detect HEV infection in immunocompetent and immunosuppressed patients in a real world setting. Patients and Methods: We performed a retrospective analysis of 1165 patients tested for HEV antibodies and HEV PCR at the same time point. Clinical, laboratory and virological data were taken from patient charts. HEV IgA was measured in a subgroup of 185 patients. Results: HEV RNA was detectable in 61 patients (5.2%); most of them (n = 49, 80.3%/n = 43, 70.5%) were HEV IgM+ and IgG+; however, 12 patients (19.6%) were HEV RNA positive/HEV IgM negative and 17 patients (27.8%) were HEV RNA positive/HEV IgG negative. Ten HEV RNA positive patients (16.4%) had neither HEV IgG nor IgM antibodies. Importantly, all of them were immunosuppressed. HEV IgA testing was less sensitive than HEV IgM for HEV diagnosis. Conclusions: HEV infection can be overlooked in patients without HEV specific antibodies. Performing PCR is necessary to diagnose or exclude HEV infection in immunocompromised hosts. In immunocompetent patients, a screening based on HEV antibodies (IgG/IgM) is sufficient.
Evoked potentials in the amplitude-time spectrum of the electroencephalogram are commonly used to assess the extent of brain responses to stimulation with noxious contact heat. The magnitude of the N- and P-waves are used as a semi-objective measure of the response to the painful stimulus: the higher the magnitude, the more painful the stimulus has been perceived. The strength of the N-P-wave response is also largely dependent on the chosen reference electrode site. The goal of this study was to examine which reference technique excels both in practical and theoretical terms when analyzing noxious contact heat evoked potentials (CHEPS) in the amplitude-time spectrum. We recruited 21 subjects (10 male, 11 female, mean age of 55.79 years). We applied seven noxious contact heat stimuli using two temperatures, 51°C, and 54°C, to each subject. During EEG analysis, we aimed to identify the referencing technique which produces the highest N-wave and P-wave amplitudes with as little artifactual influence as possible. For this purpose, we applied the following six referencing techniques: mathematically linked A1/A2 (earlobes), average reference, REST, AFz, Pz, and mathematically linked PO7/PO8. We evaluated how these techniques impact the N-P amplitudes of CHEPS based on our data from healthy subjects. Considering all factors, we found that mathematically linked earlobes to be the ideal referencing site to use when displaying and evaluating CHEPS in the amplitude-time spectrum.
Wie es Eltern und ihren Kindern während der Corona-Pandemie geht, wie ihr aktuelles Wohlbefinden ist, was ihren Alltag kennzeichnet, wie die Passung zu den Regelungen der Kitabetreuung, Schulöffnung und auch der Arbeitgeber*innen ist – dies sind die Kernfragen der Onlinebefragung KiCo, welche im Zeitraum vom 24.04.2020 – 03.05.2020 durchgeführt wurde. Dieses Papier präsentiert erste Ergebnisse der Studie, an der über 25.000 Personen teilgenommen haben. Die Studie wurde umgesetzt vom Forschungsverbund "Kindheit – Jugend – Familie in der Corona-Zeit", der sich aus den Universitäten Hildesheim, Frankfurt und Bielefeld zusammensetzt.
Dieses Papier präsentiert erste Ergebnisse der bundesweiten Studie JuCo – Erfahrungen und Perspektiven von jungen Menschen während der Corona-Maßnahmen. Die Befragung wurde vom Forschungsverbund "Kindheit – Jugend – Familie in der Corona-Zeit" umgesetzt, der sich aus den Universitäten Hildesheim, Frankfurt und Bielefeld zusammensetzt. Über 5.000 Jugendliche und junge Erwachsene zwischen 15 und 30 Jahren sind in die Analysen eingeflossen und zeigen auf, wie es den jungen Menschen geht und welche Botschaften sie haben.
Hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) – a retrospective study
(2020)
Background: The aim of this study was to verify the validity of clinical history and oral provocation challenges of patients with NSAID hypersensitivity and to identify safe alternatives. The COX‐2 inhibitor etoricoxib, in particular, was studied.
Patients and methods: In all, 104 patients with confirmed diagnoses of NSAID hypersensitivity treated at the Department of Dermatology, Frankfurt University Hospital, Germany between 2004 and 2012 were retrospectively studied.
Results: The medical history and hypersensitivity symptoms during oral provocation testing (OPT) largely coincided and were mostly mild to moderate. Acetylsalicylic acid (ASA) was the most frequent trigger both anamnestically (27.9 %) and during OPT (47.8 %). Etoricoxib caused the fewest reactions during OPT (4.2 %). Acetaminophen led to reactions in only 6.7 % of the cases studied although it was named more often in clinical histories (14 %).
Conclusions: OPT should be the aim whenever possible as most symptoms are mild to moderate. To distinguish between selective and cross‐hypersensitivity reactions, ASA should be part of the test protocol. Furthermore, the findings of this study indicate that etoricoxib and acetaminophen are safe treatment alternatives in case of NSAID hypersensitivity. However, these drugs should not be administered without prior OPT in an inpatient setting, as severe symptoms can occur.
Aims: Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)‐guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.
Methods and results: A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP‐guided HF management. One‐year rates of freedom from device‐ or system‐related complications and from sensor failure (co‐primary outcomes) were 98.3% [95% confidence interval (CI) 95.8–100.0] and 99.6% (95% CI 97.6–100.0), respectively. Survival rate was 86.2%. For the 12 months post‐ vs. pre‐implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient‐year; hazard ratio 0.38, 95% CI 0.31–0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9‐item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001).
Conclusion: Haemodynamic‐guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician‐directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms.
Andropogon virginicus is an invasive weed that seriously threatens agricultural production and economics worldwide. In this research, dried aerial parts of A. virginicus were extracted, applying Soxhlet and liquid-liquid phase methods to acquire the total crude (T-Anvi), hexane (H-Anvi), ethyl acetate (E-Anvi), butanol (B-Anvi), and water (W-Anvi) extracts, respectively. In which, T-Anvi contains the highest total phenolic and flavonoid contents (24.80 mg gallic acid and 37.40 mg rutin equivalents per g dry weight, respectively). Via anti-radical (ABTS and DPPH), and reducing power assays, E-Anvi exhibits the most potent activities (IC50 = 13.96, 43.59 and 124.11 µg/mL, respectively), stronger than butylated hydroxytoluene (BHT), a standard antioxidant, while the lipid peroxidation inhibitory effect of E-Anvi (LPI = 90.85% at the concentration of 500 µg/mL) is close to BHT. E-Anvi shows the most substantial inhibition (IC50 = 2.58 mg/mL) on tyrosinase. Notably, α-amylase is significantly suppressed by H-Anvi (IC50 = 0.72 mg/mL), over twice stronger than the positive control, palmitic acid. In the cytotoxic assay, E-Anvi is the strongest extract inhibiting K562 cells (IC50 = 112.01 µg/mL). Meanwhile, T-Anvi shows the highest prevention on Meg-01 expansion (IC50 = 91.40 µg/mL). Dominant compounds detected in E-Anvi by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) are identified as flavonoids. However, among four major compounds identified in H-Anvi by gas chromatography-mass spectrometry (GC-MS), palmitic acid and phytol are the most abundant compounds with peak areas of 27.97% and 16.42%, respectively. In essence, this is the first report describing that A. virginicus is a potential natural source of antioxidants, tyrosinase and α-amylase inhibitors, and anti-chronic myeloid leukemia (CML) agents which may be useful in future therapeutics as promising alternative medicines.
Across the entire animal kingdom, sociality, i.e. the tendency of individual animals to form a group with conspecifics, is a common trait. Environmental changes have to be met with corresponding, quick adaptations. For social species, the presence of conspecifics is important for survival and if social animals are deprived of access to conspecifics, this can lead to strong and lasting changes on a physiological level as well as behaviour. Gene expression changes responsible for these adaptations have so far not been understood in detail. As social isolation leads to changes on a neuronal level, it is important to investigate the gene expression changes that are induced in the brain. In this thesis, next-generation RNA-sequencing was applied to zebrafish, a well-established model organism characterized by its high degree of companionship. Within the entire brain, gene expression was analysed in zebrafish that were raised either with conspecifis or in isolation, ranging from 5 to 21 days post fertilization. Using this approach, several genes were identified that were downregulated by social isolation. In this thesis, I focused on one of these consistently downregulated genes, parathyroid hormone 2 (pth2). The expression of pth2 was demonstrated to be bidirectionally regulated by the number of conspecifics present and to be responsive to changes in the social environment within 30 minutes. Regulation of pth2 does not occur by visual or chemosensory access to conspecifcs, but is mediated by mechanosensory perception of other fish via the lateral line. In an experiment using an artificial mechanical stimulation paradigm, it was shown that the features necessary to elicit pth2 transcription closely mimick the locomotion of actual zebrafish. Other, similar stimulation paradigms are not capable to induce this transcriptional response.
Learning in the eyes: specific changes in gaze patterns track explicit and implicit visual learning
(2020)
What is the link between eye movements and sensory learning? Although some theories have argued for a permanent and automatic interaction between what we know and where we look, which continuously modulates human information- gathering behavior during both implicit and explicit learning, there exist surprisingly little evidence supporting such an ongoing interaction. We used a pure form of implicit learning called visual statistical learning and manipulated the explicitness of the task to explore how learning and eye movements interact. During both implicit exploration and explicit visual learning of unknown composite visual scenes, eye movement patterns systematically changed in accordance with the underlying statistical structure of the scenes. Moreover, the degree of change was directly correlated with the amount of knowledge the observers acquired. Our results provide the first evidence for an ongoing and specific interaction between hitherto accumulated knowledge and eye movements during both implicit and explicit learning.
Large carnivores often impact human livelihoods and well‐being. Previous research has mostly focused on the negative impacts of large carnivores on human well‐being but has rarely considered the positive aspects of living with large carnivores. In particular, we know very little on people's direct experiences with large carnivores like personal encounters and on people's awareness and tolerance toward their exposure to large carnivores. Here, we focus on the wolf (Canis lupus), and report on a phone survey in Germany. We examined whether encounters with wolves were positive or negative experiences and quantified people's awareness and tolerance related to their exposure to wolves. We found that the majority of people reported positive experiences when encountering wolves, regardless of whether wolves were encountered in the wild within Germany, in the wild abroad, or in captivity. The frequency of encounters did not affect the probability to report positive, neutral, or negative experiences. Moreover, people in Germany expressed a high tolerance of living in close vicinity to wolves. These findings are novel and important because they highlight the positive aspects of living in proximity with large carnivores in human‐dominated landscapes.
Background: Research on desired emotions revealed that individuals want to feel negative emotions if they expect these emotions to yield certain benefits. In previous studies, the pursuit of sadness (e.g., via pursuing art that evokes sadness) has been attributed to hedonic motives, i.e., to feel pleasure. We propose that in individuals with major depressive disorder (MDD) the pursuit of sadness may be more strongly related to self-verification motives, i.e., to sustain their sense of self through feeling sad.
Methods: Participants with MDD (n = 50) were compared to non-depressed controls (n = 50) in their desired emotional states, as indicated by selected music (sad, happy and neutral), and in their motives (hedonic vs. self-verification) for choosing sad music. Groups were also compared in their self-reported general preference for sadness and the perceived functionality of sadness.
Results: MDD participants showed a significant higher desire for sadness; more than half of them deliberately chose sad music. Whereas MDD participants had a marked preference for self-verification over hedonic motives, the reverse was true for non-depressed controls. MDD participants also agreed more strongly with self-verifying functions of sadness and expressed a stronger general preference for sadness.
Conclusion: Findings indicate that emotion regulation in MDD might be driven by self-verification motives. They point to the relevance of exploring patients’ desired emotional states and associated motives. The systematic integration of positive affect into the self-image of depressed patients might help to deemphasize the self-verifying function of sadness, thereby overcoming the depression.
Background: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy).
Methods: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS).
Results: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding
renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status
decreased by 18.1 points (95%-CI: 7.1–29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively.
Conclusions: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together
with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.
Trial registration: The study is registered with ClinicalTrials.gov (NCT01180504). Registered 12 August 2010 – retrospectively registered.
Of the 16 non-structural proteins (Nsps) encoded by SARS CoV-2, Nsp3 is the largest and plays important roles in the viral life cycle. Being a large, multidomain, transmembrane protein, Nsp3 has been the most challenging Nsp to characterize. Encoded within Nsp3 is the papain-like protease PLpro domain that cleaves not only the viral protein but also polyubiquitin and the ubiquitin-like modifier ISG15 from host cells. We here compare the interactors of PLpro and Nsp3 and find a largely overlapping interactome. Intriguingly, we find that near full length Nsp3 is a more active protease compared to the minimal catalytic domain of PLpro. Using a MALDI-TOF based assay, we screen 1971 approved clinical compounds and identify five compounds that inhibit PLpro with IC50s in the low micromolar range but showed cross reactivity with other human deubiquitinases and had no significant antiviral activity in cellular SARS-CoV-2 infection assays. We therefore looked for alternative methods to block PLpro activity and engineered competitive nanobodies that bind to PLpro at the substrate binding site with nanomolar affinity thus inhibiting the enzyme. Our work highlights the importance of studying Nsp3 and provides tools and valuable insights to investigate Nsp3 biology during the viral infection cycle.
Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli. Cerebellar ataxias and corticospinal motor neuron degeneration are determined by gain/loss in ATXN2 function, so we aimed to identify key molecules in this atrophic process, as potential disease progression markers. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. The earliest changes were detected at three months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found to be affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with the weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, primarily impacting excitability and communication.
In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re‐transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15‐year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re‐DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re‐DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re‐DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.
L'osservazione secondo la quale lo scarto come oggetto di ricerca sia allo stesso tempo un effetto della sua ricerca è ciò che l'articolo traccia in tre studi sulla spazzatura: Rubbish! di William Rathje e Cullen Murphy, Un mondo usa e getta di Guido Viale e Das Miill-System di Volker Grassmuck e Christian Unverzagt. Questi tre studi esemplificano tre modi di presentare lo scarto: esplorazione, problema e ricie/aggio. Guardarli come argomenti scientifici ci permette di discutere di ciò che è considerato scarto ponendo domande di presentazione testuale e, allo stesso tempo, di chiedere quali conseguenze abbia la presentazione per il concetto scientifico dello scarto.
Two-person neuroscience (2 PN) is a recently introduced conceptual and methodological framework used to investigate the neural basis of human social interaction from simultaneous neuroimaging of two or more subjects (hyperscanning). In this study, we adopted a 2 PN approach and a multiple-brain connectivity model to investigate the neural basis of a form of cooperation called joint action. We hypothesized different intra-brain and inter-brain connectivity patterns when comparing the interpersonal properties of joint action with non-interpersonal conditions, with a focus on co-representation, a core ability at the basis of cooperation. 32 subjects were enrolled in dual-EEG recordings during a computerized joint action task including three conditions: one in which the dyad jointly acted to pursue a common goal (joint), one in which each subject interacted with the PC (PC), and one in which each subject performed the task individually (Solo).
A combination of multiple-brain connectivity estimation and specific indices derived from graph theory allowed to compare interpersonal with non-interpersonal conditions in four different frequency bands. Our results indicate that all the indices were modulated by the interaction, and returned a significantly stronger integration of multiple-subject networks in the joint vs. PC and Solo conditions. A subsequent classification analysis showed that features based on multiple-brain indices led to a better discrimination between social and non-social conditions with respect to single-subject indices. Taken together, our results suggest that multiple-brain connectivity can provide a deeper insight into the understanding of the neural basis of cooperation in humans.
The metasomatised continental mantle may play a key role in the generation of some ore deposits, in particular mineral systems enriched in platinum-group elements (PGE) and Au. The cratonic lithosphere is the longest-lived potential source for these elements, but the processes that facilitate their pre-concentration in the mantle and their later remobilisation to the crust are not yet well-established. Here, we report new results on the petrography, major-element, and siderophile- and chalcophile-element composition of native Ni, base metal sulphides (BMS), and spinels in a suite of well-characterised, highly metasomatised and weakly serpentinised peridotite xenoliths from the Bultfontein kimberlite in the Kaapvaal Craton, and integrate these data with published analyses. Pentlandite in polymict breccias (failed kimberlite intrusions at mantle depth) has lower trace-element contents (e.g., median total PGE 0.72 ppm) than pentlandite in phlogopite peridotites and Mica-Amphibole-Rutile-Ilmenite-Diopside (MARID) rocks (median 1.6 ppm). Spinel is an insignificant host for all elements except Zn, and BMS and native Ni account for typically <25% of the bulk-rock PGE and Au. High bulk-rock Te/S suggest a role for PGE-bearing tellurides, which, along with other compounds of metasomatic origin, may host the missing As, Ag, Cd, Sb, Te and, in part, Bi that are unaccounted for by the main assemblage.
The close spatial relationship between BMS and metasomatic minerals (e.g., phlogopite, ilmenite) indicates that the lithospheric mantle beneath Bultfontein was resulphidised by metasomatism after initial melt depletion during stabilisation of the cratonic lithosphere. Newly-formed BMS are markedly PGE-poor, as total PGE contents are <4.2 ppm in pentlandite from seven samples, compared to >26 ppm in BMS in other peridotite xenoliths from the Kaapvaal craton. This represents a strong dilution of the original PGE abundances at the mineral scale, perhaps starting from precursor PGE alloy and small volumes of residual BMS. The latter may have been the precursor to native Ni, which occurs in an unusual Ni-enriched zone in a harzburgite and displays strongly variable, but overall high PGE abundances (up to 81 ppm). In strongly metasomatised peridotites, Au is enriched relative to Pd, and was probably added along with S. A combination of net introduction of S, Au +/− PGE from the asthenosphere and intra-lithospheric redistribution, in part sourced from subducted materials, during metasomatic events may have led to sulphide precipitation at ~80–120 km beneath Bultfontein. This process locally enhanced the metallogenic fertility of this lithospheric reservoir. Further mobilisation of the metal budget stored in these S-rich domains and upwards transport into the crust may require interaction with sulphide-undersaturated melts that can dissolve sulphides along with the metals they store.
Abstract
The mineralogy, chemical composition, and physical properties of cratonic mantle eclogites with oceanic crustal protoliths can be modified by secondary processes involving interaction with fluids and melts, generated in various slab lithologies upon subduction (auto‐metasomatism) or mantle metasomatism after emplacement into the cratonic lithosphere. Here we combine new and published data to isolate these signatures and evaluate their effects on the chemical and physical properties of eclogite. Mantle metasomatism involving kimberlite‐like, ultramafic carbonated melts (UM carbonated melts) is ubiquitous though not pervasive, and affected between ~20% and 40% of the eclogite population at the various localities investigated here, predominantly at ~60–150 km depth, overlapping cratonic midlithospheric seismic discontinuities. Its hallmarks include lower jadeite component in clinopyroxene and grossular component in garnet, an increase in bulk‐rock MgO ± SiO2, and decrease in FeO and Al2O3 contents, and LREE‐enrichment accompanied by higher Sr, Pb, Th, U, and in part Zr and Nb, as well as lower Li, Cu ± Zn. This is mediated by addition of a high‐temperature pyroxene from a UM carbonated melt, followed by redistribution of this component into garnet and clinopyroxene. As clinopyroxene‐garnet trace‐element distribution coefficients increase with decreasing garnet grossular component, clinopyroxene is the main carrier of the metasomatic signatures. UM carbonated melt‐metasomatism at >130–150 km has destroyed the diamond inventory at some localities. These mineralogical and chemical changes contribute to low densities, with implications for eclogite gravitational stability, but negligible changes in shear‐wave velocities, and, if accompanied by H2O‐enrichment, will enhance electrical conductivities compared to unenriched eclogites.
Plain Language Summary
Oceanic crust formed at spreading ridges is recycled in subduction zones and undergoes metamorphism to eclogite. Some of this material is captured in the overlying lithospheric mantle, where it is exhumed by passing magmas. Having formed in spreading ridges, these eclogites have proven invaluable archives for the onset of plate tectonics, for the construction of cratons during subduction/collision, as probes of the convecting mantle from which their precursors formed, and as generators of heterogeneity upon recycling into Earth's convecting mantle. During subduction and until exhumation, interaction with fluids and melts (called metasomatism) can change the mineralogy, chemical composition, and physical properties of mantle eclogites, complicating their interpretation, but a comprehensive study of these effects is lacking so far. We investigated mantle eclogites from ancient continents (cratons) around the globe in order to define hallmarks of metasomatism by subduction‐related fluids and small‐volume ultramafic carbonated mantle melts. We find that the latter is pervasive and occurs predominantly at midlithospheric depths where seismic discontinuities are detected, typically causing diamond destruction and a reduction in density. This has consequences for their gravitational stability and for the interpretation of shearwave velocities in cratons.
Workaholism and overcommitment are often used as interchangeable constructs describing an individual’s over-involvement toward their own job. Employees with high levels in both constructs are characterized by an excessive effort and attachment to their job, with the incapability to detach from it and negative consequences in terms of poor health and job burnout. However, few studies have simultaneously measured both constructs, and their relationships are still not clear. In this study, we try to disentangle workaholism and overcommitment by comparing them with theoretically related contextual and personal antecedents, as well as their health consequences. We conducted a nonprobability mixed mode research design on 133 employees from different organizations in Italy using both self- and other-reported measures. To test our hypothesis that workaholism and overcommitment are related yet different constructs, we used partial correlations and regression analyses. The results confirm that these two constructs are related to each other, but also outline that overcommitment (and not workaholism) is uniquely related to job burnout, so that overcommitment rather than workaholism could represent the true negative aspect of work drive. Additionally, workaholism is more related to conscientiousness than overcommitment, while overcommitment shows a stronger relationship with neuroticism than workaholism. The theoretical implications are discussed.
The case for corona bonds
(2020)
Corona bonds are feasible and important to preserve the European project. We set out a number of principles that might serve as a blueprint for the European institutions. Importantly, Corona bonds could be issued through a new public law entity and include all the safeguards required for the protection of the fundamental values of the EU. This proposal is pragmatic in the sense that it facilitates the choice European leaders have to make now; necessary to secure the resilience of the European Union. The political risks are significantly higher now than in 2010. The gargantuan challenge of tackling the combined impact of climate change, migration, digitalization, geopolitical shifts, and the spread of autocracy, requires leadership and joint action by the Council and the Eurogroup.
Governments, economists and intellectuals have called for common European bonds or increased own EU funds to address the recession induced by Covid19. Unfortunately, the German government, joined by the other members of the “Frugal Four” (Austria, Finland, the Netherlands), has categorically rejected to look into any such measures and favours using the ESM. This reaction created a déjà vu experience for citizens and governments of the heavily affected southern Member States of the EU. The proposal to use the ESM raises fears of another wave of austerity amounting to yet another lost decade for economic, social, and ecological development in Europe.
The paper compares provision of public infrastructure via public-private partnerships (PPPs) with provision under government management. Due to soft budget constraints of government management, PPPs exert more effort and therefore have a cost advantage in building infrastructure. At the same time, hard budget constraints for PPPs introduce a bankruptcy risk and bankruptcy costs. Consequently, if bankruptcy costs are high, PPPs may be less efficient than public management, although this does not result from PPPs’ higher interest costs.
Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
Nematophilic bacteria as a source of novel macrocyclised antimicrobial non-ribosomal peptides
(2020)
A solution to ineffective clinical antimicrobials is the discovery of new ones from under-explored sources such as macrocyclic non-ribosomal peptides (NRP) from nematophilic bacteria. In this dissertation an antimicrobial discovery process –from soil sample to inhibitory peptide– is demonstrated through investigations on six nematophilic bacteria: Xenorhabdus griffiniae XN45, X. griffiniae VH1, Xenorhabdus sp. nov. BG5, Xenorhabdus sp. nov. BMMCB, X. ishibashii and Photorhabdus temperata. To demonstrate the first step of bacterium isolation and species delineation, endosymbionts were isolated from Steinernema sp. strains BG5 and VH1 that were isolated directly from soil samples in Western Kenya. After genome sequencing and assembly of novel Xenorhabdus isolates VH1 and BG5, species delineation was done via three overall genome relatedness indices. VH1 was identified as X. griffiniae VH1, BG5 as Xenorhabdus sp. nov. BG5 and X. griffiniae BMMCB was emended to Xenorhabdus sp. nov. BMMCB. The nematode host of X. griffiniae XN45, Steinernema sp. scarpo was highlighted as a putative novel species. To demonstrate the second step of genome mining and macrocyclic non-ribosomal peptide structure elucidation, chemosynthesis and biosynthesis, the non-ribosomal peptide whose production is encoded by the ishA-B genes in X. ishibashii was investigated. Through a combination of refactoring the ishA-B operon by a promoter exchange mechanism, isotope labelling experiments, high resolution tandem mass spectrometry analysis, bioinformatic protein domain analysis and chemoinformatic comparisons of actual to hypothetical mass spectrometry spectra, the structures of Ishipeptides were elucidated and confirmed by chemical synthesis. Ishipeptide A was a branch cyclic depsidodecapeptide macrocyclised via an ester bond between serine and the terminal glutamate. It chemosynthesis route was via a late stage macrolactamation and linearised Ishipeptide B was synthesised via solid phase iterative synthesis. Ishipeptides were not N-terminally acylated despite being biosynthesised from the IshA protein that had a C-starter domain. It was highlighted that more than restoration of the histidine active site of this domain is required to restore N-terminal acylation activity.
To demonstrate the final step of determination of antimicrobial activity, minimum inhibitory concentrations of Ishipeptides and Photoditritide from Photorhabdus temperata against fungi and bacteria were determined. None were antifungal while only the macrocyclic compounds were inhibitory, with Ishipeptide A inhibitory to Gram-positive bacteria at 37 µM. The cationic Photoditritide, a cyclic hexapeptide macrocyclised via a lactam bond between homoarginine and tryptophan, was 12 times more inhibitory (3.0 µM), even more effective than a current clinical compound, Ampicillin (4.2 µM). For both, macrocyclisation was hypothesised to contribute to antimicrobial activity. Ultimately, this dissertation demonstrated not only nematophilic bacteria as a source of novel macrocyclic antimicrobial non-ribosomal peptides but also a process of antimicrobial discovery–from soil sample to inhibitory peptide– from these useful bacteria genera. This is significant for the fight against antimicrobial resistance.
Nematophilic bacteria as a source of novel macrocyclised antimicrobial non-ribosomal peptides
(2020)
A solution to ineffective clinical antimicrobials is the discovery of new ones from under-explored sources such as macrocyclic non-ribosomal peptides (NRP) from nematophilic bacteria. In this dissertation an antimicrobial discovery process –from soil sample to inhibitory peptide– is demonstrated through investigations on six nematophilic bacteria: Xenorhabdus griffiniae XN45, X. griffiniae VH1, Xenorhabdus sp. nov. BG5, Xenorhabdus sp. nov. BMMCB, X. ishibashii and Photorhabdus temperata. To demonstrate the first step of bacterium isolation and species delineation, endosymbionts were isolated from Steinernema sp. strains BG5 and VH1 that were isolated directly from soil samples in Western Kenya. After genome sequencing and assembly of novel Xenorhabdus isolates VH1 and BG5, species delineation was done via three overall genome relatedness indices. VH1 was identified as X. griffiniae VH1, BG5 as Xenorhabdus sp. nov. BG5 and X. griffiniae BMMCB was emended to Xenorhabdus sp. nov. BMMCB. The nematode host of X. griffiniae XN45, Steinernema sp. scarpo was highlighted as a putative novel species. To demonstrate the second step of genome mining and macrocyclic non-ribosomal peptide structure elucidation, chemosynthesis and biosynthesis, the non-ribosomal peptide whose production is encoded by the ishA-B genes in X. ishibashii was investigated. Through a combination of refactoring the ishA-B operon by a promoter exchange mechanism, isotope labelling experiments, high resolution tandem mass spectrometry analysis, bioinformatic protein domain analysis and chemoinformatic comparisons of actual to hypothetical mass spectrometry spectra, the structures of Ishipeptides were elucidated and confirmed by chemical synthesis. Ishipeptide A was a branch cyclic depsidodecapeptide macrocyclised via an ester bond between serine and the terminal glutamate. It chemosynthesis route was via a late stage macrolactamation and linearised Ishipeptide B was synthesised via solid phase iterative synthesis. Ishipeptides were not N-terminally acylated despite being biosynthesised from the IshA protein that had a C-starter domain. It was highlighted that more than restoration of the histidine active site of this domain is required to restore N-terminal acylation activity.
To demonstrate the final step of determination of antimicrobial activity, minimum inhibitory concentrations of Ishipeptides and Photoditritide from Photorhabdus temperata against fungi and bacteria were determined. None were antifungal while only the macrocyclic compounds were inhibitory, with Ishipeptide A inhibitory to Gram-positive bacteria at 37 µM. The cationic Photoditritide, a cyclic hexapeptide macrocyclised via a lactam bond between homoarginine and tryptophan, was 12 times more inhibitory (3.0 µM), even more effective than a current clinical compound, Ampicillin (4.2 µM). For both, macrocyclisation was hypothesised to contribute to antimicrobial activity. Ultimately, this dissertation demonstrated not only nematophilic bacteria as a source of novel macrocyclic antimicrobial non-ribosomal peptides but also a process of antimicrobial discovery–from soil sample to inhibitory peptide– from these useful bacteria genera. This is significant for the fight against antimicrobial resistance.
Eleştirel Kuram, 20. yüzyılın başlarında, daha sonra Frankfurt Okulu olarak bilinecek olan “Frankfurt Toplumsal Araştırmalar Enstitüsü” adı altında, bir grup akademisyen tarafından oluşturulmuş bir düşünce akımıdır. Bu düşünsel yaklaşımda, farklı dönemlerde farklı görüşler benimsenmiş olmakla birlikte, özünde pozitivizm ve araçsal akıl başta olmak üzere, modern kapitalist toplumsal düzen eleştirilmektedir. Aydınlanmanın, modernizmin ve modern aklın, kapitalizmin hizmetine girdiğinden yakınılmakta, bireylerin yaşamlarının kontrol edildiği ve onların belirli kalıplar içerisinde davranmaya zorlandığı bir sistemin varlığına karşı çıkılmaktadır. Bu çalışmada, diğer kuramsal yaklaşımlardan ve ideolojilerden negatif ve eleştirel bir bakış açısına sahip olması nedeniyle farklılaşan Eleştirel Kuram’, Kamu Yönetimi disiplini ile ilişkilendirerek açıklanmaya çalışılacaktır. Kuramsal tartışmaların, analitik bir biçimde sistematize edilerek kurgulanmasıyla oluşturulacak metodoloji, çalışmanın inşa edilmesinde temel yöntem olarak kullanılacaktır.
Einleitung: Die akute Tonsillitis gehört zu den Infektionen der oberen Atemwege und ist eine sehr häufige Erkrankung in einer Kinder- und Jugendarztpraxis. Ziel unserer Untersuchung war es, das virale und bakterielle Erregerspektrum der akuten Tonsillitis, ihre saisonale Verteilung, ihre Altersverteilung, die klinische Symptomatik und den Einfluss einer Rauchexposition zu untersuchen. Gleichzeitig sollte erneut die Sensitivität und Spezifität des angewandten StrepA ST überprüft werden.
Methoden: In drei Kinder- und Jugendarztpraxen im Rhein-Main Gebiet wurden zwischen April 2009 und Mai 2010 insgesamt 1720 Patienten mit akuten Halsschmerzen untersucht. Mit einem Anamnesebogen wurden Alter, klinische Symptomatik und die Rauchexposition erfasst. Bei allen Patienten wurde ein StrepA ST durchgeführt. In einer Praxis (Praxis 1) wurden bei 306 Patienten zusätzlich ein Abstrich für eine bakterielle Kultur und für eine Multiplex PCR auf Viren durchgeführt.
Resultate: In 84% der Fälle tritt die GAS Tonsillitis im Alter zwischen 2 und 12 Jahren auf. Es konnte keine saisonale Häufung der GAS nachgewiesen werden. Mit 64 (42%) StrepA ST positiven Patienten von 152 Raucher-Familien und 74 (37%) von 200 Nichtraucher-Raucher-Familien zeigt sich kein signifikant erhöhtes Risiko an einer GAS Tonsillitis zu erkranken, wenn mindestens ein Elternteil raucht. Bei 306 Rachenabstrichen konnten 145 (47,5%) mal Streptokokken nachgewiesen werden. Davon waren mit 133 vorwiegend GAS (92%). Die anderen Streptokokken der Gruppen C (4,8%), G (2,1%) und B (1,4%) kommen deutlich seltener vor und spielen eine untergeordnete Rolle. Die Sensitivität und Spezifität des StrepA ST war mit 89,9% und 94,1% ausgezeichnet. Bei 306 Tonsillitiden gelang bei 110 Patienten (35,8%) ein Virusnachweis. Wie erwartet fanden sich doppelt so viele Virusnachweise (46%) bei Patienten ohne GAS Nachweis als Ko-Infektionen bei einer GAS (24%). Der Anteil der Entero-/Rhinoviren unter den nachgewiesenen Viren war mit 54% am höchsten. Adenoviren waren mit 15% und Influenza- 9% die nächst häufigen Viren, Para- und Coronaviren bildeten kleinere Gruppen. Während Entero-/Rhinoviren ganzjährig vorkommen sind Influenzaviren eher in der kalten Jahreszeit für akute Tonsillitiden verantwortlich. Die Rolle der Ko-Infektion in der Entstehung und im Verlauf der akuten Tonsillitis muss in weiteren Untersuchungen erforscht werden.
Diese Arbeit etabliert eine nicht-invasive, volloptische Methode zur in-vivo Beobachtung des Membranpotentials in erregbaren Zellen des Fadenwurms C. elegans, die als Ersatz oder komplementär zu invasiven, elektrophysiologischen Methoden verwendet werden kann.
New innovative neuropsychological tests in attention deficit hyperactivity disorder ADHD have been proposed as objective measures for diagnosis and therapy. The current study aims to investigate two different commercial continuous performance tests (CPT) in a head-to-head comparison regarding their comparability and their link with clinical parameters. The CPTs were evaluated in a clinical sample of 29 adult patients presenting in an ADHD outpatient clinic. Correlational analyses were performed between neuropsychological data, clinical rating scales, and a personality-based measure. Though inattention was found to positively correlate between the two tests (r = 0.49, p = 0.01), no association with clinical measures and inattention was found for both tests. While hyperactivity did not correlate between both tests, current ADHD symptoms were positively associated with Nesplora Aquarium’s motor activity (r = 0.52 to 0.61, p < 0.05) and the Qb-Test’s hyperactivity (r = 0.52 to 0.71, p < 0.05). Conclusively, the overall comparability of the tests was limited and correlation with clinical parameters was low. While our study shows some interesting correlation between clinical symptoms and sub-scales of these tests, usage in clinical practice is not recommended.
i-TED is an innovative detection system which exploits Compton imaging techniques to achieve a superior signal-to-background ratio in (n,γ) cross-section measurements using time-of-flight technique. This work presents the first experimental validation of the i-TED apparatus for high-resolution time-of-flight experiments and demonstrates for the first time the concept proposed for background rejection. To this aim both 197Au(n,γ) and 56Fe(n,γ) reactions were measured at CERN n\_TOF using an i-TED demonstrator based on only three position-sensitive detectors. Two \cds detectors were also used to benchmark the performance of i-TED. The i-TED prototype built for this study shows a factor of ∼3 higher detection sensitivity than state-of-the-art \cds detectors in the ∼10~keV neutron energy range of astrophysical interest. This paper explores also the perspectives of further enhancement in performance attainable with the final i-TED array consisting of twenty position-sensitive detectors and new analysis methodologies based on Machine-Learning techniques.
233U is the fissile nuclei in the Th-U fuel cycle with a particularily small neutron capture cross setion which is on average about one order of magnitude lower than its fission cross section. Hence, the measurement of the 233U(n, γ) cross section relies on a method to accurately distinguish between capture and fission γ-rays. A measurement of the 233U α-ratio has been performed at the n_TOF facility at CERN using a so-called fission tagging setup, coupling n_TOF 's Total Absorption Calorimeter with a novel fission chamber to tag the fission γ-rays. The experimental setup is described and essential parts of the analysis are discussed. Finally, a preliminary 233U α-ratio is presented.
Unresolved inflammation maintained by release of danger‐associated molecular patterns, particularly high‐mobility group box‐1 (HMGB1), is crucial for hepatocellular carcinoma (HCC) pathogenesis. To further characterize interactions between leucocytes and necrotic cancerous tissue, a cellular model of necroinflammation was studied in which murine Raw 264.7 macrophages or primary splenocytes were exposed to necrotic lysates (N‐lys) of murine hepatoma cells or primary hepatocytes. In comparison to those derived from primary hepatocytes, N‐lys from hepatoma cells were highly active—inducing in macrophages efficient expression of inflammatory cytokines like C‐X‐C motif ligand‐2 , tumor necrosis factor‐α, interleukin (IL)‐6 and IL‐23‐p19. This activity associated with higher levels of HMGB1 in hepatoma cells and was curbed by pharmacological blockage of the receptor for advanced glycation end product (RAGE)/HMGB1 axis or the mitogen‐activated protein kinases ERK1/2 pathway. Analysis of murine splenocytes furthermore demonstrated that N‐lys did not comprise of functionally relevant amounts of TLR4 agonists. Finally, N‐lys derived from hepatoma cells supported inflammatory splenic Th17 and Th1 polarization as detected by IL‐17, IL‐22 or interferon‐γ production. Altogether, a straightforward applicable model was established which allows for biochemical characterization of immunoregulation by HCC necrosis in cell culture. Data presented indicate a remarkably inflammatory capacity of necrotic hepatoma cells that, at least partly, depends on the RAGE/HMGB1 axis and may shape immunological properties of the HCC microenvironment.
Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.
Pulmonary failure is the main cause of morbidity and mortality in the human chromosomal instability syndrome Ataxia-telangiectasia (A-T). Major phenotypes include recurrent respiratory tract infections and bronchiectasis, aspiration, respiratory muscle abnormalities, interstitial lung disease, and pulmonary fibrosis. At present, no effective pulmonary therapy for A-T exists. Cell therapy using adipose-derived mesenchymal stromal/stem cells (ASCs) might be a promising approach for tissue regeneration. The aim of the present project was to investigate whether ASCs migrate into the injured lung parenchyma of Atm-deficient mice as an indication of incipient tissue damage during A-T. Therefore, ASCs isolated from luciferase transgenic mice (mASCs) were intravenously transplanted into Atm-deficient and wild-type mice. Retention kinetics of the cells were monitored using in vivo bioluminescence imaging (BLI) and completed by subsequent verification using quantitative real-time polymerase chain reaction (qRT-PCR). The in vivo imaging and the qPCR results demonstrated migration accompanied by a significantly longer retention time of transplanted mASCs in the lung parenchyma of Atm-deficient mice compared to wild type mice. In conclusion, our study suggests incipient damage in the lung parenchyma of Atm-deficient mice. In addition, our data further demonstrate that a combination of luciferase-based PCR together with BLI is a pivotal tool for tracking mASCs after transplantation in models of inflammatory lung diseases such as A-T.
Surface temperature is a fundamental parameter of Earth’s climate. Its evolution through time is commonly reconstructed using the oxygen isotope and the clumped isotope compositions of carbonate archives. However, reaction kinetics involved in the precipitation of carbonates can introduce inaccuracies in the derived temperatures. Here, we show that dual clumped isotope analyses, i.e., simultaneous ∆47 and ∆48 measurements on the single carbonate phase, can identify the origin and quantify the extent of these kinetic biases. Our results verify theoretical predictions and evidence that the isotopic disequilibrium commonly observed in speleothems and scleractinian coral skeletons is inherited from the dissolved inorganic carbon pool of their parent solutions. Further, we show that dual clumped isotope thermometry can achieve reliable palaeotemperature reconstructions, devoid of kinetic bias. Analysis of a belemnite rostrum implies that it precipitated near isotopic equilibrium and confirms the warmer-than-present temperatures during the Early Cretaceous at southern high latitudes.
Single-molecule localization microscopy (SMLM) reports on protein organization in cells with near-molecular resolution and in combination with stoichiometric labeling enables protein counting. Fluorescent proteins allow stoichiometric labeling of cellular proteins; however, most methods either lead to overexpression or are complex and time demanding. We introduce CRISPR/Cas12a for simple and efficient tagging of endogenous proteins with a photoactivatable protein for quantitative SMLM and single-particle tracking. We constructed a HEK293T cell line with the receptor tyrosine kinase MET tagged with mEos4b and demonstrate full functionality. We determine the oligomeric state of MET with quantitative SMLM and find a reorganization from monomeric to dimeric MET upon ligand stimulation. In addition, we measured the mobility of single MET receptors in vivo in resting and ligand-treated cells. The combination of CRISPR/Cas12a-assisted endogenous protein labeling and super-resolution microscopy represents a powerful tool for cell biological research with molecular resolution.
Die Kommunikation von Zellen mit ihrer Umgebung wird durch Rezeptorproteine arrangiert, die sich in der Plasmamembran befinden. Membranrezeptoren werden durch die Bindung von extrazellulären Liganden, Pathogenen oder Zell-Zell-Interaktionen aktiviert, wodurch die Bildung eines aktiven Zustands gefördert wird, der eine intrazelluläre Reaktion einleitet. Eine Beschreibung auf molekularer Ebene, wie sich Membranrezeptoren in Proteinanordnungen organisieren und wie diese Proteinanordnungen eine spezifische funktionelle Aufgabe ausführen, ist der Ausgangspunkt für das Verständnis der molekularen Mechanismen, die Gesundheit und Krankheit zugrunde liegen.
Die Fluoreszenzmikroskopie gibt Aufschluss über die Lage von Proteinen in Zellen, und mit der Einführung der höchstauflösenden Mikroskopie wurde der Nachweis einzelner Proteingruppierungen möglich. Eine Einschränkung der meisten Methoden der höchstauflösenden Mikroskopie ist, dass einzelne Komponenten einer Proteingruppierung optisch nicht aufgelöst werden können, was an der geringen Größe und dichten Packung der Bestandteile im Vergleich zur erreichbaren räumlichen Auflösung liegt. Eine Lösung, die für Einzelmolekül-Lokalisierungsmethoden gezeigt wurde, besteht darin, zusätzliche experimentelle Informationen in die Analyse zu implementieren, also „die Aufl sungsgrenze der höchstauflösenden Mikroskopie zu umgehen". Bei der Einzelmolekül-Bildgebung kann diese zusätzliche Information zum Beispiel die Kinetik von mehrfachen und wiederkehrenden
Emissionsereignissen sein, die bei einzelnen Fluorophoren beobachtet werden, was als "Blinken" bezeichnet wird. Das Ziel dieser Arbeit war die Entwicklung einer höchstauflösenden Fluoreszenzmikroskopiemethode zur Detektion von Proteinmonomeren und -dimeren in der Plasmamembran von Zellen durch die Verwendung der kinetischen Information.
Im ersten Teil dieser Arbeit wurden photoschaltbare fluoreszierende Proteine als Reporter verwendet, deren photoschaltbare Kinetik mit kinetischen Gleichungen analysiert wurden.
Synthetische, genetische und zelluläre Referenzproteine wurden konstruiert und dienten als Kalibrierungsreferenzen für monomere und dimere Proteine.
Im zweiten Teil dieser Arbeit wurde das kinetische Modell, das zur Annäherung des Häufigkeitshistogramms von Blinkereignissen einzelner Fluorophore verwendet wird, auf Oligomere höherer Ordnung erweitert. Ein Vergleich mit einem zuvor entwickelten Modell zeigte, dass das erweiterte Modell genauere Ergebnisse für Oligomere höherer Ordnung und Mischungen verschiedener Oligomere liefert. Zusätzlich wird die Anwesenheit von unerkannten Oligomeren berücksichtigt. Die erweiterte Theorie bietet somit die Grundlage, um größere Oligomere und Mischungen unterschiedlicher Stöchiometrie mit besserer Genauigkeit zu untersuchen.
Im dritten Teil dieser Arbeit wurde eine Methode zur stöchiometrischen endogenen Markierung von Proteinen verwendet, um zwei Rezeptortyrosinkinasen, MET und EGFR, mit einem photoschaltbaren fluoreszierenden Protein zu markieren. Das Vorkommen von monomerem und dimerem MET-Rezeptor wurde auf der Plasmamembran von HEK293T- Zellen mittels quantitativer höchstauflösender Mikroskopie bestimmt. Der Diffusionskoeffizient und der Diffusionsmodus des MET-Rezeptors in lebenden HEK293T-Zellen wurden mit
Einzelpartikelverfolgung gemessen. Dieser Teil der Arbeit zeigte, dass die Kombination von CRISPR/Cas12a-gestützter endogener Markierung und Einzelmolekül-Lokalisierungsmikroskopie ein leistungsfähiges Werkzeug zur Untersuchung der molekularen Organisation und Dynamik von Membranproteinen ist.
Im vierten Teil dieser Arbeit wurde die Einzelmoleküldatenanalyse durch ein Softwaretool beschleunigt, das eine automatisierte und unvoreingenommene Detektion von Einzelmolekül-Emissionsereignissen ermöglicht. Der Anteil von Monomeren und Dimeren von fluoreszierenden Reportern wurde durch die Implementierung eines neuronalen Netzwerks bestimmt (die Software wurde von Alon Saguy geschrieben; Gruppe von Prof. Yoav Shechtman, Technion, Israel). Der oligomere Zustand der monomeren und dimeren Referenzproteine CD86 und CTLA-4 wurde erfolgreich bestimmt. Die automatisierte Detektion einzelner Proteingruppierungen ermöglichte die Analyse von MET-mEos4b in einzelnen Zellen, wodurch die Heterogenität zwischen den Zellen bestimmt und das Expressionsniveau des Rezeptors mit der Dimerisierung korreliert werden konnte.
Zusammenfassend wurden in dieser Arbeit Ergebnisse zu elementaren Aspekten hin zu einer molekularen Quantifizierung von Proteinzahlen mittels Einzelmolekül-
Lokalisationsmikroskopie generiert, die fluoreszierende Reporter, stöchiometrische Markierung von zellulären Proteinen und Bildanalyse umfassen. Das Potential dieser
Entwicklungen wurde anhand der Beobachtung der Liganden-induzierten Verschiebung von monomeren zu dimeren MET-Rezeptoren in einzelnen HEK293T-Zellen gezeigt.
We determine the magnetic susceptibility of thermal QCD matter by means of first principles lattice simulations using staggered quarks with physical masses. A novel method is employed that only requires simulations at zero background field, thereby circumventing problems related to magnetic flux quantization. After a careful continuum limit extrapolation, diamagnetic behavior (negative susceptibility) is found at low temperatures and strong paramagnetism (positive susceptibility) at high temperatures. We revisit the decomposition of the magnetic susceptibility into spin- and orbital angular momentum- related contributions. The spin term — related to the normalization of the photon lightcone distribution amplitude at zero temperature — is calculated non-perturbatively and extrapolated to the continuum limit. Having access to both the full magnetic susceptibility and the spin term, we calculate the orbital angular momentum contribution for the first time. The results reveal the opposite of what might be expected based on a free fermion picture. We provide a simple parametrization of the temperature- and magnetic field-dependence of the QCD equation of state that can be used in phenomenological studies.
Background and Objectives: Red blood cell (RBC) transfusions are needed by almost every acute myeloid leukaemia (AML) patient undergoing induction chemotherapy and constitute a cornerstone in supportive measures for cancer patients in general. Randomized controlled trials have shown non‐inferiority or even superiority of restrictive transfusion guidelines over liberal transfusion guidelines in specific clinical situations outside of medical oncology. In this study, we analysed whether more restrictive RBC transfusion reduces blood use without affecting hard outcomes.
Materials and Methods: A total of 352 AML patients diagnosed between 2007 and 2018 and undergoing intensive induction chemotherapy were included in this retrospective analysis. In the less restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 8 g/dl (2007–2014). In the restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 7 g/dl (2016–2018). Liberal transfusion triggers were never endorsed.
Results: A total of 268 (76·1%) and 84 (23·9%) AML patients fell into the less restrictive and restrictive transfusion groups, respectively. The less restrictive transfusion group had 1 g/dl higher mean haemoglobin levels, received their first RBC transfusions earlier and needed 1·5 more units of RBC during the hospital stay of induction chemotherapy. Febrile episodes, C‐reactive protein levels, admission to the intensive care unit, length of hospital stay as well as response and survival rates did not differ between the two cohorts.
Conclusion: From our retrospective analysis, we conclude that a more restrictive transfusion trigger does not affect important outcomes of AML patients. The opportunity to test possible effects of the more severe anaemia in the restrictive transfusion group on quality of life was missed.
Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.
Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. We have reconstituted the core machinery for regulating lipid saturation in baker’s yeast to study its molecular mechanism. By combining molecular dynamics simulations with experiments, we uncover a remarkable sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains, and provide insights into the molecular rules of membrane adaptation. Our data challenge the prevailing hypothesis that membrane fluidity serves as the measured variable for regulating lipid saturation. Rather, we show that Mga2 senses the molecular lipid-packing density in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such properties in the future.
The way in which dendrites spread within neural tissue determines the resulting circuit connectivity and computation. However, a general theory describing the dynamics of this growth process does not exist. Here we obtain the first time-lapse reconstructions of neurons in living fly larvae over the entirety of their developmental stages. We show that these neurons expand in a remarkably regular stretching process that conserves their shape. Newly available space is filled optimally, a direct consequence of constraining the total amount of dendritic cable. We derive a mathematical model that predicts one time point from the previous and use this model to predict dendrite morphology of other cell types and species. In summary, we formulate a novel theory of dendrite growth based on detailed developmental experimental data that optimises wiring and space filling and serves as a basis to better understand aspects of coverage and connectivity for neural circuit formation.
The digital and information age has fundamentally transformed the way in which students learn and the study material they have at their disposal, especially in higher education. Students need to possess a number of higher-order cognitive and metacognitive skills, including effective information processing and critical reasoning to be able to navigate the Internet and use online sources, even those found outside of academically curated domains and in the depths of the Internet, and to solve (domain-specific) problems. Linking qualitative and quantitative research and connecting the humanities to empirical educational science studies, this article investigates the role of narratives and their impact on university students’ information seeking and their critical online reasoning (COR). This study focuses on the link between students’ online navigation skills, information seeking behavior and critical reasoning with regard to the specific domains: economics and medicine. For the empirical analysis in this article, we draw on a study that assesses the COR skills of undergraduate students of economics and medicine at two German universities. To measure COR skills, we used five tasks from the computer-based assessment “Critical Online Reasoning Assessment” (CORA), which assesses students’ skills in critically evaluating online sources and reasoning using evidence on contentious issues. The conceptual framework of this study is based on an existing methodology – narrative economics and medicine – and discusses its instructional potential and how it can be used to develop a new tool of “wise interventions” to enhance students’ COR in higher education. Based on qualitative content analyses of the students’ written responses, i.e., short essays, three distinct patterns of information seeking behavior among students have been identified. These three patterns – “Unambiguous Fact-Checking,” “Perspective-Taking Without Fact-Checking,” and “Web Credibility-Evaluating” – differ substantially in their potential connection to underlying narratives of information used by students to solve the CORA tasks. This analysis suggests that training university students in narrative analysis can strongly contribute to enhancing their critical online reasoning.
Die Extrakorporale Membranoxygenierung (ECMO) ist ein extrakorporales Organersatzverfahren, welches heutzutage insbesondere als Lungenersatzverfahren oder als kreislaufunterstützendes Verfahren zum Einsatz kommt. Seit dem ersten Einsatz 1971 im Rahmen eines posttraumatischen „Acute Respiratory Distress Syndrom“ (ARDS) ist die Zahl der ECMO-Behandlungen im kardiopulmonalen Bereich massiv gestiegen. Dennoch wird der Nutzen der ECMO kontrovers diskutiert. Die aktuellste randomisiert kontrollierte Studie aus dem Jahre 2018 konnte keinen signifikanten Nachweis erbringen, dass die Therapie des ARDS mittels einer ECMO einen Überlebensvorteil bringt. Randomisiert kontrollierte Studien bei Patienten mit kardiogenem Schock liegen zum gegenwärtigen Zeitpunkt nicht vor und für den Einsatz bei septischem Schock ist die Datenlage und Evidenz schwach. Angesichts der ungeklärten Evidenz und weil die ECMO ein komplexes, kostenintensives und mit Risiken verbundenes Verfahren ist, scheint eine sorgfältige Indikationsstellung unverzichtbar zu sein. Das Ziel unserer Studie war daher die Analyse der Mortalität bei Patienten mit Lungenversagen, kardiogenem Schock und septischem Schock. Darüber hinaus sollten mit der Mortalität assoziierte prognostische Variablen identifiziert werden. Des Weiteren sollte untersucht werden, ob sich mit steigender Fallzahl eine Lernkurve beobachten lässt.
Zu diesem Zwecke führten wir eine retrospektive Kohortenstudie an 131 Patienten durch, die zwischen April 2011 und Juli 2016 in der Asklepios Klinik Langen mit einer ECMO behandelt wurden. Die Patienten wurden hierbei in die drei oben genannten Gruppen kategorisiert. Mithilfe logistischer Regression erfolgte die Identifizierung prognostischer Variablen. Eine Lernkurve wurde anhand des „non-risk-adjusted cumulative observed minus expected failure graph“-Verfahrens erstellt.
Die Analyse der Daten ergab eine Gesamtmortalität von 56%. Die Mortalität bei Patienten mit Lungenversagen, kardiogenem Schock und septischem Schock betrug 54%, 59% bzw. 58%. Bei Patienten mit Lungenversagen waren das Alter, das Jahr und weniger als 20 Fälle pro Jahr signifikant mit der Mortalität assoziiert. Bei Patienten mit kardiogenem Schock waren mit der Mortalität assoziierte Variablen das Alter, der SAPS II-Score, der pH-Wert, der Serumlaktatwert prä-ECMO, der Basenüberschuss prä-ECMO sowie eine Hyperlipidämie. Bei Patienten mit septischem Schock konnten keine mit der Mortalität assoziierten Variablen identifiziert werden. In der multivariaten Regressionsanalyse nach Modellabbau zeigten sich in der gesamten Kohorte das Alter, das prä-ECMO Serumlaktat sowie weniger als 20 Fälle pro Jahr als signifikant mit der Mortalität assoziierte Variablen. Patienten, die vor 2014 behandelt wurden, also in einem Zeitraum mit weniger als 20 ECMO-Fällen pro Jahr, hatten eine signifikant höhere Mortalität als Patienten die im Intervall 2014-2016 behandelt wurden. Mit steigender Fallzahl konnte eine Lernkurve nachgewiesen werden, die einen Wendepunkt im Jahr 2014 zeigte. Der im Jahr 2014 beginnende Abwärtstrend signalisierte eine geringere Sterblichkeitsrate als erwartet.
Zusammenfassend ist die Mortalität in allen Indikationen weiter hoch. Die Fallzahl und damit auch die Erfahrung scheint eine wichtige Rolle in Bezug auf die Mortalität zu spielen. Des Weiteren unterstützen unsere Ergebnisse frühere Studien, die einen Einfluss des Alters und des prä-ECMO Laktat-Wertes auf die Mortalität zeigen konnten.
Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterised by a proliferation of fibroblasts in the tumour microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancerassociated fibroblasts (CAF). However, to date a deep molecular understanding of these fibroblasts is lacking. Aim of the present study therefore was a comprehensive
characterisation of these fibroblasts. Moreover, only a few studies describe the interplay of HRS cells and CAF. The paracrine communication and direct interaction of these two
cellular fractions have been investigated within this study. Finally, the influence of a few HRS cells within a lymph node orchestrate the mere alteration of its architecture and
morphology. Gene expression and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic - inflammatory phenotype characterised by MYOCD, CNN1 and IL-6 expression. TIMP3, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. Treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble
factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin(BV) induced cell death. However, HRS cells adherent to fibroblasts were protected from BV-induced injury. The cHL specific interaction of both cell fractions reveals an initiation of inflammatory key regulators such as IL13 and IL4. Among important adhesion molecules known from literature the blocking of integrin beta 1 solely interrupted the adhesion of HRS cells to CAF. In summary, this study proves the stable reprograming of CAF phenotype and expression derived from NS cHL. It presents a suitable in vitro model for studying the interaction of HRS cells and CAF by paracrine factors and adherence. Most importantly the observations confirm the importance of fibroblasts for HRS cells´ inflammatory niche and cell survival associated with TIMP3 which probably acts as a major factor to the typical accumulation of fibrosis observed in NS cHL.
The ongoing biodiversity crisis becomes evident in the widely observed decline in abundance and diversity of species, profound changes in community structure, and shifts in species’ phenology. Insects are among the most affected groups, with documented decreases in abundance up to 76% in the last 25–30 years in some terrestrial ecosystems. Identifying the underlying drivers is a major obstacle as most ecosystems are affected by multiple stressors simultaneously and in situ measurements of environmental variables are often missing. In our study, we investigated a headwater stream belonging to the most common stream type in Germany located in a nature reserve with no major anthropogenic impacts except climate change. We used the most comprehensive quantitative long‐term data set on aquatic insects available, which includes weekly measurements of species‐level insect abundance, daily water temperature and stream discharge as well as measurements of additional physicochemical variables for a 42‐year period (1969–2010). Overall, water temperature increased by 1.88 °C and discharge patterns changed significantly. These changes were accompanied by an 81.6% decline in insect abundance, but an increase in richness (+8.5%), Shannon diversity (+22.7%), evenness (+22.4%), and interannual turnover (+34%). Moreover, the community's trophic structure and phenology changed: the duration of emergence increased by 15.2 days, whereas the peak of emergence moved 13.4 days earlier. Additionally, we observed short‐term fluctuations (<5 years) in almost all metrics as well as complex and nonlinear responses of the community toward climate change that would have been missed by simply using snapshot data or shorter time series. Our results indicate that climate change has already altered biotic communities severely even in protected areas, where no other interacting stressors (pollution, habitat fragmentation, etc.) are present. This is a striking example of the scientific value of comprehensive long‐term data in capturing the complex responses of communities toward climate change.
Although the 12C(n,p)12B and 12C(n,d)11B reactions are of interest in several fields of basic and applied Nuclear Physics the present knowledge of these two cross-sections is far from being accurate and reliable, with both evaluations and data showing sizable discrepancies. As part of the challenging n_TOF program on (n,cp) nuclear reactions study, the energy differential cross-sections of the 12C(n,p)12B and 12C(n,d)11 B reactions have been measured at CERN from the reaction thresholds up to 30 MeV neutron energy. Both measurements have been recently performed at the long flight-path (185 m) experimental area of the n_TOF facility at CERN using a pure (99.95%) rigid graphite target and two silicon telescopes. In this paper an overview of the experiment is presented together with a few preliminary results.
The novel coronavirus (SARS-CoV-2), identified in China at the end of December 2019 and causing the disease COVID-19, has meanwhile led to outbreaks all over the globe, with about 571,700 confirmed cases and about 26,500 deaths as of March 28th, 2020. We present here the preliminary results of a mathematical study directed at informing on the possible application or lifting of control measures in Germany. The developed mathematical models allow to study the spread of COVID-19 among the population in Germany and to asses the impact of non-pharmaceutical interventions.