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Objective: Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD.
Design: A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol.
Results: A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34–5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73–3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure.
Conclusion: Our study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects.
In Germany, a grave labor shortage in the nursing and elderly care sectors has prompted the response of recruiting skilled nursing staff from abroad in recent years. This article analyzes these recruitment practices as forms of “migration management”: German migration policy has changed according to this paradigm to attempt utilitarian control over migration processes and mediate between labor market concerns on the one hand and isolationist, politico-cultural seclusion on the other. Based on original research through interviews and document analysis, we identify four relevant levels of analysis in researching migration management in the context of the recruitment of skilled nurses: (1) Definition of problem areas: How is migration programmatically legitimized as a solution to social problems? (2) Categorization of migration: How are migration processes classified? (3) Change in statehood: How are sites and actors of migration control being privatized and diversified? (4) Technologies: By means of which procedures, legal foundations and political instruments does migration management take place in the everyday? We believe that taking these four foci as points of departure would be beneficial for further inquiries in critical migration research.
Leben braucht Licht und den täglichen Wechsel von Licht und Dunkel. Das gilt auch für den Menschen. Licht dient unserer Orientierung – nicht nur im Raum, sondern auch in der Zeit. Der Tag-Nacht-Wechsel ist der wichtigste Umweltreiz für die Taktung unserer Inneren Uhr. Zu wenig Licht am Tag und zu viel Licht in der Nacht kann sie aus dem Takt bringen und zu Schlafstörungen und Depressionen führen.
Die Erkenntnis, dass das Gehirn Hormone produziert, gehört heute zum Allgemeingut des biomedizinischen Wissens. Ausgangspunkt der modernen Neuroendokrinologie ist das weit gespannte biologische Konzept der Neurosekretion, das Ernst und Berta Scharrer in den 1930er Jahren aus einer Reihe von fundamentalen Einzelentdeckungen entwickelten. Das Fundament dieses Konzeptes legte das Paar am Neurologischen Institut (Edinger Institut) in Frankfurt am Main.
In their study on "The modern anthropology of Southeast Asia", Victor King and William Wilder raise the question in how far the region can be taken as a field of anthropological enquiry. After their initial discussion of cultural and social trends as well as anthropological studies, they conclude that the common issue of the region is its diversity. They come to the rather pragmatic solution that "South-East Asia constitutes a convenient unit of study, ... but ... we should not think of it in terms of a bounded, unified and homogenous socio-cultural area" (King/Wilder 2003: 24). We doubt that there are homogenous socio-cultural areas anywhere else. These are usually constructed through the invention of traditions and ideological simulations. The interesting case with regards to Southeast Asia is, why no such homogeneity has been constructed, not even by anthropologists or sociologists. ...
Gegenstand der Untersuchung ist eine umfassende Analyse der zeitgenössischen Medienprominenz, hier deutschsprachige Singer-Songwriter, eingebettet in die Kontexte ‘psychische Störungen‘ (erhoben mit dem SKID-II/M.I.N.I.), ‘Kreativität‘ (TSD-Z) und ‘Perfektionismus hinsichtlich des Aussehens‘ (AAS), mit der Zielsetzung dieses heterogene Phänomen mittels einer ganzheitlichen Perspektive zu erfassen. An der Studie nahmen insgesamt 31 prominente und 31 nicht promiente deutschsprachige Singer-Songwriter teil, wobei 15 der prominenten Singer-Songwriter in Besitz von mindestens einem ‘ECHO‘, 14 in Besitz von mindestens einer ‘Goldenen Schallplatte‘ und 2 mit mehr als 200 Nennungen in der Gruner + Jahr Pressedatenbank verzeichnet sind. Zunächst geht die Arbeit der Fragestellung nach, ob sich die prominenten Singer-Songwriter in den Störungsbildern ‘affektive Störung‘, ‘narzisstische Persönlichkeitsstörung‘, ‘Borderline-Persönlichkeitsstörung‘, ‘Alkoholmissbrauch/-abhängigkeit und ‘Substanzmissbrauch/-abhängigkeit‘ von den nicht prominenten Singer-Songwritern unterscheiden. Die Ergebnisse zeigen auf, dass prominente Singer-Songwriter signifikant häufiger unter einer narzisstischen Persönlichkeitsstörung, Alkoholabhängigkeit und Substanzmissbrauchs leiden als nicht prominente Singer-Songwriter. Außerdem wird ersichtlich, dass die prominenten Singer-Songwriter vermehrt Kokain und die nicht prominenten Singer-Songwriter vermehrt Marihuana konsumieren. Die Werte der prominenten und nicht prominenten Singer-Songwriter in Bezug auf die narzisstische Persönlichkeitsstörung sowie Alkoholmissbrauch/-abhängigkeit übersteigen bei weitem die Prävalenzzahlen der deutschen Allgemeinbevölkerung. Als nächstes wurde geprüft, ob prominente Singer-Songwriter kreativer sind als nicht prominente Singer-Songwriter. Diese Annahme konnte, ebenso wie die darauffolgende Annahme, nämlich dass die Kreativität den Zusammenhang zwischen einer psychischen Störung und der Prominenz erklärt, nicht bestätigt werden. Die Kreativität stellt des Weiteren auch kein Moderatoreffekt dar und wirkt somit nicht, gemeinsam mit einer narzisstischen Persönlichkeitsstörung, verstärkend auf die Prominenz. Wiederum ergab sich hypothesenkonform, dass prominente Singer-Songwriter perfektionistischer hinsichtlich ihres Aussehens eingestellt sind als nicht prominente Singer-Songwriter. Zuletzt zeigen die Ergebnisse, dass die Prominenz den Zusammenhang zwischen einer narzisstischen Persönlichkeitsstörung und der perfektionistischen Einstellung hinsichtlich des Aussehens nicht erklärt, jedoch verstärkt die Prominenz den Einfluss einer Depression auf die soziale Isolation.
Previous reports of improved oral reading performance for dyslexic children but not for regular readers when between-letter spacing was enlarged led to the proposal of a dyslexia-specific deficit in visual crowding. However, it is in this context also critical to understand how letter spacing affects visual word recognition and reading in unimpaired readers. Adopting an individual differences approach, the present study, accordingly, examined whether wider letter spacing improves reading performance also for non-impaired adults during silent reading and whether there is an association between letter spacing and crowding sensitivity. We report eye movement data of 24 German students who silently read texts presented either with normal or wider letter spacing. Foveal and parafoveal crowding sensitivity were estimated using two independent tests. Wider spacing reduced first fixation durations, gaze durations, and total fixation time for all participants, with slower readers showing stronger effects. However, wider letter spacing also reduced skipping probabilities and elicited more fixations, especially for faster readers. In terms of words read per minute, wider letter spacing did not provide a benefit, and faster readers in particular were slowed down. Neither foveal nor parafoveal crowding sensitivity correlated with the observed letter-spacing effects. In conclusion, wide letter spacing reduces single word processing time in typically developed readers during silent reading, but affects reading rates negatively since more words must be fixated. We tentatively propose that wider letter spacing reinforces serial letter processing in slower readers, but disrupts parallel processing of letter chunks in faster readers. These effects of letter spacing do not seem to be mediated by individual differences in crowding sensitivity.
The reading acceleration phenomenon refers to the effect that experimentally induced time constraints can generate instantaneous improvements of reading rate, accuracy and comprehension among typical and reading impaired readers of different age groups. An overview of studies applying the fading manipulation (i.e., letters are erased in reading direction), which induces the time constraints causing the acceleration phenomenon, is provided in the first part of this review. The second part summarises the outcomes of studies using a training approach called the reading acceleration program (RAP) that integrated core principles of the acceleration phenomenon to generate persistent reading performance improvements. Our review shows ample evidence for the validity of the acceleration phenomenon, since it has been replicated across various languages and populations. However, although there are several explanatory approaches for underlying mechanisms, none of them is well substantiated by empirical evidence so far. Similarly, although generally positive effects of RAP training were reported for several languages and groups of readers, the exact mechanisms causing improved reading rates and comprehension are not well understood. Our critical discussion points out several limitations of RAP that call for further research. However, we also highlight several benefits regarding RAP's potential as an intervention approach for enhancements in reading performance. Video abstract link: https://youtu.be/wO6aEXavk8w
Higher N170 amplitudes to words and to faces were recently reported for faster readers of German. Since the shallow German orthography allows phonological recoding of single letters, the reported speed advantages might have their origin in especially well-developed visual processing skills of faster readers. In contrast to German, adult readers of Hebrew are forced to process letter chunks up to whole words. This dependence on more complex visual processing might have created ceiling effects for this skill. Therefore, the current study examined whether also in the deep Hebrew orthography visual processing skills as reflected by N170 amplitudes explain reading speed differences. Forty university students, native speakers of Hebrew without reading impairments, accomplished a lexical decision task (i.e., deciding whether a visually presented stimulus represents a real or a pseudo word) and a face decision task (i.e., deciding whether a face was presented complete or with missing facial features) while their electroencephalogram was recorded from 64 scalp positions. In both tasks stronger event related potentials (ERPs) were observed for faster readers in time windows at about 200 ms. Unlike in previous studies, ERP waveforms in relevant time windows did not correspond to N170 scalp topographies. The results support the notion of visual processing ability as an orthography independent marker of reading proficiency, which advances our understanding about regular and impaired reading development.
We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52–0.67) and 0.56 (95% CI 0.43–0.68). The relapse rate was high (PP 0.33, 95% CI 0.27–0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and “symptomatic” etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48–0.89) or corticosteroids (PP 0.72, 95% CI 0.54–0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02–0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.
Key points
* Systematic review resulting in low to moderately solid evidence on the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroid treatment in children with epilepsy other than infantile spasms.
* Meta-analysis based on aggregate data from 2 controlled prospective, 5 uncontrolled prospective, and 31 retrospective studies.
* Pooled data showing a seizure response in 60% and electroencephalography (EEG) response in 56% of patients, with no major differences between drugs. However, 30%–40% of patients relapse after the cessation of treatment.
* The most frequent adverse effects are obesity and Cushing's syndrome, occurring in 70% of patients under continuous treatment for some weeks, but in less than 10% undergoing pulsed, intermittent regimens.
* More prospective, randomized-controlled studies are needed to improve the level of evidence and define the optimal doses and treatment duration.
Background: Because Endomyocardial Biopsy has low sensitivity of about 20%, it can be performed near to myocardium that presented as Late Gadolinium Enhancement (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of comparing topography of CMR and histological findings has not yet been investigated. Thus the current study was performed using an animal model of myocarditis. Results: In 10 male Lewis rats Experimental Autoimmune myocarditis was induced, 10 rats served as control. On day 21 animals were examined by CMR to compare topographic distribution of LGE to histological inflammation. Sensitivity, specificity, positive and negative predictive values for LGE in diagnosing myocarditis were determined for each segment of myocardium. Latter diagnostic values varied widely depending on topographic distribution of LGE and inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to 76% (left lateral myocardium) and positive predictive values were up to 85% (left lateral myocardium), whereas sensitivity and positive predictive value dropped to 0 - 33% (left inferior myocardium). Conclusions: Topographic distribution of LGE and histological inflammation seem to influence sensitivity, specifity, positive and negative predictive values. Nevertheless, positive predictive value for LGE of up to 85% indicates that Endomyocardial Biopsy should be performed "MR-guided". LGE seems to have greater sensitivity than Endomyocardial Biopsy for the diagnosis of myocarditis.
Background: High-intensity focused ultrasound (HIFU) allows to inflict intracorporal thermal lesions without penetrating the skin or damaging the surrounding tissue. This analysis intends to assess the magnitude of HIFU-induced ablations within benign thyroid nodules using scintigraphic imaging with 99mTc.
Methods: Ten cold, hot, or indifferent nodules were treated using multiple pulses of HIFU to induce temperatures of around 85°C within the ablation zone. Pre- and posttreatment, uptake values of 99mTc pertechnetate or 99mTc-MIBI were recorded. The pre-post reduction of nodular uptake was evaluated to assess ablation magnitude.
Results: Relative nodular uptake in relation to total thyroidal uptake decreased after one session of HIFU in all cases. Median 99mTc-MIBI uptake reduction was 35.5% (ranging from 11% to 57%; p < 0.1), while 99mTc-pertechnetate scintigraphy showed a median uptake reduction of 27% (range 10% to 44%; p < 0.1). No major complications were observed.
Conclusions: HIFU appears to be safe and is an easy to perform means of thermal ablation. This study shows that HIFU treatment in thyroidal nodules can be evaluated by scintigraphic means shortly after the intervention. Due to small sample size, the exact magnitude of HIFU ablation efficiency in thyroidal nodules remains a value to beassessed in a larger study.
Previous studies document a relationship between gambling activity at the aggregate level and investments in securities with lottery-like features. We combine data on individual gambling consumption with portfolio holdings and trading records to examine whether gambling and trading act as substitutes or complements. We find that gamblers are more likely than the average investor to hold lottery stocks, but significantly less likely than active traders who do not gamble. Our results suggest that gambling behavior across domains is less relevant compared to other portfolio characteristics that predict investing in high-risk and high-skew securities, and that gambling on and off the stock market act as substitutes to satisfy the same need, e.g., sensation seeking.
The ongoing pandemic caused by the Betacoronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) demonstrates the urgent need of coordinated and rapid research towards inhibitors of the COVID-19 lung disease. The covid19-nmr consortium seeks to support drug development by providing publicly accessible NMR data on the viral RNA elements and proteins. The SARS-CoV-2 genome encodes for approximately 30 proteins, among them are the 16 so-called non-structural proteins (Nsps) of the replication/transcription complex. The 217-kDa large Nsp3 spans one polypeptide chain, but comprises multiple independent, yet functionally related domains including the viral papain-like protease. The Nsp3e sub-moiety contains a putative nucleic acid-binding domain (NAB) with so far unknown function and consensus target sequences, which are conceived to be both viral and host RNAs and DNAs, as well as protein-protein interactions. Its NMR-suitable size renders it an attractive object to study, both for understanding the SARS-CoV-2 architecture and drugability besides the classical virus’ proteases. We here report the near-complete NMR backbone chemical shifts of the putative Nsp3e NAB that reveal the secondary structure and compactness of the domain, and provide a basis for NMR-based investigations towards understanding and interfering with RNA- and small-molecule-binding by Nsp3e.
The current outbreak of the highly infectious COVID-19 respiratory disease is caused by the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). To fight the pandemic, the search for promising viral drug targets has become a cross-border common goal of the international biomedical research community. Within the international Covid19-NMR consortium, scientists support drug development against SARS-CoV-2 by providing publicly available NMR data on viral proteins and RNAs. The coronavirus nucleocapsid protein (N protein) is an RNA-binding protein involved in viral transcription and replication. Its primary function is the packaging of the viral RNA genome. The highly conserved architecture of the coronavirus N protein consists of an N-terminal RNA-binding domain (NTD), followed by an intrinsically disordered Serine/Arginine (SR)-rich linker and a C-terminal dimerization domain (CTD). Besides its involvement in oligomerization, the CTD of the N protein (N-CTD) is also able to bind to nucleic acids by itself, independent of the NTD. Here, we report the near-complete NMR backbone chemical shift assignments of the SARS-CoV-2 N-CTD to provide the basis for downstream applications, in particular site-resolved drug binding studies.
The family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing, and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately-100-kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA- and RNA-binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerise, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species.
Background: Infection is a main cause of morbidity and mortality after heart surgery, with multi-resistant pathogens increasingly representing a challenge. Daptomycin provides bactericidal activity against gram-positive organisms that are resistant to standard treatment including vancomycin.
Methods: A cohort of cardiac surgical patients, treated with daptomycin for major infection at two tertiary care centers, were retrospectively studied with a particular focus on the type of infection, causative pathogens and co-infections, daptomycin dosage, adverse events and outcome in order to provide evidence for the efficiency and safety of daptomycin in a distinct high-risk patient population.
Results: Sixty-five patients (87.7 % males, 60.4 ± 13.5 years) who had undergone aortic surgery (20.0 %), ventricular assist device (VAD) implantation (21.5 %), combined procedures (21.5 %), coronary artery bypass grafting (12.3 %), isolated valve surgery (15.4 %) and heart transplantation (7.7 %) were diagnosed with catheter-related infection (26.1 %), valve endocarditis (18.8 %), sternal wound (13.0 %), VAD-associated (11.6 %), cardiac implantable electrophysiological device (CIED)-associated (4.1 %), respiratory tract (4.3 %), bloodstream (4.3 %) and other infection (4.3 %). In 13.0 %, no focus of infection was identified though symptoms of severe infection were present. The most frequent pathogens were Staphylococcus epidermidis (30.4 %), Staphylococcus aureus (23.1 %) and Enterococcus species (10.1 %). Daptomycin doses ranging from 3 mg/kg every 48 h to 10 mg/kg every 24 h were administered for 15.4 ± 11.8 days. 87.0 % of the cases were classified as success, 7.2 % as treatment failure and 5.8 as non-evaluable. Adverse events were limited to one case of mild and one case of moderate neutropenia with recovery upon termination of treatment.
Conclusion: Daptomycin proved safe and effective in major infection in high-risk cardiac surgical patients.
Left ventricular non-compaction cardiomyopathy and left ventricular assist device: a word of caution
(2016)
BACKGROUND: In patients with left ventricular non-compaction (LVNC), implantation of a left ventricular assist device (LVAD) may be performed as a bridge to transplantation. In this respect, the particular characteristics of the left ventricular myocardium may represent a challenge.
CASE PRESENTATION: We report a patient with LVNC who required urgent heart transplantation for inflow cannula obstruction nine months after receiving a LVAD. LVAD parameters, echocardiography and examination of the explanted heart suggested changes of left ventricular configuration brought about by LVAD support as the most likely cause of inflow cannula obstruction.
CONCLUSIONS: We conclude that changes experienced by non-compacted myocardium during LVAD support may give rise to inflow cannula obstruction and flow reduction. Presence of LVNC mandates tight surveillance for changes in LV configuration and LVAD flow characteristics and may justify urgent transplantation listing status.
Device-related infections in recipients of left ventricular assist devices (LVAD) have been recognized as a major source of morbidity and mortality. They require a high level of diagnostic effort as part of the overall burden resulting from infectious complications in LVAD recipients. We present a multi-allergic patient who was treated for persistent sterile intrathoracic abscess formation and pericardial empyema following minimally invasive LVAD implantation including use of a sheet of e-polytetrafluoroethylene (ePTFE) membrane to restore pericardial integrity. Sterile abscess formation and pericardial empyema recurred after surgical removal until the ePTFE membrane was removed, suggesting that in disposed patients, ePTFE may be related to sterile abscess formation or sterile empyema.
Mast cells are long-lived tissue-resident leukocytes, located most abundantly in the skin and mucosal surfaces. They belong to the first line of defence of the body, protecting against invading pathogens, toxins and allergens. Their secretory granules are densely packed with a plethora of mediators, which can be released immediately upon activation of the cell. Next to their role in IgE-mediated allergic diseases and in promoting inflammation, potential anti-inflammatory functions have been assigned to mast cells, depending on the biological setting. The aim of this thesis was to contribute to a better understanding of the role of mast cells during the resolution of a local inflammation. Therefore, in a first of step a suitable model of a local inflammation had to be identified. Since comparison of the two Toll-like receptor (TLR)-agonists zymosan and lipopolysaccharide (LPS), which are most commonly used to locally induce inflammation, revealed a systemic response after LPS-injection and a local inflammation after zymosan-injection, the TLR2 agonist zymosan was chosen for the subsequent experiments. Multi epitope ligand cartography (MELC) combined with statistical neighbourhood analysis showed that mast cells are located in an anti-inflammatory microenvironment next to M2 macrophages during resolution of inflammation, while neutrophils and M1 macrophages are located in the zymosan-filled core of the inflammation. Furthermore, infiltrating neutrophils during peak inflammation and an increasing population of macrophages phagocytosing neutrophils during resolution of inflammation could be observed. MELC as well as flow cytometry analysis of mast cell-deficient mice revealed a decreased phagocytosing activity of macrophages in the absence of mast cells. As an untargeted approach to identify mast cell-derived mediators induced by zymosan, mRNA sequencing of bone marrow-derived mast cells (BMMCs) was performed. Gene ontology term analysis of the sequencing data revealed the induction of the type I interferon (IFN) pathway as the dominant response. Contradicting previous studies, I could validate the production of IFN-β by mast cells in response to zymosan and LPS in vitro. Furthermore IFN-β expression by mast cells was also detected in vivo. In accordance with previous studies regarding other cell types the release of IFN-β by mast cells depends on endosomal signaling. The potential of IFN-β to enhance the phagocytosing activity of macrophages has been demonstrated recently. Besides IFN-β, various other mediators with reported enhancing effects on macrophage phagocytosis were also induced by zymosan in BMMCs, including Interleukin (IL)-1β, IL-4, IL-13, and Prostaglandin (PG) E2. Thus, either one of these mediators alone or a combination of them could promote macrophage phagocytosis.
In conclusion, I herein present mast cells as a novel source for IFN-β induced by non-viral TLR ligands and demonstrate their enhancing effect on macrophage phagocytosis, thereby contributing to the resolution of inflammation.
Bacterial and fungal toll-like receptor activation elicits type I IFN responses in mast cells
(2021)
Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-β synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-β was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-β, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.
Die neoklassische Arbitragetheorie setzt voraus, daß alle Marktteilnehmer identische Erwartungen bezüglich der künftigen zustandsabhängigen Auszahlungen von risikobehafteten Wertpapieren bilden. Die Unsicherheit besteht dann im Eintritt des Zustandes selber, jedoch nicht in dessen Ausprägung.
In diesem Artikel wird untersucht, wie eine zusätzliche Unsicherheit in Form des Unwissens über die genaue Ausprägung eines Umweltzustandes modelliert werden kann. Dazu werden die klassischen Finanzwirtschaftstheorien mit der Fuzzy Set Theorie (Theorie unscharfer Mengen) verbunden.
Ziel ist es, sowohl eine einperiodige als auch eine mehrperiodige Arbitragebewertung so zu modifizieren, daß vage Erwartungen der Marktteilnehmer unterstellt werden können.
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Am 27. Dezember 2015 verabschiedete der Ständige Ausschuss des Nationalen Volkskongresses das erste Antiterrorgesetz in der Geschichte der Volksrepublik China (VRC). Damit wurde eine über 25 Jahre erarbeitete umfangreiche Antiterrorstrategie zu Papier gebracht und mit ihr endlich eine verbindliche rechtliche Definition von „Terrorismus.“ Bereits gängige Praktiken wie öffentliche Medienzensur oder die Verpflichtung von Telekommunikationsunternehmen und Internetprovidern zur Bereitstellung von Inhaltsdaten wurden formalisiert und verschärft, sowie auch die Mobilisierung zivilgesellschaftlicher Organisationen auf eine rechtliche Grundlage gestellt. Allerdings stellt das Gesetz nur den finalen, formalen Schritt einer fünfundzwanzigjährigen Entwicklung dar. Tatsächlich kämpft Beijing seit Anfang der 1990er Jahre in der Provinz Xinjiang mit einer Mischung aus separatistisch und islamistisch motivierter politischer Gewalt, an deren Spitze seit spätestens 2008 das East Turkestan Independence Movement (ETIM) steht. ETIM weist ideell und organisatorisch eine Nähe zu Al Qaeda auf, und arbeitet transnational mit der Islamischen Bewegung Usbekistans, Tehrik-i-Taliban (Pakistan) und der al-Nusra Front (Syrien) zusammen...
This dissertation explores the breadth and variation of authoritarian counter-terrorism strategies and their legitimacy-related origins to challenge prevailing assumptions in Terrorism Studies. Research and analysis are conducted in the form of a Structured Focused Comparison of domestic counter-terrorism strategies in two electoral autocracies. The first case is Russia’s domestic engagement against a mix of ethno-separatist and Islamist terrorism emanating from its North Caucasus republics between 1999 and 2018. The second case is China’s engagement vis-à-vis a similar type of terrorism in its Xinjiang Uyghur Autonomous Region between 1990 and 2018.
The comparison shows that, contrary to prevailing assumptions, the two strategies differ immensely from one another while containing significant if not predominant non-coercive elements. It further shows that the two strategies are closely related to the two states’ sources and resources of legitimacy, both in their original motivation to tackle the terrorist threat and in the design of counter-terrorism strategies. Drawing on David Beetham’s theory of The Legitimation of Power and on the Comparative Politics, Terrorism Studies and Civil War literatures, the dissertation explores the influence of five sources and (re)sources of legitimacy on the two counter-terrorism strategies: responsiveness, performance legitimacy, ideology, discursive power and co-optation. While governmental discursive power is discarded as a source of variation, findings are significant with respect to the influence of ideology and performance legitimacy. Reliance on ideology or related patterns for legitimation raise vulnerability to terrorism and constrain or facilitate the adoption of communicative and preventive measures that accommodate the grievances of potentially defective or even violently terrorist groups. Performance legitimacy is a key motivator in counter-terrorism and an influence on certain types of counter-terrorism policies. Responsiveness and co-optation are identified as potential sources of variation, based on idiosyncratic concurrence with policy choices.
Der vorliegende Beitrag beschreibt den theoretischen Hintergrund und das Design des Projekts GLUE (Gemeinsame Lern-Umgebungen Entwickeln). Die Konzeption der Gemeinsamen Lern-Umgebungen zielt im Sinne der Prinzipien des ‚Universal Design of Learning‘ (Hall, Meyer & Rose, 2012) darauf ab, den inklusiven Mathematikunterricht von einem gemeinsamen Lerngegenstand aus zu denken, der einerseits Zugänglichkeit für alle Lernenden schafft und andererseits Unterstützungsmaßnahmen auf unterschiedlichen Niveaustufen zulässt.
Das Projekt geht der Frage nach, wie sich die Kompetenzentwicklung von berufserfahrenen Lehrkräften der allgemeinen Schule und für sonderpädagogische Förderung durch Fortbildungsangebote zum inklusiven Mathematikunterricht wirksam unterstützen lässt. Hierzu wurde ein Blended-Learning-Angebot zur Entwicklung gemeinsamer Lernumgebungen für alle Kinder einer Lerngruppe erarbeitet, die sich auch von mehreren Lehrkräften gemeinsam entwickeln lassen.
In diesem Beitrag werden der theoretische Hintergrund, die Konzeption und die methodische Anlage des Projekts vorgestellt. Kapitel 1 befasst sich mit Differenzieren und Fördern im Mathematikunterricht der Primarstufe, Kapitel 2 diskutiert zentrale Befunde zur Wirksamkeit von Lehrerfortbildungsmaßnahmen sowie zu Blended-Learning-Angeboten. Im dritten Kapitel werden auf dieser Grundlage die Ziele des Projekts (Kap. 3.1), die Inhalte und die Struktur des Fortbildungsangebots (Kap., 3.2), die Forschungsfragen (Kap. 3.3) und das Design der Interventionsstudie dargestellt (Kap. 3.4). Die Wirksamkeit wird in einem ausbalancierten Prä-Post-Follow-Up-Test-Design im Vergleich zu unbegleiteten Online-Angeboten evaluiert, die Ergebnisse sollen in einer Folgepublikation kommuniziert werden.
Physical exercise has been shown to alter sensory functions, such as sensory detection or perceived pain. However, most contributing studies rely on the assessment of single thresholds, and a systematic testing of the sensory system is missing. This randomised, controlled cross-over study aims to determine the sensory phenotype of healthy young participants and to assess if sub-maximal endurance exercise can impact it. We investigated the effects of a single bout of sub-maximal running exercise (30 min at 80% heart rate reserve) compared to a resting control in 20 healthy participants. The sensory profile was assessed applying quantitative sensory testing (QST) according to the protocol of the German Research Network on Neuropathic Pain. QST comprises a broad spectrum of thermal and mechanical detection and pain thresholds. It was applied to the forehead of study participants prior and immediately after the intervention. Time between cross-over sessions was one week. Sub-maximal endurance exercise did not significantly alter thermal or mechanical sensory function (time × group analysis) in terms of detection and pain thresholds. The sensory phenotypes did not indicate any clinically meaningful deviation of sensory function. The alteration of sensory thresholds needs to be carefully interpreted, and only systematic testing allows an improved understanding of mechanism. In this context, sub-maximal endurance exercise is not followed by a change of thermal and mechanical sensory function at the forehead in healthy volunteers.
Does it pay to invest in art? A selection-corrected returns perspective : [draft october 15, 2013]
(2013)
This paper shows the importance of correcting for sample selection when investing in illiquid assets with endogenous trading. Using a large sample of 20,538 paintings that were sold repeatedly at auction between 1972 and 2010, we find that paintings with higher price appreciation are more likely to trade. This strongly biases estimates of returns. The selection-corrected average annual index return is 6.5 percent, down from 10 percent for traditional uncorrected repeat sales regressions, and Sharpe Ratios drop from 0.24 to 0.04. From a pure financial perspective, passive index investing in paintings is not a viable investment strategy once selection bias is accounted for. Our results have important implications for other illiquid asset classes that trade endogenously.
Structured RNA regions are important gene control elements in prokaryotes and eukaryotes. Here, we show that the mRNA of a cyanobacterial heat shock gene contains a built-in thermosensor critical for photosynthetic activity under stress conditions. The exceptionally short 5´-untranslated region is comprised of a single hairpin with an internal asymmetric loop. It inhibits translation of the Synechocystis hsp17 transcript at normal growth conditions, permits translation initiation under stress conditions and shuts down Hsp17 production in the recovery phase. Point mutations that stabilized or destabilized the RNA structure deregulated reporter gene expression in vivo and ribosome binding in vitro. Introduction of such point mutations into the Synechocystis genome produced severe phenotypic defects. Reversible formation of the open and closed structure was beneficial for viability, integrity of the photosystem and oxygen evolution. Continuous production of Hsp17 was detrimental when the stress declined indicating that shutting-off heat shock protein production is an important, previously unrecognized function of RNA thermometers. We discovered a simple biosensor that strictly adjusts the cellular level of a molecular chaperone to the physiological need.
Background: The increasing number of cases and hospital admissions due to COVID-19 created an urgent need for rapid, reliable testing procedures for SARS-CoV-2 in Emergency Departments (ED) in order to effectively manage hospital resources, allocate beds and prevent nosocomial spread of infection. The ID NOW™ COVID-19 assay is a simple, user-friendly, rapid molecular test run on an instrument with a small footprint enabling point-of-care diagnostics.
Methods: In the first wave, outsourced RT-PCR testing regularly required 36-48 hours before results were available. This prospective study was conducted in the second wave (October 2020-April 2021) and evaluated the impact the implementation of the ID NOW™ COVID-19 test in the ED had on clinical care processes and patient pathways. 710 patients were recruited upon arrival at the ED which included those presenting clinical symptoms, asymptomatic individuals or persons fulfilling epidemiological criteria. The first anterior nasal swab was taken by trained nurses in the ambulance or a separate consultation room. The ID NOW™ COVID-19 test was performed in the ED in strict compliance with the manufacturer’s instructions and positive or suspected cases were additionally tested with RT_PCR (cobas SARS-COV-2 RT-PCR, Roche) following collection of a second nasopharyngeal NP specimen.
Results: Swabs directly tested with the ID NOW™ COVID-19 test showed a diagnostic concordance of 98 % (sensitivity 99.59 %, specificity 94.55 %, PPV 97.6 %, NPV 99.05 %) compared to RT-PCR as reference. The 488 patients that tested positive with the ID NOW™ COVID-19 had a Ct range in RT-PCR results between 7.94 to 37.42 (in 23.2 % > 30). Two false negative results (0.28%) were recorded from patients with Ct values > 30. 14 (1.69%) discordant results were reviewed case-by-case and usually associated with either very early or very advanced stages of infection. Furthermore, patients initially negative with the ID NOW™ COVID-19 test and admitted to the hospital were tested again on days 5 and 12: no patient became positive.
Discussion: The ID NOW™ COVID-19 test for detection of SARS-CoV-2 demonstrated excellent diagnostic agreement with RT-PCR under the above-mentioned patients pathways implemented during the second wave. The main advantage of the system was the provision of reliable results within a few minutes. This not only allowed immediate initiative of appropriate therapy and care for COVID-19 (patient benefit) but provided essential information on isolation and thus available beds. This drastically helped the overall finances of the department and additionally allowed more patients to be admitted including those requiring immediate attention; this was not possible during the first wave since beds were blocked waiting for diagnostic confirmation. Our findings also show that when interpreting the results, the clinical condition and epidemiological history of the patient must be taken into account, as with any test procedure. Overall, the ID NOW™ COVID-19 test for SARS-CoV-2 provided a rapid and reliable alternative to laboratory-based RT-PCR in the real clinical setting which became an acceptable part of the daily routine within the ED and demonstrated that early patient management can mitigate the impact of the pandemic on the hospital.
Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats.
Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed.
Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling.
Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension.
The optimal follow-up care for relapse detection in acute myeloid leukemia (AML) patients in first remission after consolidation therapy with intensive chemotherapy is not established. In this retrospective study, we evaluate the diagnostic value of an intensive relapse surveillance strategy by regular bone marrow aspirations (BMA) in these patients. We identified 86 patients with newly diagnosed non-promyelocytic AML who had reached complete remission (CR) after intensive induction and consolidation chemotherapy between 2007 and 2019. Annual relapse rates were 40%, 17%, and 2% in years 1–3, respectively. Patients in CR were surveilled by BMA scheduled every 3 months for 2 years, followed by BMA every 6 months. This surveillance regimen detected 29 of 55 relapses (53%), 11 of which were molecular relapses (20%). The remaining 26 of 55 relapses (47%) were diagnosed by non-surveillance BMA prompted by specific suspicion of relapse. Most patients showed concurrent morphological abnormalities in peripheral blood (PB) at time of relapse. Seven percent of all morphological relapses occurred without simultaneous PB abnormalities and would have been delayed without surveillance BMA. Intensified monthly PB assessment paired with BMA every 3 months during the first 2 years may be a highly sensitive relapse surveillance strategy.
Objectives and Methods: Intracranial hemorrhage (ICH) in acute myeloid leukemia (AML) patients is a major concern due to the increased risk of mortality. Few studies have examined ICH specifically in newly diagnosed AML patients receiving intensive induction chemotherapy (IC) and prophylactic platelet transfusions during thrombocytopenia <10/nL. This retrospective cohort study included 423 newly diagnosed AML patients without acute promyelocytic leukemia who underwent IC between 2007 and 2019. We assessed risk factors, clinical features, and outcomes of ICH.
Results: 17 of 423 patients (4%) suffered ICH during hospital stay, and 4 patients (24%) died directly because of ICH despite routine prophylactic platelet transfusions. Patients with ICH had a negatively impacted overall survival (median OS, 20.1 vs. 104.8 months) and were more likely not to continue with curative treatment. Main risk factors were female gender, severe thrombocytopenia, and decreased fibrinogen. Patients with subsequent ICH also had laboratory signs of liver dysfunction.
Conclusions: Intracranial hemorrhage remains a potentially deadly complication with notable incidence despite prophylactic platelet substitution, suggesting that additional prophylactic interventions may be required to further reduce the frequency of ICH in high-risk patients. Unrecognized genetic factors may simultaneously predispose to AML and platelet dysfunction with ICH.
Background: We have analyzed the outcome of patients with localized extraskeletal Ewing sarcoma (EES) treated in three consecutive Cooperative Weichteilsarkomstudiengruppe (CWS) soft tissue sarcoma (STS) studies: CWS-91, CWS-96, and CWS-2002P.
Methods: Patients were treated in CWS-91 with four- (vincristine, dactinomycin, doxorubicin, and ifosfamide [VAIA] or cyclophosphamide [VACA II]) or five-drug (+etoposide [EVAIA]) cycles, in CWS-96 they were randomly assigned to receive VAIA or CEVAIE (+carboplatin and etoposide), and in CWS-2002P with VAIA III plus optional maintenance therapy (MT) with cyclophosphamide and vinblastine. Local therapy consisted of resection and/or radiotherapy (RT).
Results: Two hundred forty-three patients fulfilled the eligibility criteria. The 5-year event-free survival (EFS) and overall survival (OS) were 63% (95% confidence interval [CI] 57–69) and 73% (95% CI 67–79), respectively. The 5-year EFS by study was 64% (95% CI 54–74) in CWS-91, 57% (95% CI 48–66) in CWS-96, and 79% (95% CI 67–91) in CWS-2002P (n.s.). The 5-year OS was 72% (95% CI 62–82) in CWS-91, 70% (95% CI 61–79) in CWS-96, and 86% (95% CI 76–96) in CWS-2002P (n.s.). In CWS-96, 5-year EFS and OS in the VAIA arm versus the CEVAIE were 65% (95% CI 52–81) versus 55% (95% CI 39–76) log-rank p = .13, and 85% (95% CI 75–96) versus 61% (95% CI 45–82), log-rank p = .09.
Conclusion: Our analysis provides interesting information on the treatment and specificities of EES, which can be useful for a better understanding of this rare entity and should be considered in the development of future clinical trials for Ewing sarcoma defined as FET–ETS fusion positive tumors.
We document the structure of firm-bank relationships across the eleven largest euro area countries and present new stylised facts using novel data from the recent credit registry of the Eurosystem - AnaCredit. We look at the number of banking relationships, reliance on the main bank, credit instruments, loan maturity and interest rates. The granularity of the data allows us to account for cross country differences in firm characteristics. Firms in Southern European countries borrow from a larger number of banks and obtain a lower share of credit from the main bank compared to those in Northern European countries. They also tend to borrow more on short term, more expensive instruments and to obtain loans with shorter maturity. This is consistent with the hypothesis that Southern European countries rely less on relationship banking and obtain credit less conducive to firm growth, in line with the smaller average size of Southern European firms. Instead, no clear pattern emerges in terms of interest rates, consistent with the idea that banks appropriate part of the surplus generated by relationship lending through higher rates.
This dissertation presents the development of a new radio frequency quadrupole (RFQ) structure of the 4-rod type with an operating frequency of 108 MHz for the acceleration of heavy ions with mass-to-charge ratios of up to 8.5 at high duty cycles up to CW operation ("continuous wave") at the High Charge Injector (HLI) of the GSI Helmholtz Centre for Heavy Ion Research in Darmstadt.
The need to develop a completely new RFQ for the HLI arises from the fact that with the previously designed and built 4-rod RFQ structure, which was commissioned at the HLI in 2010 as part of the planned HLI upgrade program, the desired operating modes in both pulsed and CW operation could not be achieved even after several years of operating experience and considerable efforts to eliminate or at least mitigate the severe operational instabilities. Mechanical vibrations of the electrodes, which result in strong modulated power reflection, as well as the high thermal sensitivity proved to be particularly problematic.
In addition to the RF design of the new RFQ by simulations performed with the CST Microwave Studio software, the focus of the investigations fell on the mechanical analysis of vibrations on the electrode rods caused by RF operation, for which the ANSYS Workbench software was used. Due to the high thermal load of the RFQ structure of more than 30 kW/m in CW operation, an accurate analysis of the thermal effects on electrode deformation as well as resulting frequency detuning of the resonator is also required, which was investigated by simulations within the capabilities of CST Mphysics Studio.
Based on the results of the design studies carried out by simulations and the thereby achieved design optimizations, a 4-rod RFQ prototype with 6 stems was finally manufactured, on which most of the properties expected from the simulations could be validated by measurements of the RF characteristics as well as of the vibration behavior.
Finally, based on the results of the pre-tests and considering a newly developed beam dynamics concept, a completely revised RF design for a new full-length HLI-RFQ was derived from the prototype design.
The RFQ direct injection project (RFQ-DIP) for the neutrino physics experiment IsoDAR aims at an efficient injection of a high-current H²⁺ beam into the dedicated 60 MeV driver cyclotron. Therefore, it is intended to use a compact 32.8 MHz RFQ structure of the split-coaxial type as a pre-buncher. To determine the thermal elongation of the 1.4 m long electrode rods as well as the thermal frequency detuning of the RF structure at a maximum nominal power load of 3.6 kW, an extensive thermal and structural mechanical analysis using COMSOL Multiphysics was conducted. The water heating along the cooling channels as well as the properties of heat transfer from the copper structure to the cooling water were taken into account, which required CFD simulations of the cooling water flow in the turbulent regime. Here we present the methods and results of the sophisticated thermal and structural mechanical simulations using COMSOL and provide a comparison to more simplistic simulations conducted with CST Studio Suite.
Rezension zu: Social preferences: an introduction to behavioural economics and experimental research, by Michalis Drouvelis, Newcastle upon Tyne: Agenda Publishing, 2021, 205 pages, £22.99, ISBN 978-1-78821-417-9 (paperback).
This paper explores consequences of consumer education on prices and welfare in retail financial markets when some consumers are naive about shrouded add-on prices and firms try to exploit it. Allowing for different information and pricing strategies we show that education is unlikely to push firms to disclose prices towards all consumers, which would be socially efficient. Instead, price discrimination emerges as a new equilibrium. Further, due to a feedback on prices, education that is good for consumers who become sophisticated may be bad for consumers who stay naive and even for the group of all consumers as a whole
We provide evidence on the extent to which survey items in the Preference Survey Module and the resulting Global Preference Survey measuring social preferences − trust, altruism, positive and negative reciprocity − predict behavior in corresponding experimental games outside the original participant sample of Falk et al. (2022). Our results, which are based on a replication study with university students in Tehran, Iran, are mixed. While quantitative items considering hypothetical versions of the experimental games correlate significantly and economically meaningfully with individual behavior, none of the qualitative items show significant correlations. The only exception is altruism where results correspond more closely to the original findings.
How to write (international) legal histories that would be true to their protagonists while simultaneously relevant to present audiences? Most of us would also want to write "critically" – that is to say, at least by aiming to avoid Eurocentrism, hagiography and commitment to an altogether old-fashioned view of international law as an instrument of progress. Hence we write today our histories "in context". But this cannot be all. Framing the relevant "context" is only possible by drawing upon more or less conscious jurisprudential and political preferences. Should attention be focused on academic debates, military power, class structures or assumptions about the longue durée? Such choices determine for us what we think of as relevant "contexts", and engage us as participants in large conversations about law and power that are not only about what once "was" but also what there will be in the future.
In The Gentle Civilizer of Nations, I suggested that international law began in the 1860’s as part of liberal entrenchment in Europe as the clouds of nationalism, racism and socialism were rising in the political horizon. It began as a project of practicalmen, attorneys and lawyers active in politics and parliament, and not out of philosophical contemplation or system-construction. University professors were involved, but these were professors of something that was seen more as a craft than a science. What they aimed at was to "civilize" the behaviour of their nations, but also the colonies, and to do this by coordinating liberal legislative reform in Europe, by supporting formal empire in the colonies, and by doing all this as part of a set of cosmopolitan legal projects they grouped into their "international law" (Droit international, diritto internazionale, Völkerrecht). ...
Political theology’s recent rise to academic prominence has, no doubt, been inspired by the sense of a certain staleness of standard (read: Anglo-American) analytical political and legal theory. Especially postcolonial and postmodern philosophy has resuscitated debates about the reality of secularization in Europe, pointing out that much of our shared political metaphysic is indeed that – a metaphysic – with close historical links to debates in theology. That should be no surprise. For almost half a millennium theology stood as the primus inter pares among the three "higher faculties" at European universities. The best minds at work in Europe explained the social and political changes to European audiences within a fully God-centric intellectual universe. Awareness of that fact, as Wim Decock points out in this massive and brilliant work, not only assists us in understanding the development of our political and legal vocabularies. It also enables us to grasp the contingency of our present debates, the way opposite standpoints on political and legal obligation refer back to assumptions about human nature, the roles of individual and society and the nature of "law" that are hard to detach from religious speculation. ...
The article presents a brief overview of research and publication in the history of international law in Europe today. The upsurge of interest in historical studies is traced back to a sense of present transformation, with historical studies seeking to explore both aspects of continuity and change in the international legal system. The article outlines three tasks for the discipline in the future: to begin work for international law’s Ideengeschichte, to focus on the relationship between the West and its "Other", and to undertake studies in the historical sociology of international law.
This paper discusses the implications of transnational media production and diasporic networks for the cultural politics of migrant minorities. How are fields of cultural politics transformed if Hirschmann’s famous options ‘exit’ and ‘voice’ are no longer constituting mutually exclusive responses to dissent within a nation-state, but modes of action that can combine and build upon each other in the context of migration and diasporic media activism? Two case studies are discussed in more detail, relating to Alevi amateur television production in Germany and to a Kurdish satellite television station that reaches out to a diaspora across Europe and the Middle East. Keywords: migrant media, transnationalism, Alevis, Kurds, Turkey, Germany
Migranten werden in politischen Debatten oft als festgefügte Gemeinschaft betrachtet, die in ihrer eigenen nach außen abgeschotteten Welt leben – in einer Parallelgesellschaft. Doch ist das wirklich so? Wie gestalten insbesondere junge Leute mit Migrationshintergrund ihre sozialen Bindungen, wenn sie sich in der urbanen Clubszene europäischer Großstädte bewegen? Das Team um die Soziologin und Kulturanthropologin Kira Kosnick untersucht die Dynamiken dieser Prozesse.