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Asia and its Hindu Kush Himalayan (HKH) region is particularly vulnerable to environmental change, especially climate and land use changes further influenced by rapid population growth, high level of poverty and unsustainable development. Asia has been a hotspot of dengue fever and chikungunya mainly due to its dense human population, unplanned urbanization and poverty. In an urban cycle, dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by Aedes aegypti and Ae. albopictus mosquitoes which are also competent vectors of Zika virus (ZIKV). Over the last decade, DENV and CHIKV transmissions by Ae. aegypti have extended to the Himalayan countries of Bhutan and Nepal and ZIKV could follow in the footsteps of these viruses in the HKH region. The already established distribution of human-biting Aedes mosquito vectors and a naïve population with lack of immunity against ZIKV places the HKH region at a higher risk of ZIKV. Some of the countries in the HKH region have already reported ZIKV cases. We have documented an increasing threat of ZIKV in Asia and its HKH region because of the high abundance and wide distribution of human-biting mosquito vectors, climate change, poverty, report of indigenous cases in the region, increasing numbers of imported cases and a naïve population with lack of immunity against ZIKV. An outbreak anywhere is potentially a threat everywhere. Therefore, in order to ensure international health security, all efforts to prevent, detect, and respond to ZIKV ought to be intensified now in Asia and its HKH region. To prepare for possible ZIKV outbreaks, Asia and the HKH region can also learn from the success stories and strategies adopted by other regions and countries in preventing ZIKV and associated complications. The future control strategies for DENV, CHIKV and ZIKV should be considered in tandem with the threat to human well-being that is posed by other emerging and re-emerging vector-borne and zoonotic diseases, and by the continuing urgent need to strengthen public primary healthcare systems in the region.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Pediatric patients with disease refractory to last chemotherapy, relapse after allogeneic hematopoietic stem-cell transplantation (alloHSCT), or second or further relapse have a particularly poor prognosis. Intensive chemotherapy followed by alloHSCT after achieving remission can result in cure for some patients. However, survival is still low with this approach. Thus, additional treatment modalities with acceptable toxicity are needed to improve long-term survival. ...
Background: To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue.
Methods: The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters.
Results: Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = − 0.354; p = 0.013), D’Amico risk stratification (ρ = − 0.336; p = 0.012), ISUP grade (ρ = − 0.321; p = 0.017) and Gleason score (ρ = − 0.342; p = 0.011).
Conclusions: This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.
Background: With the aging population and a rising incidence of squamous cell carcinoma of the head and neck (SCCHN), there is an emerging need for developing strategies to treat elderly patients.
Patients and Methods: We retrospectively analyzed 158 patients treated with definitive, concurrent chemoradiotherapy (CRT) for SCCHN. Clinicopathological characteristics, acute toxicities, and oncological outcomes were compared between patients younger and older than (or of age equal to) 65, 70, and 75 years.
Results: RT dose, chemotherapy regimen, and total chemotherapy dose were balanced between the groups. After a median follow-up of 29 months, overall survival (OS), progression-free survival (PFS), local control rate, and distant metastasis-free survival stratified by age of ≥65, ≥70, or ≥75 years revealed no differences. The rate of acute toxicities was also not higher for older patients. Worse ECOG performance score (ECOG 2-3) was associated with impaired OS () and PFS ().
Conclusion: Definitive treatment with CRT for SCCHN is feasible and effective; even in advanced age treatment decisions should be made according to general condition and comorbidity, rather than calendar age alone.
This review provides an overview on components of the sphingolipid superfamily, on their localization and metabolism. Information about the sphingolipid biological activity in cell physiopathology is given. Recent studies highlight the role of sphingolipids in inflammatory process. We summarize the emerging data that support the different roles of the sphingolipid members in specific phases of inflammation: (1) migration of immune cells, (2) recognition of exogenous agents, and (3) activation/differentiation of immune cells.
Das Hodgkin Lymphom besteht aus zwei verschiedenen Typen, dem klassischen Hodgkin Lymphom (cHL) mit einem Anteil von 95% und dem nodulären lymphozytenprädominanten Hodgkin Lymphom (NLPHL). Letzteres kann sehr unterschiedliche histopathologische Wachstumsmuster zeigen, die nach Fan et al. grob in ein typisches knotiges (Muster A) und in atypische diffuse Wachstumsmuster (Muster C und E) unterteilt werden können. Patienten mit einem NLPHL, das zum diffus wachsenden Subtyp zählt, präsentieren sich häufiger in klinisch fortgeschrittenen Stadien als jene Patienten mit einem NLPHL, das ein knotiges Wachstumsmuster zeigt. Im Gegensatz dazu präsentiert sich das T-Zell/Histiozytenreiche großzellige B-Zell Lymphom (THRLBCL) in einem fortgeschrittenen Stadium mit einer oftmals schlechten Prognose. NLPHL vom diffusen Typ weisen starke Ähnlichkeiten mit dem THRLBCL sowohl in Bezug auf Histomorphologie als auch klinische Eigenschaften auf und sind dadurch manchmal nur schwer voneinander zu unterscheiden.
Das Wachstumsmuster eines Tumors hängt unter anderem von der Verteilung der Blutgefäße im Tumorgewebe ab. Viele aktuelle Studien weisen darauf hin, dass die Gefäßneubildung (Angiogenese) eine wichtige Rolle in der Entwicklung von hämatologischen Tumoren spielt. Durch diesen Prozess kann der Tumor zu ausreichend Sauerstoff und Nährstoffen gelangen, um invasiv zu wachsen und zu metastasieren. Die Gefäßdichte ist ein anerkannter Marker für die Auswertung von Gefäßneubildung in verschiedenen Tumoren.
Ein Ziel der Arbeit bestand darin, Parameter der Angiogenese, u.a. die Gefäßdichte und den queren Gefäßdurchmesser, in verschiedenen Subtypen des NLPHL und in THRLBCL im Hinblick auf eine mögliche Unterscheidbarkeit des diffusen NLPHL und des THRLBCL zu untersuchen sowie sie mit anderen Typen von malignen Lymphomen und reaktiven Lymphadenitiden (LA) zu vergleichen.
Von T-Lymphozyten ist bekannt, dass sie mit den Tumorzellen in Lymphomen in engem Kontakt stehen und einen nicht unerheblichen Anteil des Tumormikromilieus bilden. Die CD4+ Lymphozyten treten gewöhnlich über Gefäße, den hochendothelialen Venolen (HEVs), in den Lymphknoten ein.
Ein weiteres Ziel der Arbeit war es, eine mögliche Korrelation zwischen dem TLymphozyten-Zustrom und der Tumormorphologie in den betroffenen Lymphknoten zu untersuchen, um herauszufinden, ob dies die unterschiedliche Zusammensetzung im Mikromilieu der Lymphome erklären kann. Als Maß für den Zustrom wurde die Anzahl der intravaskulären T-Lymphozyten herangezogen. Zum Vergleich wurden weitere maligne Lymphome, die ein prominentes Tumormikromilieu besitzen, untersucht.
Im diffusen NLPHL und THRLBCL fanden wir eine niedrigere Gefäßdichte mit einer diffusen Blutgefäßverteilung. Im Gegensatz dazu zeigte das NLPHL mit einem typischen Wachstumsmuster, das cHL vom gemischtzelligen Typ (cHL MC) und das Angioimmunoblastische Lymphom (AITL) in den interfollikulären Arealen eine verstärkte Gefäßbildung. Es zeigte sich in allen Subtypen des NLPHL eine signifikant geringere Gefäßdichte, verglichen mit dem AITL oder den LA Fällen. LA wiesen insgesamt die höchste interfollikuläre Gefäßdichte auf. Das THRLBCL zeigte die niedrigste Gefäßdichte von allen malignen Lymphomen, die untersucht wurden, allerdings war der Vergleich von THRLBCL und den verschiedenen Subtypen des NLPHL nicht signifikant. Wir konnten zeigen, dass die diffusen Subtypen des NLPHL und das THRLBCL ein ähnliches Wachstumsmuster der Blutgefäße mit einer verminderten Gefäßdichte und nicht mehr identifizierbaren follikulären Bereichen vorweisen, im Gegensatz zu den beibehaltenen follikulären Mustern, die wir im typischen NLPHL fanden. Die Anzahl der intravaskulären T-Zellen war am höchsten im cHL MC sowie im typischen NLPHL. Signifikant geringer fielen die intravaskulären TLymphozyten-Werte im THRLBCL im Vergleich mit dem typischen NLPHL Muster A, C und dem cHL MC aus.
Da die LA Fälle eine hohe interfollikuläre Gefäßdichte und kleine Gefäßdurchmesser zeigten, kann man davon ausgehen, dass die Gefäße durch die schnell anschwellenden Keimzentren komprimiert wurden. In den atypischen NLPHL und THRLBCL Fällen lassen die geringe Gefäßdichte und relativ große Gefäßdurchmesser eine langsame Dehnung des Gefäßgerüstes des Lymphknotens annehmen. Die Resultate der T-Zell Quantifizierung legen den Schluss nahe, dass die relativ geringe Anzahl von intravaskulären T-Lymphozyten im THRLBCL zusammen mit einer geringen Gefäßdichte möglicherweise verantwortlich ist für die gewöhnlich relativ geringe Anzahl an T-Lymphozyten pro Fläche und hierdurch die hohe Anzahl an Makrophagen im Mikromilieu im THRLBCL hervorgerufen wird. Dies könnte im Zusammenhang stehen mit einer absolut verminderten T-Lymphozytenzahl im Blut oder einem reduzierten Eintritt der T-Lymphozyten in den Lymphknoten.
The vacuolar-type H+-ATPase (v-ATPase) is the major proton pump that acidifies intracellular compartments of eukaryotic cells. Since the inhibition of v-ATPase resulted in anti-tumor and anti-metastatic effects in different tumor models, this enzyme has emerged as promising strategy against cancer. Here, we used the well-established v-ATPase inhibitor archazolid, a natural product first isolated from the myxobacterium Archangium gephyra, to study the consequences of v-ATPase inhibition in endothelial cells (ECs), in particular on the interaction between ECs and cancer cells, which has been neglected so far. Human endothelial cells treated with archazolid showed an increased adhesion of tumor cells, whereas the transendothelial migration of tumor cells was reduced. The adhesion process was independent from the EC adhesion molecules ICAM-1, VCAM-1, E-selectin and N-cadherin. Instead, the adhesion was mediated by β1-integrins expressed on tumor cells, as blocking of the integrin β1 subunit reversed this process. Tumor cells preferentially adhered to the β1-integrin ligand collagen and archazolid led to an increase in the amount of collagen on the surface of ECs. The accumulation of collagen was accompanied by a strong decrease of the expression and activity of the protease cathepsin B. Overexpression of cathepsin B in ECs prevented the capability of archazolid to increase the adhesion of tumor cells onto ECs. Our study demonstrates that the inhibition of v-ATPase by archazolid induces a pro-adhesive phenotype in endothelial cells that promotes their interaction with cancer cells, whereas the transmigration of tumor cells was reduced. These findings further support archazolid as a promising anti-metastatic compound.
Purpose: The aim of the study was to compare three different elastography methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave Elastography (2D-SWE), in the same study population for the differentiation of thyroid nodules.
Materials and methods: All patients received a conventional ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI-Imaging. Cytology/histology of thyroid nodules was used as a reference method. SE measures the relative stiffness within the region of interest (ROI) using the surrounding tissue as reference tissue. ARFI mechanically excites the tissue at the ROI using acoustic pulses to generate localized tissue displacements. 2D-SWE measures tissue elasticity using the velocity of many shear waves as they propagate through the tissue.
Results: 84 nodules (73 benign and 11 malignant) in 62 patients were analyzed. Sensitivity, specificity and NPV of SE were 73%, 70% and 94%, respectively. Sensitivity, specificity and NPV of ARFI and 2D-SWE were 90%, 79%, 98% and 73%, 67%, 94% respectively, using a cut-off value of 1.98m/s for ARFI and 2.65m/s (21.07kPa) for 2D-SWE. The AUROC (Area under the Receiver Operating Characteristic) of SE, ARFI and 2D-SWE for the diagnosis of malignant thyroid nodules were 52%, 86% and 71%, respectively. A significant difference in AUROC was found between SE and ARFI (p = 0.008), while no significant difference was found between ARFI and SWE (86% vs. 71%, p = 0.31), or SWE and SE (71% vs. 52%, p = 0.26).
Conclusion: pSWE using ARFI and 2D-SWE showed comparable results for the differentiation of thyroid nodules. ARFI was superior to elastography using SE.
Particle physics is living it’s golden age: petabytes of high precision data are being recorded at experimental facilities such as the Relativistic Heavy Ion Collider (RHIC) and the Large Hadron Collider (LHC). Despite the significant theoretical progress achieved in the last years the complete understanding of the internal structure of protons, not computable with perturbative QCD, remains as one of the most challenging unsolved problems in the physics of elementary interactions. Besides its fundamental interest, pinning down the relevant degrees of freedom and their properties, such as their spatial distribution, has profound implications in several phenomenological aspects of high-energy collisions. Currently one of the subjects undergoing intense study is the possibility that droplets of quark-gluon plasma (QGP) are being created not only in heavy ion collisions but in more dilute systems such as high-multiplicity proton-proton interactions. This is a data driven debate as it is rooted in the similar patterns observed across the different collision systems at the LHC (p+p,p+Pb and Pb+Pb) in the flow harmonic analyses: one of the golden probes of QGP formation specially sensitive to the initial collision geometry. Another domain in which the proton structure plays a central role is the description of multi-parton interactions, the mechanism that dominates the underlying event at LHC energies, in Monte Carlo event generators. All in all a precise characterization of the hadronic structure is a crucial ingredient of the physics program of the LHC.
A full characterization of a hadron would require momentum, spatial and spin information, the so-called Wigner distribution. So far obtaining this information experimentally has not been achieved. From a theoretical point of view several complications arise such as non-universality and breaking of factorization theorems. Then, in general, the description of the hadron structure relies on phenomenological tools that require theoretical modeling constrained by experimental data. The main goal of this thesis to characterize the transverse structure of the proton. For that purpose, a wide variety of phenomenological problems that are sensitive to the proton structure have been addressed.
First, elastic scattering data on proton-proton interactions constitutes a powerful probe of the geometry of the collision. A dedicated analysis of this observable focusing on the extraction of the inelasticity density from it at √s=62.5 GeV and √s=7 TeV is presented. In the TeV regime, a unexpected phenomenon, dubbed the hollowness effect, arises: the inelasticity density, a measurement of how effective is the collision producing secondary particles, reaches its maximum at non-zero impact parameter. We provide the first dynamical explanation of the hollowness effect by constructing the elastic scattering amplitude in impact parameter representation according to the Glauber model. For that purpose we relied on a composite description of the proton. More concretely, the relevant degrees of freedom that participate in the scattering process were considered to be gluonic hot spots. The probability distribution for the transverse positions of hot spots inside the proton includes repulsive short-range correlations between all pairs of hot spots controlled by an effective repulsive core rc that effectively enlarges the mean transverse separation distance between them. The main results extracted from this work are as follows. To begin with, we found that our model was not able to describe a growing behavior of the inelasticity density at zero impact parameter in the absence of non-trivial spatial correlations. However, even in the presence of correlations, the emergence of the hollowness effect couldn’t be described when the number of hot spots was smaller than 3. Both features set solid constraints in the proton structure within our model. Finally, we pinpoint the transverse diffusion of the hot spots with increasing collision energy to be the dynamical mechanism underlying the onset of the hollowness effect.
A convenient playground to test further implications of this novel geometric description of the proton are the initial state properties of high energy proton-proton interactions in the context of QGP physics. The parametrization of the geometry of the collision is mandatory in any theoretical model attempting to describe the striking experimental results that suggest collective behavior in proton-proton interactions at the LHC, such as the non-zero value of the flow harmonic coefficients (vn). A quantitative way to characterize the initial geometry anisotropy of the overlap region is to compute the spatial eccentricity moments (εn) that fluctuate on an event by event basis. For that purpose we develop a Monte Carlo Glauber event generator. A systematic investigation of the effect of non-trivial spatial correlations in the spatial eccentricity moments from ISR to LHC energies within our Monte Carlo Glauber approach is presented. We found that both the eccentricity (ε2) and the triangularity (ε3) are affected by the inclusion of short-range repulsive correlations. In particular, the correlated scenario yielded larger values of ε2(3) in ultra-central collisions while reducing them in minimum bias.
Moreover, we explore not only the eccentricities mean but their fluctuations in terms of symmetric cumulants. The experimental measurement by the CMS Collaboration at √s=13 TeV indicates a anti-correlation of v2 and v3 around the same number of tracks in the three collision systems available at the LHC. We lay out, for the first time in the literature, a particular mechanism that permits an anti-correlation of ε2 and ε3 in the highest centrality bins as dictated by data. When modeling the proton as composed by 3 gluonic hot spots, the most common assumption in the literature, we find that the inclusion of spatial correlations is indispensable to reproduce the negative sign. Further, we perform a systematic investigation of the parameter space of the model i.e. radius of the hot spot, radius of the proton, repulsive core and number of hot spots in each proton. Our results suggest that the interplay of the different scales is decisive and confirm the discriminating power of this observable on initial state models. Together with their drastic impact on the description of the hollowness effect and the absolute values of the eccentricities, the symmetric cumulant study adds evidence to the fact that the inclusion of spatial correlations between the sub nucleonic degrees of freedom of the proton modifies the initial state properties of p+p interactions at LHC energies.
Cyprus is one of the few areas in the E Mediterranean where the distribution areas of Silene colorata s. str. and S. oliveriana overlap. Opinion about taxonomy and rank of the latter is much divided. Our field observations in Cyprus as well as literature and herbarium studies support the view to treat the latter taxon at species rank. Additionally, it is more widespread in Cyprus than previously assumed.
Zielsetzung: Beteiligung von Medizinstudierenden im Rahmen der konzeptionellen Entwicklung eines zielgruppenspezifischen und attraktiven allgemeinmedizinischen Lehrangebots im ländlichen Raum.
Methodik: Es wurde ein Fragebogen entwickelt, der die Bewertung der Studierenden hinsichtlich des aktuellen Ablaufs ihres Studiums, den späteren Berufswunsch sowie die Anforderungen an ein zu entwickelndes allgemeinmedizinisches Schwerpunktprogramm im ländlichen Raum erfasst. Mittels einer Online-Befragung wurden im Sommer 2015 alle Medizinstudierende ab dem vierten vorklinischen Semester (n=2.150) der Goethe-Universität Frankfurt einmalig befragt. Die statistische Auswertung erfolgte primär deskriptiv. Die persönliche Einstellung hinsichtlich der Bereitschaft, als Hausarzt tätig zu werden, wurde auf statistische Signifikanz überprüft. Zudem wurde erhoben, ob ein messbarer Zusammenhang zwischen der eigenen Herkunft und dem späteren Wunscharbeitsort besteht.
Ergebnisse: Von insgesamt 2.150 kontaktierten Studierenden nahmen 617 an der Befragung teil (Rücklaufquote=28,7%). Die Ergebnisse repräsentieren eine große Bandbreite an Ideen und Anregungen, die sowohl die Meinung von Befürwortern als auch eher kritisch gegenüber der Lehre in der Allgemeinmedizin eingestellten Medizinstudierenden widerspiegeln. Von dem geplanten Schwerpunktprogramm erwarten die Studierenden einen starken Praxisbezug ebenso wie das Kennenlernen administrativer sowie wirtschaftlicher Hintergründe zum Führen einer Praxis.
Schlussfolgerungen: Durch die Einbeziehung der Zielgruppe am Entwicklungsprozess bestand die Möglichkeit, das zu entwickelnde Schwerpunktprogramm auf die späteren Teilnehmer passgenauer zuzuschneiden. Zudem ist zu erwarten, dass die Beteiligung der Studierenden zu einer höheren Akzeptanz des Programms führt. Die gewonnenen Ergebnisse zur Gestaltung eines Lehrangebots können als Orientierung für die mögliche Entwicklung ähnlicher Schwerpunktprogramme an anderen medizinischen Fakultäten dienen.
Aim: Participation of medical students in the conceptual development of targeted and attractive teaching content for rural areas.
Method: A questionnaire was developed to gather information on students' views of their current medical studies, career interests, and what requirements should be met by an optional rural health program in general practice. By means of an online survey in summer 2015, all medical students from the fourth preclinical semester onwards (n=2,150) at Goethe University Frankfurt were surveyed on one occasion. Statistical analysis was mainly descriptive. Personal attitudes towards a career as a family practitioner were examined for statistical significance. Further information was gathered on whether a measurable correlation exists between personal background and desired work location.
Results: Of the 2,150 students that were contacted, 617 participated in the survey (response rate=28.7%). The results covered a wide range of ideas and recommendations and were representative both of medical students with a positive attitude toward general practice, as well as those that were rather critical of teaching in general practice. The students expected the planned health program to be of strong practical relevance and to acquaint them with the administrative and economic aspects of running a practice.
Conclusions: By including the target group in the development process, it was possible to tailor the health program to meet the needs of future participants more precisely. Student participation can also be expected to result in greater acceptance of the program. The results on teaching content may also provide other medical faculties with orientation when developing comparable programs.
Ribosome biogenesis is essential for cellular function and involves rRNA synthesis, rRNA processing and modification, and ribosomal protein assembly. Ribosome biogenesis factors and small nucleolar RNA assist these events. Ribosomal maturation takes place in the nucleolus, the nucleoplasm, and the cytosol in a coordinated and controlled manner. For example, some ribosomal proteins are thought to be assembled in the cytoplasm based on the observations in Saccharomyces cerevisiae. Here, we used cellular fractionation to demonstrate that cleavage of the 20S intermediate, the precursor to mature 18S rRNA, does not occur in the nucleoplasm of Arabidopsis thaliana. It most likely occurs in the cytoplasm. Further, we verified the proposed localization of RPS10e, RPS26e, and RPL24a/b in the nucleus and RPP1 in the nucleolus of A. thaliana by ribosome profiling, immunofluorescence, and analysis of the localization of GFP fusion proteins. Our results suggest that the order of events during ribosomal protein assembly in the ribosome biogenesis pathway differs between plants and yeast.
Hydrogenation of CO₂ at ambient pressure catalyzed by a highly active thermostable biocatalyst
(2018)
Background: Replacing fossil fuels as energy carrier requires alternatives that combine sustainable production, high volumetric energy density, easy and fast refueling for mobile applications, and preferably low risk of hazard. Molecular hydrogen (H2) has been considered as promising alternative; however, practical application is struggling because of the low volumetric energy density and the explosion hazard when stored in large amounts. One way to overcome these limitations is the transient conversion of H2 into other chemicals with increased volumetric energy density and lower risk hazard, for example so-called liquid organic hydrogen carriers such as formic acid/formate that is obtained by hydrogenation of CO2. Many homogenous and heterogenous chemical catalysts have been described in the past years, however, often requiring high pressures and temperatures. Recently, the first biocatalyst for this reaction has been described opening the route to a biotechnological alternative for this conversion.
Results: The hydrogen-dependent CO2 reductase (HDCR) is a highly active biocatalyst for storing H2 in the form of formic acid/formate by reversibly catalyzing the hydrogenation of CO2. We report the identification, isolation, and characterization of the first thermostable HDCR operating at temperatures up to 70 °C. The enzyme was isolated from the thermophilic acetogenic bacterium Thermoanaerobacter kivui and displays exceptionally high activities in both reaction directions, substantially exceeding known chemical catalysts. CO2 hydrogenation is catalyzed at mild conditions with a turnover frequency of 9,556,000 h−1 (specific activity of 900 µmol formate min−1 mg−1) and the reverse reaction, H2 + CO2 release from formate, is catalyzed with a turnover frequency of 9,892,000 h−1 (930 µmol H2 min−1 mg−1). The HDCR of T. kivui consists of a [FeFe] hydrogenase subunit putatively coupled to a tungsten-dependent CO2 reductase/formate dehydrogenase subunit by an array of iron–sulfur clusters.
Conclusions: The discovery of the first thermostable HDCR provides a promising biological alternative for a chemically challenging reaction and might serve as model for the better understanding of catalysts able to efficiently reduce CO2. The catalytic activity for reversible CO2 hydrogenation of this enzyme is the highest activity known for bio- and chemical catalysts and requiring only ambient temperatures and pressures. The thermostability provides more flexibility regarding the process parameters for a biotechnological application.
Patients after orthopic liver transplantation (OLT) are at risk of developing graft dysfunction. Sphingolipids (SL’s) have been identified to play a pivotal role in the regulation of hepatocellular apoptosis, inflammation and immunity. We aimed to investigate the serum SL profile in a prospective real-world cohort of post-OLT patients. From October 2015 until July 2016, 149 well-characterized post-OLT patients were analyzed. SL’s were assessed in serum probes via Liquid Chromatography/Tandem Mass Spectrometry. Twenty-nine (20%) patients had a biopsy proven graft rejection with decreased C20-ceramide (Cer) (p = 0.042), C18-dihydroceramide (DHC) (p = 0.022) and C24DHC (p = 0.060) levels. Furthermore, C18DHC (p = 0.044) and C24DHC (p = 0.011) were significantly down-regulated in patients with ischemic type biliary lesions (ITBL; n = 15; 10%). One-hundred and thirty-three patients (89%) have so far received tacrolimus as the main immunosuppressive agent with observed elevations of C14Cer (p = 0.052), C18Cer (p = 0.049) and C18:1Cer (p = 0.024). Hepatocellular carcinoma (HCC) pre-OLT was associated with increases in C24:1Cer (p = 0.024) and C24:1DHC (p = 0.024). In this large prospective cross-sectional study of patients, post-OLT serum levels of (very-)long chain (dihydro-)ceramides associate with graft rejection, ITBL, tacrolimus intake and HCC pre-OLT. Hence, serum SL’s may be indicative of graft complications. Further research is necessary to identify their diverse mechanistic role in regulating immunity and inflammation in patients post-OLT.
More than 70 human adenoviruses with type-dependent pathogenicity have been identified but biological information about the majority of these virus types is scarce. Here we employed multiple sequence alignments and structural information to predict receptor usage for the development of an adenoviral vector with novel biological features. We report the generation of a cloned adenovirus based on human adenovirus type 17 (HAdV17) with high sequence homology to the well characterized human adenovirus type 37 (HAdV37) that causes epidemic keratoconjunctivitis (EKC). Our study revealed that human CD46 (CD46) is involved in cell entry of HAdV17. Moreover, we found that HAdV17 infects endothelial cells (EC) in vitro including primary cells at higher efficiencies compared to the commonly used human adenovirus type 5 (HAdV5). Using a human CD46 transgenic mouse model, we observed that HAdV17 displays a broad tropism in vivo after systemic injection and that it transduces ECs in this mouse model. We conclude that the HAdV17-based vector may provide a novel platform for gene therapy.
Purpose: Collaborative care is effective in improving symptoms of patients with depression. The aims of this study were to characterize symptom trajectories in patients with major depression during one year of collaborative care and to explore associations between baseline characteristics and symptom trajectories.
Methods: We conducted a cluster-randomized controlled trial in primary care. The collaborative care intervention comprised case management and behavioral activation. We used the Patient Health Questionnaire-9 (PHQ-9) to assess symptom severity as the primary outcome. Statistical analyses comprised latent growth mixture modeling and a hierarchical binary logistic regression model.
Results: We included 74 practices and 626 patients (310 intervention and 316 control recipients) at baseline. Based on a minimum of 12 measurement points for each intervention recipient, we identified two latent trajectories, which we labeled "fast improvers" (60.5%) and "slow improvers" (39.5%). At all measurements after baseline, "fast improvers" presented higher PHQ mean values than "slow improvers". At baseline, "fast improvers" presented fewer physical conditions, higher health-related quality of life, and had made fewer suicide attempts in their history.
Conclusions: A notable proportion of 39.5% of patients improved only "slowly" and probably needed more intense treatment. The third follow-up in month two could well be a sensible time to adjust treatment to support "slow improvers".
The mechanisms of transfer of crustal material from the subducting slab to the overlying mantle wedge are still debated. Mélange rocks, formed by mixing of sediments, oceanic crust, and ultramafics along the slab-mantle interface, are predicted to ascend as diapirs from the slab-top and transfer their compositional signatures to the source region of arc magmas. However, the compositions of melts that result from the interaction of mélanges with a peridotite wedge remain unknown. Here we present experimental evidence that melting of peridotite hybridized by mélanges produces melts that carry the major and trace element abundances observed in natural arc magmas. We propose that differences in nature and relative contributions of mélanges hybridizing the mantle produce a range of primary arc magmas, from tholeiitic to calc-alkaline. Thus, assimilation of mélanges into the wedge may play a key role in transferring subduction signatures from the slab to the source of arc magmas.
Introduction: Migrants are overrepresented in the European HIV epidemic. We aimed to understand the barriers and facilitators to HIV testing and current treatment and healthcare needs of migrants living with HIV in Europe.
Methods: A cross‐sectional study was conducted in 57 HIV clinics in nine countries (Belgium, Germany, Greece, Italy, The Netherlands, Portugal, Spain, Switzerland and United Kingdom), July 2013 to July 2015. HIV‐positive patients were eligible for inclusion if they were as follows: 18 years or older; foreign‐born residents and diagnosed within five years of recruitment. Questionnaires were completed electronically in one of 15 languages and linked to clinical records. Primary outcomes were access to primary care and previous negative HIV test. Data were analysed using random effects logistic regression. Outcomes of interest are presented for women, heterosexual men and gay/bisexual men.
Results: A total of 2093 respondents (658 women, 446 heterosexual men and 989 gay/bisexual men) were included. The prevalence of a previous negative HIV test was 46.7%, 43.4% and 82.0% for women, heterosexual and gay/bisexual men respectively. In multivariable analysis previous testing was positively associated with: receipt of post‐migration antenatal care among women, permanent residency among heterosexual men and identifying as gay rather than bisexual among gay/bisexual men. Access to primary care was found to be high (>83%) in all groups and was strongly associated with country of residence. Late diagnosis was common for women and heterosexual men (60.8% and 67.1%, respectively) despite utilization of health services prior to diagnosis. Across all groups almost three‐quarters of people on antiretrovirals had an HIV viral load <50 copies/mL.
Conclusions: Migrants access healthcare in Europe and while many migrants had previously tested for HIV, that they went on to test positive at a later date suggests that opportunities for HIV prevention are being missed. Expansion of testing beyond sexual health and antenatal settings is still required and testing opportunities should be linked with combination prevention measures such as access to PrEP and treatment as prevention.
Himalopsyche Banks, 1940 (Trichoptera, Rhyacophilidae) is a genus of caddisflies inhabiting mountain and alpine environments in Central and East Asia and the Nearctic. Of 53 known species, only five species have been described previously in the aquatic larval stage. We perform life stage association using three strategies (GMYC, PTP, and reciprocal monophyly) based on fragments of two molecular markers: the nuclear CAD, and the mitochondrial COI gene. A total of 525 individuals from across the range of Himalopsyche (Himalayas, Hengduan Shan, Tian Shan, South East Asia, Japan, and western North America) was analysed and 32 operational taxonomic units (OTUs) in our dataset delimited. Four distinct larval types of Himalopsyche are uncovered, and these are defined as the phryganea type, japonica type, tibetana type, and gigantea type and a comparative morphological characterisation of the larval types is presented. The larval types differ in a number of traits, most prominently in their gill configuration, as well as in other features such as setal configuration of the pronotum and presence/absence of accessory hooks of the anal prolegs.
Microangiopathy with subsequent organ damage represents a major complication in several diseases. The mechanisms leading to microvascular occlusion include von Willebrand factor (VWF), notably the formation of ultra-large von Willebrand factor fibers (ULVWFs) and platelet aggregation. To date, the contribution of erythrocytes to vascular occlusion is incompletely clarified. We investigated the platelet-independent interaction between stressed erythrocytes and ULVWFs and its consequences for microcirculation and organ function under dynamic conditions. In response to shear stress, erythrocytes interacted strongly with VWF to initiate the formation of ULVWF/erythrocyte aggregates via the binding of Annexin V to the VWF A1 domain. VWF-erythrocyte adhesion was attenuated by heparin and the VWF-specific protease ADAMTS13. In an in vivo model of renal ischemia/reperfusion injury, erythrocytes adhered to capillaries of wild-type but not VWF-deficient mice and later resulted in less renal damage. In vivo imaging in mice confirmed the adhesion of stressed erythrocytes to the vessel wall. Moreover, enhanced eryptosis rates and increased VWF binding were detected in blood samples from patients with chronic renal failure. Our study demonstrates that stressed erythrocytes have a pronounced binding affinity to ULVWFs. The discovered mechanisms suggest that erythrocytes are essential for the pathogenesis of microangiopathies and renal damage by actively binding to ULVWFs.
Die forensische Entomologie nutzt nekrophage Insekten, hauptsächlich Dipteren und ihre juvenilen Stadien, zur Schätzung der minimalen Leichenliegezeit. Dem liegt zugrunde, dass nekrophage Dipteren binnen Minuten nach dem Todeseintritt potentiell in der Lage sind, einen Leichnam zu detektieren und zu besiedeln. Das anschließende Wachstum und die Entwicklung der juvenilen Stadien erfolgt als Funktion von der Art und der Umgebungstemperatur.
Mit Hilfe von Laborstudien konnten bislang für einige forensisch relevante Fliegenarten Entwicklungsdaten erhoben werden, die eine Altersbestimmung der sich an einem Leichnam entwickelnden Larven und Puppen erlauben und so eine Schätzung der minimalen Leichenliegezeit ermöglichen. Als Nährsubstrat für Laborstudien werden tierische Gewebe verwendet. Eine Übertragbarkeit der Daten auf humanes Gewebe wurde aber bislang nicht verifiziert. In der vorliegenden Arbeit wurde das larvale Wachstum und die juvenile Entwicklungsgeschwindigkeit der forensisch relevanten Schmeißfliege Calliphora vicina (Diptera: Calliphoridae) auf humanem Muskelgewebe untersucht und mit dem Wachstum auf Schweineleber, magerem Schweinemuskelfleisch und Schweinehackfleisch verglichen. Die auf humanem Gewebe heranwachsenden Individuen waren mit bis zu 3,5 mm signifikant länger als die Individuen, die sich auf Leber und dem mageren Schweinemuskelfleisch entwickelten. Bei der Verwendung von Hackfleisch vom Schwein zeigte sich kein Unterschied. Darauf basierend wird die Empfehlung ausgesprochen, für zukünftige Entwicklungsstudien Schweinehackfleisch als Ersatz für humanes Gewebe zu verwenden.
Zahlreiche Anleitungen zur Asservierung forensisch-entomologischer Spuren empfehlen das Sammeln getrennt nach Körperregionen eines Leichnams. Dies soll eine mögliche gewebespezifische Entwicklungsrate berücksichtigen. Das für die vorliegende Arbeit durchgeführte systematische Absammeln von Fliegenlarven von 51 Leichnamen getrennt nach Körperregionen zeigte keine artspezifischen Präferenzen für bestimmte Gewebe oder Körperregionen. Das Artenspektrum entsprach größtenteils dem aufgrund von Studien an Schweinekadavern zu erwartendem Artenspektrum für Deutschland und Mitteleuropa. Insgesamt konnten 15 Schmeißfliegenarten nachgewiesen werden, von denen in der Regel mehrere gleichzeitig an einem Leichnam zu finden waren. Dies zeigt, dass ein Faktor wie interspezifische Konkurrenz in Zukunft mehr Beachtung in der Forschung erhalten sollte.
Bislang wurde in der forensischen Entomologie die minimale Leichenliegezeit durch die Untersuchung juveniler Stadien von Fliegen eingegrenzt. Eine eventuell mögliche Ausweitung dieses Zeitfensters könnte durch eine Altersbestimmung der adulten Fliegen oder der leeren Puparien gelingen. Der Nachweis, dass die dafür untersuchten Fliegen bzw. Puparien tatsächlich von dem fraglichen Leichnam stammen, war bislang nicht möglich. Die forensische relevante Schmeißfliege Lucilia sericata wurde in der vorliegenden Arbeit auf humanem Gewebe und Gewebe von elf weiteren Tierarten großgezogen. Durch die Analyse stabiler Kohlen- und Stickstoffisotope konnte ein von diesen elf Tierarten abgrenzbares humanes Isotopenprofil sowohl für die adulten Fliegen von L. sericata, als auch für ihre leeren Puparien detektiert werden. Dieses Profil spiegelte die Nahrungszusammensetzung der Wirte wider.
Die vorliegende Arbeit erhebt Daten zur Entwicklung einer forensisch relevanten Schmeißfliegenart auf humanem Gewebe, belegt das bislang lediglich am tierischen Modell erhobene Schmeißfliegeninventar als für menschliche Leichen relevant und hinterfragt die gewebespezifische Asservierungsempfehlung als ein akademisches Artefakt. Auf dieser Basis konnten Empfehlungen für die Weiterzucht fallrelevanter entomologischer Spuren ausgesprochen werden, die gerichtsverwertbar sind und die Verwendung von tierischem Gewebe oder Tierkadaver in der forensisch-entomologischen Forschung legitimieren. Die Analyse stabiler Isotope legt darüber hinaus einen neuen, innovativen Grundstein für die routinemäßige Spurenzuordnung älterer Entwicklungsstadien und ist damit Vorreiter auf dem Gebiet der forensischen Entomologie.
The interaction between the T4 bacteriophage gp37 adhesin and the bacterial lipopolysaccharide (LPS) is a well-studied system, however, the affinity and strength of the interaction haven’t been analyzed so far. Here, we use atomic force microscopy to determine the strength of the interaction between the adhesin and its receptor, namely LPS taken from a wild strain of E. coli B. As negative controls we used LPSs of E. coli O111:B and Hafnia alvei. To study the interaction an AFM tip modified with the gp37 adhesin was used to scan surfaces of mica covered with one of the three different LPSs. Using the correlation between the surface topography images and the tip-surface interaction we could verify the binding between the specific LPS and the tip in contrast to the very weak interaction between the tip and the non-binding LPSs. Using force spectroscopy we could then measure the binding strength by pulling on the AFM tip until it lifted off from the surface. The force necessary to break the interaction between gp37 and LPS from E. coli B, LPS from E. coli O111:B and LPS from H. alvei were measured to be 70 ± 29 pN, 46 ± 13 pN and 45 ± 14 pN, respectively. The latter values are likely partially due to non-specific interaction between the gp37 and the solid surface, as LPS from E. coli O111:B and LPS from H. alvei have been shown to not bind to gp37, which is confirmed by the low correlation between binding and topography for these samples.
The dopamine (DA) system plays a major role in cognitive functions through its interactions with several brain regions including the prefrontal cortex (PFC). Conversely, disturbances in the DA system contribute to cognitive deficits in psychiatric diseases, yet exactly how they do so remains poorly understood. Here we show, using mice with disease-relevant alterations in DA signaling (D2R-OE mice), that deficits in working memory (WM) are associated with impairments in the WM-dependent firing patterns of DA neurons in the ventral tegmental area (VTA). The WM-dependent phase-locking of DA neurons to 4 Hz VTA-PFC oscillations is absent in D2R-OE mice and VTA-PFC synchrony deficits scale with their WM impairments. We also find reduced 4 Hz synchrony between VTA DA neurons and selective impairments in their representation of WM demand. These results identify how altered DA neuron activity—at the level of long-range network activity and task-related firing patterns—may underlie cognitive impairments.
Die vorliegende Arbeit beschäftigt sich mit dem Thema Stemmatologie, d.h. primär der Rekonstruktion der Kopiergeschichte handschriftlich fixierter Dokumente. Zentrales Objekt der Stemmatologie ist das Stemma, eine visuelle Darstellung der Kopiergeschichte, welche i.d.R. graphtheoretisch als Baum bzw. gerichteter azyklischer Graph vorliegt, wobei die Knoten Textzeugen (d.s. die Textvarianten) darstellen während die Kanten für einzelne Kopierprozesse stehen. Im Mittelpunkt des Wissenschaftszweiges steht die Frage des Autorenoriginals (falls ein einziges solches existiert haben sollte) und die Frage der Rekonstruktion seines Textes. Das Stemma selbst ist ein Mittel zu diesem Hauptzweck (Cameron 1987). Der durch für manuelle Kopierprozesse kennzeichnende Abweichungen zunehmend abgewandelte Originaltext ist meist nicht direkt überliefert. Ziel der Arbeit ist es, die semi-automatische Stemmatologie umfassend zu beschreiben und durch Tools und analytische Verfahren weiterzuentwickeln. Der erste Teil der Arbeit beschreibt die Geschichte der computer-assistierten Stemmatologie inkl. ihrer klassischen Vorläufer und mündet in der Vorstellung eines einfachen Tools zur dynamischen graphischen Darstellung von Stemmata. Ein Exkurs zum philologischen Leitphänomen Lectio difficilior erörtert dessen mögliche psycholinguistische Ursachen im schnelleren lexikalischen Zugriff auf hochfrequente Lexeme. Im zweiten Teil wird daraufhin die existenziellste aller stemmatologischen Debatten, initiiert durch Joseph Bédier, mit mathematischen Argumenten auf Basis eines von Paul Maas 1937 vorgeschlagenen stemmatischen Models beleuchtet. Des Weiteren simuliert der Autor in diesem Kapitel Stemmata, um den potenziellen Einfluss der Distribution an Kopierhäufigkeiten pro Manuskript abzuschätzen.
Im nächsten Teil stellt der Autor ein eigens erstelltes Korpus in persischer Sprache vor, welches ebenso wie 3 der bekannten artifiziellen Korpora (Parzival, Notre Besoin, Heinrichi) qualitativ untersucht wird. Schließlich wird mit der Multi Modal Distance eine Methode zur Stemmagenerierung angewandt, welche auf externen Daten psycholinguistisch determinierter Buchstabenverwechslungswahrscheinlichkeiten beruht. Im letzten Teil arbeitet der Autor mit minimalen Spannbäumen zur Stemmaerzeugung, wobei eine vergleichende Studie zu 4 Methoden der Distanzmatrixgenerierung mit 4 Methoden zur Stemmaerzeugung durchgeführt, evaluiert und diskutiert wird.
We propose a spatiotemporal approach for modeling risk spillovers using time-varying proximity matrices based on observable financial networks and introduce a new bilateral specification. We study covariance stationarity and identification of the model, and analyze consistency and asymptotic normality of the quasi-maximum-likelihood estimator. We show how to isolate risk channels and we discuss how to compute target exposure able to reduce system variance. An empirical analysis on Euro-area cross-country holdings shows that Italy and Ireland are key players in spreading risk, France and Portugal are the major risk receivers, and we uncover Spain's non-trivial role as risk middleman.
We show that bond purchases undertaken in the context of quantitative easing efforts by the European Central Bank created a large mispricing between the market for German and Italian government bonds and their respective futures contracts. On top of the direct effect the buying pressure exerted on bond prices, we show three indirect effects through which the scarcity of bonds, resulting from the asset purchases, drove a wedge between the futures contracts and the underlying bonds: the deterioration of bond market liquidity, the increased bond specialness on the repurchase agreement market, and the greater uncertainty about bond availability as collateral.
We study the role of various trader types in providing liquidity in spot and futures markets based on complete order-book and transactions data as well as cross-market trader identifiers from the National Stock Exchange of India for a single large stock. During normal times, short-term traders who carry little inventory overnight are the primary intermediaries in both spot and futures markets, and changes in futures prices Granger-cause changes in spot prices. However, during two days of fast crashes, Granger-causality ran both ways. Both crashes were due to large-scale selling by foreign institutional investors in the spot market. Buying by short-term traders and cross-market traders was insufficient to stop the crashes. Mutual funds, patient traders with better trade-execution quality who were initially slow to move in, eventually bought sufficient quantities leading to price recovery in both markets. Our findings suggest that market stability requires the presence of well-capitalized standby liquidity providers.
An important assumption underlying the designation of some insurers as systemically important is that their overlapping portfolio holdings can result in common selling. We measure the overlap in holdings using cosine similarity, and show that insurers with more similar portfolios have larger subsequent common sales. This relationship can be magnified for some insurers when they are regulatory capital constrained or markets are under stress. When faced with an exogenous liquidity shock, insurers with greater portfolio similarity have even larger common sales that impact prices. Our measure can be used by regulators to predict which institutions may contribute most to financial instability through the asset liquidation channel of risk transmission.
This paper investigates inertia within and across banks in retail deposit markets using detailed panel data on consumer choices and account characteristics. In a structural choice model, I find that costs of inertia are around one third higher for switching accounts across compared to switching within banks. Observable proxies of bank-level switching costs (number and type of additional financial products) explain most of this cost premium, while online banking usage reduces inertia. Consistent with theory, I provide evidence that banks incorporate inertia in their pricing as older accounts pay lower rates than comparable newer accounts. Counterfactual policies reducing inertia shift market share to more competitive smaller banks, but only eliminating inertia within banks already results in high potential gains in consumer surplus. This suggests that facilitating bank switching alone might be insufficient to improve consumer choices.
In recent years European financial regulation has experienced a tremendous reorientation with respect to the shadow banking system, which manifested first and foremost in its reframing as market-based finance. Initially identified as a source of systemic risk certain initiatives did not only fall much behind the envisaged changes but all to the contrary have been substantially modified in a way that they now aim at revitalizing these activities. The reorientation of European regulatory agency on shadow banking post-crisis, from curtailing it to facilitating resilient market-based finance, has been a cause for irritation by academic observers, dismissed by some as mere rebranding or taken as a sign of regulatory capture. All to the contrary, this paper documents the central role of regulatory agency in shadow banking’s reconfiguration. It does so by analyzing the European initiatives concerning the regulation of Asset-Backed Commercial Paper (ABCP) and another prime example of shadow banking, Money Market Mutual Funds (MMFs). Based on documentary analysis and expert interviews we trace the way the recently published EU frameworks for MMFs and ABCP have been designed (in particular the STS, CRR and MMF regulation in 2017). Furthermore, we show how they have been transformed in such a way that their final versions allow to re-establish the shadow banking chain linking MMFs, the ABCP market and arguably the regular banking system. This transformation is driven by a new form of pro-active European regulatory agency which aims at creating a regulatory infrastructure able to sustain the orderly flow of real economy debt. Far from being captured by the industry, they did so consciously and in cooperation with private actors in order to maintain a channel for credit creation outside of bank credit, a task made more complicated by the rushed politicized final negotiations coupled with technical complexity. This paper thereby contributes to a new strand of literature, seeing the creation and reconfiguration of the shadow banking system as characterized by the active and conscious role of state actors.
We propose a unified framework to measure the effects of different reforms of the pension system on retirement ages and macroeconomic indicators in the face of demographic change. A rich overlapping generations (OLG) model is built and endogenous retirement decisions are explicitly modeled within a public pension system. Heterogeneity with respect to consumption preferences, wage profiles, and survival rates is embedded in the model. Besides the expected direct effects of these reforms on the behavior of households, we observe that feedback effects do occur. Results suggest that individual retirement decisions are strongly influenced by numerous incentives produced by the pension system and macroeconomic variables, such as the statutory eligibility age, adjustment rates, the presence of a replacement rate, and interest rates. Those decisions, in turn, have several impacts on the macro-economy which can create feedback cycles working through equilibrium effects on interest rates and wages. Taken together, these reform scenarios have strong implications for the sustainability of pension systems. Because of the rich nature of our unified model framework, we are able to rank the reform proposals according to several individual and macroeconomic measures, thereby providing important support for policy recommendations on pension systems.
The paper investigates the determinants of the idiosyncratic volatility puzzle by allowing linkages across asset returns. The first contribution of the paper is to show that portfolios sorted by increasing indegree computed on the network based on Granger causality test have lower expected returns, not related to idiosyncratic volatility. Secondly, empirical evidence indicates that stocks with higher idiosyncratic volatility have the lower exposition on the indegree risk factor.
We examine how a firms' investment behavior affects the investment of a neighboring firm. Economic theory yields ambiguous predictions regarding the direction of firm peer effects and consistent with earlier work, we find that firms display similar investment behavior within an area using OLS analysis. Exploiting time-variation in the rise of U.S. states' corporate income taxes and utilizing heterogeneity in firms' exposure to increases in corporate income tax rates, we identify the causal impact of local firms' investments. Using this as an instrumental variable in a 2SLS estimation, we find that an increases in local firms' investment reduces the investment of a local peer firm. This effect is more pronounced if local competition among firms is stronger and supports theories that firm investments are strategic substitutes due to competition.
We use minutes from 17,000 financial advisory sessions and corresponding client portfolio data to study how active client involvement affects advisor recommendations and portfolio outcomes. We find that advisors confronted with acquiescent clients stick to their standards and recommend expensive but well diversified mutual fund portfolios. However, if clients take an active role in the meetings, advisors deviate markedly from their standards, resulting in poorer portfolio diversification and lower Sharpe ratios. Our findings that advisors cater to client requests parallel the phenomenon of doctors prescribing antibiotics to insistent patients even if inappropriate, and imply that pandering diminishes the quality of advice.
This paper provides a complete characterization of optimal contracts in principal-agent settings where the agent's action has persistent effects. We model general information environments via the stochastic process of the likelihood-ratio. The martingale property of this performance metric captures the information benefit of deferral. Costs of deferral may result from both the agent's relative impatience as well as her consumption smoothing needs. If the relatively impatient agent is risk neutral, optimal contracts take a simple form in that they only reward maximal performance for at most two payout dates. If the agent is additionally risk-averse, optimal contracts stipulate rewards for a larger selection of dates and performance states: The performance hurdle to obtain the same level of compensation is increasing over time whereas the pay-performance sensitivity is declining.
"Naming Gender" von Susanne Oelkers (2003) ist die erste Studie, die sich eingehend mit der Geschlechtskennzeichnung von Rufnamen befasst. Für die Herstellung und Darstellung von Geschlecht stellt nicht nur Sprache generell, sondern zuvörderst das Namensystem ein zentrales Zeichensystem zur Verfügung. Namen haben damit beträchtlichen Anteil an Ordnungsstiftung und Komplexitätsreduktion. Die deutsche Onomastik hat sich bis 2003 kaum für die soziale Differenz Gender interessiert, sie hat die linguistische und soziologische Genderforschung nicht rezipiert. Umgekehrt haben auch Genderlinguistik und Soziologie die Personennamen weitgehend übersehen (von Lindemann 1996 und Gerhards 2003 abgesehen). Dies steht der Relevanz entgegen, die Namen für die Etablierung und Prozessierung der Geschlechterordnung haben. Selbst Sprachen ohne jegliche grammatische Genus- oder Gendermarkierung können mit ihren Rufnamen Geschlecht indizieren (z.B. Finnisch und Estnisch, die nicht einmal bei den Personalpronomen der 3. Person Geschlecht markieren).
Based on the concept of oxidative stress, reactive oxygen species (ROS) have been incriminated as the drivers behind almost every cardiovascular pathology. Redox alterations are, however, omnipresent bystanders to changes in cellular activity state. Even when ROS levels are altered, their contribution to pathology is not necessarily causal. Researchers should hesitate to engage in global ROS measurements and rather aim on identifying individual molecular targets of redox regulation.
Objectives: The SAVI-TF (Symetis ACURATE neo Valve Implantation Using Transfemoral Access) registry was initiated to study the ACURATE neo transcatheter heart valve in a large patient population treated under real-world conditions.
Background: The self-expanding, supra-annular ACURATE neo prosthesis is a transcatheter heart valve that gained the Conformité Européene mark in 2014, but only limited clinical data are available so far.
Methods: This prospective, multicenter registry enrolled 1,000 patients at 25 European centers who were followed for 1 year post-procedure.
Results: Mean patient age was 81.1 ± 5.2 years; mean logistic European System for Cardiac Operative Risk Evaluation I score, European System for Cardiac Operative Risk Evaluation II score, and Society of Thoracic Surgeons score were 18.1 ± 12.5%, 6.6 ± 7.5%, and 6.0 ± 5.6%, respectively. At 1 year, 8.0% (95% confidence interval [CI]: 6.3% to 9.7%) of patients had died, 2.3% (95% CI: 1.3% to 3.2%) had disabling strokes, and 9.9% (95% CI: 8.1% to 11.8%) had permanent pacemaker implantations. Through 1 year, 5 reinterventions (0.5%; 95% CI: 0.1% to 1.0%) were performed: 3 valve-in-valve and 2 surgical aortic valve replacements. Mean effective orifice area was 1.84 ± 0.43 cm2, mean gradient was 7.3 ± 3.7 mm Hg, and greater than mild paravalvular leakage was observed in 3.6% of patients.
Conclusions: Transfemoral implantation of the ACURATE neo prosthesis resulted in favorable 1-year clinical and echocardiographic outcomes with very low mortality and new pacemaker rates.
Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy.
Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation.
Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers.
Conclusions: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin.
Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement—almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.
Background: A diagnosis of post-traumatic stress disorder (PTSD) requires the identification of one or more traumatic events, designated the index trauma, which serves as the basis for assessment of severity of PTSD. In patients who have experienced more than one traumatic event, severity may depend on the exact definition of the index trauma. Defining the index trauma as the worst single incident may result in PTSD severity scores that differ from what would be seen if the index trauma included multiple events.
Objective: This study aimed to investigate the impact of the definition of the index trauma on PTSD baseline severity scores and treatment outcome.
Method: A planned secondary analysis was performed on data from a subset (N = 58) of patients enrolled in a trial evaluating the efficacy of a 12 week residential dialectical behavioural therapy programme for PTSD related to childhood abuse (DBT-PTSD). Assessments of the severity of PTSD were conducted at admission, at the end of the 12 week treatment period, and at 6 and 12 weeks post-treatment, using the Clinician-Administered PTSD Scale. The index trauma was defined with respect to both the worst single incident and up to three qualitatively distinct traumatic events.
Results: When the index trauma included multiple traumas, PTSD severity scores were significantly higher and improvements from pre- to post-treatment were significantly lower than when the index trauma was defined as the worst single incident.
Conclusions: In patients with PTSD who have experienced multiple traumas, defining the index trauma as the worst single incident may miss some aspects of clinically relevant symptomatology, thereby leading to a possibly biased interpretation of treatment effects. In DBT-PTSD, treatment effects were lower when the index trauma included multiple traumatic events. More research is needed to determine the impact of the various index trauma definitions on the evaluation of other trauma-focused treatments.
Objectives: In the AURA3 trial, individuals received osimertinib 80 mg once daily or chemotherapy for advanced non-small cell lung cancer. Here, we explore patient-reported symptoms possibly related to treatment.
Materials and methods: AURA3 was an open-label, randomized phase III trial involving 419 patients. As part of the trial’s exploratory objectives, individuals were asked to complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) electronically, first weekly for 18 weeks and then every 3 weeks for up to 57 weeks, subject to the availability of validated local-language versions (English, German, Japanese and Spanish versions were available).
Results: In total, 161 patients (38%; 102 receiving osimertinib, 59 receiving chemotherapy) provided data for PRO-CTCAE analyses (mean age: 64 years; 63% women). Diarrhea was reported more commonly with osimertinib than with chemotherapy, and was mostly graded as occurring rarely or occasionally. Decreased appetite was reported less commonly with osimertinib than with chemotherapy. The proportion of patients reporting nausea changed little from baseline with osimertinib and increased with chemotherapy. Few patients reported vomiting. Both nausea and vomiting were generally graded as mild in severity. Fatigue was reported less commonly with osimertinib than with chemotherapy, and was mostly graded as mild or moderate. Of patients reporting fatigue, the proportion grading it as interfering at least ‘somewhat’ with their usual or daily activities was lower with osimertinib than with chemotherapy.
Conclusion: Symptoms were generally mild and not frequent, with some differences in symptom patterns between the two treatment groups. The results support and complement the AURA3 trial data and give insight into patients’ experience with treatment.
Effects of single-point acupuncture (HT7) in the prevention of test anxiety : results of a RCT
(2018)
Background: The number of students using neuro enhancement to improve their performance and to prevent test anxiety is increasing. The acupuncture point Heart 7 (HT7) has been described as being prominent in reducing states of anxiety.
Methods: We conducted a randomized placebo-controlled, two-armed pilot trial to investigate the efficacy of a single-point acupuncture treatment at bilateral HT7 compared to sham laser acupuncture on test anxiety. Test anxiety was induced applying the standardised protocol of the Trier Social Stress Test. Outcome measures included saliva samples analysed for cortisol and amylase, anxiety questionnaires and heart rate variability.
Results: Twenty-five male subjects (age 28 ± 5 years) were allocated to either verum acupuncture (n = 12) or sham laser acupuncture (n = 13). Cortisol peaked 20 min after the stress test (2-fold, 18.11 ± 2 nmol/l) and amylase 10 min after (2-fold, 259 ± 49 U/ml) with no difference between groups. There were no differences between groups regarding either anxiety questionnaires or physiological parameters. Compared to reference data (3-fold increase in cortisol), increase in stress hormones and heart rate seemed somewhat reduced.
Conclusions: Acupuncture may be a possible approach for the treatment of anxiety. Due to the lack of a no control treatment group, we cannot determine the magnitude of possible specific needle effects at HT7 to promote specific effects in the neuroendocrine system. Finally this study only examines the efficacy of a single time treatment.
kurz und kn@pp news : Nr. 43
(2018)
The liver as the biggest endocrine gland of the human body plays a central role in many metabolic pathways such as detoxification, storage of carbohydrates and distribution of lipids. As the liver receives blood supply from the gut by the portal vein, liver cells are often challenged with high concentrations of nutrients and components of our commensal microbiota. Therefore, the immune system of the liver induces a tolerant state, meaning no or low inflammatory reactions to those constant stimuli. Yet, as various pathogens target the liver, the hepatic immune system also needs the capability to induce strong immune responses quickly. Chronical damage to the liver, which can be caused by alcohol, pathogens or toxins, might lead to liver cirrhosis, where the amount of functional liver tissue is decreased dramatically. This pathology can worsen and lead to acute-on-chronic liver failure, whose high mortality is due to high inflammation and multi-organ failure. Interleukin-7 is a cytokine known for its pro-survival functions especially in lymphopoiesis. However, it is also very important for maintenance of mature immune cells in the liver. As mouse experiments have demonstrated an induction of Interleukin-7 in the liver as a response to bacterial lipopolysaccharide, we aimed to characterize the role of Interleukin-7 in hepatic immunoregulation in both health and disease.
The experiments were mostly based on in vitro approaches. Induction of Interleukin-7 in liver cells was analyzed using ELISA, quantitative PCR, and Immunoblotting. Knockdown of signal transduction components was performed by siRNA transfection. Primary immune cells isolated from healthy donor buffy coat were studied for their ability to respond to Interleukin-7. Activation of downstream signal transduction was assessed by Immunoblotting. Functional consequences of Interleukin-7 signaling, such as alterations in cellular metabolism, cellular survival and endotoxin tolerance, were studied in monocyte-derived macrophages. Finally, serum concentrations of Interleukin-7 and frequencies of Interleukin-7 receptor positive immune cells were quantified in patients with compensated or decompensated liver cirrhosis or acute-on-chronic liver failure.
Interleukin-7 expression could be observed in human hepatic cell lines and primary hepatic sinusoidal endothelial cells when stimulated with IFNα or IFNγ, but not IFNλ. IRF-1 was identified as a key regulator of Interleukin-7 expression, as its transcription, translation and nuclear translocation were induced and enhanced upon IFNα or IFNγ, but not IFNλ treatment. We identified LPS-primed macrophages as innate immune target cells of Interleukin-7, which responded by an inhibitory phosphorylation of GSK3. This signal transduction led to enhanced production of pro-inflammatory cytokines and abolished endotoxin tolerance. In parallel, cellular fitness was reduced as demonstrated by reduced intracellular ATP concentration and intracellular WST-1 staining. Finally, we could identify components of the in vitro signal transduction also in liver cirrhosis patients. However, Interleukin-7 serum concentrations were significantly in liver cirrhosis patients compared to healthy controls. In addition, the frequencies of Interleukin-7 receptor positive immune cell populations differed in patients and controls.
We identify Interleukin-7 as a pro-inflammatory cytokine in hepatic immunoregulation. It is part of a cascade where its induction is regulated by type I and type II Interferons and mainly restricted by the presence of IRF1. We demonstrate the importance of Interleukin-7 also for innate immune cells, where the abolishment of endotoxin tolerance may provide an interesting strategy of liver cirrhosis patients. In addition, reduced viability of macrophages in response to Interleukin-7 is a striking contrast to the well-described survival functions in lymphocytes. The decrease of serum Interleukin-7 levels and alterations of Interleukin-7 receptor positive immune cell populations suggest an important role for Interleukin-7 also in the diseased liver. Due to the identified mechanisms of action, Interleukin-7 may be an interesting candidate for immunotherapeutic approaches of liver cirrhosis and acute-on-chronic liver failure.
Eastern boundary upwelling provides the conditions for high marine productivity in the Canary Current System off NW-Africa. Despite its considerable importance to fisheries, knowledge on this marine ecosystem is only limited. Here, parasites were used as indicators to gain insight into the host ecology and food web of two pelagic fish species, the commercially important species Trichiurus lepturus Linnaeus, 1758, and Nealotus tripes Johnson, 1865. Fish specimens of T. lepturus (n = 104) and N. tripes (n = 91), sampled from the Canary Current System off the Senegalese coast and Cape Verde Islands, were examined, collecting data on their biometrics, diet and parasitisation. In this study, the first parasitological data on N. tripes are presented. T. lepturus mainly preyed on small pelagic Crustacea and the diet of N. tripes was dominated by small mesopelagic Teleostei. Both host species were infested by mostly generalist parasites. The parasite fauna of T. lepturus consisted of at least nine different species belonging to six taxonomic groups, with a less diverse fauna of ectoparasites and cestodes in comparison to studies in other coastal ecosystems (Brazil Current and Kuriosho Current). The zoonotic nematode Anisakis pegreffii occurred in 23% of the samples and could pose a risk regarding food safety. The parasite fauna of N. tripes was composed of at least thirteen species from seven different taxonomic groups. Its most common parasites were digenean ovigerous metacercariae, larval cestodes and a monogenean species (Diclidophoridae). The observed patterns of parasitisation in both host species indicate their trophic relationships and are typical for mesopredators from the subtropical epi- and mesopelagic. The parasite fauna, containing few dominant species with a high abundance, represents the typical species composition of an eastern boundary upwelling ecosystem.
Systemic treatment is necessary for one third of patients with renal cell carcinoma. No valid biomarker is currently available to tailor personalized therapy. In this study we established a representative panel of patient derived xenograft (PDX) mouse models from patients with renal cell carcinomas and determined serum levels of high mobility group B1 (HMGB1) protein under treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus and bevacizumab. Serum HMGB1 levels were significantly higher in a subset of the PDX collection, which exhibited slower tumor growth during subsequent passages than tumors with low HMGB1 serum levels. Pre-treatment PDX serum HMGB1 levels also correlated with response to systemic treatment: PDX models with high HMGB1 levels predicted response to bevacizumab. Taken together, we provide for the first time evidence that the damage associated molecular pattern biomarker HMGB1 can predict response to systemic treatment with bevacizumab. Our data support the future evaluation of HMGB1 as a predictive biomarker for bevacizumab sensitivity in patients with renal cell carcinoma.
Mutations causing aberrant splicing are frequently implicated in human diseases including cancer. Here, we establish a high-throughput screen of randomly mutated minigenes to decode the cis-regulatory landscape that determines alternative splicing of exon 11 in the proto-oncogene MST1R (RON). Mathematical modelling of splicing kinetics enables us to identify more than 1000 mutations affecting RON exon 11 skipping, which corresponds to the pathological isoform RON∆165. Importantly, the effects correlate with RON alternative splicing in cancer patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear ribonucleoprotein H (HNRNPH) as a key regulator of RON splicing in healthy tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the functionally most relevant HNRNPH binding sites and demonstrate how cooperative HNRNPH binding facilitates a splicing switch of RON exon 11. Our results thereby offer insights into splicing regulation and the impact of mutations on alternative splicing in cancer.
When mapping eye-movement behavior to the visual information presented to an observer, Areas of Interest (AOIs) are commonly employed. For static stimuli (screen without moving elements), this requires that one AOI set is constructed for each stimulus, a possibility in most eye-tracker manufacturers' software. For moving stimuli (screens with moving elements), however, it is often a time-consuming process, as AOIs have to be constructed for each video frame. A popular use-case for such moving AOIs is to study gaze behavior to moving faces. Although it is technically possible to construct AOIs automatically, the standard in this field is still manual AOI construction. This is likely due to the fact that automatic AOI-construction methods are (1) technically complex, or (2) not effective enough for empirical research. To aid researchers in this field, we present and validate a method that automatically achieves AOI construction for videos containing a face. The fully-automatic method uses an open-source toolbox for facial landmark detection, and a Voronoi-based AOI-construction method. We compared the position of AOIs obtained using our new method, and the eye-tracking measures derived from it, to a recently published semi-automatic method. The differences between the two methods were negligible. The presented method is therefore both effective (as effective as previous methods), and efficient; no researcher time is needed for AOI construction. The software is freely available from https://osf.io/zgmch/.
Predicting the requirement for renal replacement therapy in intensive care patients with sepsis
(2018)
Sepsis is one of the most frequent causes of acute kidney injury (AKI) in critically ill patients, with initial organ impairment often followed by dysfunction in other systems. Renal dysfunction may therefore represent one facet in the evolution towards multiple organ dysfunction syndrome (MODS) or, alternatively, may be indicative of system-wide endothelial damage caused by hyperinflammation and a positive fluid balance. Whilst numerous biomarkers have been investigated to predict renal replacement therapy (RRT) requirement, including NGAL, TIMP-2 and IGFBP-7, mid-regional proadrenomedullin (MR-proADM) may also be of interest due to its involvement in capillary leakage, endothelial dysfunction and the initial stages of multiple organ failure development. ...
Im Jahr 1564 veröffentlicht der Ulmer Militärexperte und -schriftsteller Leonhard Fronsperger die Schrift "Von dem Lob deß Eigen Nutzen", in der er darlegt, dass die konsequente Verfolgung des eigenen Nutzens als individuelle Handlungsmaxime im Ergebnis zu einer Förderung des Gemeinwohls führt. Das etwas mehr als hundert Seiten umfassende Werk wird in Frankfurt am Main, einem Zentrum des europäischen Buchdrucks und -handels, verlegt und findet Erwähnung im ersten veröffentlichten Katalog der Frankfurter Buchmesse. Fronsperger präsentiert seine für die damalige Zeit durchaus revolutionäre These in der Form eines satirischen Enkomions und unterlegt sie mit einer umfangreichen Gesellschaftsanalyse. Er stellt fest, dass die politischen Herrschaftsformen, die gesellschaftlichen Institutionen und die wirtschaftlichen Handelsbeziehungen auf einer konsequenten Verfolgung des eigenen Nutzens aller Akteure beruhen und dass sich die von der Kirche geforderte Ausrichtung des individuellen Handelns am Gemeinwohl in der Realität nicht finden lässt. Vielmehr hält er die Kritik der Theologen am egoistischen Handeln des Einzelnen für falsch, empfindet er doch den Staat, Wirtschaft und Gesellschaft im Großen und Ganzen als gut funktionierend.
Im Folgenden dokumentieren wir zunächst die Biografie des Autors, die Entstehung und Verbreitung des Werks und seine besondere literarische Form. Anschließend diskutieren wir die zentrale These in drei verschiedenen geistesgeschichtlichen Kontexten, die jeweils von besonderer Bedeutung für die Herausbildung der neuzeitlichen Gesellschafts- und Wirtschaftstheorien sind. Erkenntnis- und staatstheoretisch weist Fronspergers Werk deutliche Parallelen zu den Analysen auf, die Niccolò Machiavelli und später Giovanni Botero in Italien zur Bedeutung der auf den individuellen fürstlichen Interessen basierenden Staatsräson bzw. zu den Triebkräften erfolgreicher Stadtentwicklung vorlegten. Markante Unterschiede gibt es dagegen zu den Ansichten der deutschsprachigen Reformatoren im Anschluss an Luther, die zwar die Unterscheidung zwischen geistlicher und weltlicher Sphäre propagieren und damit die Entwicklung einer eigenständigen Moral für das Wirtschaftsleben befördern, dort allerdings mehrheitlich die Orientierung am "Gemeinen Nutzen" propagieren. Indem Fronsperger dagegen die Verfolgung des Eigennutzes fordert, nimmt er wirtschafts- und gesellschaftstheoretische Einsichten über das Wesen und die Auswirkungen der Arbeitsteilung vorweg, die erst 150 Jahre und später von Bernard Mandeville und Adam Smith in England und Schottland formuliert wurden. Das Werk Fronspergers bietet damit ein herausragendes Beispiel dafür, wie sich aus dem Zusammenspiel von wirtschaftlichem Erfolg, einem realistischen Menschenbild und manchen Aspekten der Reformation in deren Folge ein neues normatives Verständnis von den Antriebskräften ökonomischer und gesellschaftlicher Dynamik entwickelt, das später als der "Geist des Kapitalismus" bezeichnet wird.
Complex I couples the free energy released from quinone (Q) reduction to pump protons across the biological membrane in the respiratory chains of mitochondria and many bacteria. The Q reduction site is separated by a large distance from the proton-pumping membrane domain. To address the molecular mechanism of this long-range proton-electron coupling, we perform here full atomistic molecular dynamics simulations, free energy calculations, and continuum electrostatics calculations on complex I from Thermus thermophilus. We show that the dynamics of Q is redox-state-dependent, and that quinol, QH2, moves out of its reduction site and into a site in the Q tunnel that is occupied by a Q analog in a crystal structure of Yarrowia lipolytica. We also identify a second Q-binding site near the opening of the Q tunnel in the membrane domain, where the Q headgroup forms strong interactions with a cluster of aromatic and charged residues, while the Q tail resides in the lipid membrane. We estimate the effective diffusion coefficient of Q in the tunnel, and in turn the characteristic time for Q to reach the active site and for QH2 to escape to the membrane. Our simulations show that Q moves along the Q tunnel in a redox-state-dependent manner, with distinct binding sites formed by conserved residue clusters. The motion of Q to these binding sites is proposed to be coupled to the proton-pumping machinery in complex I.
The retinal rod pathway, featuring dedicated rod bipolar cells (RBCs) and AII amacrine cells, has been intensely studied in placental mammals. Here, we analyzed the rod pathway in a nocturnal marsupial, the South American opossum Monodelphis domestica to elucidate whether marsupials have a similar rod pathway. The retina was dominated by rods with densities of 338,000–413,000/mm². Immunohistochemistry for the RBC-specific marker protein kinase Cα (PKCα) and the AII cell marker calretinin revealed the presence of both cell types with their typical morphology. This is the first demonstration of RBCs in a marsupial and of the integration of RBCs and AII cells in the rod signaling pathway. Electron microscopy showed invaginating synaptic contacts of the PKCα-immunoreactive bipolar cells with rods; light microscopic co-immunolabeling for the synaptic ribbon marker CtBP2 confirmed dominant rod contacts. The RBC axon terminals were mostly located in the innermost stratum S5 of the inner plexiform layer (IPL), but had additional side branches and synaptic varicosities in strata S3 and S4, with S3-S5 belonging to the presumed functional ON sublayer of the IPL, as shown by immunolabeling for the ON bipolar cell marker Gγ13. Triple-immunolabeling for PKCα, calretinin and CtBP2 demonstrated RBC synapses onto AII cells. These features conform to the pattern seen in placental mammals, indicating a basically similar rod pathway in M. domestica. The density range of RBCs was 9,900–16,600/mm2, that of AII cells was 1,500–3,260/mm2. The numerical convergence (density ratio) of 146–156 rods to 4.7–6.0 RBCs to 1 AII cell is within the broad range found among placental mammals. For comparison, we collected data for the Australian nocturnal dunnart Sminthopsis crassicaudata, and found it to be similar to M. domestica, with rod-contacting PKCα-immunoreactive bipolar cells that had axon terminals also stratifying in IPL strata S3-S5.
Die Verknüpfung des Fahrrades mit dem Öffentlichen Verkehr (ÖV) kann den Umweltverbund stärken, den Übergang von einem Verkehrssystem auf das andere erleichtern und eine attraktive Alternative zum motorisierten Individualverkehr schaffen. Die vorliegende Arbeit repräsentiert den zweiten umfassenden Projektbericht innerhalb des Forschungsprojektes „Verbesserte Integration des Fahrrads in den öffentlichen Verkehr – Systematische Erschließung von Handlungsoptionen und Bewertung von Best-Practices“. Im ersten Projektbericht (ebenfalls in dieser Arbeitspapierreihe erschienen – Nr. 15) wurden die Entwicklungen der letzten Jahre in den infrastrukturellen Themenfeldern Fahrradmitnahme, Fahrradverleihsysteme und Fahrradabstellanlagen aufgearbeitet und Fragen zu Kommunikation und Marketing der Angebote sowie zu Möglichkeiten der fortschreitenden Digitalisierung zur verbesserten Integration von Fahrrad und Öffentlichem Verkehr diskutiert. Darauf aufbauend werden im vorliegenden Bericht die Ergebnisse vertiefender Fallstudien dargestellt, mit dem Ziel, Erfolgsfaktoren und Hemmnisse für die Integration von Fahrrad mit Öffentlichem Verkehr aufzuzeigen und in einem späteren Schritt daraus Handlungsempfehlungen zur Stärkung dieser Integration für Kommunen und Verkehrsanbieter geben zu können. Für die Fallstudien wurden solche Beispiele ausgewählt, die einen Vorbildcharakter haben und als nachahmenswert für andere Städte und Regionen gelten können bzw. aus denen sich Erkenntnisse für die Stärkung der Integration von Fahrradverkehr mit dem ÖV ziehen lassen. Zudem sollten die verschiedenen infrastrukturellen Themenfelder abgedeckt sein. Neben einer Darstellung der jeweils fallspezifischen Besonderheiten wird zu jedem Fallbeispiel das Betreiber- und Geschäftsmodell dargestellt und es erfolgt eine Bewertung, die sowohl die Sicht der Betreiber als auch die der Nutzenden beachtet.
Folgende Fallbeispiele werden behandelt:
Die hessischen Verkehrsverbünde Rhein-Main-Verkehrsverbund (RMV) und Nordhessischer Verkehrsverbund (NVV) bieten eine kosten- und sperrzeitfreie Mitnahmeregelung für Fahrräder an.
Das MVGmeinRad Mainz ist als Fahrradverleihsystem ein Teil des kommunalen ÖPNV-Unternehmens.
Zu den Fahrradabstellanlagen an Bahnhöfen wurden in der Fallstudie drei unterschiedlich große Anlagen einbezogen: Dein Radschloss des Verkehrsverbundes Rhein-Ruhr (VRR) für kleine, das Radhaus Offenburg für mittelgroße und die Radstation Düsseldorf für große Standorte.
München wurde schließlich für eine kommunale Strategie zur verbesserten Verknüpfung von Fahrrad und Öffentlichem Verkehr ausgewählt, da dort eine Vielzahl von Maßnahmen zur Stärkung der Fahrradmobilität sichtbar sind.
SAFE Newsletter : 2018, Q3
(2018)
Die am Ende des 19. Jahrhunderts in Frankreich entstandene Décadence hatte einen wichtigen Einfluss auf europäische Literaturen. Charles Baudelaire, Paul Bourget, Hermann Bahr und Friedrich Nietzsche sind unter den Vertretern dieser literarischen Bewegung aufzuzählen. Die Wirkung der Décadence auf derzeitige türkische Literatur ist aus vielen Werken erkennbar. Yakup Kadris frühe Werke tragen auch klare Spuren der 'Décadence'. In seinem Roman 'Yaban' – obwohl es ein realistischer Roman ist – sind viele dekadente Eigenschaften zu betrachten. Der große Abgrund zwischen den türkischen Intellektuellen und den Dörfern ist ein wichtiges Thema des Werkes. Der Protagonist Ahmet Celâl beschließt nach dem Ersten Weltkrieg in einem kleinen Dorf Anatoliens zu leben. Durch seine Erfahrungen und Beziehungen mit den Dörflern treten zahlreiche dekadente Eigenschaften der Dörfler und des Protagonisten in Vordergrund. Ahmet Celâl konfrontiert die Einsamkeit, Krankheiten, Hilflosigkeit, Entfremdung und allerart soziokulturellen Verfall im Dorf, was die dekadente Seite des Dorfes zeigt. Andererseits sind seine dekadenten Haltungen wie Zurückgezogenheit, Übertreibung der Hässlichkeit und Schönheit, Widrigkeit, Verschönerung des Todes und Pessimismus im Werk zu sehen. In dieser Arbeit wird eine kurze Information über die Dekadenz und deren Vertreter vermittelt. Anhand der Décadence-Auffassungen von Nietzsche, Bourget und Bahr werden dekadente Motive in Yakup Kadris Roman Yaban dargestellt.
Das Ziel dieser Arbeit ist es, die Dekadenz als literarische Vorlage in den Werken von Tezer Özlü und Hugo von Hofmannsthal zu untersuchen. Hierbei wird der Tod in den Werken 'Die kalten Nächte der Kindheit' und 'Das Märchen der 672. Nacht' mit Hilfe der hermeneutischen Methode analysiert. Anhaltspunkt für die Analyse ist die Dekadenzdichtung nach Bourget und Bahr. Bourgets Vergleich der Gesellschaft mit Organismen und deren Verfall im Falle einer Verweigerung der Kooperation sind neben Bahrs Romantik der Nerven, Hang nach dem Künstlichen, Sucht nach dem Mystischen und letztlich dem Zug ins Ungeheure und Schrankenlose Hauptuntersuchungskriterien bei der Motivselektion. Die ausgesuchten Motive werden in Passagen ausgeschnitten und den dekadenten Vorgaben gemäß interpretiert und kontrastiv verglichen. Man sieht, dass die Dekadenzdichtung nicht zeitengebunden ist, da beide Werke verschiedenen Epochen angehören. Was sie vereint, ist einzig und allein der Hang zur Abweichung, wie auch Huysmanns Roman A rebours es sagt, nämlich gegen den Strich.
Hofmannsthal ist vom Orient fasziniert. In seinem lyrischen Drama "Hochzeit der Sobeide" wie in vielen seiner Werke und Erzählungen sind Einflüsse der orientalischen Kultur auffällig. Der Handlungsort des Dramas "Die Hochzeit der Sobeide" ist eine alte Stadt im Königreich Persien. Dass der orientalische Schauplatz hier eine dekorative Bedeutung hat, bestätigt eine spätere Version, in der die Geschichte von Persien nach Ragusa verlegt wird. Aus der Stadt in Persien wird dann eine italienische Kaufmannsrepublik. Dennoch stellt sich die Frage: Warum die Geschichte zunächst im Orient spielt. Mein Beitrag wird die Deutung orientalischer Spuren in dem Theaterstück thematisieren.
Background: Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells (NPCs), especially their biological behavior under the influence of exogenous stem cells, specifically the gene expression and regulation pattern. In the present study, we aimed to determine messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), which are differentially expressed during the co-culturing process with adipose-derived mesenchymal stem cells (ASCs) and to explore the involved signaling pathways and the regulatory networks.
Methods: We compared degenerative NPCs co-cultured with ASCs with those cultured solely using lncRNA-mRNA microarray analysis. Based on these data, we investigated the significantly regulated signaling pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Moreover, 23 micro RNAs (miRNAs), which were demonstrated to be involved in IDD were chosen; we investigated their theoretic regulatory importance associated with our microarray data.
Results: We found 632 lncRNAs and 1682 mRNAs were differentially expressed out of a total of 40,716 probes. We then confirmed the microarray data by real-time PCR. Furthermore, we demonstrated 197 upregulated, and 373 downregulated Gene Ontology terms and 176 significantly enriched pathways, such as the mitogen-activated protein kinase (MAPK) pathway. Also, a signal-net was constructed to reveal the interplay among differentially expressed genes. Meanwhile, a mRNA-lncRNA co-expression network was constructed for the significantly changed mRNAs and lncRNAs. Also, the competing endogenous RNA (ceRNA) network was built.
Conclusion: Our results present the first comprehensive identification of differentially expressed lncRNAs and mRNAs of degenerative NPCs, altered by co-culturing with ASCs, and outline the gene expression regulation pattern. These may provide valuable information for better understanding of stem cell therapy and potential candidate biomarkers for IDD treatment.
Background: The rate of caesarean sections increased in the last decades to about 30% of births in western populations. Many caesarean sections are electively planned without an urgent medical reason for mother or child. Especially in women with a foregoing caesarean section, the procedure is planned early. An early caesarean section though may harm the newborn. Our aim is to evaluate the gestational time point after the 37th gestational week (after prematurity = term) of performing an elective caesarean section with the lowest morbidity for mother and child.
Methods: This is an update of a systematic review previously carried out on behalf of the German Federal Ministry of Health. We will perform a systematic literature search in MEDLINE, EMBASE, CENTRAL and CINAHL. Our primary outcome is the rate of admissions to the neonatal intensive care unit in early versus late term neonates. We will include (quasi) randomized controlled trials and cohort studies. The studies should include pregnant women who have an elective caesarean section at term. We will screen titles and abstracts and the identified full texts of studies for eligibility. Risk of bias will be assessed with the Cochrane Risk of Bias Tool for Randomized Trials or with the Risk of Bias Tool for Non-Randomized Studies of Interventions (ROBINS-I). These tasks will be performed independently by two reviewers. Data will be extracted in beforehand piloted extraction tables. A dose-response meta-analysis will be performed.
Discussion: Our aim is to reach a higher validity in the assessment of the time point of elective caesarean sections by performing a meta-analysis to support recommendations for clinical practice. We assume to identify less randomized controlled trials but a large number of cohort studies analyzing the given question. We will discuss similarities and differences in included studies as well as methodological strengths and weaknesses.
Systematic review registration: PROSPERO CRD42017078231
Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off valve are a useful tool to reliably inject chemotherapeutics into the ventricles. In order to systematically assess feasibility, safety, and efficacy of this procedure, we performed a retrospective analysis of all patients with leptomeningeal metastases who had received a shunt system at our institution. In total, six adult patients had a ventriculoperitoneal shunt equipped with an on-off valve implanted. Out of these six patients, two patients subsequently received intraventricular injections of chemotherapeutics. The configuration of the valve setting and the intraventricular injections were easily feasible in the setting of a neuro-oncology department. The complication of a shunt leakage occurred in one patient following the first intraventricular injection. No extra-central nervous system (CNS) toxicities were observed. In summary, ventriculoperitoneal shunts with on-off valves are useful tools for reliable intraventricular administration of therapeutics.
Background/Aims: Sphingosine 1-phosphate (S1P) is considered as a key molecule regulating various cell functions including cell growth and death. It is produced by two sphingosine kinases (SK) denoted as SK-1 and SK-2. Whereas SK-1 has been extensively studied and has been appointed a role in promoting cell growth, the function of SK-2 is controversial, and both pro-proliferative and pro-apoptotic functions have been suggested. In this study we investigated whether renal mesangial cells isolated from transgenic mice overexpressing the human Sphk2 gene (hSK2-tg) showed an altered cell response towards growth-inducing and apoptotic stimuli.
Methods: hSK2-tg mice were generated by using a Quick KnockinR strategy. Renal mesangial cells were isolated by a differential sieving method and further cultivated in vitro. Lipids were quantified by mass spectrometry. Protein expression was determined by Western blot analysis, cell proliferation was determined by 3H-thymidine incorporation, and apoptosis was determined by a DNA fragmentation ELISA.
Results: We show here that kidneys and mesangial cells from hSK2-tg mice express the hSK2 as well as the endogenous mouse mSK2. hSK2 and mSK2 predominantly resided in the cytosol of quiescent transgenic cells. However, S1P accumulated strongly in the nucleus and only minimally in the cytosol of transgenic cells. Functionally, hSK2-tg cells proliferated less than control cells under normal growth conditions and were also more sensitive towards stress-induced apoptosis. On the molecular level, this was reflected by reduced ERK and Akt/PKB activation, and upon staurosporine treatment, by a sensitized mitochondrial pathway as manifested by reduced anti-apoptotic Bcl-XL expression and increased cleavage of caspase-9, downstream caspase-3 and PARP-1.
Conclusion: Altogether, these data demonstrate that SK-2 exerts an antiproliferative and apoptosis-sensitizing effect in renal mesangial cells which suggests that selective inhibitors of SK-2 may promote proliferation and reduce apoptosis and this may have impact on the outcome of proliferation-associated diseases such as mesangioproliferative glomerulonephritis.
Akt and mTORC1 signaling as predictive biomarkers for the EGFR antibody nimotuzumab in glioblastoma
(2018)
Glioblastoma (GB) is the most frequent primary brain tumor in adults with a dismal prognosis despite aggressive treatment including surgical resection, radiotherapy and chemotherapy with the alkylating agent temozolomide. Thus far, the successful implementation of the concept of targeted therapy where a drug targets a selective alteration in cancer cells was mainly limited to model diseases with identified genetic drivers. One of the most commonly altered oncogenic drivers of GB and therefore plausible therapeutic target is the epidermal growth factor receptor (EGFR). Trials targeting this signaling cascade, however, have been negative, including the phase III OSAG 101-BSA-05 trial. This highlights the need for further patient selection to identify subgroups of GB with true EGFR-dependency. In this retrospective analysis of treatment-naïve samples of the OSAG 101-BSA-05 trial cohort, we identify the EGFR signaling activity markers phosphorylated PRAS40 and phosphorylated ribosomal protein S6 as predictive markers for treatment efficacy of the EGFR-blocking antibody nimotuzumab in MGMT promoter unmethylated GBs. Considering the total trial population irrespective of MGMT status, a clear trend towards a survival benefit from nimotuzumab was already detectable when tumors had above median levels of phosphorylated ribosomal protein S6. These results could constitute a basis for further investigations of nimotuzumab or other EGFR- and downstream signaling inhibitors in selected patient cohorts using the reported criteria as candidate predictive biomarkers.
In the insect brain, the mushroom body is a higher order brain area that is key to memory formation and sensory processing. Mushroom body (MB) extrinsic neurons leaving the output region of the MB, the lobes and the peduncle, are thought to be especially important in these processes. In the honeybee brain, a distinct class of MB extrinsic neurons, A3 neurons, are implicated in playing a role in learning. Their MB arborisations are either restricted to the lobes and the peduncle, here called A3 lobe connecting neurons, or they provide feedback information from the lobes to the input region of the MB, the calyces, here called A3 feedback neurons. In this study, we analyzed the morphology of individual A3 lobe connecting and feedback neurons using confocal imaging. A3 feedback neurons were previously assumed to innervate each lip compartment homogenously. We demonstrate here that A3 feedback neurons do not innervate whole subcompartments, but rather innervate zones of varying sizes in the MB lip, collar, and basal ring. We describe for the first time the anatomical details of A3 lobe connecting neurons and show that their connection pattern in the lobes resemble those of A3 feedback cells. Previous studies showed that A3 feedback neurons mostly connect zones of the vertical lobe that receive input from Kenyon cells of distinct calycal subcompartments with the corresponding subcompartments of the calyces. We can show that this also applies to the neck of the peduncle and the medial lobe, where both types of A3 neurons arborize only in corresponding zones in the calycal subcompartments. Some A3 lobe connecting neurons however connect multiple vertical lobe areas. Contrarily, in the medial lobe, the A3 neurons only innervate one division. We found evidence for both input and output areas in the vertical lobe. Thus, A3 neurons are more diverse than previously thought. The understanding of their detailed anatomy might enable us to derive circuit models for learning and memory and test physiological data.
Strong electron correlations can give rise to extraordinary properties of metals with renormalized Landau quasiparticles. Near a quantum critical point, these quasiparticles can be destroyed and non-Fermi liquid behavior ensues. YbRh2Si2 is a prototypical correlated metal exhibiting the formation of quasiparticle and Kondo lattice coherence, as well as quasiparticle destruction at a field-induced quantum critical point. Here we show how, upon lowering the temperature, Kondo lattice coherence develops at zero field and finally gives way to non-Fermi liquid electronic excitations. By measuring the single-particle excitations through scanning tunneling spectroscopy, we find the Kondo lattice peak displays a non-trivial temperature dependence with a strong increase around 3.3 K. At 0.3 K and with applied magnetic field, the width of this peak is minimized in the quantum critical regime. Our results demonstrate that the lattice Kondo correlations have to be sufficiently developed before quantum criticality can set in.
Despite being an essential consideration when deciding rule changes, injury prevention strategies, and athlete development models, there is little epidemiological data of U18 field hockey player injuries–something explicitly referred to in the 2015 International Olympic Committee’s Consensus Statement on Youth Athlete Development. The aim of this study was to quantify incidence and characteristics of injuries in elite youth field hockey players during a major international tournament. Standardized reporting forms detailing time, location on pitch, mechanism and anatomical location of injury were completed for new musculoskeletal conditions resulting in a time stoppage by the umpire and where a player was noticeably affected by an injury for up to 20 s regardless of time stoppage. Injury incidence was 1.35 and 2.20 injuries/match or 53 and 86 injuries per 1000 player match hours for boys (B) and girls (G) respectively; girls were over three times more likely to have a minor injury. Most injuries were contusions due to being hit by the ball or stick (B: 12, G: 27), with high numbers of injuries to the torso (B: 8) and head/face (G: 7). Injuries during the penalty corner (B: 3, G: 4) were to the lower limb and hand, and boys were less likely to wear facial protection (B: 65.9%, G: 86.4%). Results form an essential initial dataset of injuries in U18 field hockey players. Current reporting protocols under-report injuries and must be addressed by the international governing body. The high number of head/face injuries, particularly in females, requires further investigation.
Introduction: The clinical management of breech presentations at term is still a controversially discussed issue among clinicians. Clear predictive criteria for planned vaginal breech deliveries are desperately needed to prevent adverse fetal and maternal outcomes and to reduce elective cesarean section rates. The green-top guideline considers an estimated birth weight of 3.8 kg or more an indication to plan a cesarean section despite the lack of respective evidence.
Objective: To compare maternal and neonatal outcome of vaginal intended breech deliveries of births with children with a birth weight of 2.5 kg– 3.79 kg and children with a birth weight of 3.8 kg and more.
Design: Prospective cohort study.
Sample: All vaginal intended deliveries out of a breech position of newborns weighing between 2.5 kg and 4.5 kg at the Obstetrics department at Goethe University Hospital Frankfurt from January 2004 until December 2016
Methods: Neonatal and maternal outcome of a light weight group (LWG) (< 3.8 kg) was compared to and a high weight group (HWG) (≥ 3.8 kg) using Pearson’s Chi Square test and Fishers exact test. A logistic regression analysis was performed to detect an association between cesarean section rates, fetal outcome and the birth weight.
Results: No difference in neonatal morbidity was detected between the HWG (1.8%, n = 166) and the LWG (2.6%, n = 888). Cesarean section rate was significantly higher in the HWG with 45.2% in comparison to 28.8% in the LWG with an odds ratio of 1.57 (95% CI 1.29–1.91, p<0.0001). In vaginal deliveries, a high birth weight was not associated with an increased risk of maternal birth injuries (LWG in vaginal deliveries: 74.3%, HWG in vaginal deliveries: 73.6%; p = 0.887; OR = 1.9 (95% CI 0.9–1.1))
Conclusion: A fetal weight above 3.79 kg does not predict increased maternal or infant morbidity after delivery from breech presentation at term. Neither the literature nor our analyses document evidence for threshold of estimated birth weight that is associated with maternal and/or infant morbidity. However, patients should be informed about an increased likelihood of cesarean sections during labor when attempting vaginal birth from breech position at term in order to reach an informed shared decision concerning the birth strategy. Further investigations in multi center settings are needed to advance international guidelines on vaginal breech deliveries in the context of estimated birth weight and its impact on perinatal outcome.
Marie Wrona präsentiert in ihrem Beitrag "Ist das ein Komma oder kann das weg? - Topologische Felder und Kommasetzung. Erste empirische Befunde" ein Experiment zur Kommadidaktik. Sie untersucht, inwiefern sich die Kommasetzungskompetenz von SchülerInnen verbessert, wenn diese mithilfe des topologischen Feldermodells vermittelt wird, das auf der Verbklammer im Deutschen aufbaut, anstatt wie bei traditionellen Ansätzen mithilfe von Signalwörtern wie Subjunktionen. Die SchülerInnen lernten, das finite Verb zu bestimmen und so zu entscheiden, ob ein Komma gesetzt werden muss oder nicht. Nach der Unterrichtseinheit setzten die SchülerInnen v.a. deutlich weniger falsche Kommata
Johanna Hartwig beschäftigt sich mit der Deklination entlehnter Farbadjektive wie lila, orange und rosa ("Gibt es denn jetzt lilane Kühe oder nicht? - Einflussfaktoren auf den Gebrauch indeklinabler Farbadjektive"). Diese Adjektive wurden ursprünglich nicht flektiert (das lila/rosa Haus). Hartwig führt ein Produktionsexperiment durch, um zu überprüfen, inwiefern die Frequenz und die Endung eines Adjektivs Einfluss auf dessen Flexion nehmen. Dabei stellt sie fest, dass frequente Adjektive zur Flexion neigen, jedoch auch die Endung eine Rolle spielt. So bleiben Adjektive auf [a] wie bspw. lila trotz hoher Frequenz unflektiert. Adjektive auf Frikativ weisen hingegen umso mehr Flexion auf, je frequenter sie sind. Für seltene Adjektive (creme) konnte Hartwig eine Vermeidungsstrategie feststellen: Creme wurde in ihrem Experiment am häufigsten in ein Derivat (cremefarben) umgewandelt, das eine Flexion des Adjektivs ermöglicht (das cremefarbene Haus).
Wie Hashtags bei Twitter als Teile von Komposita verwendet werden, zeigt Markus Majewski in seinem Beitrag #Erdogan-Diktatur - Hashtags als Elemente von Substantivkomposita in politischen Tweets. Als Grundlage dient ihm das Korpus aus Tweets von SpitzenpolitikerInnen der großen Parteien während des Wahlkampfs, in dem er alle Substantivkomposita mit einem Hashtag als Bestandteil wie #Energiewende auf funktionale, graphematische und strukturelle Aspekte untersucht. Insbesondere bei der Schreibung der Komposita zeigt sich eine große Kreativität. Zudem lassen sich Twitter-spezifische Kommunikationsfunktionen der Hashtag-Erstglieder beobachten.
Für den Wandel und die Variation der Präposition wegen interessieren sich Lea Heese und Fabiola Kaiser in ihrem Beitrag "Die menschliche Zunge ist faul. Assoziationen zu der Verwendungsweise der Präposition wegen mit dem Genitiv und dem Dativ". Wegen schwankt im Standard-deutschen zwischen Genitiv- und Dativrektion. Obwohl sie seit langem existiert, wird die Dativvariante von SprecherInnen oftmals als Zeichen für Sprachverfall gedeutet. Heese und Kaiser erhoben mithilfe einer Onlineumfrage Daten zum Gebrauch der Präposition in informellen und formellen Registern sowie Assoziationen zu den beiden Varianten. Wie bereits das Titelzitat des Beitrags zeigt, wird der Dativ unter anderem als Zeichen für Nachlässigkeit interpretiert.
Carlotta J. Hübener diskutiert in ihrem Beitrag "Nicht/keinen/kein Fußball spielen? - Inkorporationsprozesse in Substantiv-Verb-Verbindungen" Inkorporationprozesse bei Substantiv-Verb-Verbindungen wie bspw. Fußball spielen. Hierbei fokussiert sie auf die Negation: Während kein(en) Fußball spielen einen Hinweis darauf gibt, dass Fußball noch als eigenständiges Substantiv interpretiert wird, ist nicht Fußball spielen ein Indiz dafür, dass Fußball und spielen als eine konzeptionelle Einheit wahrgenommen werden. Kein negiert nämlich Nomen (Ich mag keinen Spinat), während nicht Verben negiert (Ich hab‘ noch nicht gegessen). Hübener überprüft in ihrem Beitrag anhand des Deutschen Referenzkorpus, inwiefern Frequenz, Idiomatik und Individuiertheit Einfluss auf die Negation von Substativ-Verb-Verbindungen nehmen können.
Brit Schwerin nimmt sich in ihrem Artikel "die bisher jedermann unbekannt gewesen [ist/war/sei/wäre] -Zum Rückgang des ersparten Finitums in Nebensätzen des frühen Neuhochdeutsch" des Phänomens der afiniten Nebensätze an, die in der Frühen Neuzeit im deutschen Sprachraum weit verbreitet waren. Ihre Analyse von Nebensätzen mit und ohne finites Verb in Texten aus dem 17. und 18. Jh. ergibt, dass der Rückgang der afiniten Konstruktionen in Verbindung mit dem Bedürfnis nach eindeutiger Markierung grammatischer Kategorien wie Tempus und Modus steht. Die diachronen Studien decken somit Sprachwandel auf verschiedenen Ebenen ab.
Wie sich Konzessivkonnektoren im 18. und 19. Jh. entwickelt haben, untersuchen Lisa Bürgerhoff, Jana Giesenschlag, Linda Kunow und Alexandra Kern für ihren Beitrag "Von ob ich schon wanderte zu obschon ich wanderte?! - Eine Korpusuntersuchung zur Konzessivität von 1700-1900". Ihre Untersuchungen im Deutschen Textarchiv zeigen unter anderem einen Zusammenhang zwischen der Zusammenschreibung der Konnektoren und einer eindeutig konzessiven Lesart, der für obschon, obgleich, obwohl und obzwar allerdings unterschiedlich stark ist. Auch die Faktizität der Teilsätze und das Auftreten verstärkender Partikeln sind für die Entwicklung der ob-Gruppe von Bedeutung. Als eindeutigste und frequenteste Konzessivkonnektoren stellen sich insgesamt obwohl und vor allem obzwar heraus.
Mit der mittelhochdeutschen Nebensilbenabschwächung beschäftigt sich Tanja Stevanovićs Beitrag "Wo sind die vollen Vokale geblieben? Eine Untersuchung möglicher Einflussfaktoren auf die Nebensilbenabschwächung". Dafür hat sie in einer Korpusuntersuchung im Referenzkorpus Mittelhochdeutsch schwache Verben analysiert, die trotz der fortschreitenden Nebensilbenabschwächung noch im Mittelhochdeutschen Vollvokale in Endsilben aufweisen.
Lena Schnee analysiert in ihrem Beitrag "Eingenordet - Morphologische Assimilation mittelniederdeutscher Lehnwörter im Altnordischen" die Liste mittelniederdeutscher Entlehnungen im Altnordischen Etymologischen Wörterbuch und zeigt, wie die mittelniederdeutschen Wörter, die in der Hansezeit in die skandinavischen Sprachen entlehnt wurden, an das Altnordische angepasst wurden. Dabei wendet sie ein Transderivationsmodell an, um die morphologische Assimilation nicht nur von ganzen Lexemen, sondern auch von Affixen und Wortstämmen nachzuvollziehen. Schnees Untersuchung ergibt, dass bei der Entlehnung in das Altnordische hauptsächlich die Affixe adaptiert wurden. Die mittelniederdeutschen Affixe wurden überwiegend durch native oder entlehnte altnordische ersetzt, was darauf hinweist, dass die Morphemgrenzen und Wortbildungselemente bei der Entlehnung als solche erkannt wurden. Als Erklärung hierfür führt Schnee die typologische Ähnlichkeit der beiden Sprachen an.
Die hier abgedruckten Beiträge sind in einem Lehrprojekt zum Thema "Wie verändern wir Sprache?" entstanden. Das im Rahmen des Universitätskollegs 2.0 aus Mitteln des BMBF geförderte Projekt fand vom Sommersemester 2017 bis zum Wintersemester 2017/18 an der Universität Hamburg statt. Insgesamt 17 Studierende beschäftigten sich über ein Jahr hinweg mit aktuellen und historischen Sprachwandelphänomenen und führten eigene empirische Forschungsprojekte durch, die sie auf der studentischen Tagung am 1.-3. Februar 2018 präsentierten. Die Beiträge beschäftigen sich aus diachroner sowie synchroner Perspektive mit Sprachvariation und -wandel.
Diyalog 2018/1
(2018)
Im Fachbereich der Deutschen Literatur äußert sich der erste Artikel zur Autorinszenierung in Rolf Schneiders Erzählung "Metamorphosen". Eine Deutung orientalischer Spuren in Hofmannsthals lyrischem Drama "Die Hochzeit der Sobeide" bildet den Schwerpunkt des zweiten Artikels dieser Rubrik. Im dritten Beitrag dieses Fachbereichs geht es um das Leben und Schreiben von Wolfgang Hilbig und die Schwierigkeiten ein Mann zu sein. Der vierte Beitrag stellt "Leutnant Gustl" als eine repräsentative Figur für die Identitätdefizite in der Gesellschaft in den Mittelpunkt. Erich Maria Remarques Roman "Im Westen nichts Neues" bildet den Ausgangspunkt für die Analyse von 'Kriegstrauma' als eine der bedeutendsten Herausforderungen in der Antikriegsliteratur, was im fünften Beitrag der Rubrik Deutsche Literatur nachgelesen werden kann. Dem Fachbereich Komparatistik sind zwei Artikel zuzuordnen. Der erste stellt anhand eines episch dekadenten Dialogs einen dekadenten Vergleich des Todes in den Werken von Tezer Kıral und Hugo von Hofmannsthal in den Mittelpunkt. Im zweiten Beitrag erfolgt eine Analyse des Romans 'Yaban' von Yakup Kadri im Sinne der Dekadenz. Sieben Beiträge bearbeiten Themen aus der Erziehungswissenschaft bzw. aus dem DaF-Bereich. Überlegungen hinsichtlich der Vermittlung von Speicherstrategien beim Lernen mit der Wortliste des Goethe-Zertifikats B1 bilden den Fokus des ersten Beitrags dieser Rubrik. Der zweite Beitrag präsentiert Ergebnisse einer Studie zur fehleranalytischen Kompetenz der Studenten/innen in der Deutschlehrerausbildung. Der dritte Artikel analysiert und bewertet Sprachlernspiele in dem Lehrwerk 'MOMENT MAL 1' und 'MOMENT MAL 2'. Der vierte Beitrag dieses Fachbereichs ist in Türkisch verfasst und stellt Überlegungen zur Entwicklung von digitalen Spielen und zu gamifizierten Anwendungen in dem Fremdsprachenunterricht in den Mittelpunkt. Ebenfalls in Türkisch verfasst ist der fünfte Aufsatz, der bei der Lehre von Türkisch als Zweitsprache Nutzen aus den Modellen und Erfahrungen thematisiert, die bei der Vermittlung von Deutsch als zweite Sprache mit in Deutschland lebendenden Migranten gemacht worden sind. Thema des sechsten Artikels ist die Erforschung von Stereotypen in DaF- und TRaF-Lehrwerken und ihr Potenzial als Störfaktor oder Impulsgeber. Der letzte Beitrag des Bereichs Erziehungswissenschaft bzw. DaF fokussiert eine korpusbasierte Studie am Beispiel der Germanistikstudenten der Ege Universität, in der die pragmatisch-diskursive Fähigkeit in den mündlichen Prüfungsgesprächen analysiert wird. Dem Bereich Translationswissenschaft sind vier Aufsätze zugehörig. In dem ersten Beitrag wird eine empirische Studie präsentiert, die die Rolle sprachlicher und kultureller Kompetenz in der "Funktionalen Übersetzung" zum Thema hat. In Türkisch verfasst ist der zweite Artikel dieser Rubrik, der Maßstäbe der Textwahl im Übersetzungsunterricht behandelt. Informationen zur Konzeption des Türkischen Übersetzerlexikons werden im dritten Aufsatz gegeben. Der in Türkisch verfasste vierte Beitrag dieses Fachbereichs gibt einen allgemeinen Überblick über ins Türkische übersetzte deutsche Literatur. Der Forum-Teil ist dem in Türkisch verfassten Beitrag vorbehalten, der mit Edmund Husserl in Bezug auf das Museum des 11. Septembers als Erinnerungszeichen die Suche nach Sinn fokussiert. In der Rubrik Berichte werden im Rückblick Informationen zu zwei Konferenzen mitgeteilt. In dem ersten Tagungsbericht wird die Stärke und Rolle der deutschen Sprache in Mitteleuropa betont, so, wie sie in einer linguistischen Konferenz vermittelt worden ist. In dem zweiten Tagungsbericht werden Erfahrungen und Informationen zum XI. Internationalen Kongress der Germanisten Rumäniens wiedergegeben. Neben den Aufsätzen und Berichten gibt es in dieser Ausgabe auch eine in Türkisch geschriebene Rezension zum Werk "Lernabenteuer Deutsch - Das Geheimnis der Himmelsscheibe".
Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.
A key function of reversible protein phosphorylation is to regulate protein–protein interactions, many of which involve short linear motifs (3–12 amino acids). Motif‐based interactions are difficult to capture because of their often low‐to‐moderate affinities. Here, we describe phosphomimetic proteomic peptide‐phage display, a powerful method for simultaneously finding motif‐based interaction and pinpointing phosphorylation switches. We computationally designed an oligonucleotide library encoding human C‐terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. We incorporated these oligonucleotides into a phage library and screened the PDZ (PSD‐95/Dlg/ZO‐1) domains of Scribble and DLG1 for interactions potentially enabled or disabled by ligand phosphorylation. We identified known and novel binders and characterized selected interactions through microscale thermophoresis, isothermal titration calorimetry, and NMR. We uncover site‐specific phospho‐regulation of PDZ domain interactions, provide a structural framework for how PDZ domains accomplish phosphopeptide binding, and discuss ligand phosphorylation as a switching mechanism of PDZ domain interactions. The approach is readily scalable and can be used to explore the potential phospho‐regulation of motif‐based interactions on a large scale.
Background: Ever since it was discovered that zoophilic vectors can transmit malaria, zooprophylaxis has been used to prevent the disease. However, zoopotentiation has also been observed. Thus, the presence of livestock has been widely accepted as an important variable for the prevalence and risk of malaria, but the effectiveness of zooprophylaxis remained subject to debate. This study aims to critically analyse the effects of the presence of livestock on malaria prevalence using a large dataset from Indonesia.
Methods: This study is based on data from the Indonesia Basic Health Research ("Riskesdas") cross-sectional survey of 2007 organized by the National Institute of Health Research and Development of Indonesia’s Ministry of Health. The subset of data used in the present study included 259,885 research participants who reside in the rural areas of 176 regencies throughout the 15 provinces of Indonesia where the prevalence of malaria is higher than the national average. The variable "existence of livestock" and other independent demographic, social and behavioural variables were tested as potential determinants for malaria prevalence by multivariate logistic regressions.
Results: Raising medium-sized animals in the house was a significant predictor of malaria prevalence (OR = 2.980; 95% CI 2.348–3.782, P < 0.001) when compared to keeping such animals outside of the house (OR = 1.713; 95% CI 1.515–1.937, P < 0.001). After adjusting for gender, age, access to community health facility, sewage canal condition, use of mosquito nets and insecticide-treated bed nets, the participants who raised medium-sized animals inside their homes were 2.8 times more likely to contract malaria than respondents who did not (adjusted odds ratio = 2.809; 95% CI 2.207–3.575; P < 0.001).
Conclusions: The results of this study highlight the importance of livestock for malaria transmission, suggesting that keeping livestock in the house contributes to malaria risk rather than prophylaxis in Indonesia. Livestock-based interventions should therefore play a significant role in the implementation of malaria control programmes, and focus on households with a high proportion of medium-sized animals in rural areas. The implementation of a "One Health" strategy to eliminate malaria in Indonesia by 2030 is strongly recommended.
Background: The focus of this case report is on the role of inflammation as a contributor to pain in plantar fasciitis and its cure by the injection of local anesthetics.
Case presentation: This is a case report on a 24-year-old white man, a middle-distance runner, with chronic unilateral plantar fasciitis and perceived heel pain for almost 1.5 years. He was treated with neural therapy (that is, injection of < 1 ml procaine 1% which is a local anesthetic with strong anti-inflammatory properties) of the surgical scar and along the surgical puncture channel. The follow-up period from the time of first presentation until publication was 2.5 years. At admission, pain intensity (visual analog scale) in the affected leg was severe (10 cm, visual analog scale; range 0–10 cm) when walking and moderate (5 cm, visual analog scale) when standing. After the first session of injections he could stand pain-free and pain when walking was markedly reduced (− 90%). After the third session, he reported no pain in the affected leg and could return to sports at his former level (no difference in training load compared to non-injured state). There was no recurrence of inflammatory signs or heel pain despite intense athletics training up to the date of publication.
Conclusions: In prolonged cases of plantar fasciitis, inflammation is an important component in the development of persistent pain. The results of our case describe the effects of three neural therapy sessions that abolished inflammation and associated heel pain. Neural therapy might be an effective and time-efficient approach in the treatment of plantar fasciitis, enabling an early return to sports.
Objective: Amyloid β (Aβ) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post‐translationally modified Aβ in plaques characterizes distinct biochemical stages of Aβ maturation. However, the molecular composition of vascular Aβ deposits in CAA and its relation to plaques remain enigmatic.
Methods: Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated Aβ in the medial temporal and occipital lobe of 24 controls, 27 pathologically‐defined preclinical AD, and 20 symptomatic AD cases.
Results: Sequential deposition of Aβ in CAA resembled Aβ maturation in plaques and enabled the distinction of three biochemical stages of CAA. B‐CAA stage 1 was characterized by deposition of Aβ in the absence of pyroglutaminated AβN3pE and phosphorylated AβpS8. B‐CAA stage 2 showed additional AβN3pE and B‐CAA stage 3 additional AβpS8. Based on the Aβ maturation staging in CAA and plaques, three case groups for Aβ pathology could be distinguished: group 1 with advanced Aβ maturation in CAA; group 2 with equal Aβ maturation in CAA and plaques; group 3 with advanced Aβ maturation in plaques. All symptomatic AD cases presented with end‐stage plaque maturation, whereas CAA could exhibit immature Aβ deposits. Notably, Aβ pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia.
Interpretation: Balance of Aβ maturation in CAA and plaques defines distinct pathological subgroups of β‐amyloidosis. The association of CAA‐related Aβ maturation with cognitive decline, the individual contribution of CAA and plaque pathology to the development of dementia within the defined Aβ pathology subgroups, and the subgroup‐related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.
Neuronal calcium signals propagating by simple diffusion and reaction with mobile and stationary buffers are limited to cellular microdomains. The distance intracellular calcium signals can travel may be significantly increased by means of calcium-induced calcium release from internal calcium stores, notably the endoplasmic reticulum. The organelle, which can be thought of as a cell-within-a-cell, is able to sequester large amounts of cytosolic calcium ions via SERCA pumps and selectively release them into the cytosol through ryanodine receptor channels leading to the formation of calcium waves. In this study, we set out to investigate the basic properties of such dendritic calcium waves and how they depend on the three parameters dendrite radius, ER radius and ryanodine receptor density in the endoplasmic membrane. We demonstrate that there are stable and abortive regimes for calcium waves, depending on the above morphological and physiological parameters. In stable regimes, calcium waves can travel across long dendritic distances, similar to electrical action potentials. We further observe that abortive regimes exist, which could be relevant for spike-timing dependent plasticity, as travel distances and wave velocities vary with changing intracellular architecture. For some of these regimes, analytic functions could be derived that fit the simulation data. In parameter spaces, that are non-trivially influenced by the three-dimensional calcium concentration profile, we were not able to derive such a functional description, demonstrating the mathematical requirement to model and simulate biochemical signaling in three-dimensional space.
Background: Chrysomya megacephala is a blow fly species of medical and forensic importance worldwide. Understanding its bionomics is essential for both designing effective fly control programs and its use in forensic investigations.
Methods: The daily flight activity, seasonal abundance related to abiotic factors (temperature, relative humidity and rainfall) and reproductive potential of this species was investigated. Adult flies were sampled twice a month for one year from July 2013 to June 2014 in three different ecotypes (forest area, longan orchard and palm plantation) of Chiang Mai Province, northern Thailand, using semi-automatic funnel traps. One-day tainted beef offal was used as bait.
Results: A total of 88,273 flies were sampled, of which 82,800 flies (93.8%) were caught during the day (from 06:00 to 18:00 h); while 5473 flies (6.2%) were caught at night (from 18:00 to 06:00 h). Concurrently, the abundance of C. megacephala was higher in the forest area (n = 31,873; 36.1%) and palm plantation (n = 31,347; 35.5%), compared to the longan orchard (n = 25,053; 28.4%). The number of females was significantly higher than that of males, exhibiting a female to male sex ratio of 2.36:1. Seasonal fluctuation revealed the highest abundance of C. megacephala in summer, but low numbers in the rainy season and winter. Fly density was significantly positively correlated with temperature, but negatively correlated with relative humidity. No correlation between numbers of C. megacephala with rainfall was found. Activity occurred throughout the daytime with high numbers from 06:00 to 18:00 h in summer and 12:00 to 18:00 h in the rainy season and winter. As for the nocturnal flight activity, a small number of flies were collected in summer and the rainy season, while none were collected in the winter. Dissection of the females indicated that fecundity was highest during the rainy season, followed by winter and summer.
Conclusions: Since the assessment of daily, seasonal activity and the reproductive potential of C. megacephala remains a crucial point to be elucidated, this extensive study offers insights into bionomics, which may be considered for integrated fly control strategies and forensic entomology issues.
Background: Sputum induction is an important noninvasive method for analyzing bronchial inflammation in patients with asthma and other respiratory diseases. Most frequently, ultrasonic nebulizers are used for sputum induction, but breath-controlled nebulizers may target the small airways more efficiently. This treatment may produce a cell distribution similar to bronchoalveolar lavage (less neutrophils and more macrophages) and provide deeper insights into the underlying lung pathology. The goal of the study was to compare both types of nebulizer devices and their efficacy in inducing sputum to measure bronchial inflammation, i.e., cell composition and cytokines, in patients with mild allergic asthma and healthy controls.
Methods: The population of this study consisted of 20 healthy control subjects with a median age of 17 years, range: 8–25 years, and 20 patients with a median age of 12 years, range: 8–24 years, presenting with mild, controlled allergic asthma who were not administered an inhaled steroid treatment. We induced sputum in every individual using both devices on two separate days. The sputum weight, the cell composition and cytokine levels were analyzed using a cytometric bead assay (CBA) and by real-time quantitative PCR (qRT-PCR).
Results: We did not observe significant differences in the weight, cell distribution or cytokine levels in the sputum samples induced by both devices. In addition, the Bland-Altman correlation revealed good concordance of the cell distribution. As expected, eosinophils and IL-5 levels were significantly elevated in patients with asthma.
Conclusions: The hypothesis that sputum induction with a breath-controlled "smart" nebulizer is more efficient and different from an ultrasonic nebulizer was not confirmed. The Bland-Altman correlations showed good concordance when comparing the two devices.
Trial registration: NCT01543516 Retrospective registration date: March 5, 2012.
Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs.
Methods: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality.
Results: Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival.
Conclusions: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany.
Trial registration: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807) on May 1, 2017.
This study explores anomalies in stock returns found in their seasonal patterns. These are verified through multiple trading strategies based on past-performance returns that require information up to 20 years in the past. Some of the presented strategies deliver relatively high performance, especially for those strategies based on returns in the same calendar month from past years. In order to minimize any possible bias due to omitted delisting returns, those are incorporated into the monthly returns. Furthermore, to find an explanation for this seasonal effect, behavioral theories are discussed and the returns are controlled for risk and mispricing factors. However, empirical evidence indicates no evidence of explanation based on these factors for the seasonal patterns. Furthermore, possible reasons why the returns persist are discussed.
A growing body of literature shows the importance of financial literacy in households' financial decisions. However, fewer studies focus on understanding the determinants of financial literacy. Our paper fills this gap by analyzing a specific determinant, the educational system, to explain the heterogeneity in financial literacy scores across Germany. We suggest that the lower financial literacy observed in East Germany is partially caused by a different institutional framework experienced during the Cold War, more specifically, by the socialist educational system of the GDR which affected specific cohorts of individuals. By exploiting the unique set-up of the German reunification, we identify education as a channel through which institutions and financial literacy are related in the German context.
Authoritarian regimes and religious institutions in the Muslim majority world see eye-to-eye on the topic of atheism. United by their fear of losing control over their populations and their desire for conformity, consecutive governments have pushed for unfair restrictions on their subjects’ beliefs since their inception. But even in society, non-belief remains a taboo. Should atheists in Muslim majority world become more vocal?
With the rise of big data, internet-of-things, machine learning, targeted advertising, face recognition algorithms, virtual assistants, cyberbullying, cyberstalking, and cyberwarfare, we find more and more people and policy makers around the world debating whether technological advances are helping us or hurting us. Such debates often focus on trying to figure out a way to balance the need to preserve human values with the desire to not interfere with technological progress. The central problem that arises then is what to do when values and progress come into direct conflict with each other. Should we err on the side of caution and rein in companies like Google, Twitter, and Facebook so they do not interfere with personal privacy and national democracy? Or should we take a more pioneering perspective and view the occasional rights violation as a necessary risk that can be outweighed by the rewards for medicine, manufacturing, and media? Or should we try to find a middle path and have tech companies and policy makers work together to develop guidelines for “responsible research and innovation”?
Large-scale digitisation has brought cultural heritage objects and materials from the remotest places of the world to our computer screens. At first sight, this innovation seems to make cultural heritage accessible to everyone like never before. However, technological advances have not eliminated social inequalities between powerful and marginalized communities and ethical issues in communicating cultural heritage. These issues became much more vivid and obvious when the spread of cultural heritage reached the global scale.