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The third dataset dedicated to the Open Guided Waves platform aims at carbon fiber composite plates with an additional omega stringer at constant temperature conditions. The two structures used in this work are representative for real aircraft components. Comprehensive measurements were recorded in order to study (I) the impact of the omega stringer on guided wave propagation, and (II) elliptical reference damages of different sizes located at three separate positions on the structure. Measurements were recorded for narrowband excitation (5-cycle toneburst with varying carrier frequencies) and broadband excitation (using chirp waveforms). The paper presents the results of a technical validation including numerical modelling, and enables further research, for example related to probability of detection (POD) analysis.
Vegetation responds to drought through a complex interplay of plant hydraulic mechanisms, posing challenges for model development and parameterization. We present a mathematical model that describes the dynamics of leaf water-potential over time while considering different strategies by which plant species regulate their water-potentials. The model has two parameters: the parameter λ describing the adjustment of the leaf water potential to changes in soil water potential, and the parameter Δψww describing the typical ‘well-watered’ leaf water potentials at non-stressed (near-zero) levels of soil water potential. Our model was tested and calibrated on 110 time-series datasets containing the leaf- and soil water potentials of 66 species under drought and non-drought conditions. Our model successfully reproduces the measured leaf water potentials over time based on three different regulation strategies under drought. We found that three parameter sets derived from the measurement data reproduced the dynamics of 53% of an drought dataset, and 52% of a control dataset [root mean square error (RMSE) < 0.5 MPa)]. We conclude that, instead of quantifying water-potential-regulation of different plant species by complex modeling approaches, a small set of parameters may be sufficient to describe the water potential regulation behavior for large-scale modeling. Thus, our approach paves the way for a parsimonious representation of the full spectrum of plant hydraulic responses to drought in dynamic vegetation models.
Obtaining sufficient numbers of functional natural killer (NK) cells is crucial for the success of NK-cell-based adoptive immunotherapies. While expansion from peripheral blood (PB) is the current method of choice, ex vivo generation of NK cells from hematopoietic stem and progenitor cells (HSCs) may constitute an attractive alternative. Thereby, HSCs mobilized into peripheral blood (PB-CD34+) represent a valuable starting material, but the rather poor and donor-dependent differentiation of isolated PB-CD34+ cells into NK cells observed in earlier studies still represents a major hurdle. Here, we report a refined approach based on ex vivo culture of PB-CD34+ cells with optimized cytokine cocktails that reliably generates functionally mature NK cells, as assessed by analyzing NK-cell-associated surface markers and cytotoxicity. To further enhance NK cell expansion, we generated K562 feeder cells co-expressing 4-1BB ligand and membrane-anchored IL-15 and IL-21. Co-culture of PB-derived NK cells and NK cells that were ex-vivo-differentiated from HSCs with these feeder cells dramatically improved NK cell expansion, and fully compensated for donor-to-donor variability observed during only cytokine-based propagation. Our findings suggest mobilized PB-CD34+ cells expanded and differentiated according to this two-step protocol as a promising source for the generation of allogeneic NK cells for adoptive cancer immunotherapy.
Background: This study investigated whether work ability is associated with the duration of unemployment, heart rate variability (HRV), and the level of physical activity. Methods: Thirty-four unemployed persons (mean 55.7 ± standard deviation 33.3 years, 22 female, 12 male, unemployed: range 1–22.5 years) participated in the cross-sectional study. The Work Ability Index (WAI) and International Physical Activity Questionnaire (IPAQ) were applied. Short-term (five minutes) resting HRV (Low Frequency (LF), High Frequency (HF), Total Power (TP)) was collected. Results: Work ability was positively associated with the HRV: LF (r = 0.383; p = 0.025), HF (r = 0.412; p = 0.015) and TP (r = 0.361; p = 0.036). The WAI showed a positive linear correlation with the amount of total physical activity (r = 0.461; p = 0.006) as well as with the amount of moderate to vigorous physical activity (r = 0.413; p = 0.015). No association between the WAI and the duration of unemployment occurred. Conclusions: the relation between self-perceived work ability, health-associated parameters, the HRV and the level of physical activity points out the relevance of health-care exercise and the need of stress-reducing interventions to improve perceived work ability. Our results point out the need for the further and more holistic development of healthcare for the unemployed.
Nightly selection of resting sites and group behavior reveal antipredator strategies in giraffe
(2020)
This study presents the first findings on nocturnal behavior patterns of wild Angolan giraffe. We characterized their nocturnal behavior and analyzed the influence of ecological factors such as group size, season, and habitat use. Giraffe were observed using night vision systems and thermal imaging cameras on Okapuka Ranch, Namibia. A total of 77 giraffe were observed during 24 nights over two distinct periods—July–August 2016 (dry season) and February–March 2017 (wet season). Photoperiod had a marked influence on their activity and moving behavior. At dusk, giraffe reduced the time spent moving and increasingly lay down and slept at the onset of darkness. Body postures that likely correspond to rapid eye movement (REM) sleep posture (RSP) were observed 15.8 ± 18.3 min after giraffe sat down. Season had a significant effect with longer RSP phases during the dry season (dry: 155.2 ± 191.1 s, n = 79; wet: 85.8 ± 94.9 s, n = 73). Further analyses of the influence of social behavior patterns did not show an effect of group size on RSP lengths. When a group of giraffe spent time at a specific resting site, several individuals were alert (vigilant) while other group members sat down or took up RSP. Simultaneous RSP events within a group were rarely observed. Resting sites were characterized by single trees or sparse bushes on open areas allowing for good visibility in a relatively sheltered location.
According to the free radical theory of aging, reactive oxygen species (ROS) have been proposed to be a major cause of aging for a long time. Meanwhile, it became clear that ROS have diverse functions in a healthy organism. They act as second messengers, and as transient inhibitors of phosphatases and others. In fact, their detrimental role is highly dependent on the context of their production. NADPH oxidases (Nox) have been discovered as a controllable source of ROS. NoxO1 enables constitutive ROS formation by Nox1 by acting as a constitutively active cytosolic subunit of the complex. We previously found that both Nox1 and NoxO1 were highly expressed in the colon, and that NoxO1-/- deficiency reduces colon health. We hypothesized that a healthy colon potentially contributes to longevity and NoxO1 deficiency would reduce lifetime, at least in mouse. In contrast, here we provide evidence that the knockout of NoxO1 results in an elongated life expectancy of mice. No better endothelial function, nor an improved expression of genes related to longevity, such as Sirt1, were found, and therefore may not serve as an explanation for a longer life in NoxO1 deficiency. Rather minor systemic differences, such as lower body weight occur. As a potential reason for longer life, we suggest better DNA repair capacity in NoxO1 deficient mice. Although final fatal DNA damage appears similar between wildtype and NoxO1 knockout animals, we identified less intermediate DNA damage in colon cells of NoxO1-/- mice, while the number of cells with intact DNA is elevated in NoxO1-/- colons. We conclude that NoxO1 deficiency prolongs lifetime of mice, which correlates with less intermediate and potentially fixable DNA damage at least in colon cells.
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
In power systems, flow allocation (FA) methods enable to allocate the usage and costs of the transmission grid to each single market participant. Based on predefined assumptions, the power flow is split into isolated generator-specific or producer-specific sub-flows. Two prominent FA methods, Marginal Participation (MP) and Equivalent Bilateral Exchanges (EBEs), build upon the linearized power flow and thus on the Power Transfer Distribution Factors (PTDFs). Despite their intuitive and computationally efficient concepts, they are restricted to networks with passive transmission elements only. As soon as a significant number of controllable transmission elements, such as high-voltage direct current (HVDC) lines, operate in the system, they lose their applicability. This work reformulates the two methods in terms of Virtual Injection Patterns (VIPs), which allows one to efficiently introduce a shift parameter q to tune contributions of net sources and net sinks in the network. In this work, major properties and differences in the methods are pointed out, and it is shown how the MP and EBE algorithms can be applied to generic meshed AC-DC electricity grids: by introducing a pseudo-impedance ω¯ , which reflects the operational state of controllable elements and allows one to extend the PTDF matrix under the assumption of knowing the current flow in the system. Basic properties from graph theory are used to solve for the pseudo-impedance in dependence of the position within the network. This directly enables, e.g., HVDC lines to be considered in the MP and EBE algorithms. The extended methods are applied to a low-carbon European network model (PyPSA-EUR) with a spatial resolution of 181 nodes and an 18% transmission expansion compared to today’s total transmission capacity volume. The allocations of MP and EBE show that countries with high wind potentials profit most from the transmission grid expansion. Based on the average usage of transmission system expansion, a method of distributing operational and capital expenditures is proposed. In addition, it is shown how injections from renewable resources strongly drive country-to-country allocations and thus cross-border electricity flows.
Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.
Competition anxiety has been demonstrated to decrease sports performance while increasing burnout risk. To date, its degree in CrossFit (CF) is unknown. The present study, therefore, examines competition fear and relevant coping skills as well as potential correlates of both in individuals participating in CF events. A total of n = 79 athletes answered a battery of three questionnaires (competition fear index, athletic coping skills inventory, mindfulness attention awareness scale). Substantial levels of anxiety, particularly regarding the somatic dimension of the competition fear index, were reported. The most pronounced coping skill was freedom of worry. While age or level of competition showed no/very small associations with survey data, sex was correlated to the psychological characteristics: women reported higher competition fears and lower coping skill levels (p > 0.05). Competition fears are highly prevalent in CF athletes and the preventive value of population-specific interventions, particularly in females, should be investigated in future trials.
We study the influence of the baryon chemical potential μB on the properties of the Quark–Gluon–Plasma (QGP) in and out-of equilibrium. The description of the QGP in equilibrium is based on the effective propagators and couplings from the Dynamical QuasiParticle Model (DQPM) that is matched to reproduce the equation-of-state of the partonic system above the deconfinement temperature Tc from lattice Quantum Chromodynamics (QCD). We study the transport coefficients such as the ratio of shear viscosity η and bulk viscosity ζ over entropy density s, i.e., η/s and ζ/s in the (T,μ) plane and compare to other model results available at μB=0 . The out-of equilibrium study of the QGP is performed within the Parton–Hadron–String Dynamics (PHSD) transport approach extended in the partonic sector by explicitly calculating the total and differential partonic scattering cross sections based on the DQPM and the evaluated at actual temperature T and baryon chemical potential μB in each individual space-time cell where partonic scattering takes place. The traces of their μB dependences are investigated in different observables for symmetric Au + Au and asymmetric Cu + Au collisions such as rapidity and mT -distributions and directed and elliptic flow coefficients v1,v2 in the energy range 7.7 GeV ≤sNN−−−−√≤200 GeV.
Background: Body dysmorphic disorder (BDD) is characterized by an excessive preoccupation with one or more perceived flaws in one’s own appearance. Previous studies provided evidence for deficits in configural and holistic processing in BDD. Preliminary evidence suggests abnormalities at an early stage of visual processing. The present study is the first examining early neurocognitive perception of the own face in BDD by using electroencephalography (EEG). We investigated the face inversion effect, in which inverted (upside-down) faces are disproportionately poorly processed compared to upright faces. This effect reflects a disruption of configural and holistic processing, and in consequence a preponderance of featural face processing.
Methods: We recorded face-sensitive event-related potentials (ERPs) in 16 BDD patients and 16 healthy controls, all unmedicated. Participants viewed upright and inverted (upside-down) images of their own face and an unfamiliar other face, each in two facial emotional expressions (neutral vs. smiling). We calculated the early ERP components P100, N170, P200, N250, and the late positive component (LPC), and compared amplitudes among both groups.
Results: In the early P100, no face inversion effects were found in both groups. In the N170, both groups exhibited the common face inversion effects, with significantly larger N170 amplitudes for inverted than upright faces. In the P200, both groups exhibited larger inversion effects to other (relative to own) faces, with larger P200 amplitudes for other upright than inverted faces. In the N250, no significant group differences were found in face processing. In the LPC, both groups exhibited larger inversion effects to other (relative to own) faces, with larger LPC amplitudes for other inverted than upright faces. These overall patterns appeared to be comparable for both groups. Smaller inversion effects to own (relative to other) faces were observed in none of these components in BDD, relative to controls.
Conclusions: The findings suggest no evidence for abnormalities at all levels of early face processing in our observed sample of BDD patients. Further research should investigate the neural substrates underlying BDD symptomatology.
Die vorliegende Studie versucht einen Beitrag zur Erforschung von Implementationsmöglichkeiten des bilingualen Sprachvermögens von Schüler*innen mit Migrationshintergrund für den Regelschulkontext zu leisten, indem ein bilinguales Interaktionsangebot beim Peer-Learning für türkisch-deutschsprachig aufwachsende Schüler*innen der dritten und vierten Klasse in einem quasi-experimentellen Setting unter Verwendung von Mixed Methods untersucht wird.
This open access book presents a unique collection of practical examples from the field of pharma business management and research. It covers a wide range of topics such as: "Brexit and its Impact on pharmaceutical Law - Implications for Global Pharma Companies", "Implementation of Measures and Sustainable Actions to Improve Employee's Engagement", "Global Medical Clinical and Regulatory Affairs (GMCRA)", and "A Quality Management System for R&D Project and Portfolio Management in a Pharmaceutical Company".
The chapters are summaries of master’s theses by "high potential" Pharma MBA students from the Goethe Business School, Frankfurt/Main, Germany, with 8-10 years of work experience and are based on scientific know-how and real-world experience. The authors applied their interdisciplinary knowledge gained in 22 months of studies in the MBA program to selected practical themes drawn from their daily business.
We study how the Eurosystem Collateral Framework for corporate bonds helps the European Central Bank (ECB) fulfill its policy mandate. Using the ECBs eligibility list, we identify the first inclusion date of both bonds and issuers. We find that due to the increased supply and demand for pledgeable collateral following eligibility, (i) securities lending market trading activity increases, (ii) eligible bonds have lower yields, and (iii) the liquidity of newly-issued bonds declines, whereas the liquidity of older bonds is unaffected/improves. Corporate bond lending relaxes the constraint of limited collateral supply, thereby making the market more cohesive and complete. Following eligibility, bond-issuing firms reduce bank debt and expand corporate bond issuance, thus increasing overall debt size and extending maturity.
WiWi news [1/2020]
(2020)
Since the publication of Nikolas Rose’s ‘The Politics of Life Itself’ (2001) there has been vivid discussion about how biopolitical governance has changed over the last decades. This article uses what Rose terms ‘molecular politics’, a new socio-technical grip on the human body, as a contrasting background to ask anew his question ‘What, then, of biopolitics today?’ – albeit focusing not on advances in genetics, microbiology, and pharmaceutics, as he does, but on the rapid proliferation of wearables and other sensor-software gadgets. In both cases, new technologies providing information about the individual body are the common ground for governance and optimization, yet for the latter, the target is habits of moving, eating and drinking, sleeping, working and relaxing. The resulting profound differences are carved out along four lines: ‘somatic identities’ and a modified understanding of the body; the role of ‘expert knowledge’ compared to that of networks of peers and self-experimentation; the ‘types of intervention’ by which new technologies become effective in our everyday life; and the ‘post-discipline character’ of molecular biopolitics. It is argued that, taken together, these differences indicate a remarkable shift which could be termed aretaic: its focus is not ‘life itself’ but ‘life as it is lived’, and its modality are new everyday socio-technical entanglements and their more-than-human rationalities of (self-)governance.
A non-fundamentalist return to origin: the new Islamic reformers’ methodology of (re)interpretation
(2020)
Focusing on some contemporary Islamic reformers’ solutions, in particular, Abolkarim Soroush, Mohsen Kadivar, and Fazlur Rahman, to concrete issues in Muslim societies, this article examines two different methodological strategies of alternative readings of the Sunna: an archeological one and a genealogical one. In the archeological perspective, the holy text has been considered as a repository of answers to all sorts of questions. Through a pathological analysis, this view suggests solutions to correct distortions and looks for new windows seeking an original interpretation of the Qur’an. The genealogical view, on the other hand, puts aside this pathology and instead insists on the idea of the contingency of any interpretation. Regardless of accuracy and validity, according to the genealogical view, all interpretations have addressed temporal and contextual questions. What is important in this perspective is not returning to an original source for finding the exact message of Allah, or correcting previous interpretations, but recurrently referring to an open-ended text in order to explore the futures of the Qur’an.
Introduction: Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large.
Material and Methods: 85 bipolar disorder patients were recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort).
Results: Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration.
Discussion: When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.
Introduction: Affective disorders are a major global burden, with approximately 15% of people worldwide suffering from some form of affective disorder. In patients experiencing their first depressive episode, in most cases it cannot be distinguished whether this is due to bipolar disorder (BD) or major depressive disorder (MDD). Valid fluid biomarkers able to discriminate between the two disorders in a clinical setting are not yet available.
Material and Methods: Seventy depressed patients suffering from BD (bipolar I and II subtypes) and 42 patients with major MDD were recruited and blood samples were taken for proteomic analyses after 8 h fasting. Proteomic profiles were analyzed using the Multiplex Immunoassay platform from Myriad Rules Based Medicine (Myriad RBM; Austin, Texas, USA). Human DiscoveryMAPTM was used to measure the concentration of various proteins, peptides, and small molecules. A multivariate predictive model was consequently constructed to differentiate between BD and MDD.
Results: Based on the various proteomic profiles, the algorithm could discriminate depressed BD patients from MDD patients with an accuracy of 67%.
Discussion: The results of this preliminary study suggest that future discrimination between bipolar and unipolar depression in a single case could be possible, using predictive biomarker models based on blood proteomic profiling.
With increasing importance of organizational effectivity and efficiency measures like Balanced Scorecard and optimization of employee work behavior to achieve higher organizational efficiency, Human Resource activities concerning leadership development and academic leadership research are growing. Throughout the course of the twentieth century, a multitude of empirical studies show primarily positive relationships between different constructs of leadership models and desirable variables of organizational behavior. It becomes apparent, though, that in academic research the selection of analyzed leadership models and their consequences is very heterogeneous. This Master Thesis has the objective to contribute to Leadership Research by applying a comparative empirical study in the–until today–often neglected study population of in-house and sales personnel within the pharmaceutical industry. For this purpose, an online employee survey with N = 137 participants from a leading pharmaceutical company in Germany was conducted. Based on contemporary leadership theory, a range of Hypotheses regarding consequences of modern leadership models is empirically tested. The results of the study reconfirm Identification with Manager, Trust & Loyalty and Employee Satisfaction as consequences of Authentic as well as Transformational leadership. Work context as in-house vs. sales setting shows moderating effects on some of the leadership-consequences relationships. As the research involves multiple structurally different variables as well as constructs and compares feedback of different study populations, tangible management implications to boost desirable work attitudes and behaviors can be derived and appropriately adapted to match the respective work context. Ramifications for future scientific research are also presented.
Hintergrund: Das genaue Wissen um die Umstände eines jeden tödlichen Arbeitsunfalls ist Voraussetzung für die Identifizierung von Unfallschwerpunkten und ermöglicht eine effektive Präventionsarbeit. Mit dieser rechtsmedizinischen Studie zum Arbeitsunfallgeschehen soll ein Beitrag dazu geleistet werden, die Zahl tödlicher Arbeitsunfälle in Deutschland zu senken.
Material und Methode: Zur Untersuchung kamen die tödlichen Arbeitsunfälle, die sich im Einzugsbereich des rechtsmedizinischen Instituts Frankfurt am Main in den Jahren von 2005 bis 2016 ereigneten. Ausgewertet wurden Obduktionsprotokolle sowie die dem Institut zur Verfügung gestellten staatsanwaltschaftlichen Ermittlungsakten.
Ergebnisse: Es fanden sich 87 tödliche Arbeitsunfälle in dem genannten Zwölfjahreszeitraum. Die Altersstruktur reichte vom jugendlichen Alter bis in das Rentenalter. Betroffen waren zum größten Teil männliche Arbeiter (96,6 %, p < 0,0001), verhältnismäßig häufig ausländischer Nationalität (34,5 %). Die meisten Unfälle ereigneten sich in der 2. Jahreshälfte (58,6 %), an Montagen (26,4 %), kurz vor und nach der Mittagspause. In 3 Fällen lag die Blutalkoholkonzentration über 0,5‰. Die Baubranche (55,2 %) war der unfallträchtigste Wirtschaftszweig. Der Absturz (28,7 %) war der häufigste Unfallmechanismus und das Polytrauma (39,1 %) gemeinsam mit dem Schädel-Hirn-Trauma (24,1 %) gemäß dem ISS die häufigste Todesursache.
Diskussion: Nach den Ergebnissen dieser Studie sollten Alter der Arbeiter sowie die Tages‑, Wochen- und Jahreszeit bei der Ausführung risikoreicher Arbeiten im Baugewerbe berücksichtigt werden. Besonderes Augenmerk sollten Arbeitgeber auf die Kontrolle von Sicherheitsvorkehrungen bei Arbeiten in der Höhe sowie auf die Durchsetzung der Helmpflicht gerade auch bei ausländischen Arbeitnehmern legen.
In der Krise sind wir um einiges fremdbestimmter und befolgen die unterschiedlichsten neuen Regeln; die Museen sind geschlossen und mit ihren Werken können wir uns nur aus der Ferne auseinandersetzen. Line Kroms Arbeiten geben die Möglichkeit, Strukturen und Abläufe, in denen wir leben, zu hinterfragen.
This Policy Letter presents a proposal for designing a program of government assistance for firms hurt by the Coronavirus crisis in the European Union (EU). In our recent Policy Letter 81, we introduced a new, equity-type instrument, a cash-against-tax surcharge scheme, bundled across firms and countries in a European Pandemic Equity Fund (EPEF). The present Policy Letter 84 focuses on the principles and conditions relevant for the operationalization of a EPEF. Our proposal has several desirable features. It: a) offers better risk sharing opportunities, augmenting the resilience of businesses and EU economies; b) is need-based, thereby contributing to an effective use of resources; c) builds on conditions and credible controls, addressing adverse selection and moral hazard; d) is accessible to smaller and medium-sized firms, the backbone of Europe’s economy; e) applies Europe-wide uniform eligibility criteria, strengthening support among member states; f) is a scheme of limited duration, reducing (perceived) government interference in businesses; g) creates a template for a growth-oriented public policy, aligning public and private sector interests; and h) builds on the existing institutional infrastructure and requires minimal legislative adjustments.
Einen Überblick über neueste Forschungsergebnisse der Wissenschaftler am IMFS, Berichte von Konferenzen und Vorträgen sowie ausführliche Informationen zum derzeit größten Forschungsprojekt Macroeconomic Modeling and Comparison Initiative (MMCI) bietet der IMFS-Jahresbericht 2019, der jetzt veröffentlicht ist. Darüber hinaus gibt IMFS-Professor Michael Haliassos im Interview einen Einblick in seine Arbeit zum Finanzverhalten der privaten Haushalte und die ehemaligen Mitarbeiter Philipp Lieberknecht und Felix Strobel berichten, wie sie im Berufsleben auf ihrer Forschung am IMFS aufbauen können.
Auf rund 100 Seiten zeigt der Bericht die Highlights des Jahres, alle Mitarbeiter sowie die Projekte, Publikationen sowie die Veranstaltungen des IMFS, darunter „The ECB and Its Watchers“ zu finden. Der Jahresbericht ist auf Englisch erschienen und steht im PDF-Format zur Verfügung.
Inappropriate land management leads to soil loss with destruction of the land’s resource and sediment input into the receiving river. Part of the sediment budget of a catchment is the estimation of soil loss. In the Ruzizi catchment in the Eastern Democratic Republic of the Congo (DRC), only limited research has been conducted on soil loss mainly dealing with local observations on geomorphological forms or river load measurements; a regional quantification of soil loss is missing so far. Such quantifications can be calculated using the Universal Soil Loss Equation (USLE). It is composed of four factors: precipitation (R), soil (K), topography (LS), and vegetation cover (C). The factors can be calculated in different ways according to the characteristics of the study area. In this paper, different approaches for calculating the single factors are reviewed and validated with field work in two sub-catchments of Ruzizi River supplying the water for the reservoirs of Ruzizi I and II hydroelectric dams. It became obvious that the (R)USLE model provides the best results with revised R and LS factors. C factor calculations required to conduct a supervised classification using the Maximum Likelihood Procedure. Different C factor values were assigned to the land cover classes. The calculations resulted in a soil loss rate for the predominantly occurring Ferralsols and Leptosols of around 576 kt/yr in both catchments, when 2016 landcover and precipitation are used. This represents an area-normalized value of 40.4 t/ha/yr for Ruzizi I and 50.5 t/ha/yr for Ruzizi II due to different landcover in the two sub-catchments. The mean value for the whole study area is 47.8 t/ha/yr or even 27.1 t/ha/yr when considering land management techniques like terracing on the slopes (P factor). This work has shown that the (R)USLE model can serve as an easy to handle tool for soil loss quantification when comprehensive field work results are sparse. The model can be implemented in Geographic Information Systems (GIS) with free data; hence, a validation is crucial. It becomes apparent that the use of high resolution Sentinel 2a MSI data as the basis for C factor calculations is an appropriate method for considering heterogeneous Land Use Land Cover (LULC) patterns. To transfer the approach to other regions, the calculation of factor R needs to be modified
Der Mensch ist ein emotionales Tier: Gefühle beeinflussen jedes menschliche Verhalten – auch jenes von Wissenschaftler/innen. Meist wird diese Emotionalität im Dienst wissenschaftlicher Objektivität vermieden oder unterdrückt. Dabei hat sie entscheidenden Anteil an Erkenntnisprozessen sowohl in der Generierung von Daten als auch in deren Interpretation und in der Präsentation von Wissensbeständen. Dies gilt ganz besonders für die Primatologie, gerade dort, wo mit unseren nächsten Artverwandten, den anderen Affen, im Feld geforscht wird. Primatologische Erkenntnisse wiederum affizieren ein großes Publikum und können deswegen leicht popularisiert werden. - Diese Open-Access-Publikation untersucht anhand primatologischer Forschungsmemoiren die Form und Funktion von Emotionen, Affekten und Gefühlen in der Feldforschung, die Affektpoetik und Emotionsregime der Primatologie sowie die Rolle, welche Fiktionen für die Reflexion des Verhältnisses von Mensch, Affe und Affekt spielen. Sie stellt damit die Frage nach der Rolle von Emotionalität in der Primatologie als Frage nach den epistemischen, poetologischen und politischen Grundlagen einer gegenwärtigen Leitwissenschaft der Anthropologie.
Use banks the right way
(2020)
Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.
Leider geschlossen! Theater spielt sich normalerweise auf der Bühne und im besten Fall vor ausverkauftem Haus ab. Da gerade nichts normal ist und die Spielstätten geschlossen sind, versuchen viele Schauspielhäuser ihren kulturellen Beitrag online zu leisten. Ein kurzer Einblick in digitale Wege der Schauspielkunst zu Krisenzeiten.
Our study is the first to objectively assess sleep and sleep-related respiration in orchestra musicians. We hypothesized low sleep quality due to high work demands and irregular work-sleep schedules, and a better respiration for wind instrument (WI) players than string instrument (SI) players due to habitual upper airway muscles training. We recorded overnight polysomnography with 29 professional orchestra musicians (21 men, 14 WI/ 15 SI). The musicians presented a sleep efficiency of 88% (IQR 82–92%) with WI having a significant higher sleep efficiency than SI (89%, 85–93% vs. 85%, 74–89%; p = 0.029). The group had a total sleep time around 6 hours (377min, 340-421min) with signs of increased NREM 1 (light sleep) and decreased REM (dream sleep). The musicians displayed an apnea-hypopnea-index of 2.1events/hour (0.7–5.5) and an oxygen saturation of 98% (97–100%). While SI player exhibited declining sleep-related respiration with age (breathing events: r = 0.774, p = 0.001, oxygen: r = -0.647, p = 0.009), WI player showed improved respiration with age (breathing events: r = -0.548, p = 0.043; oxygen: r = 0.610, p = 0.020). Our study is the first objective investigation of sleep pattern and respiration during sleep with overnight polysomnography in professional orchestra musicians. While sleep and respiration were unexpectedly good, our results revealed possible signs of sleep deprivation and an interesting age-related pattern on respiration depending on instrument. While sample size was small and results modest, these findings present first objective evidence towards the assumption that habitual playing of a WI–and training of the upper airway muscles–may have a protective effect on respiration.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis
(2020)
Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.
The Nok Culture of Central Nigeria is known for its sophisticated terracotta figurines initially described in the 1950s by the British archaeologist Bernard Fagg. Since 2009, the Nok Culture has been the subject of research at the Goethe University Frankfurt within the scope of a long-term project funded by the German Research Foundation (DFG). This book is the outcome of a PhD thesis that involved pXRF analysis of features associated with the Nok Culture, namely stone-pot-arrangements and pit features.
Stone-pot-arrangements are considered to be burials, indicated by arranged and modified stones associated with complete pots and, in a few cases, a necklace made of stone beads. However, the absence of bones and other skeletal remains meant that their interpretation as burials was unresolved. The interpretation of pits or pit-like structures, of various shapes and sizes, also remained inconclusive.
Employing pXRF analysis succeeded in revealing traces of a decomposed body, supporting the hypothesis of stone-pot-arrangements being interments. Together with the analysis of pits, new ideas about the formation and use of Nok sites were advanced. These culminated in a 'patchwork model' that assumes a repetitive cycle of utilising land for farming, settlements and burials, followed by abandonment and subsequent re-visiting and re-use of the formerly abandoned land.
Der Sammelband widmet sich dem Verhältnis von Erziehungswissenschaft, Medienpädagogik und Online-Forschung. Den Ausgangspunkt bildet die Frage, welche Bedeutung die umfassende Mediatisierung und Digitalisierung beinahe aller Lebensbereiche für Gesellschaft und Individuen aus einer erziehungswissenschaftlichen Perspektive hat. In den Fokus gerückt werden hier die mit dem digitalen Wandel verbundenen theoretisch-begrifflichen wie empirisch-methodischen Herausforderungen für die (medienpädagogische) Forschung, insbesondere die Online-Forschung.
Die bisherigen erziehungswissenschaftlichen und medienpädagogischen Diskurse zur Forschung im und mit dem Internet können als verstreut und disparat bezeichnet werden. Ziel dieses Bandes ist es daher zum einen, die (medien-) pädagogischen Zugänge zur Online-Forschung zu bündeln, zu diskutieren und zu bilanzieren. Zum anderen werden die Herausforderungen des skizzierten Wandels für die Online-Forschung in theoretisch-methodologischer, methodischer und forschungsthematischer Hinsicht in den Blick genommen.
Die zunehmende Nutzung von Online-Kommunikationskanälen vereinfacht nicht nur den alltäglichen, zwischenmenschlichen Austausch, sondern eröffnet auch der erziehungswissenschaftlichen Forschung neue Möglichkeiten. Gleichzeitig stehen Chancen wie der Reichweitenerhöhung von Forschungsaktivitäten auch Herausforderungen bspw. im Bereich der Validität gegenüber. Vor diesem Hintergrund geht der Beitrag der Frage nach, ob sich diese Nachteile durch die methodologisch fundierte Kombination von Offline- und Online-Umgebungen kompensieren lassen. Anhand eines Forschungsszenarios werden drei verschiedene Designs konzipiert, die auf genau diese Herausforderung eingehen. Dazu wird eine Mixed Methods Perspektive eingenommen, um verschiedene Möglichkeiten aufzuzeigen, die einzelne Schwächen der Methoden adäquat ausgleichen oder sogar Synergieeffekte erzielen.
Die Wettbewerbsfähigkeit der deutschen Wirtschaft steht vor gewaltigen Herausforderungen. Traditionell starke Sektoren wie die Automobilindustrie oder der Maschinenbau befinden sich angesichts disruptiver Veränderungen durch neue Technologien, den Kampf gegen den Klimawandel und veränderte regulatorische Rahmenbedingungen in einer Umbruchphase. Zahlreiche Industriezweige wandeln sich durch den Einsatz von Künstlicher Intelligenz zu „Smart Industries“. Gleichzeitig gewinnt die Kompetenz in Querschnittstechnologien wie Cloud Computing oder Cyber Security an Bedeutung, da diese den effektiven Einsatz von Künstlicher Intelligenz erst ermöglichen. Eine Analyse der Wettbewerbsposition der deutschen Wirtschaft zeigt auf, dass in manchen Zukunftsfeldern ein erheblicher Nachholbedarf besteht.
Stinginess was yesterday
(2020)
Geiz war gestern
(2020)
In Deutschland ist die Wohneigentumsquote innerhalb der OECD am zweitniedrigsten. Eine wichtige Rolle spielt dabei die Wohnungspolitik, die hierzulande Anreize für das Mieten schafft. Neue Studien zeigen, dass eine veränderte Politik die Wohneigentumsquote erhöhen und die Vermögensungleichheit verringern könnte.
In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I–VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests’ antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II–III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.
Vor zwei Monaten traf ich Sascia Bailer, die Künstlerischen Leiterin des M.1 der Arthur Boskamp-Stiftung in Hohenlockstedt, um über ihr Programm "Care" zu sprechen. Seitdem haben die dramatischen Geschehnisse uns gezwungen, die Realität neu zu überdenken. Bailers Konzept hat in der gegenwärtigen Krise nur an Aktualität gewonnen: Wir alle werden uns noch lange erinnern, wie sich die Care-Arbeitenden – Krankenschwestern, Pfleger*innen, Ärzt*innen und Sozialarbeiter*innen – in den Zeiten der höchsten Not, um uns gekümmert haben. Das Programm in der Ausstellungshalle M.1 hat das Ziel, die Unsichtbarkeit der Fürsorge und ihre Überlastung zu thematisieren und dieser entgegenzuwirken. Im Moment sind die Räume des M.1 sowie alle anderen Museen in Deutschland geschlossen, es lohnt sich aber, genau hinzuschauen, wie neue Dialoge in unserer Gemeinschaft hergestellt werden und welche Rolle dabei die Kunst spielen kann.
Household finance
(2020)
Household financial decisions are complex, interdependent, and heterogeneous, and central to the functioning of the financial system. We present an overview of the rapidly expanding literature on household finance (with some important exceptions) and suggest directions for future research. We begin with the theory and empirics of asset market participation and asset allocation over the lifecycle. We then discuss house-hold choices in insurance markets, trading behavior, decisions on retirement saving, and financial choices by retirees. We survey research on liabilities, including mortgage choice, refinancing, and default, and household behavior in unsecured credit markets, including credit cards and payday lending. We then connect the household to its social environment, including peer effects, cultural and hereditary factors, intra-household financial decision making, financial literacy, cognition and educational interventions. We also discuss literature on the provision and consumption of financial advice.
This essay discusses the current Europeanization of national museums in different European countries and considers it against the background of media theories and feminist epistemologies. Taking the example of the European Solidarity Centre Gdansk, the Deutsches Historisches Museum Berlin and the Musée des civilisations de l’Europe et de la Méditerranée Marseille, it suggests two approaches to the dynamics of travel and locatedness in the museum. Firstly, using the concept of what I call “Europoeic media” this essay shows how “Europe” as a travelling memory is shaped by and in media. Secondly, I argue that the locatedness both of memories and the memory researcher are not detrimental but instead produce “situated knowledges”. Thus, in combining media-sensitivity and standpoint-reflexivity, the paper proposes new ways of taking into account the travels and locatedness of both memories and memory research.
Der vorliegende Beitrag diskutiert, wie mithilfe von Unterrichtsvideographien die Reflexionskompetenz angehender Englischlehrkräfte bereits in der ersten Ausbildungsphase angebahnt und geschult werden kann. Er geht von der Annahme aus, dass praktizierenden Lehrkräften häufig die Gelegenheiten oder auch die Kompetenzen zur systematischen Reflexion fehlen (vgl. Kittel & Rollett, 2017) und diese bereits vorher grundgelegt werden müssen. Anhand von zwei Seminarbeispielen aus der Englischdidaktik, welche sich auf die disziplinspezifischen Heterogenitätsdimensionen Mehrsprachigkeit (vgl. u.a. Elsner & Wildemann, 2012; Niesen, 2018) und Transkulturalität (vgl. u.a. Viebrock, 2018; Kreft, 2019a, 2019b) beziehen, werden praktische Umsetzungsmöglichkeiten bzw. die wechselseitige Integration theoretischer Konzepte und unterrichtlicher Handlungen/Interaktionen illustriert. Die vorgestellten Aufgabenformate beziehen sich auf die kasuistische Fallarbeit (nach Lindow & Münch, 2014) sowie auf VierSchritt-Analysen (nach Santagata & Guarino, 2011). Als grundlegende Struktur für die Entwicklung von Reflexionskompetenz in videobasierten Lernsettings wird eine adaptierte Fassung des Modells von Aeppli und Lötscher (2016) mit den Verfahrensschritten „Erleben“, „Erkennen“, „Darstellen“, „Analysieren“ und „Alternative Szenarien entwickeln“ verwendet. Es zeigt sich, dass die gewählte Vorgehensweise Studierende in die Lage versetzt, die konzeptionelle und unterrichtspraktische Bedeutung von sprachlicher und kultureller Heterogenität im Englischunterricht zu erkennen und, in einem weiteren Schritt, Möglichkeiten zur Förderung von transkulturalitäts- bzw. mehrsprachigkeits-sensitivem Handeln zu identifizieren und somit ihre Reflexionskompetenzen zu schulen.
L'osservazione secondo la quale lo scarto come oggetto di ricerca sia allo stesso tempo un effetto della sua ricerca è ciò che l'articolo traccia in tre studi sulla spazzatura: Rubbish! di William Rathje e Cullen Murphy, Un mondo usa e getta di Guido Viale e Das Miill-System di Volker Grassmuck e Christian Unverzagt. Questi tre studi esemplificano tre modi di presentare lo scarto: esplorazione, problema e ricie/aggio. Guardarli come argomenti scientifici ci permette di discutere di ciò che è considerato scarto ponendo domande di presentazione testuale e, allo stesso tempo, di chiedere quali conseguenze abbia la presentazione per il concetto scientifico dello scarto.
This paper offers a description and account of the patterns of 'ex-situ' focus in Dagbani. We show that there are two syntactic strategies for creating 'ex-situ' focus in the language, one involving A’-movement to the left periphery, and the second involving base generation in the left periphery combined with coreference to a resumptive pronoun. Furthermore, we argue that subjects are difficult to move from Spec,TP to Spec,CP in the left-periphery because of 'anti-locality', which creates a tension when trying to focus subjects, which are required to derivationally fill the specifier of both positions. We further show that what looks to be a two-way distinction between the behaviour of subjects and non-subjects in the language is in fact a three-way distinction between subjects that are focussed to a local left-periphery, subjects that are focussed to a non-local left-periphery, and non-subjects. These distinctions arise due to there being two methods for Dagbani to resolve the antilocality problem of subject movement, and so local subjects solve the problem differently to non-local subjects.
At a site in the Bolivian Chiquitano region composed by a mosaic of pastureland and primary Chiquitano Dry Forest&nbsp;(CDF) we conducted a camera-trapping study to (1) survey the mammals, and (2) compare individual Jaguar numbers&nbsp;with other Chiquitano sites. Therefore, we installed 13 camera stations (450 ha polygon) over a period of six months.&nbsp;On 1,762 camera-days and in 1,654 independent capture events, we recorded 24 mammalian species that represent the&nbsp;native fauna of large and medium-sized mammals including apex-predators (Puma, Jaguar), meso-carnivores (Ocelot,&nbsp;Jaguarundi, Margay), and large herbivores (Tapir, Collared and White lipped Peccary). We identified six adult Jaguars&nbsp;and found indications of successful reproductive activity. Captures of Jaguars were higher in CDF than in altered habitats.&nbsp;In summary, we believe that (1) the mammal species richness, (2) the high capture numbers of indicator species,&nbsp;and (3) the high capture numbers of Jaguar indicate that our study area has a good conservation status. Future efforts&nbsp;should be undertaken to keep this, and monitoring programs in this region are necessary to further evaluate the potential&nbsp;importance of the Chiquitano region as a possible key region for mammals, especially Jaguars, in South America.
URPOSE: Today, the majority of medical graduates in countries such as the UK, the US or Germany are female. This poses a major problem for workforce planning especially in urology. We here use first the first time the previously established Brüggmann Groneberg (BG) index to assess if female academic career options advance in urology.
METHODS: Different operating parameters (student population, urology specialist population, urology chair female:male (f:m) ratio) were collected from the Federal Office of Statistics, the Federal Chamber of Physicians and the medical faculties of 36 German universities. Four time points were monitored (2000, 2005, 2010 and 2015). From these data, female to male (f:m) ratios and the recently established career advancement (BG) index have been calculated.
RESULTS: The German hospital urology specialists' f:m ratios were 0.257 (499 female vs. 1944 male) for 2015, 0.195 for 2010, 0.133 for 2005 and 0.12 for 2000. The career advancement (BG) index was 0.0007 for 2000, 0,0005 for 2005, 0.094 for 2010 and 0.073 for 2015. The decrease from 2010 to 2015 was due to an increase in the f:m ratio of hospital urologists and female medical students.
CONCLUSION: The BG index clearly illustrated that there is an urgent need for special academic career funding programs to counteract gender problems in urology. The BG index has been shown to be an excellent tool to assess female academic career options and will be very helpful to assess and document positive or negative changes in the next decades.
BACKGROUND: Although phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level. We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple therapy in sputum cells and whole blood of patients with COPD and chronic bronchitis.
METHODS: Whole genome gene expression analysis was carried out by microarray in 54 patients before and after 32 days treatment with CHF6001 800 and 1600 μg and placebo twice daily (BID) in a randomised crossover study.
RESULTS: CHF6001 had a strong effect in sputum, with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-adjusted for False Discovery Rate < 0.05) with 800 and 1600 μg BID, respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (> 87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumour necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. The effect in blood was not significant.
CONCLUSIONS: Inhaled PDE4 inhibition by CHF6001 on top of triple therapy in patients with COPD and chronic bronchitis significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimising unwanted systemic class-effects.
TRIAL REGISTRATION: ClinicalTrial.gov, EudraCT, 2015-005550-35. Registered 15 July 2016.
Correction to: Scientifc Reports https://doi.org/10.1038/s41598-019-43857-5, published online 17 May 2019. In the original version of this Article, Jan-Hendrik Trösemeier was incorrectly affiliated with ‘Division of Allergology, Paul Ehrlich Institut, Langen, Germany’. Te correct afliations are listed below...
Biofabrication of SDF-1 functionalized 3D-printed cell-free scaffolds for bone tissue regeneration
(2020)
Large segmental bone defects occurring after trauma, bone tumors, infections or revision surgeries are a challenge for surgeons. The aim of our study was to develop a new biomaterial utilizing simple and cheap 3D-printing techniques. A porous polylactide (PLA) cylinder was printed and functionalized with stromal-derived factor 1 (SDF-1) or bone morphogenetic protein 7 (BMP-7) immobilized in collagen type I. Biomechanical testing proved biomechanical stability and the scaffolds were implanted into a 6 mm critical size defect in rat femur. Bone growth was observed via x-ray and after 8 weeks, bone regeneration was analyzed with µCT and histological staining methods. Development of non-unions was detected in the control group with no implant. Implantation of PLA cylinder alone resulted in a slight but not significant osteoconductive effect, which was more pronounced in the group where the PLA cylinder was loaded with collagen type I. Addition of SDF-1 resulted in an osteoinductive effect, with stronger new bone formation. BMP-7 treatment showed the most distinct effect on bone regeneration. However, histological analyses revealed that newly formed bone in the BMP-7 group displayed a holey structure. Our results confirm the osteoinductive character of this 3D-biofabricated cell-free new biomaterial and raise new options for its application in bone tissue regeneration.
Hepatocellular carcinoma (HCC) shows a remarkable heterogeneity and is recognized as a chemoresistant tumor with dismal prognosis. In previous studies, we observed significant alterations in the serum sphingolipids of patients with HCC. This study aimed to investigate the in vitro effects of sorafenib, which is the most widely used systemic HCC medication, on the sphingolipid pathway as well as the effects of inhibiting the sphingolipid pathway in HCC. Huh7.5 and HepG2 cells were stimulated with sorafenib, and inhibitors of the sphingolipid pathway and cell proliferation, viability, and concentrations of bioactive metabolites were assessed. We observed a significant downregulation of cell proliferation and viability and a simultaneous upregulation of dihydroceramides upon sorafenib stimulation. Interestingly, fumonisin B1 (FB1) and the general sphingosine kinase inhibitor SKI II were able to inhibit cell proliferation more prominently in HepG2 and Huh7.5 cells, whereas there were no consistent effects on the formation of dihydroceramides, thus implying an involvement of distinct metabolic pathways. In conclusion, our study demonstrates a significant downregulation of HCC proliferation upon sorafenib, FB1, and SKI II treatment, whereas it seems they exert antiproliferative effects independently from sphingolipids. Certainly, further data would be required to elucidate the potential of FB1 and SKI II as putative novel therapeutic targets in HCC.
Some anaerobic bacteria use biotin-dependent Na+-translocating decarboxylases (Bdc) of β-keto acids or their thioester analogs as key enzymes in their energy metabolism. Glutaconyl-CoA decarboxylase (Gcd), a member of this protein family, drives the endergonic translocation of Na+ across the membrane with the exergonic decarboxylation of glutaconyl-CoA (ΔG0’ ≈−30 kJ/mol) to crotonyl-CoA. Here, we report on the molecular characterization of Gcd from Clostridium symbiosum based on native PAGE, size exclusion chromatography (SEC) and laser-induced liquid bead ion desorption mass spectrometry (LILBID-MS). The obtained molecular mass of ca. 400 kDa fits to the DNA sequence-derived mass of 379 kDa with a subunit composition of 4 GcdA (65 kDa), 2 GcdB (35 kDa), GcdC1 (15 kDa), GcdC2 (14 kDa), and 2 GcdD (10 kDa). Low-resolution structural information was achieved from preliminary electron microscopic (EM) measurements, which resulted in a 3D reconstruction model based on negative-stained particles. The Gcd structure is built up of a membrane-spanning base primarily composed of the GcdB dimer and a solvent-exposed head with the GcdA tetramer as major component. Both globular parts are bridged by a linker presumably built up of segments of GcdC1, GcdC2 and the 2 GcdDs. The structure of the highly mobile Gcd complex represents a template for the global architecture of the Bdc family.
Requirements analysis and specification for a molecular tumor board platform based on cBioPortal
(2020)
Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements from the first round were created. Requirements that cBioPortal already meets were skipped during the second round. In the end, 24 requirements with sometimes several conceivable options were identified and 54 screenshot mockups were created. Some of the identified requirements have already been suggested to the community by other users or are currently being implemented in cBioPortal. This shows, that the results are in line with the needs expressed by various disciplines. According to our findings, cBioPortal has the potential to significantly improve the processes and analyses of an MTB after the implementation of the identified requirements.
Introduction: Reliable and cost-effective diagnostics for hepatitis E virus (HEV) infection are necessary. The aim of our study was to investigate which diagnostic test is most accurate to detect HEV infection in immunocompetent and immunosuppressed patients in a real world setting. Patients and Methods: We performed a retrospective analysis of 1165 patients tested for HEV antibodies and HEV PCR at the same time point. Clinical, laboratory and virological data were taken from patient charts. HEV IgA was measured in a subgroup of 185 patients. Results: HEV RNA was detectable in 61 patients (5.2%); most of them (n = 49, 80.3%/n = 43, 70.5%) were HEV IgM+ and IgG+; however, 12 patients (19.6%) were HEV RNA positive/HEV IgM negative and 17 patients (27.8%) were HEV RNA positive/HEV IgG negative. Ten HEV RNA positive patients (16.4%) had neither HEV IgG nor IgM antibodies. Importantly, all of them were immunosuppressed. HEV IgA testing was less sensitive than HEV IgM for HEV diagnosis. Conclusions: HEV infection can be overlooked in patients without HEV specific antibodies. Performing PCR is necessary to diagnose or exclude HEV infection in immunocompromised hosts. In immunocompetent patients, a screening based on HEV antibodies (IgG/IgM) is sufficient.
The efficacy of cisplatin-based chemotherapy in ovarian cancer is often limited by the development of drug resistance. In most ovarian cancer cells, cisplatin activates extracellular signal-regulated kinase1/2 (ERK1/2) signalling. Phosphoprotein enriched in astrocytes (PEA-15) is a ubiquitously expressed protein, capable of sequestering ERK1/2 in the cytoplasm and inhibiting cell proliferation. This and other functions of PEA-15 are regulated by its phosphorylation status. In this study, the relevance of PEA-15 phosphorylation state for cisplatin sensitivity of ovarian carcinoma cells was examined. The results of MTT-assays indicated that overexpression of PEA-15AA (a non-phosphorylatable variant) sensitised SKOV-3 cells to cisplatin. Phosphomimetic PEA-15DD did not affect cell sensitivity to the drug. While PEA-15DD facilitates nuclear translocation of activated ERK1/2, PEA-15AA acts to sequester the kinase in the cytoplasm as shown by Western blot. Microarray data indicated deregulation of thirteen genes in PEA-15AA-transfected cells compared to non-transfected or PEA-15DD-transfected variants. Data derived from The Cancer Genome Atlas (TCGA) showed that the expression of seven of these genes including EGR1 (early growth response protein 1) and FLNA (filamin A) significantly correlated with the therapy outcome in cisplatin-treated cancer patients. Further analysis indicated the relevance of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signalling for the favourable effect of PEA-15AA on cisplatin sensitivity. The results warrant further evaluation of the PEA-15 phosphorylation status as a potential candidate biomarker of response to cisplatin-based chemotherapy.
Short linear motifs (SLiMs) located in disordered regions of multidomain proteins are important for the organization of protein–protein interaction networks. By dynamic association with their binding partners, SLiMs enable assembly of multiprotein complexes, pivotal for the regulation of various aspects of cell biology in higher organisms. Despite their importance, there is a paucity of molecular tools to study SLiMs of endogenous proteins in live cells. LC3 interacting regions (LIRs), being quintessential for orchestrating diverse stages of autophagy, are a prominent example of SLiMs and mediate binding to the ubiquitin-like LC3/GABARAP family of proteins. The role of LIRs ranges from the posttranslational processing of their binding partners at early stages of autophagy to the binding of selective autophagy receptors (SARs) to the autophagosome. In order to generate tools to study LIRs in cells, we engineered high affinity binders of LIR motifs of three archetypical SARs: OPTN, p62, and NDP52. In an array of in vitro and cellular assays, the engineered binders were shown to have greatly improved affinity and specificity when compared with the endogenous LC3/GABARAP family of proteins, thus providing a unique possibility for modulating LIR interactions in living systems. We exploited these novel tools to study the impact of LIR inhibition on the fitness and the responsiveness to cytarabine treatment of THP-1 cells – a model for studying acute myeloid leukemia (AML). Our results demonstrate that inhibition of LIR of a single autophagy receptor is insufficient to sensitize the cells to cytarabine, while simultaneous inhibition of three LIR motifs in three distinct SARs reduces the IC50 of the chemotherapeutic.
Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.
Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.
Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).
Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.
Background: Previously, we used inhibitors blocking BET bromodomain binding proteins (BRDs) in Ewing sarcoma (EwS) and observed that long term treatment resulted in the development of resistance. Here, we analyze the possible interaction of BRD4 with cyclin-dependent kinase (CDK) 9. Methods: Co-immunoprecipitation experiments (CoIP) to characterize BRD4 interaction and functional consequences of inhibiting transcriptional elongation were assessed using drugs targeting of BRD4 or CDK9, either alone or in combination. Results: CoIP revealed an interaction of BRD4 with EWS-FLI1 and CDK9 in EwS. Treatment of EwS cells with CDKI-73, a specific CDK9 inhibitor (CDK9i), induced a rapid downregulation of EWS-FLI1 expression and block of contact-dependent growth. CDKI-73 induced apoptosis in EwS, as depicted by cleavage of Caspase 7 (CASP7), PARP and increased CASP3 activity, similar to JQ1. Microarray analysis following CDKI-73 treatment uncovered a transcriptional program that was only partially comparable to BRD inhibition. Strikingly, combined treatment of EwS with BRD- and CDK9-inhibitors re-sensitized cells, and was overall more effective than individual drugs not only in vitro but also in a preclinical mouse model in vivo. Conclusion: Treatment with BRD inhibitors in combination with CDK9i offers a new treatment option that significantly blocks the pathognomonic EWS-ETS transcriptional program and malignant phenotype of EwS.
Background: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy).
Methods: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS).
Results: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding
renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status
decreased by 18.1 points (95%-CI: 7.1–29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively.
Conclusions: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together
with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.
Trial registration: The study is registered with ClinicalTrials.gov (NCT01180504). Registered 12 August 2010 – retrospectively registered.
Despite the great success of antiretroviral therapy, both in the treatment and prevention of HIV-1 infection, a vaccine is still urgently needed to end the epidemic. According to UNAIDS, in 2018, about 35% of HIV-1 infected persons did not receive antiretroviral therapy (ART), resulting in 1.7 million new infections in that year...
Purpose: Diffuse cortical damage in relapsing–remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex.
Materials and Methods: Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects.
Results: Across the whole cortex, MD was increased in patients (p < 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03).
Conclusion: Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies.
Experiments in cadavers have demonstrated significant mechanical interactions between constituents of myofascial chains. However, evidence for such force transmission effects is scarce under in vivo conditions. The purpose of this trial was to examine the impact of ankle motion on soft tissue displacement of the dorsal thigh. Eleven healthy active individuals (26.8 ± 4.3 years, six males), in prone position and with the knee extended, underwent passive calf stretches (ankle dorsal extension) imposed by an isokinetic dynamometer. High-resolution ultrasound was used to simultaneously capture the displacement of the semimembranosus muscle, which was quantified by means of cross-correlation analysis. Inactivity of the leg muscles was controlled using surface electromyography (EMG). One participant had to be excluded due to major EMG activity during the experiment. According to a one-sample t test testing the difference to the neutral zero position, ankle dorsal extension induced substantial caudal muscle displacements (5.76 ± 2.67 mm, p < 0.0001). Correlation analysis (Spearman), furthermore, revealed a strong association between maximal dorsal extension and semimembranosus motion (rho = 0.76, p = 0.02). In conclusion, the present trial provides initial in vivo evidence for a mechanical force transmission between serially connected skeletal muscles. This means that local alterations of the mechanical tissue properties may modify flexibility in neighboring (superior or inferior) joints.
The quantified behavioral test - a confirmatory test in the diagnostic process of adult ADHD?
(2020)
The differential diagnosis of attention deficit hyperactivity disorder (ADHD) in adulthood is complicated by comorbid disorders, but also by the overlapping of main symptoms such as inattentiveness, impulsivity, and hyperactivity with other disorders. Neuropsychological tests like continuous performance tests (CPT) try to solve this dilemma by objectively measurable parameters. We investigated in a cohort of n=114 patients presenting to an ADHD outpatient clinic how well a commercially available CPT test (QbTest®) can differentiate between patients with ADHD (n=94) and patients with a disconfirmed ADHD diagnosis (n=20). Both groups showed numerous comorbidities, predominantly depression (27.2% in the ADHD group vs. 45% in the non-ADHD group) and substance-use disorders (18.1% vs. 10%, respectively). Patients with ADHD showed significant higher activity (2.07 ± 1.23) than patients without ADHD (1.34 ± 1.27, dF=112; p=0.019), whereas for the other core parameters, inattention and impulsivity no differences could be found. Reaction time variability has been discussed as a typical marker for inattention in ADHD. Therefore, we investigated how well ex-Gaussian analysis of response time can differentiate between ADHD and other patients, showing, that it does not help to identify patients with ADHD. Even though patients with ADHD showed significantly higher activity, this parameter differed only poorly between patients (accuracy AUC 65% of an ROC-Curve). We conclude that CPTs do not help to identify patients with ADHD in a specialized outpatient clinic. The usability of this test for differentiating between ADHD and other psychiatric disorders is poor and a sophisticated analysis of reaction time did not decisively increase the test accuracy.
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
Macrophage and tumor cell cross-talk is fundamental for lung tumor progression: we need to talk
(2020)
Regardless of the promising results of certain immune checkpoint blockers, current immunotherapeutics have met a bottleneck concerning response rate, toxicity, and resistance in lung cancer patients. Accumulating evidence forecasts that the crosstalk between tumor and immune cells takes center stage in cancer development by modulating tumor malignancy, immune cell infiltration, and immune evasion in the tumor microenvironment (TME). Cytokines and chemokines secreted by this crosstalk play a major role in cancer development, progression, and therapeutic management. An increased infiltration of Tumor-associated macrophages (TAMs) was observed in most of the human cancers, including lung cancer. In this review, we emphasize the role of cytokines and chemokines in TAM-tumor cell crosstalk in the lung TME. Given the role of cytokines and chemokines in immunomodulation, we propose that TAM-derived cytokines and chemokines govern the cancer-promoting immune responses in the TME and offer a new immunotherapeutic option for lung cancer treatment.
BAG3, a multifunctional HSP70 co-chaperone and anti-apoptotic protein that interacts with the ATPase domain of HSP70 through its C-terminal BAG domain plays a key physiological role in cellular proteostasis. The HSP70/BAG3 complex determines the levels of a large number of selective client proteins by regulating their turnover via the two major protein degradation pathways, i.e. proteasomal degradation and macroautophagy. On the one hand, BAG3 competes with BAG1 for binding to HSP70, thereby preventing the proteasomal degradation of its client proteins. By functionally interacting with HSP70 and LC3, BAG3 also delivers polyubiquitinated proteins to the autophagy pathway. BAG3 exerts a number of key physiological functions, including an involvement in cellular stress responses, proteostasis, cell death regulation, development, and cytoskeletal dynamics. Conversely, aberrant BAG3 function/expression has pathophysiological relevance correlated to cardiomyopathies, neurodegeneration, and cancer. Evidence obtained in recent years underscores the fact that BAG3 drives several key hallmarks of cancer, including cell adhesion, metastasis, angiogenesis, enhanced autophagic activity, and apoptosis inhibition. This review provides a state-of-the-art overview on the role of BAG3 in stress and therapy resistance of cancer, with a particular focus on BAG3-dependent modulation of apoptotic signaling and autophagic/lysosomal activity.
Cancer-induced pain occurs frequently in patients when tumors or their metastases grow in the proximity of nerves. Although this cancer-induced pain states poses an important therapeutical problem, the underlying pathomechanisms are not understood. Here, we implanted adenocarcinoma, fibrosarcoma and melanoma tumor cells in proximity of the sciatic nerve. All three tumor types caused mechanical hypersensitivity, thermal hyposensitivity and neuronal damage. Surprisingly the onset of the hypersensitivity was independent of physical contact of the nerve with the tumors and did not depend on infiltration of cancer cells in the sciatic nerve. However, macrophages and dendritic cells appeared on the outside of the sciatic nerves with the onset of the hypersensitivity. At the same time point downregulation of perineural tight junction proteins was observed, which was later followed by the appearance of microlesions. Fitting to the changes in the epi-/perineurium, a dramatic decrease of triglycerides and acylcarnitines in the sciatic nerves as well as an altered localization and appearance of epineural adipocytes was seen. In summary, the data show an inflammation at the sciatic nerves as well as an increased perineural and epineural permeability. Thus, interventions aiming to suppress inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity may present new approaches for the treatment of tumor-induced pain.
In Germany, a grave labor shortage in the nursing and elderly care sectors has prompted the response of recruiting skilled nursing staff from abroad in recent years. This article analyzes these recruitment practices as forms of “migration management”: German migration policy has changed according to this paradigm to attempt utilitarian control over migration processes and mediate between labor market concerns on the one hand and isolationist, politico-cultural seclusion on the other. Based on original research through interviews and document analysis, we identify four relevant levels of analysis in researching migration management in the context of the recruitment of skilled nurses: (1) Definition of problem areas: How is migration programmatically legitimized as a solution to social problems? (2) Categorization of migration: How are migration processes classified? (3) Change in statehood: How are sites and actors of migration control being privatized and diversified? (4) Technologies: By means of which procedures, legal foundations and political instruments does migration management take place in the everyday? We believe that taking these four foci as points of departure would be beneficial for further inquiries in critical migration research.
Diurnal valley winds frequently form over complex topography, particularly under fair weather conditions, and have a significant impact on the local weather and climate. Since diurnal valley winds result from complex and multi-scale interactions, their representation in numerical weather prediction models is challenging. Better understanding of these local winds based on observations is crucial to improve the accuracy of the forecasts. This study investigates the diurnal evolution of the three-dimensional mean wind structure in a deep Alpine valley, the Rhone valley at Sion, using data from a radar wind profiler and a surface weather station operated continuously from 1 September 2016 to 17 July 2017. In particular, the wind profiler data was analyzed for a subset of days on which fair weather conditions allowed for the full development of thermally driven winds. A pronounced diurnal cycle of the wind speed, as well as a reversal of the wind direction twice per day is documented for altitudes up to about 2 km above ground level (AGL) in the warm season and less than 1 km AGL in winter. The diurnal pattern undergoes significant changes during the course of the year. Particularly during the warm-weather months of May through to September, a low-level wind maximum occurs, where mean maximum up-valley velocities of 8–10 m s−1 are found between 15–16 UTC at altitudes around 200 m AGL. In addition, during nighttime, a down-valley jet with maximum wind speeds of 4–8 m s−1 around 1 km AGL is found. A case study of a three-day period in September 2016 illustrates the occurrence of an elevated layer of cross-valley flow around 1–1.5 km AGL.
An incoming or outgoing hadron in a hard collision with large momentum transfer gets squeezed in the transverse direction to its momentum. In the case of nuclear targets, this leads to the reduced interaction of such hadrons with surrounding nucleons which is known as color transparency (CT). The identification of CT in exclusive processes on nuclear targets is of significant interest not only by itself but also due to the fact that CT is a necessary condition for the applicability of factorization for the description of the corresponding elementary process. In this paper we discuss the semiexclusive processes A(e,e′π+) , A(π−,l−l+) and A(γ,π−p) . Since CT is closely related to hadron formation mechanism, the reduced interaction of ’pre-hadrons’ with nucleons is a common feature of generic high-energy inclusive processes on nuclear targets, such as hadron attenuation in deep inelastic scattering (DIS). We will discuss the novel way to study hadron formation via slow neutron production induced by a hard photon interaction with a nucleus. Finally, the opportunity to study hadron formation effects in heavy-ion collisions in the NICA regime will be considered.