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Acquired von Willebrand Syndrome (AVWS) is a rare coagulation disorder which can be associated with IgM paraproteinaemia. Recently, recombinant von Willebrand factor (rVWF) has become available for the treatment of bleedings in patients with inherited von Willebrand disease, but experience in patients with AVWS is limited. We report on 2 patients with AVWS with underlying IgM paraproteinaemia with distinct underlying pathomechanisms. In 1 patient, the paraprotein built unspecific complexes with von Willebrand factor (VWF). In the other patient, we were able to detect an IgM antibody against VWF. Bleeding in this patient was successfully treated with rVWF. To our knowledge, this is the first report about the successful use of rVWF in a patient with AVWS with the detection of a VWF-specific antibody.

Laupheimer Gespräche 2016. Bekannt aus Fernsehen, Film und Funk, hg. vom Haus der Geschichte Baden-Württemberg, Heidelberg: Universitätsverlag Winter 2017. 252 S. ISBN 978-3-8253-6765-7. € 16,–

Melanie Elze / Rosemarie Godel-Gaßner / Alfred Hagemann / Sabine Krehl (Hg.), Jenny Heymann (1890 – 1996). Lebensstationen einer jüdischen Lehrerin mit bildungsgeschichtlichen Streifzügen durch Württemberg (Ludwigsburger Hochschulschriften, Bd. 18 der Reihe TRANSFER). Hohengehren: Schneider Verlag 2020. 366 S. ISBN 978-3-8340-2067-3. Geb. € 39,80

It is generally held that >100 TeV emission from astrophysical objects unambiguously demonstrates the presence of PeV protons or nuclei, due to the unavoidable Klein-Nishina suppression of inverse Compton emission from electrons. However, in the presence of inverse Compton dominated cooling, hard high-energy electron spectra are possible. We show that the environmental requirements for such spectra can naturally be met in spiral arms, and in particular in regions of enhanced star formation activity, the natural locations for the most promising electron accelerators: powerful young pulsars. Our scenario suggests a population of hard ultra-high energy sources is likely to be revealed in future searches, and may also provide a natural explanation for the 100 TeV sources recently reported by HAWC., Accepted for publication in ApJL

Christiane Twiehaus, Synagogen im Großherzogtum Baden (1806–1918), Eine Untersuchung zu ihrer Rezeption in den öffentlichen Medien, Heidelberg: Universitätsverlag Winter 2012. 251 S., 1 CD. ISBN 978-3-8253-5917-1. € 45,–

Laupheimer Gespräche 2012, „Ich glaube an das Alter, lieber Freund“, Vom Älterwerden und Alter (nicht nur) im Judentum, hg. vom Haus der Geschichte Baden-Württemberg, Heidelberg: Universitätsverlag Winter GmbH 2013. 189 S. ISBN 978-3-8253-6185-3. € 14,–

Gudrun Silberzahn-Jandt, Esslingen am Neckar im System von Zwangssterilisation und „Euthanasie“ während des Nationalsozialismus, Strukturen – Orte – Biographien, Esslinger Studien 24, hg. vom Stadtarchiv Esslingen am Neckar, Ostfildern: Jan Thorbecke Verlag 2015. 360 S., 53 Abb., 6 Tab. ISBN 978-3-7995-0647-2. € 24,90

Gretchen Kahn, Tagebücher von Juli 1905 bis Oktober 1915. Jüdisches Leben in Stuttgart. Transkribiert und mit Anmerkungen versehen von Rainer Redies (Veröffentlichungen des Archivs der Stadt Stuttgart, Sonderband), Ubstadt-Weiher: verlag regionalkultur 2017. 724 S. mit 30 Abb. ISBN 978-3-95505-005-4. € 39,–

Sigfried Kahn / Seligmann Kahn, Sieghaft schön und wohlgeeignet, einen Mann zu fesseln. Jüdische Ehevermittlung 1911 bis 1921 – Schadchen-Briefe aus dem „Copirbuch“. Transkribiert, eingeleitet und kommentiert von Rainer Redies, mit einem Geleitwort von Matthias Morgenstern (Tübinger Judaistische Studien, Bd. 5), Berlin: LIT-Verlag 2018. 160 S. ISBN 978-3-654-13888-0. € 29,90

GCJZ Stuttgart (Hg.), Zeitzeichen. 70 Jahre Gesellschaft für Christlich-Jüdische Zusammenarbeit Stuttgart e. V., Essen: Klartext Verlag 2018. 235 S., zahlr. Abb. ISBN 978-3-8375-2027-9. € 12,95

The article analyses Brunner’s attitude towards Zionism from the time when he conceived »Der Judenhass und die Juden«, focussing on his writings on Antisemitism and on questions of German-Jewish belonging. There is something remarkable about the historical moment when Brunner engaged with the question of Antisemitism. Whereas the rise of Antisemitism in the 1870 s prompted a number of Jewish public reactions and analyses, there was a visible decline in their number after the turn of the century. On the other hand, it was by no means extraordinary that Brunner connected his critical reflections on anti-Jewish sentiments with a negative attitude towards Zionism. The radicalism of his position becomes evident, however, in the fact that he treated both the hatred of Jews and Zionism as just two aspects of the same tragedy. While after 1912 his explicit anti-Zionism was, to a certain degree, shared by many members of the »Centralverein«, his position with respect to nation and nationhood tended towards the more radical views of Max Naumann, who associated Jewish identity with German nationalism.

Hypothesis The application of dynamic light scattering (DLS) is well-established for measuring diffusion coefficients related to either molecular or translational micelle diffusion. The simultaneous determination of both transport properties should be feasible, but has not been reported in the literature yet. Experiments Different diffusion modes present in a microemulsion and selected subsystems consisting of a polyol mixture, a binary surfactant mixture, and carbon dioxide (CO2) were investigated systematically by DLS at temperatures of (314, 333, and 353) K and corresponding pressures of (10, 13, and 16) MPa. Findings Diffusion coefficients related to molecular and translational micelle diffusion could be measured simultaneously and increase with increasing temperature. From the translational diffusion coefficients, an increase in the hydrodynamic diameter of the micelles from their non-swollen to the CO2-swollen state being in agreement with literature data for the same and similar microemulsions was found. The effective diffusion coefficients related to the faster molecular diffusion process only observable in the presence of CO2 are not affected significantly by the surfactant. The time-dependent parts of the recorded intensity correlation functions related to molecular diffusion processes are heterodyne because the scattered light modulated by molecular concentration fluctuations is superimposed with light scattered by the micelles.

Das Tagebuch der jüdischen Kriegskrankenschwester Rosa Bendit, 1914 bis 1917. Hg. und kommentiert von Susanne Rueß und Astrid Stölzle (Medizin, Gesellschaft und Geschichte. Jahrbuch des Instituts für Geschichte der Medizin der Robert-Bosch-Stiftung, Beiheft 43). Stuttgart: Franz Steiner Verlag 2012. 174 S. 6 Abb. ISBN 978-3-515-10124-0. € 29,–

Background: Most non-small cell lung cancers occur in elderly and frequently comorbid patients. Therefore, it is necessary to evaluate the efficacy of biomodulatory active therapy regimen, concertedly interfering with tumor-associated homeostatic pathways to achieve tumor control paralleled by modest toxicity profiles. Patients and Methods: The ModuLung trial is a national, multicentre, prospective, open-label, randomized phase II trial in patients with histologically confirmed stage IIIB/IV squamous (n = 11) and non-squamous non-small cell (n = 26) lung cancer who failed first-line platinum-based chemotherapy. Patients were randomly assigned on a 1:1 ratio to the biomodulatory or control group, treated with nivolumab. Patients randomized to the biomodulatory group received an all-oral therapy consisting of treosulfan 250 mg twice daily, pioglitazone 45 mg once daily, clarithromycin 250 mg twice daily, until disease progression or unacceptable toxicity. Results: The study had to be closed pre-maturely due to approval of immune checkpoint inhibitors (ICi) in first-line treatment. Thirty-seven patients, available for analysis, were treated in second to forth-line. Progression-free survival (PFS) was significantly inferior for biomodulation (N = 20) vs. nivolumab (N = 17) with a median PFS (95% confidence interval) of 1.4 (1.2–2.0) months vs. 1.6 (1.4–6.2), respectively; with a hazard ratio (95% confidence interval) of 1.908 [0.962; 3.788]; p = 0.0483. Objective response rate was 11.8% with nivolumab vs. 5% with biomodulation, median follow-up 8.25 months. The frequency of grade 3–5 treatment related adverse events was 29% with nivolumab and 10% with biomodulation. Overall survival (OS), the secondary endpoint, was comparable in both treatment arms; biomodulation with a median OS (95% confidence interval) of 9.4 (6.0–33.0) months vs. nivolumab 6.9 (4.6–24.0), respectively; hazard ratio (95% confidence interval) of 0.733 [0.334; 1.610]; p = 0.4368. Seventy-five percent of patients in the biomodulation arm received rescue therapy with checkpoint inhibitors. Conclusions: This trial shows that the biomodulatory therapy was inferior to nivolumab on PFS. However, the fact that OS was similar between groups gives rise to the hypothesis that the well-tolerable biomodulatory therapy may prime tumor tissues for efficacious checkpoint inhibitor therapy, even in very advanced treatment lines where poor response to ICi might be expected with increasing line of therapy.

Aims. Colliding wind binary systems have long been suspected to be high-energy (HE; 100 MeV < E < 100 GeV) {\gamma}-ray emitters. {\eta} Car is the most prominent member of this object class and is confirmed to emit phase-locked HE {\gamma} rays from hundreds of MeV to ~100 GeV energies. This work aims to search for and characterise the very-high-energy (VHE; E >100 GeV) {\gamma}-ray emission from {\eta} Car around the last periastron passage in 2014 with the ground-based High Energy Stereoscopic System (H.E.S.S.). Methods. The region around {\eta} Car was observed with H.E.S.S. between orbital phase p = 0.78 - 1.10, with a closer sampling at p {\approx} 0.95 and p {\approx} 1.10 (assuming a period of 2023 days). Optimised hardware settings as well as adjustments to the data reduction, reconstruction, and signal selection were needed to suppress and take into account the strong, extended, and inhomogeneous night sky background (NSB) in the {\eta} Car field of view. Tailored run-wise Monte-Carlo simulations (RWS) were required to accurately treat the additional noise from NSB photons in the instrument response functions. Results. H.E.S.S. detected VHE {\gamma}-ray emission from the direction of {\eta} Car shortly before and after the minimum in the X-ray light-curve close to periastron. Using the point spread function provided by RWS, the reconstructed signal is point-like and the spectrum is best described by a power law. The overall flux and spectral index in VHE {\gamma} rays agree within statistical and systematic errors before and after periastron. The {\gamma}-ray spectrum extends up to at least ~400 GeV. This implies a maximum magnetic field in a leptonic scenario in the emission region of 0.5 Gauss. No indication for phase-locked flux variations is detected in the H.E.S.S. data., Comment: 9 pages, 4 figures, 3 tables, in press with A&A

Background Maintaining gastrointestinal (GI) microbiome diversity plays a key role during allogeneic stem cell transplantation (ASCT), and loss of diversity correlates with acute GI graft versus host disease (GvHD) and poor outcomes. Methods In this retrospective analysis of 161 ASCT patients, we used serial analyses of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters within the first 10 days after ASCT to identify potential commensal microbiota–sparing antibiotics. Based on antibiotic activity, we formed 3 subgroups (Rifaximin without systemic antibiotics, Rifaximin with systemic antibiotics, and Ciprofloxacin/Metronidazole with/without systemic antibiotics). Results Mono-antibiosis with Rifaximin revealed higher 3-IS levels (P < .001), higher Clostridium cluster XIVa (CCXIVa) abundance (P = .004), and higher Shannon indices (P = .01) compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics. Rifaximin followed by systemic antibiotics maintained microbiome diversity compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics, as these patients showed still higher 3-IS levels (P = .04), higher CCXIVa copy numbers (P = .01), and higher Shannon indexes (P = .01). Even for this larger cohort of patients, the outcome was superior with regard to GI GvHD (P = .05) and lower transplant-related mortality (P < .001) for patients receiving Rifaximin plus systemic antibiotics compared to other types of systemic antibiotic treatment. Antibiosis with Ciprofloxacin/Metronidazole (n = 12, P = .01), Piperacillin/Tazobactam (n = 52, P = .01), Meropenem/Vancomycin (n = 16, P = .003), Ceftazidime (n = 10, P = .03), or multiple systemic antibiotics (n = 53, P = .001) showed significantly lower 3-IS levels compared to mono-antibiosis with Rifaximin (n = 14) or intravenous Vancomycin (n = 4, not statistically significant). Conclusions Different types of antibiotic treatments show different impacts on markers of microbiome diversity. The identification of antibiotics sparing commensal bacteria remains an ongoing challenge. However, Rifaximin allowed a higher intestinal microbiome diversity, even in the presence of systemic broad-spectrum antibiotics.

Vischer’s Shakespeare studies not only provide valuable insights into the bard’s plays, they also advance the type of positivist approach later practised by Bradley and others. This study focuses on Hamlet, the play most prominent in nineteenth-century German Shakespeare criticism. Two aspects are of particular interest: (1) Vischer’s nationalist approach, placing Shakespeare solely into a Northern European, Germanic environment. (2) Vischer’s primary concern with character studies. By removing Hamlet from the idealised pedestal on which the Romantics had placed him, Hamlet is no longer seen as the philosopher prince, tormented by moral scruples, but as caught in a net of adverse circumstances which he has to overcome in order to fulfil his father’s command. Vischer thereby liberates Shakespeare criticism from the constraints of domestic tragedy and its bourgeois morality.

Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time‐consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus‐specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high‐risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis.

Taking advantage of 10 years of Fermi-LAT data, we perform a new and deep analysis of the pulsar wind nebula (PWN) HESS J1825-137. We present the results of the spectral analysis and of the first energy-resolved morphological study of the PWN HESS J1825-137 from 1 GeV to 1 TeV. This PWN is an archetypal system making it a perfect laboratory for studying particle transport mechanisms. Combining this analysis with recent H.E.S.S. results enables a more complete picture of the nebula to emerge., Comment: 7 pages, 6 figures, published in in proceedings of science for the 36th International Cosmic Ray Conference (ICRC2019

Acute gastrointestinal (GI) graft-versus-host disease (GvHD) is a life-threating complication in patients after allogeneic stem cell transplantation (ASCT). In 60 sonographic analyses, a novel scoring system for non-invasive diagnosis of severe GI GvHD was developed. The score comprised morphological and vascular changes using B-mode and color-coded Doppler sonography, changes of mural stiffness using compound elastography, and dynamic microvascularisation using contrast-enhanced ultrasound (CEUS). Furthermore, inflammatory parameters such as CRP, Calprotectin, and regenerating islet-derived protein 3α (Reg3α) were obtained. ROC curve analysis of our novel GvHD sum score revealed an area under the curve of 1.0 (95% CI: 0.99-1.00) in diagnosing GI GvHD and 0.88 (95% CI: 0.79-0.96) for severe GI GvHD. A sum score above 5 correlated with GI GvHD with a sensitivity of 97.6% (41/42) and a specificity of 94.4% (17/18) and score values above 10 with severe GI GvHD with a sensitivity of 91.7% (11/12) and specificity of 79.2% (38/48). The additional use of inflammatory parameters did not improve the predictive power. CEUS is a promising, non-invasive tool for the diagnosis of acute GI GvHD. Together with further descriptive parameters for inflammatory processes, it gains significant diagnostic accuracy in identifying patients with severe stages of acute intestinal GvHD.

Background The ModuLung trial addresses the medical need for low-toxic therapies in frequently comorbid patients with relapsed or refractory non-small cell lung cancer (NSCLC). We evaluated safety and efficacy of a biomodulatory approach in > =2nd-line, aiming for induction of anakoinosis i.e. communicative reprogramming of dysregulated cellular and intercellular homeostasis. Methods Patients with stage IIIB/IV squamous or non-squamous NSCLC and disease progression during or after at least one platinum-based chemotherapy were stratified according to histology, and randomly assigned 1:1 to treosulfan 250 mg twice daily, pioglitazone 45 mg once daily and clarithromycin 250 mg twice daily (experimental arm) or nivolumab 3 mg/kg every 2 weeks (control arm). The primary endpoint was progression-free survival (PFS). Results Due to the approval of checkpoint inhibitors in first-line, the study was prematurely closed after randomization of 40 of the 86 initially planned patients. The main efficacy and safety results are presented in the table and show no statistically significant difference between groups. The two-year survival rate achieved in the biomodulatory arm was 10% (95% CI, 1.2 to 31.7) and 5.9% (95% CI, 0.1 to 28.7) in the nivolumab arm. 75% and 53% of the patients proceeded to a further line of therapy, respectively. Table . 1570P Results Biomodulatory Arm (n = 20) 35% > 2nd-line Nivolumab Arm (n = 17) 41.2% > 2nd-line HR & 95% CI or p-value PFS, median in months 1.6 2.1 HR = 1.17; 95% CI, 0.59--2.34 OS, median in months 8.2 6.9 HR = 0.86; 95% CI, 0.38-1.96 ORR, n (%) 2 (10%) 0 (0%) P = 0.49 Grade 3-5 AE, n (%) 2 (10%) 6 (35%) P = 0.11 Conclusions Combination of clarithromycin, pioglitazone and metronomic chemotherapy is active in the > =2nd line treatment of NSCLC and warrants further investigations. Nivolumab did not induce any tumor response and was relatively toxic in this population. Novel treatment approaches are urgently needed for patients who previously received platinum-based chemotherapy for advanced squamous and non-squamous NSCLC (Funded by Anticancer Fund, EudraCT number 2014-004095-31). Clinical trial identification EudraCT: 2014-004095-31, Start Date: 2015-07-13. Legal entity responsible for the study Freistaat Bayern respresented by University of Regensburg represented by Kaufmannischer Direktor. Funding Anticancer Fund, Brussels, Belgium. Disclosure All authors have declared no conflicts of interest.